Communications medicine最新文献

Background: Maternal chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes. However, the overall risk of congenital malformations (CMs) in offspring of mothers with kidney disease, including CKD and end-stage kidney disease (ESKD), remains unclear.

Methods: In this nationwide cohort study, we analyzed National Health Insurance Service (NHIS) data from 2,680,092 women who gave birth between 2008 and 2017. Major CMs were identified using the International Classification of Diseases-10 (ICD-10) codes during the first 12 months after birth. A multivariable generalized estimating equation model was used to compare the risk of CMs between women with CKD or ESKD, including those on dialysis and post-kidney transplantation (KT), and healthy controls.

Results: Major CMs prevalence is 4.79% in offspring of healthy mothers, 5.29% in CKD mothers, and 9.65% in ESKD mothers, with congenital heart defects being the most common anomaly across all groups. After adjustment, mothers with kidney diseases show a higher risk of major CMs than healthy controls (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03-1.11 in CKD; aOR, 1.71; 95% CI, 1.16-2.52 in ESKD, respectively). Among ESKD patients, KT recipients show an increased risk (aOR, 1.65; 95% CI, 1.06-2.59), but dialysis patients do not reach statistical significance (aOR, 2.02; 95% CI, 0.92-4.41).

Conclusions: Our findings suggest that neonates born to mothers with kidney diseases have an increased risk of CMs compared to those born to healthy mothers.

Background: Parkinson's disease is a progressive neurodegenerative disorder with both motor and non-motor symptoms. Mental and behavioural non-motor symptoms such as cognitive impairment, sleep disturbances, depression, and anxiety greatly affect quality of life but remain difficult to assess with traditional tools. Artificial intelligence has shown potential in healthcare, yet its role in evaluating these symptoms in Parkinson's disease remains under-reviewed. This systematic review aims to evaluate the performance of artificial intelligence tools in diagnosing, assessing, and managing these symptoms.

Methods: Five databases (Medline, Embase, Scopus, Web of Science and PubMed) were searched up to June 2024 for peer-reviewed studies applying artificial intelligence to mental or behavioural symptoms in adults with Parkinson's disease. Studies published before 2010 or lacking artificial-intelligence technologies were excluded. Study quality and risk of bias were assessed using QUADAS-2. Extracted data include study objectives, data sources, algorithms, best model, and diagnostic performance (accuracy, sensitivity, specificity). The study received no external financial support.

Results: Here we show sixteen studies examine cognitive impairment and seven examine sleep disorders. However, only three studies focus on depression and one on anxiety, revealing a research gap. No meta-analysis was performed due to heterogeneity.

Conclusions: Artificial intelligence shows promise for assessing mental and behavioural symptoms in Parkinson's disease, particularly cognitive and sleep disorders. Multimodal models demonstrate higher accuracy than single-source models, though external validation is necessary. The limited studies on depression and anxiety reflect existing diagnostic challenges and data limitations. Future research should refine diagnostic tools and expand multimodal approaches to these symptoms.

Background: Vascular properties of the retina are indicative of both ocular and systemic cardio- and cerebrovascular health. However, the specific relationships between retinal and non-retinal vascular phenotypes have not been systematically investigated in large samples. This study aims to compare cross-organ phenotypic and genetic relationships between vascular characteristics across different body sites.

Methods: We compared vascular image-derived phenotypes from the brain, carotid artery, aorta, and retina, using UK Biobank sample sizes ranging from 18,808 to 68,740 participants. We examined phenotypic and genetic correlations, as well as common associated genes and pathways.

Results: Here we show that white matter hyperintensities are positively correlated with carotid intima-media thickness (r = 0.03), lumen diameter (r = 0.14), and aortic cross-sectional areas (r = 0.09), but negatively correlated with aortic distensibilities (r ≤ -0.05). Arterial retinal vascular density shows negative correlations with white matter hyperintensities (r = -0.04), intima-media thickness (r = -0.04), lumen diameter (r = -0.06), and aortic areas (r = -0.05), while positively correlating with aortic distensibilities (r = 0.04). Significant correlations also persist after correcting for hypertension.

Conclusions: Our findings shed light on the complex interplay between vascular morphology across different organs, revealing both shared and distinct genetic underpinnings. Retinal vascular features reflect broader systemic vascular morphology and offer an accessible window into cardio- and cerebrovascular health.

Background: The population distribution of age-related functional impairments (ARFIs) and their associations with mortality and life expectancy (LE) among Chinese adults remain poorly understood.

Methods: We included 12,906 participants (mean age: 62.6 years) from the China Health and Retirement Longitudinal Study. Visual impairment, hearing impairment, cognitive impairment, sleep disorder, depressive symptoms, and disability in activities of daily living (ADL) were assessed. Cox proportional hazards models were used to estimate the associations of ARFIs with all-cause mortality. Life expectancy at age 50 was estimated by the presence and number of key ARFIs.

Results: The six ARFIs exhibit distinct distributions by ages and provinces across China. During the 9-year follow-up, ADL disability, cognitive impairment, and depressive symptoms are independently associated with 64% (95% confidence interval [CI]: 48%-80%), 41% (21%-64%), and 20% (8%-33%) higher risks of mortality, corresponding to LE losses of 4.45, 3.08, and 1.59 years at the age of 50 years. A greater number of key ARFIs is associated with higher mortality risk in a dose-response manner (hazard ratios [95% CI] vs. none: 1.23 [1.11-1.36] for one, 1.42 [1.26-1.61] for two, and 1.86 [1.47-2.36] for three) and greater LE loss (1.63 [1.35-1.90] years for one, 3.37 [3.02-3.71] for two, and 4.96 [4.22-5.71] for three, with three ARFIs accounting for 17% of total LE).

Conclusions: The study highlights the important roles of co-existing ARFIs in mortality and LE loss. Integrated prevention strategies and management systems for multiple functional impairments are warranted in the context of rapid population aging.

Background: Colorectal cancer (CRC) patients exhibit distinct gut microbiota disruption, known as dysbiosis, which is believed to play a causative role in CRC. One of the key bacterial species implicated in CRC dysbiosis is Bacteroides fragilis, which presents a paradox as it is also present in most healthy individuals. This discrepancy underscores the need for analysis beyond species-level associations and to investigate intraspecies variation within B. fragilis.

Methods: From a highly specific collection of B. fragilis isolates from CRC patients and controls, a pangenome-wide association study was conducted, identifying intraspecies genetic variations associated with CRC. The CRC association of these genetic variations were then validated in a metagenome sequencing cohort of faecal samples from 877 individuals, with and without CRC. To test group differences a mixed effects logistic regression with cohort as a random effect was performed for each genetic variation.

Results: Here we show that CRC-associated B. fragilis isolates are infected with specific Caudoviricetes prophages, significantly more often than negative controls. The initial discovery was made in our highly specific isolate collection and then validated in an independent metagenome sequencing cohort, finding that CRC patients were twice as likely to have detectable levels of these phages (OR = 2.05, p = 2.522E-7, SE = 0.139).

Conclusions: To our knowledge, these findings mark the first link between one of the most implicated driver bacteria and phages in CRC and suggest a more complex role of phages in CRC dysbiosis than current models suggest and highlights the potential of phages as CRC biomarkers.

Background: There are known sex disparities in temperature perception with lower thermal detection thresholds found in people assigned female at birth compared to people assigned male at birth. However, underlying mechanisms of these differences and the influences of sex hormones are not yet sufficiently understood.

Methods: To assess the effects of sex hormones on temperature perception, we measured in a prospective observational cohort study temperature detection and pain thresholds with quantitative sensory testing and subjective temperature sensation in transgender patients undergoing gender-affirming hormone therapy (GAHT). We included 12 trans women (male-to-female transgender) and 17 trans men (female-to-male transgender) before and 3 and 6 months after start of GAHT. As a control group, we measured 13 cis women and 10 cis men without hormone treatment at the same timepoints.

Results: Here we show that temperature detection thresholds in persons assigned female at birth at baseline are lower than in persons assigned male at birth. Accordingly, in trans women, temperature detection thresholds decrease with GAHT. Pain detection thresholds do not differ between sexes assigned at birth and do not change with time.

Conclusions: We demonstrate that in trans women undergoing GAHT with estradiol and cyproterone acetate sensitivity to temperature changes increases, consistent with the greater temperature sensitivity observed in cis women compared to cis men. Future studies need to assess at which neurobiological processing stages the relevant changes occur and what molecular mechanisms play a role.

Trial registration: NCT04838249.

Background: Congenital heart disease (CHD) affects about 1% of births and is linked to differences in thinking and learning. Understanding how birth, genetic, clinical, and environmental factors together explain cognitive variability can inform monitoring and care. This study builds a multivariate model predicting cognition across multiple domains in adolescents and young adults with CHD.

Methods: We studied 89 adolescents and young adults (AYAs; mean age 16 years) with CHD who completed structural and diffusion MRI and fifteen neurocognitive tests across seven domains. Using an enhanced forward-inclusion and backward-elimination strategy with cross-validation, we built multivariate models incorporating biological, socioeconomic, clinical, genetic, and brain imaging features. Performance was evaluated using Pearson correlation ($r$) between observed and inferred scores, mean absolute error (MAE), and inverse inferability score (IIS).

Results: Here we show that models infer scores with moderate accuracy ($r$ = 0.245-0.648; MAE = 1.6-12.0 points; mean MAE = 6.3). Highest correlations include Digit Span ($r$ = 0.65; p < 0.001), Verbal Comprehension Index ($r$ = 0.594; p < 0.001), and Matrix Reasoning ($r$ = 0.574; p < 0.001). Domain ranking by IIS shows the best (lowest) scores for general intelligence (0.0886), followed by working memory (0.7100), and a higher (worse) score for perceptual reasoning (1.9199).

Conclusions: A multivariate approach combining brain imaging with genetic, clinical, and environmental factors provides clinically meaningful inference of individual cognitive performance in AYAs with CHD. These findings suggest complementary roles of brain, genetic, and contextual factors in shaping cognitive variability and motivate validation in larger cohorts.

Background: Epigenetic modulators may sensitize platinum-resistant ovarian cancer (PROC) to immune checkpoint inhibition by reprogramming the tumor microenvironment.

Methods: We report clinical and translational findings from a phase II non-randomized study of pembrolizumab and oral azacitidine in 34 women with PROC (NCT02900560). Key eligibility criteria included age 18 years or older, performance status of 0-1, measurable disease, platinum-resistant disease and histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma. Primary endpoints included safety, tolerability, overall response rate (ORR) and disease control rate (DCR). Secondary endpoints included CA-125 response. The effect of combined epigenetic and immunotherapy was evaluated by transcriptomic analyses of 72 serially biopsied tumors.

Results: We show that the combination is moderately well tolerated and most common grade 3-4 adverse events are gastrointestinal side effects and anemia. ORR is 2.9% and DCR is 50%; with 3 of the 27 evaluable patients attaining a CA-125 response. Differential gene expression analyses reveal an upregulation of inflammatory and cytolytic genes and co-inhibitory checkpoints 6 weeks on-therapy. Upregulation of interferon signaling, antigen presentation and immune cell adhesion and migration gene sets are prominent on-therapy, together with an increase in density of CD8 + T-cells. Patients with a CA-125 and/or clinical response show an enrichment of adaptive and conserved immune response gene sets on-therapy.

Conclusions: Our findings highlight the potential of epigenetic modulators to re-shape the tumor microenvironment of PROC toward a more inflammed phenotype and may point to approaches to augment immunotherapy response.

Background: Desmoglein-2 (DSG2) is an essential cardiac desmosomal cadherin, and its alteration underlies a broad spectrum of arrhythmogenic cardiomyopathy (ACM). Yet, the clinical significance of many DSG2 variants remains uncertain. This study aimed to systematically characterize the spectrum, structural impact, and clinical relevance of DSG2 variants by integrating large-scale genomic evidence, published data, and a deeply phenotyped validation cohort.

Methods: We conducted a systematic literature review (115 studies; 145 curated variants) and analyzed population-scale datasets (3570 variants in gnomAD; 1847 in ClinVar). All variants were uniformly reclassified following ACMG/ClinGen criteria. A validation cohort of 95 Italian DSG2-carriers underwent detailed phenotyping. Structural modeling via AlphaFold, supported protein modeling, calcium-binding site prediction, and DynaMut stability analysis were performed to evaluate the functional consequences of key variants.

Results: Literature and database integration reveal domain-specific variant clustering, with high-impact missense variants enriched in calcium-binding extracellular domains, the furin cleavage site, and the intracellular PKP2-binding region. In the validation cohort, penetrance among genotype-positive relatives is 42%, while 13% of definite ACM cases experience major ventricular arrhythmias; transplantation and mortality each occur in 3%. Biallelic and digenic variants are associated with earlier onset and more severe biventricular involvement. Structural modeling confirms that pathogenic missense substitutions destabilize DSG2 architecture or impair calcium-dependent adhesion.

Conclusions: This study refines the classification of DSG2 variants and highlights the importance of domain-level and multilocus interpretation in ACM. These findings support comprehensive genetic screening, structural modeling for variant assessment, and lifelong follow-up of DSG2 carriers to improve diagnosis and risk stratification.

Background: It is commonly believed that Africa largely evaded the worst of the COVID-19 pandemic, with fewer cases than other continents. However, regional comparisons that ignore differences in testing intensity may misrepresent dynamics. Studying the spread and case-fatality relationship during COVID-19 across WHO regions requires explicitly adjusting for time-varying test volumes.

Methods: We build a weekly panel dataset spanning May 2020 to December 2021 for the WHO regions: Africa, Eastern Mediterranean, South-East Asia, the Americas, Western Pacific, and Europe. Data on tests, confirmed cases, and COVID-19-attributed deaths were sourced from Our World in Data. We apply a novel metric that corrects for fluctuating test volumes to quantify week-to-week acceleration in infections and in mortality. We then compare the frequency, magnitude, and timing of these acceleration episodes across regions.

Results: Accounting for testing dynamics, we show that Africa exhibits multiple infection-acceleration episodes whose magnitude and frequency match those in other regions. Mortality accelerations in Africa closely follow infection surges, with an average lag of ten weeks. A positive correlation between infection acceleration in Africa and the Americas further indicates synchrony. These findings hold when using a larger secondary dataset of 140 countries.

Conclusions: Contrary to prevailing assumptions, Africa was not spared from the pandemic's severe dynamics. Infection surges were on par with those elsewhere and were followed by mortality accelerations. These results underscore that accounting for testing variability is essential to accurately assess pandemic progression, and they highlight the urgent need to strengthen surveillance and healthcare capacity across all regions.