CCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice.

Macrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage-associated CCL2 secretion, its influence on mesenchymal stem/progenitor cell (MSPC) chemotaxis, and in vivo cell recruitment using Ccr2 (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre-osteoblasts, MSPC) upregulated CCL2.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Microplastics inhibit the decomposition of soil organic matter by adult darkling beetles (Coleoptera: Tenebrionidae).

Microplastics (MPs) are a growing problem worldwide. Soils are long-term storage sinks of MPs because of the many pathways they enter the soil and their long degradation period. Knowing how MPs influence soil organisms, the effects of organisms on the fate of MPs, and what this means for soil additions, losses, transformations, and translocations is paramount.

Steatotic liver disease in metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor.

Purpose: In early-stage breast cancer, steatotic liver disease (SLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy (ET) increases the risk of SLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) on SLD and prognostic association in metastatic breast cancer is unknown.

Proactive esophageal cooling during radiofrequency cardiac ablation: data update including applications in very high-power short duration ablation.

Introduction: Proactive esophageal cooling reduces injury during radiofrequency (RF) ablation of the left atrium (LA) for the treatment of atrial fibrillation (AF). New catheters are capable of higher wattage settings up to 90 W (very high-power short duration, vHPSD) for 4s. Varying power and duration however does not eliminate the risk of thermal injury.

Competitive Antagonism of Xylazine on α7 Nicotinic Acetylcholine Receptors and Reversal by Curcuminoids.

Co-use of xylazine with opioids is a major health threat in the United States. However, a critical knowledge gap exists in the understanding of xylazine-induced pharmacological and pathological impact. Xylazine is mostly known as an agonist of α2-adrenergic receptors (α2-ARs), but its deleterious effects on humans cannot be fully reversed by the α2-AR antagonists, suggesting the possibility that xylazine targets receptors other than α2-ARs.

Microsimulation Estimates of Decision Uncertainty and Value of Information Are Biased but Consistent.

Purpose: Individual-level state-transition microsimulations (iSTMs) have proliferated for economic evaluations in place of cohort state transition models (cSTMs). Probabilistic economic evaluations quantify decision uncertainty and value of information (VOI). Previous studies show that iSTMs provide unbiased estimates of expected incremental net monetary benefits (EINMB), but statistical properties of iSTM-produced estimates of decision uncertainty and VOI remain uncharacterized.

Is duchenne gene therapy a suitable treatment despite its immunogenic class effect?

Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle weakness and eventual death due to cardiomyopathy or respiratory complications. Currently, there is no cure for DMD, with standard treatments primarily focusing on symptom management. Using immunosuppressive measures and optimized vector designs allow for gene therapies to better address the underlying genetic cause of the disease.

Rare Prekallikrein Deficiency Identified During Workup of Isolated Prolonged Activated Partial Thromboplastin Time.

Prolongation of the activated partial thromboplastin time (aPTT) may signify an intrinsic factor deficiency or the presence of an inhibitor of coagulation, potentially placing a patient at increased risk for bleeding. However, a contact factor (ie, factor XII, prekallikrein, and high molecular weight kininogen) deficiency, which may also cause a prolonged aPTT, is not associated with clinical bleeding. A 71-year-old female had an isolated prolonged aPTT discovered during preoperative laboratory testing.

Inferring strain-level mutational drivers of phage-bacteria interaction phenotypes arising during coevolutionary dynamics.

The enormous diversity of bacteriophages and their bacterial hosts presents a significant challenge to predict which phages infect a focal set of bacteria. Infection is largely determined by complementary-and largely uncharacterized-genetics of adsorption, injection, cell take-over, and lysis. Here we present a machine learning approach to predict phage-bacteria interactions trained on genome sequences of and phenotypic interactions among 51 strains and 45 phage λ strains that coevolved in laboratory conditions for 37 days.

Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses.

Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion.

Optimizing regulatory frameworks for gene therapies in rare diseases: Challenges and solutions.

The advent of genetic medicines and advanced diagnostics has revolutionized the treatment landscape for rare diseases and, with over 10,000 identified conditions affecting millions globally, has the potential to improve many lives. Despite this progress, only 5% of rare diseases have FDA-approved therapies, highlighting a significant unmet need. This article examines the critical need for optimizing the regulatory environment to support the development and approval of gene therapies for rare and ultrarare diseases, which often face unique challenges due to their complexity in the midst of a rapidly evolving field.

Corrigendum: Role of bilingualism and biculturalism as assets in positive psychology: conceptual dynamic GEAR model.

[This corrects the article DOI: 10.3389/fpsyg.2019.

Extracellular acidification stimulates OGR1 to modify osteoclast differentiation and activity through the Ca2+‑calcineurin‑NFATc1 pathway.

The aim of the present study was to explore the role of ovarian cancer G protein-coupled receptor 1 (OGR1) in osteoclast differentiation and activity induced by extracellular acid. The impact of extracellular acidification on osteoclasts was investigated. Briefly, osteoclasts were generated from RAW 264.

An analysis of different modalities of bone mineral densitometry evaluation in cage subsidence in anterior cervical discectomy and fusion.

Objective: To compare the effectiveness of different measurement methods on bone miner density (BMD), including cervical HU of CT, MRI-based cervical vertebral bone quality (C-VBQ), and value of DEXA, for predicting cage subsidence after single-level ACDF.

Methods: This is a retrospective study, and patients who underwent single-level ACDF from June 2019 to June 2022 were recruited. We collected preoperative total segmental vertebral height (pre-TSVH), cage subsidence height, cervical angle (CA), T1-slope, straight or reverse cervical curvature, mean HU value of C3-7 (C-HU), mean HU of segment (seg-HU), C-VBQ, segmental C-VBQ (seg-VBQ), and total lumbar value ( value).

Depression of Ca1.2 activation and expression in mast cells ameliorates allergic inflammation diseases.

Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca level, but the intake and effects of the intracellular Ca remain unclear. The Ca influx is controlled by members of Ca channels, among which calcium voltage-gated channel subunit alpha1 C (Ca1.2) is the most robust.

Association between major depressive disorder or depressive symptoms and the risk of vascular complications among patients with type 2 diabetes, and the mediating role of metabolic biomarkers: an analysis of the UK Biobank cohort.

Background: Depression is a severe mental disorder commonly co-morbid with diabetes, but it remains to elucidate whether depression is associated with the risks of a wide range of vascular complications in people with type 2 diabetes mellitus (T2DM) and whether metabolic biomarkers may mediate this pathway.

Methods: We conducted this prospective analysis among the participants of the UK Biobank who were diagnosed with T2DM and free of vascular complications at baseline between March 13, 2006 and September 30, 2010. Major depressive disorder (MDD) was ascertained according to the hospital admission records and self-report of doctor-diagnosed conditions, while the presence of depressive symptoms was assessed using the Patient Health Questionnaire-2.

Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescents.

Background: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. We further explore if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection using causal mediation analysis.

TRPC5 Promotes Intermittent Hypoxia-Induced Cardiomyocyte Injury Through Oxidative Stress.

Purpose: Intermittent hypoxia (IH), a defining feature of obstructive sleep apnea (OSA), is associated with heart damage and linked to transient receptor potential canonical channel 5 (TRPC5). Nonetheless, the function of TRPC5 in OSA-induced cardiac injury remains uncertain. For this research, we aimed to explore the role and potential mechanism of TRPC5 in cardiomyocyte injury induced by intermittent hypoxia.

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV.

Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods: We followed individuals from ART initiation (protease inhibitor [PI]-, non-nucleoside reverse transcriptase inhibitor [NNRTI]-, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, 12/31/2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses).

The molecular basis of pH sensing by the human fungal pathogen TOK potassium channel.

Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested.

Use of cannabis to manage symptoms of mental and physical health conditions during pregnancy: analysis of a pro-cannabis pregnancy forum.

Introduction: Rates of prenatal cannabis use (PCU) have increased in recent years. Despite evidence of developmental health consequences to offspring and birthing person, there has been a reduction in the perception of PCU-related harms. Due to the stigma and risk of legal consequences associated with disclosing PCU, individuals are often cautious to seek information from their healthcare providers.

Genetic vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohorts.

Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.

Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.

Leveraging pre-trained machine learning models for islet quantification in type 1 diabetes.

Human islets display a high degree of heterogeneity in terms of size, number, architecture, and endocrine cell-type compositions. An ever-increasing number of immunohistochemistry-stained whole slide images (WSIs) are available through the online pathology database of the Network for Pancreatic Organ donors with Diabetes (nPOD) program at the University of Florida (UF). We aimed to develop an enhanced machine learning-assisted WSI analysis workflow to utilize the nPOD resource for analysis of endocrine cell heterogeneity in the natural history of type 1 diabetes (T1D) in comparison to donors without diabetes.

ChatGPT-4 Turbo and Meta's LLaMA 3.1: A Relative Analysis of Answering Radiology Text-Based Questions.

Aims And Objectives: This study aimed to compare the accuracy of two AI models - OpenAI's GPT-4 Turbo (San Francisco, CA) and Meta's LLaMA 3.1 (Menlo Park, CA) - when answering a standardized set of pediatric radiology questions. The primary objective was to evaluate the overall accuracy of each model, while the secondary objective was to assess their performance within subsections.