ncbi / BioREx

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run_test_pred.sh can't run on CPU #8

Closed michaelanekson closed 1 week ago

michaelanekson commented 3 weeks ago

Hello, I am trying to run your code for "predicting new data" part. I follow all your command from creating new environment, install the requirement based on your txt file, until running the bash script. However, when I ran the bash script, I get this issue:

(biorex) [michaela95@BLOOM BioREx]$ bash scripts/run_biorex_new.sh Converting the dataset into BioREx input format 2024-07-04 14:00:33.031276: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:479] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered 2024-07-04 14:00:33.054684: E external/local_xla/xla/stream_executor/cuda/cuda_dnn.cc:10575] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered 2024-07-04 14:00:33.054743: E external/local_xla/xla/stream_executor/cuda/cuda_blas.cc:1442] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered 2024-07-04 14:00:33.071248: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations. To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags. 2024-07-04 14:00:34.221688: W tensorflow/compiler/tf2tensorrt/utils/py_utils.cc:38] TF-TRT Warning: Could not find TensorRT number_unique_YES_instances 0 Generating RE predictions 2024-07-04 14:00:38.500149: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:479] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered 2024-07-04 14:00:38.524087: E external/local_xla/xla/stream_executor/cuda/cuda_dnn.cc:10575] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered 2024-07-04 14:00:38.524137: E external/local_xla/xla/stream_executor/cuda/cuda_blas.cc:1442] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered 2024-07-04 14:00:38.540547: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations. To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags. 2024-07-04 14:00:39.539068: W tensorflow/compiler/tf2tensorrt/utils/py_utils.cc:38] TF-TRT Warning: Could not find TensorRT [INFO|training_args.py:804] 2024-07-04 14:00:42,112 >> using logging_steps to initialize eval_steps to 10 [INFO|training_args.py:1023] 2024-07-04 14:00:42,112 >> PyTorch: setting up devices [INFO|training_args.py:885] 2024-07-04 14:00:42,113 >> The default value for the training argument --report_to will change in v5 (from all installed integrations to none). In v5, you will need to use --report_to all to get the same behavior as now. You should start updating your code and make this info disappear :-). [INFO|training_args_tf.py:189] 2024-07-04 14:00:42,114 >> Tensorflow: setting up strategy 07/04/2024 14:00:42 - INFO - main - n_replicas: 1, distributed training: False, 16-bits training: False 07/04/2024 14:00:42 - INFO - main - Training/evaluation parameters TFTrainingArguments( _n_gpu=0, adafactor=False, adam_beta1=0.9, adam_beta2=0.999, adam_epsilon=1e-08, bf16=False, bf16_full_eval=False, data_seed=None, dataloader_drop_last=False, dataloader_num_workers=0, dataloader_pin_memory=True, ddp_bucket_cap_mb=None, ddp_find_unused_parameters=None, debug=[], deepspeed=None, disable_tqdm=False, do_eval=True, do_predict=True, do_train=False, eval_accumulation_steps=None, eval_delay=0, eval_steps=10, evaluation_strategy=IntervalStrategy.STEPS, fp16=False, fp16_backend=auto, fp16_full_eval=False, fp16_opt_level=O1, gcp_project=None, gradient_accumulation_steps=1, gradient_checkpointing=False, greater_is_better=None, group_by_length=False, half_precision_backend=auto, hub_model_id=None, hub_strategy=HubStrategy.EVERY_SAVE, hub_token=, ignore_data_skip=False, label_names=None, label_smoothing_factor=0.0, learning_rate=5e-05, length_column_name=length, load_best_model_at_end=False, local_rank=-1, log_level=-1, log_level_replica=-1, log_on_each_node=True, logging_dir=biorex_model/runs/Jul04_14-00-42_BLOOM, logging_first_step=False, logging_nan_inf_filter=True, logging_steps=10, logging_strategy=IntervalStrategy.STEPS, lr_scheduler_type=SchedulerType.LINEAR, max_grad_norm=1.0, max_steps=-1, metric_for_best_model=None, mp_parameters=, no_cuda=False, num_train_epochs=10.0, optim=OptimizerNames.ADAMW_HF, output_dir=biorex_model, overwrite_output_dir=True, past_index=-1, per_device_eval_batch_size=32, per_device_train_batch_size=16, poly_power=1.0, prediction_loss_only=False, push_to_hub=False, push_to_hub_model_id=None, push_to_hub_organization=None, push_to_hub_token=, remove_unused_columns=True, report_to=['tensorboard'], resume_from_checkpoint=None, run_name=biorex_model, save_on_each_node=False, save_steps=10, save_strategy=IntervalStrategy.STEPS, save_total_limit=None, seed=42, sharded_ddp=[], skip_memory_metrics=True, tf32=None, tpu_metrics_debug=False, tpu_name=None, tpu_num_cores=None, tpu_zone=None, use_legacy_prediction_loop=False, warmup_ratio=0.0, warmup_steps=0, weight_decay=0.0, xla=False, xpu_backend=None, ) [INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/vocab.txt [INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/tokenizer.json [INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/added_tokens.json [INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/special_tokens_map.json [INFO|tokenization_utils_base.py:1776] 2024-07-04 14:00:42,124 >> loading file pretrained_model/tokenizer_config.json =======================>label2id {'None': 0, 'Association': 1, 'Bind': 2, 'Comparison': 3, 'Conversion': 4, 'Cotreatment': 5, 'Drug_Interaction': 6, 'Negative_Correlation': 7, 'Positive_Correlation': 8, 'None-CID': 9, 'CID': 10, 'None-PPIm': 11, 'PPIm': 12, 'None-AIMED': 13, 'None-DDI': 14, 'None-BC7': 15, 'None-phargkb': 16, 'None-GDA': 17, 'None-DISGENET': 18, 'None-EMU_BC': 19, 'None-EMU_PC': 20, 'None-HPRD50': 21, 'None-PHARMGKB': 22, 'ACTIVATOR': 23, 'AGONIST': 24, 'AGONIST-ACTIVATOR': 25, 'AGONIST-INHIBITOR': 26, 'ANTAGONIST': 27, 'DIRECT-REGULATOR': 28, 'INDIRECT-DOWNREGULATOR': 29, 'INDIRECT-UPREGULATOR': 30, 'INHIBITOR': 31, 'PART-OF': 32, 'PRODUCT-OF': 33, 'SUBSTRATE': 34, 'SUBSTRATE_PRODUCT-OF': 35, 'mechanism': 36, 'int': 37, 'effect': 38, 'advise': 39, 'AIMED-Association': 40, 'HPRD-Association': 41, 'EUADR-Association': 42, 'None-EUADR': 43, 'Indirect_conversion': 44, 'Non_conversion': 45} =======================>positive_label =======================>use_balanced_neg False =======================>max_neg_scale 2 07/04/2024 14:00:42 - INFO - main - pos_label_ids 07/04/2024 14:00:42 - INFO - main - [1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 17, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45] [INFO|configuration_utils.py:652] 2024-07-04 14:00:42,153 >> loading configuration file pretrained_model/config.json [INFO|configuration_utils.py:690] 2024-07-04 14:00:42,154 >> Model config BertConfig { "_name_or_path": "pretrained_model", "architectures": [ "BertForSequenceClassification" ], "attention_probs_dropout_prob": 0.1, "classifier_dropout": null, "finetuning_task": "text-classification", "hidden_act": "gelu", "hidden_dropout_prob": 0.1, "hidden_size": 768, "id2label": { "0": "None", "1": "Association", "2": "Bind", "3": "Comparison", "4": "Conversion", "5": "Cotreatment", "6": "Drug_Interaction", "7": "Negative_Correlation", "8": "Positive_Correlation", "9": "None-CID", "10": "CID", "11": "None-PPIm", "12": "PPIm", "13": "None-AIMED", "14": "None-DDI", "15": "None-BC7", "16": "None-phargkb", "17": "None-GDA", "18": "None-DISGENET", "19": "None-EMU_BC", "20": "None-EMU_PC", "21": "None-HPRD50", "22": "None-PHARMGKB", "23": "ACTIVATOR", "24": "AGONIST", "25": "AGONIST-ACTIVATOR", "26": "AGONIST-INHIBITOR", "27": "ANTAGONIST", "28": "DIRECT-REGULATOR", "29": "INDIRECT-DOWNREGULATOR", "30": "INDIRECT-UPREGULATOR", "31": "INHIBITOR", "32": "PART-OF", "33": "PRODUCT-OF", "34": "SUBSTRATE", "35": "SUBSTRATE_PRODUCT-OF", "36": "mechanism", "37": "int", "38": "effect", "39": "advise", "40": "AIMED-Association", "41": "HPRD-Association", "42": "EUADR-Association", "43": "None-EUADR", "44": "Indirect_conversion", "45": "Non_conversion" }, "initializer_range": 0.02, "intermediate_size": 3072, "label2id": { "ACTIVATOR": 23, "AGONIST": 24, "AGONIST-ACTIVATOR": 25, "AGONIST-INHIBITOR": 26, "AIMED-Association": 40, "ANTAGONIST": 27, "Association": 1, "Bind": 2, "CID": 10, "Comparison": 3, "Conversion": 4, "Cotreatment": 5, "DIRECT-REGULATOR": 28, "Drug_Interaction": 6, "EUADR-Association": 42, "HPRD-Association": 41, "INDIRECT-DOWNREGULATOR": 29, "INDIRECT-UPREGULATOR": 30, "INHIBITOR": 31, "Indirect_conversion": 44, "Negative_Correlation": 7, "Non_conversion": 45, "None": 0, "None-AIMED": 13, "None-BC7": 15, "None-CID": 9, "None-DDI": 14, "None-DISGENET": 18, "None-EMU_BC": 19, "None-EMU_PC": 20, "None-EUADR": 43, "None-GDA": 17, "None-HPRD50": 21, "None-PHARMGKB": 22, "None-PPIm": 11, "None-phargkb": 16, "PART-OF": 32, "PPIm": 12, "PRODUCT-OF": 33, "Positive_Correlation": 8, "SUBSTRATE": 34, "SUBSTRATE_PRODUCT-OF": 35, "advise": 39, "effect": 38, "int": 37, "mechanism": 36 }, "layer_norm_eps": 1e-12, "max_position_embeddings": 512, "model_type": "bert", "num_attention_heads": 12, "num_hidden_layers": 12, "pad_token_id": 0, "position_embedding_type": "absolute", "transformers_version": "4.18.0", "type_vocab_size": 2, "use_cache": true, "vocab_size": 28933 }

[INFO|modeling_tf_utils.py:1776] 2024-07-04 14:00:42,177 >> loading weights file pretrained_model/tf_model.h5 /media/data/biorex/lib/python3.10/site-packages/keras/src/layers/layer.py:1331: UserWarning: Layer 'tf_bert_for_sequence_classification' looks like it has unbuilt state, but Keras is not able to trace the layer call() in order to build it automatically. Possible causes:

  1. The call() method of your layer may be crashing. Try to __call__() the layer eagerly on some test input first to see if it works. E.g. x = np.random.random((3, 4)); y = layer(x)
  2. If the call() method is correct, then you may need to implement the def build(self, input_shape) method on your layer. It should create all variables used by the layer (e.g. by calling layer.build() on all its children layers). Exception encountered: ''Exception encountered when calling TFBertMainLayer.call().

'NoneType' object has no attribute 'shape'

Arguments received by TFBertMainLayer.call(): • input_ids=tf.Tensor(shape=(3, 5), dtype=int32) • attention_mask=None • token_type_ids=None • position_ids=None • head_mask=None • inputs_embeds=None • encoder_hidden_states=None • encoder_attention_mask=None • past_key_values=None • use_cache=None • output_attentions=False • output_hidden_states=False • return_dict=True • training=False'' warnings.warn( /media/data/biorex/lib/python3.10/site-packages/keras/src/layers/layer.py:372: UserWarning: build() was called on layer 'tf_bert_for_sequence_classification', however the layer does not have a build() method implemented and it looks like it has unbuilt state. This will cause the layer to be marked as built, despite not being actually built, which may cause failures down the line. Make sure to implement a proper build() method. warnings.warn( Traceback (most recent call last): File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/run_ncbi_rel_exp.py", line 884, in main() File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/run_ncbi_rel_exp.py", line 687, in main model = TFAutoModelForSequenceClassification.from_pretrained( File "/media/data/biorex/lib/python3.10/site-packages/transformers/models/auto/auto_factory.py", line 446, in from_pretrained return model_class.from_pretrained(pretrained_model_name_or_path, *model_args, config=config, kwargs) File "/media/data/biorex/lib/python3.10/site-packages/transformers/modeling_tf_utils.py", line 1803, in from_pretrained model(model.dummy_inputs) # build the network with dummy inputs File "/media/data/biorex/lib/python3.10/site-packages/keras/src/utils/traceback_utils.py", line 122, in error_handler raise e.with_traceback(filtered_tb) from None File "/media/data/biorex/lib/python3.10/site-packages/transformers/modeling_tf_utils.py", line 383, in run_call_with_unpacked_inputs return func(self, unpacked_inputs) File "/media/data/biorex/lib/python3.10/site-packages/transformers/models/bert/modeling_tf_bert.py", line 1633, in call outputs = self.bert( File "/media/data/biorex/lib/python3.10/site-packages/transformers/modeling_tf_utils.py", line 383, in run_call_with_unpacked_inputs return func(self, *unpacked_inputs) File "/media/data/biorex/lib/python3.10/site-packages/transformers/models/bert/modeling_tf_bert.py", line 850, in call encoder_outputs = self.encoder( File "/media/data/biorex/lib/python3.10/site-packages/optree/ops.py", line 594, in tree_map return treespec.unflatten(map(func, flat_args)) AttributeError: Exception encountered when calling TFBertMainLayer.call().

'NoneType' object has no attribute 'shape'

Arguments received by TFBertMainLayer.call(): • input_ids=tf.Tensor(shape=(3, 5), dtype=int32) • attention_mask=None • token_type_ids=None • position_ids=None • head_mask=None • inputs_embeds=None • encoder_hidden_states=None • encoder_attention_mask=None • past_key_values=None • use_cache=None • output_attentions=False • output_hidden_states=False • return_dict=True • training=False cp: cannot stat 'biorex_model/test_results.tsv': No such file or directory 2024-07-04 14:00:46.035576: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:479] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered 2024-07-04 14:00:46.059361: E external/local_xla/xla/stream_executor/cuda/cuda_dnn.cc:10575] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered 2024-07-04 14:00:46.059424: E external/local_xla/xla/stream_executor/cuda/cuda_blas.cc:1442] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered 2024-07-04 14:00:46.075918: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations. To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags. 2024-07-04 14:00:47.150909: W tensorflow/compiler/tf2tensorrt/utils/py_utils.cc:38] TF-TRT Warning: Could not find TensorRT Traceback (most recent call last): File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/utils/run_pubtator_eval.py", line 1557, in dump_pred_2_pubtator_file(in_pubtator_file = in_test_pubtator_file, File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/utils/run_pubtator_eval.py", line 206, in dump_pred_2_pubtator_file add_relation_pairs_dict( File "/home/michaela95/NLP_immune_checkpoint_gene/BERT_testing/BioREx/src/utils/run_pubtator_eval.py", line 83, in add_relation_pairs_dict testdf = pd.read_csv(in_gold_tsv_file, sep="\t", index_col=0) File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 1026, in read_csv return _read(filepath_or_buffer, kwds) File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 620, in _read parser = TextFileReader(filepath_or_buffer, kwds) File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 1620, in init self._engine = self._make_engine(f, self.engine) File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/readers.py", line 1898, in _make_engine return mapping[engine](f, self.options) File "/media/data/biorex/lib/python3.10/site-packages/pandas/io/parsers/c_parser_wrapper.py", line 93, in init self._reader = parsers.TextReader(src, **kwds) File "parsers.pyx", line 581, in pandas._libs.parsers.TextReader.cinit pandas.errors.EmptyDataError: No columns to parse from file

Would you tell what should I do in dealing with this situation?

ptlai commented 2 weeks ago

Hi @michaelanekson,

Here's a more native and fluent version of the message: Hi Michael, Thanks for bringing this error to our attention. It could be due to either an environment issue or a problem with the input PubTator file.

I've updated the requirements.txt to address potential environment-related issues.

As for the input file, would you mind sharing yours with me? Alternatively, you could try using the bc8_biored_task1_val.pubtator file from the BC8-BioRED dataset. You can find it in this ZIP archive: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/BC8_BioRED_Subtask1_PubTator.zip. Give it a shot and see if the program runs without errors.

Let me know if you need any further assistance!

Best, Po-Ting

michaelanekson commented 2 weeks ago

Here my input file, you can download it. Actually, my input file is already PubTator file but I don't why It doesn't work. You can see it in my uploaded file. I already see your file BioRED and the format is Pubtator as same as mine.

sample.zip

Recently, I solve the problem by loading your LLM model manually using transformers. The situation is I am trying to load Pubtator3 BioLinkBERT and it works for me. Would you see my modified LLM code? maybe you can correct me if I use your LLM model in the wrong way. modified BioREx code.zip

One more thing about environmental issue, I think if we use the most updated transformers, tensorflow, or biospacy, it does not work properly. So, I agree with your current modified requirement

ptlai commented 2 weeks ago

Hi @michaelanekson,

Thank you for sharing the files. I've taken a look at your sample file, and I noticed you're using PubTator NE types instead of BioRED NE types. If you've downloaded your sample file from PubTator, you can use the converter mentioned in this GitHub issue comment to convert it to BioRED NE types.

Since the NE type tags are different, it might negatively impact the script you provided. I'd recommend using our leaderboard's dataset and evaluation to test it before applying it to your own dataset.

Also, if you're only interested in results for PubMed abstracts, we've already processed the entire PubMed database. You can find that data here.

michaelanekson commented 2 weeks ago

Hello, I already try with your BioRED dataset and it works in annotation part but it is not working in relation extraction part. The model that I use is pretrained_model_biolinkbert. Here's the error description: 2024-07-11 15:23:21,367 - INFO - Annotation: pain, Type: DiseaseOrPhenotypicFeature, Position: 91 2024-07-11 15:23:21,367 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 169 2024-07-11 15:23:21,367 - INFO - Annotation: neurocognitive decline, Type: DiseaseOrPhenotypicFeature, Position: 202 2024-07-11 15:23:21,368 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 426 2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 539 2024-07-11 15:23:21,368 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 557 2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 792 2024-07-11 15:23:21,368 - INFO - Annotation: human, Type: OrganismTaxon, Position: 812 2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 868 2024-07-11 15:23:21,368 - INFO - Annotation: heterogeneous nuclear ribonucleoprotein complex A2/B1, Type: GeneOrGeneProduct, Position: 1032 2024-07-11 15:23:21,368 - INFO - Annotation: hnRNP A2/B1, Type: GeneOrGeneProduct, Position: 1087 2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1114 2024-07-11 15:23:21,368 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1160 2024-07-11 15:23:21,368 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1200 2024-07-11 15:23:21,368 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1261 2024-07-11 15:23:21,369 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1272 2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1350 2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1455 2024-07-11 15:23:21,369 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1477 2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1500 2024-07-11 15:23:21,369 - INFO - Annotation: miR-23a, Type: GeneOrGeneProduct, Position: 1527 2024-07-11 15:23:21,369 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 1535 2024-07-11 15:23:21,369 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1570 2024-07-11 15:23:21,369 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1673 2024-07-11 15:23:21,369 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 1695 2024-07-11 15:23:21,369 - INFO - Annotation: CD31, Type: GeneOrGeneProduct, Position: 1759 2024-07-11 15:23:21,369 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 1821 2024-07-11 15:23:21,370 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 1968 2024-07-11 15:23:21,370 - INFO - Annotation: NG2, Type: GeneOrGeneProduct, Position: 2007 2024-07-11 15:23:21,370 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 2017 2024-07-11 15:23:21,370 - INFO - Annotation: mice, Type: OrganismTaxon, Position: 2043 2024-07-11 15:23:21,370 - INFO - Annotation: morphine, Type: ChemicalEntity, Position: 2086 2024-07-11 15:23:21,370 - INFO - Annotation: neuroinflammation, Type: DiseaseOrPhenotypicFeature, Position: 2258 2024-07-11 15:23:21,370 - INFO - Document ID: BC8_BioRED_Task1_Doc1482 2024-07-11 15:23:21,370 - INFO - Text Instance: Fine mapping and identification of a candidate gene SSH1 in disseminated superficial actinic porokeratosis. 2024-07-11 15:23:21,370 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 52 2024-07-11 15:23:21,370 - INFO - Annotation: disseminated superficial actinic porokeratosis, Type: DiseaseOrPhenotypicFeature, Position: 60 2024-07-11 15:23:21,370 - INFO - Text Instance: Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP. 2024-07-11 15:23:21,371 - INFO - Annotation: Disseminated superficial actinic porokeratosis, Type: DiseaseOrPhenotypicFeature, Position: 0 2024-07-11 15:23:21,371 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 48 2024-07-11 15:23:21,371 - INFO - Annotation: keratinization disorder, Type: DiseaseOrPhenotypicFeature, Position: 96 2024-07-11 15:23:21,371 - INFO - Annotation: keratotic lesions, Type: DiseaseOrPhenotypicFeature, Position: 159 2024-07-11 15:23:21,371 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 259 2024-07-11 15:23:21,371 - INFO - Annotation: p.Ser63Asn, Type: GeneOrGeneProduct, Position: 626 2024-07-11 15:23:21,371 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 640 2024-07-11 15:23:21,371 - INFO - Annotation: p.Ser19CysfsX24, Type: GeneOrGeneProduct, Position: 683 2024-07-11 15:23:21,371 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 740 2024-07-11 15:23:21,371 - INFO - Annotation: p.Pro27ProfsX54, Type: GeneOrGeneProduct, Position: 791 2024-07-11 15:23:21,371 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 869 2024-07-11 15:23:21,371 - INFO - Annotation: SSH1, Type: GeneOrGeneProduct, Position: 875 2024-07-11 15:23:21,372 - INFO - Annotation: DSAP, Type: DiseaseOrPhenotypicFeature, Position: 1065 2024-07-11 15:23:21,372 - INFO - Document ID: BC8_BioRED_Task1_Doc1483 2024-07-11 15:23:21,372 - INFO - Text Instance: Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: frequency distribution in a healthy German population. 2024-07-11 15:23:21,372 - INFO - Annotation: venous and arterial thromboembolism, Type: DiseaseOrPhenotypicFeature, Position: 63 2024-07-11 15:23:21,372 - INFO - Text Instance: Evolvement and progression of cardiovascular diseases affecting the venous and arterial system are influenced by a multitude of environmental and hereditary factors. Many of these hereditary factors consist of defined gene polymorphisms, such as single nucleotide polymorphisms (SNPs) or insertion-deletion polymorphisms, which directly or indirectly affect the hemostatic system. The frequencies of individual hemostatic gene polymorphisms in different normal populations are well defined. However, descriptions of patterns of genetic variability of a larger extent of different factors of hereditary hypercoagulability in single populations are scarce. The aim of this study was i) to give a detailed description of the frequencies of factors of hereditary thrombophilia and their combinations in a German population (n = 282) and ii) to compare their distributions with those reported for other regions. Variants of coagulation factors [factor V 1691G>A (factor V Leiden), factor V 4070A>G (factor V HR2 haplotype), factor VII Arg353Gln, factor XIII Val34Leu, beta-fibrinogen -455G>A, prothrombin 20210G>A], coagulation inhibitors [tissue factor pathway inhibitor 536C>T, thrombomodulin 127G>A], fibrinolytic factors [angiotensin converting enzyme intron 16 insertion/deletion, factor VII-activating protease 1601G>A (FSAP Marburg I), plasminogen activator inhibitor 1-675 insertion/deletion (5G/4G), tissue plasminogen activator intron h deletion/insertion], and other factors implicated in influencing susceptibility to thromboembolic diseases [apolipoprotein E2/E3/E4, glycoprotein Ia 807C>T, methylenetetrahydrofolate reductase 677C>T] were included. The distribution of glycoprotein Ia 807C>T deviated significantly from the Hardy-Weinberg equilibrium, and a comparison with previously published data indicates marked region and ethnicity dependent differences in the genotype distributions of some other factors. 2024-07-11 15:23:21,372 - INFO - Annotation: cardiovascular diseases, Type: DiseaseOrPhenotypicFeature, Position: 30 2024-07-11 15:23:21,372 - INFO - Annotation: hereditary hypercoagulability, Type: DiseaseOrPhenotypicFeature, Position: 591 2024-07-11 15:23:21,372 - INFO - Annotation: hereditary thrombophilia, Type: DiseaseOrPhenotypicFeature, Position: 748 2024-07-11 15:23:21,372 - INFO - Annotation: factor V, Type: GeneOrGeneProduct, Position: 940 2024-07-11 15:23:21,372 - INFO - Annotation: 1691G>A, Type: GeneOrGeneProduct, Position: 949 2024-07-11 15:23:21,372 - INFO - Annotation: factor V Leiden, Type: GeneOrGeneProduct, Position: 958 2024-07-11 15:23:21,373 - INFO - Annotation: factor V, Type: GeneOrGeneProduct, Position: 976 2024-07-11 15:23:21,373 - INFO - Annotation: 4070A>G, Type: GeneOrGeneProduct, Position: 985 2024-07-11 15:23:21,373 - INFO - Annotation: factor V, Type: GeneOrGeneProduct, Position: 994 2024-07-11 15:23:21,373 - INFO - Annotation: factor VII, Type: GeneOrGeneProduct, Position: 1019 2024-07-11 15:23:21,373 - INFO - Annotation: Arg353Gln, Type: GeneOrGeneProduct, Position: 1030 2024-07-11 15:23:21,373 - INFO - Annotation: factor XIII, Type: GeneOrGeneProduct, Position: 1041 2024-07-11 15:23:21,373 - INFO - Annotation: Val34Leu, Type: GeneOrGeneProduct, Position: 1053 2024-07-11 15:23:21,373 - INFO - Annotation: beta-fibrinogen, Type: GeneOrGeneProduct, Position: 1063 2024-07-11 15:23:21,373 - INFO - Annotation: -455G>A, Type: GeneOrGeneProduct, Position: 1079 2024-07-11 15:23:21,373 - INFO - Annotation: prothrombin, Type: GeneOrGeneProduct, Position: 1088 2024-07-11 15:23:21,373 - INFO - Annotation: 20210G>A, Type: GeneOrGeneProduct, Position: 1100 2024-07-11 15:23:21,373 - INFO - Annotation: tissue factor pathway inhibitor, Type: GeneOrGeneProduct, Position: 1135 2024-07-11 15:23:21,374 - INFO - Annotation: 536C>T, Type: GeneOrGeneProduct, Position: 1167 2024-07-11 15:23:21,374 - INFO - Annotation: thrombomodulin, Type: GeneOrGeneProduct, Position: 1175 2024-07-11 15:23:21,374 - INFO - Annotation: 127G>A, Type: GeneOrGeneProduct, Position: 1190 2024-07-11 15:23:21,374 - INFO - Annotation: angiotensin converting enzyme, Type: GeneOrGeneProduct, Position: 1221 2024-07-11 15:23:21,374 - INFO - Annotation: factor VII-activating protease, Type: GeneOrGeneProduct, Position: 1281 2024-07-11 15:23:21,374 - INFO - Annotation: 1601G>A, Type: GeneOrGeneProduct, Position: 1312 2024-07-11 15:23:21,374 - INFO - Annotation: FSAP, Type: GeneOrGeneProduct, Position: 1321 2024-07-11 15:23:21,374 - INFO - Annotation: plasminogen activator inhibitor 1, Type: GeneOrGeneProduct, Position: 1338 2024-07-11 15:23:21,374 - INFO - Annotation: 675 insertion/deletion, Type: GeneOrGeneProduct, Position: 1372 2024-07-11 15:23:21,374 - INFO - Annotation: tissue plasminogen activator, Type: GeneOrGeneProduct, Position: 1404 2024-07-11 15:23:21,374 - INFO - Annotation: thromboembolic diseases, Type: DiseaseOrPhenotypicFeature, Position: 1525 2024-07-11 15:23:21,375 - INFO - Annotation: apolipoprotein E2/E3/E4, glycoprotein Ia, Type: GeneOrGeneProduct, Position: 1550 2024-07-11 15:23:21,375 - INFO - Annotation: 807C>T, Type: GeneOrGeneProduct, Position: 1591 2024-07-11 15:23:21,375 - INFO - Annotation: methylenetetrahydrofolate reductase, Type: GeneOrGeneProduct, Position: 1599 2024-07-11 15:23:21,375 - INFO - Annotation: 677C>T, Type: GeneOrGeneProduct, Position: 1635 2024-07-11 15:23:21,375 - INFO - Annotation: glycoprotein Ia, Type: GeneOrGeneProduct, Position: 1678 2024-07-11 15:23:21,375 - INFO - Annotation: 807C>T, Type: GeneOrGeneProduct, Position: 1694 2024-07-11 15:23:21,375 - INFO - Document ID: BC8_BioRED_Task1_Doc1484 2024-07-11 15:23:21,375 - INFO - Text Instance: Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome. 2024-07-11 15:23:21,375 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 26 2024-07-11 15:23:21,375 - INFO - Annotation: Marfan syndrome, Type: DiseaseOrPhenotypicFeature, Position: 70 2024-07-11 15:23:21,375 - INFO - Text Instance: PURPOSE: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS). METHODS: Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation. RESULTS: A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 (p.S1235P). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain. CONCLUSIONS: We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome. 2024-07-11 15:23:21,375 - INFO - Annotation: fibrillin-1, Type: GeneOrGeneProduct, Position: 41 2024-07-11 15:23:21,375 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 59 2024-07-11 15:23:21,375 - INFO - Annotation: Marfan syndrome, Type: DiseaseOrPhenotypicFeature, Position: 90 2024-07-11 15:23:21,375 - INFO - Annotation: MFS, Type: DiseaseOrPhenotypicFeature, Position: 107 2024-07-11 15:23:21,376 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 122 2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 422 2024-07-11 15:23:21,376 - INFO - Annotation: c.3703T>C, Type: GeneOrGeneProduct, Position: 931 2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 962 2024-07-11 15:23:21,376 - INFO - Annotation: serine by proline at codon 1235, Type: GeneOrGeneProduct, Position: 1034 2024-07-11 15:23:21,376 - INFO - Annotation: p.S1235P, Type: GeneOrGeneProduct, Position: 1067 2024-07-11 15:23:21,376 - INFO - Annotation: calcium, Type: ChemicalEntity, Position: 1257 2024-07-11 15:23:21,376 - INFO - Annotation: epidermal growth factor, Type: GeneOrGeneProduct, Position: 1273 2024-07-11 15:23:21,376 - INFO - Annotation: p.S1235P, Type: GeneOrGeneProduct, Position: 1453 2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 1474 2024-07-11 15:23:21,376 - INFO - Annotation: MFS, Type: DiseaseOrPhenotypicFeature, Position: 1516 2024-07-11 15:23:21,376 - INFO - Annotation: FBN1, Type: GeneOrGeneProduct, Position: 1580 2024-07-11 15:23:21,376 - INFO - Annotation: Marfan syndrome, Type: DiseaseOrPhenotypicFeature, Position: 1647 2024-07-11 15:23:21,376 - INFO - Document ID: BC8_BioRED_Task1_Doc1485 2024-07-11 15:23:21,377 - INFO - Text Instance: Evaluation of Ascorbic Acid Niosomes as Potential Detoxifiers in Oxidative Stress-induced HEK-293 Cells by Arsenic Trioxide. 2024-07-11 15:23:21,377 - INFO - Annotation: Ascorbic Acid, Type: ChemicalEntity, Position: 14 2024-07-11 15:23:21,377 - INFO - Annotation: as, Type: ChemicalEntity, Position: 37 2024-07-11 15:23:21,377 - INFO - Annotation: HEK-293, Type: CellLine, Position: 90 2024-07-11 15:23:21,377 - INFO - Annotation: Arsenic Trioxide, Type: ChemicalEntity, Position: 107 2024-07-11 15:23:21,377 - INFO - Text Instance: Background: As an environmental contaminant, Arsenic (As) poses many risks to human health. Increased Oxidative Stress (OS) and decreased antioxidant cell defense are the suggested mechanisms of carcinogenicity and toxicity of As. As a powerful antioxidant and water-soluble compound, vitamin C protects cells and tissues against oxidation and has a wide range of healing properties. Objectives: The current study aimed to formulate a suitable ascorbic acid (vitamin C) niosome and compare it with vitamin C in preventing As-induced toxicity in HEK-293 cells. Methods: Various formulas of vitamin C niosomes were prepared by C-SPAN mixed with cholesterol. The physicochemical characteristics of niosomal formulations, including load size, zeta-potential, and the drug release profile, were evaluated in HEK-293 cells. Then, OS biomarkers such as total reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), Antioxidant Capacity (TAC), and superoxide dismutase (SOD) activities determined the protective effects of vitamin C niosomes compared with vitamin C against As-induced toxicity. Results: The particle size and zeta potential of the optimal vitamin C niosome were 163.2 +- 6.1 nm and 23.3 +- 3.5 mV, respectively. Arsenic increased ROS and MDA levels while decreasing CAT, TAC, and SOD activities in the HEK-293 cell line. Finally, the vitamin C niosome decreased OS and increased antioxidant properties more than vitamin C. Significance: Vitamin C niosome was more effective than vitamin C in treating As-induced toxicity in vitro. 2024-07-11 15:23:21,418 - INFO - Annotation: As, Type: ChemicalEntity, Position: 12 2024-07-11 15:23:21,418 - INFO - Annotation: Arsenic, Type: ChemicalEntity, Position: 45 2024-07-11 15:23:21,418 - INFO - Annotation: As, Type: ChemicalEntity, Position: 54 2024-07-11 15:23:21,418 - INFO - Annotation: human, Type: OrganismTaxon, Position: 78 2024-07-11 15:23:21,419 - INFO - Annotation: carcinogenicity, Type: DiseaseOrPhenotypicFeature, Position: 195 2024-07-11 15:23:21,419 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 215 2024-07-11 15:23:21,419 - INFO - Annotation: As, Type: ChemicalEntity, Position: 227 2024-07-11 15:23:21,419 - INFO - Annotation: As, Type: ChemicalEntity, Position: 231 2024-07-11 15:23:21,419 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 285 2024-07-11 15:23:21,419 - INFO - Annotation: ascorbic acid, Type: ChemicalEntity, Position: 444 2024-07-11 15:23:21,419 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 459 2024-07-11 15:23:21,419 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 498 2024-07-11 15:23:21,419 - INFO - Annotation: As, Type: ChemicalEntity, Position: 522 2024-07-11 15:23:21,419 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 533 2024-07-11 15:23:21,419 - INFO - Annotation: HEK-293, Type: CellLine, Position: 545 2024-07-11 15:23:21,420 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 589 2024-07-11 15:23:21,420 - INFO - Annotation: cholesterol, Type: ChemicalEntity, Position: 643 2024-07-11 15:23:21,420 - INFO - Annotation: HEK-293, Type: CellLine, Position: 803 2024-07-11 15:23:21,420 - INFO - Annotation: as, Type: ChemicalEntity, Position: 843 2024-07-11 15:23:21,420 - INFO - Annotation: reactive oxygen species, Type: ChemicalEntity, Position: 852 2024-07-11 15:23:21,420 - INFO - Annotation: ROS, Type: ChemicalEntity, Position: 877 2024-07-11 15:23:21,420 - INFO - Annotation: malondialdehyde, Type: ChemicalEntity, Position: 883 2024-07-11 15:23:21,420 - INFO - Annotation: MDA, Type: ChemicalEntity, Position: 900 2024-07-11 15:23:21,420 - INFO - Annotation: catalase, Type: GeneOrGeneProduct, Position: 906 2024-07-11 15:23:21,420 - INFO - Annotation: CAT, Type: GeneOrGeneProduct, Position: 916 2024-07-11 15:23:21,420 - INFO - Annotation: superoxide dismutase, Type: GeneOrGeneProduct, Position: 954 2024-07-11 15:23:21,420 - INFO - Annotation: SOD, Type: GeneOrGeneProduct, Position: 976 2024-07-11 15:23:21,421 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1029 2024-07-11 15:23:21,421 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1062 2024-07-11 15:23:21,421 - INFO - Annotation: As, Type: ChemicalEntity, Position: 1080 2024-07-11 15:23:21,421 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 1091 2024-07-11 15:23:21,421 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1162 2024-07-11 15:23:21,421 - INFO - Annotation: Arsenic, Type: ChemicalEntity, Position: 1235 2024-07-11 15:23:21,421 - INFO - Annotation: ROS, Type: ChemicalEntity, Position: 1253 2024-07-11 15:23:21,421 - INFO - Annotation: MDA, Type: ChemicalEntity, Position: 1261 2024-07-11 15:23:21,421 - INFO - Annotation: CAT, Type: GeneOrGeneProduct, Position: 1289 2024-07-11 15:23:21,421 - INFO - Annotation: SOD, Type: GeneOrGeneProduct, Position: 1303 2024-07-11 15:23:21,421 - INFO - Annotation: HEK-293, Type: CellLine, Position: 1325 2024-07-11 15:23:21,422 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1357 2024-07-11 15:23:21,422 - INFO - Annotation: vitamin C., Type: ChemicalEntity, Position: 1435 2024-07-11 15:23:21,422 - INFO - Annotation: Vitamin C, Type: ChemicalEntity, Position: 1460 2024-07-11 15:23:21,422 - INFO - Annotation: vitamin C, Type: ChemicalEntity, Position: 1502 2024-07-11 15:23:21,422 - INFO - Annotation: As, Type: ChemicalEntity, Position: 1524 2024-07-11 15:23:21,422 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 1535 2024-07-11 15:23:21,422 - INFO - Document ID: BC8_BioRED_Task1_Doc1486 2024-07-11 15:23:21,422 - INFO - Text Instance: Tetrahydroindazole inhibitors of CDK2/cyclin complexes. 2024-07-11 15:23:21,422 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 33 2024-07-11 15:23:21,422 - INFO - Annotation: cyclin, Type: GeneOrGeneProduct, Position: 38 2024-07-11 15:23:21,422 - INFO - Text Instance: Over 50 tetrahydroindazoles were synthesized after 7-bromo-3,6,6-trimethyl-1-(pyridin-2-yl)-5,6,7,7a-tetrahydro-1H-indazol-4(3aH)-one (3) was identified as a hit compound in a high throughput screen for inhibition of CDK2 in complex with cyclin A. The activity of the most promising analogues was evaluated by inhibition of CDK2 enzyme complexes with various cyclins. Analogues 53 and 59 showed 3-fold better binding affinity for CDK2 and 2- to 10-fold improved inhibitory activity against CDK2/cyclin A1, E, and O compared to screening hit 3. The data from the enzyme and binding assays indicate that the binding of the analogues to a CDK2/cyclin complex is favored over binding to free CDK2. Computational analysis was used to predict a potential binding site at the CDK2/cyclin E1 interface. 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 217 2024-07-11 15:23:21,423 - INFO - Annotation: cyclin A., Type: GeneOrGeneProduct, Position: 238 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 324 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 430 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 490 2024-07-11 15:23:21,423 - INFO - Annotation: cyclin A1, E, and O, Type: GeneOrGeneProduct, Position: 495 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 636 2024-07-11 15:23:21,423 - INFO - Annotation: cyclin, Type: GeneOrGeneProduct, Position: 641 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 688 2024-07-11 15:23:21,423 - INFO - Annotation: CDK2, Type: GeneOrGeneProduct, Position: 769 2024-07-11 15:23:21,423 - INFO - Annotation: cyclin E1, Type: GeneOrGeneProduct, Position: 774 2024-07-11 15:23:21,423 - INFO - Document ID: BC8_BioRED_Task1_Doc1487 2024-07-11 15:23:21,424 - INFO - Text Instance: Cutaneous angiosarcoma treated with taxane-based chemoradiotherapy: A multicenter study of 90 Japanese cases. 2024-07-11 15:23:21,424 - INFO - Annotation: Cutaneous angiosarcoma, Type: DiseaseOrPhenotypicFeature, Position: 0 2024-07-11 15:23:21,424 - INFO - Annotation: taxane, Type: ChemicalEntity, Position: 36 2024-07-11 15:23:21,424 - INFO - Text Instance: Cutaneous angiosarcoma (CAS) is rare and most previous studies of CAS have been small case series, and randomized, phase II studies of CAS are limited. Since treatment options for CAS are controversial, and because only paclitaxel should be recommended based on high-level evidence, it is important to evaluate the efficacy of another taxane-derived agents, docetaxel, in real-world practice. The efficacy and safety profiles of chemoradiotherapy using taxane-based agents, docetaxel and paclitaxel, were retrospectively examined in the maintenance setting in 90 Japanese CAS patients, including 35 docetaxel-treated cases and 55 paclitaxel-treated cases. Overall survival and dose duration time of the patient group treated with docetaxel was equivalent to that with paclitaxel, even in the cohorts with metastasis. Adverse events due to docetaxel and paclitaxel were observed in 77.1% and 69.1% of cases, respectively. The incidence ratio of total severe adverse events tended to be higher in the docetaxel-treated group (40.0%) than in the paclitaxel-treated group (23.6%). Peripheral neuropathy occurred only in the paclitaxel-treated group, whereas high-grade interstitial pneumonia developed only in the docetaxel-treated group. In addition, we also evaluate 19 patients selected other taxanes, 17 patients selected eribulin methylate, 11 patients pazopanib, and 2 patients selected nivolumab as second-line chemotherapy. The efficacy of a monthly docetaxel regimen is equivalent to a three-weekly paclitaxel regimen evaluated by Overall survival and DDT, even in the cohorts with metastasis, and it is a tolerable protocol for CAS as a maintenance therapy in the Japanese population. 2024-07-11 15:23:21,424 - INFO - Annotation: Cutaneous angiosarcoma, Type: DiseaseOrPhenotypicFeature, Position: 0 2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 24 2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 66 2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 135 2024-07-11 15:23:21,424 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 180 2024-07-11 15:23:21,424 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 220 2024-07-11 15:23:21,424 - INFO - Annotation: taxane, Type: ChemicalEntity, Position: 335 2024-07-11 15:23:21,424 - INFO - Annotation: taxane, Type: ChemicalEntity, Position: 453 2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 488 2024-07-11 15:23:21,425 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 572 2024-07-11 15:23:21,425 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 576 2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 630 2024-07-11 15:23:21,425 - INFO - Annotation: patient, Type: OrganismTaxon, Position: 703 2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 768 2024-07-11 15:23:21,425 - INFO - Annotation: metastasis, Type: DiseaseOrPhenotypicFeature, Position: 805 2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 853 2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 1043 2024-07-11 15:23:21,425 - INFO - Annotation: Peripheral neuropathy, Type: DiseaseOrPhenotypicFeature, Position: 1077 2024-07-11 15:23:21,425 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 1120 2024-07-11 15:23:21,425 - INFO - Annotation: interstitial pneumonia, Type: DiseaseOrPhenotypicFeature, Position: 1165 2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1268 2024-07-11 15:23:21,426 - INFO - Annotation: taxanes, Type: ChemicalEntity, Position: 1292 2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1304 2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1345 2024-07-11 15:23:21,426 - INFO - Annotation: pazopanib, Type: ChemicalEntity, Position: 1354 2024-07-11 15:23:21,426 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1371 2024-07-11 15:23:21,426 - INFO - Annotation: paclitaxel, Type: ChemicalEntity, Position: 1504 2024-07-11 15:23:21,426 - INFO - Annotation: metastasis, Type: DiseaseOrPhenotypicFeature, Position: 1587 2024-07-11 15:23:21,426 - INFO - Annotation: CAS, Type: DiseaseOrPhenotypicFeature, Position: 1634 2024-07-11 15:23:21,426 - INFO - Document ID: BC8_BioRED_Task1_Doc1488 2024-07-11 15:23:21,426 - INFO - Text Instance: Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing Gastroscopy: A Randomized Controlled Study. 2024-07-11 15:23:21,426 - INFO - Annotation: Remimazolam, Type: ChemicalEntity, Position: 0 2024-07-11 15:23:21,426 - INFO - Annotation: Sufentanil, Type: ChemicalEntity, Position: 44 2024-07-11 15:23:21,426 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 66 2024-07-11 15:23:21,426 - INFO - Annotation: Liver Cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 80 2024-07-11 15:23:21,426 - INFO - Text Instance: BACKGROUND This prospective, randomized, controlled study evaluated the efficacy and safety of remimazolam tosilate sedation with adjuvant sufentanil, relative to propofol, for Chinese patients with liver cirrhosis undergoing gastroscopy. MATERIAL AND METHODS Patients with liver cirrhosis (n=148) aged 18-65 years and undergoing gastroscopy were randomly and equally allocated to receive either 0.107 mg/kg remimazolam tosilate (remimazolam group) or 2 mg/kg propofol. Patients received intravenous sufentanil 0.15 mug/kg before the study drug. If necessary, an additional dose of propofol 20 mg was used and repeated. The primary outcome was the satisfaction rating (satisfactory, fair, or unsatisfactory) of the endoscopist with the sedation. Secondary outcomes were complications (respiratory depression, apnea, body movement, bradycardia, hypotension, nausea or vomiting, somnolence, dizziness, and fever) and patient satisfaction. RESULTS Compared with the propofol group, the remimazolam group required a longer time to sedation and a shorter time to emergence. The percentage of remimazolam sedations the endoscopist rated satisfactory (90.5%) was higher than that for propofol (77.0%; P=0.026). Patients given remimazolam experienced lower rates of respiratory depression, body movement, and hypotension (2.7, 8.1, 4.1%, respectively), than did the propofol group (17.6, 23.0, 14.9%; P=0.003, 0.013, 0.025). The 2 groups were comparable regarding the other secondary outcomes. CONCLUSIONS For Chinese patients with liver cirrhosis undergoing gastroscopy, remimazolam tosilate with adjuvant sufentanil provides a satisfactory level of sedation with a good safety profile. 2024-07-11 15:23:21,426 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 95 2024-07-11 15:23:21,426 - INFO - Annotation: sufentanil, Type: ChemicalEntity, Position: 139 2024-07-11 15:23:21,427 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 163 2024-07-11 15:23:21,427 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 185 2024-07-11 15:23:21,427 - INFO - Annotation: liver cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 199 2024-07-11 15:23:21,427 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 260 2024-07-11 15:23:21,427 - INFO - Annotation: liver cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 274 2024-07-11 15:23:21,427 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 408 2024-07-11 15:23:21,427 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 430 2024-07-11 15:23:21,427 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 460 2024-07-11 15:23:21,427 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 470 2024-07-11 15:23:21,427 - INFO - Annotation: sufentanil, Type: ChemicalEntity, Position: 500 2024-07-11 15:23:21,427 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 582 2024-07-11 15:23:21,427 - INFO - Annotation: respiratory depression, Type: DiseaseOrPhenotypicFeature, Position: 785 2024-07-11 15:23:21,427 - INFO - Annotation: apnea, Type: DiseaseOrPhenotypicFeature, Position: 809 2024-07-11 15:23:21,427 - INFO - Annotation: body movement, Type: DiseaseOrPhenotypicFeature, Position: 816 2024-07-11 15:23:21,427 - INFO - Annotation: bradycardia, Type: DiseaseOrPhenotypicFeature, Position: 831 2024-07-11 15:23:21,427 - INFO - Annotation: hypotension, Type: DiseaseOrPhenotypicFeature, Position: 844 2024-07-11 15:23:21,427 - INFO - Annotation: nausea or vomiting, Type: DiseaseOrPhenotypicFeature, Position: 857 2024-07-11 15:23:21,428 - INFO - Annotation: somnolence, Type: DiseaseOrPhenotypicFeature, Position: 877 2024-07-11 15:23:21,428 - INFO - Annotation: dizziness, Type: DiseaseOrPhenotypicFeature, Position: 889 2024-07-11 15:23:21,428 - INFO - Annotation: fever, Type: DiseaseOrPhenotypicFeature, Position: 904 2024-07-11 15:23:21,428 - INFO - Annotation: patient, Type: OrganismTaxon, Position: 915 2024-07-11 15:23:21,428 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 963 2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 983 2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 1087 2024-07-11 15:23:21,428 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 1177 2024-07-11 15:23:21,428 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 1204 2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 1219 2024-07-11 15:23:21,428 - INFO - Annotation: respiratory depression, Type: DiseaseOrPhenotypicFeature, Position: 1258 2024-07-11 15:23:21,428 - INFO - Annotation: body movement, Type: DiseaseOrPhenotypicFeature, Position: 1282 2024-07-11 15:23:21,428 - INFO - Annotation: hypotension, Type: DiseaseOrPhenotypicFeature, Position: 1301 2024-07-11 15:23:21,428 - INFO - Annotation: propofol, Type: ChemicalEntity, Position: 1358 2024-07-11 15:23:21,428 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1510 2024-07-11 15:23:21,428 - INFO - Annotation: liver cirrhosis, Type: DiseaseOrPhenotypicFeature, Position: 1524 2024-07-11 15:23:21,428 - INFO - Annotation: remimazolam, Type: ChemicalEntity, Position: 1564 2024-07-11 15:23:21,428 - INFO - Annotation: sufentanil, Type: ChemicalEntity, Position: 1599 2024-07-11 15:23:21,429 - INFO - Document ID: BC8_BioRED_Task1_Doc1489 2024-07-11 15:23:21,429 - INFO - Text Instance: Downregulation of Stearoyl-CoA Desaturase 1 (SCD-1) Promotes Resistance to Imatinib in Chronic Myeloid Leukemia. 2024-07-11 15:23:21,429 - INFO - Annotation: Stearoyl-CoA Desaturase 1, Type: GeneOrGeneProduct, Position: 18 2024-07-11 15:23:21,429 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 45 2024-07-11 15:23:21,429 - INFO - Annotation: Imatinib, Type: ChemicalEntity, Position: 75 2024-07-11 15:23:21,429 - INFO - Annotation: Chronic Myeloid Leukemia, Type: DiseaseOrPhenotypicFeature, Position: 87 2024-07-11 15:23:21,429 - INFO - Text Instance: Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease resulting in the fusion of BCR and ABL genes and characterized by the presence of the reciprocal translocation t(9;22)(q34;q11). BCR-ABL, a product of the BCR-ABL fusion gene, is a structurally active tyrosine kinase and plays an important role in CML disease pathogenesis. Imatinib mesylate (IMA) is a strong and selective BCR-ABL tyrosine kinase inhibitor. Although IMA therapy is an effective treatment, patients may develop resistance to IMA therapy over time. This study investigated the possible genetic resistance mechanisms in patients developing resistance to IMA. We did DNA sequencing in order to detect BCR-ABL mutations, which are responsible for IMA resistance. Moreover, we analyzed the mRNA expression levels of genes responsible for apoptosis, such as BCL-2, P53, and other genes (SCD-1, PTEN). In a group of CML patients resistant to IMA, when compared with IMA-sensitive CML patients, a decrease in SCD-1 gene expression levels and an increase in BCL-2 gene expression levels was observed. In this case, the SCD-1 gene was thought to act as a tumor suppressor. The present study aimed to investigate the mechanisms involved in IMA resistance in CML patients and determine new targets that can be beneficial in choosing the effective treatment. Finally, the study suggests that the SCD-1 and BCL-2 genes may be mechanisms responsible for resistance. 2024-07-11 15:23:21,469 - INFO - Annotation: Chronic myeloid leukemia, Type: DiseaseOrPhenotypicFeature, Position: 0 2024-07-11 15:23:21,469 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 26 2024-07-11 15:23:21,469 - INFO - Annotation: hematopoietic stem cell disease, Type: DiseaseOrPhenotypicFeature, Position: 46 2024-07-11 15:23:21,470 - INFO - Annotation: BCR, Type: GeneOrGeneProduct, Position: 105 2024-07-11 15:23:21,470 - INFO - Annotation: ABL, Type: GeneOrGeneProduct, Position: 113 2024-07-11 15:23:21,470 - INFO - Annotation: BCR-ABL, Type: GeneOrGeneProduct, Position: 207 2024-07-11 15:23:21,470 - INFO - Annotation: BCR-ABL, Type: GeneOrGeneProduct, Position: 233 2024-07-11 15:23:21,470 - INFO - Annotation: tyrosine kinase, Type: GeneOrGeneProduct, Position: 279 2024-07-11 15:23:21,470 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 326 2024-07-11 15:23:21,470 - INFO - Annotation: Imatinib mesylate, Type: ChemicalEntity, Position: 352 2024-07-11 15:23:21,470 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 371 2024-07-11 15:23:21,470 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 446 2024-07-11 15:23:21,470 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 485 2024-07-11 15:23:21,470 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 520 2024-07-11 15:23:21,470 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 613 2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 647 2024-07-11 15:23:21,471 - INFO - Annotation: BCR-ABL, Type: GeneOrGeneProduct, Position: 693 2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 738 2024-07-11 15:23:21,471 - INFO - Annotation: BCL-2, Type: GeneOrGeneProduct, Position: 847 2024-07-11 15:23:21,471 - INFO - Annotation: P53, Type: GeneOrGeneProduct, Position: 854 2024-07-11 15:23:21,471 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 876 2024-07-11 15:23:21,471 - INFO - Annotation: PTEN, Type: GeneOrGeneProduct, Position: 883 2024-07-11 15:23:21,471 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 904 2024-07-11 15:23:21,471 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 908 2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 930 2024-07-11 15:23:21,471 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 954 2024-07-11 15:23:21,472 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 968 2024-07-11 15:23:21,472 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 972 2024-07-11 15:23:21,472 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 996 2024-07-11 15:23:21,472 - INFO - Annotation: BCL-2, Type: GeneOrGeneProduct, Position: 1044 2024-07-11 15:23:21,472 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 1105 2024-07-11 15:23:21,472 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 1140 2024-07-11 15:23:21,472 - INFO - Annotation: IMA, Type: ChemicalEntity, Position: 1224 2024-07-11 15:23:21,472 - INFO - Annotation: CML, Type: DiseaseOrPhenotypicFeature, Position: 1242 2024-07-11 15:23:21,472 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1246 2024-07-11 15:23:21,472 - INFO - Annotation: SCD-1, Type: GeneOrGeneProduct, Position: 1378 2024-07-11 15:23:21,472 - INFO - Annotation: BCL-2, Type: GeneOrGeneProduct, Position: 1388 2024-07-11 15:23:21,472 - INFO - Document ID: BC8_BioRED_Task1_Doc1490 2024-07-11 15:23:21,473 - INFO - Text Instance: 12-O-tetradecanoylphorbol-13-acetate Reduces Activation of Hepatic Stellate Cells by Inhibiting the Hippo Pathway Transcriptional Coactivator YAP. 2024-07-11 15:23:21,473 - INFO - Annotation: 12-O-tetradecanoylphorbol-13-acetate, Type: ChemicalEntity, Position: 0 2024-07-11 15:23:21,473 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 142 2024-07-11 15:23:21,473 - INFO - Text Instance: Although protein kinase C (PKC) regulates various biological activities, including cell proliferation, differentiation, migration, tissue remodeling, gene expression, and cell death, the antifibrotic effect of PKC in myofibroblasts is not fully understood. We investigated whether 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, reduced the activation of hepatic stellate cells (HSCs) and explored the involvement of the Hippo pathway transcriptional coactivator YAP. We analyzed the effect of TPA on the proliferation and expression of alpha-smooth muscle actin (SMA) in the LX-2 HSC line. We also analyzed the phosphorylation of the Hippo pathway molecules YAP and LATS1 and investigated YAP nuclear translocation. We examined whether Go 6983, a pan-PKC inhibitor, restored the TPA-inhibited activities of HSCs. Administration of TPA decreased the growth rate of LX-2 cells and inhibited the expression of alpha-SMA and collagen type I alpha 1 (COL1A1). In addition, TPA induced phosphorylation of PKCdelta, LATS1, and YAP and inhibited the nuclear translocation of YAP compared with the control. These TPA-induced phenomena were mostly ameliorated by Go 6983. Our results indicate that PKCdelta exerts an antifibrotic effect by inhibiting the Hippo pathway in HSCs. Therefore, PKCdelta and YAP can be used as therapeutic targets for the treatment of fibrotic diseases. 2024-07-11 15:23:21,473 - INFO - Annotation: protein kinase C, Type: GeneOrGeneProduct, Position: 9 2024-07-11 15:23:21,473 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 27 2024-07-11 15:23:21,473 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 210 2024-07-11 15:23:21,473 - INFO - Annotation: 12-O-tetradecanoylphorbol-13-acetate, Type: ChemicalEntity, Position: 281 2024-07-11 15:23:21,473 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 319 2024-07-11 15:23:21,473 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 327 2024-07-11 15:23:21,473 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 476 2024-07-11 15:23:21,474 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 507 2024-07-11 15:23:21,474 - INFO - Annotation: LX-2, Type: CellLine, Position: 589 2024-07-11 15:23:21,474 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 672 2024-07-11 15:23:21,474 - INFO - Annotation: LATS1, Type: GeneOrGeneProduct, Position: 680 2024-07-11 15:23:21,474 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 703 2024-07-11 15:23:21,474 - INFO - Annotation: Go 6983, Type: ChemicalEntity, Position: 750 2024-07-11 15:23:21,474 - INFO - Annotation: PKC, Type: GeneOrGeneProduct, Position: 765 2024-07-11 15:23:21,474 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 793 2024-07-11 15:23:21,474 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 845 2024-07-11 15:23:21,474 - INFO - Annotation: LX-2, Type: CellLine, Position: 878 2024-07-11 15:23:21,474 - INFO - Annotation: alpha-SMA, Type: GeneOrGeneProduct, Position: 921 2024-07-11 15:23:21,474 - INFO - Annotation: collagen type I alpha 1, Type: GeneOrGeneProduct, Position: 935 2024-07-11 15:23:21,475 - INFO - Annotation: COL1A1, Type: GeneOrGeneProduct, Position: 960 2024-07-11 15:23:21,475 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 982 2024-07-11 15:23:21,475 - INFO - Annotation: PKCdelta, Type: GeneOrGeneProduct, Position: 1013 2024-07-11 15:23:21,475 - INFO - Annotation: LATS1, Type: GeneOrGeneProduct, Position: 1023 2024-07-11 15:23:21,475 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 1034 2024-07-11 15:23:21,475 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 1081 2024-07-11 15:23:21,475 - INFO - Annotation: TPA, Type: ChemicalEntity, Position: 1118 2024-07-11 15:23:21,475 - INFO - Annotation: Go 6983, Type: ChemicalEntity, Position: 1167 2024-07-11 15:23:21,475 - INFO - Annotation: PKCdelta, Type: GeneOrGeneProduct, Position: 1202 2024-07-11 15:23:21,475 - INFO - Annotation: PKCdelta, Type: GeneOrGeneProduct, Position: 1293 2024-07-11 15:23:21,475 - INFO - Annotation: YAP, Type: GeneOrGeneProduct, Position: 1306 2024-07-11 15:23:21,475 - INFO - Annotation: fibrotic diseases, Type: DiseaseOrPhenotypicFeature, Position: 1366 2024-07-11 15:23:21,476 - INFO - Document ID: BC8_BioRED_Task1_Doc1491 2024-07-11 15:23:21,476 - INFO - Text Instance: Effect of Concurrent Use of Memantine on the Efficacy of Masupirdine (SUVN-502): A Post Hoc Analysis of a Phase 2 Randomized Placebo-Controlled Study. 2024-07-11 15:23:21,476 - INFO - Annotation: Memantine, Type: ChemicalEntity, Position: 28 2024-07-11 15:23:21,476 - INFO - Annotation: Masupirdine, Type: ChemicalEntity, Position: 57 2024-07-11 15:23:21,476 - INFO - Annotation: SUVN-502, Type: ChemicalEntity, Position: 70 2024-07-11 15:23:21,476 - INFO - Text Instance: INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT6) receptors, which are exclusively localized to the central nervous system, is reported to play an important role in learning and memory. Masupirdine is a potent and selective 5-HT6 receptor antagonist with pro-cognitive properties in animal models of cognition. METHODS: The efficacy and safety of masupirdine were evaluated in patients with moderate AD concurrently treated with donepezil and memantine. A total of 564 patients were randomized in a 1:1:1 ratio. The study consisted of a 26-week double-blind treatment period. The primary efficacy outcome was the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). In exploratory post hoc analyses, patients were subdivided based on the use of memantine dosage forms and memantine plasma concentrations, to evaluate the impact of memantine on the efficacy of masupirdine. RESULTS: In an exploratory post hoc analysis, less worsening in cognition (ADAS-Cog 11 scores) was observed with masupirdine treatment as compared with placebo in patients whose trough memantine plasma concentrations were <= 100 ng/mL. CONCLUSIONS: Although prespecified study endpoints of the phase 2 study were not met, these exploratory post hoc subgroup observations are hypothesis-generating and suggest that the efficacy of masupirdine was adversely affected by concurrent therapy with memantine. Further assessment of masupirdine to determine its potential role as a treatment option for cognitive deficits associated with AD is warranted. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02580305). 2024-07-11 15:23:21,476 - INFO - Annotation: Alzheimer's disease, Type: DiseaseOrPhenotypicFeature, Position: 14 2024-07-11 15:23:21,476 - INFO - Annotation: AD, Type: DiseaseOrPhenotypicFeature, Position: 35 2024-07-11 15:23:21,476 - INFO - Annotation: neurodegenerative disorder, Type: DiseaseOrPhenotypicFeature, Position: 44 2024-07-11 15:23:21,476 - INFO - Annotation: Masupirdine, Type: ChemicalEntity, Position: 345 2024-07-11 15:23:21,476 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 506 2024-07-11 15:23:21,476 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 536 2024-07-11 15:23:21,476 - INFO - Annotation: AD, Type: DiseaseOrPhenotypicFeature, Position: 559 2024-07-11 15:23:21,476 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 602 2024-07-11 15:23:21,476 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 628 2024-07-11 15:23:21,477 - INFO - Annotation: Alzheimer's Disease, Type: DiseaseOrPhenotypicFeature, Position: 806 2024-07-11 15:23:21,477 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 986 2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1031 2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1058 2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1117 2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1146 2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1272 2024-07-11 15:23:21,477 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1322 2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1344 2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1589 2024-07-11 15:23:21,477 - INFO - Annotation: memantine, Type: ChemicalEntity, Position: 1651 2024-07-11 15:23:21,477 - INFO - Annotation: masupirdine, Type: ChemicalEntity, Position: 1684 2024-07-11 15:23:21,477 - INFO - Annotation: cognitive deficits, Type: DiseaseOrPhenotypicFeature, Position: 1754 2024-07-11 15:23:21,477 - INFO - Annotation: AD, Type: DiseaseOrPhenotypicFeature, Position: 1789 2024-07-11 15:23:21,477 - INFO - Document ID: BC8_BioRED_Task1_Doc1492 2024-07-11 15:23:21,478 - INFO - Text Instance: ACE2 internalization induced by a SARS-CoV-2 recombinant protein is modulated by angiotensin II type 1 and bradykinin 2 receptors. 2024-07-11 15:23:21,478 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 0 2024-07-11 15:23:21,478 - INFO - Annotation: SARS-CoV-2, Type: OrganismTaxon, Position: 34 2024-07-11 15:23:21,478 - INFO - Annotation: angiotensin II type 1 and bradykinin 2 receptors, Type: GeneOrGeneProduct, Position: 81 2024-07-11 15:23:21,478 - INFO - Text Instance: AIMS: Angiotensin-converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system (RAS) recently identified as the membrane receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we aim to study whether two receptors from RAS, the angiotensin receptor type 1 (AT1R) and the bradykinin 2 receptor (B2R) modulate ACE2 internalization induced by a recombinant receptor binding domain (RBD) of SARS-CoV-2 spike protein. Also, we investigated the impact of ACE2 coexpression on AT1R and B2R functionality. MATERIALS AND METHODS: To study ACE2 internalization, we assessed the distribution of green fluorescent protein (GFP) signal in HEK293T cells coexpressing GFP-tagged ACE2 and AT1R, or B2R, or AT1R plus B2R in presence of RBD alone or in combination with AT1R or B2R ligands. To estimate ACE2 internalization, we classified GFP signal distribution as plasma membrane uniform GFP (PMU-GFP), plasma membrane clustered GFP (PMC-GFP) or internalized GFP and calculated its relative frequency. Additionally, we investigated the effect of ACE2 coexpression on AT1R and B2R inhibitory action on voltage-gated calcium channels (CaV2.2) currents by patch-clamp technique. KEY FINDINGS: RBD induced ACE2-GFP internalization in a time-dependent manner. RBD-induced ACE2-GFP internalization was increased by angiotensin II and reduced by telmisartan in cells coexpressing AT1R. RBD-induced ACE2-GFP internalization was strongly inhibited by B2R co-expression. This effect was mildly modified by bradykinin and rescued by angiotensin II in presence of AT1R. ACE2 coexpression impacted on B2R- and AT1R-mediated inhibition of CaV2.2 currents. SIGNIFICANCE: Our work contributes to understand the role of RAS modulators in the susceptibility to SARS-CoV-2 infection and severity of COVID-19. 2024-07-11 15:23:21,478 - INFO - Annotation: Angiotensin-converting enzyme 2, Type: GeneOrGeneProduct, Position: 6 2024-07-11 15:23:21,478 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 39 2024-07-11 15:23:21,478 - INFO - Annotation: renin, Type: GeneOrGeneProduct, Position: 71 2024-07-11 15:23:21,478 - INFO - Annotation: angiotensin, Type: GeneOrGeneProduct, Position: 77 2024-07-11 15:23:21,478 - INFO - Annotation: severe acute respiratory syndrome coronavirus 2, Type: OrganismTaxon, Position: 155 2024-07-11 15:23:21,478 - INFO - Annotation: SARS-CoV-2, Type: OrganismTaxon, Position: 204 2024-07-11 15:23:21,478 - INFO - Annotation: angiotensin receptor type 1, Type: GeneOrGeneProduct, Position: 274 2024-07-11 15:23:21,478 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 303 2024-07-11 15:23:21,478 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 340 2024-07-11 15:23:21,478 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 354 2024-07-11 15:23:21,478 - INFO - Annotation: SARS-CoV-2, Type: OrganismTaxon, Position: 433 2024-07-11 15:23:21,479 - INFO - Annotation: spike, Type: GeneOrGeneProduct, Position: 444 2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 495 2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 516 2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 525 2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 576 2024-07-11 15:23:21,479 - INFO - Annotation: HEK293T, Type: CellLine, Position: 672 2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 710 2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 719 2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 728 2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 736 2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 746 2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 798 2024-07-11 15:23:21,479 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 806 2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 831 2024-07-11 15:23:21,479 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1076 2024-07-11 15:23:21,479 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 1097 2024-07-11 15:23:21,480 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 1106 2024-07-11 15:23:21,480 - INFO - Annotation: calcium, Type: ChemicalEntity, Position: 1145 2024-07-11 15:23:21,480 - INFO - Annotation: CaV2.2, Type: GeneOrGeneProduct, Position: 1163 2024-07-11 15:23:21,480 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1232 2024-07-11 15:23:21,480 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1297 2024-07-11 15:23:21,480 - INFO - Annotation: angiotensin II, Type: GeneOrGeneProduct, Position: 1339 2024-07-11 15:23:21,480 - INFO - Annotation: AT1R., Type: GeneOrGeneProduct, Position: 1403 2024-07-11 15:23:21,480 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1421 2024-07-11 15:23:21,480 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 1472 2024-07-11 15:23:21,480 - INFO - Annotation: bradykinin, Type: GeneOrGeneProduct, Position: 1526 2024-07-11 15:23:21,480 - INFO - Annotation: angiotensin II, Type: GeneOrGeneProduct, Position: 1552 2024-07-11 15:23:21,482 - INFO - Annotation: AT1R., Type: GeneOrGeneProduct, Position: 1582 2024-07-11 15:23:21,482 - INFO - Annotation: ACE2, Type: GeneOrGeneProduct, Position: 1588 2024-07-11 15:23:21,482 - INFO - Annotation: B2R, Type: GeneOrGeneProduct, Position: 1618 2024-07-11 15:23:21,482 - INFO - Annotation: AT1R, Type: GeneOrGeneProduct, Position: 1627 2024-07-11 15:23:21,482 - INFO - Annotation: CaV2.2, Type: GeneOrGeneProduct, Position: 1655 2024-07-11 15:23:21,482 - INFO - Annotation: SARS-CoV-2 infection, Type: DiseaseOrPhenotypicFeature, Position: 1773 2024-07-11 15:23:21,482 - INFO - Annotation: COVID-19, Type: DiseaseOrPhenotypicFeature, Position: 1810 2024-07-11 15:23:21,482 - INFO - Document ID: BC8_BioRED_Task1_Doc1493 2024-07-11 15:23:21,482 - INFO - Text Instance: Ultrasound and laser-promoted dual-gas nano-generator for combined photothermal and immune tumor therapy. 2024-07-11 15:23:21,482 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 91 2024-07-11 15:23:21,482 - INFO - Text Instance: The combination of photothermal therapy (PTT) and immune tumor therapy has emerged as a promising avenue for cancer treatment. However, the insufficient immune response caused by inefficient immunogenic cell death (ICD) inducers and thermal resistance, immunosuppression, and immune escape resulting from the hypoxic microenvironment of solid tumors severely limit its efficacy. Herein, we report an ultrasound and laser-promoted dual-gas nano-generator (calcium carbonate-polydopamine-manganese oxide nanoparticles, CPM NPs) for enhanced photothermal/immune tumor therapy through reprogramming tumor hypoxic microenvironment. In this system, CPM NPs undergo reactive decomposition in a moderately acidic tumor, resulting in the generation of calcium, manganese ions, carbon dioxide (CO2), and oxygen (O2). Calcium and manganese ions act as adjuvants that trigger an immune response. The cancer cell membrane rupture caused by sudden burst of bubbles (CO2 and O2) under ultrasound stimulation and the photothermal properties of PDA also contributed to the ICD effect. The generation of O2 alleviates tumor hypoxia and thus reduces hypoxia-induced heat resistance and immunosuppressive effects, thereby improving the therapeutic efficacy of combination PTT and immune therapy. The present study provides a novel approach for the fabrication of a safe and effective tumor treatment platform for future clinical applications. 2024-07-11 15:23:21,482 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 57 2024-07-11 15:23:21,482 - INFO - Annotation: cancer, Type: DiseaseOrPhenotypicFeature, Position: 109 2024-07-11 15:23:21,483 - INFO - Annotation: hypoxic, Type: DiseaseOrPhenotypicFeature, Position: 309 2024-07-11 15:23:21,483 - INFO - Annotation: solid tumors, Type: DiseaseOrPhenotypicFeature, Position: 337 2024-07-11 15:23:21,483 - INFO - Annotation: calcium carbonate, Type: ChemicalEntity, Position: 455 2024-07-11 15:23:21,483 - INFO - Annotation: polydopamine, Type: ChemicalEntity, Position: 473 2024-07-11 15:23:21,483 - INFO - Annotation: manganese oxide, Type: ChemicalEntity, Position: 486 2024-07-11 15:23:21,483 - INFO - Annotation: CPM, Type: ChemicalEntity, Position: 517 2024-07-11 15:23:21,483 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 559 2024-07-11 15:23:21,483 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 595 2024-07-11 15:23:21,483 - INFO - Annotation: hypoxic, Type: DiseaseOrPhenotypicFeature, Position: 601 2024-07-11 15:23:21,483 - INFO - Annotation: CPM, Type: ChemicalEntity, Position: 643 2024-07-11 15:23:21,483 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 705 2024-07-11 15:23:21,483 - INFO - Annotation: calcium, Type: ChemicalEntity, Position: 743 2024-07-11 15:23:21,483 - INFO - Annotation: manganese, Type: ChemicalEntity, Position: 752 2024-07-11 15:23:21,483 - INFO - Annotation: carbon dioxide, Type: ChemicalEntity, Position: 768 2024-07-11 15:23:21,483 - INFO - Annotation: CO2, Type: ChemicalEntity, Position: 784 2024-07-11 15:23:21,484 - INFO - Annotation: oxygen, Type: ChemicalEntity, Position: 794 2024-07-11 15:23:21,484 - INFO - Annotation: O2, Type: ChemicalEntity, Position: 802 2024-07-11 15:23:21,484 - INFO - Annotation: Calcium, Type: ChemicalEntity, Position: 807 2024-07-11 15:23:21,484 - INFO - Annotation: manganese, Type: ChemicalEntity, Position: 819 2024-07-11 15:23:21,484 - INFO - Annotation: cancer, Type: DiseaseOrPhenotypicFeature, Position: 888 2024-07-11 15:23:21,484 - INFO - Annotation: CO2, Type: ChemicalEntity, Position: 952 2024-07-11 15:23:21,484 - INFO - Annotation: O2, Type: ChemicalEntity, Position: 960 2024-07-11 15:23:21,484 - INFO - Annotation: O2, Type: ChemicalEntity, Position: 1086 2024-07-11 15:23:21,484 - INFO - Annotation: tumor hypoxia, Type: DiseaseOrPhenotypicFeature, Position: 1100 2024-07-11 15:23:21,484 - INFO - Annotation: hypoxia, Type: DiseaseOrPhenotypicFeature, Position: 1131 2024-07-11 15:23:21,484 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 1364 2024-07-11 15:23:21,484 - INFO - Document ID: BC8_BioRED_Task1_Doc1494 2024-07-11 15:23:21,484 - INFO - Text Instance: RanBP9 controls the oligomeric state of CTLH complex assemblies. 2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 0 2024-07-11 15:23:21,485 - INFO - Text Instance: The CTLH complex is a multisubunit RING E3 ligase with poorly defined substrate specificity and flexible subunit composition. Two key subunits, Muskelin and Wdr26, specify two alternative CTLH complexes that differ in quaternary structure, thereby allowing the E3 ligase to presumably target different substrates. With the aid of different biophysical and biochemical techniques we characterized CTLH complex assembly pathways, focusing not only on Wdr26 and Muskelin, but also on the RanBP9, Twa1 and Armc8beta subunits, which are critical to establish the scaffold of this E3 ligase. We demonstrate that the ability of Muskelin to tetramerize and the assembly of Wdr26 into dimers define mutually exclusive oligomerization modules that compete with nanomolar affinity for RanBP9 binding. The remaining scaffolding subunits, Armc8beta and Twa1, strongly interact with each other and with RanBP9, again with nanomolar affinity. Our data demonstrate that RanBP9 organizes subunit assembly and prevents higher order oligomerization of dimeric Wdr26 and the Armc8beta-Twa1 heterodimer through its tight binding. Combined, our studies define alternative assembly pathways of the CTLH complex and elucidate the role of RanBP9 in governing differential oligomeric assemblies, thereby, advancing our mechanistic understanding of CTLH complex architectures. 2024-07-11 15:23:21,485 - INFO - Annotation: Muskelin, Type: GeneOrGeneProduct, Position: 144 2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 157 2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 449 2024-07-11 15:23:21,485 - INFO - Annotation: Muskelin, Type: GeneOrGeneProduct, Position: 459 2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 485 2024-07-11 15:23:21,485 - INFO - Annotation: Twa1, Type: GeneOrGeneProduct, Position: 493 2024-07-11 15:23:21,485 - INFO - Annotation: Muskelin, Type: GeneOrGeneProduct, Position: 621 2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 665 2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 774 2024-07-11 15:23:21,485 - INFO - Annotation: Twa1, Type: GeneOrGeneProduct, Position: 840 2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 889 2024-07-11 15:23:21,485 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 954 2024-07-11 15:23:21,485 - INFO - Annotation: Wdr26, Type: GeneOrGeneProduct, Position: 1041 2024-07-11 15:23:21,485 - INFO - Annotation: Twa1, Type: GeneOrGeneProduct, Position: 1065 2024-07-11 15:23:21,486 - INFO - Annotation: RanBP9, Type: GeneOrGeneProduct, Position: 1214 2024-07-11 15:23:21,486 - INFO - Document ID: BC8_BioRED_Task1_Doc1495 2024-07-11 15:23:21,486 - INFO - Text Instance: The Comparison of the Influence of Bisphenol A (BPA) and Its Analogue Bisphenol S (BPS) on the Enteric Nervous System of the Distal Colon in Mice. 2024-07-11 15:23:21,486 - INFO - Annotation: Bisphenol A, Type: ChemicalEntity, Position: 35 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 48 2024-07-11 15:23:21,486 - INFO - Annotation: Bisphenol S, Type: ChemicalEntity, Position: 70 2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 83 2024-07-11 15:23:21,486 - INFO - Annotation: Mice, Type: OrganismTaxon, Position: 141 2024-07-11 15:23:21,486 - INFO - Text Instance: Bisphenol A (BPA), commonly used as a plasticizer in various branches of industry has a strong negative effect on living organisms. Therefore, more and more often it is replaced in production of plastics by other substances. One of them is bisphenol S (BPS). This study for the first time compares the impact of BPA and BPS on the enteric neurons using double immunofluorescence technique. It has been shown that both BPA and BPS affect the number of enteric neurons containing substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), neuronal isoform of nitric oxide synthase (nNOS-a marker of nitrergic neurons) and/or vesicular acetylcholine transporter (VAChT- a marker of cholinergic neurons). The changes noted under the impact of both bisphenols are similar and consisted of an increase in the number of enteric neurons immunoreactive to all neuronal factors studied. The impact of BPS on some populations of neurons was stronger than that noted under the influence of BPA. The obtained results clearly show that BPS (similarly to BPA) administered for long time is not neutral for the enteric neurons even in relatively low doses and may be more potent than BPA for certain neuronal populations. 2024-07-11 15:23:21,486 - INFO - Annotation: Bisphenol A, Type: ChemicalEntity, Position: 0 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 13 2024-07-11 15:23:21,486 - INFO - Annotation: bisphenol S, Type: ChemicalEntity, Position: 240 2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 253 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 312 2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 320 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 418 2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 426 2024-07-11 15:23:21,486 - INFO - Annotation: substance P, Type: GeneOrGeneProduct, Position: 478 2024-07-11 15:23:21,486 - INFO - Annotation: galanin, Type: GeneOrGeneProduct, Position: 496 2024-07-11 15:23:21,486 - INFO - Annotation: GAL, Type: GeneOrGeneProduct, Position: 505 2024-07-11 15:23:21,486 - INFO - Annotation: vasoactive intestinal polypeptide, Type: GeneOrGeneProduct, Position: 511 2024-07-11 15:23:21,486 - INFO - Annotation: VIP, Type: GeneOrGeneProduct, Position: 546 2024-07-11 15:23:21,486 - INFO - Annotation: nNOS, Type: GeneOrGeneProduct, Position: 595 2024-07-11 15:23:21,486 - INFO - Annotation: vesicular acetylcholine transporter, Type: GeneOrGeneProduct, Position: 638 2024-07-11 15:23:21,486 - INFO - Annotation: VAChT, Type: GeneOrGeneProduct, Position: 675 2024-07-11 15:23:21,486 - INFO - Annotation: bisphenols, Type: ChemicalEntity, Position: 759 2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 906 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 993 2024-07-11 15:23:21,486 - INFO - Annotation: BPS, Type: ChemicalEntity, Position: 1037 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 1055 2024-07-11 15:23:21,486 - INFO - Annotation: BPA, Type: ChemicalEntity, Position: 1183 2024-07-11 15:23:21,487 - INFO - Document ID: BC8_BioRED_Task1_Doc1496 2024-07-11 15:23:21,487 - INFO - Text Instance: PTPRM methylation induced by FN1 promotes the development of glioblastoma by activating STAT3 signalling. 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 0 2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 29 2024-07-11 15:23:21,487 - INFO - Annotation: glioblastoma, Type: DiseaseOrPhenotypicFeature, Position: 61 2024-07-11 15:23:21,487 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 88 2024-07-11 15:23:21,487 - INFO - Text Instance: CONTEXT: The phosphorylation of signal transducer and activator of transcription protein 3 (STAT3) is up-regulated in glioblastoma (GBM) cells and is regulated by protein tyrosine phosphatase receptor type M (PTPRM). Fibronectin-1 (FN1) is also reported to be up-regulated in GBM. OBJECTIVE: We explored the role of FN1-induced PTPRM methylation in GBM. MATERIALS AND METHODS: The lentivirus particles of oe-PTPRM, sh-PTPRM, oe-FN1, sh-FN1, or their negative controls (NSCs) were transfected into GBM cells with or without stattic (0.5 muM, 24 h) or 5-aza (1 muM, 0, 2, 4 h) treatments. Methylation-specific PCR was performed to detect PTPRM methylation levels. RESULTS: PTPRM was down-regulated (0.373 +- 0.124- and 0.455 +- 0.109-fold), FN1 and p-STAT3 were up-regulated (p < 0.001) in A172 and U87 MG cells as compared to NSCs. Overexpressing PTPRM inhibited STAT3 phosphorylation. Interfering with PTPRM increased colony numbers in A172 and U-87 MG cells (2.253 +- 0.111- and 2.043 +- 0.19-fold), and stattic reduced them. Cell viability was reduced after treatment with 5-aza in A172 and U-87 MG cells (p < 0.05). P-STAT3 was down-regulated after 5-aza treatment. Overexpressing FN1 decreased PTPRM levels (p < 0.001), knockdown of FN1 decreased PTPRM methylation and inhibited STAT3 phosphorylation. Overexpressing FN1 increased cell viability (1.497 +- 0.114- and 1.460 +- 0.151-fold), and stattic or 5-aza reversed such effects (p < 0.05). DISCUSSION AND CONCLUSIONS: The up-regulation of FN1 reduced PTPRM by increasing its methylation, resulting in an increase of STAT3 phosphorylation and promoting GBM cell proliferation. Interfering with FN1 may be a potential therapeutic target for GBM. 2024-07-11 15:23:21,487 - INFO - Annotation: signal transducer and activator of transcription protein 3, Type: GeneOrGeneProduct, Position: 32 2024-07-11 15:23:21,487 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 92 2024-07-11 15:23:21,487 - INFO - Annotation: glioblastoma, Type: DiseaseOrPhenotypicFeature, Position: 118 2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 132 2024-07-11 15:23:21,487 - INFO - Annotation: protein tyrosine phosphatase receptor type M, Type: GeneOrGeneProduct, Position: 163 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 209 2024-07-11 15:23:21,487 - INFO - Annotation: Fibronectin-1, Type: GeneOrGeneProduct, Position: 217 2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 232 2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 276 2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 316 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 328 2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 349 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 408 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 418 2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 428 2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 436 2024-07-11 15:23:21,487 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 497 2024-07-11 15:23:21,487 - INFO - Annotation: stattic, Type: ChemicalEntity, Position: 523 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 636 2024-07-11 15:23:21,487 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 671 2024-07-11 15:23:21,487 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 739 2024-07-11 15:23:21,487 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 749 2024-07-11 15:23:21,487 - INFO - Annotation: A172, Type: CellLine, Position: 788 2024-07-11 15:23:21,487 - INFO - Annotation: U87 MG, Type: CellLine, Position: 797 2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 846 2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 862 2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 902 2024-07-11 15:23:21,488 - INFO - Annotation: A172, Type: CellLine, Position: 936 2024-07-11 15:23:21,488 - INFO - Annotation: U-87 MG, Type: CellLine, Position: 945 2024-07-11 15:23:21,488 - INFO - Annotation: stattic, Type: ChemicalEntity, Position: 1005 2024-07-11 15:23:21,488 - INFO - Annotation: A172, Type: CellLine, Position: 1084 2024-07-11 15:23:21,488 - INFO - Annotation: U-87 MG, Type: CellLine, Position: 1093 2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 1121 2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1184 2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 1198 2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1237 2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 1251 2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 1283 2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1321 2024-07-11 15:23:21,488 - INFO - Annotation: stattic, Type: ChemicalEntity, Position: 1397 2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1497 2024-07-11 15:23:21,488 - INFO - Annotation: PTPRM, Type: GeneOrGeneProduct, Position: 1509 2024-07-11 15:23:21,488 - INFO - Annotation: STAT3, Type: GeneOrGeneProduct, Position: 1574 2024-07-11 15:23:21,488 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 1610 2024-07-11 15:23:21,488 - INFO - Annotation: FN1, Type: GeneOrGeneProduct, Position: 1651 2024-07-11 15:23:21,488 - INFO - Annotation: GBM, Type: DiseaseOrPhenotypicFeature, Position: 1697 2024-07-11 15:23:21,488 - INFO - Document ID: BC8_BioRED_Task1_Doc1497 2024-07-11 15:23:21,488 - INFO - Text Instance: Screening and verification of genes related to polycystic ovary syndrome. 2024-07-11 15:23:21,488 - INFO - Annotation: polycystic ovary syndrome, Type: DiseaseOrPhenotypicFeature, Position: 47 2024-07-11 15:23:21,532 - INFO - Text Instance: OBJECTIVE: To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). METHODS: By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. RESULTS: From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. CONCLUSIONS: ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy. 2024-07-11 15:23:21,532 - INFO - Annotation: polycystic ovary syndrome, Type: DiseaseOrPhenotypicFeature, Position: 75 2024-07-11 15:23:21,532 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 102 2024-07-11 15:23:21,533 - INFO - Annotation: women, Type: OrganismTaxon, Position: 287 2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 298 2024-07-11 15:23:21,533 - INFO - Annotation: women, Type: OrganismTaxon, Position: 433 2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 444 2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 596 2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 605 2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 677 2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 689 2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 698 2024-07-11 15:23:21,533 - INFO - Annotation: women, Type: OrganismTaxon, Position: 742 2024-07-11 15:23:21,533 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 753 2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 792 2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 801 2024-07-11 15:23:21,533 - INFO - Annotation: testosterone, Type: ChemicalEntity, Position: 838 2024-07-11 15:23:21,533 - INFO - Annotation: cholesterol, Type: ChemicalEntity, Position: 852 2024-07-11 15:23:21,533 - INFO - Annotation: triglycerides, Type: ChemicalEntity, Position: 869 2024-07-11 15:23:21,533 - INFO - Annotation: ORM1, Type: GeneOrGeneProduct, Position: 884 2024-07-11 15:23:21,533 - INFO - Annotation: ORM2, Type: GeneOrGeneProduct, Position: 965 2024-07-11 15:23:21,534 - INFO - Annotation: ORM, Type: GeneOrGeneProduct, Position: 1025 2024-07-11 15:23:21,534 - INFO - Annotation: PCOS, Type: DiseaseOrPhenotypicFeature, Position: 1080 2024-07-11 15:23:21,534 - INFO - Document ID: BC8_BioRED_Task1_Doc1498 2024-07-11 15:23:21,534 - INFO - Text Instance: Inhibitors of EYA3 Protein in Ewing Sarcoma. 2024-07-11 15:23:21,534 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 14 2024-07-11 15:23:21,534 - INFO - Annotation: Ewing Sarcoma, Type: DiseaseOrPhenotypicFeature, Position: 30 2024-07-11 15:23:21,534 - INFO - Text Instance: OBJECTIVE: Among sarcomas, Ewing sarcoma (EWS) is characterized as a highly malignant type of bone tumor caused by the fusion of EWS RNA Binding Protein-1 (EWSR1)/ Friend leukemia integration 1 (FLI1) genes. The product of fusion gene gives rise to EWSR1/FLI1 which activates the activity of Eyes absent homolog 3 (EYA3) which causes tumor growth and angiogenesis. EYA3 is now considered as a therapeutic drug target for EWS . The study was designed to gather potential inhibitors for the EYA3 target using medicinal compounds. METHODS: In this study, we have obtained a list of medicinal compounds from the NuBBE database and downloaded their structural information. Then insilico screening analysis of >2,000 medicinal compounds was performed with PyRX virtual drug screening software to discover potential inhibitors for the treatment of EWS. RESULTS: Our investigation revealed that Sorbifolin and 1,7-Dihydroxy-3-methylanthracene-9.10-dione show interactive affinity for EYA3 active residues. Moreover, these compounds have adequate toxicity, can induce cytotoxicity in EWS cells, and are capable of regulating the expression of genes activated by EWSR1/FLI1. CONCLUSION: Our study concluded that Sorbifolin and 1,7-Dihydroxy-3-methylanthracene-9.10-dione are promising drug candidates for the treatment of EWS and should be further subjected to invitro testing. 2024-07-11 15:23:21,534 - INFO - Annotation: sarcomas, Type: DiseaseOrPhenotypicFeature, Position: 17 2024-07-11 15:23:21,534 - INFO - Annotation: Ewing sarcoma, Type: DiseaseOrPhenotypicFeature, Position: 27 2024-07-11 15:23:21,534 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 42 2024-07-11 15:23:21,534 - INFO - Annotation: bone tumor, Type: DiseaseOrPhenotypicFeature, Position: 94 2024-07-11 15:23:21,534 - INFO - Annotation: EWS RNA Binding Protein-1, Type: GeneOrGeneProduct, Position: 129 2024-07-11 15:23:21,534 - INFO - Annotation: EWSR1, Type: GeneOrGeneProduct, Position: 156 2024-07-11 15:23:21,534 - INFO - Annotation: Friend leukemia integration 1, Type: GeneOrGeneProduct, Position: 164 2024-07-11 15:23:21,534 - INFO - Annotation: FLI1, Type: GeneOrGeneProduct, Position: 195 2024-07-11 15:23:21,534 - INFO - Annotation: EWSR1, Type: GeneOrGeneProduct, Position: 249 2024-07-11 15:23:21,534 - INFO - Annotation: FLI1, Type: GeneOrGeneProduct, Position: 255 2024-07-11 15:23:21,535 - INFO - Annotation: Eyes absent homolog 3, Type: GeneOrGeneProduct, Position: 292 2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 315 2024-07-11 15:23:21,535 - INFO - Annotation: tumor, Type: DiseaseOrPhenotypicFeature, Position: 334 2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 365 2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 421 2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 489 2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 841 2024-07-11 15:23:21,535 - INFO - Annotation: EYA3, Type: GeneOrGeneProduct, Position: 976 2024-07-11 15:23:21,535 - INFO - Annotation: toxicity, Type: DiseaseOrPhenotypicFeature, Position: 1038 2024-07-11 15:23:21,535 - INFO - Annotation: cytotoxicity, Type: DiseaseOrPhenotypicFeature, Position: 1059 2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 1075 2024-07-11 15:23:21,535 - INFO - Annotation: EWSR1, Type: GeneOrGeneProduct, Position: 1153 2024-07-11 15:23:21,535 - INFO - Annotation: FLI1, Type: GeneOrGeneProduct, Position: 1159 2024-07-11 15:23:21,535 - INFO - Annotation: EWS, Type: GeneOrGeneProduct, Position: 1312 2024-07-11 15:23:21,535 - INFO - Document ID: BC8_BioRED_Task1_Doc1499 2024-07-11 15:23:21,535 - INFO - Text Instance: A randomized, double-blind, multicenter, phase III study on the efficacy and safety of a combination treatment involving fimasartan, amlodipine, rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. 2024-07-11 15:23:21,535 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 121 2024-07-11 15:23:21,536 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 133 2024-07-11 15:23:21,536 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 145 2024-07-11 15:23:21,536 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 161 2024-07-11 15:23:21,536 - INFO - Annotation: hypertension, Type: DiseaseOrPhenotypicFeature, Position: 185 2024-07-11 15:23:21,536 - INFO - Annotation: dyslipidemia, Type: DiseaseOrPhenotypicFeature, Position: 202 2024-07-11 15:23:21,536 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 249 2024-07-11 15:23:21,536 - INFO - Text Instance: BACKGROUND: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. METHODS: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. RESULTS: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions. CONCLUSIONS: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. TRIAL REGISTRATION: NCT03156842, Registered 17 May 2017. 2024-07-11 15:23:21,536 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 81 2024-07-11 15:23:21,536 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 93 2024-07-11 15:23:21,536 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 109 2024-07-11 15:23:21,536 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 125 2024-07-11 15:23:21,536 - INFO - Annotation: hypertension, Type: DiseaseOrPhenotypicFeature, Position: 149 2024-07-11 15:23:21,536 - INFO - Annotation: dyslipidemia, Type: DiseaseOrPhenotypicFeature, Position: 166 2024-07-11 15:23:21,536 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 202 2024-07-11 15:23:21,536 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 337 2024-07-11 15:23:21,537 - INFO - Annotation: Patients, Type: OrganismTaxon, Position: 426 2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 471 2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 536 2024-07-11 15:23:21,537 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 553 2024-07-11 15:23:21,537 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 572 2024-07-11 15:23:21,537 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 596 2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 623 2024-07-11 15:23:21,537 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 640 2024-07-11 15:23:21,537 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 662 2024-07-11 15:23:21,537 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 691 2024-07-11 15:23:21,537 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 710 2024-07-11 15:23:21,537 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1162 2024-07-11 15:23:21,537 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 1386 2024-07-11 15:23:21,538 - INFO - Annotation: ALD, Type: DiseaseOrPhenotypicFeature, Position: 1504 2024-07-11 15:23:21,538 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 1707 2024-07-11 15:23:21,538 - INFO - Annotation: amlodipine, Type: ChemicalEntity, Position: 1718 2024-07-11 15:23:21,538 - INFO - Annotation: rosuvastatin, Type: ChemicalEntity, Position: 1731 2024-07-11 15:23:21,538 - INFO - Annotation: lipid, Type: ChemicalEntity, Position: 1824 2024-07-11 15:23:21,538 - INFO - Annotation: patients, Type: OrganismTaxon, Position: 1840 2024-07-11 15:23:21,538 - INFO - Annotation: hypertension, Type: DiseaseOrPhenotypicFeature, Position: 1864 2024-07-11 15:23:21,538 - INFO - Annotation: dyslipidemia, Type: DiseaseOrPhenotypicFeature, Position: 1881 2024-07-11 15:23:21,538 - INFO - Annotation: fimasartan, Type: ChemicalEntity, Position: 1928 2024-07-11 15:23:23,707 - INFO - number_unique_YES_instances: 0 number_unique_YES_instances 0 number_unique_YES_instances: 0 2024-07-11 15:23:24,048 - INFO - Successfully wrote output TSV file: out_processed.tsv Generating RE predictions 2024-07-11 15:23:26.139808: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcudart.so.11.0'; dlerror: libcudart.so.11.0: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server 2024-07-11 15:23:26.139857: I tensorflow/stream_executor/cuda/cudart_stub.cc:29] Ignore above cudart dlerror if you do not have a GPU set up on your machine. [INFO|training_args.py:804] 2024-07-11 15:23:29,325 >> using logging_steps to initialize eval_steps to 10 [INFO|training_args.py:1023] 2024-07-11 15:23:29,325 >> PyTorch: setting up devices [INFO|training_args.py:885] 2024-07-11 15:23:29,326 >> The default value for the training argument --report_to will change in v5 (from all installed integrations to none). In v5, you will need to use --report_to all to get the same behavior as now. You should start updating your code and make this info disappear :-). INFO:main:Starting prediction ERROR:main:Error during prediction: local variable 'processor' referenced before assignment [INFO|training_args_tf.py:189] 2024-07-11 15:23:29,326 >> Tensorflow: setting up strategy 2024-07-11 15:23:29.327332: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcuda.so.1'; dlerror: libcuda.so.1: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server 2024-07-11 15:23:29.327367: W tensorflow/stream_executor/cuda/cuda_driver.cc:269] failed call to cuInit: UNKNOWN ERROR (303) 2024-07-11 15:23:29.327392: I tensorflow/stream_executor/cuda/cuda_diagnostics.cc:156] kernel driver does not appear to be running on this host (BLOOM): /proc/driver/nvidia/version does not exist 2024-07-11 15:23:29.327937: I tensorflow/core/platform/cpu_feature_guard.cc:193] This TensorFlow binary is optimized with oneAPI Deep Neural Network Library (oneDNN) to use the following CPU instructions in performance-critical operations: AVX2 AVX512F FMA To enable them in other operations, rebuild TensorFlow with the appropriate compiler flags. INFO:main:n_replicas: 1, distributed training: False, 16-bits training: False INFO:main:Training/evaluation parameters TFTrainingArguments( _n_gpu=0, adafactor=False, adam_beta1=0.9, adam_beta2=0.999, adam_epsilon=1e-08, bf16=False, bf16_full_eval=False, data_seed=None, dataloader_drop_last=False, dataloader_num_workers=0, dataloader_pin_memory=True, ddp_bucket_cap_mb=None, ddp_find_unused_parameters=None, debug=[], deepspeed=None, disable_tqdm=False, do_eval=True, do_predict=True, do_train=False, eval_accumulation_steps=None, eval_delay=0, eval_steps=10, evaluation_strategy=IntervalStrategy.STEPS, fp16=False, fp16_backend=auto, fp16_full_eval=False, fp16_opt_level=O1, gcp_project=None, gradient_accumulation_steps=1, gradient_checkpointing=False, greater_is_better=None, group_by_length=False, half_precision_backend=auto, hub_model_id=None, hub_strategy=HubStrategy.EVERY_SAVE, hub_token=, ignore_data_skip=False, label_names=None, label_smoothing_factor=0.0, learning_rate=5e-05, length_column_name=length, load_best_model_at_end=False, local_rank=-1, log_level=-1, log_level_replica=-1, log_on_each_node=True, logging_dir=biorex_model/runs/Jul11_15-23-29_BLOOM, logging_first_step=False, logging_nan_inf_filter=True, logging_steps=10, logging_strategy=IntervalStrategy.STEPS, lr_scheduler_type=SchedulerType.LINEAR, max_grad_norm=1.0, max_steps=-1, metric_for_best_model=None, mp_parameters=, no_cuda=False, num_train_epochs=10.0, optim=OptimizerNames.ADAMW_HF, output_dir=biorex_model, overwrite_output_dir=True, past_index=-1, per_device_eval_batch_size=32, per_device_train_batch_size=16, poly_power=1.0, prediction_loss_only=False, push_to_hub=False, push_to_hub_model_id=None, push_to_hub_organization=None, push_to_hub_token=, remove_unused_columns=True, report_to=['tensorboard'], resume_from_checkpoint=None, run_name=biorex_model, save_on_each_node=False, save_steps=10, save_strategy=IntervalStrategy.STEPS, save_total_limit=None, seed=42, sharded_ddp=[], skip_memory_metrics=True, tf32=None, tpu_metrics_debug=False, tpu_name=None, tpu_num_cores=None, tpu_zone=None, use_legacy_prediction_loop=False, warmup_ratio=0.0, warmup_steps=0, weight_decay=0.0, xla=False, xpu_backend=None, ) INFO:main:Task: biorex INFO:main:Data directory: None ERROR:main:Error loading model or tokenizer: local variable 'new_special_tokens' referenced before assignment cp: cannot stat 'biorex_model/test_results.tsv': No such file or directory 2024-07-11 15:23:32.327195: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcudart.so.11.0'; dlerror: libcudart.so.11.0: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server 2024-07-11 15:23:32.327239: I tensorflow/stream_executor/cuda/cudart_stub.cc:29] Ignore above cudart dlerror if you do not have a GPU set up on your machine. 2024-07-11 15:23:33.896950: W tensorflow/stream_executor/platform/default/dso_loader.cc:64] Could not load dynamic library 'libcuda.so.1'; dlerror: libcuda.so.1: cannot open shared object file: No such file or directory; LD_LIBRARY_PATH: /opt/R/4.2.2/lib/R/lib:/lib:/usr/local/lib:/usr/lib/jvm/java-1.8.0-openjdk-1.8.0.345.b01-1.el8_6.x86_64/jre/lib/amd64/server 2024-07-11 15:23:33.896995: W tensorflow/stream_executor/cuda/cuda_driver.cc:269] failed call to cuInit: UNKNOWN ERROR (303) 2024-07-11 15:23:33.897018: I tensorflow/stream_executor/cuda/cuda_diagnostics.cc:156] kernel driver does not appear to be running on this host (BLOOM): /proc/driver/nvidia/version does not exist

Darrshan-Sankar commented 2 weeks ago

Hi @michaelanekson,

Thank you for sharing the files. I've taken a look at your sample file, and I noticed you're using PubTator NE types instead of BioRED NE types. If you've downloaded your sample file from PubTator, you can use the converter mentioned in this GitHub issue comment to convert it to BioRED NE types.

Since the NE type tags are different, it might negatively impact the script you provided. I'd recommend using our leaderboard's dataset and evaluation to test it before applying it to your own dataset.

Also, if you're only interested in results for PubMed abstracts, we've already processed the entire PubMed database. You can find that data here.

@ptlai is it possiblt to use the annotation created from AIONER?

ptlai commented 1 week ago

michaela95

Sorry for the late reply. It looks like you were attempting to run BioREx with the pretrained BioLinkBERT model to predict on the BC8_BioRED_Subtask1_PubTator/bc8_biored_task1_val.pubtator file. You then encountered the error you mentioned.

I tried replicating your setup, following the installation steps from https://github.com/ncbi/BioREx/?tab=readme-ov-file#installation. I'm running Windows 11 with WSL2 (Linux subsystem). Interestingly, I was able to run the prediction without any issues, as you can see in the attached screenshot.

image

To help troubleshoot, could you provide some more details? Such complete Python package versions and operating system. Thank you

Darrshan-Sankar commented 1 week ago

michaela95

Sorry for the late reply. It looks like you were attempting to run BioREx with the pretrained BioLinkBERT model to predict on the BC8_BioRED_Subtask1_PubTator/bc8_biored_task1_val.pubtator file. You then encountered the error you mentioned.

I tried replicating your setup, following the installation steps from https://github.com/ncbi/BioREx/?tab=readme-ov-file#installation. I'm running Windows 11 with WSL2 (Linux subsystem). Interestingly, I was able to run the prediction without any issues, as you can see in the attached screenshot.

image

To help troubleshoot, could you provide some more details? Such complete Python package versions and operating system. Thank you

@ptlai Thank you for your continuous support. The problem is not with setting up the project, but due to the input mismatch (PS: Which I found 1-2 days back), which has already been clarified by you in another thread (Link: https://github.com/ncbi/BioREx/issues/9#issuecomment-2236639443) today. Thanks..

michaelanekson commented 1 week ago

Thank you for the reply. I have already solved the problem. Let's say the problem is about the input. I tried the BioRED format and it works fine. The conclusion of this issue for the readers is the author's code (run_test_pred.sh) can run fluently for the CPU (when there's a CUDA or GPU-related error, just ignore it) and the input must be transformed from Pubtator format into BioRED format before the analysis. I close this issue.

Now, the situation is I have questions about the output and I need your advice.