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Expression of the novel serum biomarker of testicular germ cell tumours miR-371a-3p in serum of pregnant women: a case-control study

Eur J Med Res. 2025 Aug 2;30(1):697. doi: 10.1186/s40001-025-02906-8.

ABSTRACT

BACKGROUND: The microRNA-371a-3p (M371) is a sensitive novel serum biomarker of testicular germ cell tumours (GCTs) and a certified test is available for consistent clinical testing. In view of the well-known biological analogies of GCTs and embryogenesis, we hypothesized that the marker substance M371 is also present in serum of pregnant women. The goal of this report was to analyse maternal serum for M371.

MATERIALS AND METHODS: M371 serum levels were measured in 36 third-trimester pregnant women. Control groups consisted of 12 non-pregnant young women, 12 healthy young males, and 12 patients with GCTs. M371 levels were measured by quantitative real time PCR using the certified M371 test with the standard cutoff of RQ = 5. Statistical methods involved receiver operating characteristics (ROC) analysis with Youden index analysis, and statistical comparisons of median serum levels of patients with those of controls as well as for comparisons of subgroups of patients according to age and infant sex.

RESULTS: All pregnant women had measurable M371 levels, with 83.3% of the patients having elevated levels above the cutoff, while traces below cutoff were detected in the remainder. Healthy female and male controls were both below cutoff. ROC analysis revealed a 100% sensitivity and 100% specificity of the test when the cutoff of RQ = 0.4 defined by Youden index analysis was employed. The median level in pregnant women was significantly lower than that in GCT patients (10.8 [interquartile range 6.1-20.3] versus RQ = 139.5 [IQR 54.9-630.3], p < 0.001). Individual M371 levels were not associated with patient age and with infant sex.

CONCLUSIONS: The evidence for elevated levels of microRNA-371a-p in maternal serum is a novel finding. This result accords with the various analogies between GCTs and embryogenesis documented previously. The finding supports the view that cells involved in human reproduction share epigenetic features with human embryonic stem cells. Further studies are required to explore if this finding could be utilized clinically.

PMID:40753402 | DOI:10.1186/s40001-025-02906-8

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Problematic smartphone use and risk behaviors in adolescents during the COVID-19 pandemic

BMC Pediatr. 2025 Aug 2;25(1):590. doi: 10.1186/s12887-025-05924-x.

ABSTRACT

BACKGROUND: This study examined the association between problematic smartphone use (PSU) and risk behaviors among Korean adolescents during the COVID-19 pandemic. It also aimed to develop preventive measures for adolescent health promotion in the event of future pandemics.

METHODS: A secondary analysis of data from the 16th Korean Youth Risk Behavior Web-based Survey (2020) was conducted, which included 54,948 middle and high school students. Smartphone use, PSU, alcohol use, and smoking status were assessed via self-reported questionnaires. Complex samples descriptive statistics and logistic regression analyses were performed using SPSS 25.

RESULTS: Korean adolescents averaged 282.8 and 393.4 min of smartphone use across weekdays and on weekends, respectively, with a 25.5% prevalence of PSU. Female and high school students exhibited significantly higher PSU rates (p <.001). Current alcohol use and smoking increased PSU risk by 1.098- and 1.295-fold, respectively.

CONCLUSIONS: The findings emphasize the need for intervention strategies targeting PSU and associated risk behaviors. Continuous monitoring in home and school settings, along with gender-specific and educational-level interventions, is recommended to promote healthy smartphone use among adolescents.

PMID:40753400 | DOI:10.1186/s12887-025-05924-x

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Extreme dipping blood pressure pattern is associated with increased mortality in hemorrhagic stroke patients: a retrospective cohort study

BMC Neurol. 2025 Aug 2;25(1):318. doi: 10.1186/s12883-025-04342-x.

ABSTRACT

BACKGROUND: Blood pressure management strategies in patients with hemorrhagic stroke remain ineffective in reducing mortality. The circadian blood pressure pattern has been shown to be associated with mortality in patients with non-hemorrhagic stroke, but few studies have explored this association in patients with hemorrhagic stroke. We aimed to investigate the relationship between circadian blood pressure pattern and mortality in patients with hemorrhagic stroke.

METHODS AND RESULTS: Adult hemorrhagic stroke patients hospitalized in intensive care unit for more than 24 h in the Medical Information Mart for Intensive Care (MIMIC-IV) database were recruited for this retrospective cohort study. All patients were divided into the dipping group, the nondipping group, the reverse dipping group and the extreme dipping group. We used binary logistic regression analysis to explore the relationship between circadian blood pressure patterns and mortality of patients with hemorrhagic stroke. The overall cohort comprised 1040 patients. The patients in the extreme dipping group had higher mortality than other groups (57.1% versus 15.6%,17.0%, and 22.3%, respectively). After adjusting for covariates, the statistical analysis showed that the extreme dipping pattern was significantly associated with the mortality of hemorrhagic stroke patients in intensive care unit (odds ratio: 4.961[95%CI: 1.289-19.086]). Interaction analysis had no statistical significance in all results.

CONCLUSIONS: The extreme dipping pattern may be an important risk factor for increased mortality in patients with hemorrhagic stroke.

PMID:40753399 | DOI:10.1186/s12883-025-04342-x

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Sensitive detection of minimal residual disease and immunotherapy targets by multi-modal bone marrow analysis in high-risk neuroblastoma – a multi-center study

J Exp Clin Cancer Res. 2025 Aug 2;44(1):224. doi: 10.1186/s13046-025-03481-w.

ABSTRACT

BACKGROUND: Bone marrow dissemination of tumor cells, common in various cancers, including neuroblastoma, is associated with poor outcome, necessitating sensitive detection methods for bone marrow minimal residual disease (MRD) and offer detection of biomarkers for therapy stratification. Current standard-of-care diagnostics, involving cytomorphological and histological assessment of bone marrow aspirates and trephine biopsies, lack sensitivity, leading to undetected MRD in many patients, and do not allow molecular biomarker assessment.

METHODS: This study evaluates advanced multi-modal high-sensitivity MRD detection techniques in 509 bone marrow specimens from 108 high-risk neuroblastoma patients across two centers. We employed automatic immunofluorescence plus interphase fluorescence in situ hybridization (AIPF) and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) panels to quantify disseminated tumor cells (DTCs), disialoganglioside 2 (GD2) and CD56/Neural cell adhesion molecule (NCAM) levels, and adrenergic (ADRN) and mesenchymal (MES)-phenotype mRNA markers.

RESULTS: This multi-modal analysis significantly improved MRD detection compared to standard-of-care methods; 395 samples yielded results for RT-qPCR-ADRN, AIPF and CM/histology and 223 showed concordant results (64 positive, 159 negative). 114 samples did not produce results as either no cytospins were prepared (n = 96) or results were inconclusive (all techniques n = 18). AIPF and RT-qPCR complemented each other in detecting MRD and characterizing ADRN- and MES-phenotypes and GD2 immunotherapy target. RT-qPCR-ADRN alone frequently detected low tumor cell burden. High DTC infiltration at diagnosis showed bilateral bone marrow disease, whereas MRD settings often involved only one side. RT-qPCR-MES, despite lower sensitivity, identified 37 additional cases and showed delayed clearance of MES markers post-chemotherapy, with increases prior to relapse.

CONCLUSIONS: Our findings demonstrate the feasibility of integrating high-sensitivity techniques with standard-of-care assessments in an international multicenter setting. Advanced multi-modal MRD detection, monitoring phenotype switches and assessing immunotherapy targets are crucial for improving patient outcomes in neuroblastoma and other cancers.

PMID:40753395 | DOI:10.1186/s13046-025-03481-w

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Evaluating intersectional variation of HPV-associated cancers in rural America

BMC Public Health. 2025 Aug 2;25(1):2627. doi: 10.1186/s12889-025-23963-y.

ABSTRACT

PURPOSE: For decades, incidence of human papillomavirus (HPV)-associated cancers has been increasing in rural communities across the United States. Although emerging evidence shows a widening rural-urban disparity, rural intersectionality has been understudied. Our study examined the incidence of HPV-associated cancers within rural communities to identify differences by race/ethnicity for males and females, and explore how these differences varied by cancer type, socioeconomic, and geographic factors.

METHODS: We accessed age-adjusted cancer incidence rates (2010-2019) from the North American Association of Central Cancer Registries (NAACCR) for HPV-associated cancers (cervical, vaginal, vulvar, penile, anal, oropharyngeal) in rural counties. Stratifying by sex, we calculated incidence rate ratios by race/ethnicity. Subgroup analyses included age, site, census-tract poverty, census tract socioeconomics, and region.

RESULTS: Between 2010 and 2019, rural HPV-associated cancer was 11.8 cases per 100,000 population. We found significant heterogeneity within male (10.5) and female (13.2) rates. For males, the lowest rate was found in non-Hispanic Asian-American/Pacific-Islander populations (3.7) and Hispanic populations (4.8), and the highest rate was found in non-Hispanic White populations (11.2). For females, the lowest rate was also found in Hispanic Asian-American/Pacific-Islander populations (8.8) and the highest rates were found in non-Hispanic Black (13.8) and non-Hispanic American Indian/Alaska Native populations (14.5). However, these racial/ethnic differences varied across rural subpopulations, geography, and poverty.

CONCLUSIONS: Appreciating the diversity of the rural cancer burden can be used to effectively develop and implement public health interventions to address HPV-related cancer disparities in rural communities. Actions are needed to prioritize reducing the burden of HPV-associated cancer in AIAN populations in high-poverty rural communities.

PMID:40753394 | DOI:10.1186/s12889-025-23963-y

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Identifying tests to evaluate in a diagnostic accuracy study for patients with vertigo in general practice: a Delphi study

BMC Prim Care. 2025 Aug 2;26(1):238. doi: 10.1186/s12875-025-02920-z.

ABSTRACT

INTRODUCTION: Vertigo is a common symptom that strongly impacts patients’ quality of life. More than 80% of patients experiencing vertigo are primarily treated by their general practitioner (GP). The GP’s’diagnostic toolkit’ for vertigo has serious limitations, though, because diagnostic accuracy studies on conditions that may cause vertigo have never been performed in a general practice setting. Our aim was to determine which tests should be investigated in a diagnostic accuracy study for patients with vertigo in general practice.

METHOD: We conducted an online Delphi procedure involving national and international experts. The experts were asked to judge a selection of 40 diagnostic tests based on the Dutch GP guideline on vestibular symptoms, supplemented by tests identified during a systematic review. Panellists were allowed to suggest additional tests after the first round. In case of consensus of at least 70%, a test was included or excluded. We also conducted a secondary sub-analysis of our Delphi procedure to demonstrate non-dominance of Dutch experts within our expert panel. Data were analysed using descriptive statistics and content analysis. Data were analysed using descriptive statistics and content analysis.

RESULTS: A panel of 20 experts from five countries, including 7 specialists in otolaryngology, 6 neurologists and 7 GPs, participated in the Delphi procedure. The panel judged 46 diagnostic tests in total, with 6 additional tests added to the original selection based on suggestions by experts. After the first two rounds (100% response rate), 16 tests were included, 22 tests were excluded and no consensus was reached on 8 tests. During the consensus round, one of the 8 tests was added to the included 16 tests. Of these 17 tests, 15 are recommended by the Dutch GP guideline, supplemented by the non-recommended Tandem walking test and the Romberg test.

CONCLUSIONS: An international expert panel reached consensus on 17 tests for vertigo in general practice that should be investigated in a diagnostic accuracy study.

PMID:40753388 | DOI:10.1186/s12875-025-02920-z

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Podiatrists’ Reflections on Content and Delivery of Their Pre-Registration Podiatry Programme at a Regional University in New South Wales, Australia: A Survey of Graduates

J Foot Ankle Res. 2025 Sep;18(3):e70053. doi: 10.1002/jfa2.70053.

ABSTRACT

INTRODUCTION: Understanding podiatrists’ perceptions of their undergraduate education is important to ensure that educational content and delivery meets the needs of the current workforce to inform future planning. This study aims to explore podiatrists’ perceptions of their undergraduate podiatry training at the University of Newcastle, Australia, and their preferences regarding educational content and delivery.

METHODS: We conducted an online survey of podiatry graduates from the University of Newcastle, Australia. Data were analysed using descriptive statistics and Fisher’s exact test to compare responses between groups. Qualitative responses were analysed using inductive content analysis.

RESULTS: A total of 114 podiatrists responded. Nail avulsions, business management and modifying orthoses were perceived as being given insufficient time and focus in undergraduate training, with a higher proportion of private (71%) compared to public (33%) podiatrists reporting business management as lacking (p = 0.02). There was strong support for embedding endorsed scheduled medicines training within the programme (80%) and for delivering theoretical content face-to-face rather than online. Inductive content analysis revealed four areas to be emphasised in future curricula: modern technologies, biomechanics, wound care and routine podiatric care. Potential strategies to reduce examination stress included mock assessments, changed assessment weighting, reduced exam structure rigidity and reducing assessor bias.

CONCLUSIONS: This study provides insights into Australian podiatrists’ preferences for pre-registration curricula. Topics to emphasise in future curricula at the University of Newcastle, Australia, include greater manual skills and business training, modern technologies, biomechanics and routine podiatric care. Our results suggest exercising caution when substituting face-to-face with online learning. These findings provide valuable guidance for future curricula in a context of declining student numbers and increasing healthcare demands.

PMID:40751492 | DOI:10.1002/jfa2.70053

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Real-World Effectiveness and Safety of JAK Inhibitors in Atopic Dermatitis: A Systematic Review and Meta-Analysis

Clin Exp Allergy. 2025 Aug 2. doi: 10.1111/cea.70125. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate the effectiveness and safety of JAK inhibitors in patients with moderate to severe atopic dermatitis by performing a systematic review and meta-analysis using data from studies in real-world settings.

DESIGN: Systematic review and meta-analysis. Pooled estimates for effectiveness and safety were assessed using the Freeman-Tukey Double ArcSine method. Statistical heterogeneity was assessed using I2 statistics. A random-effects model (DerSimonian-Laird method) was applied to consider the heterogeneity within and between studies and to give a more conservative estimate. The study quality assessment tools developed by the National Heart, Lung, and Blood Institute were used.

DATA SOURCE: Relevant studies were searched in March 2025 using four databases: PubMed, Embase, Scopus, and Web of Science.

ELIGIBILITY CRITERIA: Studies evaluating the effectiveness or safety of systemic JAK inhibitors among patients with moderate to severe atopic dermatitis in a real-world setting were included.

RESULTS: A total of 50 studies were included in this review. Regarding their effectiveness, the pooled estimates with a 95% CI of Eczema Area and Severity Index (EASI)-75 were 44% (34%-55%), 45% (28%-62%), 59% (51%-66%), 73% (64%-81%), 70% (57%-81%), and 86% (72%-96%) at 4, 8, 12, 16, 24, and 52 weeks. For safety, the most common adverse events were acne (16%), followed by increased creatine phosphokinase levels (13%) and increased lipids (12%).

CONCLUSION: Our meta-analysis of JAK inhibitors in patients with atopic dermatitis demonstrated that the overall outcomes from real-world settings are comparable to those from clinical trials.

SYSTEMATIC REVIEW REGISTRATION: Protocol Registration: PROSPERO CRD42024569258.

PMID:40751489 | DOI:10.1111/cea.70125

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Risk factors and mitigating measures associated with bile duct injury during cholecystectomy: meta-analysis

BJS Open. 2025 Jul 1;9(4):zraf076. doi: 10.1093/bjsopen/zraf076.

ABSTRACT

BACKGROUND: Cholecystectomy is a common procedure with a notable risk of iatrogenic bile duct injury. Understanding the factors contributing to bile duct injury and the effectiveness of preventative measures is crucial for improving surgical outcomes. This meta-analysis aimed to identify and synthesize high-quality evidence on risk factors and mitigating measures associated with bile duct injury after cholecystectomy.

METHODS: Following the PRISMA guidelines, a comprehensive literature search was conducted across multiple databases. Included studies reported on adult patients undergoing cholecystectomy with relevant risk factors for bile duct injury. Meta-analyses of unadjusted and adjusted risk estimates were conducted with a random-effects model to account for heterogeneity. The study period across all included studies spanned from 1989 to 2016.

RESULTS: The review included 31 studies comprising 6 513 599 cholecystectomies and 18 259 bile duct injuries. The primary risk factors identified were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.13 to 1.39) and acute cholecystitis (adjusted odds ratio 1.74, 1.27 to 2.39). The critical view of safety was inconsistently documented and not statistically linked to reduced bile duct injury. Intraoperative cholangiogram’s routine use did not show a statistically significant association with reduced incidence of bile duct injury (adjusted odds ratio 0.92, 0.70 to 1.23).

CONCLUSION: Male sex and acute cholecystitis significantly increase the risk of bile duct injury after cholecystectomy. Risk stratification for these patients before surgery would ultimately aid the shared decision-making consent process.

PMID:40751483 | DOI:10.1093/bjsopen/zraf076

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A Novel Score for Predicting Long-Term Outcomes in Recanalisation-Treated Patients With Budd-Chiari Syndrome: A Multicentre Study

Liver Int. 2025 Sep;45(9):e70259. doi: 10.1111/liv.70259.

ABSTRACT

BACKGROUND AND AIMS: A recanalisation-specific model for Budd-Chiari syndrome (BCS) is lacking. We aimed to develop a novel score for individual long-term outcome prediction and risk stratification.

METHODS: Overall, 834 BCS patients undergoing recanalisation (566 received percutaneous transluminal angioplasty alone, and 268 with routine stenting) from January 2010 to May 2019 were included from six Chinese centres. The model was developed using Cox multivariable regression, internally validated through a 1000-times bootstrapped method, and compared its performance with existing BCS prognostic models, like the Clichy score.

RESULTS: During the median follow-up period of 58.0 months, 44 patients were converted to transjugular intrahepatic portosystemic shunt (TIPS), none underwent orthotopic liver transplantation (OLT) and 75 died. The final BCS-Recanalisation score incorporated: variceal bleeding history, degree of ascites, albumin, creatinine, urea, white blood cell count and Ln (alkaline phosphatase). The score outperformed other available models with good discrimination (C-index: 0.74) and calibration in predicting TIPS-free survival in the whole cohort, internal validation and most subgroups. Moreover, patients were categorised as low-risk (BCS-Recanalisation score ≤ 2.0), intermediate-risk (2.0-2.6) and high-risk (> 2.6) groups using X-tile software, with a 5-year TIPS-free survival rate of 92.2% (95% CI: 89.5%-95.0%), 84.7% (95% CI: 80.0%-90.0%) and 67.8% (95% CI: 59.4%-77.5%), respectively (p < 0.001). Significant differences were observed in overall survival, stenting-TIPS-free survival and competing-risk adjusted outcomes (restenosis, symptom recurrence, TIPS conversion) across risk strata.

CONCLUSIONS: The BCS-Recanalisation score enables individualised outcome prediction and risk stratification in recanalisation-treated patients with BCS, showing promise for clinical application. Future external validation is required.

PMID:40751473 | DOI:10.1111/liv.70259