Leisure-Time Physical Activity, Sedentary Behavior, and Biological Aging: Evidence From Genetic Correlation and Mendelian Randomization Analyses.

Physical inactivity and sedentary behavior are associated with higher risks of age-related morbidity and mortality. However, whether they causally contribute to accelerating biological aging has not been fully elucidated. Utilizing the largest available genome-wide association study (GWAS) summary data, we implemented a comprehensive analytical framework to investigate the associations between genetically predicted moderate-to-vigorous leisure-time physical activity (MVPA), leisure screen time (LST), and four epigenetic age acceleration (EAA) measures: HannumAgeAccel, intrinsic HorvathAgeAccel, PhenoAgeAccel, and GrimAgeAccel.

Radiation doses to the breast and predicted breast cancer risk among patients treated for Hodgkin lymphoma with modern radiotherapy.

Purpose: To contrast breast radiation exposure from chest radiotherapy in 2006-2021 with 1965-1997, and to compare breast cancer (BC) risk 25 years after treatment predicted by two models.

Methods: Radiation dose distributions to the breast from 101 chest radiotherapies given 2006-2021 for Hodgkin lymphoma (HL) or other lymphoma in one German and two Dutch hospitals were compared with doses received by 505 Dutch HL patients treated 1965-1997 and sampled into a nested case-control study, weighted to represent a HL patient cohort. Dose-volume histograms, mean dose and doses to 10 breast segments were evaluated.

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

A Consistent Lack of Consistency: Definitions, Evidentiary Expectations and Potential Use of Meaningful Change Data in Clinical Outcome Assessments Across Stakeholders. Results from a DIA Working Group Literature Review and Survey.

Background: Clinical outcome assessments (COAs) measure how patients feel or function and can be used to understand which patients experience benefits of treatment and which do not. Interpretation of COA data is influenced by how meaningful change is defined. We aimed to compare how different stakeholders define, assess, and use meaningful change for decisions that impact patients.

Application of a quantitative uncertainty assessment to develop ranges of plausible toxicity values when using observational data in risk assessment: a case study examining associations between PFOA and PFOS exposures and vaccine response.

Traditional approaches for quantitatively characterizing uncertainty in risk assessment require adaptation to accommodate increased reliance on observational (vs. experimental) studies in developing toxicity values. Herein, a case study with PFOA and PFOS and vaccine response explores approaches for qualitative and-where possible-quantitative assessments of uncertainty at each step in the toxicity value development process when using observational data, including review and appraisal of individual studies, candidate study selection, dose-response modeling, and application of uncertainty factors.

Applying Results of Extended Genotyping to Management of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines.

Objective: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs.

Methods: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines.

A High-Throughput Screening Pipeline to Identify Methyltransferase and Exonuclease Inhibitors of SARS-CoV-2 NSP14.

SARS-CoV-2 infections led to a worldwide pandemic in 2020. As of 2024, therapeutics against SARS-CoV-2 have continued to be desirable. NSP14 is a dual-function methyltransferase (MTase) and exonuclease (ExoN) with key roles in SARS-CoV-2 genome propagation and host immune system evasion.

Menthol Cigarettes and Maternal Health: 2004-2022.

The United States is proposing to ban menthol cigarettes. Our objective is to examine the extent of menthol smoking among pregnant women and its association with their health. Nationally representative study of 14,226 pregnant women aged 18-44 years using the 2004-2022 National Survey on Drug Use and Health.

A new pipeline SPICE identifies novel JUN-IKZF1 composite elements.

Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements.

Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.

Purpose: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma that develops sporadically or in Neurofibromatosis type 1 patients. Its development is marked by the inactivation of specific tumor suppressor genes (TSGs): NF1, CDKN2A and SUZ12EED (Polycomb Repressor Complex 2). Each TSG loss can be targeted by particular drug inhibitors and we aimed to systematically combine these inhibitors, guided by TSG inactivation status, to test their precision medicine potential for MPNSTs.

Fresh vs. frozen: pregnancy outcomes and treatment efficacy between fresh embryo transfer vs. untested freeze-all cycles.

Objective: To compare pregnancy outcomes after single blastocyst embryo transfer among patients whose first autologous embryo transfer was either a fresh embryo transfer or a frozen embryo transfer (FET) after a freeze-all, in the absence of preimplantation genetic testing for aneuploidy (PGT-A).

Design: A multicenter retrospective cohort analysis.

Setting: National multicenter fertility practice.

A comparative study of Merkel cell carcinoma and melanoma incidence and survival in the United States, 2000-2021.

Merkel cell carcinoma (MCC) and melanoma are important contributors to skin cancer mortality in the United States. We evaluated their epidemiology using US cancer registry data. During 2000-2021, 19,444 MCCs and 646,619 melanomas of the skin were diagnosed.

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum.

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites.

Remote Lifestyle Intervention to Reduce Postpartum Weight Retention: Protocol for a Community-Engaged Hybrid Type I Effectiveness-Implementation Randomized Controlled Trial.

Background: Maternal obesity is associated with significant racial disparities. People who identify as non-Hispanic Black and Latinx are at the highest risk related adverse short- and long-term health outcomes (eg, hypertension in pregnancy and postpartum weight retention). Remote lifestyle interventions delivered during and after pregnancy hold promise for supporting healthy weight outcomes; however, few are tested in groups of people who self-identify as non-Hispanic Black and Latinx or address the neighborhood-level and psychosocial factors driving maternal health disparities.

Syphilis reactivity among blood donors in Brazil: associated factors and implications for public health monitoring.

Background: Increasing syphilis infection rates are a concerning issue worldwide. Blood donation screening is an opportunity to monitor the burden of asymptomatic infections, providing information on contemporary factors associated with infection and public health insights into transmission.

Methods: Blood donations collected at five Brazilian blood centers between January 2020 and February 2022 were screened with treponemal or non-treponemal assays according to local protocols, followed by alternate Enzyme-Linked Immunosorbent Assay (ELISA); samples with reactive or indeterminate results in the alternate ELISA were further tested with the rapid plasma reagin (RPR), and categorized as RPR-positive or RPR-negative.

Reversal gene expression assessment for drug repurposing, a case study of glioblastoma.

Background: Glioblastoma (GBM) is a rare brain cancer with an exceptionally high mortality rate, which illustrates the pressing demand for more effective therapeutic options. Despite considerable research efforts on GBM, its underlying biological mechanisms remain unclear. Furthermore, none of the United States Food and Drug Administration (FDA) approved drugs used for GBM deliver satisfactory survival improvement.

Lung cancer mortality among aircraft manufacturing workers with long-term, low-level, hexavalent chromium exposure.

Hexavalent chromium (CrVI) is known to cause lung cancer among workers exposed to high concentrations in certain historical industries. It is also a toxic air contaminant considered to pose a potentially significant cancer risk at comparatively low concentrations in urban air. However, very limited data currently exist to quantify risk at low-concentration occupational or environmental exposures.

Evaluation of the safety profile and intrapulmonary pharmacokinetics of intravenous fosfomycin in healthy adults.

Unlabelled: This Phase 1 trial described the intrapulmonary pharmacokinetics and safety profile of IV fosfomycin in healthy participants Fosfomycin, a broad-spectrum antibiotic mainly used to treat urinary tract infections, is being considered for treatment of more complex conditions, including lung infections, due to the emergence of multidrug-resistant (MDR) organisms. Despite its potential, the pharmacokinetics and safety profile of intravenous (IV) fosfomycin, particularly its penetration into the lower respiratory tract, are unknown. To address this gap, we conducted a Phase 1, open-label trial to assess the safety and pulmonary pharmacokinetics of IV fosfomycin in healthy participants.

Association Between County-Level Social Vulnerability and Vaccine-Related Attitudes and Hesitancy Toward COVID-19 Vaccination in the United States.

Background/objectives: Understanding attitudes and behaviors related to vaccination is critical for enhancing COVID-19 vaccination acceptance and reducing disparities in vaccination coverage. This study examines disparities in vaccine-related attitudes and COVID-19 vaccine hesitancy in the United States in relation to community-level social vulnerability.

Methods: This study analyzed cross-sectional national surveys conducted repeatedly between July 2020 and August 2021 ( = 6716).

Microfluidic-Chip-Based Formulation and In Vivo Evaluations of Squalene Oil Emulsion Adjuvants for Subunit Vaccines.

Background: Adjuvants play a crucial role in improving the immunogenicity of various antigens in vaccines. Squalene-in-water emulsions are clinically established vaccine adjuvants that improve immune responses, particularly during a pandemic. Current manufacturing processes for these emulsion adjuvants include microfluidizers and homogenizers and these processes have been used to produce emulsion adjuvants to meet global demands during a pandemic.

The Effect of Bilateral, Two-Level Cervical Sympathetic Chain Blocks on Specific Symptom Clusters for Traumatic Brain Injury, Independent of Concomitant PTSD Symptoms.

: The aim of this study was to determine if performing ultrasound-guided, bilateral, two-level cervical sympathetic chain blocks (2LCSBs) (performed on subsequent days) improves symptoms associated with traumatic brain injury (TBI) that do not overlap with posttraumatic stress disorder (PTSD). : A retrospective chart review was conducted between August 2022 and February 2023. We identified twenty patients who received bilateral 2LCSBs for PTSD and anxiety symptoms and who also had a history of TBI.