Discovery of a Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.

Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein, we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for the rapid identification of microbial natural products with both novel structures and potent activities.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Prognostic value of coronary artery calcium scoring in patients with non-small cell lung cancer using initial staging computed tomography.

Background: Lung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of cases. Due to the lack of early clinical signs, metastasis often occurs before diagnosis, impacting treatment and prognosis. Cardiovascular disease (CVD) is a common comorbidity in lung cancer patients, with shared risk factors exacerbating outcomes.

Comparative evaluation of spatiotemporal methods for effective dengue cluster detection with a case study of national surveillance data in Thailand.

Dengue fever poses a significant public health burden in tropical regions, including Thailand, where periodic epidemics strain healthcare resources. Effective disease surveillance is essential for timely intervention and resource allocation. Various methods exist for spatiotemporal cluster detection, but their comparative performance remains unclear.

Shared Decision-Making in Total Hip and Knee Arthroplasty: Understanding Surgeon and Patient Perspectives Regarding When It Is Time for Surgery.

Background: Although total hip and total knee arthroplasty are highly successful operations, the decision of whether and when to undergo surgery is highly subjective and discretionary, and specific guidelines regarding readiness for surgery remain elusive. The nature of these decisions underscores the importance of shared decision-making, which is founded on the concept that patients substantially contribute to determining their own readiness for surgery. The OPTION survey was developed as a conversation aid to facilitate shared decision-making in the context of total joint arthroplasty.

Retinoblastoma and beyond: pediatric orbital mass lesions.

Various space occupying lesions can arise in the orbit, ranging from developmental anomalies to malignancies, and many of the diseases occurring in children are different from the pathologies in the adult population. As the clinical presentation is frequently nonspecific, radiologic evaluation is essential for lesion detection and characterization as well as patient management. While orbital masses may in some cases involve multiple compartments, a simple compartmental approach is the key for the diagnosis on imaging studies, and MRI is the modality of choice.

High-resolution vessel wall MRI in Moyamoya disease: a systematic review and meta-analysis of diagnostic and prognostic applications.

Purpose: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by the narrowing of arteries at the brain's base. While cerebral angiography is the gold standard for diagnosis, high-resolution vessel wall magnetic resonance imaging (VW-MRI) has recently emerged as a non-invasive diagnostic tool. This systematic review aims to provide insights into the role of VW-MRI in enhancing the diagnosis and management of MMD.

Comparing adolescent glomerular disease clinical outcomes to the clinical outcomes in childhood, young adult, and adult-onset glomerular disease in the CureGN database.

Background: There is a lack of evidence to suggest that outcomes of adolescent and adult-onset glomerular disease differ. Still, most glomerular disease trials include adults but exclude adolescents.

Methods: We designed a retrospective study using the CureGN database to compare individuals with adolescent-onset glomerular disease relative to individuals with older and younger age at onset.

Rationale and Logistics of Continuous Infusion Cephalosporin Antibiotics.

Cephalosporins have traditionally been administered as an intermittent infusion. With the knowledge that cephalosporins demonstrate a time-dependent pharmacodynamic profile, administration via continuous infusion may provide more effective antibiotic exposure for successful therapy. Proposed benefits of administration via continuous infusion include less IV manipulation, decreased potential for antibiotic resistance, and potential cost savings.

Transitioning Adolescents to Adult HIV Care in the United States: Implementation Lessons from the Intervention Pilot Trial.

Although every youth in pediatric/adolescent HIV care will need to transition to adult-oriented care, there are no existing evidence-based interventions to optimize health through this process. Healthcare transition poses a persistent challenge to the health of youth living with HIV, which may result in gaps in care engagement, medication adherence, and viral suppression. Our process evaluation of , a multilevel mobile health (mHealth) intervention, included iterative interviews with youth, providers, and Transition Champions.

The Impact of Tumor Stage and Histopathology on Survival Outcomes in Esophageal Cancer Patients over the Past Decade.

Background: Esophageal cancer (EC) is the sixth leading cause of cancer-related mortality worldwide, continuing to be a significant public health concern. The purpose of this study is to assess the impact of staging and histopathology of EC on associated mortality. The study also aims to further investigate clinical characteristics, prognostic factors, and survival outcomes in patients diagnosed with EC between 2010 and 2017.

A High-Affinity Monoclonal Antibody Against the Pancreatic Ductal Adenocarcinoma Target, Anterior Gradient-2 (AGR2/PDIA17).

Background/objectives: Anterior Gradient-2 (AGR2/PDIA17) is a member of the protein disulfide isomerase (PDI) family of oxidoreductases. AGR2 is up-regulated in several solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Given the dire need for new therapeutic options for PDAC patients, we investigated the expression and function of AGR2 in PDAC and developed a novel series of affinity-matured AGR2-specific single-chain variable fragments (scFvs) and monoclonal antibodies.

Guideline Concordant Extended Pharmacologic Venous Thromboembolism Prophylaxis Utilization After Colorectal Cancer Resection Is Low Regardless of Patient Factors or Hospital Characteristics.

Background: Venous thromboembolism after colorectal cancer resection is common and highly morbid. Extended pharmacologic venous thromboembolism prophylaxis after cancer surgery lowers venous thromboembolism risk and is recommended by major professional societies. Adherence is low in contemporary local and regional studies.

Mothers' Violence Experiences and Provision of Emotional Support Following Child Sexual Abuse.

Emotional support from a non-offending caregiver, often the child's mother, is theorized to help buffer children from the consequences of child sexual abuse (CSA). However, many mothers struggle to provide effective emotional support, suggesting it may be important to assess for factors related to mothers' abilities to support their child. CSA frequently occurs in families that have experienced other types of violence, including intimate partner violence (IPV), and many mothers have their own personal history of child abuse.

Depressive symptoms after surgical and medical management of OSA: a systematic review and meta-analysis.

Purpose: To evaluate the effect of CPAP and surgical alternatives for OSA on depression and compare the results of surgery to CPAP. ​METHODS: COCHRANE Library, CINAHL, PubMed, and Scopus databases were searched for English-language articles. Meta-analysis of continuous measures (mean), proportions (%), and mean difference (Δ) with 95% confidence interval was conducted for objective and subjective outcomes before and after treatment with CPAP or surgical interventions.

Enhancement of detoxification of xenobiotic aromatic amine dyes by N-acetyltransferase 1 (NAT1) enzyme on human keratinocytes cells through structural modification.

The metabolic conversion of aromatic amines to N-acetylated forms in skin and keratinocytes depends on N-acetyltransferase-1 (NAT1). Common hair color ingredient such as para-phenylenediamine (PPD) causes allergic contact dermatitis. We explored how different electronic substituents on PPD aided NAT1 enzyme biotransform oxidative arylamine (AA) compounds G1-G13 by N-acetylation, NAT-1 activity assays, metabolism, and in vitro clearance investigations in human keratinocytes, while identifying NAT-1 protein levels by Western blot and qRT-PCR.

Sex and Gender Considerations in Orthopaedic Research: Existing Barriers, What's Needed by Institutions and Research Departments, and How to Guide Junior Investigators and Faculty.

JBJS convened a symposium to discuss the reporting of sex and gender in research studies as an imperative to improve research methods and results to benefit all patients. Barriers to improved reporting include a lack of societal and cultural acceptance of its need; a lack of education regarding appropriate terminology and appropriate statistical methods and efficient study designs; a need for increased research funding to support larger group sizes; unknown concordance of cell and animal models with humans to reflect biologic variables such as sex; and a lack of understanding of key considerations of gender, race, and other social determinants of health and how these factors intersect. Attention to developing and disseminating best-practice statistical methods and to educating investigators (at all career levels), reviewers, funders, editors, and staff in their proper implementation will aid reporting.

Accuracy of a Rapid-Response EEG's Automated Seizure-Burden Estimator: AccuRASE Study.

Background And Objectives: The use of rapid response EEG (rr-EEG) has recently expanded in limited-resource settings and as a supplement to conventional EEG to rapidly detect and treat nonconvulsive status epilepticus. The study objective was to test the accuracy of an rr-EEG's automated seizure burden estimator (ASBE).

Methods: This is a retrospective observational study using multiple blinded reviewers.

Extending the Environmental influences on Child Health Outcomes (ECHO) Cohort through 2030: Rationale and study protocol.

Early life environmental exposures, even those experienced before conception, can shape health and disease trajectories across the lifespan. Optimizing the detection of the constellation of exposure effects on a broad range of child health outcomes across development requires considerable sample size, transdisciplinary expertise, and developmentally sensitive and dimensional measurement. To address this, the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Cohort Study is an observational longitudinal pediatric cohort study.

Current Treatment Options for Diabetic Retinal Disease.

The global incidence of diabetes is rising steadily and with it the number of people living with diabetic retinal disease (DRD) is increasing. Like diabetes, DRD can be treated but not cured. In response, therapies to address DRD include targeted ocular and systemic medications.

The persistent pool of HIV-1-infected cells is formed episodically during untreated infection.

Previous studies have shown that the majority of long-lived cells harboring persistent HIV-1 proviral genomes originates from viruses circulating in the year prior to antiretroviral therapy (ART) initiation, but a smaller proportion originates from viruses circulating much earlier in untreated infection. These observations suggest that discrete biological factors influence the entry and persistence of viruses into the persistent proviral pool, and there may be periods earlier in untreated infection with increased seeding. Therefore, we examined the timing of formation of the long-lived pool of infected cells that persists during ART in seven women (after a median of 5.

Exploring Midwives' and Nurse-Midwives' Professional Identity and How Midwifery May Be Best Represented in the Public Realm: A Global Convergent Parallel Mixed-Methods Study.

Aims: With respect to midwives and nurse-midwife populations (1) measure and (2) explore professional identity and (3) explore how the midwifery profession may be best represented in the public realm.

Design: Convergent Parallel Mixed-Methods Design.

Methods: A web-based survey was used to collect data from 860 midwives and nurse-midwives from 102 countries between February and July 2022.

Breast Adenocarcinoma and Cold Agglutinin Disease: A Paraneoplastic Syndrome.

Autoimmune hemolytic anemia is a disorder that is characterized by the destruction of red blood cells through an autoimmune process, such as temperature-dependent antibodies. The two predominant types, cold agglutinin and warm agglutinin disease, typically possess different underlying etiologies. Prompt recognition and workup of autoimmune hemolytic anemia should be prioritized to potentially uncover any underlying primary cause, such as malignancy.