BMC Medicine最新文献

{"title":"The promoting effects of digital targeted cognitive training in medication treatment for children with ADHD: a randomized controlled trial.","authors":"Chen Dang, Yu Zhu, Xiangsheng Luo, Lu Liu, Yuan Feng, Guisen Wu, Shaogen Zhong, Xin Wang, Jianzhao Zhang, Yike Zhu, Siqi Liu, Ziqi Liu, Li Qin, Xiaohui Ma, Yufeng Wang, Xiaoyi Wang, Jian Yang, Changming Wang, Li Sun","doi":"10.1186/s12916-025-04192-x","DOIUrl":"10.1186/s12916-025-04192-x","url":null,"abstract":"<p><strong>Background: </strong>Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder often managed with medication. Improving cognitive functions alongside medication treatment is crucial for better outcomes. This study mainly aimed to investigate the therapeutic effects of combining digitally targeted cognitive training with medication compared to medication monotherapy on ADHD core symptoms. We hypothesized that targeted cognitive training could enhance treatment efficacy when combined with medication.</p><p><strong>Methods: </strong>This was a randomized parallel-group controlled trial. A total of 124 children with ADHD were randomly allocated to two groups: 64 received medication treatment alone (M), including atomoxetine (ATX) and methylphenidate (MPH); 60 received targeted cognitive training combined with medication (TCT + M), including TCT + ATX and TCT + MPH. Both groups received 8 weeks of treatment. The primary outcome was the changes in ADHD core symptoms measured by the ADHD Rating Scale (ADHD-RS). The secondary outcomes were parent-reported ecological executive functions, social functions, and laboratory cognitive functions.</p><p><strong>Results: </strong>Main results: When compared with M treatment, the TCT + M treatment did not show significant greater improvements in ADHD core symptoms, ecological executive functions, social functions, or laboratory cognitive functions. Post-hoc exploratory analysis results: (1) In patients who received ATX treatment, TCT + ATX led to greater improvement in ADHD-RS total, inattention, and hyperactivity/impulsivity symptoms. Similar between-group differences were observed in ecological executive functions, and the improvements were significantly correlated with changes of ADHD core symptoms. (2) In patients who received MPH treatment, no significant differences in the improvement of primary or secondary outcomes were observed between MPH monotherapy and TCT + MPH groups.</p><p><strong>Conclusions: </strong>These findings demonstrated that, in comparison to medication monotherapy, the TCT + M treatment did not lead to more improvements in the core symptoms of ADHD, nor did it show superiority in other secondary outcomes. Specifically in children treated with atomoxetine, there's a potential promoting effect of targeted cognitive training on medication treatment in terms of the alleviation of ADHD core symptoms.</p><p><strong>Trial registration: </strong>This study was pre-registered with the Chinese Clinical Trial Registry under the identifier ChiCTR2100043525.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"371"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal immune-mediated conditions and ADHD risk in offspring.","authors":"Kjersti Mæhlum Walle, Kristin Gustavson, Siri Mjaaland, Ragna Bugge Askeland, Per Magnus, Ezra Susser, W Ian Lipkin, Camilla Stoltenberg, Michaeline Bresnahan, Ted Reichborn-Kjennerud, Mady Hornig, Helga Ask","doi":"10.1186/s12916-025-04227-3","DOIUrl":"10.1186/s12916-025-04227-3","url":null,"abstract":"<p><strong>Background: </strong>Maternal immune-mediated conditions during pregnancy have been linked with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. The relative contributions of maternal inflammatory/immune responses versus shared genetic predispositions remain unclear. This study uses paternal immune-mediated conditions as a negative control to explore these factors, as we investigate associations between maternal immune-mediated conditions during pregnancy and offspring ADHD.</p><p><strong>Methods: </strong>Prospective data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) was linked with the Medical Birth Registry of Norway (MBRN) and the Norwegian Patient Registry (NPR) to assess associations between prenatal exposure to maternal immune-mediated conditions and offspring ADHD risk up to age 18. Nationwide recruitment from 1999 to 2008 yielded 104,270 eligible mother-child pairs, with 21,340 children exposed to maternal allergic conditions (asthma, allergies, atopic conditions) and 7478 to other immune conditions (autoimmune, inflammatory). Paternal self-reported immune conditions served as negative controls. Children's ADHD diagnoses were obtained from NPR, and Cox proportional hazard models estimated hazard ratios for ADHD.</p><p><strong>Results: </strong>Both overall categories were associated with increased offspring ADHD risk (allergic conditions HR 1.23, 95% CI, 1.14-1.34; other immune conditions HR 1.36, 95% CI, 1.21-1.53). Specific associations included maternal asthma (HR 1.47, 95% CI, 1.30-1.67), allergies (HR 1.20, 95% CI, 1.10-1.31), rheumatologic/musculoskeletal conditions (HR 1.64, 95% CI, 1.28-2.10), Crohn's disease/ulcerative colitis (adjusted HR 1.95, 95% CI, 1.23-3.09), and endocrine conditions (HR 1.42, 95% CI, 1.15-1.77), specifically, type 1 diabetes (adjusted HR 2.50, 95% CI, 1.66-3.75). Although some paternal immune-mediated conditions (psoriasis, ulcerative colitis, Crohn's disease) showed similar trends in ADHD risk, only paternal asthma was significantly associated (adjusted HR 1.26, 95% CI, 1.10-1.45).</p><p><strong>Conclusions: </strong>Several maternal immune-mediated conditions were associated with increased offspring ADHD risk. The higher, more consistent ADHD risk estimates with maternal conditions compared to paternal ones indicate that unmeasured genetic confounding does not fully explain these associations. These results suggest direct effects on fetal development through events at the maternal-fetal interface which may alter fetal immune responses and lead to greater ADHD risk in offspring. Asthma may be an exception to this mechanism, as paternal asthma was also linked with offspring ADHD risk.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"348"},"PeriodicalIF":7.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative risk of severe constipation in patients treated with opioids for non-cancer pain: a retrospective cohort study in Northwest England.","authors":"Belay Birlie Yimer, Mehreen Soomro, John McBeth, Carlos Raul Ramirez Medina, Mark Lunt, William G Dixon, Meghna Jani","doi":"10.1186/s12916-025-04118-7","DOIUrl":"10.1186/s12916-025-04118-7","url":null,"abstract":"<p><strong>Background: </strong>Constipation is a frequent adverse event associated with opioid medications that can have a considerable impact on patients' quality of life. In patients who require opioids for pain relief, less is known about the risk conferred by specific opioids given their diverse pharmacology and the effect of daily dose and potency. The aim of the study was to evaluate the comparative risk of severe constipation by opioid type and dose in patients with non-cancer pain admitted to hospital.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using hospital electronic health records in Northwest England between December 1, 2009, and December 31, 2020. Patients who were ≥ 18 years and without a history of cancer were included. Opioid exposure was measured using administered drug information in hospital. The outcome was a severe constipation event defined as administration of an enema or suppository. Incidence rates by opioid use status, type of opioid class and morphine milligram equivalent (MME) per day were calculated, and a Cox regression model was used to determine associations with incident constipation after adjusting for confounders.</p><p><strong>Results: </strong>The study included 80,475 eligible patients who were administered an opioid in hospital. Compared to codeine, morphine (HR 1.59, 95% CI 1.45-1.74), oxycodone (HR 1.46, 95% CI 1.32-1.63), fentanyl (HR 1.37, 95% CI 1.14-1.64) and combination opioids (HR 1.85, 95% CI 1.66-2.06) were associated with a higher risk of constipation in the fully adjusted models. Tramadol demonstrated a significantly lower risk compared to codeine (HR 0.80, 95% CI 0.64-1.00). Higher opioid doses of more than ≥ 50 MME/day in comparison to < 50 MME/day were associated with an increased risk of constipation (compared to < 50 MME/day, 50 to < 120 MME/day: HR 1.95, 95% CI 1.78-2.15; ≥ 120 MME/day: HR 1.45, 95% CI 1.32-1.60).</p><p><strong>Conclusions: </strong>Morphine, oxycodone, fentanyl and combination opioids administration were associated with a significantly higher risk of severe constipation compared to codeine. Tramadol was associated with the lowest risk of the outcome compared to codeine. Patients on ≥ 50 MME/day experienced a higher risk of severe constipation compared to those on < 50 MME/day. These results can be used to guide better shared decisions with patients to balance benefit and harms of specific opioid types and doses.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"288"},"PeriodicalIF":7.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal plasma amino acids during pregnancy and neonatal anthropometry: findings from the NICHD Fetal Growth Studies-Singleton Cohort.","authors":"Claire Guivarch, Jing Wu, Ruijin Lu, Jagteshwar Grewal, Guoqi Yu, Ling-Jun Li, Jiaxi Yang, Wei Wei Pang, Dong D Wang, Natalie L Weir, Zhen Chen, Michael Y Tsai, Cuilin Zhang","doi":"10.1186/s12916-025-04146-3","DOIUrl":"10.1186/s12916-025-04146-3","url":null,"abstract":"<p><strong>Background: </strong>Amino acids (AAs) during pregnancy are crucial for fetal growth. Prior studies measured AA concentrations at single time points in pregnancy, despite their fluctuations throughout pregnancy. We measured plasma AA profiles in blood samples longitudinally collected from early through late pregnancy and evaluated their associations with neonatal anthropometry.</p><p><strong>Methods: </strong>Concentrations of plasma aromatic AAs, branched-chain AAs, and AAs involved in one-carbon metabolism were assessed at 10-14, 15-26, 23-31, and 33-39 gestational weeks (GW) among 321 women from a case-control study from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort. Associations between AA concentrations in tertiles at each visit and neonatal anthropometric measures were assessed using weighted generalized estimating equations models, after adjusting for major confounders.</p><p><strong>Results: </strong>Women with higher concentrations of glutamine (3rd vs. 1st tertile) at 10-14 GW had offspring with greater birthweight z-score (β [95% CI] = 0.31 [0.06, 0.56], p-trend = 0.04) and birth length (1.35 cm [0.32, 2.37], p-trend = 0.04). Women with higher concentrations of aspartic acid (3rd vs. 1st tertile) at 23-31 GW, however, had offspring with smaller sum of skinfolds (- 3.9 mm [- 6.0, - 1.7], p-trend = 0.007). Similarly, women with higher concentrations of glycine (3rd vs. 1st tertile) at 10-14 GW had offspring with lower birthweight z-score (- 0.37 [- 0.65, - 0.08], p-trend = 0.04).</p><p><strong>Conclusions: </strong>Plasma AA concentrations during pregnancy appear to play a crucial role in neonatal anthropometry. Associations were observed as early as 10 GW and varied by type of AAs and gestational age.</p><p><strong>Trial registration: </strong>Clinical Trial Registry number: NCT00912132.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"343"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors.","authors":"Anqi Lin, Lihaoyun Huang, Aimin Jiang, Lingxuan Zhu, Weiming Mou, Yu Li, Chunyan Zhang, Zaoqu Liu, Jian Zhang, Quan Cheng, Ting Wei, Peng Luo","doi":"10.1186/s12916-025-04183-y","DOIUrl":"10.1186/s12916-025-04183-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are a cornerstone of modern cancer treatment, but their effectiveness is limited. Fecal microbiota transplantation (FMT), which alters the gut microbiome, has shown promise in enhancing ICIs' therapeutic effects.</p><p><strong>Methods: </strong>We conducted a comprehensive search of relevant studies available up to September 30, 2024, to analyze the clinical efficacy and safety of combining FMT with ICIs in cancer treatment. The primary endpoint was the objective response rate (ORR), with secondary evaluations of survival outcomes and safety.</p><p><strong>Results: </strong>A total of 10 studies involving 164 patients with solid tumors were included. The pooled ORR was 43% (95% CI: 0.35-0.51). Subgroup analysis revealed that the combination of anti-PD-1 and anti-CTLA-4 therapies was associated with a significantly higher ORR (60%) compared to anti-PD-1 monotherapy (37%; P = 0.01). The incidence of grade 1-2 adverse events (AEs) was 42% (95% CI: 0.32-0.52), while grade 3-4 AEs occurred in 37% of patients (95% CI: 0.28-0.46).</p><p><strong>Conclusions: </strong>This meta-analysis provides preliminary evidence supporting the use of FMT as a strategy to enhance the efficacy of ICIs in patients with advanced or refractory solid tumors. However, larger-scale randomized controlled trials with long-term follow-up are required to confirm and optimize treatment protocols.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"341"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-assisted diagnosis and prognostication in low ejection fraction using electrocardiograms in inpatient department: a pragmatic randomized controlled trial.","authors":"Dung-Jang Tsai, Chin Lin, Wei-Ting Liu, Chiao-Chin Lee, Chiao-Hsiang Chang, Wen-Yu Lin, Yu-Lan Liu, Da-Wei Chang, Ping-Hsuan Hsieh, Chien-Sung Tsai, Yuan-Hao Chen, Yi-Jen Hung, Chin-Sheng Lin","doi":"10.1186/s12916-025-04190-z","DOIUrl":"10.1186/s12916-025-04190-z","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of low ejection fraction (EF) remains challenging despite being a treatable condition. This study aimed to evaluate the effectiveness of an electrocardiogram (ECG)-based artificial intelligence (AI)-assisted clinical decision support tool in improving the early diagnosis of low EF among inpatient patients under non-cardiologist care.</p><p><strong>Methods: </strong>We conducted a pragmatic randomized controlled trial at an academic medical center in Taiwan. 13,631 inpatient patients were randomized to either the intervention group (n = 6,840) receiving AI-generated ECG results or the control group (n = 6,791) following standard care. The primary outcome was the incidence of newly diagnosed low EF (≤ 50%) within 30 days following the ECG. Secondary outcomes included echocardiogram utilization rates, positive predictive value for low EF detection, and cardiology consultation rates. Statistical analysis included hazard ratios (HR) with 95% confidence intervals (CI) for time-to-event outcomes and chi-square tests for categorical variables.</p><p><strong>Results: </strong>The intervention significantly increased the detection of newly diagnosed low EF in the overall cohort (1.5% vs. 1.1%, HR 1.50, 95% CI: 1.11-2.03, P = 0.023), with a more pronounced effect among AI-identified high-risk patients (13.0% vs. 8.9%, HR 1.55, 95% CI: 1.08-2.21). While overall echocardiogram utilization remained similar between groups (17.1% vs. 17.3%, HR 1.00, 95% CI: 0.92-1.09), the intervention group demonstrated higher positive predictive value for identifying low EF among patients receiving echocardiogram (34.2% vs. 20.2%, p < 0.001). Post-hoc analysis revealed increased cardiology consultation rates among high-risk patients in the intervention group (29.3% vs. 23.5%, p = 0.027).</p><p><strong>Conclusions: </strong>Implementation of an AI-ECG algorithm enhanced the early diagnosis of low EF in the inpatient setting, primarily by improving diagnostic efficiency rather than increasing overall healthcare utilization. The tool was particularly effective in identifying high-risk patients who benefited from increased specialist consultation and more targeted diagnostic testing.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05117970.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"342"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Projected health and economic effects of nonavalent versus bivalent human papillomavirus vaccination in preadolescence in the Netherlands.","authors":"Birgit Sollie, Johannes Berkhof, Johannes A Bogaards","doi":"10.1186/s12916-025-04170-3","DOIUrl":"10.1186/s12916-025-04170-3","url":null,"abstract":"<p><strong>Background: </strong>Most European countries offer human papillomavirus (HPV) vaccination through organised immunisation programmes, but the choice of vaccine varies. We compared the expected health and economic effects of the currently used bivalent vaccine, targeting HPV-16/18, and the nonavalent vaccine, targeting seven additional genotypes, for the Netherlands.</p><p><strong>Methods: </strong>We estimated the incremental impact of nonavalent versus bivalent vaccination in a cohort of 100,000 girls and 100,000 boys offered vaccination at age 10, by projecting type-specific infection risk reductions onto expected number of cervical screening outcomes, HPV-related cancers, and treatments for anogenital warts and recurrent respiratory papillomatosis (RRP). In the base-case, we assumed two-dose vaccination with 60% uptake, lifelong partial cross-protection against HPV-31/33/45 for the bivalent vaccine and EUR 25 extra cost per dose for the nonavalent vaccine. Cost-effectiveness was assessed from a healthcare provider perspective by comparing the incremental cost-effectiveness ratio (ICER) per life-year gained (LYG) with the Dutch threshold of EUR 20,000/LYG.</p><p><strong>Results: </strong>Compared with bivalent vaccination, nonavalent vaccination prevents an additional 1320 high-grade cervical lesions, 70 cancers, 34,000 anogenital warts episodes and 30 RRPs and generates EUR 4.1 million discounted savings from fewer treatments. The ICER is EUR 5489 (95% credible interval: 3765; 7019)/LYG in the base-case and exceeds the cost-effectiveness threshold only if the cross-protection for the bivalent vaccine extends permanently to non-31/33/45 genotypes or if the vaccine efficacy wanes past age 20 for both vaccines.</p><p><strong>Conclusions: </strong>Sex-neutral vaccination with the nonavalent vaccine is likely to be cost-effective. Long-term monitoring of type-specific vaccine effectiveness is essential because of the impact of cross-protection and waning efficacy on cost-effectiveness.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"339"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusion analysis of sMRI-DTI in patients with ulcerative colitis by multimodal CCA + joint ICA and associated neurotransmitter profiles.","authors":"Chengxiang Liu, Zi Wei, Jian Tang, Yintao Liu, Jingdong Lu, Yujia Li, Xin Liu, Peng Liu, Fenrong Chen","doi":"10.1186/s12916-025-04179-8","DOIUrl":"10.1186/s12916-025-04179-8","url":null,"abstract":"<p><strong>Background: </strong>As a chronic inflammatory disease, ulcerative colitis (UC) is characterized by complex etiology and unclear pathological mechanisms. Neuroimaging research plays a pivotal role in improving diagnostic accuracy and guiding treatment decisions, while enhancing our understanding of disease mechanisms. We aimed to explore the possible associations between gray matter volume (GMV) and white matter fractional anisotropy (FA) abnormalities as well as the neurotransmitter profiles in UC patients.</p><p><strong>Methods: </strong>Thirty-four UC patients and 21 healthy controls (HCs) participated in structural magnetic resonance imaging and diffusion tensor imaging scans. To identify the joint and specific independent components (ICs) across modalities between groups, multimodal canonical correlation analysis with joint independent component analysis was used for fusion analysis. ICs with significant group differences from the same index across two modalities were considered joint group-discriminative ICs. Joint ICs reveal cross-modal neurophysiological mechanisms of GMV-FA. A modal-specific group-discriminative IC is defined as a component that shows significant group difference only in unimodal, revealing specific neurophysiological mechanisms of GMV/FA. The relationship between neuroimaging findings and clinical characteristics was assessed. We also investigated the spatial correlations between the joint and modality-specific ICs and neurotransmitter profiles.</p><p><strong>Results: </strong>Compared to HCs, patients with UC showed one joint group-discriminating component (GMV_IC4-FA_IC4) mainly in the default mode network, thalamus, corpus callosum, corona radiata, fornix, posterior thalamic radiation, middle cerebellar peduncle, and corticospinal tract as well as one modality-specific group-discriminating component (FA_IC5). The loadings of GMV_IC5 were significantly negatively correlated with platelet levels in UC. Moreover, significant associations between the abnormalities of GMV_IC4 and the dopamine and gamma-aminobutric acid (GABAa) system, between the abnormalities of FA_IC4 and the dopamine, GABAa, acetylcholine, and glutamate system, and between the abnormalities of FA_IC5 and dopamine and serotonin systems were found in this study.</p><p><strong>Conclusions: </strong>This study suggested the complex interplay between structural alterations and associated neurotransmitter changes in neural systems subserving emotion dysregulation and visceral sensory processing in UC patients. The identified covarying GMV-FA complements previous findings of structural abnormalities. Furthermore, these findings provided novel insights into the neuropathological mechanisms and potential therapeutic targets of UC.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"345"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of GnRH agonists on endometrial immune cells in patients with adenomyosis: a prospective cohort study.","authors":"Anna Lena Zippl, Christiana Kyvelidou, Monika Frank, Elisa Gapp, Elisabeth Reiser, Anne-Sophie Braun, Katharina Feil, Stefanie Schuchter, Patrick Rockenschaub, Bettina Toth, Beata Seeber","doi":"10.1186/s12916-025-04162-3","DOIUrl":"10.1186/s12916-025-04162-3","url":null,"abstract":"<p><strong>Background: </strong>Adenomyosis is associated with lower implantation and higher miscarriage rates. Studies on recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) have shown that endometrial immune cell populations play a crucial role during implantation and early pregnancy. In women with adenomyosis, improved pregnancy outcomes following assisted reproductive technologies (ART) and pre-treatment with GnRH-agonists (GnRH-a) prior to frozen embryo transfer (FET) have been reported. We aimed to compare the endometrial immune cell populations of women with adenomyosis to those of women with RPL and RIF, and to characterise endometrial leucocyte subpopulations within the adenomyosis group before and after GnRH-a.</p><p><strong>Methods: </strong>We conducted a prospective study between 2021 and 2024. Women with infertility and adenomyosis undergoing ART underwent one endometrial biopsy 6-9 days after oocyte retrieval and a second biopsy after 3 months of GnRH-a prior to FET. Women in the RPL and RIF groups underwent one endometrial biopsy in the midluteal phase. We performed flow cytometry (FC) to characterise immune cell populations and immunohistochemistry (IHC) to analyse uterine natural killer cells (uNKs) and plasma cells (PC). The Kruskal-Wallis test was used for comparisons between the study groups, and the Wilcoxon signed rank tests were used for paired samples before and after GnRH-a.</p><p><strong>Results: </strong>Endometrial leucocyte subpopulations at baseline showed no significant differences between the adenomyosis (n = 20), the RPL (n = 40) and RIF (n = 15) group. In the adenomyosis group, following GnRH-a, we observed a significant decrease in the percentage of monocytes, from 77% (IQR 71, 82) to 71% (IQR 65, 75) (adj. p = 0.030). Baseline IHC showed elevated plasma cell concentrations (≥ 5/mm²) in 1/20 adenomyosis patients (5%), 4/40 RPL patients (10%) and 1/15 RIF patients (6.7%) while uNK cells were elevated (≥ 300/mm²) in 8/20 adenomyosis patients (40%), 11/40 RPL patients (27.5%) and 1/15 RIF patients (6.7%).</p><p><strong>Conclusions: </strong>Women with infertility and adenomyosis showed a similar endometrial immune profile as women with RPL and RIF. The beneficial effect of GnRH-a prior to FET in women with adenomyosis may be mediated through effects on monocyte subpopulations. Based on the high prevalence of elevated uNK cells in patients with adenomyosis, we suggest testing women with adenomyosis undergoing ART before FET.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"338"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape.","authors":"Gashaw Garedew Woldeamanuel, Kenean Getaneh Tlaye, Xueqin Wang, Long Nguyen-Hoang, Qiongjie Zhou, Yinan Wang, Bo Wah Leung, Yao Wang, Liona C Poon, Chi Chiu Wang","doi":"10.1186/s12916-025-04132-9","DOIUrl":"10.1186/s12916-025-04132-9","url":null,"abstract":"<p><strong>Background: </strong>Platelets play critical roles in the pathogenesis of preeclampsia, including thrombosis, endothelial dysfunction and inflammation. However, preeclampsia-associated changes in platelet gene expression and activation at the maternal-foetal interface remain unknown. Moreover, aspirin nonresponsiveness in high-risk pregnancies underscores the need for low-cost biomarkers to identify nonresponders. Nevertheless, the changes of platelet indices in women who develop preeclampsia despite aspirin prophylaxis have not yet been evaluated. In this study, we aimed to investigate the changes in platelet indices associated with aspirin nonresponsiveness, activation state and transcriptional landscape in preeclampsia.</p><p><strong>Methods: </strong>Platelet indices were compared between aspirin-responsive and nonresponsive women. Logistic regression analysis was performed to determine the associations between platelet indices and aspirin nonresponsiveness. Opal immunofluorescence staining was performed to evaluate the expression of platelet-specific (CD42b) and activation (CD62P) markers in placental villous and decidual tissues. RNA sequencing (RNA-seq) was performed to investigate the transcriptomic profile of platelets.</p><p><strong>Results: </strong>A decrease in platelet count (PC) during the second trimester as well as an increase in mean platelet volume (MPV) and a lower PC/MPV ratio in the third trimester were significantly associated with the subsequent development of aspirin nonresponsiveness. We observed significantly greater expression of CD62P in the placental villous and CD42b in the decidua of the preeclamptic group than in those of the nonpreeclamptic group. Colocalization analysis of CD42b and CD62P revealed that the preeclamptic placenta and decidua presented significant platelet activation. RNA-seq analysis revealed a total of 20, 618 and 1819 transcripts in the peripheral blood, placental villous and decidua of preeclamptic women, respectively. Functional analysis revealed that the PI3K-Akt and Wnt signalling pathways were significantly enriched in the placental villous and decidua of preeclamptic patients, respectively. RT‒qPCR analysis confirmed the upregulation of FKBP5, LAMA5, FZD5 and FGG mRNA expression in preeclampsia.</p><p><strong>Conclusions: </strong>Our findings suggest that PC in the second trimester and PC, MPV and PC/MPV ratio in the third trimester may be useful for assessing aspirin nonresponsiveness in women at high risk of preeclampsia. Furthermore, our findings demonstrate that preeclampsia is associated with increased platelet activation and significant enrichment of signalling pathways involved in platelet activation.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"346"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}