Communications medicine最新文献

Background: Despite rapid advances in treatment, breast cancer remains the leading cause of cancer mortality in women, with triple negative breast cancers having a particularly poor prognosis. Some tumors have (epi)genetic alterations causing homologous recombination deficiency, providing opportunities for targeted therapeutics including poly (ADP-ribose) polymerase inhibitors. However, the effects of targeted treatments are variable; therefore, functional assays are needed to predict the best personalized treatment options.

Methods: We developed a high-throughput spheroid-based assay using patient-derived breast cancer xenograft models sensitive and resistant to cisplatin. Methods were developed for automatic spheroid segmentation using deep learning to measure response of spheroids to treatment with cisplatin, olaparib and radiotherapy. We developed a method to distinguish between sensitive and resistant tumors based on predicting the percentage of responding and non-responding spheroids.

Results: Here we show that differences in treatment response between cisplatin-sensitive and resistant tumors faithfully correspond with the expected in vivo responses. The assay is able to discriminate between olaparib-sensitive and resistant tumors based on predicting the percentage of responding and non-responding spheroids.

Conclusions: We demonstrate that this assay, guided by automatic spheroid segmentation using deep learning, may report on the tumor's sensitivity to therapies with the potential to be applied to functional precision oncology for breast cancer.

Background: Epidemiological studies show associations between chronic noise exposure and disease, but the biological pathways remain poorly understood. In this explorative pilot study, we investigate the mechanisms that may link sleep disruption by environmental noise with disease, and the efficacy of a non-pharmacological intervention to mitigate these effects.

Methods: We conducted a cross-over trial (ClinicalTrials.gov: NCT05319262; 2022-03-09) where N = 12 healthy individuals slept for five consecutive nights in acoustically isolated bedrooms. Nights included one familiarisation night; one quiet baseline night; one night with road, rail and air traffic noise of levels 45-65 dB L_AS,max; one night with continuous 45 dB broadband pink noise; and one night with both traffic noise and pink noise. Sleep was measured with polysomnography. Perceived sleep quality and recouperation were measured with morning questionnaires. Daily blood samples were collected for metabolomics analysis.

Results: Here we show that discrete traffic noise events induced acute elevations of the odds ratio product, indicating acute sleep fragmentation, even while total sleep time and overall sleep macrostructure were preserved. Traffic noise is further associated with significant elevations in concentrations of leucine, lactic acid, and acetone relative to quiet control. Sleep and metabolic disturbances by traffic noise are attenuated when pink noise is played continuously throughout the night.

Conclusions: Noise-induced sleep fragmentation is followed by changes in metabolic processes that in the long-term may be precursors for cardiometabolic disorders. Masking of traffic noise by continuous, neutral sound may mitigate acute physiological sleep disturbance and downstream metabolic effects. These results should be interpreted cautiously, given the limited sample size and subject homogeneity.

Background: Chronic pain may involve both nociceptive pain driven by peripheral tissue damage and nociplastic pain reflecting central nervous system dysregulation, as in fibromyalgia. Electroacupuncture has been shown to modulate these pathways, but the underlying brain mechanisms remain unclear. This study investigated how electroacupuncture influences nociceptive-initiated and centrally maintained pain via changes in brain activation and functional connectivity.

Methods: In this randomized controlled trial (NCT02064296), female adults with fibromyalgia received either electroacupuncture (n = 19) or sham treatment with inactive laser stimulation (n = 25) over four weeks. Changes in brain activation and connectivity during evoked pressure-pain stimulation were assessed using functional magnetic resonance imaging before and after treatment. Here, we present a secondary analysis of data from the trial. Clinical outcomes assessed include pressure-pain tolerance and widespread pain, and analyses tested whether brain measures mediated treatment-related effects.

Results: Here we show that in the electroacupuncture group, reductions in widespread pain are associated with increases in pressure-pain tolerance. This relationship is mediated by greater activation of the primary somatosensory cortex and stronger connectivity between somatosensory and insular regions, consistent with a bottom-up mechanism linking peripheral nociceptive-initiated input to central nociplastic pain modulation. In contrast, the sham group shows reductions in widespread pain linked to decreased precuneus activity and precuneus-insula connectivity, consistent with a top-down process.

Conclusions: Electroacupuncture and sham treatments engage distinct neural pathways to influence pain perception. These findings highlight that electroacupuncture modulates nociceptive-initiated and nociplastic pain through a bottom-up sensory pathway, whereas sham treatment engages top-down control. This mechanistic dissociation may inform patient selection and optimization of acupuncture-based therapies for chronic pain.

Background: Paraneoplastic autoimmunity develops as consequences of immune reactions to cancer and exhibits a wide range of clinical manifestations. The autoimmune signs are often visible before the underlying malignancy is diagnosed, and a prompt diagnosis of paraneoplasia is crucial to enable early tumor detection. We characterized the immune responses underlying the severe mucocutaneous blistering disease paraneoplastic pemphigus.

Methods: We used a two-step approach to proteome-wide autoantibody repertoire analysis and independent validation in patients with paraneoplastic pemphigus (n = 84) and non-paraneoplastic autoimmune blistering diseases (n = 103).

Results: Our findings reveal that paraneoplastic pemphigus features a broad repertoire of disease-specific autoantibodies that mainly target tissue-specific proteins in the skin and mucous membranes. Importantly, we identify SERPINB3 as a major autoantibody target with an expression pattern and clinical association suggesting a role in bronchiolitis obliterans. Autoantibody profiles are similar across neoplasias, except in thymoma patients, who additionally express multiple cytokine autoantibodies.

Conclusions: Our findings reveal a disease-defining autoantibody repertoire in paraneoplastic pemphigus that corresponds with clinical manifestations and holds high potential for early cancer detection in patients with blistering disease.

Background: Abdominal aortic aneurysm (AAA) is a degenerative cardiovascular disorder prevalent with ageing. While accelerated biological ageing contributes to age-related diseases, its specific role in AAA risk remains unclear. This study investigates the relationships between biological ageing and risk of incident AAA and genetic predisposition to the disease.

Methods: This retrospective study used UK Biobank data from 350,483 participants without AAA at baseline. Biological age was assessed using Klemera-Doubal Method (KDMAge) and phenotypic age (PhenoAge) algorithms. Accelerated biological ageing was determined through residual analysis against chronological age, with values above 0 indicating accelerated ageing. Cox proportional hazards models evaluated the associations of biological age accelerations with AAA risk. Polygenic risk scores were calculated to evaluate genetic predisposition to AAA. We also examined the interactions between biological age accelerations and genetic predisposition on the risk of AAA.

Results: Here we show that participants with accelerated biological ageing have an elevated risk of AAA onset compared to those without, with hazard ratios (HRs) of 1.29 (95% CI 1.17-1.42) for KDMAge and 1.63 (95% CI 1.47-1.81) for PhenoAge. For joint associations, participants with accelerated biological ageing and high genetic risk have the highest risk of incident AAA (KDMAge: HR 2.15, 95% CI 1.81-2.54; PhenoAge: HR 2.72, 95% CI 2.26-3.28). There is a significant additive interaction between high genetic risk and accelerated biological ageing of PhenoAge.

Conclusions: Accelerated biological ageing is significantly associated with an increased risk of AAA incidence, suggesting its potential as a focal point for risk assessment and targeted intervention development.

Background: Frailty is often experienced by older adults, which can lead to long-term health problems. We aimed to examine associations with improvements in nutritional status, sarcopenia (age-related loss of skeletal muscle mass and strength), and frailty in four groups with different oral exercise frequencies.

Methods: We conducted a prospective, parallel multi-arm randomized controlled trial (Japan Registry of Clinical Trials (jRCT) 1062210063) to test the effects of oral exercise on frailty in older adults. Each intervention consisted of a standardized oral exercise protocol including neck exercises, lip exercises, and tongue movements, designed to improve oral function and reduce frailty. The primary outcome was the change in the number of frailty criteria from baseline to follow-up. Individuals aged ≥60 years were screened for frailty status using standardized criteria at the Department of Preventive Dentistry at Okayama University Hospital between October 2022 and December 2023. Those identified as pre-frailty or frailty were eligible and enrolled in the study. After screening 60 individuals, 58 eligible participants were randomly assigned using block randomization to one of four oral exercise frequency groups: 3 times/day & everyday, 3 times/day & 3 days/week, once/day & everyday, and once/day & 3 days/week. A two-way repeated measures analysis of variance was used to evaluate the impact of the four frequencies of oral exercise methods on frailty in older adults. Outcome assessors were blinded; participants were not.

Results: Here we show the results of the 58 participants. Group sizes are: 3 times/day & everyday (n = 14), 3 times/day & 3 days/week (n = 15), once/day & everyday (n = 14), once/day & 3 days/week (n = 15). The trial is completed as planned, and all randomized participants are analyzed. The main effect of time is significant for the number of frailty criteria (F = 14.803, p < 0.001, partial eta squared = 0.215). The mean changes from baseline to follow-up are -0.357 (95% Confidence Interval -0.787 to 0.073) in the 3 times/day & everyday group, -0.600 (95% Confidence Interval -1.255 to 0.055) in the 3 times/day & 3 days/week group, -0.571 (95% Confidence Interval -1.379 to 0.236) in the once/day & everyday group, and -0.600 (95% Confidence Interval -1.008 to -0.192) in the once/day & 3 days/week group. The main effect of time is also significant for the number of oral hypofunction criteria (F = 16.456, p < 0.001, partial eta squared = 0.234). No important adverse events or side effects related to the intervention were observed.

Conclusions: After conducting oral exercises for 3 months on older adults with pre-frailty or frailty, improvements in frailty are observed. Overall, these exercises could be a simple, low-cost way to support healthy aging in the community.

Background: Alcohol is the most widely consumed psychoactive substance globally, with significant cultural acceptance. While extensive research has examined its relationship with well-being, cross-country comparisons are essential to understanding demographic variations in drinking patterns-particularly given the lack of post-pandemic data across diverse national contexts. This study aims to describe cross-national demographic variations in alcohol use among countries participating in the Global Flourishing Study (GFS).

Methods: Using nationally representative data from 22 GFS countries (N = 202,898), we conducted a descriptive analysis of weekly alcohol consumption, examining (1) the mean number of drinks per week, (2) the prevalence of weekly alcohol use, and (3) the mean number of drinks per week among drinkers across demographic groups (age, gender, marital status, employment, education, religious service attendance, and immigration status). A random-effects meta-analysis was conducted to synthesize country-level estimates.

Results: We find significant variations across demographic groups and countries. Men, certain age categories, highly educated and employed individuals, as well as those who are divorced, separated, or cohabitating, report higher alcohol intake. Religious service attendance is generally associated with lower alcohol use.

Conclusions: This study highlights significant cross-national differences in alcohol consumption, shaped by demographic, socioeconomic, and cultural factors. Western, educated, industrialized, rich, and democratic countries and those with a lower prevalence of Muslim populations tended to report higher alcohol consumption. Religious salience should be considered in demographic studies on alcohol use. These cross-national differences underscore the need for context-specific research to inform effective alcohol policies tailored to each country's characteristics.

Background: We know relatively little about how mental health varies across countries around the world or among demographic groups in diverse nations and cultures.

Methods: The current study addresses these issues by analyzing symptoms of depression and anxiety using data from the Global Flourishing Study (GFS), an international, nationally-representative survey of 202,898 individuals from 22 geographically, economically, and culturally diverse countries collected in 2022-2023.

Results: Here we show that proportions of individuals with substantial symptoms of depression range from 0.14 in Poland to 0.50 in the Philippines. These two countries report the lowest and highest substantial symptoms of anxiety as well (0.13 and 0.48, respectively). Lower-income, non-Western countries tend to have higher proportions of both outcomes compared with higher-income, predominantly Western nations. Symptoms of depression and anxiety also vary across age, gender, marital status, education, employment status, religious service attendance, and immigration status in one or more countries. The results of random effects meta-analyses show that several demographic factors are significant predictors of both outcome variables when the results for all 22 countries are pooled.

Conclusions: While being mindful of varying cultural contexts and possible translation and interpretive issues with the survey questions, the results suggest substantial variations in symptoms of both depression and anxiety across nations and key demographic groups. This work lays the foundation for future longitudinal GFS studies of mental health from a cross-national and global perspective.

Background: Peru recorded one of the world's highest COVID-19 mortality rates, with nearly 4.5 million reported cases and 220,000 deaths by March 2024. Understanding the emergence and spread of SARS-CoV-2 variants in this context is key to informing effective public health responses. This study describes the genomic diversity, transmission dynamics, and geographic spread of SARS-CoV-2 in Peru from 2020 to 2024.

Methods: We analyzed nearly 50,000 high-quality public SARS-CoV-2 genome sequences collected nationwide between March 2020 and March 2024. Phylogeographic and mutational analyses were performed to identify variant lineages, trace their origins, and map viral movements within and beyond Peru.

Results: We show that Peru's epidemic waves were shaped by the emergence of locally evolved variants, including Lambda (C.37), Gamma (P.1.12), and Omicron (XBB.2.6 and DJ.1) sub-lineages. The city of Lima acted as the primary hub for inter-regional spread, accounting for 47.3% of inferred viral movements to other departments, notably Ancash, Cusco, and Piura. Peru was the source of various lineages that spread internationally, primarily to Chile, the USA, and Europe. Mutational analysis highlighted critical mutations in the spike protein, including L452Q and F490S in Lambda, associated with immune evasion and increased transmissibility.

Conclusions: This work demonstrates the capacity of genomic surveillance in Peru to detect and track emerging SARS-CoV-2 variants, providing insights into regional and global transmission dynamics in a high-transmission, middle-income country setting. Sustained, cost-effective genomic monitoring, combined with strengthened bioinformatics and laboratory capacity, is essential for pandemic preparedness in resource-limited settings.

Background: Heart diseases in children and teenagers, including congenital and non-congenital cardiovascular diseases remain major causes of illness and death worldwide. Yet, long-term patterns and recent changes are poorly understood. This study explores global trends and inequalities in their burden.

Methods: We used data from the Global Burden of Disease 2021 study to examine incidence, prevalence, mortality, and disability-adjusted life years among people younger than 20 years across 204 countries from 1992 to 2021. We examined trends over time and used statistical models to see how age, historical period, and year of birth influence the risk of pediatric heart diseases.

Results: Here we show that in 2021, there are 2.64 billion people under 20 years of age, mainly in countries with lower income and education levels. Heart diseases cause 309,000 deaths and 28.7 million years of healthy life lost. Congenital heart disease accounts for most deaths, while non-congenital heart disease is more common overall and rises by over one-third since 1992, with sharper increases after 2019. Death rates in poorer regions are up to eight times higher than in richer regions. Although the overall death rate declines by 55 %, adolescents and individuals born more recently face increasing risk for non-congenital conditions.

Conclusions: The burden of heart disease in the young remains heavy, with significant regional and socioeconomic inequalities. Stronger prevention, earlier detection, and better health care are urgently needed, especially in disadvantaged regions and in the years after the coronavirus pandemic.