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These guidelines replace the previous (2019) UK guidelines for the medical and laboratory screening of sperm, egg and embryo donors and were achieved by a joint working group composed of representatives from the Association of Reproductive and Clinical Scientists (ARCS), the British Fertility Society (BFS), the British Association for Sexual Health and HIV (BASHH) and the British HIV Association (BHIVA), with review and comments from their respective memberships. It was written to guide best practice in clinics but is not intended as a tool to judge the practice of centres within the UK or beyond. Guidance on core information that should be supplied to all parties involved in donation is provided. Screening tests and standards required are summarized, as are specific considerations for known donation and embryo donation. The assessment of genetic risk and heritable disorders has been fundamentally reviewed in light of technological advances. Extended carrier screening is also discussed, although we do not suggest that this is routinely performed.

Centenarian patients constitute a rapidly growing yet understudied population in emergency medicine. Evidence regarding prognostic factors and one-year outcomes in individuals aged 100 years and older presenting to the emergency department remains limited. This retrospective observational study was conducted in the emergency department of Giresun Training and Research Hospital and included centenarian patients presenting between 2010 and 2023. A total of 160 emergency department visits from 83 unique patients were evaluated. Demographic characteristics, clinical variables, comorbidities, frailty indices, and laboratory parameters obtained at admission were recorded. Frailty was assessed using a modified frailty index excluding functional dependence (mFI-4) and the Clinical Frailty Scale (CFS). The primary outcome was one-year all-cause mortality. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were performed at the patient level using the index emergency department visit. In the descriptive visit-level analysis, non-survivor visits showed higher hospitalization frequency and less favorable inflammatory and renal function marker profiles than survivor visits, while pulmonary diseases were more frequent among non-survivors and cardiovascular diseases were more common among survivors. Modified frailty index scores did not differ significantly between groups. Higher CFS categories were associated with shorter median survival times, although Kaplan-Meier analysis showed no statistically significant separation between frailty categories. In Cox regression analysis, hospitalization at the index emergency department visit and higher blood urea nitrogen levels remained independently associated with one-year mortality. In centenarian patients presenting to the emergency department, traditional comorbidity-based frailty indices show limited discriminatory value for one-year mortality. Acute clinical presentation and laboratory parameters reflecting inflammatory burden, renal function, and physiological reserve appear to be more closely associated with outcomes. The study is not registered in a clinical trial registry.

The overuse of laboratory tests in hospitals contributes to increased healthcare costs and a larger environmental footprint. This study aimed to evaluate the impact of a rational laboratory test-ordering strategy in an internal medicine department. We conducted a prospective, single-center study in an internal medicine department. The study consisted of a baseline phase without intervention followed by an intervention phase during which internal guidelines promoting rational test ordering were implemented and supervised. The primary outcomes were changes in the volume and cost of the most frequently ordered laboratory tests. Secondary outcomes included hospital activity indicators and morbidity and mortality data. A total of 1,816 patients were admitted for inpatient care between November 2023 and April 2024. Following implementation of the rational prescribing strategy, the volume of orders significantly decreased for the ten targeted laboratory tests (complete blood count, C-reactive protein, vitamins B9 and B12, lipid panel, serum protein electrophoresis, HbA1c, vitamin D, B-type natriuretic peptide [BNP], and thyroid-stimulating hormone [TSH]), with reductions ranging from 33% to 69%. The overall cost of these tests decreased by €11,334 over three months. No significant differences were observed between the two periods in terms of number of admissions, mean length of stay, transfers to intensive care, or in-hospital mortality. Implementing a rational laboratory test-ordering strategy in an internal medicine department significantly reduced the volume and cost of testing without adversely affecting hospital activity indicators or morbidity and mortality outcomes. This simple, reproducible, and well-accepted approach represents a practical opportunity for clinical, economic, and environmental optimization.

Neurofibrillary tangles in Alzheimer's disease (AD) stereotypically spread from the medial temporal lobe to association areas and then to idiotypic areas (i.e., primary motor, somatosensory, auditory, and visual). Previous studies have reported variable and clinically relevant tangle densities across the hippocampus and association cortices, but the idiotypic tangle burden is understudied. In this study, we measured tangle density using immunohistochemistry in three idiotypic cortices (primary motor, somatosensory, and visual), three association cortices (middle frontal, superior temporal, and inferior parietal), and two hippocampal sectors (CA1 and subiculum) in 144 cases with a high level of AD neuropathologic change. Clinical diagnoses included late-onset AD (LOAD, n = 50), early-onset AD (EOAD, n = 21), behavioral variant frontotemporal dementia (bvFTD, n = 19), corticobasal syndrome (CBS, n = 18), logopenic primary progressive aphasia (lvPPA, n = 21), and posterior cortical atrophy (PCA, n = 15). We algorithmically assigned cases outside the interquartile ranges of mean tangle ratios of association:hippocampal, idiotypic:association, and idiotypic:hippocampal to mutually exclusive subtypes: idiotypic-susceptible, associative-predominant, limbic-predominant, or typical Braak (for all remaining cases). Regional tangle burdens differentiated subtypes, while female sex, younger ages, and longer disease durations also influenced tangle severity. Compared to typical Braak cases, idiotypic-susceptible and associative-predominant cases exhibited shorter disease duration and younger age at death while limbic-predominant cases were older. The MAPT H1H1 haplotype also differed by subtype, being most prevalent in limbic-predominant and least common in idiotypic-susceptible and associative-predominant subtypes. Clinically, the idiotypic-susceptible subtype associated with CBS (56%), the associative-predominant subtype with bvFTD (53%), and the limbic-predominant subtype with LOAD (14%). The typical Braak subtype characterized 74-76% of amnestic AD cases and 32-53% of non-amnestic AD cases. Moreover, k-means clustering corroborated four clusters including the idiotypic-susceptible and associative-predominant patterns. Our results confirm previously described tau subtypes and describe an idiotypic-predominant subtype with clinical relevance and distinct demographic and genetic characteristics in AD.

To evaluate the safety, etiological diagnostic value, and impact on clinical treatment decisions of transjugular liver biopsy (TJLB) and percutaneous liver biopsy (PLB) in patients with liver failure. This retrospective study included patients with liver failure who underwent liver biopsy between January 1, 2017, and November 30, 2025. Demographic characteristics, clinical data, post-procedural adverse events, and pathological diagnoses were collected and subjected to statistical analysis. A total of 53 patients with liver failure were included, comprising 40 patients with acute-on-chronic liver failure (ACLF) and 13 patients with acute or subacute liver failure. 13 patients received TJLB, all of whom had ACLF. Compared with the PLB, patients in the TJLB group had a higher international normalized ratio (INR) [1.61 (1.32, 1.98)], a lower platelet count (PLT) [89.00 (73.00, 129.00) × 10⁹/L], and were more frequently complicated by moderate to large ascites. Both PLB and TJLB were successfully performed, with a low overall complication rate and no serious adverse events. Even among patients with marked coagulation abnormalities or concomitant ascites, TJLB demonstrated acceptable safety. Histopathological examination following liver biopsy enables reclassification of both chronic liver disease etiologies and acute precipitating factors in patients with ACLF, as well as etiological diagnoses in patients with acute liver failure (ALF) or subacute liver failure (SALF). A substantial proportion of drug- or toxin-related acute liver injury was identified by histopathological examination (n = 32, 60%), leading to a decreased proportion of liver failure with unclear etiology. Based on the pathological diagnosis, treatment strategies were modified in 11% of patients, including the initiation or continuation of specific therapeutic regimens. In patients with liver failure, liver biopsy provides crucial information for determining the etiology and guiding clinical decision-making. With appropriate selection of the biopsy approach and patient population, TJLB can serve as a safe and feasible option, particularly for patients with coagulation disorders or severe ascites.

Monitoring biochemical parameters is an essential component of pharmacological safety and routine clinical practice. Abnormalities in hepatic and renal function observed during hospitalization may reflect pharmacological exposure, underlying disease processes, or their interaction. However, real-world data describing the frequency and distribution of such laboratory abnormalities in hospital settings remain limited. This study aimed to evaluate the prevalence of biochemical abnormalities of hepatic and renal function among patients receiving pharmacological therapy and to assess the frequency of laboratory alterations associated with commonly prescribed drug groups. A retrospective observational study was conducted using laboratory data from the Department of Clinical Biochemistry. The analysis included 3,500 adult patients who underwent biochemical testing while receiving pharmacological therapy between January 2023 and December 2025. The evaluated parameters included alanine aminotransferase, aspartate aminotransferase, serum creatinine, urea, sodium, and potassium. Patients were categorized according to the main pharmacological therapy received, including antibiotics, non-steroidal anti-inflammatory drugs, and antihypertensive medications. Abnormal values were defined according to institutional laboratory reference ranges. Among the 3,500 patients included in the analysis, 52.3% were male and 47.7% were female, with a mean age of 56.8&#xb1;15.4 years. Antibiotics were prescribed to 41.6% of patients, non-steroidal anti-inflammatory drugs to 33.2%, and antihypertensive medications to 25.2%. Elevated alanine aminotransferase levels were observed in 18.9% of patients, while increased aspartate aminotransferase levels were detected in 15.4%. Hepatic enzyme abnormalities were more frequently observed among patients receiving antibiotics and non-steroidal anti-inflammatory drugs, with statistically significant differences between therapy groups (p<0.05). Renal function abnormalities were identified in 14.7% of patients for creatinine and 12.9% for urea, particularly among patients treated with non-steroidal anti-inflammatory drugs. Electrolyte disturbances were less frequent, with hyponatremia observed in 6.1% and hyperkalemia in 4.3% of cases. Overall, 27.6% of patients exhibited at least one clinically relevant biochemical abnormality during hospitalization while receiving pharmacological therapy. A considerable proportion of hospitalized patients receiving pharmacological therapy present with clinically significant biochemical abnormalities affecting hepatic, renal, or electrolyte parameters. Although causality cannot be established in this retrospective design, these findings underscore the importance of systematic laboratory monitoring as part of hospital-based pharmacovigilance and patient safety strategies.

Endoscopic ultrasound (EUS)- guided drainage has emerged as a novel technique for managing pelvic abscesses. This single-center retrospective case series aims to assess the safety and efficacy of EUS-guided drainage in treating pelvic abscesses of varying etiologies from 2021 to the present. Consecutive patients with pelvic abscesses who underwent EUS-guided drainage were retrospectively reviewed. Etiologies included appendiceal abscess secondary to acute appendicitis (n&#x2009;=&#x2009;1), pelvic abscesses resulting from anastomotic leaks following rectal cancer surgery (n&#x2009;=&#x2009;2), and perianal abscesses associated with Crohn's disease (n&#x2009;=&#x2009;7). The primary outcome was technical success and reduction in abscess cavity size, assessed via follow-up imaging. Clinical success was defined as significant reduction or complete resolution of the abscess cavity size on follow-up imaging at one-month post-procedure, accompanied by clinical symptom resolution and without the need for additional interventions. Secondary outcomes included post-procedural complications and resolution of the abscess without additional interventions. EUS-guided drainage was technically successful in all cases. The median reduction in abscess size was statistically significant (Mean SD: 24.1&#x2009;&#xb1;&#x2009;11.11, p&#x2009;<&#x2009;0.05). During follow-up, imaging results confirmed significant reduction in the size of pelvic abscesses in 9 patients, except for one case at the 1-month post-procedure. None of the patients required further surgical intervention, and 2 cases recurrences were observed in the sixth- and tenth-months post-procedure. Additionally, no procedure-related complications were reported. EUS-guided drainage is a safe and effective therapeutic option for managing pelvic abscesses of various etiologies. Its efficacy, particularly in Crohn's disease-related cases, and the absence of complications in this cohort, suggest significant potential for broader clinical application.

Antimicrobial resistance (AMR) is a major global public health threat, undermining the efficacy of commonly used antibiotics. Resistance patterns differ across bacterial taxa, including Enterobacteriaceae, non-fermenting Gram-negative bacilli, and Gram-positive cocci. This study aimed to provide a comparative analysis of antimicrobial susceptibility among reference strains with defined susceptible and resistant phenotypes, alongside selected clinical isolates, to evaluate the preservation of phenotypic traits and the impact of antibiotic use. Reference susceptibility strains exhibited high susceptibility across most antibiotics, whereas resistant reference strains demonstrated multidrug resistance. Among Enterobacteriaceae, reference strains harboring ESBL and AmpC mechanisms displayed resistance to penicillins, cephalosporins, and carbapenems. Non-fermenters, including Pseudomonas aeruginosa and Acinetobacter baumannii, showed both intrinsic and acquired resistance to multiple classes, particularly carbapenems and fluoroquinolones. Gram-positive cocci largely retained susceptibility to glycopeptides and linezolid, while MRSA, high-level aminoglycoside-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae posed significant therapeutic challenges. Comparative analysis revealed that antimicrobial susceptibility is influenced not only by bacterial taxonomy but also by patterns of uncontrolled or inappropriate antibiotic use. Clinical strains of Klebsiella pneumoniae and Streptococcus pneumoniae displayed reduced and more variable susceptibility compared to the predictable profiles of reference strains. These findings highlight the importance of continuous surveillance, strict adherence to antimicrobial stewardship, and the use of standardized reference strains to ensure reliable susceptibility testing. Early detection of emerging resistance patterns is essential to guide effective therapy and mitigate the public health impact of multidrug-resistant pathogens.

Portal hypertension (PH) is one of the major complications of liver cirrhosis, traditionally assessed using invasive methods such as the hepatic venous pressure gradient (HVPG). Soluble endoglin (sENG), a marker of endothelial dysfunction and fibrosis, has been proposed as a non-invasive biomarker of various liver diseases. This study aimed to evaluate serum sENG concentrations in cirrhotic patients with PH and investigate its relationship with PH severity, alcohol consumption, and smoking. Serum concentrations of sENG were measured in clinically well-examined patients with liver cirrhosis (n&#x2009;=&#x2009;60, age range 24-82 years) with PH classified as mild, moderate, or severe according to the HVPG values measured invasively using the classical wedge technique. sENG concentrations were also compared to healthy controls (n&#x2009;=&#x2009;54). Liver enzyme activities, alcohol consumption history, and smoking habits were also recorded to assess their association with sENG. sENG concentrations were significantly higher in patients with PH compared to healthy controls (6.31; 5.14-7.30 vs. 3.70; 3.24-4.20 ng/mL, p&#x2009;<&#x2009;0.001) but did not correlate with the severity of HVPG-diagnosed portal hypertension. A moderately significant correlation was observed between sENG concentrations and GGT activities (p&#x2009;<&#x2009;0.001). Alcohol consumption, but not smoking, was associated with higher serum sENG concentrations (p&#x2009;<&#x2009;0.01). Based on our results, sENG appears to be a non-invasive marker of endothelial dysfunction/fibrosis in cirrhotic patients with PH, particularly in alcohol-related liver disease. Although it does not reflect PH severity and thus cannot be used as a diagnostic tool, it has the potential for early disease detection and risk prediction as a screening component in non-invasive approaches in clinical hepatology.

Research on the gut microbiota has primarily focused on bacterial communities. However, the role of fungi-the second-largest eukaryotic component of the gut microbiome-in the development and progression of colorectal cancer (CRC) has been less extensively studied compared to bacteria. Recent studies have revealed significant fungal dysbiosis in the intestines of CRC patients, where the enrichment of specific pathogenic fungi (e.g., Aspergillus spp.) is closely associated with tumor progression, while the reduction of certain commensal fungi may weaken their protective effects. This fungal imbalance not only directly promotes tumorigenesis through carcinogenic mechanisms but also indirectly accelerates CRC progression by reshaping the bacteria-fungi interaction network and the host immune microenvironment. This article reviews the structural alterations of fungal communities in CRC, the changing patterns of specific fungal species, the relationship between fungal dysbiosis and clinicopathological features, the potential molecular mechanisms of fungi in CRC pathogenesis, the significance of cross-kingdom microbial interactions, as well as the potential diagnostic and therapeutic applications of fungi in CRC and the challenges and prospects of novel fungal-modulating therapeutic strategies.

To compare differences between candidemia and non-candidemia in the past 12 years and to construct a predictive model of candidemia to enrich clinical data and improve the diagnosis and treatment of candidemia. A matched case-control study design was used to collect the clinical data of inpatients in a tertiary hospital in Yunnan from 2013 to 2024. The patients were divided into candidemia group and non-candidemia group (control group), and accurately matched at 1:1. SPSS was used to compare the differences in epidemiological characteristics, risk factors and survival. Drug sensitivity analysis of candidemia was performed by broth dilution method. Logistic regression analysis was performed using R language and a clinical prediction model was constructed. A total of 134 cases were collected, including 67 with candidemia and 67 without candidemia. Elderly men were significantly more susceptible to candidemia and non-candidemia. The time to positivity of blood cultures, hospitalization duration, urolithiasis distribution rate, and mortality rate of patients with candidemia were significantly higher than those of patients without candidemia (all P&#x2009;<&#x2009;0.05). Five types of Candida were isolated from patients with candidemia, and the antifungal drug sensitivities of amphotericin B, anidulafungin, caspofungin, and micafungin to all detected Candida strains were 100%. Chronic kidney disease, hepatorenal syndrome, tigecycline and amikacin use, abdominal infection, and invasive pulmonary fungal infection may be potential risk factors for candidemia. Logistic regression analysis showed that the time to positivity of blood cultures (&#x2265;&#x2009;2 days) (odds ratio [OR]&#x2009;=&#x2009;121.03, P&#x2009;<&#x2009;0.001), number of concurrent infections during hospitalization (OR&#x2009;=&#x2009;3.9, P&#x2009;<&#x2009;0.01), and blood transfusion treatment (OR&#x2009;=&#x2009;6.91, P&#x2009;<&#x2009;0.05) were risk factors, whereas fibrinogen levels (OR&#x2009;=&#x2009;0.77, P&#x2009;<&#x2009;0.01) and C-reactive protein levels (OR&#x2009;=&#x2009;0.98, P&#x2009;<&#x2009;0.01) were protective factors. The receiver operating characteristic curve, calibration curve, and clinical decision curve showed that the model was meaningful. This study found that there were differences in multiple outcomes between candidemia and non-candidemia. The five potential risk factors analyzed can be used as predictors of candidemia and may provide a reference for the diagnosis and treatment of clinical candidemia.

Single-paradigm, single-measure eye-tracking protocols have demonstrated utility in distinguishing between autistic and non-autistic children although effect sizes and reproducibility vary. There is a need for brief, scalable digital behavioral biomarkers that integrate complementary information from multiple eye-tracking paradigms and achieve improved accuracy in combination. 74 autistic and 63 non-autistic children aged 24-72 months performed five different eye-tracking paradigms (facial emotion processing, gaze-following, dynamic social versus geometric patterns, social interaction, and spinning) lasting 3.25&#xa0;min in hospital or kindergarten settings. A broad set of fixation-based metrics was extracted from each paradigm. We compared discrimination performance of single-paradigm models versus a combined multi-paradigm model using random forest (RF) classifiers. In the autistic group, symptom severity was assessed using standardized clinical measures. We further evaluated whether paradigms contributed complementary information, estimated potential clinical value of multi-paradigm models, and conducted exploratory subgrouping analyses to examine whether eye-tracking-defined profiles aligned with symptom-based groupings. All individual paradigms distinguished between autistic and non-autistic children, but RF models found a combined paradigm-based model performed best, achieving an AUC of 95% and an accuracy of 90%. Representational similarity analysis indicated that paradigms contributed partially distinct information rather than reflecting a single redundant dimension of social attention. Decision curve analysis demonstrated that the multi-paradigm model provided added net benefit across clinically relevant threshold probabilities compared with strategies based on treating all or no children as autistic. Clustering of eye-tracking features revealed three autistic subgroups with distinct visual preference profiles, whereas clustering based on clinical symptoms alone identified only two subgroups. Sex imbalance and group differences in developmental quotient may have confounded some effects. Models were only internally cross-validated in a single cohort and decision curve analysis relied on assumed clinic prevalence, so external validation and testing in larger, more diverse and high-risk samples, including other neurodevelopmental conditions, are needed. A brief multi-paradigm eye-tracking battery yields robust case-control discrimination and non-redundant behavioral readouts, suggesting that it may complement symptom-based approaches and provide a scalable behavioral framework for future studies seeking to bridge molecular findings with observable autistic profiles.

Recent advances in xenotransplantation have gained substantial public and clinical attention as genetically modified porcine organs are now being transplanted into living human recipients. While only case reports have been published to date, the first clinical trials for kidney xenotransplantation are now ongoing. This transition to clinical practice presents multiple implementation challenges for establishing scalable transplant programs while ensuring patient safety. Machine perfusion is expected to play a critical role in addressing these challenges by serving as a central platform for organ preservation, assessment, transport, and therapeutic intervention. Given the limited number of designated pathogen-free (DPF) breeding facilities, regional and international organ transport depends on robust preservation strategies during transit. Additionally, perfusion devices enable essential pre-transplant screening for zoonotic pathogens, a crucial safety measure unique to xenotransplantation. Further, given recent developments that allow for multi-day perfusion of grafts, wild-type grafts could potentially be genetically modified while being perfused ex situ. Beyond these perfusion modalities of isolated whole organs, machine perfusion offers a new therapeutic approach for patients with acute liver failure. Here, cross-circulation between a perfused genetically modified porcine organ and the patient can provide temporary liver replacement therapy. This mini-review summarizes the transformative potential of machine perfusion technology in clinical xenotransplantation with a focus on livers.

Positron emission tomography (PET) instrumentation has seen significant advances over the last 20 years. In particular, substantial improvement in electronics and scalability have allowed new clinical scanners to combine high gamma stopping power and patient geometrical coverage in the total body PET paradigm. Similarly, spatial resolution has almost reached its physical limit imposed by the uncertainty caused by the positron range and acollinearity of emitted annihilation gamma rays. Time-of-flight (ToF) offers an improvement to effective sensitivity, proportional to the reverse square of detector timing resolution. In contrast to the aforementioned, this is a development direction that has not yet been sufficiently harnessed, with state of the art remaining far from the physical limit of ToF resolution. Nevertheless, existing scanners offer a glimpse of the advantages of ToF for imaging and diagnosis. In this review, analyse the limiting factors; describe the motivation for enhancing detector ToF capabilities; explore the physical mechanisms related to ToF application; describe the state-of-the-art in clinical, prototyping and laboratory stages; offer insights on emerging approaches and their capabilities to provide scalable, and cost-effective ToF; and finally envision the future of medicine, once ultraToF of the order of 10 ps has become the standard in clinically deployed scanners.

Anesthetic management of pediatric patients with rare diseases presents substantial perioperative challenges and risks. This study evaluated the clinical competency and specific educational needs of anesthesia practitioners in China regarding the perioperative management of this vulnerable patient population. A cross-sectional survey was conducted from May 2024 and March 2025, involving 2127 anesthesia practitioners across China. Data were collected via a validated anonymous questionnaire and analyzed through descriptive statistics and chi-square tests. Among the 2,127 participants, 93.5% were anesthesiologists and 6.5% were nurse anesthetists. Of these, 43.2% (919/2127) reported previous experience in administering anesthesia to children with rare diseases. Despite this exposure, self-assessed competency levels were notably insufficient. Only 9.0% (191/2127) of respondents reported comprehensive knowledge of pediatric rare diseases, and 15.0% (318/2127) expressed adequate confidence in perioperative management protocols. Objective assessment of specific knowledge domains revealed considerable deficiencies: 14.9% (317/2127) of respondents correctly identified contraindications in muscular dystrophy, 6.6% (141/2127) demonstrated adequate understanding of difficult airway indicators, and merely 3.9% (82/2127) accurately recognized depolarizing agent risks. Comparative analysis between self-rated high-familiarity and low-familiarity groups revealed that direct clinical exposure was significantly associated with practitioners' understanding of pediatric rare diseases. Regarding the development of future anesthesia support systems for pediatric rare diseases, practitioners identified two primary requirements: comprehensive diagnostic information (58.6%, 1246/2127) and detailed anesthesia contraindications (57.0%, 1212/2127). Additionally, 50.1% (1065/2127) of respondents emphasized the importance of real-time knowledge base updates to ensure access to current clinical guidelines and safety protocols. This study highlights substantial knowledge gaps and insufficient confidence among anesthesia practitioners in the perioperative management of children with rare diseases, underscoring an urgent need for enhanced training and robust support systems in this specialized area.

Interleukin-33 (IL-33), an alarmin predominantly released by keratinocytes and endothelial cells, plays a pivotal role in type 2 immune responses and has been linked to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to explore the relationship between plasma IL-33 levels and clinical features in SLE patients. A cross-sectional study was conducted involving 133 SLE patients and 81 normal controls. Plasma IL-33 levels were measured via enzyme-linked immunosorbent assay. Clinical parameters, such as SLEDAI-2K scores, photosensitivity, skin lesion distribution, laboratory indices, immunofluorescence and immunohistochemistry results were collected. SLE patients demonstrated significantly higher circulating IL-33 levels compared to healthy controls (median 342.60&#xa0;pg/ml vs. 56.77&#xa0;pg/ml, p&#x2009;<&#x2009;0.0001). IL-33 levels were positively associated with SLEDAI-2K scores (r&#x2009;=&#x2009;0.279, p&#x2009;=&#x2009;0.001), photosensitivity (p&#x2009;=&#x2009;0.02), and facial skin lesions (p&#x2009;=&#x2009;0.001). The expression levels of the IL-33 receptor (ST2) in head and face cutaneous tissues were markedly higher than those in other anatomical regions and in normal control subjects (p&#x2009;<&#x2009;0.001). Multivariate analysis revealed negative correlations with complement C3 (&#x3b2;&#x2009;=&#x2009;-&#x2009;0.303, p&#x2009;<&#x2009;0.001) and positive correlations with IgA (&#x3b2;&#x2009;=&#x2009;0.473, p&#x2009;<&#x2009;0.001) and hs-CRP (&#x3b2;&#x2009;=&#x2009;0.310, p&#x2009;<&#x2009;0.001). Notably, IL-33 levels were higher in male patients (p&#x2009;=&#x2009;0.002) and treatment-na&#xef;ve patients (p&#x2009;=&#x2009;0.03). Our data associate circulating IL-33 with SLE activity, photosensitivity, and specific serological markers. For the association between IL-33 and cutaneous photosensitivity, this study provides further histological evidence. This finding provides a novel perspective on the mechanism of photosensitivity in SLE, demonstrating the potential of IL-33 as a biomarker for patient stratification management.

Neuroimaging studies have revealed altered functional connectome dynamics in autism spectrum disorder (ASD) and linked these alterations to clinical symptoms. However, most studies have emphasized population-level contrasts, leaving interindividual variability in connectome dynamics and its structural underpinnings poorly understood. To address this gap, we analyzed resting-state functional and structural MRI data from 939 male participants (440 with ASD, 499 typically developing controls) across 18 sites in the Autism Brain Imaging Data Exchange (ABIDE). Whole-brain functional state dynamics was characterized using five leading activity modes and their expressions via eigen-microstate analysis. Age-related trajectories of mode expressions were constructed for typically developing controls using normative modeling, enabling quantification of individual-level deviations in functional dynamics. Compared with controls, ASD individuals showed greater interindividual variability in functional deviation profiles. Unsupervised clustering of these profiles identified two robust ASD subtypes with distinct mode-specific dysfunctions. One subtype primarily involved the visual, default-mode, frontoparietal, and dorsal attention networks, whereas the other subtype primarily involved the somatomotor, visual, frontoparietal, and ventral attention networks. These subtypes were clinically dissociable, differing in restricted and repetitive behaviors and social impairments, and exhibited mode-specific brain-symptom associations. Furthermore, the subtypes exhibited distinct cortical thickness alterations, and individual subtype membership was predicted with high accuracy (83%) using a random forest classifier based on cortical thickness. The main findings were replicated in an independent cohort outside ABIDE. This study delineates two reproducible and clinically dissociable ASD subtypes and links functional connectome dynamics to structural substrates, offering novel insights into the neurobiological basis behind ASD heterogeneity.

Lactate, an energy source and metabolic by-product, has been implicated in cancer progression, but its role in colorectal cancer (CRC) remains incompletely understood. This study investigated the clinical significance, biological effects, and transcriptomic responses of CRC cells to lactate. In human CRC specimens, lactate levels were positively associated with advanced clinical stage and poorer disease-free survival. Functional assays showed that lactate promoted malignant cellular behaviors in both SW480 and HCT116 cells, while pH-control experiments suggested that these effects were not merely due to extracellular acidification alone. RNA sequencing in SW480 cells identified 1,418 differentially expressed genes after lactate treatment. GO and KEGG analyses revealed alterations in multiple metabolic and signaling pathways. qRT-PCR validated the alterations of representative genes, including HK2, VEGFA, JUNB, CCNB1, MAPK4, and COX2. In addition, flow cytometry showed activation of NF-&#x3ba;B and HIF-1&#x3b1; signaling following lactate treatment, and pharmacological inhibition of either pathway significantly attenuated the lactate-induced malignant phenotypes. Together, these findings provide transcriptomic and functional evidence that lactate promotes malignant phenotypes in CRC cells and offer exploratory mechanistic insights into the involvement of NF-&#x3ba;B and HIF-1&#x3b1; signaling.

The Clinical Genome Resource (ClinGen) Von Hippel-Lindau (VHL) Variant Curation Expert Panel (VCEP) has created variant classification specifications tailored to the VHL gene, including phenotype-driven and evidence-based criteria, utilizing somatic and germline mutational hotspots, along with functional and in-silico data. Using the American College of Medical Genetics and Genomics (ACMG) guidance and the ClinGen Sequence Variant Interpretation (SVI) recommendations, the VCEP made substantial modifications to 8 evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, BP5), while 14 had minor changes, and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied two literature sets of over >428 papers in Clinical Interpretations of Variants in Cancer (CIViC) and >8700 structured annotations using Hypothesis. From 31 pilot variants, 15 remained pathogenic/likely pathogenic, 9 resolved to benign through the stand-alone benign evidence code while 7 variants with initial uncertain classifications lacking additional evidence, remained uncertain. The versioned VHL VCEP specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.