To systematically evaluate and compare geometric setup errors and calculate optimal planning target volume (PTV) margins for patients with left-sided breast carcinoma treated with three-dimensional conformal radiotherapy (3D-CRT) using free-breathing (FB) versus deep inspiration breath-hold (DIBH) techniques. A retrospective analysis was conducted on 103 postoperative breast carcinoma patients (n = 47 in the FB group; n = 56 in the DIBH group). Daily setup verification was performed using paired kilovoltage (kV) orthogonal images, yielding 348 analysed fractions. Setup deviations were measured in anterior-posterior (AP), superior-inferior (SI), and right-left (RL) directions. PTV margins were derived using the Van Herk formula. In the FB group, systematic errors were 0.16 cm (AP), 0.17 cm (SI), and 0.17 cm (RL), with random errors of 0.28 cm, 0.37 cm, and 0.29 cm, respectively. In the DIBH group, systematic errors were 0.14 cm (AP), 0.16 cm (SI), and 0.16 cm (RL), with random errors of 0.25 cm, 0.29 cm, and 0.27 cm, respectively. DIBH significantly reduced setup errors in the SI direction (p = 1.1 x 10-5). Calculated PTV margins for DIBH were smaller, particularly in the SI axis (0.61 cm vs. 0.69 cm). DIBH significantly mitigates random setup errors in the longitudinal direction by stabilizing diaphragmatic motion, allowing for reduced PTV margins and improved sparing of organs at risk.
Agentic artificial intelligence (AI) systems are emerging as a transformative approach in healthcare, enabling autonomous task execution through integrated reasoning and tool use. While early implementations have largely relied on large language models (LLMs), growing evidence suggests that smaller language models may be better suited for many healthcare workflows due to their efficiency, scalability, and practicality in real-world clinical environments. This review examines the current landscape of small language models (SLMs) used in agentic healthcare applications, including clinical documentation, decision support, patient triage, and administrative automation. We synthesize available evidence on their performance, safety, and economic implications, and discuss key considerations for clinical deployment, including regulatory alignment and governance. Overall, small language models appear to offer sufficient capability for most agentic healthcare tasks while providing meaningful advantages in deployability, cost, and operational efficiency, supporting their role as a viable and often preferable alternative for clinical implementation.
This study aims to examine the prognostic value of the video head impulse test (vHIT) and caloric test in predicting hearing recovery with Idiopathic Sudden Sensorineural Hearing Loss (ISSHL). A comprehensive literature search was conducted across PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform, covering studies published up to September 15, 2025. This meta-analysis included studies examining the association between vestibular function test parameters and hearing recovery outcomes. Data were extracted from eligible Chinese and English publications for a systematic review and meta-analysis of observational studies. This study protocol was registered with PROSPERO. This meta-analysis included 781 patients from 7 studies. Normal function of the horizontal semicircular canal in vHIT (OR = 3.14, 95% CI: 1.71-5.77, P < 0.001, I2  = 0.00%), normal function of the posterior semicircular canal in vHIT (OR = 6.929, 95% CI: 3.242-14.808, P < 0.001, I2  = 0.00%), and normal caloric test results (OR = 3.184, 95% CI: 1.818-5.575, P < 0.001, I2  = 0.00%) indicated a favorable prognosis for ISSHL patients. In contrast, normal function of the anterior semicircular canal in vHIT was not associated with prognosis in ISSHL patients (P = 0.186). vHIT, caloric tests, and Vestibular Evoked Myogenic Potentials (VEMP) can comprehensively evaluate vestibular function in patients with ISSHL. Normal vestibular function is a key factor for favorable hearing prognosis in these patients. Vestibular function testing should be performed as a routine examination in patients with ISSHL, as it provides a more comprehensive understanding of their hearing prognosis. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251156585, Identifier: CRD420251156585.
MicroRNAs (miRNAs) serve as crucial regulators of gene expression and are involved in many fundamental biological processes, including cell growth, differentiation, and programmed cell death. In recent years, a growing body of evidence has highlighted the vital role of miRNAs in the pathogenesis, prognosis, and therapeutic response of glioma tumors. Given the significant increase in research in this field over the past two decades, a comprehensive bibliometric analysis is essential to evaluate scientific trends, identify key researchers, assess international collaborations, and uncover emerging topics. Such an analysis can provide a clear overview of scientific advancements and existing knowledge gaps. This study presents a systematic bibliometric review, with data collected from the Scopus database. The search strategy combined the keywords "microRNA," "Glioma," "Research Trends," and "Brain Tumor" in article titles, abstracts, and keywords. The timeframe for this review was from 2007 to 2025, and only peer-reviewed articles published in English were considered. The extracted data were analyzed based on several metrics, including the number of annual publications, research growth trends, prominent authors, national and international scientific collaborations, and keyword co-occurrence frequency. Data visualization and analysis were performed using VOSviewer software to map co-occurrence networks. The analysis of publication trends revealed that research on microRNAs in glioma showed a consistent growth from 2010 onwards, peaking in 2020 with approximately 280 published articles, but has followed a downward trend since 2021. The co-authorship analysis by country identified China and the United States as the main hubs for scientific output and international collaboration in this domain. Among authors, Galina Gabriely (Center of Neurologic Diseases, Brigham and Women's Hospital, USA), Li Gang (Department of Neurosurgery, Huashan Hospital, Fudan University, China), Wang Y (Department of Neurosurgery, Capital Medical University, China), and You Yongping (Department of Neurosurgery, Nanjing Medical University, China) were recognized as the most prolific and influential researchers based on publication volume and centrality in the co-authorship network (Gabriely et al., 2008, Li et al., 2013, Wang et al., 2025). The use of full names and institutional affiliations facilitates accurate identification of these researchers in international databases such as PubMed. The author co-authorship map revealed several active and focused research clusters. In the keyword co-occurrence analysis, terms with the highest frequency and centrality were "glioma" (n = 653), "microRNA" (n = 589), "glioblastoma" (n = 413), "mir-21" (n = 201), "migration" (n = 180), "biomarker" (n = 164), "prognosis" (n = 139), and "therapy" (n = 132), establishing them as the core concepts of the studies. Four distinct conceptual clusters were extracted: molecular and cellular mechanisms, clinical applications, signaling pathways, and comparative studies between gliomas and other cancers.To provide readers with a clearer and more comprehensive perspective of these thematic clusters, representative signature publications within each domain are highlighted. In the molecular and cellular mechanisms cluster, studies such as Chen et al. (2021) and Beylerli et al., 2022b, Beylerli et al., 2022a have elucidated how specific microRNAs regulate glioma cell proliferation, migration, invasion, and apoptosis. Within the clinical applications cluster, Tluli et al., 2023a, Tluli et al., 2023 and Mafi et al. (2022) have emphasized the diagnostic, prognostic, and therapeutic potential of microRNA signatures in glioma patients. Regarding signaling pathways, Ahmed et al. (2021) and Makowska et al. (2023) have detailed the involvement of miRNA-mediated modulation of pathways such as PI3K/AKT, p53, and Wnt/β-catenin in glioblastoma progression. Finally, in the comparative oncology cluster, studies examining shared microRNA regulatory patterns across glioma and other malignanciesincluding hepatocellular carcinoma and osteosarcoma have been reported by Faramin Lashkarian et al. (2023) and related works, illustrating the broader oncogenic and tumor-suppressive roles of microRNAs across cancer types. The inclusion of these representative publications strengthens the conceptual interpretation of the bibliometric clusters and situates the findings within the broader scientific literature. The findings of this bibliometric study indicate that research in the field of microRNAs and glioma has experienced significant growth over the last two decades, with several key countries, institutions, and authors playing a prominent role in its advancement. Emerging topics such as diagnostic biomarkers, therapeutic targets, and miRNA-related signaling pathways in glioma tumors are central to recent research. This analysis can assist researchers and scientific policymakers in identifying knowledge gaps, strengthening international collaborations, and directing future research efforts.
Oral leukoplakia (OLK) is a prevalent oral potentially malignant disorder with limited treatment options. Our previous research showed that Azoxystrobin (AZOX) induces apoptosis and inhibits mitochondrial complex III activity. Peroxiredoxin 1 (Prx1) plays an important role in OLK progression, and preliminary evidence suggests AZOX may target Prx1 to disrupt mitochondrial function. This study aims to elucidate the precise molecular mechanism by investigating AZOX's interaction with specific Prx1 residues. We employed AutoDock Vina for molecular docking to predict AZOX-Prx1 interactions. Using seamless cloning, Prx1-WT, Prx1-Trp87 mutant, and Prx1-Thr90 mutant variants were constructed and expressed in DOK and Leuk1 OLK cell lines. Comprehensive assessments included cell viability (Cell Counting Kit-8, CCK-8), apoptosis (flow cytometry), mitochondrial ultrastructure (transmission electron microscopy, TEM), mitochondrial ROS (mtROS) production, membrane potential (MMP), complex III activity, cellular energy metabolism (mitochondrial stress assay), and expression of mitochondrial apoptosis-related proteins (Western blot/immunofluorescence). Molecular docking revealed AZOX forms four hydrogen bonds with the Gln94, Thr90, and Thr49 residues of Prx1 and engages in π-π interaction with Trp87. AZOX treatment significantly inhibited cell proliferation and activated mitochondrial apoptosis, evidenced by increased Bax/Bcl-2 ratio and Cytochrome C (Cyto C) release, which was accompanied by comprehensive mitochondrial dysfunction including structural damage, complex III suppression, elevated mtROS, reduced MMP, and inhibited energy metabolism. Critically, both Trp87 and Thr90 mutations substantially attenuated AZOX's effects on mitochondrial integrity and apoptotic induction. AZOX may bind to the Trp87 and Thr90 sites of Prx1 to inhibit mitochondrial function and energy metabolism, and induce mitochondria-mediated apoptosis, thereby suppressing the progression of OLK.
This study aimed to provide a comprehensive comparison of inhibitory control performance among children with Attention-Deficit/Hyperactivity Disorder (ADHD), Specific Learning Disorder (SLD), and comorbid ADHD+SLD, relative to typically developing peers. It sought to clarify whether inhibitory control deficits are generalized across tasks or specific to distinct types of inhibition. A total of 120 children (30 per group; aged 9-11 years) participated. Three tasks assessed different facets of inhibitory control: the Stroop Color-Word Test (interference suppression), the Cued Go/No-Go Task (prepotent response inhibition), and the Stop-Signal Task (cancellation of ongoing responses). Analyses controlled for baseline processing speed. Findings revealed distinct inhibitory profiles. Children with ADHD showed broad deficits across all tasks, most pronounced in the Cued Go/No-Go Task, indicating a core weakness in prepotent response inhibition. The SLD group demonstrated slower reaction times, particularly in the Cued Go/No-Go Task in the initial analysis. Slower responses reflect both processing-speed deficits and potential differences in motor planning and execution. However, after statistically controlling for these general speed effects, the SLD group's profile revealed a specific and significant deficit only in interference suppression, with no core impairment in prepotent response inhibition or action cancellation. The comorbid ADHD+SLD group exhibited the most severe and pervasive deficits across all measures, exceeding single-diagnosis groups, suggesting a synergistic impairment. These results support the multidimensional nature of inhibitory control and highlight disorder-specific neurocognitive signatures. The findings underscore the need for differentiated assessment and intervention approaches targeting distinct inhibitory processes and processing-speed deficits, particularly in children with comorbid conditions.
This umbrella review aims to synthesize and critically evaluate existing systematic reviews and meta-analyses to determine the efficacy of extracorporeal shock wave therapy for post-stroke spasticity, along with the quality and reliability of the evidence. A comprehensive search of eight databases (up to May 2025) was conducted to identify systematic reviews and meta-analyses evaluating extracorporeal shock wave therapy for post-stroke spasticity. Two scholars independently screened the literature and extracted data. The methodological quality of the included systematic reviews and meta-analyses was appraised using AMSTAR 2, and the certainty of evidence for each outcome was rated using the GRADE approach. Overlap of primary studies across reviews was assessed and visualized using the GROOVE tool. A total of 17 systematic reviews and meta-analyses were included. Among these, 3 were rated as high quality, 2 as moderate quality, 7 as low quality, and 5 as very low quality. Evidence mapping identified 136 nodes, indicating moderate overlap. All included systematic reviews and meta-analyses suggested that extracorporeal shock wave therapy improves post-stroke spasticity. Extracorporeal shock wave therapy helps reduce spasticity, improve sensorimotor function, increase active and passive range of motion, and alleviate pain. This umbrella review suggests that extracorporeal shock wave therapy can improve post-stroke spasticity symptoms. However, due to the generally low methodological quality of the included systematic reviews and meta-analyses, the existing evidence remains limited and inconclusive. Language restrictions and the predominance of studies from a single country may also limit their generalizability. Further high-quality research is needed to strengthen the evidence base. identifier: CRD420251124065.
Pilocytic astrocytoma (PA) is a benign tumor with a low risk of high-grade transformation. High-grade astrocytoma with piloid features (HGAP) is a recently recognized tumor entity that may arise de novo or from low-grade gliomas. Here, we report a patient harboring both a fourth ventricular PA and a spinal cord tumor. Methylation profiling classified the brain tumor as PA and the spinal tumor as HGAP. Both tumors shared a KIAA1549::BRAF fusion with identical DNA breakpoints, confirming a common clonal origin. The spinal tumor also showed complex chromosome copy number aberrations, including homozygous deletion of CDKN2A/B. These findings suggest additional molecular alterations associated with tumor progression within the piloid lineage. To our knowledge, this is the first report providing comprehensive, paired molecular characterization of both PA and HGAP in the same patient, offering insight into their potential evolutionary relationship.
Ischemic stroke remains a leading cause of morbidity and mortality worldwide, with substantial heterogeneity across regions, sexes, age groups, and levels of socioeconomic development. Previous studies have described global trends; however, integrated analyses combining long-term spatiotemporal patterns, sociodemographic stratification, and future projections remain limited. Data on ischemic stroke from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database, covering 204 countries and territories. Age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs) were analyzed by age, sex, region, and sociodemographic index (SDI). Temporal trends were assessed using estimated annual percentage change (EAPC). Future disease burden from 2022 to 2041 was projected using autoregressive integrated moving average (ARIMA) models implemented with the R package forecast (version 8.24.0). Globally, from 1990 to 2021, age-standardized incidence declined from 109.79 to 92.39 per 100,000 (EAPC = -0.67), mortality from 73.15 to 44.18 per 100,000 (EAPC = -1.83), and DALYs from 1286.31 to 837.36 per 100,000 (EAPC = -1.59), whereas prevalence showed only a modest decrease (EAPC = -0.18). Marked disparities were observed across SDI levels: middle SDI regions experienced increasing prevalence (EAPC = 0.27) and incidence (EAPC = 0.12), while high SDI regions demonstrated the most pronounced reductions in mortality and DALYs. Eastern Europe, East Asia, and Southern Sub-Saharan Africa remained high-burden regions. Pronounced sex- and age-specific patterns were identified, with men exhibiting earlier peak incidence (65-79 years) and women showing later and shifting peak prevalence toward older age groups. Projections indicate that by 2041, global age-standardized prevalence will increase by approximately 15.3%, driven primarily by a substantial rise among females (from 769.40 to 1005.77 per 100,000), despite continued declines in mortality and DALYs. This comprehensive spatiotemporal analysis reveals a paradoxical pattern of increasing ischemic stroke prevalence amid declining mortality and disability, with widening sex- and SDI-related disparities. By integrating long-term trends with sex-specific future projections, this study provides novel evidence to inform targeted prevention strategies, gender-sensitive interventions, and context-specific health policy planning to mitigate the evolving global burden of ischemic stroke.
Medication adherence in older adults with chronic diseases is a public health challenge, given the growing and irreversible aging of the population, with direct repercussions on clinical outcomes and collective wellbeing. This scope review seeks to identify the main barriers and facilitators of pharmacological adherence and effective evidence-based interventions to optimize it. A scope review was conducted for the period 2015-2025. Forty-one observational and interventional scientific studies (clinical trials) were selected from PubMed, Scopus, Web of Science, and ScienceDirect. Initially, a search was performed in six databases covering public health, medicine, life sciences, and biomedicine (PubMed and ScienceDirect), evidence-based healthcare (Cochrane Library), social sciences, arts, and humanities (Scopus and Web of Science), and research output, with an emphasis on Latin America, Spain, and Portugal. The four databases with the largest number of publications on the older adult population were selected, including topics such as medication adherence (compliance with pharmacological treatment and prescribing recommendations), medication persistence (uninterrupted continuity in medication recovery and administration), and patient prioritization interventions using automated mechanisms. The final selection of articles was carried out by three experts, who performed a critical appraisal of the evidence. The discrepancies were resolved by two other researchers, following the identification, screening, selection and inclusion phases of the PRISMA-2020 guidelines. The analysis of the information was carried out through synthesis and narrative integration. Individual barriers were identified, including demographic (age, sex, educational level, and income), psychological (anxiety, depression, and self-efficacy), cultural (beliefs, fatalism, and stigmas), physical and mental health status (multimorbidity and cognitive impairment), and pharmacological (number of medications and adverse effects) factors. Facilitators identified are related to the health system (continuity of care, fragmentation of care, assertive communication, access, and provision of medicines). The interventions include personalized health education. Medication adherence in older adults should be addressed with comprehensive and sustainable interventions. These interventions combine pharmacist education, technological support, continuous monitoring, and patient participation in therapeutic decision-making. Strategies should be designed with a collaborative approach involving patients, families, and healthcare professionals, ensuring measurable clinical outcomes and improving their quality of life.
Neurosurgery is a surgical specialty that routinely deals with life-threatening pathology that has a narrow therapeutic window and a margin of error. These clinical realities, with most emergencies being medico-legal cases, often expose neurosurgical practice to medico-legal scrutiny. Adequate literature is available on medicolegal aspects of neurosurgery from other countries such as North America, Australia, and Europe. However, literature on medicolegal issues of neurosurgery in India is relatively sparse and fragmented. Here, we attempt to review the medico-legal aspects of neurosurgery in India in the light of existing legal judgments from Indian courts. An online search using the keywords "Medical," "Negligence," "Neurosurgeon," "Neurosurgery in India," and their combination was conducted. We found five journal articles available through PubMed using these keywords. Court judgments were screened using the same keywords on Indian legal websites, including Indian Kanoon, AIROnline, and SCC Online[44-46]. After analyzing all the available medicolegal cases through legal websites, we have included 32 cases in this article for discussion. In our study, we found that the doctor was found guilty of negligence in 13 cases (40.6%), while 19 appeals were dismissed (59.4%). The proportion of established medical negligence among cranial cases was found to be 46.7% (seven out of 15), while it was 35.3% (six out of 17) in spinal cases, having a p-value of 0.55. After analyzing the details of all cases, postoperative complications were found to be the major cause for litigation. Lack of adequate informed consent and communication was another common cause. Neurosurgery is complex and is highly risky; it remains highly vulnerable to medicolegal scrutiny. Strengthening documentation, informed consent, perioperative protocols, and knowledge of medicolegal aspects and their application can save medical professionals from litigation. As per the available literature, this appears to be the first comprehensive review focusing on medicolegal aspects of neurosurgery in India.
The accurate prediction of mortality risk among critically ill children represents a major challenge in Pediatric Intensive Care Units (PICUs). Artificial Intelligence (AI) can find intricate patterns linked to mortality risk by examining large volumes of clinical data. This can help physicians better predict mortality risk and provide more efficient care. A systematic review can summarize the current evidence regarding the role of AI in predicting mortality among critically ill children in the PICU. A comprehensive and systematic search was conducted across three major electronic databases: PubMed, Scopus and Web of Science. The database searches were conducted on December 2, 2024. The screening process was conducted in two stages: title and abstract screening, and full-text review. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Prediction model study Risk Of Bias Assessment Tool (PROBAST) was used to assess the risk of bias and concerns regarding the applicability of the included studies. Ultimately, the full text of 17 articles was reviewed for study evaluation and data extraction. 76% of the relevant research was conducted in 2020 or later, while 24% of the articles were published before 2020. The most frequently used algorithm in the studies was random forest. Overall, the Area Under the Receiver Operating Characteristic (AUROC) was greater than 0.8 in 88% of the studies and less than 0.8 in 12% of the studies. The studies emphasize the crucial role of machine learning and deep learning in improving mortality prediction in PICUs. The variability in AUROC values between different methods shows that while certain models excel in certain contexts, the choice of algorithm and feature selection significantly affect prediction accuracy.
This study provides a comprehensive mapping of the global research landscape on algae, microalgae, and seaweed in food-related applications over the period 1989-2024, with particular emphasis on food additives, nutraceuticals, functional foods, and bioactive compounds. Based on 929 records retrieved from the Web of Science Core Collection, a tailored bibliometric framework is employed that integrates performance analysis, science mapping, thematic evolution, and reference-year analysis, thereby linking publication dynamics with the intellectual and conceptual structure of the field. The findings indicate a pronounced and sustained growth in algae-based food research, characterized by extensive international collaboration and a rising emphasis on functional ingredients and health-promoting compounds. Thematic and conceptual analyses delineate algal extracts, bioactive compounds, polysaccharides, proteins, and lipids as the principal knowledge clusters. The evolutionary trajectory of the field reveals a progression from primarily biochemical characterization toward more application-oriented research in food, nutraceutical, and functional health domains. Collectively, these results provide a systematic evidence base to support researchers, industry stakeholders, and policymakers in understanding current research priorities and in identifying emerging directions in algae-based food innovation.
Pulmonary vascular remodeling is increasingly recognized as an important yet underappreciated component of smoking-related lung disease and may contribute to the early development of pulmonary hypertension (PH) in susceptible individuals. This systematic review examined human studies evaluating the association between cigarette smoking and quantitative measures of pulmonary vascular remodeling assessed through histologic analysis or computed tomography (CT). A comprehensive search of PubMed, Embase, and Scopus covering publications from 1990 to 2024 identified eight eligible studies, including cross-sectional and cohort designs. Histologic investigations demonstrated thickening of the intimal and medial layers, reduction in small arterial numbers, and altered elastin deposition in smokers and individuals with mild to moderate chronic obstructive pulmonary disease (COPD). CT-based studies consistently showed distal vascular pruning, reflected by reduced blood vessel volume in vessels less than 5 mm² (BV5) to total blood vessel volume (TBV) ratios and decreased percentage of cross-sectional area in vessels under 5 mm² (%CSA<5). These findings correlated with airflow limitation, functional impairment, or hemodynamic markers relevant to PH. Across study designs, a coherent pattern emerged indicating that vascular remodeling can appear early in smoking-exposed populations and may be disproportionate to parenchymal disease. These insights suggest that quantitative CT metrics may serve as noninvasive indicators of early pulmonary vascular pathology and support the recognition of a vascular-predominant phenotype in some smokers. Further longitudinal studies integrating smoking exposure, imaging, and hemodynamic assessment are needed to clarify causality and improve risk stratification for PH in this population.
To systematically evaluate and compare the in vitro cytotoxic effects of three calcium silicate-based cements [Mineral Trioxide Aggregate (MTA), Biodentine, and Calcium Enriched Mixture (CEM) Cement], focusing on their biocompatibility with human dental pulp cells in vital pulp therapy (VPT). A comprehensive search was conducted in PubMed, Scopus, Web of Science, Cochrane, ProQuest, Wiley, and Ovid (including Embase) for in vitro studies published up to February 2023. Studies evaluating cytotoxicity via cell viability assays (e.g., MTT) were included. Among 8,004 screened records, 32 studies met the inclusion criteria, with 11 included in the meta-analysis. Overall, no significant differences in cytotoxicity were identified among Mineral Trioxide Aggregate (MTA), Biodentine, and Calcium-Enriched Mixture (CEM) cement. Nevertheless, undiluted MTA and Biodentine at a 1:4 dilution were associated with a statistically significant reduction in cell viability at 48 hours (P<0.05). No other concentrations or exposure durations showed significant cytotoxic effects. CEM cement consistently demonstrated favorable biocompatibility across the included studies. These findings indicate that MTA, Biodentine, and CEM cement generally exhibit acceptable in vitro biocompatibility for vital pulp therapy. Their biological responses may be influenced by material concentration and exposure duration, emphasizing the importance of careful and controlled clinical application.
Airborne particulate matter (PM) exposure may induce brain alterations and increase risks of cognitive impairment. Pneumoconiosis patients are exposed to harmful levels of PM for an extended period, providing an opportunity and a paradigm to study the impacts of PM and its interactions with the brain and cognition. The characteristics of cognitive function and brain alterations in pneumoconiosis, as well as their associations, remain poorly understood. Demographic, structural, and resting-state functional magnetic resonance imaging, along with neurocognitive data, were collected from a cross-sectional cohort of pneumoconiosis workers (PWs) and gender- and age-matched healthy controls. Pneumoconiosis was clinically diagnosed and staged by experienced pulmonologists based on radiological findings and comprehensive occupational histories. Cognitive function was assessed using a standardized neuropsychological battery, with domain-specific analyses. Brain alterations were quantified through measurements of gray matter volume (GMV), mean fractional amplitude of low-frequency fluctuation (mfALFF), and functional connectivity (FC). Correlational analyses were performed to examine associations between neuroimaging markers and specific cognitive domains. The PW group exhibited significantly poorer global cognitive performance, with pronounced deficits in registration memory, verbal cognitive ability, and visuospatial cognitive ability (all p < 0.05). Compared with the normal control group, the PW group showed significantly altered clusters of GMV, mfALFF and FC in specific brain regions, exhibiting mixed patterns. The significant brain alterations were correlated with specific cognitive domains. Pneumoconiosis patients exhibit worse cognitive function and significant brain alterations. These brain alterations are associated with specific cognitive domains.
Lentigines, café-au-lait macules (CALMs), and vitiligo are pigmentary disorders that seldom occur together in a single individual. Their co-occurrence may indicate underlying genetic syndromes requiring differential diagnosis. We report an 18-year-old male who developed CALMs at age 11, agminated lentigines at age 13, and vitiligo on the right chest six months thereafter. Comprehensive examinations excluded Peutz-Jeghers syndrome, Leopard syndrome, Carney complex, and Neurofibromatosis type 1. Eight-year follow-up-the longest reported for this combination-demonstrated a benign natural history: Stable vitiligo throughout and lentigines reaching a plateau by early adulthood. Negative autoimmune screening suggests localized immune dysregulation, supporting the Immunocompromised Cutaneous District hypothesis. A staged therapeutic approach prioritizing vitiligo stabilization is recommended.
Protein tyrosine phosphatase non-receptor type 12 (PTPN12), a crucial enzymatic protein involved in cellular signaling, remains understudied in colorectal cancer (CRC). This study investigates this biological macromolecule's potential as a biomarker, examining its protein-protein interactions, therapeutic relevance, and immunomodulatory functions in CRC. We conducted a comprehensive analysis of PTPN12 using public datasets and clinical samples. Bioinformatics tools were employed to predict regulators and signaling pathways associated with PTPN12. Immune infiltration analysis and re-analysis of publicly available single-cell RNA sequencing (scRNA-seq) datasets were performed to explore the immunomodulatory role of PTPN12. The relationship between PTPN12 protein levels and drug susceptibility was evaluated. Functional assays validated PTPN12's role in CRC cells and its impact on oxaliplatin resistance. PTPN12 protein is significantly upregulated in CRC tissues, with its elevated expression correlating with poor prognosis. PTPN12 correlates with increased genomic instability. PTPN12 is involved in various biological processes, including the regulation of cellular and developmental processes. Furthermore, high PTPN12 expression is positively correlated with stromal cell infiltration, suggesting a potential role in modulating the immune response. These findings collectively suggest that PTPN12 may have potential as a therapeutic candidate and immunotherapy-related biomarker. Knockdown of PTPN12 inhibited CRC cell proliferation, migration, and invasion. Notably, PTPN12 protein was overexpressed in oxaliplatin-resistant CRC cells, and its inhibition restored chemosensitivity in in vitro models.​. PTPN12 shows promise as a potential biomarker and therapeutic target candidate in CRC. Our study provides preliminary insights into the role of PTPN12 in CRC pathogenesis, treatment response, and chemoresistance, which may lay the groundwork for future development of personalized therapeutic strategies pending further in vivo validation.
Preeclampsia is a pregnancy-specific hypertensive disorder, clinically defined by new-onset hypertension with proteinuria or other maternal organ dysfunction. It is a leading cause of maternal and perinatal mortality worldwide and remains an incurable condition, with delivery as the only definitive treatment. The disorder originates in placental dysfunction, characterized by inadequate trophoblast invasion and impaired spiral uterine artery remodeling, resulting in syncytiotrophoblast stress and the release of placenta-derived factors. Increased placental secretion of antiangiogenic factors, including soluble fms-like tyrosine kinase-1 and soluble endoglin, promotes angiogenic imbalance and drives widespread maternal endothelial dysfunction. This narrative review synthesizes findings from human studies and experimental research models used to investigate angiogenic dysregulation in preeclampsia, with particular focus on in vitro and in vivo models, and emerging 3-dimensional placental platforms. In vitro models, such as trophoblast organoids, placenta-on-a-chip devices, and 3-dimensional bioprinted constructs, recapitulate key aspects of the placental microenvironment and enable detailed study of aberrant angiogenesis and how to target it, while reducing reliance on limited primary tissue and improving experimental control. Complementing in vitro models, in vivo models are essential for linking placenta-derived angiogenic imbalance to maternal disease phenotypes, therapeutic responses, and fetal outcomes. This review provides a comprehensive assessment of current literature on models that recapitulate angiogenic imbalance in preeclampsia. We emphasize the importance of integrating bioengineering, cell biology, and clinical insights to improve our understanding of preeclampsia pathogenesis and to develop predictive tools and therapeutic strategies to manage angiogenic dysregulation in preeclampsia.