Biology-inspired dynamic microphysiological system approaches to revolutionize basic research, healthcare and animal welfare.

The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure to assess fundamental scientific, industrial and regulatory trends for translational science in the MPS-field from a bird's eye view. The 2023 workshop participants at that time concluded that the technology as used within academia has matured significantly, underlined by the broad use of MPS and the steadily increasing number of high quality research publications - yet, broad industry adoption of MPS has been slow, despite strong interest. Academic research using MPS primarily aims to accurately recapitulate human biology in MPS-based organ models in areas where traditional models have been lacking key elements of human physiology, thereby enabling breakthrough discoveries for life sciences.

Preventing unrestricted and unmonitored AI experimentation in healthcare through transparency and accountability.

The integration of large language models (LLMs) into electronic health records offers potential benefits but raises significant ethical, legal, and operational concerns, including unconsented data use, lack of governance, and AI-related malpractice accountability. Sycophancy, feedback loop bias, and data reuse risk amplifying errors without proper oversight. To safeguard patients, especially the vulnerable, clinicians must advocate for patient-centered education, ethical practices, and robust oversight to prevent harm.

Predicting metabolite response to dietary intervention using deep learning.

Due to highly personalized biological and lifestyle characteristics, different individuals may have different metabolite responses to specific foods and nutrients. In particular, the gut microbiota, a collection of trillions of microorganisms living in the gastrointestinal tract, is highly personalized and plays a key role in the metabolite responses to foods and nutrients. Accurately predicting metabolite responses to dietary interventions based on individuals' gut microbial compositions holds great promise for precision nutrition.

Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures.

Background: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations.

Individualized transfusion decisions to minimize adverse cardiovascular outcomes in patients with acute myocardial infarction and anemia.

Background: Risk-benefit tradeoffs between restrictive versus liberal red blood cell transfusion strategies may vary across individuals. This exploratory analysis aimed to derive and evaluate individualized treatment effects of defined transfusion strategies in patients with acute MI and anemia with the goal of minimizing adverse cardiovascular outcomes.

Methods: This study analyzed 3,447 (98.

Validation of BEST-CLI among patients undergoing primary bypass or angioplasty with or without stenting for chronic limb-threatening ischemia.

Background: BEST-CLI established the superiority of single-segment great saphenous vein (ssGSV) conduits for revascularization in patients with CLTI; however, the generalizability of these data is unknown. Thus, we aimed to validate the long-term results of open surgical bypass (BPG) versus angioplasty with or without stenting (PTA/S) using the BEST-CLI inclusion and randomization criteria.

Methods: All patients undergoing a first-time lower extremity revascularization for CLTI at our institution from 2005 to 2022 were retrospectively reviewed.

Oral vancomycin treatment alters levels of indole derivatives and secondary bile acids modulating the expression of mTOR pathway genes in astrocytes during EAE.

Astrocytes play important roles in the central nervous system (CNS) during health and disease. Prior studies have shown that gut commensals derived indole derivatives as well as secondary bile acids modulate astrocyte function during the late stage of EAE (recovery phase). Here we show that administering vancomycin to mice starting during the early stage of EAE improved disease recovery, an effect that is mediated by the gut microbiota.

Molecular characterization of HER2-negative breast cancers reveals a distinct patient subgroup with 17q12 deletion and heterozygous loss of ERBB2.

Background: The approval of trastuzumab deruxtecan has prompted the subgrouping of human epidermal growth factor receptor 2-negative (HER2-) breast cancers (BCs) to HER2 0 and HER2 low on the basis of immunohistochemistry, although the biological significance of these subgroups remains uncertain. This study is aimed to better understand the molecular and genetic differences among HER2- tumors stratified by quantitative levels of HER2.

Patients And Methods: We analyzed the transcriptomic and genomic data from the Molecular Taxonomy of BC International Consortium (discovery cohort) and The Cancer Genome Atlas (independent validation cohort).

HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers.

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).

Patients And Methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts.

Surgical treatment for severe endodontic-periodontal lesion: A case report with 2-year follow-up.

Background: Various surgical techniques have recently been developed for periodontal tissue regeneration, especially those do not involve any incisions in the interdental papillae at the regeneration site. These techniques have significant advantages for obtaining clinical attachment gain with least amount of gingival recession, however, may also have disadvantages such as limited field of surgical view, difficulty in debridement, and limited access only from the buccal side. This case report addresses a 2-year follow-up with a novel surgical approach to achieve periodontal regeneration that overcomes these limitations: the flexible tunnel technique (FTT).

Diabetes visits in paediatric versus adult clinics for young adults (YA) with T1D: Pre-pandemic and pandemic care.

Background: Young adults (YA) with type 1 diabetes mellitus (T1D) are at high risk of worsening glycated haemoglobin (HbA1c) with fewer follow-up visits. We examined the association of demographic and diabetes characteristics with care utilization, including in-person and telehealth visits, pre- (1 April 2019 to 15 March 2020) and during the COVID-19 pandemic (30 March 2020 to 15 March 2021) for YA (ages: 18-30) with T1D, comparing those seen in paediatric versus adult diabetes clinics at a single diabetes centre.

Methods: Data were obtained from the electronic health record for YA with a pre-pandemic HbA1c.

Pediatric bladder tissue engineering: Where have we been and where do we go next?

Objectives: This review aims to (a) provide a concise overview of early clinical trials in bladder tissue engineering and the associated challenges, (b) evaluate significant advancements over the past 15 years in addressing key limitations in angiogenesis, scaffolding, cell sourcing, and immunomodulation, and (c) explore the individual and synergistic contributions of each domain toward the development of a viable engineered solution.

Materials And Methods: Relevant papers for this narrative review were selected through a PubMed search for "bladder tissue engineering" studies published between 01/01/2009 and 12/31/2024, as well as earlier clinical trials that predate this period.

Results: Along with reviewing four major clinical trials, this review highlights nearly 20 distinct studies that showcase progress in the critical domains of angiogenesis, scaffolding, cell sourcing, and immunomodulation.

Integrated Phase I Pharmacokinetics and Pharmacodynamics of Epinephrine Administered via Sublingual Film, Autoinjector, or Manual Injection.

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered via intramuscular (IM) or subcutaneous (SC) injection. AQST-109, a sublingual film containing a prodrug of epinephrine, is in development as an alternative delivery method for the treatment of severe allergic reactions including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine following administration of AQST-109 to epinephrine delivered by manual IM injection and epinephrine autoinjectors (EAIs).

Impact of Sarcoidosis in Patients Undergoing Aortic Valve Replacement: Insight from Nationwide Readmission Database 2016-2019.

It is not well-known if valve replacement outcomes differ in patients with sarcoidosis, especially in aortic valve intervention where the pressure gradients are physiologically high. In this retrospective study, we included all patients who underwent surgical/transcatheter aortic valve replacement from the National Readmission Database (2016-2019) and then divided them into those with and without sarcoidosis. Logistic and cox proportional hazard regression models were used.

Consistent direction despite wavering policy: reductions in resident physician extended duration shifts over 20 years.

We examined data from 17,498 physicians-in-training who reported on 92,662 months of work over a 20 year study interval that included three major revisions to work hour limits. Extended duration shifts (≥24 hours; EDS) are much less common than they used to be. On average, first-year resident physicians (PGY1s) currently work a total of 4 EDS per year and 3 EDS per month during months in which any EDS are worked.

Veterans' Motivation, Preference, and Feedback After Completing a Novel Physical Therapy Treatment.

Objectives: This study evaluated Veterans' motivation and perception of different components of a novel physical therapy (PT) treatment aimed at increasing mobility, motivation, and exercise adoption.

Methods: Patient-satisfaction surveys were administered to middle-aged to older Veterans (≥50 years old) with slow walking speed who completed the 8-week PT treatment. Mixed methods were employed to assess rating-based responses and examine themes derived from open-ended responses.

Tumor-infiltrating lymphocytes in HER2-positive breast cancer: potential impact and challenges.

Introduction: In this review, we evaluate the role of stromal tumor-infiltrating lymphocytes (sTILs) as a biomarker in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, exploring the prognostic and predictive potential in various treatment settings.

Methods: Data from multiple clinical trials in the early and metastatic settings, focusing on TILs' correlation with pathologic complete response (pCR), progression-free survival (PFS), and overall survival across early and metastatic HER2-positive breast cancer were summarized. This review also discusses TILs' assessment methods, interobserver variability, and emerging technologies to assess TILs.

Low Utility of Routine Thyroid Function Testing for Bowel Symptoms: A Population-Based Assessment.

Background: Chronic constipation, diarrhea, and fecal incontinence (FI) are prevalent with significant impact on quality of life and healthcare utilization. Thyroid dysfunction was recognized as a potential contributor to bowel disturbances in selected populations, but the strength/consistency of this association remain unclear.

Aims: To investigate the relationship between thyroid function and bowel health measures (constipation, diarrhea, and FI) in a nationally representative sample of the U.

Targeting ultra-processed foods for prevention of type 2 diabetes: state of the evidence and future directions.

The incidence of type 2 diabetes has risen globally, in parallel with the obesity epidemic and environments promoting a sedentary lifestyle and low-quality diet. There has been scrutiny of ultra-processed foods (UPFs) as a driver of type 2 diabetes, underscored by their increasing availability and intake worldwide, across countries of all incomes. This narrative review addresses the accumulated evidence from investigations of the trends in UPF consumption and the relationship with type 2 diabetes incidence.

Characterization of the Phenotypic Consequences of the Duffy-Null Genotype.

A wealth of research focused on African American populations has connected rs2814778-CC ("Duffy-null") to decreased neutrophil (neutropenia) and leukocyte counts (leukopenia). While it has been proposed that this variant is benign, prior studies have shown that the misinterpretation of Duffy-null associated neutropenia and leukopenia can lead to unnecessary bone marrow biopsies, inequities in cytotoxic and chemotherapeutic treatment courses, under-enrollment in clinical trials, and other disparities. To investigate the phenotypic correlates of Duffy-null status, we conducted a phenome-wide association study (PheWAS) across more than 1,400 clinical conditions in All of Us, the Vanderbilt University Medical Center's Biobank, and the Million Veteran Program.

Structuring Palliative Care Education for Medical Students: Impact of a Novel Framework and Pocket Card.

Introduction: Palliative care (PC) education is not uniformly provided across U.S. medical schools.