Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2.

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2 cell subsets, which was distinct from that of ancestral cases.

Efficacy of yeast beta-glucan 1,3/1,6 supplementation on respiratory infection, fatigue, immune markers and gut health among moderate stress adults in Klang Valley of Malaysia: protocol for a randomised, double-blinded, placebo-controlled, parallel-group study.

Introduction: Yeast beta-glucan (YBG) are recognised for enhancing the immune system by activating macrophages, a key defence mechanism. Given the global prevalence and impact of upper respiratory tract infections (URTIs) on productivity and healthcare costs, YBG has shown promise as a potential therapeutic and preventive strategy for recurrent respiratory tract infections. However, little is known regarding the efficacy of YBG at lower dosages in relation to URTI, fatigue, immune response and uncertainties of how they affect the gut microbiota composition.

Novel Concept of Electrocoagulation and Tumor Cell Implantation: Creation of Minimally Invasive Orthotopic Murine Model of Pancreatic Cancer.

Background: Orthotopic murine models of pancreatic cancer represent an important tool for evaluating treatment strategies. Several genetically modified mouse tumors and xenograft models have been reported. Genetic models have unpredictable growth and variable waiting period, while orthotopic models are operative ones, difficult to create and result in irregular metastasis.

The CD123 antibody-drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia.

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models ( = 39).

Soluble Immune Checkpoint Protein and Lipid Network Associations with All-Cause Mortality Risk: Trans-Omics for Precision Medicine (TOPMed) Program.

Adverse cardiovascular events are emerging with the use of immune checkpoint therapies in oncology. Using datasets in the Trans-Omics for Precision Medicine program (Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study [JHS], and Framingham Heart Study), we examined the association of immune checkpoint plasma proteins with each other, their associated protein network with high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the association of HDL-C- and LDL-C-associated protein networks with all-cause mortality risk. Plasma levels of LAG3 and HAVCR2 showed statistically significant associations with mortality risk.

Rev-RRE activity modulates HIV-1 replication and latency reactivation: Implications for viral persistence and cure strategies.

The HIV-1 Rev-RRE regulatory axis plays a crucial role in viral replication by facilitating the nucleo-cytoplasmic export and expression of viral mRNAs with retained introns. In this study, we investigated the impact of variation in Rev-RRE functional activity on HIV-1 replication kinetics and reactivation from latency. Using a novel HIV-1 clone with an interchangeable Rev cassette, we engineered viruses with different Rev functional activities and demonstrated that higher Rev-RRE activity confers greater viral replication capacity while maintaining a constant level of Nef expression.

Characterization and automated classification of sentences in the biomedical literature: a case study for biocuration of gene expression and protein kinase activity.

Biological knowledgebases are essential resources for biomedical researchers, providing ready access to gene function and genomic data. Professional, manual curation of knowledgebases, however, is labor-intensive and thus high-performing machine learning methods that improve biocuration efficiency are needed. Here we report on sentence-level classification to identify biocuration-relevant sentences in the full text of published references for two gene function data types: gene expression and protein kinase activity.

The SinR•SlrR heteromer attenuates transcription of a long operon of flagellar genes in .

During growth, differentiates into subpopulations of motile individuals and non-motile chains, associated with dispersal and biofilm formation respectively. The two cell types are dictated by the activity of the alternative sigma factor SigD encoded as the penultimate gene of the 27 kb long flagellar operon. The frequency of SigD-ON motile cells is increased by the heteromeric transcription factor SwrA•DegU that activates the promoter.

Integrative co-registration of elemental imaging and histopathology for enhanced spatial multimodal analysis of tissue sections through TRACE.

Summary: Elemental imaging provides detailed profiling of metal bioaccumulation, offering more precision than bulk analysis by targeting specific tissue areas. However, accurately identifying comparable tissue regions from elemental maps is challenging, requiring the integration of hematoxylin and eosin (H&E) slides for effective comparison. Facilitating the streamlined co-registration of whole slide images (WSI) and elemental maps, TRACE enhances the analysis of tissue regions and elemental abundance in various pathological conditions.

Diabetes Centers' Participation in the T1D Exchange Quality Improvement Collaborative Advances Health Equity and Clinical Outcomes.

As the learning health network known as the T1D Exchange Quality Improvement Collaborative (T1DX-QI) has expanded on a significant scale to provide care for more than 120,000 people since its inception in 2016, assessing the quality improvement (QI) culture and monitoring clinical outcome improvements of participating centers has become vital to understanding the network's progress and success. Centers participating in the T1DX-QI complete regular QI culture self-assessments to quantify four evidence-based areas of culture: QI team structure, QI foundation, QI capacity, and QI success. This study builds on a previous baseline analysis to demonstrate self-reported improvements in T1DX-QI centers' QI culture from 2021 to 2022 and summarizes QI successes experienced by participating centers.

Characteristics of nursing homes with high rates of invasive methicillin-resistant Staphylococcus aureus infections.

Background: Nursing home residents experience a large burden of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Data are limited regarding nursing home characteristics associated with differences in facility-level invasive MRSA rates.

Methods: We analyzed 2011-2015 data from CDC's Emerging Infections Program (EIP) active population- and laboratory-based surveillance for invasive MRSA cases within seven states.

C2-Selective Palladium-Catalyzed C-S Cross-Coupling of 2,4-Dihalopyrimidines.

Under most conditions, 2,4-dihalopyrimidines undergo substitution reactions at C4. Here we report that Pd(II) precatalysts supported by bulky -heterocyclic carbene ligands uniquely effect C2-selective cross-coupling of 2,4-dichloropyrimidine with thiols. The regioselectivity of this reaction stands in stark contrast to ∼1500 previously reported Pd-catalyzed cross-couplings that favor C4 in the absence of other substituents on the pyrimidine ring.

Outcomes of Augmented versus Standard Baseplates in Reverse Shoulder Arthroplasty.

Background: Glenoid bone loss presents a complex challenge in the management of patients with glenohumeral osteoarthritis (GHOA) undergoing Reverse Shoulder Arthroplasty (RSA). Eccentric reaming and bone grafting have been utilized to address this issue but are associated with their own set of challenges. This study explores the effectiveness of augmented glenoid baseplate RSA in addressing glenoid bone loss.

Low-dose aspirin versus placebo in postpartum venous thromboembolism: a multi-national, pilot, randomised, placebo-controlled trial.

Background: Despite the morbidity and mortality of venous thromboembolism, there is little evidence to guide postpartum thromboprophylaxis in patients at moderate risk. We aimed to assess the feasibility of conducting a double-blind, randomised trial of aspirin versus placebo in postpartum individuals with two or more venous thromboembolism risk factors, mild-to-moderate thrombophilia, or both.

Methods: The pilot PARTUM trial, a multi-national, randomised, double-blind, placebo-controlled trial, was conducted in seven centres across Canada, France, Ireland, and the Netherlands.

County socioeconomic status and premature mortality from cancer in the United States.

Introduction: There are consistent data demonstrating socioeconomic status (SES) is associated with cancer survivorship among older adults, but research on the relationship between area-level SES and risk of premature mortality from cancer remains not well understood. This study investigated the association between county-level SES and premature mortality from cancer.

Methods: Demographic characteristics and causes of death were ascertained from the national death certificate data for years 2016-2020.

Fish as environmental sentinels for metal contaminants of human health concern in the Lower Mississippi River Basin.

Industrial expansion and population growth have lowered water quality, polluting aquatic ecosystems world-wide. Metal pollution in the rivers across the United States are a major health concern. The level of metal contamination in fish from the Lower Mississippi River Basin and their threat to public health were last evaluated 20 years ago.

Self-Directed Violence Among Black Young Adults with Negative Police Experiences.

The current study assessed associations between negative experiences with police and self-directed violence (SDV) among a United States (US) sample of Black young adults ages 18-29 reporting lifetime police stops. Data come from the "INtervening on Self-Harm and Policing to Increase Racial Equity" (INSPIRE) survey (N = 672) and were collected between December 2023 and March 2024. This high-risk sample exhibited elevated rates of self-harm ideation or NSSI (27.

Maize2035: A decadal vision for intelligent maize breeding.

Maize, a cornerstone of global food security, has undergone remarkable transformations through breeding, yet it faces mounting challenges in a changing world. In this review, we trace the historical successes of maize breeding which laid the foundation for present opportunities. We examine both the specific and shared breeding goals related to diverse geographies and end-use demands.

Generation of a human iPSC line (UCLi025-A) from a patient with PHARC syndrome harbouring biallelic variants in ABHD12.

A human induced pluripotent stem cell (hiPSC) line (UCLi025-A) was generated from dermal fibroblast cells from a 42-year-old female donor with polyneuropathy, hearing loss, retinitis pigmentosa and early-onset cataract (PHARC) syndrome carrying a homozygous nonsense variant in ABHD12 c.193C>T, p.(Arg65*).

Novel Therapies for Right Ventricular Failure.

Purpose Of Review: Traditionally viewed as a passive player in circulation, the right ventricle (RV) has become a pivotal force in hemodynamics. RV failure (RVF) is a recognized complication of primary cardiac and pulmonary vascular disorders and is associated with a poor prognosis. Unlike treatments for left ventricular failure (LVF), strategies such as adrenoceptor signaling inhibition and renin-angiotensin system modulation have shown limited success in RVF.