Deception and Fraud in the Justification of "Pediatric Drug Development": A Challenge at the Interface of Medicine and Law.

United States and European Union laws demand separate clinical studies in children as a condition for drugs' marketing approval. Justified by carefully framed pseudo-scientific wordings, more so the European Medicines Agency than the United States Food and Drug Administration, "Pediatric Drug Development" is probably the largest abuse in medical research in history. Preterm newborns are immature and vulnerable, but they grow.

Antimelanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis: clinical features and outcomes in a racially diverse patient cohort.

Background: The anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis is known for its association with rapidly progressive interstitial lung disease (RP-ILD) and ulcerative skin lesions, often presenting with or without muscle involvement. The aim of this study was to identify distinct clinical and laboratory features that could be used to evaluate disease progression in an ethnically diverse cohort of anti-MDA5 dermatomyositis patients at a U.S.

Imagining Coat-Hangers and Pills: A Qualitative Exploration of Abortion Beliefs and Attitudes in Hostile Policy Contexts in the United States.

Objective: We explored awareness of and attitudes about the safety of various methods people use to attempt to end a pregnancy without medical assistance, which we refer to in this study collectively as self-managed abortion (SMA).

Methods: In 2020, we invited individuals living in eight United States (US) states considered "hostile" to abortion rights or with a history of criminalizing abortions performed outside the formal healthcare system to participate in semi-structured telephone interviews regarding their attitudes toward these practices. We analyzed coded transcripts for content and themes.

Characterization of trends in preoperative hemoglobin A1c testing prior to metabolic and bariatric surgery: a retrospective, observational study.

Background: Irrespective of baseline diabetes status, preoperative hemoglobin A1c (A1C) influences perioperative care in patients undergoing metabolic and bariatric surgery (MBS). Accordingly, the American Society of Metabolic and Bariatric Surgery (ASMBS) endorses that patients undergoing MBS should receive a preoperative A1C test. We aimed to assess the proportion of MBS patients who received a preoperative A1C test and determine whether baseline diabetes status influences receipt of a test.

Human migrations, anthropogenic changes, and insect-borne diseases in Latin America.

Rapid urbanization and migration in Latin America have intensified exposure to insect-borne diseases. Malaria, Chagas disease, yellow fever, and leishmaniasis have historically afflicted the region, while dengue, chikungunya, and Zika have been described and expanded more recently. The increased presence of synanthropic vector species and spread into previously unaffected areas due to urbanization and climate warming have intensified pathogen transmission risks.

Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2.

Background: Patient-derived lung cancer organoids (PD-LCOs) demonstrate exceptional potential in preclinical testing and serve as a promising model for the multimodal management of lung cancer. However, certain lung cancer cells derived from patients exhibit limited capacity to generate organoids due to inter-tumor or intra-tumor variability. To overcome this limitation, we have created an in vitro system that employs mesenchymal stromal cells (MSCs) or fibroblasts to serve as a supportive scaffold for lung cancer cells that do not form organoids.

Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer's disease ligands.

TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry.

Sarcolemma resilience and skeletal muscle health require O-mannosylation of dystroglycan.

Background: Maintaining the connection between skeletal muscle fibers and the surrounding basement membrane is essential for muscle function. Dystroglycan (DG) serves as a basement membrane extracellular matrix (ECM) receptor in many cells, and is also expressed in the outward-facing membrane, or sarcolemma, of skeletal muscle fibers. DG is a transmembrane protein comprised of two subunits: alpha-DG (α-DG), which resides in the peripheral membrane, and beta-DG (β-DG), which spans the membrane to intracellular regions.

Effect of daily alcohol intake on sex hormone levels among postmenopausal breast cancer survivors on aromatase inhibitor therapy: a randomized controlled crossover pilot study.

Background: Alcohol intake is associated with a higher risk of estrogen receptor-positive (ER+) breast cancer (BC), presumably through its confirmed ability to increase sex hormone levels. Whether consuming alcohol within the recommended limit of one serving per day increases sex hormone levels among postmenopausal women taking aromatase inhibitors (AI) to inhibit estrogen production remains unknown. Therefore, we compared sex hormone levels following white wine to levels following white grape juice among ER + BC survivors taking AIs.

Brain iron deposition and cognitive decline in patients with cerebral small vessel disease : a quantitative susceptibility mapping study.

Background: Quantitative susceptibility mapping (QSM) can study the susceptibility values of brain tissue which allows for noninvasive examination of local brain iron levels in both normal and pathological conditions.

Purpose: Our study compares brain iron deposition in gray matter (GM) nuclei between cerebral small vessel disease (CSVD) patients and healthy controls (HCs), exploring factors that affect iron deposition and cognitive function.

Materials And Methods: A total of 321 subjects were enrolled in this study.

Retrospective analysis of the occurrence, potential risk factors and medical significance of pulmonary complications after total shoulder arthroplasty from the National Inpatient Sample database (2010-2019).

Background: In USA, total shoulder arthroplasty (TSA) ranks amongst the top five surgeries that require hospitalization. As a result, the healthcare system in USA could face a considerable financial strain due to the emergence of subsequent pulmonary problems. This study aimed to conduct a thorough examination of the prevalence, influential factors and medical importance of pulmonary complications, with emphasis on pneumonia, respiratory failure and pulmonary embolism (PE) following total shoulder arthroplasty (TSA) procedures in USA.

Country economic status is strongly associated with burn survival - validation of the (modified) ABSI.

Background: Predicting burn-related mortality is vital for family counseling, triage, and resource allocation. Several of the burn-specific mortality prediction scores have been developed, including the Abbreviated Burn Severity Index (ABSI) in 1982. However, these scores are not tested for accuracy to support contemporary estimates of the global burden of burn injury.

A phase Ia study of a novel anti-HER2 antibody-drug conjugate GQ1001 in patients with previously treated HER2 positive advanced solid tumors.

Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.

Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks.

Racial, socioeconomic, and payer status disparities in utilization of unicompartmental knee arthroplasty in the USA.

Background: Unicompartmental knee arthroplasty (UKA) is a surgical treatment for knee osteoarthritis associated with lower morbidity compared with total knee arthroplasty (TKA) in patients with isolated unicompartmental knee arthritis. As disparities have been noted broadly in arthroplasty care, it follows that such disparities might be present in the utilization of UKA relative to TKA. This study therefore examined racial/ethnic, socioeconomic, and payer status differences in utilization of UKA.

Multi-omics integration and immune profiling identify possible causal networks leading to uterine microbiome dysbiosis in dairy cows that develop metritis.

Background: Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition.

SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis.

Background: Oncolytic viruses (OVs) are increasingly recognized as promising tools for cancer therapy, as they selectively infect and destroy tumor cells while leaving healthy cells unharmed. Despite considerable progress, the limited therapeutic efficacy of OV-based virotherapy continues to be a significant challenge in cancer treatment.

Methods: The SMAC/DIABLO gene was inserted into the genome of vesicular stomatitis virus (VSV) to generate VSV-S.

Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.

Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.

Graph pangenome reveals the regulation of malate content in blood-fleshed peach by NAC transcription factors.

Background: Fruit acidity and color are important quality attributes in peaches. Although there are some exceptions, blood-fleshed peaches typically have a sour taste. However, little is known about the genetic variations linking organic acid and color regulation in peaches.

Study protocol for a hybrid type 3 effectiveness-implementation trial of a team-based implementation strategy to support educators' use of a social engagement intervention.

Background: Remaking Recess (RR) is a school-based evidence-based peer social engagement intervention for autistic students. RR involves direct training and coaching with educators; however, educators face several barriers to implementation at both the individual- and organizational-levels. This protocol paper describes a multi-site study that will test whether an educator-level implementation strategy, coaching, with or without a school-level implementation strategy, school-based teams, will maximize educators' use (fidelity and sustainment) of RR for autistic students and their peers who are socially-isolated, rejected, or peripheral and may need additional support during recess.

Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.

Background: Up to 23% of breast cancer patients recurred within a decade after trastuzumab treatment. Conversely, one trial found that patients with low HER2 expression and metastatic breast cancer had a positive response to trastuzumab-deruxtecan (T-Dxd). This indicates that relying solely on HER2 as a single diagnostic marker to predict the efficacy of anti-HER2 drugs is insufficient.

Changes in pulse pressure variation induced by passive leg raising test to predict preload responsiveness in mechanically ventilated patients with low tidal volume in ICU: a systematic review and meta-analysis.

Background: Pulse pressure variation (PPV) is limited in low tidal volume mechanical ventilation. We conducted this systematic review and meta-analysis to evaluate whether passive leg raising (PLR)-induced changes in PPV can reliably predict preload/fluid responsiveness in mechanically ventilated patients with low tidal volume in the intensive care unit.

Methods: PubMed, Embase, and Cochrane databases were screened for diagnostic research relevant to the predictability of PPV change after PLR in low-tidal volume mechanically ventilated patients.

Understanding barriers and facilitators to implementation of a patient safety bundle for pregnancy-related severe hypertension in 3 North Carolina outpatient clinics: a qualitative study.

Background: Pregnancy related hypertension is a leading cause of preventable maternal morbidity and mortality in the US, with consistently higher rates affecting racial minorities. Many complications are preventable with timely treatment, in alignment with the Alliance for Innovation on Maternal Health's Patient Safety Bundle ("Bundle"). The Bundle has been implemented successfully in inpatient settings, but 30% of preeclampsia-related morbidity occurs in outpatient settings in North Carolina.

Effectiveness of a comic book intervention on mental health literacy among adolescents and youth in Burkina Faso: a randomized controlled trial protocol.

Background: In Burkina Faso, nearly half of the population is under 15 years old, and one in four adolescents experience depression. This underscores the critical need to enhance mental health literacy among adolescents and youth, empowering them to manage their mental well-being effectively. Comic books offer an engaging approach to health education, yet their effectiveness in addressing mental health remains largely untested.

Influence of hip morphology on gluteal muscle biomechanics: a computational modeling study.

Background: Hip morphology variations, particularly in femoral neck shaft angle (NSA) and iliac wing width (IWW), have been associated with gluteal tendinopathy. However, the biomechanical implications of these morphological differences on gluteal muscle function are not well understood. This study investigates how NSA and IWW influence gluteal muscle forces, moment arms, and estimated tendon loads during walking, aiming to provide insights into the potential biomechanical pathways that may contribute to altered lateral hip loading patterns.

Predicting loss of independence among geriatric patients following gastrointestinal surgery.

Background: While existing risk calculators focus on mortality and complications, elderly patients are concerned with how operations will affect their quality of life, especially their independence. We sought to develop a novel clinically relevant and easy-to-use score to predict elderly patients' loss of independence after gastrointestinal surgery.

Methods: This retrospective cohort study included patients age ≥ 65 years enrolled in the American College of Surgeons National Surgical Quality Improvement Program database and Geriatric Pilot Project who underwent pancreatic, colorectal, or hepatic surgery (January 1, 2014- December 31, 2018).