Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part I. Phases of Chronic GVHD, Supportive Care, and Systemic Therapy Discontinuation.

Current literature lacks details on the impact of pediatric chronic graft-versus-host disease (cGVHD) on long-term survivorship after allogeneic hematopoietic cell transplantation (HCT). Nonetheless, cGVHD remains a leading cause of post-transplant morbidity and mortality in children and adolescents, which is particularly relevant given the longer life-expectancy after HCT (measured in decades) compared to older adults. To address this knowledge gap, leaders of the Pediatric Transplant and Cellular Therapy Consortium convened a multidisciplinary taskforce of experts in pediatric cGVHD and HCT late effects known as RESILIENT after Chronic GVHD (Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD).

The changing global landscape of national cancer control plans.

Global efforts to highlight cancer and non-communicable diseases (NCDs) as a growing burden were first raised in 2005 World Health Assembly Resolution 58.22 and reinforced with Resolution 70.12 and the Global NCD action plan in 2017.

An adenoviral vector encoding an inflammation-inducible antagonist, HMGB1 Box A, as a novel therapeutic approach to inflammatory diseases.

Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs.

The childhood cancer data initiative: enabling data sharing to drive research advances and transform pediatric cancer diagnosis and treatment.

Purpose Of Review: With growing emphasis on data-driven research in pediatric oncology, particularly in the context of advances in molecular characterization and precision medicine, there is an urgent need for comprehensive data-sharing initiatives. This review explores how the Childhood Cancer Data Initiative (CCDI) addresses this critical need.

Recent Findings: CCDI plays a key role in enhancing pediatric cancer research by improving data integration, sharing, and collaboration.

Differential Mobility Spectrometry Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets.

We report the first implementation of ion mobility mass spectrometry combined with an ultrahigh throughput sample introduction technology for high-throughput screening (HTS). The system integrates differential mobility spectrometry (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the substrates and products of isomerase-mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens, offering an opportunity as a drug target for a variety of microbial and parasite borne diseases.

Assessment of sex disparities in prevalence of diagnosed and undiagnosed diabetes mellitus: results from the Bangladesh demographic and health survey data.

Background: The global health concern regarding the low prevalence of diagnosed diabetes mellitus (DDM) is evident, but the prevalence of DDM is increasing. This is attributed to the frequent underestimation of undiagnosed diabetes mellitus (UDM). Given the limited research on this matter in Bangladesh, there is a need to investigate sex differences in both the prevalence and risk factors of DDM among Bangladeshi adults.

Structural mechanism of CBR binding to peripheral and biased inverse agonists.

The cannabinoid receptor 1 (CBR) regulates synaptic transmission in the central nervous system, but also has important roles in the peripheral organs controlling cellular metabolism. While earlier generations of brain penetrant CBR antagonists advanced to the clinic for their effective treatment of obesity, such molecules were ultimately shown to exhibit negative effects on central reward pathways that thwarted their further therapeutic development. The peripherally restricted CBR inverse agonists MRI-1867 and MRI-1891 represent a new generation of compounds that retain the metabolic benefits of CBR inhibitors while sparing the negative psychiatric effects.

Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation.

Inflammatory biomarkers like C-reactive protein (CRP) are elevated in a subset of patients with depression and have been associated with lower functional connectivity (FC) in a ventral striatum (VS) to ventromedial prefrontal cortex (vmPFC) reward circuit and symptoms of anhedonia. Evidence linking these relationships to the effects of inflammation on dopamine is consistent with our recent findings that acute levodopa (L-DOPA) increased VS-vmPFC FC in association with deceased anhedonia in depressed patients with higher but not lower CRP (>2 versus ≤ 2 mg/L). To determine whether repeated L-DOPA administration caused sustained effects on FC and behavior in these patients, medically stable depressed outpatients with CRP > 2 mg/L and anhedonia (n = 18) received one week of three doses of L-DOPA (150-450 mg/day/week with carbidopa) or placebo in a randomized order.

A randomized trial for combination nicotine replacement therapy for smoking cessation among people with HIV in a low-resourced setting.

Objective: The purpose of this study was to evaluate the efficacy of combination nicotine replacement therapy (c-NRT) for smoking cessation among people with HIV (PWH) in South Africa.

Design: We conducted an open label, individually randomized clinical trial.

Methods: Using a two-armed approach, PWH who smoke were randomized to receive either 1) intensive anti-smoking behavioral counseling (BC) or 2) intensive anti-smoking BC plus c-NRT (nicotine patches augmented by nicotine gum).

Outcomes Associated With Airway Management of Adult Trauma Patients Admitted to Surgical Intensive Care.

Introduction: Advanced airway management and ventilation of trauma patients are often needed during acute stabilization and resuscitation and later, in those admitted. In addition to endotracheal intubation for advanced airway management, tracheostomy is commonly used in critically ill patients when prolonged mechanical ventilation is required. However, the outcomes associated with airway management approaches and the timing of a tracheostomy in critically ill patients are mixed.

Genotype-phenotype associations in individuals with Diamond Blackfan anaemia.

Introduction: Diamond Blackfan anaemia (DBA) is a rare disorder characterized by failure of red blood cell production, congenital abnormalities and cancer predisposition, primarily caused by pathogenic germline variants in genes encoding ribosomal proteins.

Methods: We conducted a genotype-phenotype and outcome study of 121 patients with DBA spanning the 20-year history of the National Cancer Institute's Inherited Bone Marrow Failure Syndromes study. Patient phenotypes were compared by large versus small ribosomal protein genes, across genes with >5 cases (, , and ) and by type of pathogenic variants (hypomorphic versus null, large deletions versus others).

Size-Up, Size-Down: Accuracy of Component Sizing with Computerized Tomography and Robotic-Assisted Total Knee Arthroplasty.

Templating prior to total knee arthroplasty (TKA) can help to improve surgical efficiency and potentially improve alignment and outcomes. The purpose of this article is to evaluate the ability of computed tomography (CT)-based preoperative templating to accurately predict implant sizes. A total of 724 Stryker MAKO robotic-assisted TKA cases were retrospectively evaluated from a prospectively collected database between January 2020 and October 2023.

Inside the Mind of the DMC: A Review of Principles and Issues with Case Studies.

A data monitoring committee (DMC) can have an extremely challenging job. Stop a trial too soon, and results are inconclusive and the trial fails to obtain answers to important questions that could inform future clinical practice. Stop a trial too late, and trial participants are exposed to potentially harmful or ineffective interventions longer than necessary.

Conceptual Framework for African American Kinship Caregiver's Susceptibility to Alzheimer's Disease.

Kinship caregivers (e.g., grandparents raising grandchildren) have been increasing over the last several decades.

Population Pharmacokinetics of Meropenem Across the Adult Lifespan.

Background And Objective: We conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens.

Methods: A total of 99 patients were included. The population pharmacokinetic models used had two compartments: zero-order input and linear elimination.

A prospective, multi-center post-marketing surveillance cohort study to monitor the safety of the recombinant zoster vaccine in Chinese adults ≥50 years of age.

This post-marketing surveillance study evaluated the safety of the adjuvanted recombinant zoster vaccine (RZV) in Chinese adults, given the limited country-specific safety data accumulated since the 2019 licensure of RZV in China for adults ≥ 50 years of age (YOA). This descriptive, prospective cohort study enrolled adults ≥ 50 YOA who voluntarily received RZV per routine clinical practice in six centers in China. The primary outcomes were occurrence, intensity, and causal relationship to vaccination of medically attended adverse events (MAEs) within 30 days post-any dose.

High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation.

Favipiravir, a high dose antiviral drug effective for oral treatment for COVID-19, with poor water solubility is formulated using a simple, low-cost melt coating and granulation methodology. High-dose (82.5 % w/w API) tablets (600 mg and 800 mg) with desired release profiles are developed while minimizing excipient burden.

Comparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups.

Nanobodies, or single-domain antibody fragments, are promising candidates for molecular imaging due to their small size, rapid tissue penetration, and high target specificity. However, a significant challenge in their use is high renal uptake and retention, which can limit the therapeutic efficacy and complicate image interpretation. This study compares five different fluorine-18-labeled prosthetic groups for nanobodies, aiming to optimize pharmacokinetics and minimize kidney retention while maintaining tumor targeting.

In vitro safety evaluation of dopamine D3R antagonist, R-VK4-116, as a potential medication for the treatment of opioid use disorder.

R-VK4-116 is currently being developed as a medication to treat opioid use disorder (OUD). To characterize in vitro safety properties of R-VK4-116, metabolic stability in hepatocytes or liver microsomes, metabolite identification, metabolism/transporter-mediated drug interactions, lysosomal perturbation, mitochondrial toxicity, off-target enzyme effects, cellular and nuclear receptor functional assays, electrophysiological assays, CiPA, KINOMEscanTM, plasma protein binding, phospholipidosis and steatosis assays were performed. Overall, R-VK4-116 was metabolically stable in hepatocytes and microsomes.

"Crying in the Wilderness"-The Use of Web-Based Support in Telomere Biology Disorders: Thematic Analysis.

Background: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.

Objective: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.

Impact of rapid antibiotic susceptibility testing for Gram-negative bacteremia varies by pathogen type and resistance: a secondary analysis of the RAPIDS GN trial.

In this secondary analysis of 386 subjects with Gram-negative bacteremia enrolled in the RAPIDS GN trial, rapid antibiotic susceptibility testing had a greater benefit on the management of bacteremia caused by antibiotic-resistant compared to antibiotic-susceptible isolates, especially for species and species.IMPORTANCERapid blood culture diagnostics are costly, and their use has not demonstrated clear clinical benefit for patients with Gram-negative sepsis, possibly because prior trials did not enroll sufficient numbers of patients with antibiotic-resistant infections. This analysis of patients with sepsis previously enrolled in a randomized controlled clinical trial demonstrates that rapid susceptibility testing of bacteria from blood cultures had the greatest impact for patients with antibiotic-resistant infections.