Coherent Excitation of the CH Stretching Vibrations in CH : The Role of the Derivative Coupling Studied by the Quantum Ehrenfest Method.

We report nonadiabatic dynamics computations on CH initiated on a coherent superposition of the five lowest cationic states, employing the Quantum Ehrenfest method. In addition to the totally symmetric carbon-carbon double bond stretch and carbon-hydrogen stretches, we see that the three non-totally symmetric modes become stimulated; torsion and three different CH stretching patterns. Thus, a coherent superposition of states, of the type involved in an attochemistry experiment, leads to the stimulation of specific non-totally symmetric motions.

S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.

S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer.

Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

PSTK exerts protective role in cisplatin-tubular cell injury via BAX/BCL2/Caspase3 pathway.

Cisplatin is a widely used anticancer drug, but its accumulation in renal tubular epithelial cells (TECs) can cause acute kidney injury. Phosphoseryl-tRNA kinase (PSTK) is an intermediate product produced under oxidative stress conditions. This study aimed to elucidate whether PSTK could protect TECs and its possible mechanisms.

Not seeing the trees for the forest. The impact of neighbours on graph-based configurations in histopathology.

Background: Deep learning (DL) has set new standards in cancer diagnosis, significantly enhancing the accuracy of automated classification of whole slide images (WSIs) derived from biopsied tissue samples. To enable DL models to process these large images, WSIs are typically divided into thousands of smaller tiles, each containing 10-50 cells. Multiple Instance Learning (MIL) is a commonly used approach, where WSIs are treated as bags comprising numerous tiles (instances) and only bag-level labels are provided during training.

BenchAMRking: a Galaxy-based platform for illustrating the major issues associated with current antimicrobial resistance (AMR) gene prediction workflows.

Background: The Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) networks 'Seq4AMR' and 'B2B2B AMR Dx' were established to promote collaboration between microbial whole genome sequencing (WGS) and antimicrobial resistance (AMR) stakeholders. A key topic discussed was the frequent variability in results obtained between different microbial WGS-related AMR gene prediction workflows. Further, comparative benchmarking studies are difficult to perform due to differences in AMR gene prediction accuracy and a lack of agreement in the naming of AMR genes (semantic conformity) for the results obtained.

Orphanhood and caregiver death among children in the United States by all-cause mortality, 2000-2021.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.

Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

Longitudinal study of care needs and behavioural changes in people living with dementia using in-home assessment data.

Background: People living with dementia often experience changes in independence and daily living, affecting their well-being and quality of life. Behavioural changes correlate with cognitive decline, functional impairment, caregiver distress, and care availability.

Methods: We use data from a 3-year prospective observational study of 141 people with dementia at home, using the Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory and cognitive assessments, alongside self-reported and healthcare-related data.

Building the Capacity of Young Professionals in Family Planning to Publish: Insights from the ICFP2022 WHO Scientific Writing, Mentoring and Coaching Course.

Objectives: We describe the development, delivery, and evaluation of a program to support junior professionals to publish their work in a scientific journal.

Study Design: Conference delegates with an accepted abstract at the International Conference on Family Planning (ICFP), self-identifying as junior professionals and from a low- or middle-income country (LMIC) or working predominantly in LMIC settings, were eligible for the program. The program involved: (i) Four face-to-face workshops at ICFP from the 14 to 17 of November 2022; (ii) mentoring meetings at ICFP; (iii) a six-month post-conference online coaching program; and (iv) post-conference learning webinars from December 2022 to May 2023.

The influence of phosphoinositide lipids in the molecular biology of membrane proteins: recent insights from simulations.

The phosphoinositide family of membrane lipids play diverse and critical roles in eukaryotic molecular biology. Much of this biological activity derives from interactions of phosphoinositide lipids with integral and peripheral membrane proteins, leading to modulation of protein structure, function, and cellular distribution. Since the discovery of phosphoinositides in the 1940s, combined molecular biology, biophysical, and structural approaches have made enormous progress in untangling this vast and diverse cellular network of interactions.

Unlocking the diagnostic potential of electrocardiograms through information transfer from cardiac magnetic resonance imaging.

Cardiovascular diseases (CVD) can be diagnosed using various diagnostic modalities. The electrocardiogram (ECG) is a cost-effective and widely available diagnostic aid that provides functional information of the heart. However, its ability to classify and spatially localise CVD is limited.

Redesigning protonic ceramic electrochemical cells to lower the operating temperature.

Protonic ceramic electrochemical cells (PCECs) can operate at intermediate temperatures (450° to 600°C) for power generation and hydrogen production. However, the operating temperature is still too high to revolutionize ceramic electrochemical cell technology. Lowering the operating temperature to <450°C will enable a wider material choice and reduce system costs.

ctDNA: A Gateway for Personalized Risk Stratification in Surgically Resectable Hepatocellular Cancer.

While deemed potentially curative, surgical resection of hepatocellular carcinoma (HCC) is associated with >70% risk of post-operative relapse. Recurrence is uniquely multifactorial in HCC, potentially stemming from metachronous re-occurrence of the original tumor or de novo cancerization. Circulating tumor DNA may improve personalized risk stratification post-resection, a setting where adjuvant immunotherapy has failed to provide survival benefits.

What Impact Does Net Zero Action on Road Transport and Building Heating Have on Exposure to UK Air Pollution?

This study explores the cobenefits of reduced nitrogen dioxide (NO), ozone (O), and particulate matter (PM), through net zero (NZ) climate policy in the UK. Two alternative NZ scenarios, the balanced net zero (BNZP) and widespread innovation (WI) pathways, from the UK Climate Change Committee's Sixth Carbon Budget, were examined using a chemical transport model (CTM). Under the UK existing policy, Business as Usual (BAU), reductions in NO and PM were predicted by 2030 due to new vehicle technologies but plateau by 2040.

Epigenetic Inhibitors Differentially Impact TGF-β1 Signaling Cascades in COPD Airway Smooth Muscle Cells.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression.

Excessive Supraventricular Ectopic Activity in Patients With Acute Ischemic Stroke Is Associated With Atrial Fibrillation Detection Within 24 Months After Stroke: A Predefined Analysis of the MonDAFIS Study.

Background: Excessive supraventricular ectopic activity (ESVEA) is regarded as a risk marker for later atrial fibrillation (AF) detection.

Methods And Results: The investigator-initiated, prospective, open, multicenter MonDAFIS (Impact of Standardized Monitoring for Detection of Atrial Fibrillation in Ischemic Stroke) study randomized 3465 patients with acute ischemic stroke without known AF 1:1 to usual diagnostic procedures for AF detection or additive Holter monitoring in hospital for up to 7 days, analyzed in a core laboratory. Secondary study objectives include the comparison of recurrent stroke, myocardial infarction, major bleeding, and all-cause death within 24 months in patients with ESVEA (defined as ectopic supraventricular beats ≥480/day or atrial runs of 10-29 seconds or both) versus patients with newly diagnosed AF versus patients without ESVEA or AF (non-ESVEA/AF), randomized to the intervention group.

Strategies to Increase Response Rate and Reduce Nonresponse Bias in Population Health Research: Analysis of a Series of Randomized Controlled Experiments during a Large COVID-19 Study.

Background: High response rates are needed in population-based studies, as nonresponse reduces effective sample size and bias affects accuracy and decreases the generalizability of the study findings.

Objective: We tested different strategies to improve response rate and reduce nonresponse bias in a national population-based COVID-19 surveillance program in England, United Kingdom.

Methods: Over 19 rounds, a random sample of individuals aged 5 years and older from the general population in England were invited by mail to complete a web-based questionnaire and return a swab for SARS-CoV-2 testing.

HLA-E/ specific CD4 and CD8 T cells have a memory phenotype in individuals with TB infection.

Introduction: Tuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted specific CD8 T cells are present in the circulation of individuals with active TB (aTB) and infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB.

Probing the Design Rules for Optimizing Electron Spin Relaxation in Densely Packed Triplet Media for Quantum Applications.

Quantum technologies using electron spins have the advantage of employing chemical qubit media with tunable properties. The principal objective of material engineers is to enhance photoexcited spin yields and quantum spin relaxation. In this study, we demonstrate a facile synthetic approach to control spin properties in charge-transfer cocrystals consisting of 1,2,4,5-tetracyanobenzene (TCNB) and acetylated anthracene.

Severe neonatal hypotonia due to variant affecting function of ZnT5 zinc transporter.

The tightly-regulated spatial and temporal distribution of zinc ion concentrations within cellular compartments is controlled by two groups of Zn transporters: the 14-member ZIP/SLC39 family, facilitating Zn influx into the cytoplasm from the extracellular space or intracellular organelles; and the 10-member ZnT/SLC30 family, mobilizing Zn in the opposite direction. Genetic aberrations in most zinc transporters cause human syndromes. Notably, previous studies demonstrated osteopenia and male-specific cardiac death in mice lacking the ZnT5/ zinc transporter, and suggested association of two homozygous frameshift variants with perinatal mortality in humans, due to hydrops fetalis and hypertrophic cardiomyopathy.

Impact of cardiovascular magnetic resonance in single ventricle physiology: a narrative review.

Background And Objective: Cardiovascular magnetic resonance (CMR) is a routine cross-sectional imaging modality in adults with congenital heart disease. Developing CMR techniques and the knowledge that CMR is well suited to assess long-term complications and to provide prognostic information for single ventricle (SV) patients makes CMR the ideal assessment tool for this patient cohort. Nevertheless, many of the techniques have not yet been incorporated into day-to-day practice.