Psoriasis and Crohn's disease are chronic immune-mediated inflammatory diseases affecting distinct barrier organs, yet epidemiological, genetic, transcriptomic, and therapeutic evidence supports partial immune convergence between them. This review argues that the relationship between psoriasis and Crohn's disease reflects partial immune convergence shaped by tissue context, rather than a single shared disease entity. TNF-α and IL-23-centered type 17 immunity represent the most clinically relevant shared upstream programs, whereas downstream effector pathways, especially IL-17-related responses, are shaped differently by skin and gut barrier architecture, resident immune ecology, microbial exposure, and repair demands. We discuss the gut-skin axis with caution: barrier dysfunction, dysbiosis, microbial metabolites, and immune-cell trafficking may connect skin and intestinal inflammation, but direct causal evidence in humans remains limited. TNF inhibitors, IL-12/23 blockade, and selective IL-23 inhibitors are the most plausible options for selected patients requiring treatment compatible with both skin and gut disease, whereas IL-17 blockade and paradoxical psoriasiform reactions illustrate organ-specific therapeutic tensions. Future progress will depend on patient stratification using clinical phenotypes, biomarkers, tissue profiling, and treatment history to identify patients in whom skin and intestinal inflammation are driven by overlapping immune mechanisms.
Oral cancer and cardiovascular disease share common modifiable risk factors and contribute substantially to the global burden of non-communicable diseases. However, evidence on their sex-specific coexisting burden at the population level remains limited, particularly in middle-income countries such as Malaysia. We conducted a national level, population-based analysis of the coexisting burden of oral cancer and cardiovascular disease in Malaysia using estimates from the Global Burden of Disease 2023 study. Age-standardized incidence rates, mortality rates, and disability-adjusted life year (DALY) rates from 1990 to 2023 were examined by sex. Joinpoint regression was applied to quantify temporal trends, and uncertainty intervals were propagated for all sex ratios. Risk-attributable fractions for tobacco and alcohol use were extracted from Global Burden of Disease's comparative risk assessment framework, and a combined metric of shared risk-attributable DALY burden was calculated. Population-level smoking prevalence data were obtained from the World Health Organization. In 2023, pronounced sex differences were observed for both conditions. Males exhibited higher age-standardized DALY and mortality rates than females, with male-to-female ratios of 1.68 (95% uncertainty intervals [UIs]: 1.31-2.10) for cardiovascular disease and 1.32 (95% UI: 1.08-1.61) for oral cancer age-standardized DALY rates. Despite comparable oral cancer incidence between sexes (M:F ratio = 0.97, 95% UI: 0.66-1.26), males had a 19% higher mortality-to-incidence ratio proxy (59.7% vs 50.2%). Tobacco use was the dominant driver of sex disparities, accounting for 37.9% of oral cancer DALYs and 25.8% of cardiovascular DALYs in males, compared with 7.8% and 8.7% in females. Joinpoint analysis revealed a recent upturn in male cardiovascular mortality (2019-2023) and a sharp rebound in oral cancer DALYs after 2018 in both sexes. This study quantifies a substantial sex-specific risk-attributable coexisting burden of oral cancer and cardiovascular disease in Malaysia, with males experiencing consistently higher mortality and DALY burden. Quantifying the shared risk contribution, males bore a 5-fold higher combined tobacco- and alcohol-attributable DALY burden than females (1702 vs 342 per 100,000), driven predominantly by tobacco use. The findings underscore the importance of integrated, sex-sensitive prevention strategies addressing shared risk factors and provide population-level evidence to inform public health policy in Malaysia and similar middle-income settings.
Professionals engaged in HIV research at the end-of-life face ongoing emotional demands, yet there is limited evidence on whether brief compassion-based interventions can support resilience and team functioning in this context. To explore how members of the Last Gift team experienced a brief compassion training program and to examine its perceived value and acceptability within an emotionally demanding end-of-life HIV research setting. We conducted this qualitative study within the Last Gift, a rapid research autopsy program involving people with HIV and life-limiting illness at the University of California San Diego. Following completion of a four-week compassion training program, we held three focus group discussions with interdisciplinary team members (n = 10). We audio-recorded, transcribed, and analyzed discussions using conventional content analysis. We identified three major themes: (1) intrapersonal growth and improved inner awareness when navigating emotionally intense work; (2) changes in interpersonal relationships with enhanced capacity to extend and receive compassion; and (3) strengthening community and shared purpose in workplace culture. Participants described applying compassion practices both at work and in daily life, contributing to improved interpersonal interactions, reduced emotional reactivity, and greater workplace satisfaction. Brief compassion training programs may offer a feasible and meaningful approach to supporting well-being, emotional resilience, and team cohesion among professionals working in end-of-life HIV research, particularly when embedded within supportive organizational contexts. Further research is needed to examine sustainability and broader implementation in palliative and end-of-life research settings. Why was the study done? Professionals working in HIV research at the end of life regularly engage with participants who are seriously ill and dying. While this work is deeply meaningful, it can also be emotionally demanding. There is limited research on how to support the well-being and resilience of professionals in these settings. We wanted to understand whether a brief compassion training program could help. What did the researchers do? We offered a four-week compassion training program to members of the Last Gift research team, a rapid research autopsy program involving people with HIV and life-limiting illness at the University of California San Diego. After the program, we conducted group discussions with team members to learn about their experiences. We analyzed these discussions to identify common themes. What did the researchers find? Participants described greater self-awareness and improved ability to manage difficult emotions. They reported stronger relationships with colleagues, increased ability to give and receive compassion, and a deeper sense of shared purpose within the team. Many shared that they used the practices both at work and in their personal lives, leading to less emotional reactivity and greater workplace satisfaction. What do the findings mean? A brief compassion training program may be a practical and meaningful way to support emotional resilience and team connection among professionals working in end-of-life research. Supportive workplace cultures may further strengthen these benefits. More research is needed to examine long-term impact and broader use in palliative care and research settings.
Alzheimer's blood-based biomarker (BBM) tests using single biomarkers or ratios are well characterized, but head-to-head comparisons of multi-analyte algorithmic tests on shared cohorts are lacking. We compared a five-biomarker algorithmic immunoassay (LucentAD Complete) with an algorithmic immunoprecipitation mass-spectrometry (IP-MS) benchmark on a shared plasma cohort. Symptomatic individuals (n = 192) with longitudinal samples from Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed versus amyloid positron emission tomography (PET). Cross-sectional (n = 115) and longitudinal (n = 179; 12-year span) cohorts representing disease progression were used. The immunoassay amyloid risk score demonstrated a 0.94 area under the curve (AUC) and 92%-93% accuracy, achieving performance parity with IP-MS metrics on shared samples. The two-cutoff design yielded an intermediate zone of 10.4%-12.8%. These results establish diagnostic parity between algorithmic immunoassay and algorithmic IP-MS assay. In addition, providing individual biomarker results alongside a validated risk score offers a more granular foundation for comprehensive management than amyloid status alone, supporting premium reimbursement for multi-analyte algorithmic BBMs in clinical practice.
One of the seminal discoveries from genetic studies of autism spectrum disorder and related neurodevelopmental disorders (NDD) has been that loss-of-function (LoF) mutations in genes that impact transcriptional regulation confer substantial liability to NDD. Haploinsufficiency of the epigenetic regulator POGZ represents one of the strongest such associations; however, little is known about the mechanisms by which POGZ LoF alters early neuronal development. Here, we created an allelic series of CRISPR-engineered human induced pluripotent stem cell (hiPSC) clones harboring mono- and biallelic POGZ deletions. In hiPSC-derived neural stem cells (NSC) and Neurogenin 2-induced neurons (iN), POGZ LoF altered the expression of genes associated with synaptic and intracellular signaling and extracellular matrix organization. Our multiomics profiling also showed altered footprinting of critical transcription factors (e.g., activator protein 1 complexes) that were enriched at promoters of differentially expressed genes associated with synaptic function. To further interrogate the shared molecular changes associated with NDD, we compared our results to deletions of the transcription factor MEF2C and the sodium channel gene SCN2A that we generated in these same isogenic iN. These analyses revealed strong enrichment of extracellular matrix and intracellular signaling disruption associated with POGZ and MEF2C deletion, whereas POGZ and SCN2A haploinsufficiency exhibited shared transcriptional effects on gene modules enriched for NDD-associated genes with opposing regulatory effects. Notably, we also observed alterations to synaptic firing rate and neurite extension with biallelic deletions. These shared molecular consequences suggest key points of convergence that connect gene regulation to neuronal function in the etiology of neurodevelopmental pathologies.
Group C rotavirus (RVC) infections occur globally, but are still considered a relatively rare cause of acute gastroenteritis compared to group A rotaviruses. Prior to this outbreak, RVC had not been reported in southwestern China, and routine surveillance predominantly focused on group A rotaviruses. Most characterized Chinese RVC strains belong to the M3 genotype. This investigation documented the first laboratory-confirmed RVC outbreak in southwestern China, which affected 32 students across multiple grades. Spatiotemporal analysis linked the transmission cluster to shared school facilities, specifically classrooms adjacent to male restrooms on floors 2 to 5. Whole-genome sequencing revealed that all five sequenced strains shared an identical genotype (G4-P[2]-I2-R2-C2-M2-A2-N2-T2-E2-H2) with 0-1 single-nucleotide polymorphism differences, confirming a single-source transmission chain. Phylogenetic analysis revealed that the Luzhou strains belonged to the M2 genotype and clustered with recent strains from the Yunnan Province, Russia, and European countries, challenging the previous understanding that Chinese RVC strains predominantly belong to the M3 genotype. Public health laboratories should enhance surveillance of non-group A rotaviruses in gastroenteritis outbreaks with negative group A results, particularly in school settings. Standardized control measures effective for norovirus outbreaks, including proper vomitus management, dedicated toilet facilities, and strict hand hygiene enforcement, successfully contained this RVC outbreak within one incubation period, and should be adopted for RVC outbreaks despite the absence of pathogen-specific guidelines.
Lower educational attainment is associated with obesity and type 2 diabetes (T2D), but prospective evidence, external validation, mediator patterns, and genetic triangulation have rarely been integrated. UK Biobank analyses included 501,932 participants at baseline and 474,659 participants without baseline diabetes prospectively. Logistic and Cox models estimated associations of higher educational attainment with prevalent and incident diabetes. T2D pathway analyses evaluated adiposity, health behaviors, and cardiometabolic biomarkers. NHANES 2011-2018 provided weighted cross-sectional validation. Public GWAS summary statistics were used for genetic correlation, Mendelian randomization (MR), tissue enrichment, candidate-gene analyses, shared-locus analyses, and S-PrediXcan transcriptome-wide association analyses (TWAS). In fully adjusted UK Biobank models, higher educational attainment was associated with lower odds of prevalent T2D (OR 0.76, 95% CI 0.72-0.79) and lower risk of incident T2D (HR 0.70, 95% CI 0.68-0.72). Detailed qualification categories showed lower prevalent T2D odds for college/university degree versus no qualifications (OR 0.69, 95% CI 0.65-0.72). In NHANES, college graduation or above was associated with lower prevalent T2D odds (OR 0.69, 95% CI 0.61-0.78; n=20,502). Adiposity, smoking, alcohol use, lipids, blood pressure, and C-reactive protein attenuated the education-T2D association. Genetically predicted educational attainment was inversely associated with BMI and T2D, and BMI/T2D brain TWAS identified 19 shared multi-SNP gene signals, including NPC1, HSD17B12, MAP2K5, DHX36, BHMT, and LEPROT. Higher educational attainment was consistently associated with lower T2D risk across UK Biobank, NHANES, and genetic analyses. The results highlight modifiable metabolic and behavioral pathways relevant to T2D prevention.
Family-integrated care (FIC), grounded in the principles of family-centered care (FCC), has become an important approach for supporting children and families during pediatric intensive care. Although post-intensive care syndrome in pediatrics (PICS-p) provides one important rationale for family engagement, the scope of FIC extends beyond PICS-p to include bedside participation, communication, shared decision-making, rehabilitation, psychosocial support, and transition planning. This narrative review aims to synthesize current applications, reported benefits, implementation barriers, and future priorities for FIC in the pediatric intensive care unit (PICU). We conducted a narrative review of literature on FIC/FCC in pediatric critical care. Searches were performed in PubMed/MEDLINE, CINAHL, Embase, Web of Science, and the Cochrane Library, with emphasis on contemporary literature from 2015 to April 2026 and inclusion of selected foundational papers when conceptually necessary. Eligible evidence included observational, qualitative, mixed-methods, quality-improvement, pre-post, interventional, guideline, and review literature relevant to family participation in PICU care. The review identifies several recurring themes: the transition from restricted visitation to partnership-based care; practical family participation in routine care, communication, shared decision-making, rehabilitation, and end-of-life contexts; patient- and family-centered outcomes; structural, cultural, linguistic, and resource-related barriers; and the role of interdisciplinary teams, institutional policy, staff education, and digital tools in supporting implementation. Current evidence suggests that FIC may improve family experience, communication, parental confidence, and selected psychosocial outcomes, while its effects on long-term child outcomes and PICS-p require further pediatric-specific evaluation. Future work should prioritize clearer definitions, standardized implementation models, inclusive study designs, and pragmatic outcome measures that reflect both child and family priorities.
To evaluate empowerment and quality of life in adolescents (10-19 years of age) with chronic conditions and/or disabilities from neurology and orthopedic clinics and identify areas to improve their care and empowerment. We utilized a mixed-methods design with an explanatory sequential approach. Participants were recruited from neurology and orthopedic clinics at BC Children's Hospital and completed a demographic survey and two validated online tools: The Gothenburg Young Person's Empowerment Scale (GYPES) and Pediatric Quality of Life (PedsQL) 4.0 self-report. Semi-structured interviews were conducted to gain a deeper understanding of adolescents' feelings of empowerment. Linear regression analysis was performed to identify demographic variables associated with decreased empowerment and quality of life. Interviews were analyzed using an interpretive description framework. Forty-eight participants completed the survey. The mean reported GYPES and PedsQL scores were 58.15 ± 8.46 and 61.57 ± 22.32, respectively. Theoretical sufficiency was reached after 14 interviews. Four environmental factors leading to feelings promoting empowerment were identified: (1) shared decision-making enabled advocacy and independence, (2) education (particularly involving genetics) increased knowledge and understanding, (3) sharing stories led to empowering others, and (4) participation in physical activities promoted a sense of belonging. This study was the first to use the GYPES in adolescents with diverse disabilities and/or chronic conditions from neurology and orthopedic clinics. Adolescent patients felt empowered when they were actively involved in their health care and informed about the genetics of their diagnosis. Participants also wanted opportunities to empower others going through similar experiences. This study emphasizes the need for access to genetic counseling and opportunities for shared expression to facilitate empowerment.
Bilateral pelvic ectopic kidneys represent an exceptionally rare congenital anomaly. Their co-occurrence with Müllerian anomalies reflects shared embryological disruption of the metanephric and paramesonephric systems and carries significant clinical implications, particularly during pregnancy. A 37-year-old woman with no previous urological history presented with left flank pain. Renal ultrasound demonstrated bilateral pelvic ectopic kidneys and a 5 mm non-obstructing left renal calculus. Oral analgesia and increased fluid intake were advised. Repeat ultrasound six months later confirmed spontaneous passage of the calculus with no residual stone burden. The patient was concurrently under gynecological follow-up for a bicornuate uterus. A non-contrast pelvic magnetic resonance imaging (MRI), performed by the gynecology department, to characterize the uterine anomaly and deferred to a non-contrast protocol due to concurrent pregnancy, confirmed bilateral ectopic kidneys situated in the presacral and rectovaginal pouch of Douglas with aberrant vascular supply arising near the common iliac artery bifurcation. Renal function tests and urinalysis remained within normal limits throughout the follow-up period, including during pregnancy. The patient delivered at 37+3 weeks of gestation by elective cesarean section without maternal or urological complications and was maintained under urological surveillance post-partum, with computed tomography urography planned for full anatomical delineation. This case illustrates a rare embryologically linked combination of bilateral pelvic ectopic kidneys and a bicornuate uterus. Awareness of this association may aid multidisciplinary management across urology, gynecology, and obstetrics. Consideration should be given to evaluation for co-existing Müllerian anomalies when congenital renal anomalies are identified, and vice versa.
Motivation: Proportional Venn diagrams provide a compact representation of the relationships between sets. Each relationship is represented with a region whose area reflects the number of elements shared by a given combination of sets. This means that the number of regions grows exponentially with the number of sets, which is why proportional Venn diagrams with more than five sets are cumbersome to interpret and seldom used. However, Venn diagrams with a large number of sets may still be legible if enough regions are empty and do not need to be represented. Results: Here, we present nVenn2, the second version of the nVenn algorithm, to create quasi-proportional Venn diagrams. This new version uses a different, more flexible approach which includes steps to minimize the complexity of the diagram. Thus, computation time for nVenn2 mainly grows with the number of non-empty diagram regions, rather than with the number of sets. This property allows users to create interpretable quasi-proportional Venn diagrams with large numbers of sets. Availability and implementation: The nVenn2 algorithm is freely available as an executable program, as a web page, as an R package (nVennR2) and as a Python package (nVennPy). All interfaces allow users to edit the appearance of the resulting diagram.
Patients who receive a rare cancer diagnosis begin a diagnostic and treatment journey which is complicated by personal fear of the unknown and the reality of a scientific and clinical research community which may not have many insights, options, and definitive answers to enable long-term survival. Patients and families may initially struggle to find clinicians well-informed in the rare cancer and clinical trials of emerging therapies. Patient advocacy groups focused on specific rare cancers have established an important role and point of contact for connecting patients who share the same diagnosis, for sharing experience and perspective along the clinical journey. In this article, a patient diagnosed with uveal melanoma (UM) relates the elements of his unfolding clinical journey and the influence of a unique patient advocacy group impacting his care, decisions, personal advocacy for optimizing his own care, and quest for new and meaningful therapeutic opportunities. This journey is accompanied by a rapid evolution of prognostic analytical and clinical therapeutic research overlapping the same time frame. Key insights along the patient journey identify opportunities for clinicians to more closely observe and resolve acute and late sequelae which significantly impact quality of life after the initial diagnosis and treatment. In this article, a patient with a diagnosis of uveal melanoma recounts their diagnostic and treatment experience over 6 years. The author's insights on clinical interactions and miscues may help inform those involved in cancer research on revolutionary advances in prognostic genomics in a rare disease.
To assess the cross-software reproducibility of Computed Tomography (CT) radiomic features extracted using three widely adopted platforms (Siemens syngo.via Frontier, 3D Slicer/PyRadiomics, and mint Lesion) and to identify a subset of highly robust features suitable for multi-platform and multi-center radiomics applications. A retrospective cohort of 97 lesions (primary colorectal cancer, colorectal liver metastases, and hepatocellular carcinoma) who underwent contrast-enhanced Computed Tomography (CT) in the portal venous phase was analyzed. Semi-automatic 3D lesion segmentations were exported for radiomic extraction across the three platforms. Shared radiomic features among tools were harmonized and z-score normalized. Cross-platform similarity was assessed using distribution distance metrics, hierarchical clustering, and the Adjusted Rand Index (ARI). A novel Composite Robustness Index (CI) integrating Pearson correlation, Kolmogorov-Smirnov statistics, and mean fold-difference was developed to quantify feature-level reproducibility. First-order intensity features and key GLCM descriptors (e.g., Correlation, Joint Average, Sum Entropy) demonstrated the highest cross-software stability, with nearly superimposable distributions and strong concordance in clustering structure. Siemens syngo.via Frontier and 3D Slicer/PyRadiomics showed the highest agreement (mean ARI >0.85), while mint Lesion™-which lacks higher-order texture families-showed moderate deviations (mean ARI ≈ 0.70-0.75). High-order features, particularly GLDM and GLRLM metrics, exhibited substantial variability across platforms. The CI ranking enabled identification of a reproducible set of "highly reproducible features, " including glcm_Correlation, firstorder_Mean, firstorder_RMS, firstorder_90Percentile, and shape axis-length descriptors. Despite intrinsic software differences, a consistent subset of radiomic features remains reproducible across heterogeneous extraction tools. The combined use of distribution analysis, hierarchical clustering, and the Composite Robustness Index offers a rigorous framework for evaluating cross-platform reliability. These findings support the feasibility of multi-tool radiomics and provide a validated feature set for harmonized quantitative imaging pipelines.
Systematic reviews are essential for evidence-based practice but remain resource-intensive, particularly during full-text data extraction and structured risk-of-bias appraisal in prognostic research. These challenges are amplified in complex autoimmune diseases such as systemic lupus erythematosus (SLE). Recent advances in large language models (LLMs) have raised interest in their potential; however, rigorous benchmarking against expert reviewers in real-world rheumatology settings is limited. To evaluate the feasibility, agreement, and efficiency of customized GPT-based LLMs across two systematic-review tasks: 1) study-level data extraction in metabolomics studies of SLE, and 2) prognostic risk-of-bias appraisal in rheumatology studies using QUIPS. This two-part methodological study was nested within two PROSPERO-registered reviews. For data extraction, fifteen full-text SLE metabolomics studies were processed by human reviewers and by a customized GPT model using a shared, structured template; concordance across predefined fields and extraction time per study were compared. For prognostic appraisal, nineteen rheumatology prognostic studies with adjudicated human QUIPS domain ratings (Low/Moderate/High) were reappraised in 2025 using a customized ChatGPT model (GPT-Reviewer). Agreement with the human reference was quantified using weighted kappa (quadratic weights) with 95% confidence intervals. GPT-Reviewer generated complete domain-level QUIPS judgments for all 19 studies, with heterogeneous concordance versus adjudicated human ratings. Domain-specific κw was 0.001 for study participation (95% CI 0.000-0.002) and outcome measurement, 0.129 for study attrition (95% CI 0.028-0.241), 0.137 for prognostic factor measurement (95% CI 0.000-0.478), 0.286 for statistical analysis/reporting (95% CI 0.161-0.322), and 0.681 for study confounding (95% CI 0.488-0.847). The mean extraction time was shorter for the GPT model than for human reviewers (5.7 vs. 30.4 minutes per study). Customized GPT-based LLMs are best deployed as complementary tools within human-in-the-loop workflows; improved handling of tables/supplements and domain-specific calibration are needed before routine use in complex rheumatology evidence synthesis.
Streptomyces avermitilis NRRL 8165 is an industrial model strain for the production of abamectin. Phage contamination during the fermentation process can lead to significant economic losses. At present, the known phages of S. avermitilis NRRL 8165 are scarce, making it difficult to meet the demands of research on pollution control mechanisms. Here, we isolated a novel phage, termed CW39, from soil samples. This phage exhibits a unique biological characteristic of solid-dependent infection. Transmission electron microscopy (TEM) revealed that the head measures approximately 65 nm in diameter, while the tail has a length of roughly 266 nm. Whole-genome sequencing revealed phage CW39 was 122,122 bp in genome size, exhibiting a GC content of 49.34%. Average nucleotide identity (ANI) analysis showed that phage CW39 shares only 64.4% nucleotide identity with its closest relative in the genus Samistivirus, which is significantly below the 70% genus-level classification threshold set forth by the International Committee on Taxonomy of Viruses (ICTV). Phylogenetic tree analysis further revealed that phage CW39 forms an independent monophyletic branch at the root. These findings indicate that phage CW39 likely represents a novel putative genus within the class Caudoviricetes. CRISPR-Cas9 plasmids targeting three key proteins of CW39 (the major capsid protein, head maturation protease, and portal protein) were separately transformed into S. avermitilis NRRL 8165, and all conferred enhanced phage resistance. This study not only enriches the Streptomyces phage resource library, but also provides a feasible strategy for using the CRISPR-Cas9 system to prevent and control phage contamination in industrial fermentation.
Visual tool processing (VTP), functional grasp planning (FGP) and tool use pantomimes (TUP) are typically associated with left-lateralized cerebral mechanisms. Yet, specific relationships between their neural underpinnings and levels of processing involved are largely unknown. We studied whether similar cerebral asymmetries are observed in the three tasks across different handedness groups, and how they link to the three-action system (3AS) model. Sixty-two participants (34 non-righthanders) were scanned with fMRI. The same stimuli-12 tools and 12 control objects-were utilized in each task. Whole-brain voxel wise analyses were performed and laterality indices (LIs) calculated in critical regions of interest (ROIs) for the assessment of hemispheric dominance, links to handedness, and global between-task relationships. Depending on the region, VTP was not left lateralized, unlike FGP and TUP. The contributions of the dorso-dorsal, ventro-dorsal, and ventral stream-in 3AS associated with affordance processing, mechanical, and function knowledge-were contingent on task and phenotypic complexity. LIs for VTP and TUP, and FGP and TUP were significantly correlated. VTP and FGP LIs, unlike the TUP LIs, were linked to handedness. The global between-task relationships were contingent on processing levels. These findings shed new light on affordance encoding, and their ability to automatically invoke neurocognitive mechanisms underlying tool functions and related actions. Future models should consider the mechanisms shared, the levels of processing involved, and their contingence on task complexity, individual variability, and sensorimotor integration, regardless of the involvement of manual responses.
Janus kinase inhibitors (JAKi) and tumor necrosis factor inhibitors (TNFi) demonstrate therapeutic efficacy in psoriatic arthritis (PsA), yet comparative real-world safety data remain limited. This study quantified adverse outcome risks between JAKi and TNFi in PsA patients. Retrospective cohort study utilized the TriNetX Global Collaborative Network electronic health records. Adults aged 18-99 years with PsA initiating JAKi or TNFi without prior exposure to the alternative class were identified. Cohorts underwent rigorous 1:1 propensity score matching on 42 baseline covariates, including inflammatory markers and indication-bias proxies. Incident adverse outcomes at 1-1825 days after treatment initiation were assessed using Kaplan-Meier analysis and absolute risk calculations. Post-matching analysis included 2723 patients per cohort. Over a 5-year follow-up, JAKi initiation was associated with increased all-cause mortality [96 vs. 63 events; hazard ratio (HR) 2.012, 95% confidence interval 1.462-2.771, P = 0.048], herpes zoster (HR 1.888, P < 0.001), pneumonia (HR 1.380, P = 0.011), and sepsis (HR 1.421, P = 0.045). TNFi use demonstrated an increased risk of skin and soft tissue infections compared with JAKi (189 vs. 147 events; risk difference -0.017, P = 0.016). Rigorous adjustment eliminated a previously suspected signal for osteomyelitis. No significant differences were observed for major adverse cardiovascular events or venous thromboembolism. JAKi and TNFi exhibit distinct safety profiles in PsA. JAKi were associated with higher risks of mortality and severe or viral infections, whereas TNFi carried a higher skin and soft tissue infection risk. These findings emphasize the need for rigorous methodological adjustment in observational data and support individualized shared decision-making.
To synthesize the available evidence on the diagnostic performance of artificial intelligence for sagittal skeletal classification using lateral cephalometric radiographs and to identify methodological limitations affecting clinical translation. PubMed, Embase, Scopus, and Web of Science were searched up to July 13, 2025, following PRISMA guidelines. Eligible studies used artificial intelligence to classify skeletal Class I, II, and III relationships from lateral cephalograms and reported diagnostic performance metrics. Non-image-based models, landmarking-only studies, commercial software evaluations, and non-original reports were excluded. Risk of bias was assessed using QUADAS-2. Exploratory random-effects meta-analyses using restricted maximum likelihood were performed, with subgroup analyses by skeletal class. Because of the small number of eligible studies, heterogeneity, and multiple model-level results from shared data sets, pooled estimates were interpreted cautiously. Ninety-one records were screened, 12 underwent full-text review, four met the inclusion criteria, and three were included in quantitative synthesis, comprising an effective test sample of 2,743 across nine model arms. One study was excluded from pooling because it used combined posteroanterior and lateral inputs with best-fold reporting, limiting comparability. The pooled multiclass performance showed sensitivity of 87.0%, specificity of 91.1%, accuracy of 85.3%, and area under the receiver operating characteristic curve of 0.94. DenseNet-based models generally showed the strongest performance, whereas the Swin-T transformer model showed the weakest performance. QUADAS-2 indicated low to moderate risk of bias, with major concerns related to single-center sampling and lack of external validation. Artificial intelligence shows promising diagnostic performance for sagittal skeletal classification from lateral cephalograms. However, the current evidence remains limited, heterogeneous, and mainly single center. Therefore, pooled estimates should be considered exploratory rather than definitive indicators of clinical performance. تجميع الأدلة المتعلقة بالأداء التشخيصي للذكاء الاصطناعي في التصنيف الهيكلي السهمي باستخدام الصور الشعاعية السيفالومترية الجانبية للرأس، وتحديد الفجوات المنهجية التي قد تؤثر في تطبيقه سريريًا. وفقًا لإرشادات PRISMA، جرى البحث في قواعد بيانات PubMed وEmbase وScopus وWeb of Science حتى 13 يوليو 2025. شملت الدراسات المؤهلة تلك التي طبّقت الذكاء الاصطناعي على الصور السيفالومترية الجانبية لتصنيف العلاقات الهيكلية إلى الصنف الأول والثاني والثالث، مع الإبلاغ عن مؤشرات الأداء التشخيصي. واستُبعدت النماذج غير المعتمدة على الصور، والدراسات التي اقتصرت على تحديد النقاط المرجعية، وتقييمات البرمجيات التجارية، والتقارير غير الأصلية. جرى تقييم خطر التحيز باستخدام أداة QUADAS-2. كما أُجريت تحليلات تلوية استكشافية باستخدام نموذج التأثيرات العشوائية بطريقة الاحتمالية العظمى المقيدة REML، مع إجراء تحليلات فرعية حسب الصنف الهيكلي. ونظرًا لمحدودية عدد الدراسات المشمولة، ووجود تباين ملحوظ بينها، وتعدد النتائج على مستوى النماذج المستندة إلى مجموعات بيانات مشتركة، فُسرت التقديرات المجمعة بحذر. جرى فحص 91 سجلًا، وخضع 12 منها للمراجعة بالنص الكامل، واستوفت أربع دراسات معايير الاشتمال، بينما أُدرجت ثلاث دراسات في التحليل الكمي المجمع، بإجمالي حجم عينة اختبار فعّال بلغ 2743، وتسعة أذرع للنماذج. واستُبعدت دراسة واحدة من التحليل المجمع بسبب عدم قابليتها للمقارنة، إذ استخدمت مدخلات مشتركة من الصور الخلفية الأمامية والجانبية، واعتمدت على الإبلاغ عن أفضل تقسيم تدريبي. بلغ الأداء المجمع للتصنيف متعدد الفئات: حساسية قدرها 87.0% بفاصل ثقة 95%: 85.6–88.4، ونوعية قدرها 91.1% بفاصل ثقة 95%: 87.3–94.9، ودقة كلية قدرها 85.3% بفاصل ثقة 95%: 79.9–90.7، ومساحة تحت منحنى ROC قدرها 0.94 بفاصل ثقة 95%: 0.90–0.98. وقد أظهرت نماذج DenseNet أداءً أفضل عمومًا، في حين سجّل نموذج المحوّلات Swin-T الأداء الأضعف. وأشار تقييم QUADAS-2 إلى وجود خطر تحيز منخفض إلى متوسط، مع ملاحظات تتعلق بالاعتماد على عينات من مركز واحد وغياب التحقق الخارجي. يُظهر الذكاء الاصطناعي أداءً تشخيصيًا واعدًا في التصنيف الهيكلي السهمي اعتمادًا على الصور السيفالومترية الجانبية للرأس، إلا أن قاعدة الأدلة ما تزال محدودة على مستوى الدراسات، ومتباينة، وتعتمد غالبًا على دراسات أحادية المركز. لذلك، ينبغي تفسير التقديرات المجمعة بوصفها تقديرات استكشافية، وليست تقديرات نهائية للأداء السريري.
The nature of doctor-patient relationships (DPRs) and decision-making style (DMS) is related to patient satisfaction, clinical outcomes, and the occurrence of disputes. Given the importance of understanding the current state of DPRs, we conducted an exploratory analysis of the current state of DPRs and DMS in clinical settings in China and Japan. We explored similarities and differences between the two countries, as well as influential factors in DPRs and DMS. Twenty doctors in China and 20 doctors in Japan were recruited through the authors' personal networks as well as snowball sampling, and semi-structured interviews were conducted. Doctors were asked about mainstream DPR models and DMS in current medical practice, and their responses were analyzed using qualitative descriptive methods. Results of the analysis suggest that, in both China and Japan, a diverse mosaic of DPRs and DMS coexists. In both countries, there are paternalistic relationships between doctors and patients, as well as teacher-and-student relationships, but there are also cases in which patients make final decisions and those which adopt shared decision-making. Some doctors referred to DPRs as a friendship. Furthermore, attitudes of individual doctors and patients, the medical environment, trust between the two parties, and national and cultural characteristics strongly impact the formation of DPRs. Our findings highlight the importance of carefully monitoring the current state and various influencing factors of DPRs in order to realize effective human relationships in clinical settings.
This study aimed to elucidate the composition and diversity of microbial communities associated with bitter white lupine (BWL) root nodules, BWL rhizosphere soil, and neighboring triticale (×Triticosecale Wittmack) rhizosphere soil via 16S rRNA gene sequencing. Significant differences in microbial composition and diversity were observed among the sample types. BWL nodules harbored distinct bacterial communities dominated by nitrogen-fixing Bradyrhizobium (61.09%). While both BWL and triticale rhizosphere soils had high bacterial diversity dominated by Actinobacteriota and Proteobacteria (32.81 and 25.18% in BWL, and 27.73 and 26.41% in triticale, respectively). Although BWL and triticale rhizosphere soils shared some microbial taxa, each had substantial unique bacterial communities. Alpha diversity analysis revealed higher bacterial diversity in rhizosphere soils than in nodules. Edaphic factors, such as the organic carbon to clay ratio (soil health indicator), available phosphorus, and clay content, are important factors of rhizosphere microbial community structure. Positive correlations were found between soil organic matter, total nitrogen, and microbial diversity in rhizosphere soils. These findings provide novel insights into plant-microbe interactions in acidic, nutrient-poor soils of northwestern Ethiopia and suggest that microbiome management could enhance soil health and crop productivity in marginal agricultural lands.