Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes.

Background: Our previous study demonstrated that alcohol induced the expression of the α4 subunit of nicotinic acetylcholine receptors (nAChRs) in the livers of wild type mice (WT), and that whole-body α4 nAChR knockout mice (α4KO) showed protection against alcohol-induced steatosis, inflammation, and injury. Based on these findings, we hypothesized that hepatocyte-specific α4 nAChRs may directly contribute to the detrimental effects of alcohol on the liver.

Methods: Hepatocyte-specific α4 knockout mice (α4HepKO) were generated, and the absence of α4 nAChR was confirmed through PCR of genomic DNA.

Biomonitoring PhIP, a Potential Prostatic Carcinogen, in the Hair of Healthy Men of African and European Ancestry.

Heterocyclic aromatic amines (HAAs), formed during the cooking of meat, are potential human carcinogens, underscoring the need for long-lived biomarkers to assess exposure and cancer risk. Frequent consumption of well-done meats containing 2-amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP), a prevalent HAA that is a prostatic carcinogen in rodents and DNA-damaging agent in human prostate cells, has been linked to aggressive prostate cancer (PC) pathology. African American (AA) men face nearly twice the risk for developing and dying from PC compared to White men.

Fast Hadamard-Encoded 7T Spectroscopic Imaging of Human Brain.

: The increased SNR available at 7T combined with fast readout trajectories enables accelerated spectroscopic imaging acquisitions for clinical applications. In this report, we evaluate the performance of a Hadamard slice encoding strategy with a 2D rosette trajectory for multi-slice fast spectroscopic imaging at 7T. : Moderate-TE (~40 ms) spin echo and J-refocused polarization transfer sequences were acquired with simultaneous Hadamard multi-slice excitations and rosette in-plane encoding.

Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

Differential Impact of Risk Factors for Cognitive Decline in Heterosexual and Sexual Minority Older Adults in England.

Background/objectives: Sexual minority older adults (SMOAs) report greater subjective cognitive decline (SCD) than heterosexual older adults (HOAs). This study aimed to compare the impact of multiple psycho-social risk factors on objective and subjective cognitive decline in HOAs and SMOAs.

Methods: Two samples of self-identified HOAs and SMOAs were selected from the English Longitudinal Study of Ageing.

Initial Psychometric Testing of the Harm Reduction Self-Efficacy Scale (HRSES).

Abstinence self-efficacy, belief in one's ability to abstain, has been identified as a predictor of substance use behavior change. Yet, many people who use substances do not want to abstain. Self-efficacy for achieving a range of goals (i.

Efficacy of cartilage-targeted IGF-1 in a mouse model of growth hormone insensitivity.

Recombinant human IGF-1 is used to treat severe primary IGF-1 deficiency, but this treatment requires twice-daily injection, often does not fully correct the growth deficit, and has important off-target effects. We therefore sought to target IGF-1 to growth plate cartilage by generating fusion proteins combining IGF-1 with single-chain human antibody fragments that target matrilin-3, a cartilage matrix protein. We previously showed that this cartilage-targeting IGF-1 fusion protein (CV1574-1) promoted growth plate function in a GH-deficient (lit) mouse model.

A Tutorial on Analyzing Ecological Momentary Assessment Data in Psychological Research With Bayesian (Generalized) Mixed-Effects Models.

In this tutorial, we introduce the reader to analyzing ecological momentary assessment (EMA) data as applied in psychological sciences with the use of Bayesian (generalized) linear mixed-effects models. We discuss practical advantages of the Bayesian approach over frequentist methods and conceptual differences. We demonstrate how Bayesian statistics can help EMA researchers to (a) incorporate prior knowledge and beliefs in analyses, (b) fit models with a large variety of outcome distributions that reflect likely data-generating processes, (c) quantify the uncertainty of effect-size estimates, and (d) quantify the evidence for or against an informative hypothesis.

Acute beneficial effects of a functional energy shot on cognitive performance and mood states during cognitively demanding task performance: a randomized, double-blind, placebo-controlled, crossover trial.

Introduction: Functional beverages are increasingly popular but it is important to validate their purported effects through research. The aim of the current study was to investigate the effects of a new functional energy shot on cognitive performance and mood states in healthy adults, with a focus on measuring mental energy enhancement and attenuation of negative effects associated with extended performance of mentally demanding tasks.

Methods: This study was a randomized, double-blind, placebo-controlled, crossover trial.

Improving the solubility of pseudo-hydrophobic chemicals through co-crystal formulation.

Natural products are ligands and in vitro inhibitors of Alzheimer's disease (AD) tau. Dihydromyricetin (DHM) bears chemical similarity to known natural product tau inhibitors. Despite having signature polyphenolic character, DHM is ostensibly hydrophobic owing to intermolecular hydrogen bonds that shield hydrophilic phenols.

Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.

Adjuvants play a central role in enhancing the immunogenicity of otherwise poorly immunogenic vaccine antigens. Combining adjuvants has the potential to enhance vaccine immunogenicity compared with single adjuvants, although the cellular and molecular mechanisms of combination adjuvants are not well understood. Using the influenza virus hemagglutinin H5 antigen, we define the immunological landscape of combining CpG and MPLA (TLR-9 and TLR-4 agonists, respectively) with a squalene nanoemulsion (AddaVax) using immunologic and transcriptomic profiling.

Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis.

Background: Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation and the infiltration of immune cells into the brain contribute to this process. However, no study has investigated the role of peripheral blood immune cells in ALS pathophysiology using single-cell RNA sequencing (scRNAseq).

Methods: We aimed to characterize immune cells from blood and identify ALS-related immune alterations at single-cell resolution.

Chemical Logic of Peptide Branching by Iterative Nonlinear Nonribosomal Peptide Synthetases.

Branch-point syntheses in nonribosomal peptide assembly are rare but useful strategies to generate tripodal peptides with advantageous hexadentate iron-chelating capabilities, as seen in siderophores. However, the chemical logic underlying the peptide branching by nonribosomal peptide synthetase (NRPS) often remains complex and elusive. Here, we review the common strategies for the biosynthesis of branched nonribosomal peptides (NRPs) and present our biochemical investigation on the NRPS-catalyzed assembly of fimsbactin A, a branched mixed-ligand siderophore produced by the human pathogenic strain .

Exposure to Secondhand Cannabis Smoke Among Children.

Importance: The degree that in-home cannabis smoking can be detected in the urine of resident children is unclear.

Objective: Test association of in-home cannabis smoking with urinary cannabinoids in children living at home.

Design, Setting, And Participants: This cross-sectional study used baseline data from Project Fresh Air, a 2012-2016 randomized clinical trial to reduce fine particulate matter levels.

Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.

Lessons Learned: Intravenous paricalcitol did not improve the efficacy of pembrolizumab, likely related to the short half-life.

Background: Immunotherapy has limited benefit in the treatment of advanced pancreatic cancer with the tumor microenvironment playing a key role in immune resistance. In preclinical studies, vitamin D receptor (VDR) agonists have been shown to sensitize pancreatic tumors to PD-1 blockade.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Two Clinically Implementable Digital PCR Assessments of DNA Methylation for Diagnosing Heavy Alcohol Consumption.

Background: Heavy alcohol consumption (HAC) has a profound adverse effect on human health. Unfortunately, there is a relative lack of tools that are easily implementable in clinical settings and that can be used to supplement self-reporting in the diagnosis and management of HAC. In part, this paucity is due to limitations of currently available biological measures and a mismatch between available biological measures and the needs of clinicians managing HAC.

Chemical structure-biological activity of 1,4-naphthoquinone analogs as potential Aedes aegypti larvicides.

Background: 1,4-Naphthoquinone compounds have shown pesticidal activity against Aedes aegypti larvae, a key vector of diseases such as dengue and Zika. However, limited knowledge of their structure-activity relationships has hindered their optimization for pesticide development. This study investigates the structure-activity relationships of 1,4-naphthoquinone, particularly 2-hydroxy-1,4-naphthoquinone and its derivatives.

Gender differences in early posttraumatic stress disorder symptoms: a network analysis.

Despite known gender/sex differences in the prevalence of posttraumatic stress disorder (PTSD), potential differences in the associations among PTSD symptoms between men and women in the early post-trauma period are not well-characterized. This study utilized network analysis to assess potential differences in the associations among PTSD symptom clusters between men and women during the early post-trauma period. We included  = 475 participants (57.

Safety of tenecteplase vs. alteplase in telestroke: a large multistate experience (STAT).

Introduction: Prompt treatment with IV thrombolytics (IVT) in acute ischemic stroke (AIS) patients is critical for improved recovery and survival. Recently, hospital systems have switched to the IVT tenecteplase (TNK) instead of the FDA-approved alteplase (tPA) for treatment. Multiple studies and meta-analyses evaluating the efficacy and safety of TNK demonstrate similar or superior outcomes when compared to tPA.

Examining the Proximal Relationship between Religious Coping and Depression among Trauma-Exposed Adults.

Depression is a common consequence of sexual victimization. Although religious coping has been previously studied within the context of sexual victimization, there is a dearth of research examining the potential reciprocal relationships between religious coping and depression among adults with a history of sexual victimization at the daily level. The current study addresses this important gap by leveraging an intensive longitudinal design and data analysis to explore bidirectional daily relations between religious coping and depression symptoms in a community sample of adults with a history of sexual victimization.

Antimicrobial stewardship: a definition with a One Health perspective.

Antimicrobial stewardship (AMS) is a commonly advocated approach to address antimicrobial resistance. However, AMS is often defined in different ways depending on where it is applied, such that a range of definitions is now in use. These definitions may be functional and well-structured for a given context but are often ill-adapted for collaborative work, creating difficulties for intersectoral communication on AMS and complicating the design, implementation, and evaluation of AMS interventions from a One Health perspective.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.