Prostate-specific antigen (PSA) is widely used for prostate cancer (PC) screening, but its relatively low diagnostic accuracy may compromise early diagnosis and clinical management. There is an urgent need to identify convenient, cost-effective, and non-invasive diagnostic methods to reduce the rates of false positives and false negatives associated with PSA testing for prostate cancer. Serum miRNAs hold great promise as diagnostic tumor biomarkers. This study aimed to identify a novel serum miRNA panel for PC detection, with the goal of addressing the two major limitations of PSA: high false-positive and false-negative rates. This study was conducted in three phases: biomarker screening, training, and validation. First, candidate miRNAs associated with prostate cancer were screened using the PubMed and ENCORI databases. Subsequently, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to analyze miRNA expression in serum samples from the training group: 28 PC and 28 normal controls (NC), and the validation group: 84 PC and 84 NC, and to identify differentially expressed miRNAs. We assessed their diagnostic performance using receiver operating characteristic (ROC) curves and the area under the curve (AUC). We then constructed miRNA panel diagnostic models comprising different numbers of miRNAs to balance diagnostic performance and detection costs. Finally, bioinformatics analyses were performed to identify their target genes and functional pathways. During the screening phase, 10 candidate miRNAs associated with PC were identified. In the training phase, 6 candidate miRNAs showed significant differential expression in PC compared with NC. In the validation phase, 5 candidate miRNAs (miR-101-3p, miR-154-5p, miR-199a-5p, miR-145-5p, and miR-30-5p) demonstrated favorable diagnostic performance for PC. After balancing diagnostic performance and detection costs, we ultimately selected the optimal 4-miRNA panel (miR-101-3p, miR-154-5p, miR-199a-5p, and miR-145-5p) as the final diagnostic biomarker panel for PC. This panel showed favorable diagnostic performance (AUC = 0.825, sensitivity = 83.33%, specificity = 69.05%). Bioinformatics analysis indicated that the NFASC gene may serve as a common target of this 4-miRNA panel and was significantly enriched in cancer-related pathways, suggesting its potential involvement in the development and progression of PC. A panel consisting of miR-101-3p, miR-154-5p, miR-199a-5p, and miR-145-5p exhibited excellent diagnostic efficacy for PC. This serum miRNA panel possesses translational potential and provides a novel strategy to address the two major limitations of PSA testing: high false-positive and false-negative rates. https://www.chictr.org.cn/showproj.html?proj=187882, identifier ChiCTR2200066840.
Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), but its toxicity results from multiple harmful constituents. Nicotine is a chemically defined and biologically active tobacco-related compound, yet its COPD-related molecular features remain unclear. This study aimed to identify nicotine-related transcriptomic signatures in COPD and explore their immune and single-cell relevance. Nicotine-related targets were collected from PubChem, ChEMBL, and SwissTargetPrediction. COPD transcriptomic data from GSE57148 were used to identify differentially expressed genes, which were intersected with nicotine-related targets to obtain candidate genes. CIBERSORT was applied to evaluate immune infiltration. LASSO regression and multiple machine learning algorithms were used to construct diagnostic models. Molecular subtypes were defined using consensus clustering based on SVM-derived important genes, followed by GSVA and GSEA. Single-cell RNA-seq data from GSE173896 were analyzed to characterize cell composition, gene set activity, cell-cell communication, and myeloid-cell trajectories. Molecular docking, scTenifoldKnk-based virtual knockout, and RT-qPCR validation were further performed. A total of 132 nicotine-related target genes were obtained. Nicotine-related differentially expressed genes showed distinct expression patterns between COPD and control samples and were associated with immune cell infiltration. Machine learning analysis identified an SVM model with the best diagnostic performance, achieving an AUC of 0.923. Five key genes, including CHKA, EBP, RPS6KA5, NCSTN, and CHRM3, were ranked as the most important features. COPD samples were further divided into two molecular subtypes with different immune infiltration and pathway activity. Single-cell analysis showed that nicotine-related diagnostic gene activity was enriched mainly in epithelial, stromal, endothelial, and myeloid-lineage cells. Myeloid-cell reclustering revealed inflammatory, antigen-presenting, and lipid-metabolic states. Pseudotime analysis linked SVM-prioritized genes to myeloid-cell state transitions. Molecular docking suggested potential interactions between nicotine and key target proteins. RT-qPCR confirmed decreased expression of CHKA and EBP, and increased expression of CHRM3, NCSTN, and RPS6KA5 in COPD samples. This study identified a nicotine-related diagnostic gene panel associated with immune infiltration, molecular subtypes, and myeloid-cell remodeling in COPD. These findings provide insight into nicotine-related molecular alterations, while indicating that nicotine-related signals represent only one component of cigarette smoke-associated COPD biology.
Over recent years, public awareness of ADHD has increased, alongside a rise in assessment referrals. There is urgent need for large-scale evidence on the prevalence and incidence of recorded ADHD to understand diagnostic coverage in England. Data were used from CPRD Aurum, a large longitudinal database of records from primary care practices across England. Point prevalence of recorded ADHD was estimated at a fixed index date (30.06.2025). Estimates of ADHD population prevalence from previous research were used as reference values to contextualise recorded diagnosis rates. Crude incidence of recorded ADHD per 1000 person-years was calculated overall. Annual incidence over the study period (2000-2024) was also calculated to understand trends in ADHD recording over time. Data from 3,536,476 to 42,241,788 patients were used for prevalence and incidence analyses respectively. Point prevalence of recorded ADHD was 1.19% (95%CI = 1.18-1.21), with higher prevalence in males than females, and decreasing prevalence with age. Comparisons of these estimates with documented population prevalence of ADHD showed that ADHD diagnosis rates in England remain substantially lower than published estimates of prevalence. The gap between recorded diagnosis rates and published reference prevalence estimates varied across groups, ranging from 28.71% (males aged 18-24) to 93.51% (males and females aged 65+). Crude incidence of recorded ADHD was 0.61 per 1000 person-years (95%CI = 0.61-0.61). Annual incidence rates increased markedly over the study period, with an acceleration of ADHD recording from 2020. Highest incidence was observed in males aged <18, and lowest incidence was in males and females aged 65+, for whom rates of ADHD remained stable and low across follow-up. Findings provide a detailed picture of current diagnostic coverage and temporal change. Results indicate that although ADHD diagnoses have increased substantially over the past decade, recorded ADHD diagnosis rates in England remain substantially lower than published estimates of ADHD prevalence, particularly in older age, suggesting potential under-recognition. Findings highlight an urgent need for diagnostic services that are accessible across the lifespan and adequately resourced to meet need. Medical Research Foundation (MRF-RGM-MH-24-114); British Academy (PFSS23∖230043).
Onychomycosis requires laboratory confirmation before prolonged oral antifungal therapy is initiated. Periodic acid-Schiff (PAS) staining is highly sensitive for the histopathologic diagnosis of onychomycosis but increases cost and turnaround time. This study evaluated the diagnostic accuracy of fluorescence microscopy of routine hematoxylin-eosin (H&E)-stained nail sections compared with PAS-stained nail sections. A diagnostic accuracy study was performed using archived nail clipping slides from patients evaluated between 2019 and 2023. Fluorescence microscopy of H&E-stained nail clippings served as the index test, while PAS-stained nail clippings served as the reference standard. Slides were randomly selected from de-identified records and independently assessed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. A total of 84 slides were included, comprising 42 PAS-positive onychomycosis slides and 42 PAS-negative non-onychomycosis slides. Fluorescence microscopy showed a sensitivity of 80.95% (95% confidence interval [CI], 65.88-91.40%) and a specificity of 97.62% (95% CI, 87.43-99.94%). The PPV and NPV were 97.14% (95% CI, 85.08-99.93%) and 83.67% (95% CI, 70.34-92.68%), respectively. False-negative results were primarily associated with sparse fungal elements and yeast forms lacking pseudohyphae, while the single false-positive result was associated with fluorescent plasma globules and neutrophils. Fluorescence microscopy of H&E-stained nail sections exhibits high specificity and may serve as a rapid, lower-cost adjunctive diagnostic method for confirming onychomycosis, particularly in resource-limited settings where fluorescence microscopy is available.
Phosphaturic mesenchymal tumor (PMT) is extremely rare, yet it is the most common cause of tumor-induced hypophosphatemic osteomalacia (TIO). Accurate histopathological diagnosis is critical for treatment. Nevertheless, its rarity and variable histomorphology make the diagnosis highly challenging. Notably, grungy calcification serves as a key morphological diagnostic clue for PMT. Herein, we report a case of a 57-year-old female patient who presented with a three-year history of recurrent bone pain. Laboratory investigations revealed hypophosphatemia. Whole-body positron emission tomography/computed tomography (PET/CT) showed an osteolytic lesion in the scapula. Biopsy demonstrated tumor cells arranged in a patchy pattern around the bone trabeculae and intermingled with mature adipose tissue. Myxoid degeneraty -30ion was observed in the stroma, but no calcification was identified. Immunohistochemically, the tumor cells expressed SATB2, SSTR2A, ERG, and CD56. The diagnosis of scapular PMT was ultimately established based on histopathological, clinical, and laboratory correlations, and the postoperative course showed substantial relief of bone pain and a progressive increase in serum phosphorus, which strongly reinforced this diagnosis. We report an unusual case of PMT arising in the scapula, characterized by the absence of calcification, which initially made the histopathological diagnosis elusive. This case highlights that pathologists must integrate clinical and laboratory findings, as these often provide greater diagnostic value than morphology alone, underscoring the importance of a multidisciplinary approach in diagnosing rare tumors.
Glioblastoma (GBM) rarely presents with spontaneous intracerebral hemorrhage (ICH) as the initial symptom. A massive hematoma can completely obscure the underlying tumor on imaging, leading to misdiagnosis and treatment delay. Cerebrospinal fluid (CSF) cytology is simple and inexpensive, but is underutilized in the diagnostic workup of atypical ICH. A 60-year-old man with poorly controlled hypertension presented with sudden left-sided weakness and vomiting. CT showed a large right basal ganglia hemorrhage (87.1 mL, 72.8 HU) with a midline shift of 17.8 mm. After endoscopic hematoma evacuation, hypertensive ICH was diagnosed. However, two months after discharge, the patient was readmitted with bone-flap bulging and elevated intracranial pressure. Follow-up MRI showed only a cystic lesion, interpreted as postoperative or inflammatory change. Lumbar puncture was performed for CSF cytology. Three consecutive punctures all revealed numerous atypical cells with high nuclear-to-cytoplasmic ratios, pseudopod-like protrusions, and atypical mitotic figures. CSF biochemistry showed markedly elevated protein (7.03 g/L) and decreased glucose (0.9 mmol/L). Pathology later confirmed IDH1-wildtype glioblastoma (WHO grade IV) with leptomeningeal spread. When a large hematoma masks an underlying tumor on imaging and atypical imaging features or abnormal clinical recovery are present, CSF cytology can provide a crucial diagnostic clue. This case highlights that CSF cytology should be actively pursued in patients with atypical ICH, especially when follow-up imaging shows only non-specific changes.
This study aimed to assess whether multimodal large language models (LLMs) can distinguish cholesteatoma from non-cholesteatomatous chronic otitis media (COM) on representative key-image temporal bone high-resolution computed tomography (HRCT) and to evaluate the short-interval reproducibility of their outputs. This retrospective, single-center study (2019-2024) included 101 patients (48 with cholesteatoma, 53 with non-cholesteatomatous COM) who underwent surgical treatment. The reference standard was intraoperative diagnosis with histopathological confirmation for cholesteatoma and surgical documentation for COM. For each case, six anonymized representative HRCT images reflecting standard diagnostic criteria were selected by consensus between a 4th-year radiology resident and a board-certified head and neck radiologist, both unaware of the diagnosis. Subsequently, the same images were analyzed by the GPT-5 and Gemini 2.5 Pro LLMs through their official web interfaces, utilizing structured prompts and a zero-shot approach. These evaluations were conducted in two distinct sessions (S1 and S2) with a 1-week interval. The primary endpoint was accurate binary classification. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals [(CIs); Wilson method] agreement with the reference standard and between sessions and models was assessed with the Cohen kappa (κ) coefficient; and differences in classification were assessed with the McNemar test. The radiologist achieved an accuracy of 96.0% (95% CI: 90.3-98.4) with almost perfect agreement with the reference standard (κ: 0.921). In S1, GPT-5 and Gemini 2.5 Pro achieved accuracies of 43.6% and 49.5%, and in S2, 46.5% and 47.5%, respectively. Both models combined high sensitivity (83.3%-97.9%) with low specificity (1.9%-13.2%), and balanced accuracy ranged from 0.45 to 0.52. Between-session reproducibility was fair for GPT-5 (κ: 0.360) and moderate for Gemini 2.5 Pro (κ: 0.485), and inter-model agreement was slight at both sessions (κ: 0.035 at S1 and κ: 0.086 at S2). Accuracy did not differ significantly between the two models (P = 0.211). In this single-center study, GPT-5 and Gemini 2.5 Pro, in the versions evaluated, combined high sensitivity with low specificity and showed only fair-to-moderate between-session reproducibility and exhibited slight inter-model agreement on temporal bone key-image HRCT. These findings do not support their use as independent second readers, and broader generalization to other multimodal LLMs would require the evaluation of additional models. The evaluated models lacked the spatial precision and consistency required for the accurate assessment of complex middle ear structures. This finding underscores the necessity for verification by a radiologist and continuous monitoring.
Contrast-enhanced spectral mammography (CESM) provides diagnostic capability comparable to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); however, in Japan, CESM is not routinely performed because the use of iodinated contrast agents for CESM is not approved. Evidence on CESM from Japan is therefore scarce. This study assessed the feasibility, diagnostic performance, and patient experience of CESM in Japanese patients with breast cancer. This study enrolled women aged 20-80 years with histologically confirmed breast cancer who were scheduled for surgery. CESM and DCE-MRI were performed within two months preoperatively. Images were independently interpreted by a breast radiologist. Tumor size, Breast Imaging Report and Data System (BI-RADS) category, and breast density were assessed and compared with postoperative pathology. Average glandular dose (AGD) and contrast-related reactions were evaluated. Patients answered questions regarding examination time, comfort, positioning, and preferred modality. Pearson correlation coefficients were calculated to assess the relationship among tumor sizes measured on CESM, DCE-MRI, and pathology. A total of nine patients (11 malignant lesions) were analyzed. CESM detected 10 lesions (detection rate 90.9%) and DCE-MRI detected all lesions (100%). Tumor size measured by CESM (r = 0.95) and DCE-MRI (r = 0.94) showed strong correlation with pathology. AGD averaged 3.1 mGy, and no allergic reactions occurred. Patients preferred CESM primarily due to shorter examination time, while noise and long duration were the main disadvantages of DCE-MRI. CESM demonstrated high diagnostic performance that was comparable to DCE-MRI and superior to mammography, particularly for dense breasts. Considering its shorter examination time and favorable patient acceptance, CESM may serve as a valuable diagnostic option in Japan, thus warranting further clinical research.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can obscure underlying malignancies, particularly aggressive B-cell lymphoma. Severe cytopenias and coagulopathy often preclude conventional biopsy, delaying diagnosis. To assess the diagnostic utility of transjugular liver biopsy (TJLB) in adult patients presenting with HLH, transfusion-refractory thrombocytopenia, and predominant hepatic involvement, and to explore mechanisms of thrombocytopenia. Three adult patients with HLH, hepatic lesions, and severe thrombocytopenia unresponsive to platelet transfusions were retrospectively analyzed. Conventional biopsy was contraindicated due to bleeding risk. TJLB was performed for histopathological confirmation, followed by lymphoma-directed therapy. Laboratory, imaging, and histopathological data were reviewed. TJLB established aggressive B-cell lymphoma in all patients, enabling timely chemophagocytic therapy. Platelet counts normalized within 2-4 weeks (case 1 and 2), and HLH-related hyperinflammation resolved. Thrombocytopenia was multifactorial, reflecting hemophagocytosis, immune-mediated platelet destruction, hepatic sequestration, and cytokine-mediated suppression of megakaryopoiesis. HLH may be the first manifestation of occult lymphoma. TJLB is a safe, effective diagnostic strategy in patients with hepatic involvement and high bleeding risk, facilitating early curative therapy. These cases highlight the value of a multidisciplinary, risk-adapted diagnostic approach and provide mechanistic insight into cytopenia in HLH-associated lymphoma.
Esophageal cancer (EC) remains a major public health challenge in high-incidence, resource-limited county settings, where fragmented services often lead to delayed diagnosis, suboptimal multidisciplinary care, and poor continuity of follow-up. We developed a county-adapted, integrated "prevention-screening-treatment" model with full-cycle closed-loop management and evaluated its effectiveness. We conducted a controlled pilot study in Anxi County, Fujian Province, China. The intervention was delivered through a county-township-village three-tier service network supported by a digital management platform and standardized quality-of-life (QoL) assessment. Two hundred adults with pathologically confirmed EC were enrolled and assigned (non-randomly, based on enrollment in the program pathway at first presentation) to the intervention group receiving the integrated full-cycle management model (n=100) or to a control group receiving usual county-level care (n=100). Primary outcomes included diagnostic delay, multidisciplinary team (MDT) participation, standardized follow-up, and survival outcomes. Secondary outcomes included treatment adherence, complications, QoL (EORTC QLQ-C30 and QLQ-OES18), and cost-utility (cost per quality-adjusted life year, QALY). Between-group comparisons used χ² tests and t tests; longitudinal QoL used repeated-measures analysis; and survival used Cox regression. Compared with controls, the intervention group had shorter diagnostic delay (46.8 ± 13.2 vs 88.5 ± 17.6 days; p < 0.001), higher MDT participation (91.0% vs 34.0%; p < 0.001), higher standardized follow-up (86.0% vs 32.0%; p < 0.001), and lower loss to follow-up (4.0% vs 17.0%; p = 0.001). One-, two-, and three-year overall survival was higher in the intervention group (88.0%, 75.0%, and 67.0%) than in controls (71.0%, 57.0%, and 55.0%). QoL improved more over time in the intervention group, with significant group-by-time interactions for key functional and symptom domains (all p < 0.001). Direct medical and indirect costs were lower, while QALYs were higher (0.696 ± 0.127 vs 0.602 ± 0.119; p < 0.001), resulting in a lower cost per QALY. A county-adapted, integrated full-cycle EC management model supported by a three-tier service network, digital tools, and standardized QoL measurement improved care processes, outcomes, and cost-utility. This approach appears feasible and potentially scalable to similar high-incidence county settings.
Traumatic optic nerve and retinal injuries can lead to severe visual impairment, with undetermined underlying molecular mechanism and few reliable molecular biomarkers. This study aims to identify dysregulated genes and signaling pathways potentially involved in these injuries. We first identified differentially expressed genes (DEGs) and their enriched functions using two time-course gene expression profile datasets after retinal injury of rats. The hub genes were then obtained from DEGs by protein-protein interaction network, and then assessed by receiver operating characteristic curve analysis to check their diagnostic potential in experimental datasets. The potential miRNAs and transcriptional factors (TFs) of hub genes were also investigated. We identified 312 and 262 DEGs from the two datasets, respectively, with 31 overlapped up DEGs in injury group. These co-up DEGs were highly enriched in immune response-associated pathways and visual system development pathways, including the pivotal JAK-STAT signaling pathway. We then identified 7 hub genes, of which six (Aif1, Cntf, Gfap, Lcn2, Stat1, and Stat3) were validated to be associated with diagnostic relevance in experimental datasets. We predicted 54 miRNAs and 25 TFs participating in the regulatory network of hub genes. Finally, we identified that STAT1 and STAT3 were potential transcriptional regulators in hub genes. We identified six critical hub genes and potential regulators that may participate in traumatic optic nerve injury, extending the underlying mechanisms of retinal injury.
This report describes the diagnostic and therapeutic management of Sweet's syndrome (SS) presenting as a painful forehead plaque in a patient with refractory ulcerative colitis (UC) during apparent endoscopic remission. It highlights the association between active intestinal inflammation and extraintestinal manifestations (EIMs) and evaluates the efficacy of the Janus kinase (JAK) inhibitor upadacitinib after anti-TNF therapy failure. A case study was conducted on a 60-year-old woman with refractory UC who presented with new-onset cutaneous lesions accompanied by fever. Diagnostic evaluation included skin biopsy histopathology, comprehensive microbiological cultures, serological testing, and sequential colonoscopies to assess UC activity. Histopathology revealed a dense neutrophilic infiltrate highly suggestive of SS. Infectious etiologies were ruled out. Repeat colonoscopy revealed active colitis in the setting of newly diagnosed SS. After infliximab failure, upadacitinib 45 mg/day led to pain resolution within one week and complete plaque healing by week 8, with mucosal healing and normalized inflammatory markers at follow-up. Maintenance with 30 mg/day sustained remission. Active UC may drive severe neutrophilic EIMs such as SS, even when prior endoscopy suggests remission. Re-assessment of bowel disease activity is crucial in this context. Upadacitinib rapidly controlled both conditions in this anti-TNF-refractory case, supporting JAK inhibition for similar overlapping immune-mediated presentations.
Progressive Supranuclear Palsy (PSP) is the most prevalent primary 4R-tauopathy, characterized by the pathogenic accumulation of misfolded tau protein within neurons and glial cells. Historically, clinical diagnosis relied upon the identification of Richardson's Syndrome, however, the recognition of diverse clinical phenotypes that overlap with Parkinson's disease, corticobasal syndrome, and frontotemporal dementia has complicated the diagnostic landscape and hindered the success of developing therapeutic interventions. As the field transitions toward a precision medicine paradigm, there is a growing need for validated biomarkers that can provide molecular specificity, facilitate early diagnosis, and accurately track disease progression. This paper reviews the recent advancements in neuroimaging and fluid-based biomarkers, assessing their potential to delineate PSP from similar neurodegenerative conditions and unlock the 4R-tau therapeutic pipeline. In the domain of neuroimaging, while structural magnetic resonance imaging (MRI) and the Magnetic Resonance Parkinsonism Index (MRPI) continue to provide measures of subcortical atrophy, the emergence of second-generation tau-selective positron emission tomography (PET) radioligands represents a transformative shift. New tau PET tracers offer the ability to visualize tau pathology in vivo, providing a more direct assessment of the underlying proteinopathy than traditional volumetric measures. These advancements are complemented by significant progress in fluid biomarkers. Plasma phosphorylated tau at residue 217 (p-tau217) has gained prominence as a robust marker for Alzheimer's disease, and its primary utility in PSP research currently serves as a critical negative signature to exclude amyloid-associated co-pathology. In contrast, novel assays targeting microtubule-binding region tau fragments show burgeoning potential for the specific identification of 4R-tau isoforms. Furthermore, neurofilament light chain (NfL) has been firmly established as a sensitive, albeit non-specific, indicator of neuroaxonal injury and clinical severity. Additional advancements with digital health approaches and electrophysiological assessments add to the opportunities for improved objective measures. This review concludes that the shift from clinical-only diagnostic criteria to a biomarker-enabled molecular framework is the necessary catalyst for developing effective disease-modifying therapies for PSP and related 4R-tauopathies. The synthesis of these multimodal biomarkers into a unified framework will be essential to improve participant stratification, enable the use of adaptive trial models, and provide supportive evidence of target engagement for future clinical trials.
Tick-borne diseases represent an increasing public health concern worldwide, including human granulocytic anaplasmosis (HGA). HGA is gaining relevance in travel medicine due to its expanding geographic distribution. Its true incidence remains unknown, largely due to underreporting and diagnostic challenges. HGA manifests itself by nonspecific symptoms and may be misdiagnosed as another tick-borne disease. This study aimed to direct focus on clinical manifestations of this disease and to examine the role of co-infection with other tick-borne pathogens on its clinical manifestations and laboratory results. An additional aim was to compare the obtained results with previous analysis performed on 120 patients. A retrospective clinical evaluation was conducted for all patients based on data extracted from their medical records. Each patient was assessed by the same team of physicians with extensive expertise in tick-borne diseases. The clinical assessment included a detailed history focused on key epidemiological and exposure-related factors. Patients had laboratory tests performed and all of them also had polymerase chain reaction tests to confirm infection. Overall, 22 patients with anaplasmosis were qualified. This study presents symptoms that can differentiate patients with HGA mono-infection and co-infected group with significantly elevated aspartate aminotransferase observed in the mono-infection group. Including anaplasmosis in the differential diagnosis is essential in travel medicine, particularly in febrile patients with cytopenias following travel to endemic or rural areas. A thorough diagnostic approach-integrating epidemiological history, clinical manifestations (such as fever, cytopenias, transaminase elevation, especially elevated aspartate aminotransferase levels after excluding non-infectious causes), targeted laboratory investigations, and confirmatory polymerase chain reaction testing-is critical for timely and accurate identification of HGA.
Tremor is one of the most common motor symptom across movement disorders, and its precise diagnosis has become increasingly critical. However, existing studies remain fragmented. They often focus on specific disease manifestations or isolated diagnostic techniques, but lack systematic analysis. A comprehensive review is therefore needed to consolidate insights and guide future diagnostic advancements. We systematically searched the Web of Science Core Collection (WoSCC) and ClinicalTrials.gov (January 2016-August 2025), identifying 1,145 publications and 47 trials. Bibliometric networks were then visualized and analyzed using CiteSpace, VOSviewer, and the R package "bibliometrix." Annual publication volume increased steadily, while citations rose from 2016 and peaked in 2021. The United States led in publications, whereas Germany held the highest betweenness centrality. Yale University ranked first in publication output, and University College London had the greatest betweenness centrality. Louis, Elan D was the most influential author, leading in publication count, citation frequency, and betweenness centrality. Parkinsonism and Related Disorders was the most productive journal. Clinical trials predominantly focused on essential tremor (ET) and majorly employed device-based methodologies. Research centered on four themes including quantitative tremor assessment and digital health technologies, neurophysiological evaluation, neuroimaging, and pathophysiology and biomarkers, with machine learning (ML) and deep learning (DL) emerging as key frontiers. This study comprehensively maps the research landscape in tremor diagnosis and differential diagnosis over the past decade. On this basis, it identifies current limitations, and predicts emerging research frontiers, thereby offering valuable insights and guidance for future scientific investigation.
Septic arthritis of native joints requires prompt diagnosis to prevent joint destruction and sepsis. Traditional diagnostic methods, such as synovial fluid culture and cell counts, are time-consuming and can be unreliable. The Synovasure® Alpha Defensin Lateral Flow Test (Zimmer Biomet, Claymont, DE, USA) detects alpha defensin in synovial fluid and is well-established for diagnosing periprosthetic joint infections. However, its diagnostic value in native joints remains insufficiently studied. This prospective cohort study enrolled 25 adults presenting with suspected septic arthritis of the knee. Patients were excluded if they had prior knee arthroplasty or orthopedic implants. Demographics, comorbidities, vitals, and lab values were collected. Patients who tested positive for alpha defensin on aspirated synovial fluid were compared to those who tested negative. Infection was defined as a positive synovial culture, while gout was defined as positive synovial crystals. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Nineteen patients tested positive for alpha defensin, of whom four had culture-confirmed septic arthritis. All six alpha defensin test-negative patients had negative cultures. The test demonstrated a sensitivity of 100% (CI: 39%-100%), specificity of 29% (CI: 11%-52%), PPV of 21% (CI: 16%-25%), and NPV of 100% (CI: 54%-100%). Demographics, comorbidities, and serum inflammatory markers were similar between test-positive and test-negative groups. Alpha defensin test-positive patients had a significantly higher synovial polymorphonuclear neutrophil (PMN) percentage (p<0.001). All nine patients with positive synovial crystals tested positive (p=0.04). The high sensitivity and NPV of the Synovasure® Alpha Defensin Lateral Flow Test (Zimmer Biomet) demonstrate its potential utility to rapidly rule out septic arthritis in native knees. However, the test's low specificity warrants caution, as false-positive results may occur with noninfectious inflammatory processes. While the rapid turnaround may aid in early triage and exclusion of infection, confirmatory evaluation with synovial culture remains essential to prevent misdiagnosis and overtreatment.
Community sport clubs serve as important participation environments for children with neurodevelopmental disorders (NDDs). Yet, nationwide data on their enrollment in specific sports remain scarce. This study estimated the proportions of participants identified by instructors as requiring additional support and instructor-known NDD diagnoses in judo clubs and programs. A cross-sectional survey covering all 47 Japanese prefectures was conducted in 2025. Instructors of 1,104 clubs and programs reported the total number of participants, the number requiring additional support, and instructor-known diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), specific learning disorder (SLD), and developmental coordination disorder (DCD). Proportions and 95% confidence intervals (Wilson score method) were estimated by age category. A Cochran-Armitage trend test was used to assess linear trends across ordered age groups. Overall, 1,079 of 15,360 participants (7.02%, 95% CI 6.63-7.44) were identified as requiring additional support. Proportions generally decreased with advancing age category: preschool 12.13% (10.29-14.25), elementary school 7.24% (6.66-7.88), junior high school 7.59% (6.84-8.41), high school 5.21% (4.34-6.25), and university 0.79% (0.38-1.62) (Cochran-Armitage trend test: Z = -8.64, p < 0.001). Instructor-known diagnoses were reported for 1.57% (ADHD), 0.68% (ASD), 0.70% (SLD), and 0.09% (DCD) of participants. Diagnostic categories were not mutually exclusive. The summed proportion of instructor-known diagnostic reports (3.04%) therefore represents an upper bound on the proportion of participants with any known diagnosis. Even this upper bound remained well below the instructor-identified support-need proportion (7.02%). This gap indicates that support needs in community judo extend beyond disclosed diagnoses. Participants requiring additional support are present in Japanese judo clubs and programs across prefectures. Crucially, diagnosis-independent, and age- and setting-sensitive accommodation in community sport is important. Finally, the 7.02% figure should be interpreted as a context-specific indicator of the support demand instructors perceive rather than as a clinical prevalence estimate.
Drought stress severely limits both yield and nut quality of Chinese chestnut (Castanea mollissima Blume), an economically and ecologically important woody grain species native to China. However, the genetic basis of drought tolerance in Chinese chestnut remains a research gap. Our study fills this gap by identifying novel drought-responsive genes, which represents the first comprehensive molecular characterization of drought adaptation in this species. To dissect the genetic basis of drought tolerance and develop functional markers, we investigated 316 F1 seedlings derived from the cross between the drought-tolerant 'Yanlong' cultivar and the drought-sensitive 'Shuofeng'. Bulked segregant analysis coupled with next-generation sequencing (BSA-seq) identified 80 drought-associated quantitative trait loci (QTLs) across 12 chromosomes. Integration of BSA-seq, RNA-seq, and parental resequencing resulted in the identification of a core candidate gene, CmRABE1c, encoding a ras-related protein. CmRABE1c overexpression in tobacco and poplar confirmed its negative regulatory role in drought tolerance. Notably, a GG-to-AA substitution at -312/-313 bp in the CmRABE1c promoter disrupted the GT1-motif and was significantly associated with drought tolerance across 60 chestnut accessions. Furthermore, transgenic tobacco and poplar assays proved this SNP may be diagnostic by showing that the AA allele confers superior drought tolerance compared to the GG allele. This diagnostic marker likely can be directly applied in marker-assisted selection (MAS) to screen and develop drought-tolerant chestnut cultivars, thereby accelerating breeding efficiency. In summary, this study provides valuable genetic resources and a robust functional SNP marker for drought resistance breeding in Chinese chestnut.
Irritable bowel syndrome (IBS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic, debilitating disorders characterized by substantial symptom burden, impaired quality of life, and high healthcare utilization. IBS is a disorder of gut-brain interaction with a global prevalence ranging from 3.8% to 9.2%, while ME/CFS is defined by persistent, exertion-intolerant fatigue and multisystem dysfunction. Growing evidence suggests frequent co-occurrence of these conditions, implicating shared mechanisms such as immune dysregulation, autonomic imbalance, and altered gut-brain signaling. However, the magnitude of their association has not been comprehensively quantified. We conducted a systematic review and meta-analysis by searching Embase, PubMed, Scopus, and Google Scholar databases from inception through February 2026. Eligible observational studies reporting associations or prevalence between IBS and ME/CFS were included. Random-effects meta-analyses were performed to pool odds ratios (ORs) and prevalence estimates. Heterogeneity was assessed using I2 statistics. We evaluated for publication bias and assessed for risk of bias. Twenty-two studies were included in the systematic review and 18 in the meta-analysis. Individuals with ME/CFS had significantly higher odds of IBS compared with controls (OR = 7.20; 95% CI: 2.77-18.76; I2 = 72.1%). The pooled prevalence of IBS among individuals with ME/CFS was 37% (95% CI: 23-54%), with substantial heterogeneity (I2 = 99.5%). Subgroup analysis revealed that diagnostic criteria significantly influenced prevalence (p < 0.0001), while meta-regression identified ME/CFS diagnostic criteria as a significant moderator. IBS and ME/CFS are strongly associated, suggesting shared underlying mechanisms. These findings support integrated screening approaches and coordinated, multidisciplinary management to improve outcomes in affected patients. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251006255.
This study aimed to explore the risk factors for malignant solitary pulmonary nodules (SPNs) and to develop an early integrated diagnostic model by analyzing patients' demographic data, clinical laboratory indicators, and imaging findings. This retrospective study analyzed the medical records of 516 patients with a solitary pulmonary nodule(SPN) between December 2022 and August 2025. The cohort consisted of 402 patients with benign SPN and 114 with malignant SPN. Baseline characteristics were analyzed using SPSS 25 (version 25), and all subsequent statistical analyzes were performed using R 4.1.0. Variables were treated as categorical, with a two-sided p ≤ 0.05 considered statistically significant. Independent predictors of malignant SPN were identified using logistic regression and least absolute shrinkage and selection operator (LASSO) regression models. Model performance was evaluated and compared using the area under the receiver operating characteristic curve (ROC-AUC), calibration curves, and decision curve analysis (DCA). Based on a comprehensive comparison, the final predictive model was selected and presented as a nomogram to facilitate individualized clinical decision-making. Logistic regression analysis identified five independent predictors for the benign or malignant status of pulmonary nodules:age (p = 0.04), smoking history (p = 0.02), nodule diameter (p = 0.01), lobulation (p = 0.02), and spiculation (p = 0.02). The least absolute shrinkage and selection operator (LASSO) regression model indicated that spiculation, nodule diameter, carcinoembryonic antigen, and smoking history possessed independent predictive value. Based on a comparison of predictive performance, the logistic regression model (both univariate and multivariate) demonstrated superior discrimination and calibration compared to the LASSO regression model. Consequently, a visual nomogram was developed based on the results of the logistic regression analysis. This study employed dual modeling with logistic regression and LASSO regression. The analysis identified five independent predictors for malignant SPN: age, smoking history, nodule diameter, lobulation, and spiculation. In comparison, the logistic regression model demonstrated superior discrimination and calibration. Based on these findings, a visual nomogram was developed to facilitate clinical application.