Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer.

Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group.

Asymptomatic female softball pitchers have altered hip morphology and cartilage composition.

Few studies have explored hip morphology and cartilage composition in female athletes or the impact of asymmetric repetitive loading, such as occurs during softball pitching. The current cross-sectional study assessed bilateral bony hip morphology on computed tomography imaging in collegiate-level softball pitchers ('Pitch1', n = 25) and cross-country runners ('Run', n = 13). Magnetic resonance imaging was used to assess cartilage relaxation times in a second cohort of pitchers ('Pitch2', n = 10) and non-athletic controls ('Con', n = 4).

Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.

Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility.

Congenital Pulmonary Vascular Anomalies and Disease.

Congenital pulmonary vascular disease is a daunting and diverse topic spanning both pulmonary arterial and venous anomalies. Given advancements in treatment, patients with congenital anomalies have longer life expectancies into adulthood and practicing radiologists are bound to come across these patients during their daily practice. Additionally, many anomalies are discovered incidentally on imaging, yet may still have implications for patient care.

Efficacy and Safety of Endovenous Microwave Ablation versus Endovenous Laser Ablation for Varicose Veins in Chronic Great Saphenous Vein Insufficiency: A Meta-Analysis.

Background: Although guidelines have established endovenous laser ablation (EVLA) as the first-line option for patients with varicose veins (VVs) in chronic Great saphenous vein (GSV) insufficiency, however, Chronic Vein Insufficiency (CVI) remains a significant healthcare burden. Endovenous microwave ablation (EMA) is a promising alternative. This review aims to analyze the Endovenous Microwave Ablation versus Endovenous Laser Ablation for Varicose Veins in Chronic Great Saphenous Vein Insufficiency METHODS: Randomized controlled trials (RCTs) and cohort studies across PubMed, Scopus, Science Direct, and the Cochrane Library up to November 11, 2024 was searched.

Challenges for complement functional assays in the clinical laboratory: From test validation to clinical interpretation.

Complement functional assays are essential first-tier tests for a gamut of disorders spanning from inborn errors of the immune system which lead to recurrent severe infections, to angioedema attacks, presentation of autoimmune disease, thrombotic microangiopathies and rare kidney disorders. These assays evaluate the activity of the three complement pathways and specific complement components, which helps in differential diagnosis and monitoring disease progression. The rising use of complement inhibitors for treating complement-mediated thrombotic microangiopathies has heightened the demand for personalized treatment plans and laboratory assessment of complement blockage.

Mechanisms of dual modulatory effects of spermine on the mitochondrial calcium uniporter complex.

The mitochondrial Ca uniporter is the Ca channel responsible for mitochondrial Ca uptake. It plays crucial physiological roles in regulating oxidative phosphorylation, intracellular Ca signaling, and cell death. The uniporter contains the pore-forming MCU subunit, the auxiliary EMRE protein, and the regulatory MICU1 subunit, which blocks the MCU pore under resting cellular Ca concentrations.

Longitudinal integrated proteomic and metabolomic skin changes in atopic dermatitis patients treated with dupilumab.

Background: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Promoting longus colli muscle activation: Force direction in sitting matters.

Background: There is limited evidence to inform exercise prescription for deep neck flexor activation out of supine.

Objective: To compare activation of longus colli (LC) and sternocleidomastoid (SCM) from supine to sitting, and to compare the effect of craniocervical flexion (CCF) exercises in sitting on activation.

Methods: Twenty-four individuals without neck pain (mean age 28.

Utilizing pharmacy technicians for medication adherence patient outreach in an ambulatory care setting.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Evaluation of the Pediatric Regional Anesthesia Time-Out Checklist: A Simulation Study.

Introduction: The Society for Pediatric Anesthesia Quality and Safety Committee developed the Pediatric Regional Anesthesia Time-Out Checklist, consisting of 14 safety items intended to be reviewed by an anesthesia team prior to a regional anesthetic. Primarily, we hypothesized that use of this Checklist would increase the number of safety items performed compared with no checklist, evaluating the usefulness of this tool. Secondarily, we hypothesized that, after checklist training, subjects would show better clinical judgment by electing to perform a regional anesthetic in scenarios in which no programmed error existed and electing to not perform a regional anesthetic in scenarios in which a programmed error did exist.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).

Machine Learning-Assisted Drug Repurposing Framework for Discovery of Aurora Kinase B Inhibitors.

Aurora kinase B (AurB) is a pivotal regulator of mitosis, making it a compelling target for cancer therapy. Despite significant advances in protein kinase inhibitor development, there are currently no AurB inhibitors readily available for therapeutic use. This study introduces a machine learning-assisted drug repurposing framework integrating quantitative structure-activity relationship (QSAR) modeling, molecular fingerprints-based classification, molecular docking, and molecular dynamics (MD) simulations.

Hemoglobin Variants as Targets for Stabilizing Drugs.

Hemoglobin is an oxygen-transport protein in red blood cells that interacts with multiple ligands, e.g., oxygen, carbon dioxide, carbon monoxide, and nitric oxide.

Novel Approaches to Monitor Pharmacokinetics and Metabolism of Gemcitabine-Ibandronate Conjugate in Mice and Dogs.

Background: The use of the bone-seeking properties of bisphosphonates (BPs) to target the delivery of therapeutic drugs is a promising approach for the treatment of bone metastases. Currently, the most advanced example of this approach is a gemcitabine-ibandronate conjugate (GEM-IB), where the bone-targeting BP ibandronate (IB) is covalently linked to the antineoplastic agent gemcitabine (GEM) via a spacer phosphate group. In the present study, we describe the development of a new analytical platform to evaluate the metabolism and pharmacokinetics of GEM-IB in mice and dogs and the results of proof-of-concept studies assessing the pharmacokinetics of GEM-IB in dogs and mice.

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer.

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.

VX-770, C-A1, and Increased Intracellular cAMP Have Distinct Acute Impacts upon CFTR Activity.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that is dysfunctional in individuals with cystic fibrosis (CF). The permeability of CFTR can be experimentally manipulated though different mechanisms, including activation via inducing the phosphorylation of residues in the regulatory domain as well as altering the gating/open probability of the channel. Phosphorylation/activation of the channel is achieved by exposure to compounds that increase intracellular cAMP, with forskolin and IBMX commonly used for this purpose.

Prognostic Significance of Lymph Node Ratio in Intrahepatic and Extrahepatic Cholangiocarcinomas.

. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC.

Ruthenium(II) Complex with 8-Hydroxyquinoline Exhibits Antitumor Activity in Breast Cancer Cell Lines.

Background/objectives: Breast cancer (BC) remains one of the most prevalent and deadly cancers worldwide, with limited access to advanced treatments in developing regions. There is a critical need for novel therapies with unique mechanisms of action, especially to overcome resistance to conventional platinum-based drugs. This study investigates the anticancer potential of the ruthenium complex Bis(quinolin-8-olato)bis(triphenylphosphine)ruthenium(II) (Ru(quin)) in ER-positive (T47D) and triple-negative (MDA-MB-231) BC cell lines.

Supporting Holistic Health and Gestational Diabetes Mellitus Risk Reduction Among Young Native Females Prior to Pregnancy: A Qualitative Exploration.

AI/AN communities are disproportionately impacted by food insecurity and gestational diabetes mellitus (GDM). Decreasing the risk of GDM can interrupt the intergenerational cycle of diabetes in AI/AN families, and can decrease diabetes-related health disparities. The goal of this study was to explore ways of supporting holistic health and reducing the risk of GDM among young American Indian and Alaska Native (AI/AN) females prior to pregnancy.

A Scoping Review of the Current Knowledge of the Social Determinants of Health and Infectious Diseases (Specifically COVID-19, Tuberculosis, and H1N1 Influenza) in Canadian Arctic Indigenous Communities.

Social determinants of health (SDHs) and the impact of colonization can make Canadian Arctic Indigenous communities susceptible to infectious diseases, including the coronavirus disease 2019 (COVID-19). This scoping review followed the PRISMA guidelines for scoping reviews and studied what is known about selected pandemics (COVID-19, tuberculosis, and H1N1 influenza) and SDHs (healthcare accessibility, food insecurity, mental health, cultural continuity, housing, community infrastructure, and socioeconomic status (SES)) for Canadian Arctic Indigenous communities. Original studies published in English and French up to October 2024 were located in databases (PubMed, Medline, and CINAHL), , and through reference tracking.

Enlightening Nursing Care: A Protocol for a Multicenter Observational Study Measuring Nursing Work in Hospital Settings.

: Rising costs and demands for improved quality of care present complex challenges for existing healthcare systems. The strain on healthcare resources is exacerbated by the increasing complexity of patient conditions. The Diagnosis-Related Group (DRG) system classifies inpatients according to clinical and treatment criteria, controls healthcare expenditures, and ensures the sustainability of procedures.

Interplay of aurora kinase a functional residues and Epstein-barr Nuclear Antigen 1 in Epstein-barr virus associated Gastric cancer using AGS cells.

Epstein-Barr virus (EBV), an oncogenic gamma-herpesvirus, belongs to group 1 carcinogen and is implicated in various cancers, including gastric cancer. Aurora Kinase A is a major mitotic protein kinase that regulates mitotic progression; overexpression and hyperactivation of AURKA commonly promote genomic instability in many tumours. However, the relationship of functional residues of AURKA and EBV in gastric cancer progression remains unknown.

A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.

Background: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

Design: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

Methods: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment.