Raffertymohammad7190

Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown.

In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays.

We found that CPs had showed less complexed. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.Ferroptosis, an iron-dependent form of non-apoptotic cell death, is believed to strongly contribute to the pathogenesis of multiple cancers. Recently, the positive association between ferroptosis and urologic malignancies has drawn considerable attention, while a comprehensive review focused on this issue is absent. Based on this review, ferroptosis has been implicated in the development and therapeutic responses of prostate cancer, kidney cancer, and bladder cancer. Mechanistically, a large number of biomolecules and tumor-associated signaling pathways, including DECR1, PANX2, HSPB1, ACOT8, SUV39H1, NCOA4, PI3K-AKT-mTOR signaling, VHL/HIF-2α pathway, and Hippo/TAZ signaling pathway, have been reported to regulate ferroptosis in urologic cancers. Ferroptosis inducers, such as erastin, ART, CPNPs, and quinazolinyl-arylurea derivatives, exert potential therapeutic effects per se and/or enhance the anticancer response of other anticancer drugs in urologic oncology. A better understanding of ferroptosis may provide a promising way to treat therapy-resistant urologic cancers.

With the advancement of next generation sequencing technologies (NGS), whole-genome sequencing (WGS) has been deployed to a wide range of clinical scenarios. Rapid and accurate classification of drug-resistant Mycobacterium tuberculosis (MTB) would be advantageous in reducing the amplification of additional drug resistance and disease transmission.

In this study, a long-read sequencing approach was subjected to the whole-genome sequencing of clinical MTB clones with susceptibility test profiles, including isoniazid (INH) susceptible clones (n = 10) and INH resistant clones (n = 42) isolated from clinical specimens. Non-synonymous variants within the katG or inhA gene associated with INH resistance was identified using Nanopore sequencing coupled with a corresponding analytical workflow.

In total, 54 nucleotide variants within the katG gene and 39 variants within the inhA gene associated with INH resistance were identified. Consistency among the results of genotypic profiles, susceptibility test, and minimal inhibitory concentration, the high-INH resistance signature was estimated using the area under the receiver operating characteristic curve with the existence of Ser315Thr (AUC = 0.822) or Thr579Asn (AUC = 0.875).

Taken together, we curated lists of coding variants associated with differential INH resistance using Nanopore sequencing, which may constitute an emerging platform for rapid and accurate identification of drug-resistant MTB clones.

Taken together, we curated lists of coding variants associated with differential INH resistance using Nanopore sequencing, which may constitute an emerging platform for rapid and accurate identification of drug-resistant MTB clones.

The discharge summary is the main vector of communication at the time of hospital discharge, but it is known to be insufficient. Direct phone contact between hospitalist and primary care physician (PCP) at discharge could ensure rapid transmission of information, improve patient safety and promote interprofessional collaboration. The objective of this study was to evaluate the feasibility and benefit of a phone call from hospitalist to PCP to plan discharge.

This study was a prospective, single-center, cross-sectional observational study. It took place in an acute medicine unit of a French university hospital. The hospitalist had to contact the PCP by telephone within 72 h prior discharge, making a maximum of 3 call attempts. The primary endpoint was the proportion of patients whose primary care physician could be reached by telephone at the time of discharge. The other criteria were the physicians' opinions on the benefits of this contact and its effect on readmission rates.

275 patients were eligible. 8 hospitalists and 130 PCPs gave their opinion. Calls attempts were made for 71% of eligible patients. Call attempts resulted in successful contact with the PCP 157 times, representing 80% of call attempts and 57% of eligible patients. The average call completion rate was 47%. The telephone contact was perceived by hospitalist as useful and providing security. The PCPs were satisfied and wanted this intervention to become systematic. Telephone contact did not reduce the readmission rate.

Despite the implementation of a standardized process, the feasibility of the intervention was modest. The main obstacle was hospitalists lacking time and facing difficulties in reaching the PCPs. PI4KIIIbetaIN10 However, physicians showed desire to communicate directly by telephone at the time of discharge.

French C.N.I.L. registration number 2108852. Registration date October 12, 2017.

French C.N.I.L. registration number 2108852. Registration date October 12, 2017.

In Kenya, people who inject drugs (PWID) are disproportionately affected by HIV and hepatitis C (HCV) epidemics, including HIV-HCV coinfections; however, few have assessed factors affecting their access to and engagement in care through the lens of community-embedded, peer educators. This qualitative study leverages the personal and professional experiences of peer educators to help identify HIV and HCV barriers and facilitators to care among PWID in Nairobi, including resource recommendations to improve service uptake.

We recruited peer educators from two harm reduction facilities in Nairobi, Kenya, using random and purposive sampling techniques. Semi-structured interviews explored circumstances surrounding HIV and HCV service access, prevention education and resource recommendations. A thematic analysis was conducted using the Modified Social Ecological Model (MSEM) as an underlying framework, with illustrative quotes highlighting emergent themes.

Twenty peer educators participated, including six womed medicalized approaches within law enforcement. Participant resource recommendations include (i) additional medical, social and ancillary support services, (ii) national strategies to address stigma and violence and (iii) HCV prevention education.

Peer educators provided intimate knowledge of PWID barriers and facilitators to HIV and HCV care, described at each level of the MSEM, and should be given careful consideration when developing future initiatives. Recommendations emphasized policy and community-level interventions including educational campaigns and program suggestions to supplement existing HIV and HCV services.

Peer educators provided intimate knowledge of PWID barriers and facilitators to HIV and HCV care, described at each level of the MSEM, and should be given careful consideration when developing future initiatives. Recommendations emphasized policy and community-level interventions including educational campaigns and program suggestions to supplement existing HIV and HCV services.

Growing evidence has shown that the prognosis for colon cancer depends on changes in microenvironment. The purpose of this study was to elucidate the prognostic value of long noncoding RNAs (lncRNAs) related to immune microenvironment (IM) in colon cancer.

Single sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of colon cancer based on the immune genomes of 29 immune signatures. Cox regression analysis identified a lncRNA signatures associated with immune infiltration. The Tumor Immune Estimation Resource database was used to analyze immune cell content.

Colon cancer samples were divided into three subtypes by unsupervised cluster analysis. Cox regression analysis identified an immune infiltration-related 5-lncRNA signature. This signature combined with clinical factors can effectively improve the predictive ability for the overall survival (OS) of colon cancer. At the same time, we found that the expression of H19 affects the content of B cells and macrophages in the microenvironment of colon cancer and affects the prognosis of colon cancer. Finally, we constructed the H19 regulatory network and further analyzed the possible mechanisms. We found that knocking down the expression of H19 can significantly inhibit the expression of CCND1 and VEGFA. At the same time, the immunohistochemical assay found that the expression of CCND1 and VEGFA protein was significantly positively correlated with the infiltration of M2 type macrophages.

The findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer.

The findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer.

Clear guidelines exist to guide the dosing of direct-acting oral anticoagulants (DOACs). It is not known how consistently these guidelines are followed in practice.

We studied patients from the Veterans Health Administration (VA) with non-valvular atrial fibrillation who received DOACs (dabigatran, rivaroxaban, apixaban) between 2010 and 2016. We used patient characteristics (age, creatinine, body mass) to identify which patients met guideline recommendations for low-dose therapy and which for full-dose therapy. We examined how often patient dosing was concordant with these recommendations. We examined variation in guideline-concordant dosing by site of care and over time. We examined patient-level predictors of guideline-concordant dosing using multivariable logistic models.

A total of 73,672 patients who were prescribed DOACS were included. Of 5837 patients who were recommended to receive low-dose therapy, 1331 (23%) received full-dose therapy instead. Of 67,935 patients recommended to receive full-dose therapy, 4079 (6%) received low-dose therapy instead. Sites varied widely on guideline discordant dosing; on inappropriate low-dose therapy, sites varied from 0 to 15%, while on inappropriate high-dose therapy, from 0 to 41%. Guideline discordant therapy decreased by about 20% in a relative sense over time, but its absolute numbers grew as DOAC therapy became more common. The most important patient-level predictors of receiving guideline-discordant therapy were older age and creatinine function being near the cutoff value.

A substantial portion of DOAC prescriptions in the VA system are dosed contrary to clinical guidelines. This phenomenon varies widely across sites of care and has persisted over time.

A substantial portion of DOAC prescriptions in the VA system are dosed contrary to clinical guidelines. This phenomenon varies widely across sites of care and has persisted over time.