Clinical Manifestations.

Background: Neuropsychological assessments are often affected by demographic factors, such as age, education, and sex. These demographic variables frequently lead to differences in test scores between minorities and non-minorities, lowering diagnostic accuracy of Alzheimer's disease (AD) among minoritized groups. A new test (quick Behavioral Exam to Advance Neuropsychological Screening, or qBEANS) has been developed to assess early signs of AD.

Monocyte Anisocytosis is Associated with Sepsis in Children with Suspected Infection.

Background: Early, accurate determination of disease severity in an emergency setting is paramount for improving patient outcomes and healthcare costs. Monocyte anisocytosis, quantified as monocyte distribution width (MDW), has been shown to correspond with immune dysregulation. We hypothesize that MDW is broadly associated with illness severity related to sepsis and serious infection in children.

Bringing Pandemic Science to the Classroom: Building Public Health Capacity at a Rural Kentucky High School.

In response to the COVID-19 pandemic, a multidisciplinary team at the University of Kentucky developed an interdisciplinary science, technology, engineering, and mathematics and environmental health unit-the Wastewater Assessment for Coronavirus in Kentucky: Implementing Enhanced Surveillance Technology (WACKIEST) Unit-for high school students in summer 2022. This case study outlines the WACKIEST Unit, which focused on wastewater surveillance and COVID-19, the obstacles faced during development and recruitment, and implementation of the WACKIEST Unit in conjunction with a rural wastewater surveillance initiative. The unit was implemented in spring 2023 at a rural high school in Kentucky, spanning 12 days and engaging 190 students.

Population Pharmacokinetics and Pharmacodynamics of Sotalol Following Expedited Intravenous Loading in Patients With Atrial Arrhythmias.

Sotalol, a class III antiarrhythmic agent, is used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter (AFIB/AFL). Despite its efficacy, sotalol's use is limited by its potential to cause life-threatening ventricular arrhythmias due to QT interval prolongation. Traditionally, sotalol administration required hospitalization to monitor these risks.

KPRR: a novel machine learning approach for effectively capturing nonadditive effects in genomic prediction.

Nonadditive genetic effects pose significant challenges to traditional genomic selection methods for quantitative traits. Machine learning approaches, particularly kernel-based methods, offer promising solutions to overcome these limitations. In this study, we developed a novel machine learning method, KPRR, which integrated a polynomial kernel into ridge regression to effectively capture nonadditive genetic effects.

Simple Isolation of Human Bone Marrow Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells.

Bone marrow adipose tissue (BMAT) has garnered significant attention due to its critical roles in leukemia pathogenesis, cancer metastasis, and bone marrow failure. BMAT is a metabolically active, distinct tissue that differs from other fat depots. Marrow adipocytes, closely interacting with hematopoietic stem/progenitor cells and osteoblasts, play a pivotal role in regulating their functions.

Post-acute sequela of COVID-19 infection in individuals with multiple sclerosis.

Background: Many common symptoms in post-acute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) overlap with those of multiple sclerosis (MS). We examined symptoms and performance of the PASC score, developed in the general population, in MS based on infection history.

Methods: We surveyed North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants regarding infections and categorized participants based on infection history.

Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.

Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.

Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

A trial of radiolabeled antibody yttrium-90-FF-21101 for the treatment of advanced ovarian and other cancers.

Background: Yttrium-90 FF-21101 (Y-FF-21101) is a radiopharmaceutical that targets P-cadherin as a therapy against solid tumors. A previously reported, first-in-human study determined that a dose of 25 mCi/m was safe, and a patient with clear cell carcinoma of the ovary achieved a complete response. In this article, the authors report the results of Y-FF-21101 treatment in an ovarian carcinoma expansion cohort and in patients with selected solid tumors who had known high P-cadherin expression.

Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

A Lactobacillus consortium provides insights into the sleep-exercise-microbiome nexus in proof of concept studies of elite athletes and in the general population.

Background: The complex relationship among sleep, exercise, and the gut microbiome presents a unique opportunity to improve health and wellness. Here, we conducted the first large-scale investigation into the influence of a novel elite athlete-derived probiotic, consisting of a multi-strain Lactobacillus consortium, on sleep quality, exercise recovery, and gut microbiome composition in both elite athletes (n = 11) and the general population (n = 257).

Results: Our two-phase study design, which included an open-label study followed by a controlled longitudinal study in a professional soccer team, allowed us to identify key interactions between probiotics, the gut microbiome, and the host.

Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials.

Background: Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through Week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.

Heart-retina time analysis using electrocardiogram-coupled time-resolved dynamic optical coherence tomography.

The eye and the heart are two closely interlinked organs, and many diseases affecting the cardiovascular system manifest in the eye. To contribute to the understanding of blood flow propagation towards the retina, we developed a method to acquire electrocardiogram (ECG) coupled time-resolved dynamic optical coherence tomography (OCT) images. This method allows for continuous synchronised monitoring of the cardiac cycle and retinal blood flow dynamics.

Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial.

GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

Machine learning-based analysis of microfluidic device immobilized C. elegans for automated developmental toxicity testing.

Developmental toxicity (DevTox) tests evaluate the adverse effects of chemical exposures on an organism's development. Although current testing primarily relies on large mammalian models, the emergence of new approach methodologies (NAMs) is encouraging industries and regulatory agencies to evaluate novel assays. C.

Liver-specific gene PGRMC1 blocks c-Myc-induced hepatocarcinogenesis through ER stress-independent PERK activation.

Roles of liver-specific genes (LSGs) in tumor initiation and progression are rarely explored in hepatocellular carcinoma (HCC). Here we show that LSGs are generally downregulated in HCC tumor tissues compared to non-HCC liver tissues, and low-LSG HCCs show poor prognosis and the activated c-Myc pathway. Among the c-Myc- and patient prognosis-associated LSGs, PGRMC1 significantly blocks c-Myc-induced orthotopic HCC formation.

Food Safety Evaluation of Recombinant Humanized Type III Collagen Produced by Komagataella phaffii SMD1168-2COL3.

Collagens are biofunctional proteins that have been widely used in many fields, including biomedical, cosmetics, and skin care for their value in maintaining the integrity of cellular membranes. Collagens are also commonly consumed in foods and provide a source of protein and amino acids. As part of the safety assessment for this particular recombinant humanized type III (RHTypeIII) collagen produced by Komagataella phaffii SMD1168-2COL3, a series of toxicological tests were conducted.

Comparison of Two-Point Versus Three-Point Fixation in Treatment of Zygomaticomaxillary Complex Fractures: An Updated Meta-Analysis.

Purpose: Zygomaticomaxillary complex (ZMC) fractures are a prevalent form of craniofacial trauma. However, no universally accepted fixation method has been established to prevent postreduction displacement in ZMC fractures.

Methods: Computerized and additional manual searches of the Medline, Embase, Chinese National Knowledge Infrastructure, and Cochrane Central database for potential studies, published from inception to May 2024, were performed.

Acquired torticollis due to an ocular surface foreign body.

Ocular torticollis is traditionally attributed to eye misalignment, nystagmus, ptosis, or refractive error. We present 3 pediatric cases of acquired torticollis caused by a foreign body beneath the upper eyelid. The head posturing presumably developed to minimize contact of the foreign body with the corneal surface and mitigate ocular discomfort.

Body Composition Measurements as Predictive Variables for Outcomes of Canine Appendicular Osteosarcoma Treated With Stereotactic Body Radiation Therapy.

Body composition measurements (BCM), obtained via computed tomography (CT), have been used as predictors of survival, tumour recurrence, and post-surgical infections in human oncology. There are no reports on using BCM to predict outcomes of dogs with cancer. Elevated BCM is hypothesised to place extra stress on bones weakened by cancer.

Washing with buffered vitamin C after corrosive chemical (sodium hypochlorite) exposure reduces ocular depth of injury.

Chemical eye injuries occur in home, industrial, and military settings. The standard recommended treatment after exposure of the eyes to chemical toxins is washing with tap water for at least 15 min. An estimated 80 % of ocular toxins are associated with reactive oxygen species and/or extreme pH.

A Multidisciplinary Approach to Navigating Variants of Uncertain Significance in Sudden Infant Deaths: A Case Report of 2 Siblings With an SCN10A VUS.

The sudden death of a previously healthy infant is a devastating event for a family-the death of 2 even more unimaginable. Prior to the debunking of Meadow's law, a legal concept attributing multiple unexplained infant deaths to Munchausen by proxy, these events could lead to the wrongful prosecution of those who had lost their children to "sudden unexpected infant death (SUID)." Today, these cases, wherein multiple infants within one family pass inexplicably, raise suspicion for a possible genetic cause and point toward a need for postmortem genetic testing.