NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

Juvenile Incarceration in an Adult Facility and Violent Victimization During Adulthood.

Introduction: A growing body of research indicates that being incarcerated in an adult jail or prison as a juvenile can elevate one's exposure to adverse childhood experiences, including violent and sexual victimization and neglect, and may lead to several long-term difficulties. This study investigates the relationship between being confined in an adult jail or prison as a minor and experiencing violent victimization as an adult.

Methods: Data from the National Longitudinal Survey of Youth-1997 cohort were used in the study.

Low-Dose Emicizumab Versus Low-/Intermediate-Dose Factor VIII Secondary Prophylaxis for Noninhibitor Haemophilia A Patients With Severe Bleeding Phenotype.

Background: Subcutaneous emicizumab, a factor VIII (FVIII)-mimicking bispecific monoclonal antibody, can effectively prevent bleeds in haemophilia A (HA) patients with/without inhibitors; however, its standard-dose regimens are financially burdensome. Low-dose emicizumab prophylaxis may alternatively be applied to noninhibitor HA patients in resource-limited settings.

Methods: During 2023, Thai patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype (historical annualized bleeding rate [ABR] >5 bleeds/year before regular FVIII prophylaxis) who received low-/intermediate-dose FVIII secondary prophylaxis ≥8 months were enrolled.

Guidelines for the standardization of pre-analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group.

There is a pressing need for accessible biomarkers with high diagnostic accuracy for Alzheimer's disease (AD) diagnosis to facilitate widespread screening, particularly in underserved groups. Saliva is an emerging specimen for measuring AD biomarkers, with distinct contexts of use that could complement blood and cerebrospinal fluid and detect various analytes. An interdisciplinary, international group of AD and related dementias (ADRD) researchers convened and performed a narrative review of published studies on salivary AD biomarkers.

Increasing Aridity May Threaten the Maintenance of a Plant Defence Polymorphism.

It is unclear how environmental change influences standing genetic variation in wild populations. Here, we characterised environmental conditions that protect versus erode polymorphic chemical defences in Boechera stricta (Brassicaceae), a short-lived perennial wildflower. By manipulating drought and herbivory in a 4-year field experiment, we measured the effects of driver variation on vital rates of genotypes varying in defence chemistry and then assessed interacting driver effects on total fitness (estimated as each genotype's lineage growth rate, λ) using demographic models.

Like Father, Like Daughter: A Family With a Constitutional Thrombocytopenia Variant Due to a Novel Heterozygous Missense Mutation in GP1BA.

Constitutional platelet disorders have become better understood since Bernard and Soulier first described a case in 1948. Their diagnosis can also be challenging due to overlap in clinical presentation and lab findings with platelet type von Willebrand. Bernard-Soulier syndrome is a disorder caused by GPIb receptor mutations that decrease its affinity for von Willebrand factor resulting in reduced platelet function and macrothrombocytopenia.

Contemporary Cytomegalovirus (CMV) Infections in Low-Risk CMV Seronegative Recipients of Solid Organ Transplants From CMV Seronegative Donors (D-/R-): Time to Reexamine Donor CMV Serostatus.

Background: Early posttransplant cytomegalovirus (CMV) infections in CMV seronegative solid organ transplant recipients (SOTR) with CMV seronegative donors (D-/R-) are often attributed transfusion-transmitted CMV. The prevalence of false-negative donor CMV serology in D-/R- SOTR with early CMV infections has not been explored.

Methods: We determined the frequency and characteristics of CMV DNAemia that occurred within 90 days of transplant among adult SOTR classified as D-/R- who underwent a first SOT at a single center between February 25, 2014 and February 25, 2024.

Improving STEMI Management Internationally: Initial Report of the American College of Cardiology-Global Heart Attack Treatment Initiative.

Background: The burden of ST-segment elevation myocardial infarction (STEMI) worldwide is increasing as the leading cause of death; there are scant data on system-based initiatives and performance metrics relative to its management in low- and middle-income countries where resources are frequently limited.

Objectives: The Global Heart Attack Treatment Initiative (GHATI) ultimate aim is improving evidence-based STEMI care, adherence to guidelines, and tracking of clinical and institutional indicators in low- and middle-income countries. To achieve that goal, the process of care and outcomes of STEMI patients in those nations will be studied.

Methods families use to raise funds for anorectal malformation treatment at a single public referral hospital in Southwestern Uganda.

Background: In Uganda, only two public hospitals provide pediatric surgery services. With less than 10 pediatric surgeons serving approximately 20 million children in Uganda, most patients with anorectal malformations (ARMs) must make several trips to the hospital before undergoing surgery. As a result, households borrow money, sell assets, or solicit contributions from friends and relatives to meet healthcare expenses.

Ocular and perineal squamous cell carcinomas in a Holstein Friesian cow.

Background: Squamous cell carcinoma (SCC) in domestic cattle is an economically significant malignant neoplasm and has been documented primarily in ocular and periocular tissues, vulva, and perineum. SCCs are often slow-growing and locally invasive, but metastasis is uncommon. Increased risk of developing SCC has been predominantly associated with high levels of sunlight exposure and hypopigmentation (skin and conjunctiva).

Comparison of Physical Frailty Assessments in Heart Failure With Preserved Ejection Fraction.

Background: Frailty is a known determinant of poor clinical outcomes in heart failure with preserved ejection fraction (HFpEF). However, prevalence estimates and effect sizes vary in part due to multiple tools available to measure frailty.

Objectives: This study aimed to compare the prevalence and prognostic value of six commonly used frailty assessments in adults with HFpEF.

The Recent Increase in Invasive Bacterial Infections: A Report From the National COVID Cohort Collaborative.

Background: When coronavirus disease 2019 (COVID-19) mitigation efforts waned, viral respiratory infections (VRIs) surged, potentially increasing the risk of postviral invasive bacterial infections (IBIs). We sought to evaluate the change in epidemiology and relationships between specific VRIs and IBIs [complicated pneumonia, complicated sinusitis and invasive group A streptococcus (iGAS)] over time using the National COVID Cohort Collaborative (N3C) dataset.

Methods: We performed a secondary analysis of all prospectively collected pediatric (<19 years old) and adult encounters at 58 N3C institutions, stratified by era: pre-pandemic (January 1, 2018, to February 28, 2020) versus pandemic (March 1, 2020, to June 1, 2023).

Intersections of Structural State-Level Racism and Neighborhood Deprivation on Nutrition and Obesity for Black Adolescents.

Purpose: Black adolescents in the United States face disproportionate poor nutrition and obesity risk due to racism. Intersections of larger structural contexts that pose differential access to Black adolescents' health resources, such as state-level racism and neighborhood-level disadvantage, may govern these risks. The purpose of this correlational study was to examine the associations between state-level racism, neighborhood disadvantage, and their intersection with nutrition and obesity for Black adolescents in a longitudinal study.

Rapid degradation of pharmaceutical pollutants using poly(1-naphthylamine) decorated BaFeO nanohybrids under microwave irradiation.

Unlabelled: Metformin, a widely used antidiabetic drug, has become a growing concern due to its persistence in the environment. It is one of the most frequently detected pharmaceuticals in wastewater and surface water because it is excreted largely unchanged by patients and is not fully removed in conventional wastewater treatment plants. The present study focuses on the synthesis and characterization of BaFeO/poly(1-naphthylamine) (PNA) nanohybrids and their application as microwave-active catalysts for the degradation of metformin.

A Long Way From Home: A Rare Case of Cutaneous Metastasis to the Scalp of Hepatocellular Carcinoma.

Cutaneous metastases of hepatocellular carcinoma (HCC) are uncommon but important to recognize for timely diagnosis and management. We present a case of a 70-year-old man with a history of HCC who developed a painless nodule on the scalp. Histopathological examination and immunohistochemistry confirmed the nodule as cutaneous metastasis of HCC.

Variability in Notification of Positive Newborn Screening Results for Sickle Cell Trait Across the United States.

Universal in the United States (US) since 2006, newborn screening (NBS) programs for sickle cell disease (SCD) allow for early identification of the disease and, as an unintentional byproduct, identification of sickle cell trait (SCT). Unlike other carrier states, SCT is highly prevalent and is found in nearly 3 million Americans, which results in important reproductive implications. Currently, all NBS programs in the US are responsible for their own policies regarding SCT notification, and little is known about how SCT notification practices are performed and how these practices vary across NBS programs.

Acute Decompensated Valvular Disease in the Intensive Care Unit.

Acute decompensated valvular disease encompasses a group of complex and challenging conditions, which are often the primary reason for admission to the cardiac intensive care unit and can also complicate the management of other primary cardiac disorders. Critically ill patients with valvular disease also present unique diagnostic and management challenges. Historically, medical and percutaneous interventional therapies have been limited and surgery was the only definitive treatment; however, surgical risk can at times be prohibitive.

A spatially constrained independent component analysis jointly informed by structural and functional network connectivity.

There are a growing number of neuroimaging studies motivating joint structural and functional brain connectivity. The brain connectivity of different modalities provides an insight into brain functional organization by leveraging complementary information, especially for brain disorders such as schizophrenia. In this paper, we propose a multimodal independent component analysis (ICA) model that utilizes information from both structural and functional brain connectivity guided by spatial maps to estimate intrinsic connectivity networks (ICNs).

CoCoNest: A continuous structural connectivity-based nested family of parcellations of the human cerebral cortex.

Despite the widespread exploration and availability of parcellations for the functional connectome, parcellations designed for the structural connectome are comparatively limited. Current research suggests that there may be no single "correct" parcellation and that the human brain is intrinsically a multiresolution entity. In this work, we propose the Continuous Structural Connectivitity-based, Nested (CoCoNest) family of parcellations-a fully data-driven, multiresolution family of parcellations derived from structural connectome data.

Decoding aging in the heart via single cell dual omics of non-cardiomyocytes.

To understand heart aging at the single-cell level, we employed single-cell dual omics (scRNA-seq and scATAC-seq) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardiomyocytes. Our analysis revealed aging response heterogeneity and its dynamics over time.

Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy.

Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5-30 mg every 2 weeks or 2-10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines.

Effect of randomized treatment withdrawal of budesonide oral suspension on clinically relevant efficacy outcomes in patients with eosinophilic esophagitis: a post hoc analysis.

Background: Relapse after corticosteroid withdrawal in eosinophilic esophagitis is not well understood.

Objectives: Budesonide oral suspension (BOS) 2.0 mg twice daily (b.

Examining the Relationship between Aptamer Complexity and Molecular Discrimination of a Low-Epitope Target.

Aptamers are oligonucleotide-based affinity reagents that are increasingly being used in various applications. Systematic evolution of ligands by exponential enrichment (SELEX) has been widely used to isolate aptamers for small-molecule targets, but it remains challenging to generate aptamers with high affinity and specificity for targets with few functional groups. To address this challenge, we have systematically evaluated strategies for optimizing the isolation of aptamers for (+)-methamphetamine, a target for which previously reported aptamers have weak or no binding affinity.

Proton-Transfer Dynamics Regulates CO Electroreduction Products via Hydrogen Coverage.

Electrochemical conversion of CO to hydrocarbons is a promising approach to carbon neutrality and energy storage. The formation of reaction intermediates involves crucial steps of proton transfer, making it essential to understand the role of protons in the electrochemical process to control the product selectivity and elucidate the underlying catalytic reaction mechanism of the CO electrochemical reduction (CORR). In this work, we proposed a strategy to regulate product selectivities by tuning local proton transport rates through a surface resin layer over cuprous oxides.

Leveraging anatomical constraints with uncertainty for pneumothorax segmentation.

Background: Pneumothorax is a medical emergency caused by the abnormal accumulation of air in the pleural space-the potential space between the lungs and chest wall. On 2D chest radiographs, pneumothorax occurs within the thoracic cavity and outside of the mediastinum, and we refer to this area as "lung + space." While deep learning (DL) has increasingly been utilized to segment pneumothorax lesions in chest radiographs, many existing DL models employ an end-to-end approach.