Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights.

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs.

Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review.

Background: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

Early treatment discontinuation in patients with deficient mismatch repair or microsatellite instability high metastatic colorectal cancer receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy.

Altered thrombin generation with prothrombin complex concentrate is not detected by viscoelastic testing: an in vitro study.

Background: Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity.

Pathogenic mechanisms of immune checkpoint inhibitor (ICI)-associated retinal and choroidal adverse reactions.

Purpose: To summarize and categorize postulated mechanisms of immune checkpoint inhibitor (ICI)-mediated retinal and choroidal inflammation and discuss resulting implications for evaluation and management of these adverse reactions.

Design: Targeted literature review with interpretation and perspective Methods: We performed a review of selected literature describing immune-mediated retinal and choroidal adverse reactions associated with ICI therapy, synthesizing and categorizing the likely underlying pathogenic mechanisms. Based on these mechanistic categories, we provide perspective on a rational approach to the evaluation of patients with ICI-associated inflammatory disorders of the retina and choroid.

Quantifying the effect of particulate impurities on the ice nucleation behavior of pharmaceutical solutions.

Numerous commercially available biopharmaceuticals are frozen or freeze-dried in vials. The temperature at which ice nucleates and its distribution across vials in a batch is critical to the design of freezing and freeze-drying processes. Here we study experimentally how the level of particulate impurities - a key parameter in pharmaceutical manufacturing - affects the ice nucleation behavior.

Severe maternal morbidity contributed by obstetric hemorrhage: Maryland, 2020-2022.

Background: Obstetric hemorrhage is the leading cause of maternal mortality and severe maternal morbidity (SMM) in Maryland and nationally. Currently, through a quality collaborative, the state is implementing the Alliance for Innovation on Maternal Health (AIM) patient safety bundle on obstetric hemorrhage.

Objective: To describe SMM events contributed by obstetric hemorrhage and their preventability in Maryland.

Relationship of Time to First Therapy and Survival Outcomes of Neoadjuvant Chemotherapy Versus Upfront Surgery Approach in Resectable Pancreatic Ductal Adenocarcinoma.

Introduction: Evidence demonstrating overall survival benefit of neoadjuvant chemotherapy (NAC) followed by surgical resection over upfront surgical resection for resectable pancreatic ductal adenocarcinoma (PDAC) has been mixed. The time to first therapy (TTFT) variable has not been studied as a contributing factor.

Methods: A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T1 and T2 PDACs from 2010 to 2020.

Damage Control Surgery in the Era of Globalization of Health Care - Military and International Outcomes: A SystematicReview.

Introduction: Damage Control Surgery (DCS) is a surgical technique used to manage critically ill and injured patients. This study examines the most recent 10-y outcomes related to DCS, with the secondary goal of scrutinizing the outcomes after DCS across surgical theaters.

Methods: Studies published between 2012 and 2021 that described adult patients undergoing Abdominal DCS after traumatic injury were included.

Associations Between Age-for-Grade, Sex, and Interpersonal Violence Among U.S. High School Students.

The current study examines how atypical age-for-grade (i.e., being old- or young-for-grade) is associated with various types of interpersonal violence (e.

Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury.

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days.

Land Use Change Consistently Reduces α- But Not β- and γ-Diversity of Bees.

Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e.

Histopathologic Features of Acral Skin Biopsies in Dermatomyositis Patients and Comparison to Histopathologic Features in Non-Acral Biopsies.

Background: Acral lesions may represent the best/only skin lesions to biopsy in patients suspected to have dermatomyositis (DM). However, histopathologic features of acral DM skin lesions are poorly characterized.

Methods: We reviewed 50 acral biopsies from 46 DM patients and assessed numerous histopathologic features.

Complement inhibition targets a rich-club within the neuroinflammatory network after stroke to improve radiographic and functional outcomes.

Following recent advances in post-thrombectomy stroke care, the role of neuroinflammation and neuroprotective strategies in mitigating secondary injury has gained prominence. Yet, while neuroprotection and anti-inflammatory agents have re-emerged in clinical trials, their success has been limited. The neuroinflammatory response in cerebral ischemia is robust and multifactorial, complicating therapeutic approaches targeting single pathways.

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

Sources of HIV information and women's HIV knowledge in Southwest Sumba Indonesia: a cross-sectional study with mediation analysis.

Background: Despite multiple years of government HIV educational efforts, the growing trend of new cases among women in Indonesia runs parallel with their seemingly overall lack of comprehensive knowledge about HIV. A major prevention challenge for the Indonesian government lies in delivering HIV prevention education across the world's largest archipelago. This study investigates comprehensive HIV knowledge among reproductive-age women in Southwest Sumba, Indonesia, and the sources through which they report having learned about HIV along with potential mediators of the relationship between socioeconomic status (SES) and HIV knowledge.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Deep learning-based pelvimetry in pelvic MRI volumes for pre-operative difficulty assessment of total mesorectal excision.

Background: Specific pelvic bone dimensions have been identified as predictors of total mesorectal excision (TME) difficulty and outcomes. However, manual measurement of these dimensions (pelvimetry) is labor intensive and thus, anatomic criteria are not included in the pre-operative difficulty assessment. In this work, we propose an automated workflow for pelvimetry based on pre-operative magnetic resonance imaging (MRI) volumes.

The Role of Diet, Glycaemic Index and Glucose Control in Polycystic Ovary Syndrome (PCOS) Management and Mechanisms of Progression.

Purpose Of Review: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with several causal pathways including impaired glucose tolerance, insulin resistance (IR), compensatory hyperinsulinemia and excess androgens (hyperandrogenism). This heterogeneous condition causes a range of reproductive, metabolic and psychological implications, the severity of which can differ between individuals depending on factors such as age, diet, ethnicity, genetics, medication, contraceptive use, adiposity, and Body Mass Index (BMI).

Recent Findings: Dietary interventions that focus on a low glycaemic index and glucose control are an efficient first-line dietary solution for the management of impaired glucose tolerance and IR, which subsequently improves weight management, quality of life and PCOS-related symptoms in individuals with this condition.

Demonstration of active neutron interrogation of special nuclear materials using a high-intensity short-pulse-laser-driven neutron source.

Detecting shielded special nuclear material, such as nuclear explosives, is a difficult challenge pursued by non-proliferation, anti-terrorism, and nuclear security programs worldwide. Interrogation with intense fast-neutron pulses is a promising method to characterize concealed nuclear material rapidly but is limited by suitable source availability and proven instrumentation. In this study we have pioneered a demonstration of such an interrogation method using a high-intensity, short-pulse, laser-driven neutron source that offers potential benefits compared to conventional neutron sources.

Increased Prevalence of Skeletal Anomalies on Ultrasound Evaluation of Buprenorphine-Exposed Human Fetuses.

Objectives: In this study, buprenorphine was the primary source of maternal opioid exposure at the time of initial prenatal evaluation. Current recommendations advise that level II ultrasounds be performed in patients with substance use disorders. For some patients, distance, transportation, and costs associated with obtaining ultrasounds from a specialist pose significant barriers.