Characterization of LIPUS Parameters Suitable for Hip Bone Fracture.

Objective: To investigate the effects of ultrasound treatment on the healing of hip bone fractures using frequencies of 0.5 MHz and 1.5 MHz with constant intensity (30 mW/cm) at the fractured site.

Ligand-restricted synNotch switches enable precision cell therapy.

Lim and colleagues demonstrate that synNotch transcriptional circuits engineered into T cells can be used to precisely control location-specific expression of payloads responding to antigen triggers, thus locally inhibiting unwanted immunity or neuroinflammation. With no off-tumor toxicity or systemic immunosuppression upon elimination of mouse brain tumors, this approach can achieve better efficacy than anticipated.

Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g.

Interleukin-17: A pleiotropic cytokine implicated in inflammatory, infectious, and malignant disorders.

IL-17A, referred to as IL-17, is the founding member of a family of pro-inflammatory cytokines, including IL-17B, IL-17C, IL-17D, IL-17E (or IL-25), and IL-17F, which act via receptors IL-17RA to IL-17RE, and elicit potent cellular responses that impact diverse diseases. IL-17's interactions with various cytokines include forming a heterodimer with IL-17F and being stimulated by IL-23's activation of Th17 cells, which can lead to inflammation and autoimmunity. IL-17 is implicated in infectious diseases and inflammatory disorders such as rheumatoid arthritis and psoriasis, promoting neutrophil recruitment and anti-bacterial immunity, but potentially exacerbating fungal and viral infections, revealing its dual role as protective and pathologic.

Ischemic ulcers do not significantly impact endoscopic recurrence score in Crohn's disease: A multicenter comparative study after right-side colectomy.

Background: Postoperative recurrence (POR) occurs in up to 70% of patients with Crohn's disease (CD). The Rutgeerts score (RS) system may overestimate the prevalence of "real" anastomotic recurrence. Hence, we aimed to compare the prevalence of anastomotic POR in CD and the presence of ulcers at anastomotic sites in patients with right-side resection for colonic cancer (CC).

Problem Adaptation Therapy for Older Adults with Chronic Pain and Negative Emotions in Primary Care (PATH-Pain): A Randomized Clinical Trial.

Objective: To test the efficacy of Problem Adaptation Therapy for Pain (PATH-Pain) versus Usual Care (UC) in reducing pain-related disability, pain intensity, and depression among older adults with chronic pain and negative emotions.

Design: RCT assessing the between-group differences during the acute (0-10 weeks) and follow-up (weeks 11-24) phase of treatment.

Setting: A geriatrics primary care site.

Pharmacotherapy of type 1 diabetes - part 1: Yesterday.

Introduction: Type 1 diabetes is a unique autoimmune attack on the β cell of the pancreatic islet resulting in progressive destruction of these cells and as a result the ability of the body to maintain insulin production. The consequences of insulin deficiency are very severe, and the disease was fatal prior to the ability to extract insulin from animal pancreas in 1921. We review progress in the treatment of childhood type 1 diabetes over the past 100 years.

The association between Guardian Cap use during practices and sport-related concussion risk in high school American football players.

Objective: Guardian Caps (GCs) have been widely implemented at all levels of American football participation based on laboratory evidence that they may reduce head impact forces. The purpose of this study was to determine if GC use during practice was associated with a lower risk of sport-related concussion (SRC) during practices and games among high school football players.

Methods: Data were collected on 2610 athletes from 41 Wisconsin schools that self-selected into GC or Non-GC cohorts.

Impact of changes in primary care attachment: a scoping review.

Objectives: Primary care attachment represents an inclusive, equitable and cost-effective way of enhancing health outcomes globally. However, the growing shortage of family physicians threatens to disrupt patient-provider relationships. Understanding the consequences of these disruptions is essential for guiding future research and policy.

Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma.

Background: Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (T) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.

Incidentally discovered inflammatory pseudotumour of the spleen: understanding clinical manifestations and diagnosis.

A splenic inflammatory pseudotumour (IPT) is a rare condition in which inflammatory cells and non-cancerous specialised cells known as myofibroblasts abnormally replicate in the spleen. Patients with IPT may experience symptoms like abdominal pain, fever and weight loss, making it difficult to distinguish from processes like cancer. As a result, diagnosing IPT often requires imaging studies and microscopic examination.

Epstein-Barr virus associated multicentric Castleman's disease disguised as infectious mononucleosis.

Castleman's disease (CD), also called angiofollicular lymphoid hyperplasia, is a rare lymphoproliferative illness with two unique variants: unicentric disease and multicentric disease (MCD). The multicentric variant is rare and presents as a systemic illness with symptoms like peripheral lymphadenopathy, splenomegaly, anaemia and systemic inflammatory symptoms. Given the vague and systemic presentation, this variant can be difficult to differentiate from infection and other autoimmune diseases.

Partner fidelity, not geography, drives co-diversification of gut microbiota with hominids.

Bacterial strains that inhabit the gastrointestinal tracts of hominids have diversified in parallel (co-diversified) with their host species. The extent to which co-diversification has been mediated by partner fidelity between strains and hosts or by geographical distance between hosts is not clear due to a lack of strain-level data from clades of hosts with unconfounded phylogenetic relationships and geographical distributions. Here, I tested these competing hypotheses through meta-analyses of 7121 gut bacterial genomes assembled from wild-living ape species and subspecies sampled throughout their ranges in equatorial Africa.

Elevated plasma Tau-PT217 linked to decreased hippocampal functional connectivity in patients with knee osteoarthritis.

Background: Osteoarthritis is associated with a higher risk of developing dementia, though the underlying biological mechanisms have remained unclear. Recent studies suggest that blood phosphorylated tau proteins, particularly Tau-PT217, are sensitive biomarkers capable of detecting cognitive decline in its early stages, making it useful for early diagnosis of Alzheimer's disease and other forms of cognitive impairment.

Methods: In this study, we investigated the plasma phosphorylated tau protein levels (Tau-PT217 and Tau-PT181), hippocampus functional connectivity, and cognitive function in people with knee osteoarthritis compared to age and gender matched pain-free controls.

Olfactory testing in infants with perinatal asphyxia: enhancing encephalopathy risk stratification for future health outcomes.

Perinatal asphyxia (PA) is a leading cause of neonatal morbidity and mortality, often resulting in long-term neurodevelopmental challenges. Despite advancements in perinatal care, predicting long-term outcomes remains difficult. Early diagnosis is essential for timely interventions to reduce brain injury, with tools such as Magnetic Resonance Imaging, brain ultrasound, and emerging biomarkers playing a possible key role.

"Multimodal Sleep Signal Tensor Decomposition and Hidden Markov Modeling for Temazepam-Induced Anomalies Across Age Groups".

Background: Recent advances in multimodal signal analysis enable the identification of subtle drug-induced anomalies in sleep that traditional methods often miss.

New Method: We develop and introduce the Dynamic Representation of Multimodal Activity and Markov States (DREAMS) framework, which embeds explainable artificial intelligence (XAI) techniques to model hidden state transitions during sleep using tensorized EEG, EMG, and EOG signals from 22 subjects across three age groups (18-29, 30-49, and 50-66 years). By combining Tucker decomposition with probabilistic Hidden Markov Modeling, we quantified age-specific, temazepam-induced hidden states and significant differences in transition probabilities.

A simple model for the analysis of epidemics based on hospitalization data.

An epidemiological model with a minimal number of parameters is introduced and its structural and practical identifiabity is investigated both analytically and numerically. The model is useful when a high percentage of unreported cases is suspected, hence only hospitalization data are used to fit the model parameters and calculate the basic reproductive number R and the effective reproductive number R. As a case study, the model is used to study the initial surge and the Omicron wave of the COVID-19 epidemic in Belgium.

Lack of mpox transmission in a long-term-care facility despite widespread exposure - Kentucky, 2023.

A certified nursing assistant (CNA) at a long-term care-facility (LTCF) worked 3 shifts while infectious with monkeypox virus providing direct care to most or all 56 LTCF residents. Despite exposures and a delay of 16 days from symptom onset to diagnosis and public health notification, there is no evidence that transmission occurred. We describe details of this healthcare-associated exposure, public health response, situational risk factors for transmission, and discuss factors that might have contributed to the lack of transmission.

TFEB-dependent autophagy-lysosomal pathway is required for NRF2-driven antioxidative action in obstructive sleep apnea-induced neuronal injury.

Nearly one billion individuals worldwide suffer from obstructive sleep apnea (OSA) and are potentially impacted by related neurodegeneration. TFEB is considered a master regulator of autophagy and lysosomal biogenesis, but little is known about its role in neuronal oxidative stress and resultant injury induced by OSA. This study aimed to investigate these issues.

Novel compound heterozygous CYP17A1 mutations identified in a family with two siblings affected by 17α-hydroxylase/17,20-lyase deficiency.

Background: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), caused by mutations in the CYP17A1 gene. It typically manifests clinically as variable degree of hypertension, hypokalemia, and disorders of sexual development (DSD), which can include abnormal sexual differentiation in males and sexual infantilism in females. Over 100 mutations in CYP17A1 have been identified, with most cases involving missense mutations or small deletions.

Safety and Immunogenicity of Omicron Protein Vaccines in mRNA-Vaccinated Adolescents: A Phase 3, Randomised Trial.

Objectives: Safety and immunogenicity assessment of updated monovalent and bivalent SARS-CoV-2 vaccines in adolescents.

Methods: This phase 3, double-blinded study randomised 12-<18-year-old participants, who received ≥2 prior doses of an approved/authorised mRNA-based COVID-19 vaccine, 1:1 to receive NVX-CoV2601 (XBB.1.

The Global Prevalence of Reported Penicillin Allergy: A Systematic Review and Meta-Analysis.

Objectives: Patients labelled with penicillin allergy (PenA) often receive broader spectrum antibiotics, associated with antimicrobial resistance and poorer outcomes. However, ~95% of patients are likely mis-labelled. Whilst de-labelling programmes are gaining momentum, they have been restricted to a few countries.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.

Tactical Behaviors in Men's and Women's Middle-Distance Global Championship Track Finals.

Purpose: To analyze tactical behaviors associated with performance in track middle-distance global championship finals.

Methods: Finalists' season-best finishing race time, 100-m section times, and intermediate positions were obtained from 800- and 1500-m men's and women's finals in 2 Olympic Games and 5 World Championships. Differences between medalists, fourth- to eighth-ranked (T8), and ninth- to 12th/13th-ranked finalists in relative performance (relative to season-best), race time, and section times were determined.

Associations Between Leisure-Time Physical Activity and Mortality by Sociodemographic Factors.

Background: The 2018 Physical Activity Guidelines 2nd Edition Advisory Committee Scientific Report recommended research to understand whether the health benefits of physical activity (PA) differed by sociodemographic factors. This study examined associations between meeting PA guidelines in leisure time and all-cause, heart disease, and cancer mortality across sociodemographic characteristics.

Methods: Nationally representative data on 567,483 eligible US adults from the 1998-2018 US National Health Interview Survey and 2019 public-use linked mortality files were used.