Longitudinal Changes in Patient- and Clinical-Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study.

Background: Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients.

Objectives: To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6.

Methods: We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls.

Isolation and spectroscopic characterization of anticancer phytochemicals from : a combined experimental and theoretical investigation using ADMET analysis and in silico molecular docking simulation against key cancer targets.

, a high-altitude medicinal herb, possesses diverse therapeutic properties. This study conducted a comprehensive phytochemical analysis of the whole plant, leading to the isolation of 15 secondary metabolites (1-15) across various classes: flavonoids (), triterpenoids (, ), sesquiterpenoid lactones (, ) and furanocoumarins (, ) along with three steroids (). These compounds were characterized using NMR (HNMR,C NMR, 2D NMR), IR, HRMS and UV-VIS.

Competing addition processes give distinct growth regimes in the assembly of 1D filaments.

We present a model to describe the concentration-dependent growth of protein filaments. Our model contains two states, a low entropy/high affinity ordered state and a high entropy/low affinity disordered state. Consistent with experiments, our model shows a diffusion-limited linear growth regime at low concentration, followed by a concentration-independent plateau at intermediate concentrations, and rapid disordered precipitation at the highest concentrations.

Synaptic cleft geometry modulates NMDAR opening probability by tuning neurotransmitter residence time.

Synaptic morphology plays a critical role in modulating the dynamics of neurotransmitter diffusion and receptor activation in interneuron communication. Central physical aspects of synaptic geometry, such as the curvature of the synaptic cleft, the distance between the presynaptic and postsynaptic membranes, and the surface area-to-volume ratio of the cleft, crucially influence glutamate diffusion and N-Methyl-D-Aspartate receptor (NMDAR) opening probabilities. In this study, we developed a stochastic model for receptor activation using realistic synaptic geometries.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

Assessment of a New CT Detector and Filtration Technology: Part 1 - X-ray Beam Characterization and Radiation Dosimetry.

Purpose: This study evaluated beam quality and radiation dosimetry of a CT scanner equipped with a novel detector and filtration technology called PureVision Optics (PVO). PVO features miniaturized electronics, a detector cut with microblade technology, and increased filtration in order to increase x-ray detection and reduce image noise.

Methods: We assessed the performance of two similar 320-detector CT scanners: one equipped with PVO and one without.

Assessment of a New CT Detector and Filtration Technology: Part 2-Image Quality in Phantoms, Cadavers, and Patients.

Purpose: The purpose of this work was to evaluate the image quality of a commercial CT scanner equipped with a novel detector and filtration technology called PureVision Optics (PVO).

Methods: CT number, noise, contrast-to-noise ratio (CNR), modulation transfer function (MTF), and noise power spectrum (NPS) were assessed using the ACR CT Accreditation phantom scanned with various acquisitions at 80 kV, 100 kV, 120 kV, and 135 kV, each with multiple CTDIvol values of 20 mGy, 40 mGy, and 65 mGy. Artifacts were evaluated in an anthropomorphic head phantom, a cadaver head, and in patient studies.

Phenotypic Expansion of Knobloch Syndrome Type 2 in an Individual With a De Novo PAK2 Variant.

P21-activated kinase 2 (PAK2) is a serine/threonine kinase essential for a variety of cellular processes including signal transduction, cellular survival, proliferation, and migration. A recent report proposed monoallelic PAK2 variants cause Knobloch syndrome type 2 (KNO2)-a developmental disorder primarily characterized by ocular anomalies. Here, we identified a novel de novo heterozygous missense variant in PAK2, NM_002577.

Pharmacokinetics of Depemokimab Delivered by Safety Syringe Device or Autoinjector in Healthy Adults: A Phase I, Single-Dose Study.

This Phase I, randomized, multicenter, open-label, parallel-group, single-dose study assessed the relative bioavailability of the anti-interleukin-5 antibody depemokimab (100 mg) when administered subcutaneously via either a safety syringe device (SSD) or an autoinjector (AI). Healthy adult participants were randomized I:I to SSD or AI treatment arms and I:I:I to the injection site (upper arm, abdomen, or thigh). Participants were followed up for 30 weeks; blood samples were collected for pharmacokinetic (PK) assessment before dosing on Day 1 and up to Week 26.

Plant-based eating pattern and psychological symptoms: a cross-sectional survey among patients with migraine.

Objectives: The present study evaluated the association between plant-based diet index (PDI) and psychological symptoms, including depressive symptoms, stress, and anxiety among Iranian women diagnosed with migraine headaches.

Methods: A cross-sectional study was conducted on 262 patients with migraine (aged 20-50 years; body mass index, 18.5-30 kg/m²).

Evaluating the Effectiveness of a Novel Pongamia pinnata Derived Herbal Mouth-Dissolving Film for Treating Oral Disorders and Evaluating Its Anticancer Properties.

The present study aimed to optimize a mouth-dissolving film (MDF) made from Pongamia pinnata stem bark extract to increase patient compliance and accelerate oral disease therapy. Several stem bark extracts were prepared, and karanjin was used as an herbal marker for the extracts. The ethanolic extract showed the maximum yield (12.

Development of Electronic Objective Structured Clinical Examinations (e-OSCEs) for Prosthodontic Clinical Assessment.

Introduction: Objective Structured Clinical Examinations (OSCEs) serve as a reliable assessment tool for clinical and competency evaluation. Traditional OSCEs, involving live patients, present logistical challenges and evoke student anxiety. In an effort to create a comprehensive clinical series of examinations, electronic OSCEs (e-OSCEs) were developed for assessing clinical competencies in prosthodontics at a large dental school.

Insights from the First Five Years of the Prospective Ocular Tumor Study.

Purpose: Standardized data collection is needed to improve research for rare diseases. In this manuscript, we describe our experience establishing the Prospective Ocular Tumor Study (POTS).

Methods: The ongoing POTS captures all patients with an ocular tumor seen on the Ocular Oncology Service at Mayo Clinic Rochester and collects patient demographics, tumor features, treatment, and outcomes.

Residential Exposure to PM Constituents and Fecundability in a Danish Preconception Cohort.

Background: Epidemiologic studies have demonstrated that ambient concentrations of particulate matter < 2.5 μm (PM) are associated with reduced fecundability, the per cycle probability of conception. The specific constituents driving this association are unknown.

Functional Morphology of Hatching: Ontogeny and Distribution of Hatching Gland Cells in Red-Eyed Treefrogs and a New Marker for Anuran Hatching Enzyme.

Environmentally cued hatching (ECH) is widespread in animals and requires regulation of hatching mechanisms. Enzymatic digestion of the egg membrane is a common hatching mechanism in vertebrates and invertebrates. In amphibians and fishes, hatching enzymes (HE) are synthesized and released by hatching gland cells (HGC), whose functional ontogeny determines when hatching can occur.

IQ Survey Results on Current Industry Practices-Part 1: Immunogenicity Risk Assessment.

An immunogenicity risk assessment (IRA) is a relatively new expectation of health authorities that is increasingly incorporated into the drug development process across the pharmaceutical/biotech industry. The guiding principle for an IRA includes a comprehensive evaluation of product- and patient-related factors that may influence the immunogenic potential of a biotherapeutic drug and a potential action plan. The Immunogenicity Working Group from the IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices for conducting IRAs and relevant aspects of bioanalysis.

Submucosal Microbiome Profiles in Paired and Unpaired Samples From Healthy and Peri-Implantitis Dental Implants.

Background: This cross-sectional study aimed to compare the composition of the submucosal microbiome of peri-implantitis with paired and unpaired healthy implant samples.

Methods: We evaluated submucosal plaque samples obtained in 39 cases, including 13 cases of peri-implantitis, 13 cases involving healthy implants from the same patient (paired samples), and 13 cases involving healthy implants from different individuals (unpaired samples). The patients were evaluated using next-generation genomic sequencing (Illumina) based on 16S rRNA gene amplification.

Integrated Longitudinal Population Dose-Hemoglobin Response of Daprodustat Following Dose Titration in Patients With Anemia in Chronic Kidney Disease.

Daprodustat, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor is approved in the United States for the treatment of anemia due to chronic kidney disease (CKD) in adults receiving dialysis for at least 4 months. Pharmacodynamic dose-hemoglobin (Dose-Hgb) models were developed as daprodustat progressed through development. To support global phase III development, a dose-titration algorithm, guided by simulations from the initial Dose-Hgb model based on phase II clinical data, was implemented.

Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).

Toward Developing Alternative Opioid Antagonists for Treating Community Overdose: A Model-Based Evaluation of Important Pharmacological Attributes.

In response to increased illicit use of synthetic opioids, various μ-receptor antagonist formulations, with varied pharmacological characteristics, have been and are being developed. To understand how pharmacologic characteristics such as absorption rate and clearance rate affect reversal in treating community opioid overdose, we used our previously published translational opioid model. We adapted this model with in vitro receptor binding data and clinical pharmacokinetic data of three intranasal nalmefene formulations along with an intranasal naloxone formulation to study the reversal of fentanyl and carfentanil-induced respiratory depression in chronic opioid users.

Scanning K-edge subtraction (SKES) imaging with laser-compton x-ray sources.

Background: K-edge subtraction (KES) imaging is a dual-energy imaging technique that enhances contrast by subtracting images taken with x-rays that are above and below the K-edge energy of a specified contrast agent. The resulting reconstruction spatially identifies where the contrast agent accumulates, even when obscured by complex and heterogeneous distributions of human tissue. This method is most successful when x-ray sources are quasimonoenergetic and tunable, conditions that have traditionally only been met at synchrotrons.

Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS.

1-Aminocyclopropane-1-carboxylate synthase (ACCS) catalyzes the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylate (ACC), a rate-limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure.

The Associations Between Sleep Duration and Various Metabolic Health Indices Among Adults in the United States: A Multivariate Analysis of Variance (MANOVA) Using National Health and Nutrition Examination Survey (NHANES) 2021 to 2023 Dataset.

Objective: This study explores the associations between various sleep durations and metabolic health indices, including systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol levels, high-density lipoprotein (HDL) cholesterol, and waist circumference.

Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2021 to 2023, were analyzed. MANOVA and Bonferroni-adjusted ANOVAs were conducted to examine the relationships between sleep duration (sleep deprivation (≤5 h), short sleep (5-7 h), recommended sleep (7-9 h), and long sleep (>9 h)) and metabolic health indices.

Midterm Survivorship and Clinical Outcomes in Fresh Osteochondral Allograft Transplantation for the Treatment of Large Bipolar Lesions of the Knee.

Background: Fresh osteochondral allograft (OCA) transplantation is an established treatment option for patients with chondral or osteochondral lesions of the knee. Predictably positive outcomes are seen in situations of focal or isolated cartilage defects. However, OCA transplantation may also be performed in more complex joint salvage situations in young patients.