Ultrasound exam Elastography for your Evaluation of Lymph Nodes

6 million mutated binding site protein-ligand complexes constructed using a multithreaded virtual screening workflow. It provides a web interface to explore and visualize the protein-ligand complexes and a REST API to programmatically access the different aspects of the database contents. PSnpBind is open source and freely available at https//psnpbind.org .Osteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole "organ" including cartilage, subchondral bone, synovium, and muscles. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the pathogenesis of age-related diseases including OA. In this review, we mainly focus on the role of the senescent skeletal cells (chondrocytes, osteoblasts, osteoclasts, osteocyte, and muscle cells) in initiating the development and progression of OA alone or through cross-talk with the macrophages/synovial cells. Accordingly, we summarize the current OA-targeted therapies based on the abovementioned theory, e.g., by eliminating senescent skeletal cells and/or inhibiting the senescence-associated secretory phenotype (SASP) that drives senescence. Furthermore, the existing animal models for the study of OA from the perspective of senescence are highlighted to fill the gap between basic research and clinical applications. Overall, in this review, we systematically assess the current understanding of cellular senescence in OA, which in turn might shed light on the stratified OA treatments.
Dysfunctional p53 signaling is one of the major causes of hepatocellular carcinoma (HCC) tumorigenesis and development, but the mechanisms underlying p53 inactivation in HCC have not been fully clarified. The role of Krüppel-associated box (KRAB)-type zinc-finger protein ZNF498 in tumorigenesis and the underlying mechanisms are poorly understood.
Clinical HCC samples were used to assess the association of ZNF498 expression with clinicopathological characteristics and patient outcomes. A mouse model in which HCC was induced by diethylnitrosamine (DEN) was used to explore the role of ZNF498 in HCC initiation and progression. ZNF498 overexpression and knockdown HCC cell lines were employed to examine the effects of ZNF498 on cellular proliferation, apoptosis, ferroptosis and tumor growth. Western blotting, immunoprecipitation, qPCR, luciferase assays and flow cytometry were also conducted to determine the underlying mechanisms related to ZNF498 function.
ZNF498 was found to be highly expressed in HCC, and ZNF498 suppresses apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation in hepatocellular carcinogenesis, revealing a novel ZNF498-PKCδ-p53INP1-p53 axis in HCC cells that would enrich the non-mutation p53-inactivating mechanisms in HCC.
Ovarian cancer (OC) is one of the most common and lethal malignant tumors worldwide and the prognosis of OC remains unsatisfactory. Transcription factors (TFs) are demonstrated to be associated with the clinical outcome of many types of cancers, yet their roles in the prognostic prediction and gene regulatory network in patients with OC need to be further investigated.
TFs from GEO datasets were collected and analyzed. Differential expression analysis, WGCNA and Cox-LASSO regression model were used to identify the hub-TFs and a prognostic signature based on these TFs was constructed and validated. Moreover, tumor-infiltrating immune cells were analyzed, and a nomogram containing age, histology, FIGO_stage and TFs-based signature were established. Potential biological functions, pathways and the gene regulatory network of TFs in signature was also explored.
In this study, 6 TFs significantly associated with the prognosis of OC were identified. These TFs were used to build up a TFs-based signature for prestudy may facilitate the clinical decision-making for patients with OC and help to elucidate the underlying mechanism of TFs in OC.
To our best knowledge, it is for the first time to develop a prognostic signature based on TFs in OC. The TFs-based signature is proven to be effective in predicting the survival of patients with OC. Our study may facilitate the clinical decision-making for patients with OC and help to elucidate the underlying mechanism of TFs in OC.
Single-stranded DNA (ssDNA) coated with replication protein A (RPA) acts as a key platform for the recruitment and exchange of genome maintenance factors in DNA damage response. Yet, how the formation of the ssDNA-RPA intermediate is regulated remains elusive.
Here, we report that the lamin-associated protein LAP2α is physically associated with RPA, and LAP2α preferentially facilitates RPA deposition on damaged chromatin via physical contacts between LAP2α and RPA1. Importantly, LAP2α-promoted RPA binding to ssDNA plays a critical role in protection of replication forks, activation of ATR, and repair of damaged DNA. We further demonstrate that the preference of LAP2α-promoted RPA loading on damaged chromatin depends on poly ADP-ribose polymerase PARP1, but not poly(ADP-ribosyl)ation.
Our study provides mechanistic insight into RPA deposition in response to DNA damage and reveals a genome protection role of LAP2α.
Our study provides mechanistic insight into RPA deposition in response to DNA damage and reveals a genome protection role of LAP2α.Recovering high-quality metagenome-assembled genomes (MAGs) from complex microbial ecosystems remains challenging. Recently, high-throughput chromosome conformation capture (Hi-C) has been applied to simultaneously study multiple genomes in natural microbial communities. We develop HiCBin, a novel open-source pipeline, to resolve high-quality MAGs utilizing Hi-C contact maps. HiCBin employs the HiCzin normalization method and the Leiden clustering algorithm and includes the spurious contact detection into binning pipelines for the first time. HiCBin is validated on one synthetic and two real metagenomic samples and is shown to outperform the existing Hi-C-based binning methods. HiCBin is available at https//github.com/dyxstat/HiCBin .Identifying genomic regions with hypervariable ChIP-seq or ATAC-seq signals across given samples is essential for large-scale epigenetic studies. In particular, the hypervariable regions across tumors from different patients indicate their heterogeneity and can contribute to revealing potential cancer subtypes and the associated epigenetic markers. We present HyperChIP as the first complete statistical tool for the task. HyperChIP uses scaled variances that account for the mean-variance dependence to rank genomic regions, and it increases the statistical power by diminishing the influence of true hypervariable regions on model fitting. A pan-cancer case study illustrates the practical utility of HyperChIP.
Medical students have a higher risk for depression, anxiety, stress-related symptoms, burnout, and suicide, and more rarely seek professional help or treatment than the general population. Appeals are being made to address the mental health and resilience of physicians-to-be. The novel program Training for Awareness, Resilience, and Action (TARA) was originally developed to treat depressed adolescents, targeting specific neuroscientific findings in this population. TARA has shown feasibility and preliminary efficacy in clinically depressed adolescents and corresponding brain-changes in mixed community adolescent samples. The present study investigated the feasibility and acceptability of TARA as a potential indicated prevention program for symptoms of depression, anxiety, stress and burnout in Swedish medical students.
We conducted a single-arm trial with 23 self-selected students in their early semesters of medical school (mean age 25.38 years, 5 males and 18 females), with or without mental disorders. Aedly during the intervention. Qualitative content analysis resulted in a main theme labeled "An uncommon meeting-ground for personal empowerment", with 4 themes; "Acknowledging unmet needs", "Entering a free zone", "Feeling connected to oneself and others" and "Expanding self-efficacy".
TARA is feasible and acceptable in a mixed sample of Swedish medical students. The students' reports of entering an uncommon meeting-ground for personal empowerment supports effectiveness studies of TARA in this context.
TARA is feasible and acceptable in a mixed sample of Swedish medical students. The students' reports of entering an uncommon meeting-ground for personal empowerment supports effectiveness studies of TARA in this context.Since the outbreak of coronavirus disease 2019 (COVID-19), traditional Chinese medicine (TCM) has made an important contribution to the prevention and control of the epidemic. This review aimed to evaluate the efficacy and explore the mechanisms of TCM for COVID-19. We systematically searched 7 databases from their inception up to July 21, 2021, to distinguish randomized controlled trials (RCTs), cohort studies (CSs), and case-control studies (CCSs) of TCM for COVID-19. Two reviewers independently completed the screening of literature, extraction of data, and quality assessment of included studies. Meta-analysis was performed using Review Manager 5.4 software. Eventually, 29 RCTs involving 3060 patients and 28 retrospective studies (RSs) involving 12,460 patients were included. The meta-analysis demonstrated that TCM could decrease the proportion of patients progressing to severe cases by 55% and the mortality rate of severe or critical patients by 49%. Moreover, TCM could relieve clinical symptoms, curtail the length of hospital stay, improve laboratory indicators, and so on. Raf inhibitor In addition, we consulted the literature and obtained 149 components of Chinese medicinal herbs that could stably bind to antiviral targets or anti-inflammatory or immune-regulating targets by the prediction of molecular docking. It suggested that the mechanisms involved anti-virus, anti-inflammation, and regulation of immunity. Our study made a systematic review on the efficacy of TCM for COVID-19 and discussed the possible mechanisms, which provided clinical reference and theoretical basis for further research on the mechanism of TCM for COVID-19.
The aim of this study was to identify and summarize how value-based healthcare (VBHC) is conceptualized in the literature and implemented in hospitals. Furthermore, an overview was created of the effects of both the implementation of VBHC and the implementation strategies used.
A scoping review was conducted by searching online databases for articles published between January 2006 and February 2021. Empirical as well as non-empirical articles were included.
1729 publications were screened and 62 were used for data extraction. The majority of the articles did not specify a conceptualization of VBHC, but only conceptualized the goals of VBHC or the concept of value. Most hospitals implemented only one or two components of VBHC, mainly the measurement of outcomes and costs or Integrated Practice Units (IPUs). Few studies examined effects. Implementation strategies were described rarely, and were evaluated even less.
VBHC has a high level of interpretative variability and a common conceptualization of VBHC is therefore urgently needed.