Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

Achieving cup target as per spinopelvic assessment is associated with improved THA outcome: a prospective, multicentre study.

Background: Different methods can help to optimise sagittal cup orientation in total hip arthroplasty (THA) based on individual spinopelvic characteristics. This study aimed to: (1) assess how often combined sagittal index (CSI) and hip-spine-classification targets were achieved post THA; (2) compare anteversion/inclination between cups in-/outside optimal CSI zone; and (3) determine association with outcome.

Methods: This is a multicentre, prospective, case-cohort study of 435 primary THA for osteoarthritis (53% females; age: 65 ± 12 years; follow-up: 2.

New Infrared Spectra of the Water-CO Complex: Determination of Four Intermolecular Modes and Test of a High-Level Potential Energy Surface.

High resolution infrared spectra of water-CO dimers are further studied using tunable infrared sources to probe a pulsed slit jet supersonic expansion. The relatively weak transition of DO-CO in the DO ν fundamental region (≈2760 cm) is observed for the first time, as are various spectra of DO-CO. Combination bands involving the intermolecular in plane geared bend (disrotatory) mode are observed for HO-CO (≈1642, 2397 cm) in the HO ν and CO ν regions, for HDO-CO (≈2761 cm) in the HDO ν region, and for DO-CO (≈2386, 2705 and 2821 cm) in the CO ν, DO ν, and DO ν regions.

Ethical considerations on surrogacy†.

Surrogacy is the assisted reproductive technology (ART) practice in which a person becomes pregnant, carries, and delivers a child on behalf of another couple/person, who are the intended parent(s). Surrogacy is an especially complex practice as the interests of the intended parents, the gestational carrier, and the future child may differ. This paper considers ethical questions related to different forms of surrogacy.

The Harms of Class Imbalance Corrections for Machine Learning Based Prediction Models: A Simulation Study.

Introduction: Risk prediction models are increasingly used in healthcare to aid in clinical decision-making. In most clinical contexts, model calibration (i.e.

Precision in Liver Diagnosis: Varied Accuracy Across Subgroups and the Need for Variable Thresholds in Diagnosis of MASLD.

Background And Aims: The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.

Methods: Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included.

Factors associated with statural growth in pediatric kidney transplant recipients with focus on metabolic acidosis.

Background: We investigated factors associated with post-transplant growth in pediatric kidney transplant (KTx) recipients with a focus on plasma bicarbonate (HCO3) and estimated the effect of alkali treatment on growth.

Methods: In this study of the CERTAIN Registry, data were collected up to 5 years post-transplant. Generalized Additive Mixed Models were applied to assess the association between post-transplant growth and covariates.

Synchrotron XRF spectroscopy for reading salt-encrusted cuneiform tablets.

Cuneiform tablets were a primary writing medium in the ancient Near East from the late fourth millennium BCE to the first century CE. Although these clay tablets were durable for daily use, prolonged burial over millennia has made them vulnerable to salt damage. Fluctuations in temperature and humidity cause the migration of salts to the surface of the tablets, damaging them and covering the inscriptions, making the text unreadable.

Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery.

Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about bacterial dormancy development and recovery. Previously, we established a correlation between protein aggregation and dormancy in Escherichia coli.

Impacts of irrigation expansion on moist-heat stress based on IRRMIP results.

Irrigation rapidly expanded during the 20 century, affecting climate via water, energy, and biogeochemical changes. Previous assessments of these effects predominantly relied on a single Earth System Model, and therefore suffered from structural model uncertainties. Here we quantify the impacts of historical irrigation expansion on climate by analysing simulation results from six Earth system models participating in the Irrigation Model Intercomparison Project (IRRMIP).

The First Multiomics Association Study of Trace Element and Mineral Concentration and RNA Sequencing Profiles in Human Cancers.

Integration of various types of omics data is an important trend in contemporary molecular oncology. In this regard, high-throughput analysis of trace and essential elements in cancer biosamples is an emerging field that has not yet been sufficiently addressed. For the first time, we simultaneously obtained gene expression profiles (RNA sequencing) and essential and trace element profiles (inductively coupled plasma mass spectrometry) for a set of human cancer samples.

Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.

Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.

Immersive gamma music as a tool for enhancing glymphatic clearance in astronauts while improving their mental well-being.

Spaceflight occurs under extreme environmental conditions that pose significant risks to the physical and mental health and well-being of astronauts. Certain factors, such as prolonged isolation, monotony, disrupted circadian rhythms, heavy workload, and weightlessness in space, can trigger psychological distress and may contribute to a variety of mental health problems, including mood and anxiety disturbances. Recent findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, demonstrating enlargement of the brain's perivascular spaces from preflight to postflight, at least suggest reduced glymphatic clearance in microgravity, and have raised concerns about long-term cognitive health in astronauts.

The moderating and mediating role of the placenta in the association between prenatal exposure to air pollutants and birth weight: A twin study.

Prenatal exposure to air pollution has been linked to lower birth weight, yet the role of the placenta in this association is often overlooked. This study investigates whether placental characteristics act as moderators or mediators in the association between prenatal exposure to particulate matter (PM) and nitrogen dioxide (NO) and birth weight in twins. The study included 3340 twins (born 2002-2013) from the East Flanders Prospective Twin Survey.

Human organotypic colon in vitro microtissue: unveiling a new window into colonic drug disposition.

The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (P). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [C]mannitol were established to monitor microtissue integrity.

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Introduction: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs.

Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: the PSERENADE project.

Background: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally.

Methods: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally.

Effect of inulin supplementation on fecal and blood metabolome in alcohol use disorder patients: A randomised, controlled dietary intervention.

Background And Aims: Alcohol Use Disorder (AUD) is a psychiatric disorder characterized notably by gut microbial dysbiosis and insufficient dietary fiber intake. This study aims to investigate the effect of dietary fiber placebo-controlled intervention in patients suffering from AUD during a three-week period of alcohol withdrawal, in order to discover microbial-derived metabolites that could be involved in metabolic and behavioral status.

Methods: A randomized, double-blind, placebo-controlled study was performed with 50 AUD patients supplemented with inulin (prebiotic dietary fiber) or maltodextrin (placebo) during 17 days.

A European Delphi Consensus on the Management of Abdominal Aortic Aneurysms in Patients with Heritable Aortic Diseases.

Objective: Abdominal aortic aneurysm (AAA) in a patient with an underlying heritable aortic disease (HAD) is rare, and evidence based recommendations for its management are lacking. This study aimed to generate a consensus from multidisciplinary specialists on the diagnosis, treatment, and surveillance of AAA associated with HAD and to define topics of interest for future research.

Methods: A Delphi consensus was designed involving European multidisciplinary specialists and reported using the ACcurate COnsensus Reporting Document (ACCORD) reporting guideline.

Pulsed Field Ablation in the Elderly via a Pentaspline Multielectrode Catheter: Safety, Efficacy, and Comparison with Cryoballoon and Radiofrequency Devices.

Background: Catheter ablation is an effective treatment for atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel energy modality, which relies on high-voltage electric fields to achieve cardiac tissue ablation. Data on its efficacy in the elderly are scarce.

Survival outcomes for patients with invasive lobular cancer by MammaPrint: Results from the MINDACT phase III trial.

Background: Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited.

Patients And Methods: Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n = 5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk.