Objective To present a named entity recognition method referred to as BioBERT-Att-BiLSTM-CRF for eligibility criteria based on the BioBERT pretrained model.The method can automatically extract relevant information from clinical trials and provide assistance in efficiently formulating eligibility criteria.Methods Based on the UMLS medical semantic network and expert-defined rules,the study established medical entity annotation rules and constructed a named entity recognition corpus to clarify the entity recognition task.BioBERT-Att-BiLSTM-CRF converted the text into BioBERT vectors and inputted them into a bidirectional long short-term memory network to capture contextual semantic features.Meanwhile,attention mechanisms were applied to extract key features,and a conditional random field was used for decoding and outputting the optimal label sequence.Results BioBERT-Att-BiLSTM-CRF outperformed other baseline models on the eligibility criteria named entity recognition dataset.Conclusion BioBERT-Att-BiLSTM-CRF can efficiently extract eligibility criteria-related information from clinical trials,thereby enhancing the scientific validity of clinical trial registration data and providing assistance in the formulation of eligibility criteria for clinical trials.

Objective To explore the clinical features,treatment and prognosis of glioblastomas(GBM)in adults.Methods A retrospective cohort study was performed on 176 adult GBM patients admitted to our department from January 2015 to December 2021.Chi-square test was used to investigate the clinical differences between isocitrate dehydrogenase(IDH)mutant and wild-type GBM.Kaplan-Meier and Log-Rank tests were employed to plot survival curve and compute the survival analysis.Multivariate Cox regression model was applied to identify the independent prognostic factors.Results IDH wild-type GBM account for 89.2％and had significantly differences from the IDH-mutant GBM in terms of age of onset,Karnofsky(KPS)score at admission,symptoms of neurological deficit,and methylation status of O6-methylguanine-DNA-methyltransferase(MGMT)promoter(P＜0.05).For the IDH wild-type GBM patients receiving conventional therapy,univariate Cox hazard analysis showed gross total resection,methylation of MGMT promoter,initiation of radiation within the 5th to 6th week after surgery,and adjuvant temozolomide(TMZ)chemotherapy ≥6 cycles were favorable prognostic factors for overall survival(OS);GBMs in the left hemisphere,involvement of single lobe,methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery were favorable prognostic factors for progression free survival(PFS)(all P＜0.05).Moreover,multivariate Cox hazard regression analysis indicated that methylation of MGMT promoter,and initiation of radiation within the 5th to 6th week after surgery,and adjuvant TMZ chemotherapy ≥6 cycles were independent protective factors for OS,and GBMs in the left hemisphere,involvement of single lobe and methylation of MGMT promoter were independent protective factors for PFS in the GBM patients(all P＜0.05).Conclusion The clinical and prognostic features are totally different between IDH mutant and wild-type GBM,and molecular detections are needed for the further pathological classification.Methylation of MGMT promoter is a primary marker of favorite prognosis for IDH wild-type GBM,and slightly delay in radiotherapy(the 5th to 6th week after surgery)can effectively improve the survival prognosis of IDH wild-type GBM.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Background: Peste des petits ruminants (PPR), caused by the PPR virus (PPRV), is an acute and fatal contagious disease that mainly infects goats, sheep, and other artiodactyls.Peripheral blood mononuclear cells (PBMCs) are considered the primary innate immune cells. Objectives: PBMCs derived from goats were infected with PPRV and analyzed to detect the relationship between PPRV replication and apoptosis or the inflammatory response. Methods: Quantitative real-time polymerase chain reaction was used to identify PPRV replication and cytokines expression. Flow cytometry was conducted to detect apoptosis and the differentiation of CD4+ and CD8+T cells after PPRV infection. Results: PPRV stimulated the differentiation of CD4+ and CD8+ T cells. In addition, PPRV induced apoptosis in goat PBMCs. Furthermore, apoptosis and the inflammatory response induced by PPRV could be suppressed by Z-VAD-FMK and Z-YVAD-FMK, respectively.Moreover, the virus titer of PPRV was attenuated by inhibiting caspase-1-dependent apoptosis and inflammation. Conclusions This study showed that apoptosis and the inflammatory response play an essential role in PPR viral replication in vitro, providing a new mechanism related to the cell host response.

Here, we took base construction of neurosurgery as example to discuss and analyze according to requirements and evaluation indexes of base construction in Xinqiao Hospital, and put forward the specific objectives, measures and implementations of base construction. Foremost, we summarized experiences and overcame shortcomings through interpreting and implementing scheme of our base construction, which would help to improve the construction of standardized residency training base in China.

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell's endogenous protein degrada-tion machinery.However,the susceptibility of proteins for targeting by TPD approaches,termed"degradability",is largely unknown.Here,we developed a machine learning model,model-free anal-ysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein tar-gets.MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision-recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to inde-pendent non-kinase proteins.We found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most predictive.By structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase degradability.Finally,we extended MAPD predictions to the entire proteome to find 964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.

Chromatin immunoprecipitation sequencing (ChIP-seq) and the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) have become essential technologies to effectively measure protein–DNA interactions and chromatin accessibility. However, there is a need for a scalable and reproducible pipeline that incorporates proper normalization between samples, correction of copy number variations, and integration of new downstream analysis tools. Here we present Containerized Bioinformatics workflow for Reproducible ChIP/ATAC-seq Analysis (CoBRA), a modularized computational workflow which quantifies ChIP-seq and ATAC-seq peak regions and performs unsupervised and supervised analyses. CoBRA provides a comprehensive state-of-the-art ChIP-seq and ATAC-seq analysis pipeline that can be used by scientists with limited computational experience. This enables researchers to gain rapid insight into protein–DNA interactions and chromatin accessibility through sample clustering, differential peak calling, motif enrichment, comparison of sites to a reference database, and pathway analysis. CoBRA is publicly available online at https://bitbucket. org/cfce/cobra.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective To identify gene mutations in the BCS1L gene in a patient with Bj(o)rnstad syndrome mainly manifesting as congenital pili torti and sensorineural hearing loss.Methods Clinical data were collected and DNA was extracted from the peripheral blood of the patient and her parents.All the exons and their flanking sequences of the BCS1L gene were amplified by PCR followed by Sanger sequencing,and the sequencing results were compared with the normal sequences.A few hairs were collected from the patient,and examined by the scanning electron microscope.Results There were two mutations in BCS1L gene in the patient,i.e.,a heterozygous nonsense mutation in exon 4 and a heterozygous missense mutation in exon 8.The nonsense mutation in exon 4,which caused a change from CGA to TGA at position 144 and resulted in the substitution of arginine by termination codon (p.R144*),was a novel mutation in the BCS1L gene causing Bj(o)rnstad syndrome,and had never been repotted in the literature.The missense mutation in exon 8 led to a change from CGC to CAC at position 306 and resulted in the substitution of arginine by histidine (p.R306H).The patient's mother only carried a heterozygous mutation c.430 C＞T (p.R144*) in exon 4 of the BCS1L gene,and her father only carried a heterozygous mutation c.917 G＞A (p.R306H) in exon 8 of the BCS1L gene.Scanning electron microscopy showed that flats,grooves and longitudinal twisting irregu larly appeared at intervals on the surface of hair shafts.Conclusions A novel mutation in the BCS1L gene,which causes a change from CGA to TGA at position 144 in the BCS1L gene and results in a premature termination codon,is firstly reported in a patient with Bj(o)rnstad syndrome,and the compound heterozygous mutations c.430 C＞T and c.917 G＞A in the BCS1L gene are associated with the clinical manifestations of the patient.Genetic analvsis is helpful for the diagnosis of Bj(o)rnstad syndrome.

Objective: To investigate the effect of pricking blood therapy on behavior and brainstem c-fos and c-jun gene expression in migraine rats. Methods: A rat model of migraine was made with nitroglycerol. The rats were treated by pricking blood. Rat behavior was observed. Brainstem c-fos and c-jun gene expression was examined by immunohistochemistry. Results: Ear redness improved significantly, the number of head scratchings decreased obviously (P<0.05) and c-fos and c-jun expression was reduced markedly (P<0.01) in the treatment group after pricking blood compared with the model group and the blank group. Conclusion: Pricking blood treatment can improve behavior indices and reduce c-fos and c-jun positive expression in migraine rats.