General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease.

Parkinson's disease is a complex neurodegenerative disorder characterized by degeneration of dopaminergic neurons, with patients manifesting varying motor and nonmotor symptoms. Previous studies using single-cell RNA sequencing in rodent models and humans have identified distinct heterogeneity of neurons and glial cells with differential vulnerability. Recent studies have increasingly leveraged multiomics approaches, including spatial transcriptomics, epigenomics, and proteomics, in the study of Parkinson's disease, providing new insights into pathogenic mechanisms.

Lower Risk of New-Onset Atrial Fibrillation in Conduction System Pacing Compared With Right Ventricular Pacing.

Background: Conduction system pacing (CSP) has been reported to improve clinical outcomes in comparison of right ventricular pacing (RVP). However, the performance between CSP and RVP on the risk of new-onset atrial fibrillation (AF) remains elusive.

Methods: Four online databases were systematically searched up to July 1, 2024.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.

Intravascular Lithotripsy for Coronary Artery Calcification: An Expert Review.

Coronary artery calcification is an impediment to percutaneous coronary interventions by obstructing the device pathway or stent deployment. To facilitate percutaneous coronary intervention in such complex lesions, high-pressure balloon dilations, atherectomy procedures, and specialty balloons are used but they all come with considerable limitations and periprocedural complications like dissection and perforation. To surpass these disadvantages, intravascular lithotripsy was introduced which acts by delivering high-pressure pulsatile sonic waves circumferentially thereby destroying the calcium deposits.

The shape of cleaved tethered membranes.

A remarkable property of flexible self-avoiding elastic surfaces (membranes) is that they remain flat at all temperatures, even in the absence of a bending rigidity or in the presence of active fluctuations. Here, we report numerical results of these surfaces wherein we alter their topology by systematically cleaving internal bonds. While it is known that a random removal of membrane bonds does not disrupt the overall extended shape of the membrane, we find that cleaving an elastic surface with longitudinal parallel cuts leads to its systematic collapse into a number of complex morphologies that can be controlled by altering the number and length of the inserted cuts.

Universality in diffusion-controlled nucleation and growth.

Nucleation and growth are studied in a system that undergoes diffusion-controlled condensation under gradual changes in parameters, such as cooling. It is demonstrated that when the Gibbs-Thompson effect becomes negligible, the system falls into a universal regime. i.

H2O trimer: Rigorous 12D quantum calculations of intermolecular vibrational states, tunneling splittings, and low-frequency spectrum.

The water trimer, as the smallest water cluster in which the three-body interactions can manifest, is arguably the most important hydrogen-bonded trimer. Accurate, fully coupled quantum treatment of its excited intermolecular vibrations has long been an elusive goal. Here, we present the methodology that for the first time allows rigorous twelve-dimensional (12D) quantum calculation of the intermolecular vibration-tunneling eigenstates of the water trimer, with the monomers treated as rigid.

Using patient preference to inform ritlecitinib dose selection for alopecia areata treatment.

Ritlecitinib is an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma (JAK3/TEC) family kinase inhibitor approved for the treatment of severe alopecia areata (AA). Benefit-risk profiles of two doses of ritlecitinib (50 mg vs 30 mg once daily) were evaluated by integrating patient preferences and clinical efficacy and safety estimates for ritlecitinib. A discrete-choice experiment (DCE) was utilized to elicit preferences for benefit and safety attributes of systemic AA treatments.

Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.

Introduction: Pediatric sepsis remains a leading cause of morbidity and mortality in Africa. Nearly half of pediatric sepsis deaths occur in previously healthy children. The role of inborn errors of immunity (IEI) in susceptibility to sepsis is yet to be identified and their prevalence amongst previously healthy children admitted to the pediatric intensive care unit (PICU) is unclear.

Mortality and Function After Hip Fracture or Pneumonia in People With and Without Dementia.

Background: The extent to which disruptive surgical or medical events impact mortality and function is critical for anticipatory planning and informing goal-aligned care.

Methods: Using Health and Retirement Study data (2008-2018), we employed propensity score matching to compare the impact of hospitalization for hip fracture (a surgical event) or pneumonia (a medical event) among people with dementia to two groups: (1) people with dementia who did not experience these events; and (2) people without dementia who experienced an event. Dementia status was determined using validated cognitive assessments (Hurd method); hip fracture and pneumonia were identified from Medicare claims.

Human HKU1-reactive CD4 T cells are enriched for cytolytic potential that persists in older adults.

The emergence of SARS-CoV-2 increased interest in cellular immunity established by infections with human coronaviruses (HCoVs). Using PBMC from a cohort of human subjects collected prior to 2019, we assessed the abundance and phenotype of these CD4 T cells using cytokine Elispot assays. Unexpectedly, cytotoxic potential was uniquely enriched amongst HKU1-reactive CD4 T cells, as measured by quantification of granzyme producing cells.

The role of multi-modality imaging for the assessment of left atrium and left atrial appendage. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Structural, architectural, contractile or electrophysiological alterations may occur in the left atrium (LA). The concept of LA cardiopathy is supported by accumulating scientific evidence demonstrating that LA remodeling has become a cornerstone diagnostic and prognostic marker. The structure and the function of LA and left atrial appendage (LAA) which is an integral part of the LA, are key elements for a better understanding of multiple clinical conditions, most notably atrial fibrillation (AF), cardioembolism, heart failure and mitral valve diseases.

Improving UTI Diagnostics in Oncology: Reliability of Reflex Urine Culture in Immunosuppressed Neutropenic and Non-neutropenic Cancer Patients.

Background: Urinary tract infections are prone to overdiagnosis, and reflex urine culture protocols offer a valuable opportunity for diagnostic stewardship in this arena. However, there is no recommended standard testing approach. Cancer patients are often excluded from reflex urine culture protocols, especially if severely immunosuppressed or neutropenic.

High Gain, Low Voltage Solar-Blind Deep UV Photodetector Based on GaO/(AlGa)O/GaN nBp Heterojunction.

In this study an (AlGa)O barrier layer is inserted between β-GaO and GaN in a p-GaN/n-GaO diode photodetector, causing the dark current to decrease considerably, and device performance to improve significantly. The β-GaO/β-(AlGa)O/GaN n-type/Barrier/p-type photodetector achieves a photocurrent gain of 1246, responsivity of 237 A W, and specific detectivity of 5.23 × 10 cm Hz W under a bias of -20 V.

Assessment of clinical characteristics and mortality in patients hospitalized with SARS-CoV-2 from January 2022 to November 2022, when Omicron variants were predominant in the United States.

Objective: To describe the demographic/clinical characteristics, treatment patterns, and mortality among patients hospitalized with COVID-19 during Omicron predominance by immunocompromised and high-risk status.

Methods: Retrospective observational study of patients hospitalized with COVID-19 between January 1, 2022 and November 30, 2022, using data from the Optum de-identified Clinformatics® Data Mart Database. Patient demographic/clinical characteristics, treatments, mortality and costs, were assessed, during the emergence of BA.

Adenoid basal cell carcinoma: An underrecognized cervical malignancy.

Introduction: Adenoid basal cell carcinoma is a rare cervical malignancy which is indolent in nature but resembles more commonly occurring aggressive malignancies.

Cases: Here we describe three cases of cervical adenoid basal cell carcinoma. All patients had a history of cervical dysplasia with high-risk HPV.

Effectiveness of interventions to prevent drowning among children under age 20 years: a global scoping review.

Background: Drowning is a leading cause of death among young children. The United Nations Resolution on global drowning prevention (2021) and World Health Assembly Resolution in 2023 have drawn attention to the issue. This scoping review synthesizes the current evidence on the effectiveness of child drowning prevention interventions since the 2008 World Report on Child Injury Prevention and implications for their implementation.

Operative Time Learning Curve for an Image-Free Robotic Arm Assisted Total Knee Arthroplasty: A Cumulative Sum Analysis.

Background: Robotic arm assisted total knee arthroplasty (RA-TKA) aims to improve accuracy in bone resection, implant positioning, and joint alignment compared to manual TKA (M-TKA). However, the learning curve of RA-TKA can disrupt operating room efficiency, increase complications, and raise costs. This study examines the operative time learning curve of RA-TKA using a single robotic system.

Evaluating the Diagnostic Accuracy and Challenges of the Two-Week Wait Referral Pathway for Skin Cancers in Primary Care.

Skin cancers are among the most common cancers in the Western world, with incidence rates increasing significantly over time. Skin cancer survival rates are highly dependent upon early identification. In the United Kingdom (UK), initial assessment of skin lesions is carried out via general practitioners (GPs) who identify and refer suspected cases under the two-week pathway in compliance with the National Institute for Health and Care Excellence (NICE) guidelines.

Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC.

Objective: Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy.

Background: Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM).

Methods: In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry.

Health Disparities in Rheumatology in the United States.

Objective: Underserved populations are often at risk of experiencing systematic healthcare disparities. Existing disparities in care access, quality of care received, and treatment outcomes among patients with rheumatic disease are not well understood.

Methods: We conducted a targeted literature review to understand disparities in health outcomes, treatment patterns, and healthcare management faced by rheumatology patients in the United States, with a focus on rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).

Global regulators enable bacterial adaptation to a phenotypic trade-off.

Cellular fitness depends on multiple phenotypes that must be balanced during evolutionary adaptation. For instance, coordinating growth and motility is critical for microbial colonization and cancer invasiveness. In bacteria, these phenotypes are controlled by local regulators that target single operons, as well as by global regulators that impact hundreds of genes.