ta-analysis found that cochlear implantation for children with SSD was associated with clinically meaningful improvements in audiological and patient-reported outcomes; shorter duration of deafness may lead to better outcomes. These findings can guide future research efforts, refine cochlear implantation candidacy criteria, and aid in family counseling and shared decision-making.

This systematic review and meta-analysis found that cochlear implantation for children with SSD was associated with clinically meaningful improvements in audiological and patient-reported outcomes; shorter duration of deafness may lead to better outcomes. These findings can guide future research efforts, refine cochlear implantation candidacy criteria, and aid in family counseling and shared decision-making.

Single-cell RNA-seq allows researchers to identify cell populations based on unsupervised clustering of the transcriptome. However, subpopulations can have only subtle transcriptomic differences and the high dimensionality of the data makes their identification challenging.

We introduce ILoReg, an R package implementing a new cell population identification method that improves identification of cell populations with subtle differences through a probabilistic feature extraction step that is applied before clustering and visualization. The feature extraction is performed using a novel machine learning algorithm, called iterative clustering projection (ICP), that uses logistic regression and clustering similarity comparison to iteratively cluster data. Remarkably, ICP also manages to integrate feature selection with the clustering through L1-regularization, enabling the identification of genes that are differentially expressed between cell populations. By combining solutions of multiple ICP runs into a single consensus solution, ILoReg creates a representation that enables investigating cell populations with a high resolution. In particular, we show that the visualization of ILoReg allows segregation of immune and pancreatic cell populations in a more pronounced manner compared with current state-of-the-art methods.

ILoReg is available as an R package at https//bioconductor.org/packages/ILoReg.

Supplementary data are available at Supplementary Information and Supplementary Files 1 and 2.

Supplementary data are available at Supplementary Information and Supplementary Files 1 and 2.

In people with HIV (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction; i.e. eGFR decrease of >5mL/min/1.73m 2 per year for >3 consecutive years.

We used time-to-event analyses to measure univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical DAD CKD risk score, antiretroviral exposures, and a polygenic risk score based on 14’769 genome-wide single nucleotide polymorphisms (SNPs) in white Swiss HIV Cohort Study participants.

We included 225 participants with rapid progression (median age 42 years, 76% male, median baseline eGFR 101mL/min/1.73m 2) and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with a low risk DAD CKD risk score, participants with medium and high risk had rapid progression-HR=1.30 (0.99-1.71) and 1.82 (1.28-2.60), respectively. Compared to the first (most favorable) polygenic risk score quartile, participants in the second, third and fourth (most unfavorable) quartiles had rapid progression-HR=1.39 (0.94-2.06), 1.52 (1.04-2.24) and 2.04 (1.41-2.94), respectively. Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR=1.36 [1.06-1.76]).

An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors.

An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors.

Complications arising from the nationwide opioid epidemic led to an increase in health care use. Few studies have investigated whether this is reflected in hospital admissions for endogenous endophthalmitis.

To report changing trends in epidemiology, risk factors, hospital course, and costs associated with drug use-related endogenous endophthalmitis hospitalizations in the United States from 2003 to 2016.

Nationwide, retrospective cross-sectional study using the National Inpatient Sample. A total of 56 839 patients admitted with a diagnosis of endogenous endophthalmitis were included. Data were analyzed between 2003 and 2016.

Inpatient admission for endogenous endophthalmitis during the years 2003 to 2016.

The Nationwide Inpatient Sample was queried to identify all inpatient admissions with a diagnosis of endogenous endophthalmitis in the United States between the years 2003 and 2016. Analyses were performed to identify national and regional trends in incidence and prevalence of associated infectiouhealth care use burden. These findings support the hypothesis that clinicians should maintain a high index of suspicion for endophthalmitis when evaluating patients with intraocular inflammation in the setting of drug dependence or use.

A 4-fold increase in drug use-related endogenous endophthalmitis hospitalizations was observed in the United States from 2003 to 2016, resulting in substantial health care use burden. These findings support the hypothesis that clinicians should maintain a high index of suspicion for endophthalmitis when evaluating patients with intraocular inflammation in the setting of drug dependence or use.PubChem (https//pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem’s homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

A core symptom of posttraumatic stress disorder is persistent fear memory, which can be defined as fear memory that is resistant to updating, inhibition, or extinction. posttraumatic stress disorder emerges after traumatic stress exposure, but neurobiological mechanisms via which traumatic stress leads to persistent fear memory are not well defined. Akt signaling within the amygdala (Amy) is enhanced with traumatic stress, and phosphatidylinositol kinase 3 (PI3K) activation of Akt within the basolateral Amy (BLA) has been implicated as critical to fear memory formation. These findings raise the possibility that traumatic stress enhances PI3K→Akt signaling in the BLA, which leads to persistent fear memory.

To test this hypothesis, rats were exposed to traumatic stress using the single prolonged stress model, and changes in Akt phosphorylation were assayed in the Amy at 0 and 30 minutes after fear conditioning (FC). In a separate experiment, we inhibited PI3K→Akt signaling in the BLA prior to FC and observed the effect this had on acquisition, expression, and extinction of FC in stressed and control rats.

Enhanced Akt phosphorylation in the Amy at both time points was observed in stressed rats, but not in control rats. PI3K→Akt inhibition in the BLA had no effect on freezing in control rats but decreased freezing during extinction training and testing in stressed rats.

These findings suggest that PI3K→Akt signaling in the BLA could be a mechanism via which traumatic stress leads to fear memory that is resistant to extinction.

These findings suggest that PI3K→Akt signaling in the BLA could be a mechanism via which traumatic stress leads to fear memory that is resistant to extinction.DrugCentral is a public resource (http//drugcentral.org) that serves the scientific community by providing up-to-date drug information, as described in previous papers. The current release includes 109 newly approved (October 2018 through March 2020) active pharmaceutical ingredients in the US, Europe, Japan and other countries; and two molecular entities (e.g. mefuparib) of interest for COVID19. New additions include a set of pharmacokinetic properties for ∼1000 drugs, and a sex-based separation of side effects, processed from FAERS (FDA Adverse Event Reporting System); as well as a drug repositioning prioritization scheme based on the market availability and intellectual property rights forFDA approved drugs. In the context of the COVID19 pandemic, we also incorporated REDIAL-2020, a machine learning platform that estimates anti-SARS-CoV-2 activities, as well as the 'drugs in news’ feature offers a brief enumeration of the most interesting drugs at the present moment. The full database dump and data files are available for download from the DrugCentral web portal.

Indoleamine 2,3-dioxygenase 1 (IDO1) causes tumor immune suppression. The IDO1 pathway inhibitor indoximod combined with a taxane in patients with ERBB2-negative metastatic breast cancer was tested in a prospective clinical trial.

To assess clinical outcomes in patients with ERBB2-negative metastatic breast cancer treated with indoximod plus a taxane.

This phase 2 double-blinded randomized 11 placebo-controlled clinical trial enrolled patients at multiple international centers from August 26, 2013, to January 25, 2016. Eligibility criteria included ERBB2-negative metastatic breast cancer, ability to receive taxane therapy, good performance status, normal organ function, no previous immunotherapy use, and no autoimmune disease. The study was discontinued in June 2017 because of lack of efficacy. Data analysis was performed from February 2019 to April 2020.

A taxane (paclitaxel [80 mg/m2] weekly 3 weeks on, 1 week off, or docetaxel [75 mg/m2] every 3 weeks) plus placebo or indoximod (1200 mg) orally twionths) and overall survival (19.5 vs 20.6 months) were not statistically significant. Grade 3 or greater treatment-emergent adverse events occurred in 60% of patients in both arms.

This randomized clinical trial found that, among patients with ERBB2-negative metastatic breast cancer, addition of indoximod to a taxane did not improve PFS compared with a taxane alone.

ClinicalTrials.gov Identifier NCT01792050.

ClinicalTrials.gov Identifier NCT01792050.The Database of Antimicrobial Activity and Structure of Peptides (DBAASP) is an open-access, comprehensive database containing information on amino acid sequences, chemical modifications, 3D structures, bioactivities and toxicities of peptides that possess antimicrobial properties. DBAASP is updated continuously, and at present, version 3.0 (DBAASP v3) contains >15 700 entries (8000 more than the previous version), including >14 500 monomers and nearly 400 homo- and hetero-multimers. Of the monomeric antimicrobial peptides (AMPs), >12 000 are synthetic, about 2700 are ribosomally synthesized, and about 170 are non-ribosomally synthesized. Approximately 3/4 of the entries were added after the initial release of the database in 2014 reflecting the recent sharp increase in interest in AMPs. Despite the increased interest, adoption of peptide antimicrobials in clinical practice is still limited as a consequence of several factors including side effects, problems with bioavailability and high production costs. To assist in developing and optimizing de novo peptides with desired biological activities, DBAASP offers several tools including a sophisticated multifactor analysis of relevant physicochemical properties.