PrP Glycoprotein Is Indispensable for Maintenance of Skeletal Muscle Homeostasis During Aging.

Background: The cellular prion protein (PrP), a glycoprotein encoded by the PRNP gene, is known to modulate muscle mass and exercise capacity. However, the role of PrP in the maintenance and regeneration of skeletal muscle during ageing remains unclear.

Methods: This study investigated the change in PrP expression during muscle formation using C2C12 cells and evaluated muscle function in Prnp wild-type (WT) and knock-out (KO) mice at different ages (1, 9 and 15 months).

MetaboLINK is a novel algorithm for unveiling cell-specific metabolic pathways in longitudinal datasets.

Introduction: In the rapidly advancing field of 'omics research, there is an increasing demand for sophisticated bioinformatic tools to enable efficient and consistent data analysis. As biological datasets, particularly metabolomics, become larger and more complex, innovative strategies are essential for deciphering the intricate molecular and cellular networks.

Methods: We introduce a pioneering analytical approach that combines Principal Component Analysis (PCA) with Graphical Lasso (GLASSO).

Comparing the Efficacy of a Unique Advanced Bioengineered Type-I Collagen-Based Skin Substitute Versus an Amnion Graft With Standard of Care in the Treatment of Non-healing Diabetic Foot Ulcers: A Randomized Clinical Trial.

The increased cost and morbidity associated with diabetic foot ulcers (DFUs) place a substantial strain on the entire global healthcare system. In this trial, 24 subjects with a chronic DFU, Wagner grade 1 (University of Texas grade 1A), were treated with Standard of Care (SOC) therapy and randomized, one-half to receive advanced high-purity Type-I collagen-based skin substitute (HPTC; manufactured by Encoll Corp., Fremont, CA, USA), and the other half to receive a dehydrated human amnion/chorion membrane (dHACM) or viable cryopreserved human placental membrane (vCHPM).

Contrastive learning with transformer for adverse endpoint prediction in patients on DAPT post-coronary stent implantation.

Background: Effective management of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation is crucial for preventing adverse events. Traditional prognostic tools, such as rule-based methods or Cox regression, despite their widespread use and ease, tend to yield moderate predictive accuracy within predetermined timeframes. This study introduces a new contrastive learning-based approach to enhance prediction efficacy over multiple time intervals.

Cell surface protein-protein interaction profiling for biological network analysis and novel target discovery.

The secretome is composed of cell surface membrane proteins and extracellular secreted proteins that are synthesized via secretory machinery, accounting for approximately one-third of human protein-encoding genes and playing central roles in cellular communication with the external environment. Secretome protein-protein interactions (SPPIs) mediate cell proliferation, apoptosis, and differentiation, as well as stimulus- or cell-specific responses that regulate a diverse range of biological processes. Aberrant SPPIs are associated with diseases including cancer, immune disorders, and illness caused by infectious pathogens.

BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

Methods: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline).

New Mediastinal and Hilar Lymphadenopathy After Adjuvant Pembrolizumab in a Patient With Stage III Clear Cell Renal Cell Carcinoma.

The advent of immune checkpoint inhibitors (ICIs) has transformed the management of advanced and high-risk renal cell carcinoma (RCC). In the adjuvant setting, ICIs, such as pembrolizumab, aim to reduce the risk of recurrence following potentially curative nephrectomy. However, this therapeutic approach introduces unique challenges, particularly related to immune-related adverse events (irAEs).

Urban sensing in the era of large language models.

Urban sensing has become increasingly important as cities evolve into the centers of human activities. Large language models (LLMs) offer new opportunities for urban sensing based on commonsense and worldview that emerged through their language-centric framework. This paper illustrates the transformative impact of LLMs, particularly in the potential of advancing next-generation urban sensing for exploring urban mechanisms.

Brensocatib in patients with bronchiectasis: subgroup analyses from the WILLOW trial.

Introduction: Bronchiectasis is a chronic inflammatory airway disease. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces pulmonary inflammation by preventing the activation of neutrophil serine proteases. In the phase II WILLOW trial, brensocatib prolonged time to first exacerbation in patients with bronchiectasis.

Exploring age and gender disparities in cardiometabolic phenotypes and lipidomic signatures among Chinese adults: a nationwide cohort study.

Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies. We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort. A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China.

A descriptive report on the impact of pharmacy workflows in the operational success of hospital at home implementation at a county academic hospital system.

Background: The hospital at home (HaH) model has become more prevalent in the American healthcare system due to its ability to decrease acute care costs and readmission risk. Recent publications have provided guidance on optimizing medication management and patient safety by leveraging clinical pharmacy services. There is limited data on pharmacoeconomic impact of HaH implementation, specifically in underinsured patients.

Impact of liver cirrhosis on morbidity and mortality of patients admitted to the hospital with necrotizing fasciitis.

Background: Necrotizing fasciitis (NF) is a potentially fatal bacterial infection of the soft tissues. Liver cirrhosis appears to be a contributing factor to higher morbidity and mortality in patients with NF. This research article explores the relationship between these two conditions.

Two-Year Progressive Cranial Changes Following the Melbourne Technique for Sagittal Craniosynostosis.

Objective: The Melbourne technique for total cranial vault remodeling aims to address all aspects of scaphocephaly in sagittal craniosynostosis. These features include anterior-posterior excessive length, anteriorly displaced vertex position, frontal bossing, vertex narrowing, and occipital bulleting. This study aimed to determine the progressive cranial changes that occur following the Melbourne technique for sagittal craniosynostosis.

Parental Style, Grandchild Problematic Behaviors, and Parental Role Demands Among Grandparent Caregivers.

The present study evaluates the impact of grandchild distress on parental competence as mediated by Baumrind's parental styles in a sample of 238 custodial grandparents ( age = 58.06). AMOS structural equation findings yielded a model which indicated that both the Laissez-Faire and Authoritarian styles each predicted role stress and/or parental efficacy.

Supporting social justice through equity-based actions for a sustainable future in animal genetics (at the 39th International Society for Animal Genetics Conference).

The 39th International Society for Animal Genetics conference (ISAG) was held for the first time in Africa under the theme 'Animal genetics for a sustainable future' in 2023. The conference convened scientists, policy makers, industry professionals, and students from interdisciplinary fields to share and discuss the latest developments in the space of animal genetics. Since its inception as a society, ISAG has sought to provide a platform advocating for a just and equitable future in animal genetics.

Dual-Ligand Assisted Anisotropic Assembly for the Construction of NIR-II Light-Propelled Mesoporous Nanomotors.

The advent of autonomous nanomotors presents exciting opportunities for nanodrug delivery. However, significant potential remains for enhancing the asymmetry of nanomotors and advancing the development of second near-infrared (NIR-II) light-propelled nanomotors capable of operating within deep tissues. Herein, we developed a dual-ligand assisted anisotropic assembly strategy that enables precise regulation of the interfacial energy between selenium (Se) nanoparticle and periodic mesoporous organosilica (PMO).

Enantioselective Total Syntheses of Vallesamidine and Schizozygane Alkaloids.

A general streamlined strategy for the enantioselective total syntheses of the schizozygane family of natural products and related alkaloid vallesamidine is described. Specifically, a catalytic enantioconvergent cross-coupling sets the quaternary stereogenic center in a pluripotent intermediate adorned with an olefin and three orthogonal carboxylate groups, upon which the modularity of the synthesis relies. A late-stage catalytic oxidative lactamization of an alkyne is instrumental in the first-generation synthesis of the schizozygane alkaloids.

Extracellular vesicles as drug and gene delivery vehicles in central nervous system diseases.

Extracellular vesicles (EVs) are secreted by almost all cell types and contain DNA, RNA, proteins, lipids and other metabolites. EVs were initially believed to be cellular waste but now recognized for their role in cell-to-cell communication. Later, EVs from immune cells were discovered to function similarly to their parent cells, paving the way for their use as gene and drug carriers.

Insights into Chemical and Structural Order at Planar Defects in PbMgWO Using Multislice Electron Ptychography.

Switchable order parameters in ferroic materials are essential for functional electronic devices, yet disruptions of the ordering can take the form of planar boundaries or defects that exhibit distinct properties from the bulk, such as electrical (polar) or magnetic (spin) response. Characterizing the structure of these boundaries is challenging due to their confined size and three-dimensional (3D) nature. Here, a chemical antiphase boundary in the highly ordered double perovskite PbMgWO is investigated using multislice electron ptychography.

Are More Adults Bleeding After Tonsillectomy Than in the Past?

Objective: Post-tonsillectomy hemorrhage (PTH) rates have increased in children over the last decade. This study aimed to determine whether PTH incidence in adults had also increased over the last 15 years.

Study Design: Retrospective study.

The fungal microbiota modulate neonatal oxygen-induced lung injury.

Background: The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown.

Results: Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models.

Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to the involvement of lipid dysregulation in the development of AD. Nevertheless, the precise lipidomic landscape and the mechanistic roles of lipids in disease pathology remain poorly understood.

Chemotherapy in synergy with innate immune agonists enhances T cell priming for checkpoint inhibitor treatment in pancreatic cancer.

Background: The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.

Methods: We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.

Chromoanagenesis Is Frequently Associated With Highly Complex Karyotypes, Extensive Clonal Heterogeneity, and Treatment Refractoriness in Acute Myeloid Leukemia.

Chromoanagenesis (CAG) encompasses a spectrum of catastrophic genomic events, including chromothripsis, chromoanasynthesis, and chromoplexy. We studied CAG in 410 patients with a diagnosis of acute myeloid leukemia (AML), 292 newly diagnosed (ND), and 118 refractory/relapsed, using optical genome mapping. CAG was identified by the presence of clusters (with 10 or more breakpoints) of structural abnormalities and/or segmental copy number alterations within one or more chromosomal regions.

Multimodal Therapy May be Key to Improving Survival for Octogenarians Undergoing Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: An American Multicenter Analysis.

Background: As the population ages, the number of octogenarians with pancreatic ductal adenocarcinoma (PDAC) continues to rise. Morbidity and mortality following pancreatectomy have improved owing to safer surgery and better chemoradiation regimens. This study compares the outcomes and multimodality utilization in octogenarians (≥80 years) who underwent pancreaticoduodenectomy (PD) for PDAC, with a younger cohort.