Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers,observational study

IntroductionThe risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19.MethodsA two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the “standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under ”escalated VTE prophylaxis dose“. The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications.ResultsA total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52–2.86; P = 0.64 and OR 0.75; 95% CI 0.16–3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08–10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79–1.73; P = 0.43 and HR 1.08;95 %CI 0.76–1.53; P = 0.83, respectively).ConclusionEscalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

RNA sequencing steps toward the first line

• DNA is the sequence that codes for proteins.
• Messenger RNA is transcribed from the DNA sequence of genes and translated into protein.
• It can be difficult to predict how a change in the DNA sequence will affect messenger RNA and protein quantity and quality.
• DNA translocation changes can cause the joining of sequences from two different genes or different parts of the same gene.
• DNA sequencing is often used clinically to predict how DNA changes might affect proteins.
• Alternatively, RNA sequencing can be used as a more direct measure of the effect of DNA changes on the protein products.
• This sequencing is important for identifying changes in cancer that may indicate response to targeted therapy, prognosis, or diagnosis.

     

Comprehensive interrogation of gene lists from genome-scale cancer screens with oncoEnrichR

Genome-scale screening experiments in cancer produce long lists of candidate genes that require extensive interpretation for biological insight and prioritization for follow-up studies. Interrogation of gene lists frequently represents a significant and time-consuming undertaking, in which experimental biologists typically combine results from a variety of bioinformatics resources in an attempt to portray and understand cancer relevance. As a means to simplify and strengthen the support for this endeavor, we have developed oncoEnrichR, a flexible bioinformatics tool that allows cancer researchers to comprehensively interrogate a given gene list along multiple facets of cancer relevance. oncoEnrichR differs from general gene set analysis frameworks through the integration of an extensive set of prior knowledge specifically relevant for cancer, including ranked gene-tumor type associations, literature-supported proto-oncogene and tumor suppressor gene annotations, target druggability data, regulatory interactions, synthetic lethality predictions, as well as prognostic associations, gene aberrations and co-expression patterns across tumor types. The software produces a structured and user-friendly analysis report as its main output, where versions of all underlying data resources are explicitly logged, the latter being a critical component for reproducible science. We demonstrate the usefulness of oncoEnrichR through interrogation of two candidate lists from proteomic and CRISPR screens. oncoEnrichR is freely available as a web-based service hosted by the Galaxy platform ( https://oncotools.elixir.no ), and can also be accessed as a stand-alone R package ( https://github.com/sigven/oncoEnrichR ).     

The impact of neighborhoods and friendships on interracial anxiety among medical students and residents: A report from the medical student CHANGES study

Objective

To examine the experience of interracial anxiety among health professionals and how it may affect the quality of their interactions with patients from racially marginalized populations. We explored the influence of prior interracial exposure—specifically through childhood neighborhoods, college student bodies, and friend groups—on interracial anxiety among medical students and residents. We also examined whether levels of interracial anxiety change from medical school through residency.

Data Source

Web-based longitudinal survey data from the Medical Student Cognitive Habits and Growth Evaluation Study.

Study Design

We used a retrospective longitudinal design with four observations for each trainee. The study population consisted of non-Black US medical trainees surveyed in their 1st and 4th years of medical school and 2nd and 3rd years of residency. Mixed effects longitudinal models were used to assess predictors of interracial anxiety and assess changes in interracial anxiety scores over time.

Principal Findings

In total, 3155 non-Black medical trainees were followed for 7 years. Seventy-eight percent grew up in predominantly White neighborhoods. Living in predominantly White neighborhoods and having less racially diverse friends were associated with higher levels of interracial anxiety among medical trainees. Trainees' interracial anxiety scores did not substantially change over time; interracial anxiety was highest in the 1st year of medical school, lowest in the 4th year, and increased slightly during residency.

Conclusions

Neighborhood and friend group composition had independent effects on interracial anxiety, indicating that premedical racial socialization may affect medical trainees' preparedness to interact effectively with diverse patient populations. Additionally, the lack of substantial change in interracial anxiety throughout medical training suggests the importance of providing curricular tools and structure (e.g., instituting interracial cooperative learning activities) to foster the development of healthy interracial relationships.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

张氏头针治疗儿童多发性抽动症的随机对照临床研究＊

目的 观察张氏头针治疗儿童多发性抽动症的临床疗效。方法 2019年3月至2020年12月共招募多发性抽动症儿童60例，随机分为头针组和硫必利组，每组各30例。头针组采用毫针针刺双侧运动区、舞蹈震颤控制区及百会、印堂，每周治疗3次，1个月为1个疗程，共治疗4个疗程；硫必利组给予盐酸硫必利片50-100 mg/次，2次/天，1个月为1个疗程，共治疗4个疗程。比较两组患者治疗前后耶鲁综合抽动严重程度量表（Yale global Tic severity scale，YGTSS）、中医证候积分、SF-36健康调查简表（the MOS item short from health survey，SF-36）及临床疗效评价结果。结果 头针组合硫必利组组内比较：二组的YGTSS评分、中医证候积分与治疗前相比具有显著统计学差异（P<0.05），SF-36评分中头针组在生理功能、生理职能、总体健康、情感职能、心理健康等5个维度的评分高于治疗前，差异有统计学意义（P<0.05）；硫必利组在生理功能、生理职能、总体健康、心理健康等5个维度的评分高于治疗前，差异有统计学意义（P<0.05）；头针组合硫必利组组间比较：头针组治疗后YGTSS评分、中医证候积分均低于硫必利组，差异有统计学意义（P<0.05），头针组在SF-36量表中总体健康和心理健康2个维度照优于硫必利组，差异有统计学意义（P<0.05）；治疗结束3个月随访，头针组YGTSS评分、中医证候积分均低于硫必利组，差异有统计学意义（P<0.05）。结论 张氏头针能够很好的改善多发性抽动症的临床症状，提高其生活质量。     

基于CNKI的中医药治疗癫痫的知识图谱分析＊

目的 运用科学知识图谱的手段，分析中医药治疗癫痫的研究进程并提炼重点。方法 设置检索时间为1990年至2020年，检索对象为中国知网（CNKI）该领域的相关文献，运用CiteSpace软件科学、准确地分析这些文献的作者信息、研究（发文）机构、关键词情况。结果 共计纳入文献793篇，马融-张喜莲、刘金民、谢炜、王洪图-张丽萍等领导核心作者团队，北京、广州以及广西中医药大学、天津中医药大学第一附属医院、南方医科大学等单位为主要进行相关研究的机构，高频关键词包括大鼠、难治性癫痫、小儿癫痫、海马、脑电图等，作用机制、网络药理学、肠道菌群、氧化应激、分子生物学等为近年来的热点与前沿。结论 通过借用知识图谱的分析能帮助提炼国内中医药治疗癫痫研究领域的重点，全面分析并科学判断近年来该领域的热点及前沿，为未来的研究夯实基础并把握方向。     

细胞因子在分化型甲状腺癌诊疗中的应用进展北大核心

甲状腺癌是内分泌系统常见的恶性肿瘤之一,其发病率呈逐年上升趋势。甲状腺癌以分化型甲状腺癌(differentiated thyroid carcinoma, DTC)为主,尽管多数DTC患者经规范化治疗后预后良好,但由于部分肿瘤的病理类型侵袭性较高或肿瘤组织分化程度较低,病情进展迅速导致患者总生存时间显著缩短。近年来,有关炎症与肿瘤之间相关性的研究越来越多,炎性微环境的改变在肿瘤发病机制中的作用逐渐被证实,更多的证据表明细胞因子可作为肿瘤的良恶性鉴别、预后判断提示及诊疗方案选择等的重要参考依据。本文就部分细胞因子在DTC诊疗中的应用进展进行论述,旨在为DTC的诊疗与预后判断等提供参考依据。