Chappellsantana9856

All these tests showed that LytU-SH3b has more activity and potency than LytU. LytU-SH3b has MIC 421 fold lesser than LytU. Finally, LytU-SH3b is a novel and efficient recombinant enzybiotic that can lyse MRSA as an alternative to chemical small molecule antibiotics.Recent advances in DNA sequencing techniques have led to an increase in the identification of single nucleotide polymorphisms (SNPs) in BRCA1 and BRCA2 genes, but no further information regarding the deleterious probability of many of them is available (Variants of Unknown Significance/VUS). As a result, in the current study, different sequence- and structure-based computational tools including SIFT, PolyPhen2, PANTHER, SNPs&GO, FATHMM, SNAP, PhD-SNP, Align-GVGD, and I-Mutant were utilized for determining how resulted BRCA protein is affected by corresponding missense mutations. FoldX was used to estimate mutational effects on the structural stability of BRCA proteins. Variants were considered extremely deleterious only when all tools predicted them to be deleterious. A total of 10 VUSs in BRCA1 (Cys39Ser, Cys64Gly, Phe861Cys, Arg1699Pro, Trp1718Cys, Phe1761Ser, Gly1788Asp, Val1804Gly, Trp1837Gly, and Trp1837Cys) and 12 in BRCA2 (Leu2510Pro, Asp2611Gly, Tyr2660Asp, Leu2686Pro, Leu2688Pro, Tyr2726Cys, Leu2792Pro, Gly2812Glu, Gly2813Glu, Arg2842Cys, Asp3073Gly, and Gly3076Val) were considered as extremely deleterious. Results suggested that deleterious variants were mostly enriched in the N- and C-terminal domain of the BRCA1 and BRCA2 C-terminus. Utilizing evolutionary conservation analysis, we demonstrated that the majority of deleterious SNPs ensue in highly conserved regions of BRCA genes. Furthermore, utilizing FoldX, we demonstrated that alterations in the function of proteins are not always together with stability alterations.Primary epiploic appendagitis (PEA) is a rare and frequently underdiagnosed cause of acute abdominal pain. PEA most commonly affects obese, male patients in the 4th and 5th decade of life. Clinical presentation includes acute, localized, non-migrating pain without fever, nausea, vomiting or diarrhea and the laboratory workup is usually within normal limits. PEA is commonly mistaken as other more severe causes of acute abdominal pain, such as diverticulitis, acute appendicitis or cholecystitis and thus patients undergo unnecessary diagnostic and therapeutic procedures. The emergence of computerized tomography (CT) as the gold standard imaging test in diagnostic dilemmas of acute abdominal pain has resulted in increased recognition and diagnosis of PEA. Upon confirmation, PEA is considered a self-limiting disease and is managed conservatively with analgesics, occasionally combined with nonsteroidal anti-inflammatory drugs (NSAIDS). Persistence of symptoms or recurrence mandate the consideration of surgical management with laparoscopic appendage excision as the definitive treatment. We review the current literature of PEA, with a focus on clinical and imaging findings, in order to raise awareness about this frequently misdiagnosed entity. 2019 Annals of Translational Medicine. All rights reserved.Identified genetic variants from genome wide association studies frequently show only modest effects on the disease risk, leading to the "missing heritability" problem. Tuvusertib mw An avenue, to account for a part of this "missingness" is to evaluate gene-gene interactions (epistasis) thereby elucidating their effect on complex diseases. This can potentially help with identifying gene functions, pathways, and drug targets. However, the exhaustive evaluation of all possible genetic interactions among millions of single nucleotide polymorphisms (SNPs) raises several issues, otherwise known as the "curse of dimensionality". The dimensionality involved in the epistatic analysis of such exponentially growing SNPs diminishes the usefulness of traditional, parametric statistical methods. With the immense popularity of multifactor dimensionality reduction (MDR), a non-parametric method, proposed in 2001, that classifies multi-dimensional genotypes into one- dimensional binary approaches, led to the emergence of a fast-growing coeed for extraordinarily large sets of data. 2019 Annals of Translational Medicine. All rights reserved.Background The past decade has witnessed a rapid increase in the number of contributors per article, which has made explicitly defining the roles of each contributor even more challenging. The Contributor Roles Taxonomy (CRediT) was developed to explicitly define author roles, but there is a lack of empirical data on how CRediT is used in clinical trials. This study aimed to provide empirical data on the use of CRediT in randomized controlled trials (RCTs) and discuss some limitations of CRediT. A new taxonomy (CRediT-RCT) is proposed to explicitly define the author roles in RCTs. Methods The electronic database of PubMed was searched from July 2017 to October 2019 to identify component trials with a randomized controlled design. Publications from the Public Library of Science (PLoS) were included because they embed the CRediT roles within the authors' metadata rather than solely as a separate paragraph of text. Results A total of 446 articles involving 4,185 authors were included in the study. Most authors p0.55; 95% CI 0.40-0.75; P less then 0.001), supervision (OR 0.49; 95% CI 0.36-0.67; P less then 0.001), or resource management (OR 0.71; 95% CI 0.50-1.00; P=0.053). We further propose a novel Contributor Roles Taxonomy for Randomized Controlled Trials (CRediT-RCT) which includes 10 roles. Conclusions The present study provides empirical data on the use of CRediT for RCTs, and some limitations of the taxonomy are discussed. We further propose a new CRediT-RCT which includes 10 roles. 2019 Annals of Translational Medicine. All rights reserved.Background Depression is associated with the abnormal activation of the human inflammatory response system, which is a life-threatening disorder affecting millions of people of all ages around the world. The purposes of the present study were to examine the effect of Lonicera japonica polysaccharide (LJP), a polysaccharide extracted from Lonicera japonica Thunb., on depressed mice treated with the unpredictable emotional stress stimulation. Methods The components of LJP after extraction were detected by HPLC. Depression model is established through chronic unpredictable stimulation, and the depression behavior was assessed by mouse behavioral assessment, including open field, elevated plus maze, tail suspension, forced swim. Pathological changes in hippocampus of mice were observed by HE and toluidine blue staining. Protein expression of NLRP3 inflammasome pathway was detected by WB. Results It was showed that LJP mainly consisted of 8.7% GalA, 8.2% Rha, 16.2% Gal, 19.5% Ara, 26.9% Glc and 20.5% Man, with the average molecular weight approximately ranging from 1 to 1,000 kDa, which could significantly reduce the time in the open arms and the immobility time of the depressed mice in behavioral tests, and the expressions of NLRP3, IL-1β, and caspase-1 in the hippocampus of depressed mice were significantly upregulated. Conclusions LJP exhibited a strong protective effect on mice with depression by inhibiting NLRP3 inflammasome. The results will help to understand the potential use of Lonicera japonica Thun polysaccharide in pharmaceutical and food applications better. 2019 Annals of Translational Medicine. All rights reserved.Background This study aimed to assess gene expression alterations related to T lymphocytes function and explore their potential association with hypoxemia among septic patients. Methods This is a retrospective cohort clinical study with laboratory investigations. We studied patients enrolled in sepsis biological specimen bank from Department of Critical Care Medicine, Zhongda Hospital, fulfilling consensus criteria for sepsis without any documented immune comorbidity admitted in ICU within 48 h after onset with whole blood samples drawn within 24 h of admission. Whole genome expression by microarray assay (Human LncRNA Microarray V4.0) was compared in hypoxemia cohort versus without. Differentially expressed (DE) genes with >1 log2[fold change (FC)] and false discovery rate (FDR) less then 0.20 that enriched in T cell related biological process entered the adjusted analysis to identify the candidate genes. The correlation analysis within candidate genes or with clinical parameters were performed. We assessedrity and incidence of lymphopenia was observed following hypoxemia in sepsis and T cell-related gene signatures were associated with hypoxemia during sepsis. 2019 Annals of Translational Medicine. All rights reserved.Background Psychological resilience is an important personality trait whose decrease is associated with many common psychiatric disorders, but the neural mechanisms underlying it remain largely unclear. In this study, we aimed to explore the neural correlates of psychological resilience in healthy adults by investigating its relationship with functional brain network flexibility, a fundamental dynamic feature of brain network defined by switching frequency of its modular community structures. Methods Resting-state functional magnetic resonance imaging (fMRI) scans were acquired from 41 healthy adults, whose psychological resilience was quantified by the Connor-Davidson Resilience Scale (CD-RISC). Dynamic functional brain network was constructed for each subject, whose flexibility was calculated at all the global, subnetwork and region-of-interest (ROI) levels. After that, the associations between CD-RISC score and brain network flexibility were assessed at all levels by partial correlations controlling for age, sex, education and head motion. Correlation was also tested between the CD-RISC score and modularity of conventional static brain network for comparative purposes. Results The CD-RISC score was significant negatively correlated with the brain network flexibility at global level (r=-0.533, P=0.001), and with flexibility of the visual subnetwork at subnetwork level (r=-0.576, corrected P=0.002). Moreover, significant (corrected P0.05). Conclusions Our results suggest that excessive fluctuations of the functional brain community structures during rest may be indicative of a lower psychological resilience, and the visual and default-mode systems may play crucial roles in such relationship. These findings may provide important implications for improving our understanding of the psychological resilience. 2019 Annals of Translational Medicine. All rights reserved.Background To assess the prevalence and potential predictors of MR diffusion and perfusion abnormalities in a Chinese population with hemispheric transient ischemic attacks (TIA). Methods Patients with temporary (4 s ≥10 mL) in this Chinese population (adjusted OR =7.41, 95% CI 1.57-34.89, P=0.011). Conclusions Our results suggest that limb weakness is a strong predictor of perfusion abnormalities calculated by RAPID on Tmax maps of hemispheric TIA patients without DWI positive findings. Male patients are more likely to develop cerebral infarction. 2019 Annals of Translational Medicine. All rights reserved.Background Serous cystic neoplasms (SCN) rarely have malignant potential, so accurate diagnosis of SCN is crucial for proper clinical management, especially to avoid unnecessary surgeries. However, the misdiagnosis of other pancreatic cystic neoplasm instead of SCN may highly increase the risk of malignancy in patients who receive no surgery. Methods Data from a total of 678 patients with pathologically confirmed to have SCN at sixteen institutions in China from January 1st, 2006 to December 31st, 2016 were retrieved to evaluate the malignancy risk of SCN. Results Among the 678 patients confirmed to have SCN with postoperative pathologic analysis, 649 patients (95.7%) had only one lesion and the average maximum diameter was 3.8±2.47 cm. Four patients were pathologically verified as having serous cystadenocarcinoma, so the SCN actual malignancy rate was 0.6%, while the mortality due to pancreatic surgery in these high-volume centers was nearly 0.2-2%. However, among the 99 SCN patients based on preoperative radiology, three were confirmed to have intraductal papillary mucinous neoplasms (IPMN), nine as mucinous cystic neoplasms (MCN), and four as solid pseudopapillary tumors (SPT) after postoperative pathological analysis.