Neural substrates of individual differences in learning generalization via combined brain stimulation and multitasking training.

A pervasive limitation in cognition is reflected by the performance costs we experience when attempting to undertake two tasks simultaneously. While training can overcome these multitasking costs, the more elusive objective of training interventions is to induce persistent gains that transfer across tasks. Combined brain stimulation and cognitive training protocols have been employed to improve a range of psychological processes and facilitate such transfer, with consistent gains demonstrated in multitasking and decision-making.

Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance.

The CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. The CONSORT Dose-finding Extension (DEFINE) extends the guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such trials generally focus on safety, tolerability, activity, and recommending dosing and scheduling regimens for further clinical development.

Intestinal barrier disruption with Plasmodium falciparum infection in pregnancy and risk of preterm birth: a cohort study.

Background: Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and whether this contributes to systemic inflammation, altered angiogenesis, and preterm birth.

Methods: We quantified plasma concentrations of gut leak markers, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) from 1339 HIV-negative pregnant Malawians at <24 weeks gestational age.

Combinatorial fluorescent labeling of live anaerobic bacteria via the incorporation of azide-modified sugars into newly synthesized macromolecules.

The human gut microbiome modulates physiological functions and pathologies; however, a mechanistic understanding of microbe-host and microbe-microbe interactions remains elusive owing to a lack of suitable approaches to monitor obligate anaerobic bacterial populations. Common genetically encoded fluorescent protein reporters, derived from the green fluorescent protein, require an oxidation step for fluorescent light emission and therefore are not suitable for use in anaerobic microbes residing in the intestine. Fluorescence in situ hybridization is a useful alternative to visualize bacterial communities in their natural niche; however, it requires tissue fixation.

Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific.

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

Background: Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers.

Methods: To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets.

G protein-receptor kinases 5/6 are the key regulators of G protein-coupled receptor 35-arrestin interactions.

Human G protein-coupled receptor 35 is regulated by agonist-mediated phosphorylation of a set of five phospho-acceptor amino acids within its C-terminal tail. Alteration of both Ser and Ser to alanine in the GPR35a isoform greatly reduces the ability of receptor agonists to promote interactions with arrestin adapter proteins. Here, we have integrated the use of cell lines genome edited to lack expression of combinations of G protein receptor kinases (GRKs), selective small molecule inhibitors of subsets of these kinases, and antisera able to specifically identify either human GPR35a or mouse GPR35 only when Ser and Ser (orce; the equivalent residues in mouse GPR35) have become phosphorylated to demonstrate that GRK5 and GRK6 cause agonist-dependent phosphorylation of these residues.

Creation of a theoretically rooted workbook to support implementers in the practice of knowledge translation.

Background: Few training opportunities or resources for non-expert implementers focus on the "practice" as opposed to the "science" of knowledge translation (KT). As a guide for novice implementers, we present an open-access, fillable workbook combining KT theories, models, and frameworks (TMFs) that are commonly used to support the implementation of evidence-based practices. We describe the process of creating and operationalizing our workbook.

USNAP: fast unique dense region detection and its application to lung cancer.

Motivation: Many real-world problems can be modeled as annotated graphs. Scalable graph algorithms that extract actionable information from such data are in demand since these graphs are large, varying in topology, and have diverse node/edge annotations. When these graphs change over time they create dynamic graphs, and open the possibility to find patterns across different time points.

PGAM5 is an MFN2 phosphatase that plays an essential role in the regulation of mitochondrial dynamics.

Mitochondrial morphology is regulated by the post-translational modifications of the dynamin family GTPase proteins including mitofusin 1 (MFN1), MFN2, and dynamin-related protein 1 (DRP1). Mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5) is emerging as a regulator of these post-translational modifications; however, its precise role in the regulation of mitochondrial morphology is unknown. We show that PGAM5 interacts with MFN2 and DRP1 in a stress-sensitive manner.

Comprehensive analysis of the progression mechanisms of CRPC and its inhibitor discovery based on machine learning algorithms.

Almost all patients treated with androgen deprivation therapy (ADT) eventually develop castration-resistant prostate cancer (CRPC). Our research aims to elucidate the potential biomarkers and molecular mechanisms that underlie the transformation of primary prostate cancer into CRPC. We collected three microarray datasets (GSE32269, GSE74367, and GSE66187) from the Gene Expression Omnibus (GEO) database for CRPC.

Cosmography Using Strongly Lensed Gravitational Waves from Binary Black Holes.

Third generation gravitational wave (GW) detectors are expected to detect millions of binary black hole (BBH) mergers during their operation period. A small fraction of them (∼1%) will be strongly lensed by intervening galaxies and clusters, producing multiple observable copies of the GW signals. The expected number of lensed events and the distribution of the time delay between lensed images depend on the cosmology.

Claustral neurons projecting to frontal cortex restrict opioid consumption.

The synthetic opioid fentanyl is a major contributor to the current opioid addiction crisis. We report that claustral neurons projecting to the frontal cortex limit oral fentanyl self-administration in mice. We found that fentanyl transcriptionally activates frontal-projecting claustrum neurons.

An effective kinase inhibition strategy for metastatic recurrent childhood medulloblastoma.

Purpose: Medulloblastomas (MBs) constitute the most common malignant brain tumor in children and adolescents. MYC-amplified Group 3 MBs are characterized by disease recurrence, specifically in the leptomeninges, whereby patients with these metastatic tumors have a mortality rate nearing 100%. Despite limited research on such tumors, studies on MB metastases at diagnosis suggest targeting kinases to be beneficial.

A vital role for PICK1 in the differential regulation of metabotropic glutamate receptor internalization and synaptic AMPA receptor endocytosis.

Group I metabotropic glutamate receptors (mGluRs) play important roles in many neuronal processes and are believed to be involved in synaptic plasticity underlying the encoding of experience, including classic paradigms of learning and memory. These receptors have also been implicated in various neurodevelopmental disorders, such as Fragile X syndrome and autism. Internalization and recycling of these receptors in the neuron are important mechanisms to regulate the activity of the receptor and control the precise spatiotemporal localization of these receptors.

FAIR in action - a flexible framework to guide FAIRification.

The COVID-19 pandemic has highlighted the need for FAIR (Findable, Accessible, Interoperable, and Reusable) data more than any other scientific challenge to date. We developed a flexible, multi-level, domain-agnostic FAIRification framework, providing practical guidance to improve the FAIRness for both existing and future clinical and molecular datasets. We validated the framework in collaboration with several major public-private partnership projects, demonstrating and delivering improvements across all aspects of FAIR and across a variety of datasets and their contexts.

Quantum process tomography with unsupervised learning and tensor networks.

The impressive pace of advance of quantum technology calls for robust and scalable techniques for the characterization and validation of quantum hardware. Quantum process tomography, the reconstruction of an unknown quantum channel from measurement data, remains the quintessential primitive to completely characterize quantum devices. However, due to the exponential scaling of the required data and classical post-processing, its range of applicability is typically restricted to one- and two-qubit gates.

Synthetic dataset of speckle images for fiber optic temperature sensor.

The published data correspond to images of simulated specklegrams, which result from the calculation of the modal interference that occurs in a multimode optical fiber. These have a characteristic pattern due to the constructive or destructive interference between the light modes depending on their phase differences. The specklegram contains valuable information since the propagation of the modes varies according to the influence of some external disturbances, and therefore, the speckle pattern changes.

Lessons Learned in Mechanical Ventilation/Oxygen Support in Coronavirus Disease 2019.

The clinical spectrum of severe acute respiratory syndrome coronavirus-2 infection ranges from asymptomatic infection or mild respiratory symptoms to pneumonia, with severe cases leading to acute respiratory distress syndrome with multiorgan involvement. The clinical management of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) changed over the course of the pandemic, being adjusted as more evidence became available. This article will review how the ventilatory management of COVID-19 ARDS evolved and will conclude with current evidence-based recommendations.

JBrowse 2: a modular genome browser with views of synteny and structural variation.

We present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. It retains core features of JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. It allows users to share sessions, open multiple genomes, and navigate between views.

Association of lung recruitment and change in recruitment-to-inflation ratio from supine to prone position in acute respiratory distress syndrome.

Prone positioning is an evidence-based treatment for patients with moderate-to-severe acute respiratory distress syndrome. Lung recruitment has been proposed as one of the mechanisms by which prone positioning reduces mortality in this group of patients. Recruitment-to-inflation ratio (R/I) is a method to measure potential for lung recruitment induced by a change in positive end-expiratory pressure (PEEP) on the ventilator.

Generation and Characterization of Engineered Ubiquitin Variants to Modulate the Ubiquitin Signaling Cascade.

The ubiquitin signaling cascade plays a crucial role in human cells. Consistent with this, malfunction of ubiquitination and deubiquitination is implicated in the initiation and progression of numerous human diseases, including cancer. Therefore, the development of potent and specific modulators of ubiquitin signal transduction has been at the forefront of drug development.