Unveiling inverted D genes and D-D fusions in human antibody repertoires unlocks novel antibody diversity.

Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination.

A morphometric signature to identify ductal carcinoma in situ with a low risk of progression.

Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections.

OCT-based diagnosis of glaucoma and glaucoma stages using explainable machine learning.

Glaucoma poses a growing health challenge projected to escalate in the coming decades. However, current automated diagnostic approaches on Glaucoma diagnosis solely rely on black-box deep learning models, lacking explainability and trustworthiness. To address the issue, this study uses optical coherence tomography (OCT) images to develop an explainable artificial intelligence (XAI) tool for diagnosing and staging glaucoma, with a focus on its clinical applicability.

The effect of sarpogrelate compared to aspirin in high- or very-high-risk diabetes for primary prevention.

The benefit of aspirin in primary prevention for atherosclerotic cardiovascular diseases (ASCVD) is questionable due to bleeding complications. We analyzed the Korean National Health Insurance data to compare the efficacy and overall bleeding of sarpogrelate, an antiplatelet agent with lower bleeding risk, versus aspirin in high-/very-high-risk diabetic populations without prior ASCVD. The primary endpoint was net adverse clinical events (NACE), defined as a composite of efficacy and overall bleeding.

Differences in clinical characteristics between coronavirus disease 2019 (COVID-19) and influenza: a systematic review and meta-analysis.

The coronavirus disease 2019 (COVID-19) epidemic has brought major challenges to the global health system, and influenza is also a problem that cannot be ignored. We aimed to explore and compare the clinical characteristics of COVID-19 and influenza to deepen the understanding of these two diseases and provide some guidance for clinicians to make differential diagnoses. We searched PubMed, Embase and Web of Science for articles and performed a meta-analysis using Stata 14.

Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut.

Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens.

Half of land use carbon emissions in Southeast Asia can be mitigated through peat swamp forest and mangrove conservation and restoration.

Southeast Asia (SEA) contributes approximately one-third of global land-use change carbon emissions, a substantial yet highly uncertain part of which is from anthropogenically-modified peat swamp forests (PSFs) and mangroves. Here, we report that between 2001-2022 land-use change impacting PSFs and mangroves in SEA generate approximately 691.8±97.

Structure and function of a near fully-activated intermediate GPCR-Gαβγ complex.

Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-Gαβγ structures, these snapshots primarily capture the fully activated complex. Consequently, the functions of intermediate GPCR-G protein complexes remain elusive.

Interleaflet Translocation of Second-Harmonic-Generation-Active Dye Molecules in Phospholipid Bilayers with Transmembrane Pores.

Second harmonic generation (SHG) measurements using SHG-active dye molecules have recently attracted attention as a method to detect the formation of pores in phospholipid bilayers. The bilayers, in which the dye molecules are embedded in the outer leaflet, exhibit a noncentrosymmetric structure, generating SHG signals. However, when pores form, these dye molecules translocate through the pores into the inner leaflet, leading to a more centrosymmetric structure and the subsequent loss of the SHG signals.

Take your PIC (Program Improvement Committee): The benefits of a resident-run initiative to improve graduate medical education.

The evolving landscape of graduate medical education (GME) necessitates innovative approaches to residency program evaluation and improvement. At Detroit Medical Center/Wayne State University, a novel resident-led Program Improvement Committee (PIC) was established in June 2022 within the Diagnostic Radiology Residency Program. The PIC serves as a flexible, resident-driven structure designed to enhance engagement, provide continuous feedback, and implement actionable solutions in collaboration with residency leadership.

Ligand-restricted synNotch switches enable precision cell therapy.

Lim and colleagues demonstrate that synNotch transcriptional circuits engineered into T cells can be used to precisely control location-specific expression of payloads responding to antigen triggers, thus locally inhibiting unwanted immunity or neuroinflammation. With no off-tumor toxicity or systemic immunosuppression upon elimination of mouse brain tumors, this approach can achieve better efficacy than anticipated.

Neonatal unit admission and offspring mental health trajectories across childhood and adolescence: a nationally representative UK cohort study.

Objective: To investigate the associations between neonatal unit admission (NNU) and subsequent emotional and behavioural difficulties during childhood and adolescence.

Design: Longitudinal general population cohort study.

Setting: The Millennium Cohort Study: nationally representative UK-based cohort.

Quantitative Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) Analysis of Macular Microvascular Alterations in Bietti Crystalline Dystrophy.

Purpose: Bietti crystalline dystrophy (BCD) is a rare retinal dystrophy characterized by progressive visual impairment. This study aimed to evaluate changes in retinal and choroidal vessels and blood flow in BCD patients using swept-source optical coherence tomography angiography (SS-OCTA) and to investigate potential parameters associated with visual function.

Methods: This cross-sectional study included 166 eyes from 86 clinically diagnosed BCD patients, classified into three disease stages based on Yuzawa's classification.

Investigating the Multigenerational Effects of DDT Residues Exposure on Dental Development in Wistar Rats.

The pesticide Dichlorodiphenyltrichloroethane (DDT) and its degradation by-products (Dichlorodiphenyldichloroethane-DDD and dichlorodiphenyldichloroethylene-DDE) are health concerns. This study aimed to investigate the impact of multigenerational exposure to traces of DDD and DDE on odontogenesis Wistar rats were allocated in 4 groups over 2 generations (F1 and F2). Water was provided ad libitum throughout the animal's life groups: control - natural water; DDD - 0.

Felix A. Conte, MD 1935-2024. The endocrinologist's endocrinologist.

is not a required field for Obituaries.

Analysis of TEM micrographs with deep learning reveals APOE genotype-specific associations between HDL particle diameter and Alzheimer's dementia.

High-density lipoprotein (HDL) particle diameter distribution is informative in the diagnosis of many conditions, including Alzheimer's disease (AD). However, obtaining an accurate HDL size measurement is challenging. We demonstrated the utility of measuring the diameter of more than 1,800,000 HDL particles with the deep learning model YOLOv7 (you only look once) from micrographs of 183 HDL samples, including patients with dementia or normal cognition (controls).

Survival improvements in patients with melanoma brain metastases and leptomeningeal disease in the modern era: Insights from a nationwide study (2015-2022).

Introduction: Advances in modern therapies have improved outcomes for patients with melanoma brain metastases (MBM), though prognosis remains poor. The optimal treatment strategy for patients who do not meet clinical trial inclusion criteria is unclear.

Methods: This study included all patients with MBM diagnosed in Denmark between 2015 and 2022, identified through the Danish Metastatic Melanoma Database (DAMMED) and local surgical and radiotherapy records.

Psychiatric disorders in adolescent and young adult cancer survivors in Korea.

Background: Although adolescent and young adult (AYA) cancer survivors have an increased risk of psychiatric disorders, limited evidence has been suggested. We aimed to determine the risk of psychiatric disorders among AYA cancer survivors.

Materials And Methods: A retrospective population-based cohort study based on the Korea National Health Insurance Service database was carried out.

Natural history progression of MRI brain volumetrics in type II late-infantile and juvenile GM1 gangliosidosis patients.

Objective: GM1 gangliosidosis is a rare lysosomal storage disorder characterized by the accumulation of GM1 gangliosides in neuronal cells, resulting in severe neurodegeneration. Currently, limited data exists on the brain volumetric changes associated with this disease. This study focuses on the late-infantile and juvenile subtypes of type II GM1 gangliosidosis, aiming to quantify brain volumetric characteristics to track disease progression.

Exploring the neuroprotective potential of immunosuppressants in Parkinson's disease.

Introduction: Neuroprotective therapy to slow Parkinson's disease (PD) progression is a critical unmet need. Neuroinflammation likely represents an important pathophysiologic mechanism for disease progression. Medications that target this inflammation, such as immunosuppressants, represent potential disease-modifying therapies for PD.

Sex-Based Bias in Artificial Intelligence-Based Segmentation Models in Clinical Oncology.

Artificial intelligence (AI) advancements have accelerated applications of imaging in clinical oncology, especially in revolutionizing the safe and accurate delivery of state-of-the-art imaging-guided radiotherapy techniques. However, concerns are growing over the potential for sex-related bias and the omission of female-specific data in multi-organ segmentation algorithm development pipelines. Opportunities exist for addressing sex-specific data as a source of bias, and improving sex inclusion to adequately inform the development of AI-based technologies to ensure their fairness, generalizability and equitable distribution.

Utilization of AF4 for characterizing complex nanomaterial drug products: Reexamining sample recovery and its impact on particle size distribution as a quality attribute.

Asymmetrical flow field-flow fractionation (AF4) with multi-detection has continued to gain wider acceptance for characterizing complex drug products. An important quality attribute for these products is the measurement of the particle size distribution (PSD). Current limitations of established procedures (e.