Transcriptomic Profiling Reveals 17β-Estradiol Treatment Represses Ubiquitin-Proteasomal Mediators in Skeletal Muscle of Ovariectomized Mice.

Background: With a decline of 17β-estradiol (E2) at menopause, E2 has been implicated in the accompanied loss of skeletal muscle mass and strength. We aimed at characterizing transcriptomic responses of skeletal muscle to E2 in female mice, testing the hypothesis that genes and pathways related to contraction and maintenance of mass are differentially expressed in ovariectomized mice with and without E2 treatment.

Methods: Soleus and tibialis anterior (TA) muscles from C57BL/6 ovariectomized mice treated with placebo (OVX) or E2 (OVX + E2) for 60 days, or from skeletal muscle-specific ERα knockout (skmERαKO) mice and wild-type littermates (skmERαWT), were used for genome-wide expression profiling, quantitative real-time PCR and immunoblotting.

Likes and Hashtags: Exploring the Potential Relationship Between Social Media use and the Emotional Wellbeing of Oncology Professionals.

Purpose: To explore the potential relationship between social media (SoMe) and burnout or overall wellbeing within the field of oncology.

Design: A cross-sectional study of adult and pediatric oncology professionals conducted using an anonymous electronic survey. The survey was disseminated through the Children's Oncology Group (COG) and the SWOG Cancer Research Network (SWOG) member listservs.

Radiotherapeutics, clonal hematopoiesis, and risk of hematologic malignancies: The good, the bad, the ugly.

While radiotherapeutics have demonstrated significant clinical benefit across multiple cancer types including thyroid cancer, neuroendocrine tumors, and prostate cancer, hematological toxicities can be frequent and challenging. It remains unknown to what extent the hematologic toxicity is driven by clonal processes that preexist and are selected for by treatment induced selection pressures. In this review, we discuss the background leading to the adoption of radiotherapeutics in the treatment of solid tumor malignancies, the risk of hematologic toxicities and myeloid neoplasms and the evidence pointing to potential precursor lesions that may predispose patients to hematologic toxicities.

Ethical Challenges in Pediatric Medical Complexity: A Survey of Parents.

Objective: To understand parents' experiences of ethical challenges in the care of children with chronic and serious medical conditions and what resources they access for support.

Study Design: We recruited English-speaking parents of children with complex and serious medical conditions via family advocacy groups to complete an electronic survey from October 2022 through February 2023. We queried respondents' experiences with specific ethical challenges in the care of their child, whether their concerns persisted, and what resources they accessed.

Spin-Orbit Coupling and Admixture Coefficients in SA-CASSCF and MS-CASPT2, and Triplet Excitation Yield Simulated via Trajectory Surface Hopping and Calibrated SA-CASSCF in 1,2-Dioxetane Derivatives.

The energy gaps, spin-orbit coupling (SOC), and admixture coefficients over a series of the configurations are evaluated by the SA-CASSCF/6-31G, SA-CASSCF/6-31G*, SA-CASSCF/ANO-RCC-VDZP, and MS-CASPT2/ANO-RCC-VDZP to reveal the extent of the inaccuracy of the SA-CASSCF. By comparing the mean absolute errors for the energy gaps and the admixture coefficient magnitudes (ACMs) measured between the SA-CASSCF/6-31G, SA-CASSCF/6-31G*, or SA-CASSCF/ANO-RCC-VDZP and the MS-CASPT2/ANO-RCC-VDZP, the SA-CASSCF/6-31G is selected as the electronic structure method in the nonadiabatic molecular dynamics simulation. The major components of the ACMs of the SA-CASSCF/6-31G and MS-CASPT2/ANO-RCC-VDZP are identified and compared; we find that the ACMs are underestimated by the SA-CASSCF/6-31G, which is verified by the reasonable triplet quantum yield simulated by the trajectory surface hopping and the calibrated SA-CASSCF/6-31G.

Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

Improving MRI turbulence quantification by addressing the measurement errors caused by the derivatives of the turbulent velocity field - Sequence development and in-vitro validation.

Purpose: To improve the current method for MRI turbulence quantification which is the intravoxel phase dispersion (IVPD) method. Turbulence is commonly characterized by the Reynolds stress tensor (RST) which describes the velocity covariance matrix. A major source for systematic errors in MRI is the sequence's sensitivity to the variance of the derivatives of velocity, such as the acceleration variance, which can lead to a substantial measurement bias.

Mapping the aging brain: Insights into microstructural changes from free water-corrected fractional anisotropy.

Aging has a significant impact on brain structure, demonstrated by numerous MRI studies using diffusion tensor imaging (DTI). While these studies reveal changes in fractional anisotropy (FA) across different brain regions, they tend to focus on white matter tracts and cognitive regions, often overlooking gray matter and motor areas. Additionally, traditional DTI metrics can be affected by partial volume effects.

The Landscape of Hepatitis C Virus Infection in Pediatric Kidney Transplantation.

Hepatitis C virus (HCV) infection is increasing in prevalence due to the growing opioid epidemic; however, its impact on pediatric kidney transplantation is unknown. This study compared kidney transplant outcomes between HCV-positive and propensity-score-weighted HCV-negative pediatric recipients. It also examined HCV-positive kidney utilization for pediatric transplantation in the United States.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Are AI chatbots concordant with evidence-based cancer screening recommendations?

Objective: This study aimed to assess whether information from AI chatbots on benefits and harms of breast and prostate cancer screening were concordant with evidence-based cancer screening recommendations.

Methods: Seven unique prompts (four breast cancer; three prostate cancer) were presented to ChatGPT in March 2024. A total of 60 criteria (30 breast; 30 prostate) were used to assess the concordance of information.

Pharmacist-Directed Transition of Care Services Decrease Readmissions at a Safety-Net Hospital.

Background: Limited data exist describing the influence of pharmacist-led transition of care (TOC) services in safety-net hospital settings.

Objective: This analysis assessed the impact of pharmacist-led TOC services on hospital readmissions in a high-risk managed Medicaid population impacted by housing instability, substance use disorder (SUD), and mental health issues.

Methods: A retrospective evaluation of patients who received safety-net hospital-based TOC pharmacy services between January 1, 2022, and December 31, 2022, was conducted.

Alginate Hydrogel Beads with a Leakproof Gold Shell for Ultrasound-Triggered Release.

Focused ultrasound has advantages as an external stimulus for drug delivery as it is non-invasive, has high precision and can penetrate deep into tissues. Here, we report a gold-plated alginate (ALG) hydrogel system that retains highly water-soluble small-molecule fluorescein for sharp off/on release after ultrasound exposure. The ALG is crosslinked into beads with calcium chloride and layered with a polycation to adjust the surface charge for the adsorption of catalytic platinum nanoparticles (Pt NPs).

p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity.

p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents.

Machine Learning Models for the Early Real-Time Prediction of Deterioration in Intensive Care Units-A Novel Approach to the Early Identification of High-Risk Patients.

Predictive machine learning models have made use of a variety of scoring systems to identify clinical deterioration in ICU patients. However, most of these scores include variables that are dependent on medical staff examining the patient. We present the development of a real-time prediction model using clinical variables that are digital and automatically generated for the early detection of patients at risk of deterioration.

Purine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus.

Every year, dengue virus affects hundreds of millions of individuals worldwide. To date, there is no specific medication to treat dengue virus infections. Nucleobases, the base of a nucleoside without ribose, are understudied as potential treatments for viral infections.

Cell Type Specific Suppression of Hyper-Recombination by Human RAD18 Is Linked to Proliferating Cell Nuclear Antigen K164 Ubiquitination.

RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.

Clinical Benefit of Pegylated Liposomal Doxorubicin and High Prevalence of Pre-Existing Psychiatric Conditions in Patients with Desmoid-Type Fibromatosis.

Desmoid-type fibromatosis (DTF) is a locally invasive tumor composed of myofibroblast-like cells and collagen; it does not metastasize but can cause significant local morbidity. Most sporadic cases are associated with mutations in the CTNNB1 gene, which encodes beta-catenin. Various treatments have been used with differing efficacy and toxicity profiles.

Chronic Neutrophilic Leukemia: Advances in Diagnosis, Genetic Insights, and Management Strategies.

CNL is a rare subtype of MPNs characterized by persistent neutrophilia, bone marrow hypercellularity, and specific genetic mutations, particularly in the gene. Advances in molecular diagnostics have greatly enhanced our understanding of CNL, distinguishing it from other myeloproliferative disorders and refining diagnostic criteria. This review provides an updated overview of CNL, focusing on breakthroughs in genetic profiling, including novel mutations with potential prognostic value and implications for targeted therapy.

Vascularization, Innervation, and Inflammation: Pathways Connecting the Heart-Brain Axis and Implications in a Clinical Setting.

With an aging population, the incidence of both ischemic heart disease and strokes have become the most prevalent diseases globally. These diseases have similar risk factors, such as hypertension, diabetes, and smoking. However, there is also evidence of a relationship between the heart and the brain, referred to as the heart-brain axis.

Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.

Direct compression tablet formulation of trimetazidine through systematic screening of oxalate salts.

Salt formation has been extensively used to modulate and improve the properties of active pharmaceutical ingredients (API), such as solubility, stability and mechanical properties. Tablets of the anti-angina drug, trimetazidine (TMZ) are currently manufactured using the wet granulation process, rather than the more cost-effective direct compression method. In an effort to address the two main challenges associated with the commercial dihydrochloride salt (TMZ-2HCl), i.