Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.

The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting.

Complete elbow ankylosis secondary to heterotopic ossification: operative management leads to fair to excellent long-term outcomes.

Background: Heterotopic ossification in the elbow, often caused by trauma or neurogenic factors, can lead to limited range of motion and physical impairment, while severe cases may result in debilitating loss of function. Complete bony ankylosis of the elbow, though rare, presents challenges in treatment due to complex anatomy and high recurrence rates, with limited literature on management and outcomes. This study retrospectively investigates cases of elbow ankylosis secondary to heterotopic ossification, assessing long-term functional outcomes following operative intervention and standardized rehabilitation.

Telehealth for Goals of Care Conversations in Advanced CKD: A Mixed-Methods Pilot Study of US Veterans and Their Clinicians.

Rationale & Objective: Engaging patients with advanced chronic kidney disease (CKD) in goals of care (GOC) conversations is essential to align life-sustaining treatments with patient preferences. This pilot study described the feasibility of engaging older Veterans with advanced CKD in GOC conversations via telehealth by (1) comparing patient characteristics, including life-sustaining treatment note completion rates and preferences by visit modality, and (2) exploring Veteran and clinician perspectives surrounding telehealth GOC conversations.

Study Design: Mixed-method convergent design including a prospective, quantitative observational cohort analysis (n = 40) and qualitative, semi-structured interviews with 4 clinicians and 11 Veterans.

Application of Artificial Intelligence to Analyze Data from Randomized Controlled Trials: An Example from DECAAF-II.

Background: Causal machine learning (ML) provides an efficient way of identifying heterogeneous treatment effect groups from hundreds of possible combinations, especially for randomized trial data.

Objective: The aim of this paper is to illustrate the potential of applying causal ML on the DECAAF II trial data. We proposed a causal ML model to predict the treatment response heterogeneity.

Supporting Transition Resilience Among Newcomer Groups (STRONG): Examining effectiveness and acceptability in urban public schools.

The Supporting Transition Resilience Of Newcomer Groups (STRONG; Hoover et al., 2019) program was developed to support mental health among newcomer refugee and immigrant students by (1) promoting positive adjustment during resettlement through a trauma-informed, strengths-based approach, contextualized to meet the needs of refugee and immigrant youth; and (2) improving access to services through school-based programming. The purpose of this study was to examine the acceptability and effectiveness of STRONG on the mental health and resilience of refugee and immigrant students using a group randomized waitlist control design.

Spontaneous Anthropocentric Language Use in University Students' Explanations of Biological Concepts Varies by Topic and Predicts Misconception Agreement.

Previous research has shown that students employ intuitive thinking when understanding scientific concepts. Three types of intuitive thinking-essentialist, teleological, and anthropic thinking-are used in biology learning and can lead to misconceptions. However, it is unknown how commonly these types of intuitive thinking, or cognitive construals, are used spontaneously in students' explanations across biological concepts and whether this usage is related to endorsement of construal-consistent misconceptions.

MircoRNAs predict and modulate responses to chemotherapy in leukemic patients.

Leukemia covers a broad category of cancer malignancies that specifically affect bone marrow and blood cells. While different kinds of leukemia have been identified, effective treatments are still lacking for most forms, and even those treatments considered effective can lead to relapses. MicroRNAs, or miRNAs, are short endogenous non-coding single-stranded RNAs that help control the epigenetics of gene expression.

Microtubule acetylation is not required for HIV-1 infection or TRIM69-mediated restriction of HIV-1 infection.

Unlabelled: Microtubule acetylation, a post-translational modification catalyzing the addition of acetyl groups to lysine residues on alpha tubulin, confers mechanical resilience to microtubules and influences intracellular cargo transport. Despite its known cellular functions, its role in viral infections remains poorly understood. The goal of this study was to determine the role of microtubule acetylation in both HIV-1 infection and TRIM69-mediated restriction.

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.

Sex-specific associations between self-reported sleep characteristics and 10-year cardiovascular disease risk in men and women of African descent living in a low socioeconomic status environment.

Background: Risk factors for cardiovascular disease (CVD) and sleep health are well-known to be sex- and race-specific. To build on the established relationship between sleep duration and CVD risk, this cross-sectional study aimed to describe sex-specific associations between CVD risk and other sleep characteristics (sleep quality, sleep timing and sleep onset latency) in low-income adults of African descent.

Methods: Self-reported sleep (Pittsburgh Sleep Quality Index [PSQI], Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI]), demographic and lifestyle data were collected in 412 adults (56 % women, 35.

Protocol to study neuronal membrane proteasome function in mouse peripheral sensory neurons.

Neuronal membrane proteasomes (NMPs) are expressed on a subset of somatosensory dorsal root ganglion (DRG) neurons and influence mechanical and pain sensitivity. Here, we present a protocol for studying NMP function in mouse peripheral sensory neurons. We describe steps for procuring and culturing primary DRG neurons.

Veteran and healthcare team perspectives on the TeleWound Practice Program within the Veterans Health Administration.

Objective: The Veterans Health Administration (VHA) recently piloted the implementation of the TeleWound Practice Program (TWP), which provides interprofessional wound care to Veterans remotely. We assessed the perceptions of Veterans and healthcare team members (HCTMs), and their experiences with the TWP.

Method: We surveyed Veterans from four VHA medical centres who had received at least one TWP visit between 1 May 2020 and 31 May 2021, and HCTMs associated with any TWP encounter between 1 September 2019 and 31 March 2021.

Quantifying the Deficits of Body Water and Monovalent Cations in Hyperglycemic Emergencies.

Hyperglycemic emergencies cause significant losses of body water, sodium, and potassium. This report presents a method for computing the actual losses of water and monovalent cations in these emergencies. We developed formulas for computing the losses of water and monovalent cations as a function of the presenting serum sodium and glucose levels, the sum of the concentrations of sodium plus potassium in the lost fluids, and body water at the time of hyperglycemia presentation as measured by bioimpedance or in the initial euglycemic state as estimated by anthropometric formulas.

Synthesis of Pyrazole-Based Inhibitors of the Bacterial Enzyme -Succinyl-l,l-2,6-Diaminopimelic Acid Desuccinylase (DapE) as Potential Antibiotics.

Based on the inhibitory potencies from earlier reported tetrazole thioether analogs, we now describe the synthesis and inhibition of pyrazole-based inhibitors of -succinyl-l,l-2,6-diaminopimelic acid desuccinylase (DapE) from (DapE). The most potent pyrazole analog bears an aminopyridine amide with an IC of 17.9 ± 8.

High Rate of Complications With Early Conversion Hip Arthroplasty Following Fracture Treatment.

Background: Conversion total hip arthroplasty (THA) is associated with higher rates of complications compared with primary THA, with prior surgical fixation of fractures in the ipsilateral hip shown to further increase these rates. There is a scarcity of literature on the effect of timing of conversion THA on complication rates. In this study, we evaluated early (≤6 months of index surgery) and late (>6 months of index surgery) conversion to THA following prior fixation of the proximal femur or acetabulum.

Airway associated inflammation in post-transplant cystic fibrosis patients as a predictor of chronic lung allograft dysfunction (CLAD).

Aims: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.

Modeling of randomized hepatitis C vaccine trials: Bridging the gap between controlled human infection models and real-word testing.

Global elimination of chronic hepatitis C (CHC) remains difficult without an effective vaccine. Since injection drug use is the leading cause of hepatitis C virus (HCV) transmission in Western Europe and North America, people who inject drugs (PWID) are an important population for testing HCV vaccine effectiveness in randomized-clinical trials (RCTs). However, RCTs in PWID are inherently challenging.

Ionizing radiation improves skin bacterial dysbiosis in cutaneous T-cell lymphoma.

Introduction: Cutaneous T-cell lymphoma (CTCL) is closely associated with the host microbiome. While recent evidence suggests that shifts in specific bacterial taxa are associated with response to UV-B, a form of non-ionizing radiation, the impact of ionizing radiation (IR) has not been investigated.

Methods: 16S rRNA and gene amplicon sequencing were performed on DNA extracted from swabs of lesional/non-lesional skin of 12 CTCL patients before/after TSEBT or local IR and from 25 matched healthy controls (HC).

CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection.

Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells.

Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment: A Systematic Review.

Purpose: A glioblastoma (GBM) is a primary brain tumor with significant unmet therapeutic needs. Immune checkpoint inhibitors (ICIs) have marked therapeutic benefits in many different cancers but have yet to show benefit for most GBM patients in phase III trials.

Methods: A systematic review querying ClinicalTrials.

Objectively measured moderate-to-vigorous physical activity does not attenuate prospective weight gain among African-origin adults spanning the epidemiological transition.

Traditional obesity-related public health messaging often includes physical activity (PA) recommendations. However, at the population level, the data are conflicting, especially when comparing different self-reported vs measured techniques across different settings and populations. We measured the association between moderate-to-vigorous intensity PA (MVPA) and prospective weight change across five African-origin populations and the extent to which MVPA attenuated weight change over time.

Anxiety symptoms are distinctly related to working memory deficits in adults with ADHD.

Working memory (WM), the cognitive system that briefly stores and updates information during complex tasks, is one of the most consistently identified neurocognitive deficits in individuals with ADHD. WM deficits are linked to significant challenges in daily life. Adults with ADHD often experience co-occurring anxiety and mood disorders, which are associated with more severe clinical presentations and greater WM deficits.

The economic burden of diabetes in spinal fusion surgery: a systematic review and meta-analysis.

Purpose: This study aimed at comparing the costs of spinal fusion surgery between patients with and without diabetes.

Methods: Following PRISMA guidelines, a systematic search of four databases was conducted. A meta-analysis was performed on comparative studies examining diabetic versus non-diabetic adults undergoing cervical/lumbar fusion in terms of cost.