Communications medicine最新文献

Background: Deep learning faces a significant bottleneck in medical image analysis due to its reliance on large-scale, expert-annotated datasets. This challenge is acute in ophthalmology, particularly for detecting early-stage diseases like mild Diabetic Retinopathy (DR1), where subtle lesions and a scarcity of annotations limit supervised learning approaches.

Methods: We propose a generalizable eye disease detection framework based on Zero-shot Learning (ZSL) that mimics clinical reasoning. Using the LCFP-14M dataset, a large-scale fundus image resource we present in this work, our method first identifies disease correlations via a Siamese network. It then transfers knowledge by segmenting DR1-specific lesions from a highly correlated source disease and employs a ResNet-Agglomerative clustering pipeline to enable unsupervised detection of DR1 without using any labeled DR1 cases.

Results: Here we show that the proposed framework enables effective DR1 detection without annotated DR1 data. The model achieves an accuracy of 0.8337, precision of 0.8700, recall of 0.7456, F1 score of 0.8030, and ROC-AUC of 0.9226, outperforming most supervised baselines on external test datasets.

Conclusions: Our findings demonstrate that ZSL can simulate clinical diagnostic logic and generalize to unseen eye diseases, offering a promising approach for automated screening where labeled data are scarce.

Background: Prenatal growth is shaped by genetic and environmental influences. Prenatal exposure to famine, particularly later in gestation, stunts growth and leads to lower birth weight. Here, we evaluated the effect of prenatal famine exposure on the expression of genetic influences on birth weight and how this relationship shapes associations between the early environment and metabolic disease risk in later life.

Methods: We analysed data from the Dutch Hunger Winter Families Study, including 283 individuals conceived in the months before the 1944-45 Dutch Famine and therefore exposed during mid-to-late gestation, 145 conceived during the famine and thus exposed in early gestation, and 161 unexposed controls with available obstetric records and genetic data. Genetic influences on birth weight were assessed using a polygenic index (PGI). We tested for gene-environment interactions between the birth weight PGI and the timing of famine exposure, and examined whether deviations from genetically predicted birth weight were associated with fasting glucose and waist circumference in adulthood.

Results: While the birth weight PGI explains 14% of the variation in birth weight in controls (r = 0.38, p < 0.001), genetics does not have a detectable influence on birth weight in famine-exposed individuals, particularly those exposed in mid-to-late gestation (r = 0.10, p = 0.09) (p_interaction<0.001). Six decades later, being born lighter than genetically predicted is associated with increased fasting glucose levels and waist circumference in those exposed to famine in mid-to-late gestation as compared to controls (p_interaction<0.04).

Conclusions: Prenatal exposure to famine during mid-to-late gestation overrides genetic influences on birth weight and modifies the relationships that are observed between birth weight and metabolic risk factors in later life.

Background: Hepatectomy is considered advisable for some patients with intermediate or advanced hepatocellular carcinoma (HCC). The efficacy and safety of neoadjuvant transarterial chemoembolization with tyrosine kinase and immune checkpoint inhibitors (neoadjuvant triple therapy) for these patients remain unclear.

Methods: 583 patients who met the resectable criteria and were assigned to receive neoadjuvant triple therapy (n = 205) or direct hepatectomy (n = 378) at 20 Chinese medical centers (2019-2023) were retrospectively compared in terms of overall survival (OS), event-free survival (EFS), adverse events, and postoperative complications. The subgroup stratified includes 106 patients who underwent neoadjuvant triple therapy followed by hepatectomy or 99 patients who received it without subsequent hepatectomy.

Results: Compared to patients who undergo direct hepatectomy, those who receive neoadjuvant triple therapy show significantly higher OS (hazard ratio [HR] 0.70, 95%CI 0.53-0.92) and significantly longer median EFS (19.7 vs 10.9 months). Similar results are obtained after propensity score matching (PSM). Among patients who undergo hepatectomy, those with prior neoadjuvant triple therapy have significantly better OS (HR 0.45, 95%CI 0.31-0.66) and EFS (HR 0.49, 95%CI 0.38-0.63) than those with direct hepatectomy. Similar results are obtained after PSM. Among patients who receive neoadjuvant triple therapy, OS is significantly better among those who subsequently underwent hepatectomy (HR 0.40, 95%CI 0.24-0.67). neoadjuvant triple therapy results in a complete pathologic response rate of 34.0%. However, the regimen is associated with high rates of serious adverse events and postoperative complications, including hepatic insufficiency, bile leakage, and ascites.

Conclusions: Neoadjuvant triple therapy offers OS and EFS benefits for patients with resectable intermediate or advanced HCC, but is associated with an increased risk of adverse events and postoperative complications.

Background: Exercise training often produces less weight loss than expected, a phenomenon termed exercise-induced energy compensation, but the underlying mechanisms remain unclear. This study aimed to quantify metabolic and behavioral compensation to aerobic exercise training.

Methods: Sixteen sedentary adults with overweight completed a 12-week supervised aerobic walking intervention targeting an energy expenditure of 20 kcal/kg/week. Total daily energy expenditure was measured using doubly labeled water, and whole-room calorimetry was used to assess changes in resting and sleeping metabolic rate (RMR, SMR) and diet-induced thermogenesis (DIT). Volumes of highly metabolic organs were quantified by magnetic resonance imaging. Physical activity was monitored objectively, walking economy was assessed during standardized treadmill walking, and dietary intake was evaluated using self-report and intake-balance methods. A parallel mouse exercise model was used to explore tissue-level adaptations.

Results: Exercise training induces substantial energy compensation, resulting in minimal body weight loss despite improved body composition. Total daily energy expenditure increases, while RMR and SMR decrease, accounting for most of the compensatory response. Liver and kidney volumes decrease by 5%, while brain volume remains unchanged. Exercise improves walking economy and leads to smaller-than-expected increases in daily moderate-to-vigorous physical activity. Dietary intake and DIT remain unchanged. In mice, exercise is associated with increased cellular density and mitochondrial content in the liver, indicating structural and metabolic remodeling.

Conclusions: Aerobic exercise training engages compensatory physiological and behavioral mechanisms that constrain energy expenditure. Reductions in basal metabolism, improved movement efficiency, and selective remodeling of metabolically active organs may collectively limit exercise-induced weight loss.

Background: The most investigated form of autoimmune-long-QT-syndrome (LQTS) is caused by circulating anti-Ro/SSA(Sjögren's syndrome-related antigen-A)-52kD antibodies, which cross-react with a specific sequence of the human ether-à-go-go-related (hERG) potassium channel's pore region, reducing the rapid inward-rectifying potassium current (I_Kr) density. We designed the scaffolded monobody decoy peptide-4, MDP4, comprised of a segment of the hERG extracellular pore region fused to a carrier monobody, aiming to neutralize the circulating anti-Ro/SSA-52kD antibodies cross-reacting with hERG.

Methods: MDP4 was designed using 3D-structure-based protein engineering and optimized via conformational search and energy minimization. QT-interval prolongation was induced in an established guinea pig model of autoimmune-associated LQTS via injection of Ro/SSA-52kD antigen over 15 days. Upon confirmation of QT-interval prolongation, MDP4 was administered, and electrocardiogram parameters were monitored for 30 days. I_Kr and action potentials were measured using the patch-clamp technique in guinea pig ventricular cardiomyocytes treated with IgG isolated from the sera of an anti-Ro/SSA-52kD antibody-positive patient with LQTS and Torsades de Pointes.

Results: Guinea pigs immunized with Ro/SSA-52kD antigen exhibit QTc prolongation and hERG-cross-reactive anti-Ro/SSA-52kD serum antibodies. In vivo treatment with MDP4 reverses QTc prolongation. MDP4 in vitro treatment of guinea pig ventricular myocytes also reverses I_Kr inhibition and action potential duration prolongation by anti-Ro/SSA-52kD antibodies from patients with LQTS and Torsades de Pointes.

Conclusions: Treatment with MDP4 results in recovery of both the QT-interval prolongation in vivo and I_Kr inhibition in vitro. MDP4 and other conceptually similar molecules may represent an innovative therapeutic approach for autoimmune LQTS in humans, and, prospectively, for other forms of arrhythmogenic autoimmune cardiac channelopathies.

Background: Head and Neck Squamous Cell Carcinomas (HNSCC) are the seventh most prevalent form of cancer and are associated with human papilloma virus infection (HPV-positive) or with tobacco and alcohol use (HPV-negative). HPV-negative HNSCCs have a high recurrence rate, and individual patients' responses to treatment vary greatly due to the high level of cellular heterogeneity of the tumor and its microenvironment.

Methods: Here, we describe a HPV-negative HNSCC single cell atlas, which we created by integrating six publicly available datasets encompassing over 230,000 cells across 54 patients. We classify cell types, subpopulations, and their expression programs in the immune, mesenchymal, endothelial and epithelial compartments. We interrogate the relationship between cell types through hierarchical clustering, cell-cell communication analysis and correlating populations changing together across patients.

Results: We resolve the myeloid and fibroblast compartments, revealing an IL1B+ myeloid population previously unexplored in HNSCC and clarifying two immune cancer associated fibroblast populations that are frequently conflated, identify sex-associated changes in cell type proportions, and a unique interaction between CXCL8-positive fibroblasts and vascular endothelial cells.

Conclusions: We utilize the atlas to contextualize the relationships between existing signatures and cell populations, harmonize nomenclature across studies, and show the power of this large-scale resource to robustly identify associations between transcriptional signatures and clinical phenotypes that would not be possible to discover using fewer patients. Beyond our findings, the atlas serves as a public resource for the high-resolution characterization of tumor heterogeneity of HPV-negative HNSCC.

Background: Obesity is a major health concern linked to chronic conditions such as diabetes and cardiovascular disease. However, most neurological studies have focused on specific metabolic states, limiting understanding of how brain function changes from fasting to satiety. Furthermore, hypothesis-driven approaches may introduce bias and fail to capture complex neural interactions. This study aimed to identify brain connectivity patterns associated with obesity across different metabolic states using a data-driven approach.

Methods: Electroencephalography data were collected from 30 women with obesity and 30 women without obesity over a four-hour period encompassing fasting and post-meal states. All subjects were aged 20 to 65 years. Functional connectivity was calculated from source-localized signals, and a machine learning framework incorporating a feature selection method was applied to identify the most discriminative connectivity features between groups.

Results: Here we show that six connectivity features classify obesity with 95% accuracy across metabolic states. Reduced connectivity are observed within food-reward processing regions in the obese group, with the dorsal anterior cingulate cortex emerging as a central hub. This pattern reflects a persistent alteration in energy prediction and craving regulation that is independent of metabolic state.

Conclusions: These findings demonstrate that disrupted brain connectivity is a fundamental characteristic of obesity. The results highlight the dorsal anterior cingulate cortex as a key region underlying maladaptive reward processing and suggest that targeting this area through neuromodulation therapies may offer a promising intervention for obesity treatment.

Background: Tuberculosis (TB) is one of the leading causes of death worldwide, even though it is curable using antibiotics. Most people who die of TB never begin treatment because diagnostics are insufficiently sensitive and accessible. We aimed to measure low-abundance biomarkers and diagnose TB in urine.

Methods: We developed and clinically validated a multiplex Single Molecule Array (Simoa) assay to detect TB in urine by measuring two TB biomarkers: lipoarabinomannan (LAM) and antigen 85B (Ag85B). Using antibodies that recognize different epitopes of LAM in a four-plex assay with three LAM and one Ag85B antibody pairs, we trained a model and demonstrated its performance in retrospective cohorts totaling 576 individuals from South Africa, Peru, Vietnam, and Cambodia, including a blinded test cohort (n = 215).

Results: Here we present an assay that classifies samples with 98% specificity, 45% sensitivity overall, and 58% sensitivity among people living with the human immunodeficiency virus (HIV).

Conclusions: Different antibody pairs detecting different epitopes on LAM report diverging concentrations. We do not find that adding antibody pairs to detect different epitopes on LAM improves the assay's accuracy. Our assay is more sensitive than the existing AlereLAM lateral flow test for TB in HIV-positive individuals, uses safe and accessible urine samples, and represents a step towards an adjunctive diagnostic test to aid clinicians in starting treatment.

Background: An increasing number of children and adults who are deaf are receiving cochlear implants in both ears (bilateral CIs or BiCIs), promoting the possibility of access to binaural cues. However, their effectiveness remains limited, as they do not adequately restore key acoustic cues for sound localization, particularly interaural time differences (ITDs) at low frequencies. The cochlea, the auditory sensory organ, typically transmits information for encoding ITDs more effectively at the apical region, which is specifically "tuned" to low frequencies. However, sensitivity to electrically-stimulated ITDs does not necessarily follow the non-implanted anatomy. We hypothesized that effective restoration of robust ITD perception through electrical stimulation with BiCIs depends on targeting cochlear locations that transmit information most effectively.

Methods: We created a personalized sound-coding strategy that delivered ITDs to each participant's single "best" cochlear location. We then evaluated the spatial hearing of 14 BiCI listeners using this "Best" strategy and compared it with three control strategies.

Results: Here, we show an improvement in perception of ITDs with a tone stimulus with the "Best" strategy. However, this benefit does not seem to translate to speech stimuli.

Conclusions: This suggests that restoration of ITD sensitivity requires targeting more than one good cochlear location for redundancy when it comes to more complex sounds such as speech.

Background: Although New York City (NYC) is a hotspot for hepatitis delta virus (HDV) in the United States (US), the epidemiology of HDV remains poorly understood. We aimed to determine HDV testing and positivity rates, calculate prevalence of liver disease progression by HDV status, and assess the association between HDV and community resources.

Methods: We utilized the INSIGHT database, which contains data from the five major NYC health systems, to identify adults with laboratory and/or diagnosis code evidence of hepatitis B virus (HBV) from 2010-2023. HDV positivity included HDV RNA ≥ 20 IU/mL and/or positive results for HDV Ab, RNA, and Ag. Prevalence of liver-related complications was calculated. Community deprivation index was used to evaluate socioeconomic disparities by HDV testing and positivity status.

Results: Here we show that among 106,210 patients with HBV, 5,388 (5.1%) have received HDV testing; 294 (5.5%) are HDV + . HDV-tested individuals are more likely to be older and Asian, receive comprehensive HBV care, and have more community resources. HDV+ individuals are more likely to be female, White, and have higher prevalence of liver disease progression.

Conclusions: HDV is undertested and under-detected, even in a high-prevalence US region. Early linkage to treatment is essential given high rates of liver disease progression.