Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Discovery of Diverse CRISPR Leader Motifs, Putative Functions, and Applications for Enhanced CRISPR Detection and Subtype Annotation.

Bacteria and archaea acquire resistance to genetic parasites by preferentially integrating short fragments of foreign DNA at one end of a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR). "Leader" DNA upstream of CRISPR loci regulates transcription and foreign DNA integration into the CRISPR. Here, we analyze 37,477 CRISPRs from 39,277 bacterial and 556 archaeal genomes to identify conserved sequence motifs in CRISPR leaders.

Country-specific key lifestyle factors and health outcomes for resource allocation in the general population: a network analysis across 29 countries.

Background: We aimed to identify the central lifestyle, the most impactful among lifestyle factor clusters; the central health outcome, the most impactful among health outcome clusters; and the bridge lifestyle, the most strongly connected to health outcome clusters, across 29 countries to optimise resource allocation for local holistic health improvements.

Methods: From July 2020 to August 2021, we surveyed 16 461 adults across 29 countries who self-reported changes in 18 lifestyle factors and 13 health outcomes due to the pandemic. Three networks were generated by network analysis for each country: lifestyle, health outcome, and bridge networks.

Clinical Features and Outcomes of Patients With COVID-19 Infection and Acute Kidney Injury Requiring Hemodialysis in an Intensive Care Unit: A Retrospective Study From a Tertiary Care Center in Eastern India.

Background: During the COVID-19 pandemic, it has been observed that acute kidney injury (AKI) especially requiring intervention support of hemodialysis has notably increased mortality rates among COVID-19-positive critically ill patients; however, comprehensive data regarding this from India, especially the eastern territory, remains sparse. This study aims to outline the demographic, clinical, and biochemical characteristics, along with the outcomes, of these patients.

Methods: A retrospective study was performed at the All India Institute of Medical Sciences (AIIMS), Patna, from March 1, 2020, to March 31, 2021.

Clinical outcomes of stage IIA/IIB seminoma treated with radiotherapy and chemotherapy: should regional therapy be considered the preferred treatment approach?

Purpose: The optimal management of patients with de novo clinical stage IIA/B (CSIIA/B) or relapsed CSIIA/B (Rel-CSIIA/B) seminoma remains debated due to a lack of randomized evidence. Herein, we sought to evaluate outcomes following radiotherapy and chemotherapy in this setting.

Materials And Methods: A prospectively maintained single-institutional database was retrospectively queried for patients diagnosed between 1995-2016 with de novo or Rel-CSIIA/B.

Bosniak Classification of Cystic Renal Masses Version 2019: Proportion of Malignancy by Class and Subclass-Systematic Review and Meta-Analysis.

Bosniak classification version 2019 (v2019) was a major revision to version 2005 (v2005) that defined cystic renal mass subclasses based on wall or septa features. To determine the proportion of malignancy within cystic renal masses stratified by Bosniak classification v2019 class and feature-based subclass. MEDLINE and EMBASE databases were searched on July 24, 2023 for studies published in 2019 or later that reported cystic renal masses that underwent renal-mass CT or MRI, were assessed using Bosniak v2019, and had a reference standard (histopathology indicating benignity or malignancy or ≥5-year imaging follow-up indicating benignity).

Association between thyroid dysfunction and insulin resistance: a retrospective cohort study.

Objective: To evaluate the association between thyroid disease and diabetes markers.

Design: Retrospective cohort study.

Setting: The study was conducted in a diagnostic setting where the primary care providers recommended the patients to test for thyroid and diabetes panels.

Pain in rheumatoid arthritis: Emerging role of high mobility group box 1 protein-HMGB1.

Rheumatoid arthritis (RA) is a chronic inflammatory disease where pain, driven by both inflammatory and non-inflammatory processes, is a major concern for patients. This pain can persist even after joint inflammation subsides. High mobility group box-1 (HMGB1) is a non-histone-DNA binding protein located in the nucleus that plays a key role in processes such as DNA transcription, recombination, and replication.

Retrospective Cohort Study on the Predictive Value of Primary Non-response to Initial Biologic for Future Biologic Use in Patients with Inflammatory Bowel Disease.

Background: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, which has expanded treatment options, particularly after first biologic failure. Currently, there are limited studies investigating the predictive value of first biologic primary non-response (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive of response to subsequent biologic therapy.

Unravelling situational awareness of multi-tasking pedestrians through average gaze fixation durations: An accelerated failure time modelling approach.

Pedestrians use visual cues (i.e., gaze) to communicate with the other road users, and visual attention towards the surrounding environment is essential to be situationally aware and avoid oncoming conflicts.

Photodynamic antimicrobial therapy with Erythrosin B, Eosin Y, and Rose Bengal for the inhibition of fungal keratitis isolates: An in vitro study.

Introduction: Fungal keratitis is a leading cause of corneal blindness, with current antifungal treatments having limited efficacy. One promising treatment modality is Rose Bengal (RB) photodynamic antimicrobial therapy (PDAT) that has shown mixed success against fungal keratitis. Therefore, there is a need to explore the antimicrobial efficacy of other green-light activated photosensitizers that have deep penetration in the cornea to combat the deep fungal infections, such as Erythrosin B (EB) and Eosin Y (EY).

Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy.

Dystrophy-associated fer-1-like protein (dysferlin) conducts plasma membrane repair. Mutations in the DYSF gene cause a panoply of genetic muscular dystrophies. We targeted a frequent loss-of-function, DYSF exon 44, founder frameshift mutation with mRNA-mediated delivery of SpCas9 in combination with a mutation-specific sgRNA to primary muscle stem cells from two homozygous patients.

Single-neuron spiking variability in hippocampus dynamically tracks sensory content during memory formation in humans.

During memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world.

Opportunities and challenges for human microphysiological systems in drug development.

Microphysiological systems (MPS) are complex in vitro tools that incorporate cells derived from various healthy or disease-state human or animal tissues and organs. While MPS have limitations, including a lack of globally harmonized guidelines for standardization, they have already proven impactful in certain areas of drug development. Further research and regulatory acceptance of MPS will contribute to making them even more effective tools in the future.

Status of Serum Magnesium among Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is one of the largest public health issues and the major cause of death worldwide. Due to an increase in the incidence of systemic diseases like diabetes and hypertension, which are the two main causes of CKD and kidney damage, the prevalence of CKD is rising globally. Chronic Kidney Disease results in mineral disorders as well as profound lipid disorders due to improper balancing of the mineral & hormone levels in the body.

Effect of Serum Vitamin-D in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance and relative lack of insulin. This cross sectional study was carried out in the Department of Biochemistry, Mymensingh Medical College and in collaboration with the Department of Endocrinology, Mymensingh Medical College Hospital, Mymensingh from July 2021 to June 2022. A total of 100 subjects were included in this study.

Status of Serum Iron in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) remains a major public health problem with relatively high prevalence rates worldwide (5.0-13.0%).

NaP-TRAP reveals the regulatory grammar in 5'UTR-mediated translation regulation during zebrafish development.

The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP).

Promising antiviral inhibitors against lumpy skin disease: A vetinformatics approach.

Background: Lumpy skin disease (LSD) is a transboundary virus disease that mostly affects cattle. It has recently been reported all over the world, which highlights the need for efficient control methods. LSD poses serious economic dangers worldwide.

Evaluation of rheological properties of guar gum-based fracturing fluids enhanced with hydroxyl group bearing thermodynamic hydrate inhibitors.

Naturally occurring gas clathrates are a significant methane resource-the primary component of natural gas, regarded as the cleanest hydrocarbon and a key feedstock for producing gray and blue hydrogen. Despite the global abundance of gas hydrate reserves, extraction via depressurization has yet to achieve commercially viable production rates. The primary limitation lies in the low permeability of hydrate-bearing sediments, where solid clathrates obstruct porous pathways, hindering dissociation and slowing gas recovery.

Epidermal Collagen Reduction Drives Selective Aspects of Aging in Sensory Neurons.

Despite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron in Caenorhabditis elegans as a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits.