Patient Perspectives of Telemedicine in Outpatient Nephrology Clinics During COVID-19: A Qualitative Study.

Background: The COVID-19 pandemic notably disrupted care for patients with chronic kidney disease (CKD) care, necessitating a rapid shift to telemedicine. Despite the growing use of telemedicine, the impact of this transition on patients' experiences, particularly in Canada and considering sociocultural factors, remains underexplored. This study aims to investigate patients with CKD perspectives on telemedicine versus in-person care and to offer recommendations for enhancing telemedicine services.

mVOC 4.0: a database of microbial volatiles.

Metabolomic microbiome research has become an important topic for understanding agricultural, ecological as well as health correlations. Only the determination of both the non-volatile and the volatile organic compound (mVOC) production by microorganisms allows a holistic view for understanding the complete potential of metabolomes and metabolic capabilities of bacteria. In the recent past, more and more bacterial headspaces and culture media were analyzed, leading to an accumulation of about 3500 mVOCs in the updated mVOC 4.

TDP43 aggregation at ER-exit sites impairs ER-to-Golgi transport.

Protein aggregation plays key roles in age-related degenerative diseases, but how different proteins coalesce to form inclusions that vary in composition, morphology, molecular dynamics and confer physiological consequences is poorly understood. Here we employ a general reporter based on mutant Hsp104 to identify proteins forming aggregates in human cells under common proteotoxic stress. We identify over 300 proteins that form different inclusions containing subsets of aggregating proteins.

Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade.

Metastatic cutaneous melanoma is a fatal skin cancer. Resistance to targeted and immune therapies limits the benefits of current treatments. Identifying and adding anti-resistance agents to current treatment protocols can potentially improve clinical responses.

Antibody-Loading of Biological Nanocarrier Vesicles Derived from Red-Blood-Cell Membranes.

Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier in crossing immune systems and cellular membranes. To overcome these, various strategies have been explored including shuttling via liposomes or biocamouflaged nanoparticles. Here, we demonstrate the feasibility of loading antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell membranes, which can act as nanocarriers for intracellular delivery.

Withdrawn 2.0-update on withdrawn drugs with pharmacovigilance data.

One challenge in the development of novel drugs is their interaction with potential off-targets, which can cause unintended side-effects, that can lead to the subsequent withdrawal of approved drugs. At the same time, these off-targets may also present a chance for the repositioning of withdrawn drugs for new indications, which are potentially rare or more severe than the original indication and where certain adverse reactions may be avoidable or tolerable. To enable further insights into this topic, we updated our database Withdrawn by adding pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS), as well as mechanism of action and human disease pathway prediction features for drugs that are or were temporarily withdrawn or discontinued in at least one country.

Wavelength-Sensitive Superconducting Single-Photon Detectors on Thin Film Lithium Niobate Waveguides.

Lithium niobate, because of its nonlinear and electro-optical properties, is one of the materials of choice for photonic applications. The development of nanostructuring capabilities of thin film lithium niobate (TFLN) permits fabrication of small footprint, low-loss optical circuits. With the recent implementation of on-chip single-photon detectors, this architecture is among the most promising for realizing on-chip quantum optics experiments.

Inducible Knockout of 14-3-3β Attenuates Proliferation and Spheroid Formation in a Human Glioblastoma Cell Line U87MG.

Glioblastomas (GBs) are the most common and malignant brain tumors in adults. A protein encoded by the gene YWHAB, 14-3-3β, is commonly found to be upregulated throughout the initiation and progression of GB. The 14-3-3β has oncogenic roles in several different types of cancer cells through interactions with proteins such as Bad, FBI1, Raf-1, Cdc25b, and others.

The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis.

The oxidative balance of a cell is maintained by the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic throughout stages of carcinogenesis (including initiation, promotion, progression, and metastasis) is complex.

Exploring structural effects in a new class of NRF2 inhibitors.

NRF2 is a transcription factor that controls the cellular response to various stressors, such as reactive oxygen and nitrogen species. As such, it plays a key role in the suppression of carcinogenesis, but constitutive NRF2 expression in cancer cells leads to resistance to chemotherapeutics and promotes metastasis. As a result, inhibition of the NRF2 pathway is a target for new drugs, especially for use in conjunction with established chemotherapeutic agents like carboplatin and 5-fluorouracil.

Multivariate chemogenomic screening prioritizes new macrofilaricidal leads.

Development of direct acting macrofilaricides for the treatment of human filariases is hampered by limitations in screening throughput imposed by the parasite life cycle. In vitro adult screens typically assess single phenotypes without prior enrichment for chemicals with antifilarial potential. We developed a multivariate screen that identified dozens of compounds with submicromolar macrofilaricidal activity, achieving a hit rate of >50% by leveraging abundantly accessible microfilariae.

Pharmacological Profiling of a Brugia malayi Muscarinic Acetylcholine Receptor as a Putative Antiparasitic Target.

The diversification of anthelmintic targets and mechanisms of action will help ensure the sustainable control of nematode infections in response to the growing threat of drug resistance. G protein-coupled receptors (GPCRs) are established drug targets in human medicine but remain unexploited as anthelmintic substrates despite their important roles in nematode neuromuscular and physiological processes. Bottlenecks in exploring the druggability of parasitic nematode GPCRs include a limited helminth genetic toolkit and difficulties establishing functional heterologous expression.

wrmXpress: A modular package for high-throughput image analysis of parasitic and free-living worms.

Advances in high-throughput and high-content imaging technologies require concomitant development of analytical software capable of handling large datasets and generating relevant phenotypic measurements. Several tools have been developed to analyze drug response phenotypes in parasitic and free-living worms, but these are siloed and often limited to specific instrumentation, worm species, and single phenotypes. No unified tool exists to analyze diverse high-content phenotypic imaging data of worms and provide a platform for future extensibility.

SuperNatural 3.0-a database of natural products and natural product-based derivatives.

Natural products (NPs) are single chemical compounds, substances or mixtures produced by a living organism - found in nature. Evolutionarily, NPs have been used as healing agents since thousands of years and still today continue to be the most important source of new potential therapeutic preparations. Natural products have played a key role in modern drug discovery for several diseases.

SuperPred 3.0: drug classification and target prediction-a machine learning approach.

Since the last published update in 2014, the SuperPred webserver has been continuously developed to offer state-of-the-art models for drug classification according to ATC classes and target prediction. For the first time, a thoroughly filtered ATC dataset, that is suitable for accurate predictions, is provided along with detailed information on the achieved predictions. This aims to overcome the challenges in comparing different published prediction methods, since performance can vary greatly depending on the training dataset used.

BRAF Inhibitor Resistance Confers Increased Sensitivity to Mitotic Inhibitors.

Single agent and combination therapy with BRAF and MEK inhibitors have remarkable efficacy against melanoma tumors with activating BRAF mutations, but in most cases BRAF inhibitor (BRAFi) resistance eventually develops. One resistance mechanism is reactivation of the ERK pathway. However, only about half of BRAFi resistance is due to ERK reactivation.

Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasite Brugia malayi.

Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics that clear circulating larval parasites but are ineffective against adults. The development of effective adulticides is hampered by a poor understanding of the processes and tissues driving parasite survival in the host.

A Comparative Analysis of COVID-19 Vaccines Based on over 580,000 Cases from the Vaccination Adverse Event Reporting System.

Background: The COVID-19 pandemic is being battled via the largest vaccination campaign in history, with more than eight billion doses administered thus far. Therefore, discussions about potentially adverse reactions, and broader safety concerns, are critical. The U.

Coincident Fluorescence-Burst Analysis of the Loading Yields of Exosome-Mimetic Nanovesicles with Fluorescently-Labeled Cargo Molecules.

The possible targeting functionality and low immunogenicity of exosomes and exosome-like nanovesicles make them promising as drug-delivery carriers. To tap into this potential, accurate non-destructive methods to load them and characterize their contents are of utmost importance. However, the small size, polydispersity, and aggregation of nanovesicles in solution make quantitative characterizations of their loading particularly challenging.

A Quantitative and Qualitative Study on Patient and Physician Perceptions of Nephrology Telephone Consultation During COVID-19.

Background: COVID-19 required rapid adoption of virtual modalities to provide care for patients with a chronic disease. Care was initially provided by telephone, which has not been evaluated for its effectiveness by patients and providers. This study reports patients' and nephrologists' perceptions and preferences surrounding telephone consultation in a chronic kidney disease (CKD) clinic.

Ibrutinib Blocks YAP1 Activation and Reverses BRAF Inhibitor Resistance in Melanoma Cells.

Most B-Raf proto-oncogene (BRAF)-mutant melanoma tumors respond initially to BRAF inhibitor (BRAFi)/mitogen-activated protein kinase kinase 1 inhibitor (MEKi) therapy, although few patients have durable long-term responses to these agents. The goal of this study was to use an unbiased computational approach to identify inhibitors that reverse an experimentally derived BRAFi resistance gene expression signature. Using this approach, we found that ibrutinib effectively reverses this signature, and we demonstrate experimentally that ibrutinib resensitizes a subset of BRAFi-resistant melanoma cells to vemurafenib.

SuperTCM: A biocultural database combining biological pathways and historical linguistic data of Chinese Materia Medica for drug development.

Aim Of The Study: Botanicals used in Traditional Chinese Medicine (TCM) are a rich source for drug discovery and provide models for multi-component drug development. To facilitate the studies of the actions of TCM drugs and expand their applications, a comprehensive database is urgently required.

Methods: One online resource connects all the relevant data from multiple scientific sources and languages.