Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Electrochemical insights into the direct dissolution of impure sphalerites and their partial oxidation in an acidic environment.

This study examined the electrodissolution mechanism of five impure sphalerite samples, which differ significantly in purity levels, along with their partially oxidized counterparts in a 0.5 M HSO. Partially oxidized samples were prepared through an incomplete leaching of sphalerite using HSO with Fe(SO).

Chemical Logic of Peptide Branching by Iterative Nonlinear Nonribosomal Peptide Synthetases.

Branch-point syntheses in nonribosomal peptide assembly are rare but useful strategies to generate tripodal peptides with advantageous hexadentate iron-chelating capabilities, as seen in siderophores. However, the chemical logic underlying the peptide branching by nonribosomal peptide synthetase (NRPS) often remains complex and elusive. Here, we review the common strategies for the biosynthesis of branched nonribosomal peptides (NRPs) and present our biochemical investigation on the NRPS-catalyzed assembly of fimsbactin A, a branched mixed-ligand siderophore produced by the human pathogenic strain .

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.

Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease.

Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding , a human coronary artery disease risk locus.

Use of Intraoperative Frozen Section to Assess Surgical Margins in HPV-Related Oropharyngeal Carcinoma.

Importance: Given the favorable overall prognosis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and the morbidity of increased adjuvant therapy associated with positive surgical margins, large-scale studies on the accuracy of frozen sections in predicting final surgical margin status in HPV-related OPSCC are imperative. Final surgical margin status is the definitive assessment of tumor clearance as determined through surgeon-pathologist collaboration based on permanent analysis of frozen section margins, main specimens, and supplemental resections.

Objectives: To assess the accuracy and testing properties of intraoperative frozen section histology (IFSH) in assessing final surgical margin status in patients undergoing transoral surgery for HPV-related OPSCC.

Evolution of sleep disordered breathing in infants with achondroplasia.

Purpose: Children with achondroplasia (ACH) are at risk for sudden death in infancy due to sleep disordered breathing (SDB) and foramen magnum stenosis (FMS). Sleep studies and neuroimaging are performed in infants with ACH, but interpretation of infant studies is challenging. We sought to describe baseline data on polysomnography (PSG) indices in infants with achondroplasia as well as effects of age and surgery on these parameters.

First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors.

Purpose: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on natural killer (NK) cells/macrophages and EGFR on tumor cells, redirecting antitumor activity towards tumors. The safety and tolerability of AFM24 was evaluated in this Phase 1/2a dose escalation/dose expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

Tumour-Associated Macrophages in Oral Squamous Cell Carcinoma.

Objective: Tumour-associated macrophages (TAMs) are crucial in the progression and treatment response of oral squamous cell carcinoma (OSCC). TAMs infiltrate OSCC, adopting an M2-like phenotype that promotes tumour growth, metastasis and immune suppression. The current narrative review explored the roles of TAMs in OSCC, focusing on their impact on the tumour microenvironment, invasion, metastasis, angiogenesis, immunosuppression and potential therapeutic targeting.

Achieving reliable patient reported outcomes collection to measure health care improvement in a learning health network: lessons from pediatric rheumatology care and outcomes improvement network.

Introduction: Data from the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry suggests that reliable collection of patient-reported outcomes (PROs) varies across sites. The objective of this study was to better understand the practices of collecting PROs at PR-COIN sites.

Methods: A REDCap survey was sent to the lead representative for each PR-COIN site.

Elective hand surgery and concomitant corticosteroid injection: Confirming increased infection risk using A national dataset.

Background: Recent studies demonstrate a link between corticosteroid injection and surgical complications when procedures occur shortly after steroid administration. These publications focus on single procedures like carpal tunnel release. This study seeks to demonstrate how surgical site infection risk changes across thirteen common elective hand procedures when steroid injection is performed contemporaneously.

The 2022 ADEA Climate Study in U.S. and Canadian Dental Schools and Allied Dental Programs: Methodological Considerations.

Objectives: From January 2020 to the end of August 2020, preliminary research gathered data about the need for and the feasibility of an ADEA-led joint Climate Study of dental schools and allied dental programs in the United States and Canada. Informed by these findings, the first ever ADEA-led joint Climate Study took place in 2022. The objectives of this manuscript were to describe the timeline of this climate study and provide information about its methodology, specifically about (a) who participated in this research, (b) what was assessed, (c) how the study was conducted, and (d) how the results were communicated.

Caregiver report of infant behavior associated with autism likelihood in first year of life.

Background: Identification of prodromal indicators of autism in infancy has the potential to identify behaviors relevant to early autism screening.

Methods: We report on data from a prospective general population birth cohort with maternal reported measures at 9 and 12 months: the Survey of Well-Being of Young Children (SWYC; general developmental surveillance) and the First Year Inventory-Lite v3.1b (FYI-Lite; autism specific parent report research tool).

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Rapid and scalable personalized ASO screening in patient-derived organoids.

Personalized antisense oligonucleotides (ASOs) have achieved positive results in the treatment of rare genetic disease. As clinical sequencing technologies continue to advance, the ability to identify patients with rare disease harbouring pathogenic genetic variants amenable to this therapeutic strategy will probably improve. Here we describe a scalable platform for generating patient-derived cellular models and demonstrate that these personalized models can be used for preclinical evaluation of patient-specific ASOs.

Urinary Selenium, Cranial MRI, and Cognitive Function in American Indians: The Strong Heart Study.

Introduction: Selenium (Se), a trace element found in soil and groundwater, is necessary for many biological functions, including cerebrovascular health, through selenoprotein formation. However, high concentrations may be harmful. American Indians face elevated cerebrovascular disease rates, which may be associated with other trace elements, such as Se.

Contribution of Weak Bases to Isoxaflutole Hydrolysis: Implications for Hydrolysis in Laboratory and Natural Waters.

The hydrolysis rates of many organic chemicals are accelerated under alkaline conditions by the presence of hydroxide (HO), which is typically assumed to be the predominant species contributing to base-catalyzed hydrolysis in both natural waters and laboratory buffers used in standard protocols. In this study, we demonstrated that weak bases (e.g.

Pediatric relapsed/refractory ALK+ anaplastic large cell lymphoma treatment and outcomes in the targeted drug era.

Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL.

Artificial Intelligence In Health And Health Care: Priorities For Action.

The field of artificial intelligence (AI) has entered a new cycle of intense opportunity, fueled by advances in deep learning, including generative AI. Applications of recent advances affect many aspects of everyday life, yet nowhere is it more important to use this technology safely, effectively, and equitably than in health and health care. Here, as part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2025 initiative, which is designed to provide guidance on pressing health care issues for the incoming presidential administration, we describe the steps needed to achieve these goals.

Pretargeted Trop-2 immunoPET for rapid, selective detection of pancreatic tumors.

Purpose: Recent clinical advances with the approval of antibody-drug conjugates targeting Trop-2 such as sacituzumab-govitecan and datopotomab-deruxtecan have garnered tremendous interest for their therapeutic efficacy in numerous tumor types including breast and lung cancers. ImmunoPET can stratify tumor avidity, clarifying patient eligibility for ADC therapy as well as a diagnostic companion during therapy. Slow antibody circulation requires days to reach optimal imaging timepoints.

Life satisfaction around the world: Measurement invariance of the Satisfaction With Life Scale (SWLS) across 65 nations, 40 languages, gender identities, and age groups.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions.

Demographic Characteristics and Relational Coordination in ICU Teams: Implications for Building Diverse and Effective Healthcare Collaboration.

Objective: To determine if professional roles and demographic characteristics predict relational coordination (RC) among healthcare professionals in the ICU.

Background: Race, age, and sex diversity are increasing in the medical and nursing workforce, raising questions regarding how well healthcare professionals are collaborating. RC is a validated model for coordinating interdependent work among healthcare professionals.