Meniscal forces and knee kinematics are affected by tibial slope modifying high tibial osteotomy.

Purpose: To quantify the effect of increasing the posterior tibial slope (PTS) on knee kinematics and the resultant medial and lateral meniscal forces.

Methods: In this controlled laboratory study, a 6 degrees of freedom (DOF) robotic testing system was used to apply external loading conditions to seven fresh-frozen human cadaveric knees: (1) 200-N axial compressive load, (2) 5-N m internal tibial +10-N m valgus torque and (3) 5-N m external tibial + 10-N m varus torque. Knee kinematics and the resultant medial and lateral meniscal forces were acquired for two PTS states: (1) native PTS and (2) increased PTS.

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.

3D reconstruction of shoulder muscles in hominoid primates: Correlating scapular attachment areas with muscle volume.

Digital muscle reconstructions have gained attraction in recent years, serving as powerful tools in both educational and research contexts. These reconstructions can be derived from various 2D and 3D data sources, enabling detailed anatomical analyses. In this study, we evaluate the efficacy of surface scans in accurately reconstructing the volumes of the rotator cuff and teres major muscles across a diverse sample of hominoids.

Medical & Socioeconomic Risk Factors Associated with Lack of Neurodevelopmental Evaluation Following Neonatal Cardiac Surgery.

Neonates with congenital heart disease (CHD) who undergo cardiopulmonary bypass (CPB) are at high-risk for unfavorable neurodevelopmental (ND) outcomes and are recommended for ND evaluation (NDE); however, poor rates have been reported. We aimed to identify risk factors associated with lack of NDE. This single-center retrospective observational study included neonates < 30 days old who underwent CPB and survived to discharge between 2012 and 2018.

Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Bowel regimens before radical cystectomy: An analysis of a modern cohort.

Introduction: Bowel regimens (BR) before radical cystectomy (RC) are currently not recommended by Enhanced Recovery After Surgery (ERAS) protocols, as prior studies have shown BRs lead to worsened outcomes. However, many of those studies have used historic literature before recent surgical advancements such as minimally invasive RC and have not investigated the impact BRs have by type of urinary diversion. Our goal is to determine the outcomes of preoperative BR in patients undergoing RC based on diversion type using a modern patient cohort.

Genetic Insights Into Coronary Microvascular Disease.

Coronary microvascular disease (CMVD) affects the coronary pre-arterioles, arterioles, and capillaries and can lead to blood supply-demand mismatch and cardiac ischemia. CMVD can present clinically as ischemia or myocardial infarction with no obstructive coronary arteries (INOCA or MINOCA, respectively). Currently, therapeutic options for CMVD are limited, and there are no targeted therapies.

Convolutional Neural Networks for the segmentation of hippocampal structures in postmortem MRI scans.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming.

Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

Drug-drug interactions between palbociclib and proton pump inhibitors in early breast cancer: an exploratory analysis of PALLAS (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

Background: Concomitant intake of proton pump inhibitors (PPIs) may create drug-drug interactions, potentially impacting efficacy of anticancer agents. In the phase III PALLAS trial, the addition of palbociclib capsules to standard adjuvant endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer did not improve invasive disease-free survival (iDFS). We explored whether concomitant use of PPIs affected survival outcomes in patients treated with palbociclib in PALLAS.

4D light sheet imaging, computational reconstruction, and cell tracking in mouse embryos.

As light sheet fluorescence microscopy (LSFM) becomes widely available, reconstruction of time-lapse imaging will further our understanding of complex biological processes at cellular resolution. Here, we present a comprehensive workflow for in toto capture, processing, and analysis of multi-view LSFM experiments using the ex vivo mouse embryo as a model system of development. Our protocol describes imaging on a commercial LSFM instrument followed by computational analysis in discrete segments, using open-source software.

AI Methods for Antimicrobial Peptides: Progress and Challenges.

Antimicrobial peptides (AMPs) are promising candidates to combat multidrug-resistant pathogens. However, the high cost of extensive wet-lab screening has made AI methods for identifying and designing AMPs increasingly important, with machine learning (ML) techniques playing a crucial role. AI approaches have recently revolutionised this field by accelerating the discovery of new peptides with anti-infective activity, particularly in preclinical mouse models.

Haloperidol dopamine receptor occupancy and antagonism correspond to delirium agitation scores and EPS risk: A PBPK-PD modeling analysis.

Background: Delirium is a severe neuropsychiatric disorder associated with increased morbidity and mortality. Numerous precipitating factors and etiologies merge into the pathophysiology of this condition which can be marked by agitation and psychosis. Judicious use of antipsychotic medications such as intravenous haloperidol reduces these symptoms and distress in critically ill individuals.

The effect of epilepsy surgery on tonic-clonic seizures.

Objective: Epilepsy surgery outcomes tend to be judged by the percentage in seizure reduction without considering the effect on specific seizure types, particularly tonic-clonic seizures, which produce the greatest morbidity and mortality. We assess how often focal to bilateral tonic-clonic seizures (BTCS) stop and how often they appear de novo after epilepsy surgery.

Methods: Analysis of a prospectively maintained epilepsy surgery database between 1986 and 2022 that characterizes the burden of BTCS after resective epilepsy surgery.

BIS Guided Titration of Sevoflurane in Pediatric Patients Undergoing Elective Surgery: A Randomized Controlled Trial.

Background: In pediatric patients, the use of processed EEG monitoring may reduce the amount of anesthesia administered while maintaining adequate depth of anesthesia.

Aims: The primary aim of this study was to evaluate whether use of a BIS monitor to guide sevoflurane administration might reduce the average end tidal sevoflurane concentration used in children 4-18 years of age.

Methods: Participants in three age groups (4-8, 9-12, and 13-18 years) were randomized to either the BIS guided group or the control group.

An Open-Label Pilot Study to Examine the Safety, Tolerability and Efficacy of Deutetrabenazine in Isolated Dystonia.

Background: Dystonia may respond to VMAT2 inhibition.

Objectives: Providing pilot data on the safety, tolerability, and efficacy of deutetrabenazine in non dopa-responsive dystonia.

Methods: Deutetrabenazine was titrated by adults with isolated dystonia.

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.

Evidence for microbially-mediated tradeoffs between growth and defense throughout coral evolution.

Background: Evolutionary tradeoffs between life-history strategies are important in animal evolution. Because microbes can influence multiple aspects of host physiology, including growth rate and susceptibility to disease or stress, changes in animal-microbial symbioses have the potential to mediate life-history tradeoffs. Scleractinian corals provide a biodiverse, data-rich, and ecologically-relevant host system to explore this idea.

Audit and feedback is an effective implementation strategy to increase fidelity to a multi-component labor induction protocol designed to reduce obstetric inequities.

Background: Studies have demonstrated that standardizing labor induction (IOL), often with the use of protocols, may reduce racial inequities in obstetrics. IOL protocols are complex, multi-component interventions. To target identified implementation barriers, audit and feedback (A&F) was selected as an implementation strategy.

Evaluating generalizability of oncology trial results to real-world patients using machine learning-based trial emulations.

Randomized controlled trials (RCTs) evaluating anti-cancer agents often lack generalizability to real-world oncology patients. Although restrictive eligibility criteria contribute to this issue, the role of selection bias related to prognostic risk remains unclear. In this study, we developed TrialTranslator, a framework designed to systematically evaluate the generalizability of RCTs for oncology therapies.

MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis.

Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection against diet-induced obesity. In this study, we used temporal metabolomics on HeLa cells to show that MTCH2 deletion results in a high ATP demand, an oxidized cellular environment, and elevated utilization of lipids, amino acids, and carbohydrates, accompanied by a decrease in several metabolites.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.