Determining the effects of transcranial alternating current stimulation on corticomotor excitability and motor performance: A sham-controlled comparison of four frequencies.

Transcranial alternating current stimulation (tACS) modulates brain oscillations and corticomotor plasticity. We examined the effects of four tACS frequencies (20 Hz, 40 Hz, 60 Hz, and 80 Hz) on motor cortex (M1) excitability and motor performance. In a randomised crossover design, 12 adults received 20-minute tACS sessions, with Sham as control.

Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain.

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left.

Pragmatic Algorithm for Visual Assessment of 4-Repeat Tauopathies in [F]PI-2620 PET Scans.

Aim: Standardized evaluation of [F]PI-2620 tau-PET scans in 4R-tauopathies represents an unmet need in clinical practice. This study aims to investigate the effectiveness of visual evaluation of [F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility.

Methods: A total of 83 individuals with [F]PI-2620 PET scans were included.

Individual patient and donor seroprofiles in convalescent plasma treatment of COVID-19 in REMAP-CAP clinical trial.

Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.

Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.

Phylogeny and virulence determinant detection of Fusobacterium necrophorum strains isolated at the UK Anaerobe Reference Unit between 1982 and 2019.

Objectives: Explore the presence, or absence, of virulence genes and the phylogeny of a multi-decade UK collection of clinical and reference Fusobacterium necrophorum isolates.

Methods: Three hundred and eighty-five F. necrophorum strains (1982-2019) were recovered from storage (-80°C).

Molecular evidence for the efficacy of PBM therapy in the treatment of Oral lichen planus.

Purpose: Oral lichen planus (OLP) is a chronic inflammatory disease, in which T-Lymphocytes induce apoptosis of basal keratinocytes, leading to the formation of symptomatic lesions. It is assumed that blocking the cell death program and enhancing cell proliferation would be crucial to the healing process. The aim of the study was to verify the efficacy of Photobiomodulation (PBM) in OLP management, by evaluating the effects of laser irradiation on the processes of apoptosis and cell proliferation.

An exploration of the relationship between ineffective modes of mentalization and difficulties related to borderline personality disorder: A network approach.

Background: The mentalization-based perspective of Borderline Personality Disorder (BPD) underscores fluctuating interpersonal functionality, believed to arise from suboptimal mentalization modes, including hyper- and hypomentalizing. The connection between ineffective mentalizing and specific BPD challenges remains ambiguous. Network theory offers a unique means to investigate the hypothesis that distinct yet interconnected mental challenges ('symptoms') construct 'disorders' through their continuous mutual interactions.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Associations of Accelerometer-Derived Moderate-to-Vigorous Physical Activity and Atrioventricular Block in a Healthy Elderly Population.

Background: There is limited information on protective factors related to atrioventricular (AV) block.

Objective: This study examines the association between accelerometer-derived moderate-to-vigorous physical activity (MVPA) and AV block in healthy elderly individuals.

Methods: A total of 23,590 UK Biobank participants ≥60 years involved in a wrist-worn accelerometer study with no history of hypertension, diabetes mellitus, dyslipidemia, and coronary heart disease were analyzed.

The multifaceted function of FoxO1 in pancreatic β-cell dysfunction and insulin resistance: Therapeutic potential for type 2 diabetes.

The forkhead box O1 (FOXO1), the first discovered member of the FoxO family, is a critical transcription factor predominantly found in insulin-secreting and insulin-sensitive tissues. In the pancreas of adults, FoxO1 expression is restricted to islet β cells. We determined that in human islet microarray datasets, FoxO1 expression is higher than other FoxO transcription factors.

"Pattern Regulation in Epimorphic Fields", aka the Polar Coordinate Model.

The Polar Coordinate Model (PCM) was a model, published in 1976, to account for the properties of distal regeneration in the appendages of insects and vertebrates. It had considerable impact at the time and has continued to be cited ever since. This article describes the work that led up to the model, the genesis of the model itself, its strengths and weaknesses, and its long term impact.

Degeneration of the nucleus pulposus affects the internal volumetric strains and failure location of adjacent human metastatic vertebral bodies.

Intervertebral disc (IVD) degeneration is suspected to affect the distribution of stress and strain near the vertebral endplates and in the underlying bone. This scenario is worsened by the presence of metastatic lesions on the vertebrae (primarily thoracic vertebrae (60-80%)) which increase the risk of fracture. As such, this study aimed to evaluate the effect of IVD degeneration on the internal volumetric strains and failure modes of human metastatic vertebral bodies.

Association between Congenital Zika Syndrome and hospitalizations during early childhood: a nationwide cohort study.

Background Congenital Zika Syndrome (CZS) has been linked to a wide spectrum of abnormalities. However, differences in hospitalization patterns between children with and without CZS have not yet been investigated. Methods We compared rates of hospital admissions for all and specific diseases, proportions of admission causes, and total length of hospital stay (LOS) between children with CZS and those without the syndrome.

Effect of mass campaigns with full and fractional doses of pneumococcal conjugate vaccine (Pneumosil) on the reduction of nasopharyngeal pneumococcal carriage in Niger: a three-arm, open-label, cluster-randomised trial.

Background: In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger.

Methods: In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign.

Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.

Background: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

Methods: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales.

Single-cell RNA-seq identifies protracted mouse germline X chromosome reactivation dynamics directed by a PRC2-dependent mechanism.

Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells.

Cryo-EM reconstruction of yeast ADP-actin filament at 2.5 Å resolution. A comparison with vertebrate F-actin.

The core component of the actin cytoskeleton is the globular protein G-actin, which reversibly polymerizes into filaments (F-actin). Budding yeast possesses a single actin that shares 87%-89% sequence identity with vertebrate actin isoforms. Previous structural studies indicate very close overlap of main-chain backbones.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Prediction of future input explains lateral connectivity in primary visual cortex.

Neurons in primary visual cortex (V1) show a remarkable functional specificity in their pre- and postsynaptic partners. Recent work has revealed a variety of wiring biases describing how the short- and long-range connections of V1 neurons relate to their tuning properties. However, it is less clear whether these connectivity rules are based on some underlying principle of cortical organization.

Mechanistic basis of temperature adaptation in microtubule dynamics across frog species.

Cellular processes are remarkably effective across diverse temperature ranges, even with highly conserved proteins. In the context of the microtubule cytoskeleton, which is critically involved in a wide range of cellular activities, this is particularly striking, as tubulin is one of the most conserved proteins while microtubule dynamic instability is highly temperature sensitive. Here, we leverage the diversity of natural tubulin variants from three closely related frog species that live at different temperatures.

ABA-auxin cascade regulates crop root angle in response to drought.

Enhancing drought resistance through the manipulation of root system architecture (RSA) in crops represents a crucial strategy for addressing food insecurity challenges. Abscisic acid (ABA) plays important roles in drought tolerance; yet, its molecular mechanisms in regulating RSA, especially in cereal crops, remain unclear. In this study, we report a new mechanism whereby ABA mediates local auxin biosynthesis to regulate root gravitropic response, thereby controlling the alteration of RSA in response to drought in cereal crops.

Joint Associations of Sedentary Time and Intensity-Specific Physical Activity With Cancer Mortality: A Device-Based Cohort Study of 72,458 UK Adults.

Background: There are no studies examining the prospective joint association of device-based measures of sedentary time and physical activity (PA) with cancer mortality. We examined the joint associations of sedentary time and intensity-specific PA with cancer mortality in 72,458 adults from UK Biobank.

Methods: Participants wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days (with at least 1 weekend day).