Limb Underloading in Walking Transmits Less Dynamic Knee Joint Contact Forces after Anterior Cruciate Ligament Reconstruction.

Introduction: Individuals with anterior cruciate ligament reconstruction (ACLR) often walk with a less dynamic vertical ground reaction force (vGRF), exemplified by a reduced first peak vGRF and elevated midstance vGRF compared to uninjured controls. However, the mechanism by which altered limb loading affects actual tibial plateau contact forces during walking remains unclear.

Methods: Our purpose was to use musculoskeletal simulation to evaluate the effects of first peak vertical ground reaction force (vGRF) biofeedback on bilateral tibiofemoral contact forces relevant to the development of post-traumatic osteoarthritis (OA) in 20 individuals with ACLR.

Creation of Piezoelectricity in Quadruple Perovskite Oxides by Harnessing Cation Defects and Their Application in Piezo-Photocatalysis.

Quadruple perovskite oxides have received extensive attention in electronics and catalysis, owing to their cation-ordering structure and intriguing physical properties. However, their repertoires still remain limited. In particular, piezoelectricity from quadruple perovskites has been rarely reported due to the frustrated symmetry-breaking transition in A-site-ordered perovskite structures, disabling their piezoelectric applications.

Time-driven cost analysis of pediatric liver biopsy completed in pediatric sedation clinic and operating room.

Background: Pediatric ultrasound (US)-guided percutaneous liver biopsy is a commonly performed procedure in children, and may be performed in a variety of clinical settings. However, there is little research on the relative costs associated with different sedation methods and locations.

Objective: This study uses time-driven activity-based costing (TDABC) to identify relevant costs associated with different biopsy sedation techniques and locations to help inform providers and patients as well as guide value-conscious care.

Design and implementation of optics for the experiment for cryogenic large-aperture intensity mapping (EXCLAIM).

This work describes the design and implementation of optics for EXCLAIM, the EXperiment for Cryogenic Large-Aperture Intensity Mapping. EXCLAIM is a balloon-borne telescope that will measure integrated line emission from carbon monoxide at redshifts z < 1 and ionized carbon ([CII]) at redshifts z = 2.5 - 3.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome.

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic).

Preventing Infant Mortality Through Medicaid-Administered Prenatal Care Coordination: Evidence From Wisconsin.

Objective: To estimate associations between Wisconsin Medicaid's Prenatal Care Coordination (PNCC) program and infant mortality.

Data Sources And Study Setting: We analyzed birth records, Medicaid claims, and infant death records for all resident and in-state Medicaid-paid live deliveries during 2010-2018.

Study Design: We measured PNCC exposure during pregnancy dichotomously (none; any) and categorically (none; assessment/care plan only; service receipt).

Prophage-DB: a comprehensive database to explore diversity, distribution, and ecology of prophages.

Background: Viruses that infect prokaryotes (phages) constitute the most abundant group of biological agents, playing pivotal roles in microbial systems. They are known to impact microbial community dynamics, microbial ecology, and evolution. Efforts to document the diversity, host range, infection dynamics, and effects of bacteriophage infection on host cell metabolism are extremely underexplored.

Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection.

Protein aggregates are associated with numerous diseases. Here we report a platform for the rapid phenotypic selection of protein aggregation inhibitors from genetically encoded cyclic peptide libraries in Escherichia coli based on phage-assisted continuous evolution (PACE). We developed a new PACE-compatible selection for protein aggregation inhibition and used it to identify cyclic peptides that suppress amyloid-β42 and human islet amyloid polypeptide aggregation.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

Famished for Freedom: Pellagra and Medical Clemency at the Mississippi State Penitentiary.

This paper provides a case study of one medical experiment conducted in 1915 by the United States Public Health Service in collaboration with the Mississippi State Penitentiary. The experiment was non-therapeutic and its objective was to induce pellagra (a vitamin deficiency disease) in twelve healthy White male prisoners to confirm its etiology. Extant archival records produced by the convict participants, state politicians, and health researchers underscore that the men selected for the pellagra experiment were unique among incarcerated people in Mississippi at the time: they were White, wealthy, and politically well-connected.

HighDimMixedModels.jl: Robust high-dimensional mixed-effects models across omics data.

High-dimensional mixed-effects models are an increasingly important form of regression in which the number of covariates rivals or exceeds the number of samples, which are collected in groups or clusters. The penalized likelihood approach to fitting these models relies on a coordinate descent algorithm that lacks guarantees of convergence to a global optimum. Here, we empirically study the behavior of this algorithm on simulated and real examples of three types of data that are common in modern biology: transcriptome, genome-wide association, and microbiome data.

Are women really (not) more talkative than men? A registered report of binary gender similarities/differences in daily word use.

Women are widely assumed to be more talkative than men. Challenging this assumption, Mehl et al. (2007) provided empirical evidence that men and women do not differ significantly in their daily word use, speaking about 16,000 words per day (WPD) each.

Evaluation of subretinally delivered Cas9 ribonucleoproteins in murine and porcine animal models highlights key considerations for therapeutic translation of genetic medicines.

Genetic medicines, including CRISPR/Cas technologies, extend tremendous promise for addressing unmet medical need in inherited retinal disorders and other indications; however, there remain challenges for the development of therapeutics. Herein, we evaluate genome editing by engineered Cas9 ribonucleoproteins (eRNP) in vivo via subretinal administration using mouse and pig animal models. Subretinal administration of adenine base editor and double strand break-inducing Cas9 nuclease eRNPs mediate genome editing in both species.

Uncertainty estimation in diagnosis generation from large language models: next-word probability is not pre-test probability.

Objective: To evaluate large language models (LLMs) for pre-test diagnostic probability estimation and compare their uncertainty estimation performance with a traditional machine learning classifier.

Materials And Methods: We assessed 2 instruction-tuned LLMs, Mistral-7B-Instruct and Llama3-70B-chat-hf, on predicting binary outcomes for Sepsis, Arrhythmia, and Congestive Heart Failure (CHF) using electronic health record (EHR) data from 660 patients. Three uncertainty estimation methods-Verbalized Confidence, Token Logits, and LLM Embedding+XGB-were compared against an eXtreme Gradient Boosting (XGB) classifier trained on raw EHR data.

Informing a sinusitis clinical trial protocol: A focus group study with clinicians and staff.

This study investigates practicing clinician and staff perspectives on potential protocol modifications for the "Nasal Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Acute Sinusitis" (NOSES) study, a pragmatic randomized controlled trial aiming at improving acute rhinosinusitis management. Focus groups with clinicians and staff at the pretrial stage recommended expanding participant age inclusion criteria, incorporating patients with COVID-19, and shortening the supportive care phase. Participants also discussed patient engagement and recruitment strategies.

A shared alarmone-GTP switch underlies triggered and spontaneous persistence.

Persisters describe phenotypically switched cells refractory to antibiotic killing in a genetically susceptible population, while preserving the ability to resume growth when antibiotics are discontinued1,2. Since its proposal 70 years ago, great strides were made to build the framework regarding persistence, including defining triggered, spontaneous and antibiotic-induced persisters. However, challenges remain in characterizing the molecular determinants underlying the phenotypic switch into persistence3.

Non-colorectal Cancer Screening and Vaccinations in Patients with Inflammatory Bowel Disease: Expert Review.

Description: The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice (BPA) statements for gastroenterologists and other health care providers who provide care to patients with inflammatory bowel disease (IBD). The focus is on IBD-specific screenings (excluding colorectal cancer screening, which is discussed separately) and vaccinations. We provide guidance to ensure that patients are up to date with the disease-specific cancer screenings, vaccinations, as well as advice for mental health and general wellbeing.

Genipin-crosslinked double PLL membranes overcome the strength-diffusion trade-off in cell encapsulation without compromising biocompatibility.

Cell microencapsulation technologies allow non-autologous implantation of therapeutic cells for sustained drug delivery purposes. The perm-selective membrane of these systems provides resistance to rupture, stablishes the upper molecular weight limit in bidirectional diffusion of molecules, and affects biocompatibility. Thus, despite being a decisive factor to succeed in terms of biosafety and therapeutic efficacy, little progress has been made in its optimization so far.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

Evaluating the sustained effectiveness of a novel pharmacy-based intervention to reduce older adult misuse of over-the-counter medications: A case for non-significance.

Introduction: Misuse of over-the-counter (OTC) medications by older adults (age 65+) can comprise Drug-Age, Drug-Drug, Drug-Disease, and Drug-Label types. Pharmacies in the United States are prevalent sources of OTCs and are an apt setting to address OTC misuse. Senior Safe™ is a pharmacy-system redesign for preventing older adult OTC misuse.

Evaluating the physiological benefits of behavioral flexibility in chacma baboons (Papio ursinus) using a biophysical model.

As opportunistic generalists occupying a range of ecological niches, chacma baboons (Papio ursinus) are considered a highly flexible species of relatively low conservation priority. Underlying their ecological flexibility is a repertoire of behavioral strategies observed in response to ecological stressors. Although these strategies are relatively well-documented, we know very little about how they impact upon an individual's thermal and energetic physiology, which can influence population-level reproductive potential in the face of climatic warming.

A Lu-nucleotide coordination polymer-incorporated thermosensitive hydrogel with anti-inflammatory and chondroprotective capabilities for osteoarthritis treatment.

Osteoarthritis (OA) is a prevalent and debilitating condition characterized by cartilage destruction and inflammation. Traditional pharmacotherapies for OA are limited by their short-term efficacy and systemic side effects. Radiosynoviorthesis (RSO), involving intra-articular injection of radiopharmaceuticals, has shown promise for OA treatment but is hindered by the toxicity and rapid clearance of radioisotopes.