Point-of-care tests, diagnostic uncertainty and antimicrobial stewardship in the ICU: procalcitonin or PCR to aid antibiotic-stop decisions - an observational cohort study.

Objectives: Intensive care unit (ICU) clinicians stop antibiotics more often, with a negative infection: point-of-care test (PCR-POCT). Simulated cases of diagnostic uncertainty regarding infection resolution led clinicians to choose options such as procalcitonin (PCT) and/or PCR-POCTs +/- de-escalation to aid stop decisions. We hypothesised that a direct infection indicator, PCR-POCT, would influence stop judgements more than indirect PCT.

Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles.

Background: An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.

Methods: We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels.

A platform for multimodal pooled genetic screens reveals regulators of liver function.

Organ function requires coordinated activities of thousands of genes in distinct, spatially organized cell types. Understanding the basis of emergent tissue function requires approaches to dissect the genetic control of diverse cellular and tissue phenotypes . Here, we develop paired imaging and sequencing methods to construct large-scale, multi-modal genotype-phenotypes maps in tissue with pooled genetic perturbations.

Outcomes of X-Linked Agammaglobulinaemia Patients.

Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.

Seed sequences mediate off-target activity in the CRISPR-interference system.

The CRISPR interference (CRISPRi) system is a powerful tool for selectively and efficiently silencing genes in functional genomics research applications. However, its off-target activity has not been systematically investigated. Here, we utilized a genome-wide CRISPRi-Cas9 single-guide RNA (sgRNA) library to investigate the presence of off-target activity and its effects on gene expression.

Transforming healthcare with integrated inter-professional education in a research-driven medical school.

Singapore, located strategically at the meeting point of the Malacca Strait and the South China Sea, has established itself as a global financial and economic hub. Despite its small geographical size, Singapore is home to over 5 million people from diverse cultural backgrounds. The city-state's medical education landscape has evolved significantly over the past century.

Epigenomic and phenotypic characterization of DEGCAGS syndrome.

Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities syndrome (DEGCAGS, MIM #619488) is caused by biallelic, loss-of-function (LoF) ZNF699 variants, and is characterized by variable neurodevelopmental disability, discordant organ anomalies among full siblings and infant mortality. ZNF699 encodes a KRAB zinc finger protein of unknown function. We aimed to investigate the genotype-phenotype spectrum of DEGCAGS and the possibility of a diagnostic DNA methylation episignature, to facilitate the diagnosis of a highly variable condition lacking pathognomonic clinical findings.

Structural equation modelling of the role of cognition in functional interference and treatment nonadherence among haemodialysis patients.

Background And Objectives: Cognitive impairment is common in haemodialysis patients and associated with adverse health outcomes. This may be due to cognitive impairments interfering with daily functioning and self-care, but evidence is limited. This cross-sectional study aims to explore the interrelationships between cognition and functional outcomes in haemodialysis patients.

Coronary Vasospasm Presenting in a Catastrophic Way.

Coronary artery vasospasm is an under-recognized yet fatal condition that can manifest as sudden cardiac arrest. A 51-year-old man presented with out-of-hospital cardiac arrest due to ventricular fibrillation during exercise. Coronary angiogram showed severe disease at ostial left main coronary artery and left anterior descending artery (LAD), that was not present anymore on repeated angiography and intravascular ultrasound assessment.

Virtual Reality in Cancer Care: Enhancing Knowledge and Reducing Anxiety about Chemotherapy among Patients and Caregivers.

Virtual reality (VR) technology has evolved from entertainment to significant applications in healthcare and education. Despite its potential, there is limited research on the role of VR in cancer care. This study investigates VR's ability to simulate the chemotherapy process, aiming to enhance patients' knowledge and mitigate anxiety associated with chemotherapy.

A Novel Variant Causes Hereditary Spastic Paraplegia in a Consanguineous Pakistani Family.

Hereditary spastic paraplegia (HSP) is characterized by unsteady gait, motor incoordination, speech impairment, abnormal eye movement, progressive spasticity and lower limb weakness. Spastic paraplegia 75 (SPG75) results from a mutation in the gene that encodes myelin associated glycoprotein (MAG). Only a limited number of variants associated with SPG75 in families of European, Middle Eastern, North African, Turkish and Palestinian ancestry have been documented so far.

Chromosomal-level reference genome assembly of muskox (Ovibos moschatus) from Banks Island in the Canadian Arctic, a resource for conservation genomics.

The muskox (Ovibos moschatus), an integral component and iconic symbol of arctic biocultural diversity, is under threat by rapid environmental disruptions from climate change. We report a chromosomal-level haploid genome assembly of a muskox from Banks Island in the Canadian Arctic Archipelago. The assembly has a contig N50 of 44.

Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives.

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Recent advances highlight the role of tumor-derived extracellular vesicles (TEV) and circulating hybrid cells (CHC) in UM tumorigenesis. Bridged with liquid biopsies, a novel technology that has shown incredible performance in detecting cancer cells or products derived from tumors in bodily fluids, it can significantly impact disease management and outcome.

Design of Highly Electrophilic and Stable Metal Nitrido Complexes.

ConspectusMetal oxo (M═O) and nitrido (M≡N) complexes are two important classes of high-valent transition metal complexes. The use of M═O as oxidants in chemical and biological systems has been extensively investigated. Nature makes use of M═O in enzymes such as cytochrome to oxidize a variety of substrates.

The causal effect of gut microbiota on hepatic encephalopathy: a mendelian randomization analysis.

Background: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated.

Method: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk.

Kinesins regulate the heterogeneity in centrosome clustering after whole-genome duplication.

After whole-genome duplication (WGD), tetraploid cells can undergo multipolar mitosis or pseudo-bipolar mitosis with clustered centrosomes. Kinesins play a crucial role in regulating spindle formation. However, the contribution of kinesin expression levels to the heterogeneity in centrosome clustering observed across different cell lines after WGD remains unclear.

Imaging Anisotropic Proton Intercalation in Photochromic MoO.

Protonation represents a fundamental chemical process with promising applications in the fields of energy, environment, and memory devices. Probing the protonation mechanism, however, presents a formidable challenge owing to the elusiveness of intercalated protons. In this work, we utilize the atomic and electronic structure changes associated with protonation to directly image the proton intercalation pathways in α-MoO induced by UV illumination.

Dual Pathways in Catalytic Ammonia Oxidation by a Ruthenium Complex Bearing a Tetradentate Bipyridine-Bipyrazole Ligand: Isolation of a Diruthenium Intermediate with a μ-Hexazene Derivative.

We report herein chemical and electrochemical ammonia oxidation (AO) catalyzed by a Ru complex, [Ru(HL)(pic)] [, HL = 6,6'-di(1H-pyrazol-3-yl)-2,2'-bipyridine, pic = 4-picoline], where HL is a tetradentate ligand with a bipyridyl unit connected to two pyrazoles. functions as an efficient electrocatalyst for the oxidation of NH to N, with a low overpotential of 0.51 V vs Fc and a Faradaic efficiency of 96%.

Expanding the Mutational Landscape and Clinical Phenotype of CHD2-Related Encephalopathy.

Objectives: To present a case series of novel variants in patients presenting with genetic epileptic and developmental encephalopathy.

Background: CHD2 gene encodes an ATP-dependent enzyme, chromodomain helicase DNA-binding protein 2, involved in chromatin remodeling. Pathogenic variants in CHD2 are linked to early-onset conditions such as developmental and epileptic encephalopathy, drug-resistant epilepsies, and neurodevelopmental disorders.