Frailty and neurocognitive impairments in Chinese survivors of childhood cancer.

Purpose: This study aimed to evaluate the prevalence and predictors of frailty and the association between frailty and neurocognitive impairments among Chinese survivors of childhood cancer.

Methods: A total of 185 survivors of childhood cancer were recruited from a long-term follow-up clinic in Hong Kong (response rate: 94.4%; 48.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Characterizing Sensitivity to Vincristine, Irinotecan, and Telomerase-targeted Therapy in Diffuse Anaplastic Wilms Tumor Patient-derived Xenografts.

Background: Patients with diffuse anaplastic Wilms tumor (DAWT) experience relatively poor oncologic outcomes. Previous work has described mechanisms of telomerase upregulation in DAWT, posing a potential therapeutic target.

Methods: We assessed in vitro sensitivity to vincristine, irinotecan, and telomerase-targeting drug 6-thio-2'-deoxyguanosine (6 dG) in DAWT cell lines WiT49 and PDM115 and in spheroids derived from cell lines and four DAWT patient-derived xenografts (PDX).

Pulmonary hypertension in infancy: a reversible cause.

A term, healthy infant presented with respiratory distress and severe pulmonary hypertension (PH). With an unclear aetiology and the intent to decrease right ventricular afterload, pulmonary vasodilators were initiated. Follow-up imaging revealed a supravalvular mitral ring as the cause of the PH which resolved after surgical resection of the membrane.

The Moreton Lecture Series: The Renin-Angiotensin-Aldosterone System-Physiology, Pathophysiology, and Pharmacological Inhibition.

The renin-angiotensin-aldosterone system (RAAS) is a complex regulator comprising hormones, proteins, and enzymes. The discovery of the RAAS and its pharmacological manipulation has been essential in the management of cardiovascular diseases, including hypertension. Beyond the benefits of hypertension, RAAS inhibition has implications for heart failure, atherosclerotic disease, and kidney disease.

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Latent epigenetic programs in Müller glia contribute to stress and disease response in the retina.

Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development correlate with changes in gene expression. However, those studies lack cellular resolution. Here, we integrate single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) with bulk data to identify cell-type-specific changes in chromatin structure during human and murine development.

The gap between surgeon goal and achieved sagittal alignment in adult cervical spine deformity surgery.

Objective: Malalignment following cervical spine deformity (CSD) surgery can negatively impact outcomes and increase complications. Despite the growing ability to plan alignment, it remains unclear whether preoperative goals are achieved with surgery. The objective of this study was to assess how good surgeons are at achieving their preoperative goal alignment following CSD surgery.

Neurological and functional outcomes of 32 patients with hemorrhagic brainstem cavernous malformations: a practical guide for surgical planning.

Objective: Brainstem cavernous malformations (BSCMs) were once considered inoperable. Microsurgical resection now represents a valuable option for treating patients with hemorrhagic or symptomatic lesions. The aim of this study was to provide a practical guide for surgical planning by analyzing postoperative neurological and functional outcomes.

Trends in childhood cancer: Incidence and survival analysis over 45 years of SEER data.

Background: The SEER Registry contains U.S. cancer statistics.

Social Risks and Nonadherence to Recommended Cancer Screening Among US Adults.

Importance: Research indicates that social drivers of health are associated with cancer screening adherence, although the exact magnitude of these associations remains unclear.

Objective: To investigate the associations between individual-level social risks and nonadherence to guideline-recommended cancer screenings.

Design, Setting, And Participants: This cross-sectional study used 2022 Behavioral Risk Factor Surveillance System data from 39 US states and Washington, DC.

Basic Science and Pathogenesis.

Background: Tauopathies are a group of neurological disorders including Alzheimer's disease that involve progressive neurodegeneration, behavioral deficits, and aberrant tau accumulation. While the molecular mechanisms that regulate the progression of the tauopathy are not fully elucidated, there is evidence to suggest that accumulation of nuclear DNA damage, particularly nuclear DNA double-strand breaks (DNA DSBs), contribute to the progression of neurodegeneration. In our present work, we investigated the relationship between DNA DSB accumulation and neuroinflammation in the brains of AD patients and a mouse model of tauopathy.

Integrating Pharmacogenomics into the Broader Construct of Genomic Medicine: Efforts by the ClinGen Pharmacogenomics Working Group (PGxWG).

Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene-drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene-disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants.

Racial, Socioeconomic, and Geographic Disparities in Preamputation Vascular Care for Patients With Chronic Limb-Threatening Ischemia.

Background: Black patients, those with low socioeconomic status (SES), and those living in rural areas have elevated rates of major lower extremity amputation, which may be related to a lack of subspecialty chronic limb-threatening ischemia care. We evaluated the association between race, rurality, SES, and preamputation vascular care.

Methods: Among patients aged 66 to 86 years with fee-for-service Medicare who underwent major lower extremity amputation for chronic limb-threatening ischemia from July 2010 to December 2019, we compared the proportion who received vascular care in the 12 months before amputation by race (Black versus White), rurality, and SES (dual eligibility for Medicaid versus no dual eligibility) using multivariable logistic regression adjusting for clinical and demographic covariates.

E-portfolio in Learning and Assessment of Community Medicine for Medical Undergraduate Students.

Background: A portfolio is a specific collection of student work and achievements in various areas. E-portfolio is an electronic collection that serves the purpose of storage and showcase with the ease of access for both students and evaluators. The knowledge and skills regarding immunization in medical students are of utmost importance for the successful implementation and conduction of the Universal Immunization Program in the country.

Impact of particle size on and fat fraction estimation for accurate assessment of hepatic iron overload and steatosis using MRI.

Purpose: To investigate the impact of iron particle size on and fat fraction (FF) estimations for coexisting hepatic iron overload and steatosis condition using Monte Carlo simulations and phantoms.

Methods: Three iron particle sizes (0.38, 0.

A genome-wide association study of high-sensitivity C-reactive protein in a large Korean population highlights its genetic relationship with cholesterol metabolism.

High-sensitivity C-reactive protein (hsCRP) is a representative biomarker of systemic inflammation and is associated with numerous chronic diseases. To explore the biological pathways and functions underlying chronic inflammation, we conducted a genome-wide association study (GWAS) and several post-GWAS analyses of the hsCRP levels. This study was performed on data from 71,019 Koreans and is one of the largest East Asian studies.

PeerPub: A Device for Concurrent Operant Oral Self-Administration by Multiple Rats.

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub - a unique social operant chamber.

Physiologically Based Pharmacokinetic Modeling and Simulation to Support a Change in the FDA-Labeled Dosing Frequency of RHB-105 Low-Dose Rifabutin Triple Therapy for Helicobacter pylori Eradication.

Patient adherence is vital for Helicobacter pylori eradication. Simplifying therapy dosing schedules may promote patient adherence, enhance treatment success rates, and help mitigate the development of antibiotic resistance. We aimed to assess plasma and intragastric rifabutin, amoxicillin, and omeprazole concentrations comparing two dosing schedules of RHB-105 (every 8 h and a more flexible three-times daily schedule, at 8 a.

A framework for sequential monitoring of individual N-of-1 trials and combining results across a series of sequentially monitored N-of-1 trials.

Background: N-of-1 trials compare two or more treatment options for a single participant. These trials have been used to study options for chronic conditions such as arthritis and attention deficit hyperactivity disorder. In addition, they have been suggested as a means to study interventions in rare populations that may not be tractable to include in standard clinical trials, such as treatment options for HIV-positive patients in need of organ transplant.

MiR-675 Inhibits Primary Ovarian Tumor Growth and Metastasis by Suppressing EMT and TGFβ Signaling.

MicroRNAs (miRNAs) can function as either tumor suppressors or oncogenes. This study explores the role of miR-675 in ovarian cancer (OC) using OC cell lines and an orthotopic mouse model. We demonstrate that miR-675 expression inhibits primary tumor growth and metastasis by targeting TGFβ1, suppressing epithelial to mesenchymal transition (EMT), and attenuating the TGFβ signaling pathway.

An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup.

T-lineage acute lymphoblastic leukemia (ALL) is an aggressive cancer comprising diverse subtypes that are challenging to stratify using conventional immunophenotyping. To gain insights into subset-specific therapeutic vulnerabilities, we performed an integrative multiomics analysis of bone marrow samples from newly diagnosed T cell ALL, early T cell precursor ALL, and T/myeloid mixed phenotype acute leukemia. Leveraging cellular indexing of transcriptomes and epitopes in conjunction with T cell receptor sequencing, we identified a subset of patient samples characterized by activation of inflammatory and stem gene programs.

Inclined distance running at iso-efficient speeds: Effect on joint work.

Runners often reduce their pace during inclined running to maintain a constant metabolic workload, known as iso-efficiency speed (a speed-incline combination with the same metabolic intensity as level running). This study investigates changes in lower extremity (LE) joint work profiles when running on an incline at iso-efficiency speed. Eleven collegiate distance runners completed a treadmill running task under three conditions (0%, 4%, and 8% incline).