Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations.

Autosomal recessive coding variants are well-known causes of rare disorders. We quantified the contribution of these variants to developmental disorders in a large, ancestrally diverse cohort comprising 29,745 trios, of whom 20.4% had genetically inferred non-European ancestries.

Possibility of the optimum monitoring and evaluation (M&E) production frontier for risk-informed health governance in disaster-prone districts of West Bengal, India.

An efficient M&E system in public healthcare is crucial for achieving universal health coverage in low- and middle-income countries, especially when the need for service remains unmet due to the exposure of the population to disaster risks and uncertainties. Current research has conducted exploratory and predictive analyses to estimate the determinants of sustainable M&E solutions for ensuring uninterrupted access during and after disasters. The aim was to estimate the efficiency of reaching a higher M&E production frontier via the Cobb‒Douglas model and stochastic frontier model as the basic theoretical and empirical frameworks.

Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.

Background And Objectives: Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau), atrophy, and cognition.

From whole-slide image to biomarker prediction: end-to-end weakly supervised deep learning in computational pathology.

Hematoxylin- and eosin-stained whole-slide images (WSIs) are the foundation of diagnosis of cancer. In recent years, development of deep learning-based methods in computational pathology has enabled the prediction of biomarkers directly from WSIs. However, accurately linking tissue phenotype to biomarkers at scale remains a crucial challenge for democratizing complex biomarkers in precision oncology.

DNA signature and occult blood in stool led to diagnosis of an early-onset metastatic rectal cancer in a young pregnant woman: a case report.

Background: Colorectal cancer (CRC) is the third most common form of cancer worldwide in terms of incidence and the second in terms of mortality with 1.9 million new cases and 930,000 deaths reported in 2020. Corresponding numbers in the U.

Heart failure in Europe: Guideline-directed medical therapy use and decision making in chronic and acute, pre-existing and de novo, heart failure with reduced, mildly reduced, and preserved ejection fraction - the ESC EORP Heart Failure III Registry.

Aims: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry.

Methods And Results: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.

Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.

Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care.

Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism.

Background: Hypertension incidence increases with age and represents one of the most prevalent risk factors for cardiovascular disease. Clonal events in the hematopoietic system resulting from somatic mutations in driver genes are prevalent in elderly individuals who lack overt hematologic disorders. This condition is referred to as age-related clonal hematopoiesis (CH), and it is a newly recognized risk factor for cardiovascular disease.

Sex Differences in Hypertension and Its Management Throughout Life.

Background: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex.

Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models.

Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 years) to 93% (ages, 91-94 years).

Guided Plasma Application in Dentistry-An Alternative to Antibiotic Therapy.

Cold atmospheric plasma (CAP) is a promising alternative to antibiotics and chemical substances in dentistry that can reduce the risk of unwanted side effects and bacterial resistance. AmbiJet is a device that can ignite and deliver plasma directly to the site of action for maximum effectiveness. The aim of the study was to investigate its antimicrobial efficacy and the possible development of bacterial resistance.

Extent and Topography of Subretinal Drusenoid Deposits Associate With Rod-Mediated Vision in Aging and AMD: ALSTAR2 Baseline.

Purpose: In AMD, rod-mediated dark adaptation (RMDA) at 5° eccentricity is slower in eyes with subretinal drusenoid deposits (SDDs) than in eyes without. Here we quantified SDD burden using supervised deep learning for comparison to vision and photoreceptor topography.

Methods: In persons ≥60 years from the Alabama Study on Early Age-Related Macular Degeneration 2, normal, early AMD, and intermediate AMD eyes were classified by the AREDS nine-step system.

Update on PI-RADS Version 2.1 Diagnostic Performance Benchmarks for Prostate MRI: Systematic Review and Meta-Analysis.

Background Prostate MRI for the detection of clinically significant prostate cancer (csPCa) is standardized by the Prostate Imaging Reporting and Data System (PI-RADS), currently in version 2.1. A systematic review and meta-analysis infrastructure with a 12-month update cycle was established to evaluate the diagnostic performance of PI-RADS over time.

Fasting in Science and Clinics: A Report on Proceedings from the International Scientific Symposium and Conference on Fasting in Berlin (June 2023).

Background: A fasting conference and scientific symposium on fasting were held in Berlin in June 2023. Researchers and clinicians from around the world shared new findings, clinical insights, and work in progress during a 3-day program.

Summary: Different fasting regimens, including prolonged, short-term, intermittent fasting, and time-restricted eating were discussed for preventive and therapeutic settings.

Microbial life in preferential flow paths in subsurface clayey till revealed by metataxonomy and metagenomics.

Background: Subsurface microorganisms contribute to important ecosystem services, yet little is known about how the composition of these communities is affected by small scale heterogeneity such as in preferential flow paths including biopores and fractures. This study aimed to provide a more complete characterization of microbial communities from preferential flow paths and matrix sediments of a clayey till to a depth of 400 cm by using 16S rRNA gene and fungal ITS2 amplicon sequencing of environmental DNA. Moreover, shotgun metagenomics was applied to samples from fractures located 150 cm below ground surface (bgs) to investigate the bacterial genomic adaptations resulting from fluctuating exposure to nutrients, oxygen and water.

Childhood trauma and differential response to long-term psychoanalytic versus cognitive-behavioural therapy for chronic depression in adults.

Background: Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship.

Aims: As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive-behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma.