Unifying community whole-brain imaging datasets enables robust neuron identification and reveals determinants of neuron position in C. elegans.

We develop a data harmonization approach for C. elegans volumetric microscopy data, consisting of a standardized format, pre-processing techniques, and human-in-the-loop machine-learning-based analysis tools. Using this approach, we unify a diverse collection of 118 whole-brain neural activity imaging datasets from five labs, storing these and accompanying tools in an online repository WormID (wormid.

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.

Accuracy of Established Prognostic Staging Systems for Cardiac Transthyretin Amyloidosis in the Tafamidis Era.

Background: Biomarker-based prognostic staging systems, including the National Amyloidosis Centre (NAC) and the Mayo staging systems, are widely-used but have only been validated for treatment-naive patients with cardiac transthyretin amyloidosis (ATTR-CA).

Objectives: The purpose of this study was to assess the accuracy of the NAC and Mayo staging systems in patients with ATTR-CA treated with tafamidis.

Methods: A retrospective observational study following patients with ATTR-CA from initiation of tafamidis (baseline) to time of all-cause death was conducted.

Neonatal cost savings in hypertensive disorders of pregnancy: Economic evaluation of the sFlt-1/PlGF test with real world implementation of biomarkers.

Background: Preeclampsia is a key cause of prematurity in the U.S. and incurs significant healthcare costs.

A Targeted Feedback Framework to Move the Needle on Operative Feedback.

Objective: Actionable and impactful feedback remains a perpetual challenge in medical education despite extensive efforts to improve the feedback process. A feedback framework was adapted from a validated model and tailored to a single residency program. The purpose of this study was to evaluate the impact of the new feedback framework on the quantity and quality of perioperative feedback amongst surgical residents.

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.

Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

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.

Generative Model for Constructing Reaction Path from Initial to Final States.

Mapping the chemical reaction pathways and their corresponding activation barriers is a significant challenge in molecular simulation. Given the inherent complexities of 3D atomic geometries, even generating an initial guess of these paths can be difficult for humans. This paper presents an innovative approach that utilizes neural networks to generate initial guesses for reaction pathways based on the initial state and learning from a database of low-energy transition paths.

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.

Assessment and Reporting of Extraintestinal Manifestations and Fatigue in Phase 3 Inflammatory Bowel Disease Clinical Trials.

Background: Extraintestinal Manifestations (EIMs) of Inflammatory Bowel Disease (IBD) are frequently experienced by patients and may lead to severe symptoms and fatigue. However, the reporting patterns of these outcomes in IBD randomized controlled trials (RCTs) is not clear.

Methods: We searched placebo controlled phase 3 RCTs of advanced therapies in IBD and assessed the frequency and means of reporting EIM and fatigue data in these studies.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Establishing Reference Values in the Neuromuscular Ultrasound Laboratory Using the e-Norms Method: A Feasibility Study.

Introduction/aims: The standard procedure to establish reference values in a neuromuscular laboratory involves examining healthy controls, as nerve size varies with the population and muscle echo intensity (EI) is device-specific. We aimed to derive these reference values by extrapolation from a studied sample (the e-norms method), compare them with published reference values, and determine their diagnostic accuracy.

Methods: We retrospectively analyzed data from consecutive patients who underwent nerve and/or muscle ultrasound in our ultrasound laboratory, which is a tertiary referral center for neuromuscular diseases in Southern Poland in the years 2018-2023.

Innovative Insurance to Improve US Patient Access to Cell and Gene Therapy.

Unlabelled: Policy Points Cell and gene therapies (CGTs) offer treatment for rare and oftentimes deadly disease, but their prices are high, and payers may seek to limit spending. Total annual costs of covering all existing and expected CGTs for the entire US population 2023-2035 to amount to less than $20 per person and concentrate in commercial and state Medicaid plans. Reinsurance fees add to expected costs.

Bridging Therapies-Ex Vivo Liver Xenoperfusion and the Role of Machine Perfusion: An Update.

Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models.

Hypertensive disorders of pregnancy and gestational diabetes mellitus and predicted risk of maternal cardiovascular disease 10-14 years after delivery: A prospective cohort.

Aims: Studies evaluating the relationship between adverse pregnancy outcomes (APOs), namely hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), with the estimated risk of atherosclerotic cardiovascular disease (ASCVD) remains limited and could inform patient-centred decision-making in the postpartum period. We examined whether HDP or GDM were associated with a higher 10- and 30-year predicted risk of ASCVD measured 10-14 years after delivery.

Methods: A secondary analysis from the international prospective Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (2013-2016) cohort.

Survey and perspective on verification, validation, and uncertainty quantification of digital twins for precision medicine.

Digital twins in precision medicine provide tailored health recommendations by simulating patient-specific trajectories and interventions. We examine the critical role of Verification, Validation, and Uncertainty Quantification (VVUQ) for digital twins in ensuring safety and efficacy, with examples in cardiology and oncology. We highlight challenges and opportunities for developing personalized trial methodologies, validation metrics, and standardizing VVUQ processes.

Oxytocin levels in response to CRH administration in hypopituitarism and hypothalamic damage: a randomized, crossover, placebo-controlled trial.

Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in patients with hypopituitarism and hypothalamic damage (HHD), that might be associated with neuropsychological deficits and sexual dysfunction, leading to worse quality of life (QoL). Therefore, identifying a provocative test to diagnose an OXT-D will be important. Corticotropin-releasing hormone (CRH) is a candidate for such a test as it increases oxytocin secretion in animal models.

Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.