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.

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.

Autoregulation of the Master Regulator Spo0A Controls Cell-Fate Decisions in Bacillus subtilis.

Spo0A in Bacillus subtilis is activated by phosphorylation (Spo0A~P) upon starvation and differentially controls a set of genes involved in biofilm formation and sporulation. The spo0A gene is transcribed by two distinct promoters, a σ-recognized upstream promoter Pv during growth, and a σ-recognized downstream promoter Ps during starvation, and appears to be autoregulated by four Spo0A~P binding sites (0A1-4 boxes) localized between two promoters. However, the autoregulatory mechanisms and their impact on differentiation remain elusive.

Effective repulsive interaction between Janus polymer-grafted nanoparticles adhering to lipid vesicles.

The adhesion of nanoparticles to lipid vesicles causes curvature deformations to the membrane to an extent determined by the competition between the adhesive interaction and the membrane's elasticity. These deformations can extend over length scales larger than the size of a nanoparticle, leading to an effective membrane-curvature-mediated interaction between nanoparticles. Nanoparticles with uniform surfaces tend to aggregate into unidimensionally close-packed clusters at moderate adhesion strengths and endocytose at high adhesion strengths.

Enhancing the accuracy of XPS calculations: Exploring hybrid basis set schemes for CVS-EOMIP-CCSD calculations.

Reliable computational methodologies and basis sets for modeling x-ray spectra are essential for extracting and interpreting electronic and structural information from experimental x-ray spectra. In particular, the trade-off between numerical accuracy and computational cost due to the size of the basis set is a major challenge, since molecular orbitals undergo extreme relaxation in the core-hole state. To gain clarity on the changes in electronic structure induced by the formation of a core-hole, the use of sufficiently flexible basis for expanding the orbitals, particularly for the core region, has been shown to be essential.

Uncovering dissipation from coarse observables: A case study of a random walk with unobserved internal states.

Inferring underlying microscopic dynamics from low-dimensional experimental signals is a central problem in physics, chemistry, and biology. As a trade-off between molecular complexity and the low-dimensional nature of experimental data, mesoscopic descriptions such as the Markovian master equation are commonly used. The states in such descriptions usually include multiple microscopic states, and the ensuing coarse-grained dynamics are generally non-Markovian.

Language Predictors of Word-Problem Performance Among Third-Grade Students With Mathematics Difficulty.

We examined how generalized and mathematics-specific language skills predicted the word-problem performance of students with mathematics difficulty. Participants included 325 third-grade students in the southwestern United States who performed at or below the 25th percentile on a word-problem measure. We assessed generalized language skills in word reading, passage comprehension, and vocabulary knowledge.

Reduction of vancomycin-associated acute kidney injury with montelukast.

Background: Vancomycin ranks amongst the most utilized antimicrobial agents in the treatment of serious β-lactam-resistant Gram-positive infections, but its use has been associated with nephrotoxicity. Reduction of acute kidney injury (AKI) has been reported in pre-clinical models with adjuvant montelukast. The purpose of the study was to ascertain if montelukast was associated with a reduction in the prevalence of vancomycin-associated AKI.

Immediate skin-to-skin contact and postpartum hemorrhagic morbidity.

Objective: To examine rates of postpartum hemorrhagic (PPH) morbidity among patients who did and did not have immediate skin-to-skin contact (SSC).

Methods: This study was a retrospective cohort of all non-anomalous, term singleton vaginal births at a Level IV center over 2 years. Exclusion criteria included COVID-19.

Economic impact of reduced postoperative visits after inflatable penile prosthesis implantation.

This study assessed the economic impact of reducing one postoperative visit following inflatable penile prosthesis (IPP) implantation. Scenario analyses were used to model the effects of eliminating one 30-min IPP postoperative visit from the expected 2.5 visits accounted for by the American Medical Association resource-based relative value scale data.

Pharmacovigilance Pregnancy Data in a Population of Japanese Patients With Chronic Inflammatory Disease Exposed to Certolizumab Pegol.

Aim: Uncontrolled chronic inflammatory diseases (CIDs) before, during, and after pregnancy, as well as some CID medications, can increase the risk of impaired fertility in addition to adverse maternal/pregnancy outcomes in women of childbearing age. We report pregnancy outcomes from prospectively reported pregnancies in Japanese women treated with certolizumab pegol (CZP).

Methods: Data from July 2001 to November 2020 on CZP-exposed pregnancies from the CZP Pharmacovigilance safety database were reviewed.

Striving for Unity in a Culturally Fragmented World: Nested Multiple Cultural Identifications Associated With Well-Being Through Self-Concept Clarity.

In contemporary globalised societies, global awareness and identification, as well as local and regional identifications (other than national identity), may all become increasingly important for guiding people's sense of belonging and purpose and in turn their self-concept. As the world has become increasingly interconnected, people increasingly identify with various cultures and worldviews within both local and global contexts. Attempts to reconcile these multiple cultural identities can lead to a sense of cultural dissonance as people struggle to integrate these identities into a coherent sense of self.

Balance Changes in Adult Cancer Survivors Participating in a 16-Week Therapeutic Yoga Program.

Introduction: Balance problems arising from cancer and its treatments can significantly impact daily functionality and quality of life. Improving balance as part of a cancer treatment plan could result in better patient outcomes. Thus, the aim of this study was to determine whether an integrative therapeutic yoga intervention can improve balance in a heterogenous population of cancer survivors (CS).

Long-Term Impact of Pregnancy on Clinical Outcomes in Individuals With Hypertrophic Cardiomyopathy.

Background: The effect of pregnancy on individuals with hypertrophic cardiomyopathy (HCM) is not well investigated.

Objectives: The purpose of this study was to assess the impact of pregnancy on all-cause mortality and clinical outcomes among individuals with HCM.

Methods: Using the TriNetX research network, we identified individuals within reproductive age (≥18-45 years) with a diagnosis of HCM between 2012 and 2022 (n = 10,936).

Thoracic endovascular repair of a ruptured thoracic aortic aneurysm with in situ laser fenestration of the left subclavian and left common carotid artery.

Most thoracic aortic aneurysms (TAAs) are asymptomatic and often diagnosed at the time of rupture. TAAs involving the proximal arch require adequate coverage with thoracic endovascular aortic repair, which is timely and challenging in emergent ruptures. In situ laser fenestration is a novel method of arch revascularization.

Directed evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes.

T7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using .

Light-dark shift promotes colon carcinogenesis through accelerated colon aging.

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC.

Exosomal Galectin-3 promotes peritoneal metastases in gastric adenocarcinoma via microenvironment alterations.

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear.

Inhaled alpha-1 antitrypsin (AAT) restores lower respiratory tract protease-antiprotease homoeostasis and reduces inflammation in AAT-deficient individuals: a randomised phase 2 study.

Background: Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.

Methods: This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of "Kamada-AAT for Inhalation" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks.

Pre-Operative Management of the Penicillin Allergic Patient: A Narrative Review.

Penicillin is a frequently reported medication allergy. The beta-lactam ring shared between cephalosporins and penicillin often leads to the use of alternative antibiotics for surgical prophylaxis due to concern for cross-reactivity, despite a true IgE-mediated hypersensitivity being very rare. This misconception leads to the use of less effective second line antibiotics, such as clindamycin or vancomycin, for penicillin-allergic patients which has been shown to increase odds of postoperative infection in elective knee arthroplasty, shoulder arthroplasty and spine surgery.

Use of Immunoglobulin Replacement Therapy in Clinical Practice: A Review.

Immunoglobulins (Igs) are produced by B lymphocytes and play a key role in humoral immunity. Igs are classified into five isotypes (IgG, IgA, IgM, IgE, and IgD). Their primary function is to recognize and bind to foreign antigens.