Clinical Chemistry and Laboratory Medicine (CCLM)

Purpose To evaluate associations between optical coherence tomography angiography (OCT-A) metrics and diabetic retinopathy (DR) and compare their discrimination against conventional clinical risk factors. Methods In this cross-sectional study, 108 adult eyes (right eye if both eligible) with diabetes were recruited from tertiary ophthalmology/optometry clinics. DR was clinically graded using ETDRS categories and dichotomised as no DR vs >= mild NPDR (primary outcome). Macular 6x6 mm OCT-A (Zeiss AngioPlex) was acquired; scans with signal strength >7 and without major artefact were included. Quantitative metrics from the superficial capillary plexus included vessel density (VD) and perfusion density (PD) (central/inner/outer/full regions); structural OCT measures and FAZ parameters were secondary. Associations with >= mild NPDR were assessed using multivariable logistic regression adjusted for age, sex, HbA1c, and diabetes duration. Discrimination was evaluated with ROC curves/AUC (95% CI) and DeLong comparisons of AUCs. Results DR was present in 63% of eyes. DR was associated with lower VD (central, inner, outer, full) and lower PD (central, inner, full) (all p<=0.04). After adjustment, central VD (OR 0.82, 95% CI 0.68-0.98) and central PD (OR 0.92, 95% CI 0.86-0.99) remained independently associated with DR. The OCT-A model outperformed the clinical model (AUC 0.73 vs 0.60); the combined model yielded AUC 0.76. Conclusion VD and PD from the superficial plexus are independently associated with DR and show superior discrimination versus conventional clinical factors alone, supporting OCT-A as an adjunct for earlier DR detection.

A multiplex diagnostic test is evaluated for self-reported long COVID associated persistent symptoms and a poor recovery from a SARS-CoV-2 infection. A mass-standardised concentration of total antibodies (AC), high-quality (HQ) antibodies and percentage of HQ antibodies (HQ%) is assessed against a spectrum of spike proteins to the SARS-CoV-2 variants: Wuhan, , {delta}, and the Omicron variants BA.1, BA.2, BA.2.12.1, BA.2.75, BA.5, CH.1.1, BQ.1.1 and XBB.1.5 in three cohorts. A cohort of control patients (n = 46) recovered (CC) and a cohort of self-declared long COVID patients (n = 113) (LCC). A nested Receiver Operating Characteristic (ROC) analysis, performed for the variant with lowest HQ concentration in the spectrum, produced an area under the curve and AUC = 0.61 (0.53-0.70) for the CC vs LCC cohorts. For the LCC cohort, the cut-off thresholds for AC = 0.8 mg/L, HQ = 1.5 mg/L and HQ% of 34% were determined, leading to a 71% sensitivity and 66% specificity derived by the Youden metric. The cohorts may be fully classified based on ROC and outlier analysis to give an incidence of persistent virus 62% (95% CI 52% - 71%), hyperimmune 12% (95% CI 7% - 20%) and unclassified, 26% (95% CI 18% - 35%). The overall diagnostic accuracy for both the hyper and hypo immune is 69%. All clinical interventions can now be tailored for the heterogenous long COVID patient cohort.

Purpose: To assess the repeatability of a prototype super acuity test chart for measuring visual acuity at 12.5 cm, and its ability to detect hyperopia in adolescents and young adults. Methods: Repeatability was estimated as within-subject standard deviation of three repeated super acuity measurements performed in 41 university students (19-26 years). Associations between super acuity and cycloplegic refractive errors, ocular biometry, distance visual acuity, accommodation, age, and sex were assessed in 119 high school students (16-18 years) using linear mixed-effects models. ROC curves and Youden index were used to estimate the best super acuity thresholds to detect rest hyperopia. Results: Mean super acuities in the university and high school cohorts were 0.14 {+/-} 0.13 and 0.12 {+/-} 0.11 logMAR, respectively. Repeatability was 0.031. Super acuity was poorer in those with uncorrected hyperopia [spherical equivalent refractive error (SER) [&ge;] 1.00 D] than the others [SER < 1.00 D; P = 0.039]. There were significant associations between poorer super acuity and more positive ametropia (SER; P = 0.026), poorer accommodation amplitude (P < 0.001), shorter axial length (P = 0.013), male sex (P < 0.001), and age (P = 0.037). Sensitivity and specificity for detecting hyperopia (SER [&ge;] 1.00 D) were 63.2% and 64.2%, respectively, at a super acuity threshold of 0.09 logMAR. Discussion: The super acuity prototype shows promise as a screening indicator for hyperopia. Further studies are needed to optimize the test and testing protocol, and to assess its ability to detect uncorrected hyperopia in children.

Objectives: To evaluate the diagnostic performance of the -synuclein seed amplification assay (SAA) and characterize the impact of -synuclein co-pathology on cognitive and biological profiles in routine clinical practice. Methods: We included 398 patients from the prospective multicenter ALZAN cohort recruited from memory clinics in Montpellier, Nimes, and Perpignan. All participants underwent CSF and blood sampling with measurement of CSF biomarkers (A{beta}42/40, tau, ptau181) and plasma biomarkers (A{beta}42/40, ptau181, ptau217, GFAP, NfL). Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Clinical diagnoses were independently confirmed by two senior neurologists. Syn status was determined by SAA (RT-QuIC). Results: Of 398 patients, 19 out of 20 patients with Lewy body dementia (LBD) (95.0%) and 32 out of 203 patients with AD (15.8%) were SAA+. SAA-positivity presented a sensitivity of 95% and a specificity of 93.5% for distinguishing LBD from patients without LBD or AD. In the entire cohort, SAA+ patients showed lower MMSE scores (p<0.01), lower CSF A{beta}42/40 ratio (p<0.01), and elevated plasma GFAP (p<0.05). Within the AD group, no significant differences in CSF or blood biomarkers were observed between SAA+ and SAA- patients. Within the AD subgroup, no significant differences in CSF or blood biomarkers were observed between SAA+ and SAA- patients, except for a lower CSF A{beta}42/40 ratio in SAA+ patients (p<0.01). Interpretation: SAA demonstrates good diagnostic capabilities for detecting LBD and confirms notable Syn co-pathology in AD. This study highlights the limitations of routine CSF and emerging blood biomarkers in capturing Syn pathology and the value of integrating SAA into routine neurodegenerative disease assessment.

Diffuse Large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma in the Western world. First-line immunochemotherapy fails in approximately 30-40% of patients, with refractory and relapse patients presenting a dismal prognosis. Currently, these high-risk patients cannot be accurately identified at diagnosis. Using statistical modeling and machine learning approaches applied to large public DLBCL datasets, we identified a novel predictive signature based on the reactivation of eight normally silent tissue-dependent genes associated with survival. We then developed a multiplex RT-MLPseq based assay, compatible with formalin-fixed paraffin-embedded (FFPE) samples and transferable into routine clinical practice, enabling analysis of expression of these eight genes and validated their prognosis impact in an independent real-life cohort. This signature could be integrated with current prognostic indices and molecular classifications to improve patient stratification and guide treatment selection toward a personalized theragnostic approach, thereby enhancing management of non-responder patients.

Background: Mucormycosis is a rapidly progressive and often fatal invasive fungal infection caused by moulds in the order, Mucorales. Early diagnosis is essential for effective clinical management; however, conventional diagnostic approaches such as culture and histopathology are slow, insensitive, and require specialist mycological expertise. Although molecular methods are available for disease detection, they are not widely accessible. At present, no enzyme immunoassay (EIA) exists for the detection of mucormycosis. Methods: A murine IgG1 monoclonal antibody (mAb), FH12, was generated against extracellular polysaccharides (EPSs) produced by Mucorales pathogens during active growth. The antibody was characterised for specificity, epitope stability, and antigen localisation using ELISA, immunoblotting, and immunofluorescence techniques. The mAb was incorporated into a Sandwich-ELISA and evaluated using culture filtrates, purified EPSs spiked into human serum, and tissue homogenates from a patient with cutaneous mucormycosis caused by Lichtheimia ramosa. Results: mAb FH12 demonstrated pan-Mucorales specificity and no cross-reactivity with other clinically relevant yeasts and moulds. The epitope recognised by FH12 is periodate-insensitive and moderately heat-stable. The Sandwich-ELISA detected EPS antigens in human serum with limits of detection ranging from pg/mL to low ng/mL levels, and successfully identified the EPS biomarker in patient tissue homogenates. Conclusion: The FH12-based Sandwich-ELISA shows high sensitivity and specificity, and has the potential to be used as a laboratory-based adjunct diagnostic test for the detection of mucormycosis in humans.

Aims The oral glucose tolerance test (OGTT) is effective for detecting post-load dysglycemia, but it is burdensome and therefore not routinely used. Continuous glucose monitoring (CGM) offers a convenient way to capture real-world glucose patterns, yet it remains unclear whether CGM-derived metrics reflect OGTT-defined dysglycemia. We therefore aimed to evaluate CGM-derived and clinical metrics for predicting OGTT 2-hour glucose, classifying OGTT-defined dysglycemia, and assessing day-to-day repeatability. Methods We analyzed a cohort with paired free-living CGM and OGTT. Multiple CGM-derived metrics and clinical measures were compared for prediction of OGTT 2-hour glucose, classification of OGTT-defined dysglycemia, and day-to-day stability. Predictive performance was assessed primarily by leave-one-out (LOO) R^2, and day-to-day repeatability by intraclass correlation coefficients (ICC). Results The glycemic persistence index (GPI), a metric integrating the magnitude and duration of glycemic elevation, was the strongest single predictor of OGTT 2-hour glucose (LOO R^2 = 0.439). GPI also showed strong day-to-day repeatability (ICC = 0.665) and ranked first on a combined prediction-stability score. For classification of OGTT-defined dysglycemia, HbA1c had a slightly higher AUC than GPI, but GPI plus HbA1c performed best overall, indicating complementary information. Conclusions GPI was a strong predictor of OGTT 2-hour glucose and showed a favorable balance between predictive performance and day-to-day stability, supporting its potential utility as a CGM-derived marker of dysglycemia.

Abstract Background Timely diagnosis of tuberculosis and drug resistance remains a cornerstone of effective disease control. Multiplex open molecular platforms capable of simultaneously detecting Mycobacterium tuberculosis complex (MTBc), non-tuberculous mycobacteria (NTM), and resistance to first-line anti-tuberculosis drugs could streamline diagnostic pathways. Methods We conducted a laboratory-based evaluation of two multiplex real-time PCR assays (MTBc/NTM R-Gene and MTB-RIF/INH R-Gene) using 300 well-characterized samples, including 150 MTBc-positive culture isolates (including rifampicin-resistant, isoniazid-resistant, and drug-susceptible strains) and 150 MTBc-negative samples (50 NTM isolates and 100 mycobacteria-negative specimens). Composite reference standards included culture, MPT64 antigen testing, and line probe assay corroborated by phenotypic drug susceptibility testing for resistance profiling, with NTM speciation performed using a dedicated line probe assay. DNA extraction was performed using the QIAamp DNA Mini Kit (QIAGEN, Germany), followed by amplification on a real-time PCR platform according to manufacturer instructions. The diagnostic performance was assessed against composite reference standards. Results The analytical performance for detecting MTBc demonstrated 100% sensitivity and specificity (150/150). NTM detection showed 70.0% sensitivity (35/50) and a specificity of 100%, highlighting limitations in coverage of NTM species. Rifampicin resistance was detected with a sensitivity of 96.0% (48/50) and specificity of 100%, whereas isoniazid resistance detection was 100% sensitive and specific (50/50). Agreement with established reference standards was high ({kappa}=0.76-1.00) within this analytical context. Interpretation This analytical validation demonstrates that multiplex open real-time PCR assays can accurately and simultaneously detect MTBc, NTM, and rifampicin and isoniazid resistance using culture isolates. While these platforms offer potential advantages in flexibility and expanded resistance profiling, additional studies on clinical diagnostic accuracy, cost-effectiveness analyses, and operational feasibility are required to determine their practical utility and programmatic impact in high-burden settings

Background Group A streptococcus (GAS) infections have been associated with neuropsychiatric disorders in epidemiologic studies and animal models, but data in US health care populations are limited. GAS is also associated with autoimmune sequelae, including acute rheumatic fever (ARF)/Sydenham chorea (SC), poststreptococcal reactive arthritis (PSRA), poststreptococcal glomerulonephritis (PSGN), and guttate psoriasis (GP). Epstein-Barr virus (EBV) has been linked to systemic lupus erythematosus (SLE) and multiple sclerosis (MS) and the complexity of these associations parallels that of GAS-associated conditions, providing a useful comparison. Objectives 1) Assess the association between a positive GAS test and incident neuropsychiatric diagnoses within 1 year in a large US health care database. 2) Assess the validity of the same database in detecting well-established disease associations while avoiding false associations. Design, Setting, Participants Retrospective cohort study using TriNetX data from US health care organizations. Patients with positive or negative tests were propensity score-matched (GAS cohort n=178,301; EBV cohort n=64,854). Patients with documented neuropsychiatric diagnoses prior to testing were excluded. To approximate a primary care population, inclusion required at least one well-visit. Exposures Positive vs negative GAS test; positive vs negative EBV test (separate cohorts). Main Outcomes and Validations Main outcome: incident neuropsychiatric diagnoses within 1 year of GAS testing. Positive control outcomes: ARF/SC, PSRA, PSGN, and GP (for GAS cohort); SLE and MS (for EBV cohort). Negative control outcomes: conditions without known association with GAS. Results After matching, a positive GAS test was associated with attention-deficit/hyperactivity disorder (ADHD) (RR: 1.09; 95% CI: 1.03-1.15). Among established poststreptococcal conditions, only GP was associated with prior GAS (RR: 1.75; 95% CI: 1.06-2.89). Case counts were insufficient to evaluate ARF/SC, PSRA, and PSGN. Negative control outcomes showed no association. In the EBV cohort, no association was observed with SLE, and MS showed a decreased risk. Conclusions and Relevance A positive GAS test was associated with ADHD but not with other neuropsychiatric disorders. The database detected poststreptococcal GP but did not identify most established postinfectious autoimmune associations, likely reflecting rarity, heterogeneity, and diagnostic complexity. These findings begin to describe the range of real-world health care databases to evaluate postinfectious neuropsychiatric risk.

Aim: To comprehensively characterize the salivary proteome in periodontitis using Orbitrap Astral data-independent acquisition mass spectrometry (DIA-MS), identify an atlas of differentially expressed proteins (DEPs), and develop a machine learning-derived multi-protein biomarker panel for non-invasive diagnosis of stage III/IV periodontitis. Materials and Methods: Unstimulated saliva samples from 199 participants (periodontal health/gingivitis, n=120; stage III/IV periodontitis, n=79) were analyzed by Orbitrap Astral DIA-MS. DEPs were identified, and pathway enrichment analysis was performed. A two-tier machine learning pipeline, integrating pathway-based feature selection with cross-validated evaluation, was applied to identify the optimal diagnostic panel. Results: Orbitrap Astral DIA-MS quantified 5,597 salivary proteins and 1,966 DEPs (|log2FC|>0.5, FDR<0.05). Pathway analysis identified 14 periodontitis-relevant KEGG pathways, including Th17 cell differentiation, IL-17 signaling, neutrophil extracellular trap formation, and complement and coagulation cascades. A four-protein panel (TEC, RAC1, MAPK14, KRT17) achieved an area under the curve (AUC) of 0.985 plus-or-minus sign 0.010, with 83% sensitivity and 100% specificity. The panel was corroborated using public datasets. Conclusions: To our knowledge, this study represents the first application of Orbitrap Astral DIA mass spectrometry in periodontitis research, establishing a disease-specific DEPs atlas and a salivary biomarker panel with high diagnostic accuracy for stage III/IV periodontitis, providing a foundation for future external validation studies.

BackgroundAccelerated long-term forgetting (ALF), defined as an increased rate of memory loss over extended intervals, has so far been detected in a pilot study of patients with mild multiple sclerosis (MS). This study aimed to (I) confirm the presence of ALF in a larger, heterogeneous MS sample, (II) explore associations with patient-reported outcomes, and (III) assess the diagnostic performance of ALF tests for subjective memory impairment. MethodsThis study compared 62 MS patients and 65 age-, sex-, and education-matched healthy controls using standardized memory tests (RAVLT, WMS-IV Logical Memory subtest). Recall was assessed immediately, after 30 minutes, and after 7 days. Seven-day/30-minute recall ratios (QRAVLT, QWMS) served as primary outcomes. Self-report measures included memory complaints, fatigue, depression, and sleep disturbances. Linear regression and Receiver operating characteristic (ROC) analyses assessed predictors and diagnostic accuracy. ResultsALF was observed in multiple sclerosis since QRAVLT was lower in patients than in controls (0.64 [95% CI 0.59-0.69] vs. 0.78 [0.73-0.82], p < 0.001), as was QWMS (0.79 [95% CI 0.74-0.84] vs. 0.95 [0.90-1.00], p < 0.001), despite comparable initial learning. Greater fatigue, higher memory complaints, longer disease duration, older age, and greater disability were associated with lower ALF scores. The combined ALF score moderately discriminated subjective memory impairment (AUC 0.74; sensitivity 0.73; specificity 0.73). ConclusionMS patients showed ALF despite normal initial learning, indicating a specific memory deficit undetected by standard tests. Long-delay recall using RAVLT and WMS-IV Logical Memory subtest may improve cognitive impairment detection in MS.

BackgroundChronic relapsing inflammatory optic neuropathy (CRION) is a steroid-dependent form of optic neuritis with incompletely understood pathophysiology. The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) in a substantial patient subset has challenged the diagnostic and therapeutic management. The aim of this study was to investigate clinical profiles and treatment outcomes of patients with CRION, comparing MOG-IgG-positive (MOG+) and seronegative (MOG-) subgroups. MethodsPatients from six European tertiary centers fulfilling diagnostic criteria for CRION were included. All underwent cell-based autoantibody testing. Clinical outcomes (visual acuity, annualized relapse rate), laboratory and imaging findings (MRI, OCT), and treatment responses were retrospectively analyzed. ResultsSixty patients were included (median age 33 years; 70% female); 27 (45%) were MOG+. MOG+ CRION was associated with later onset, higher ARR before treatment (median [IQR] 2 [1-3] vs. 1 [1-2], p = 0.023), and a trend toward shorter inter-relapse intervals. Additional distinguishing features included higher frequencies of antinuclear antibody positivity, elevated CSF interleukin-6, and extensive optic neuritis on MRI. Relapse burden correlated with visual acuity decline and retinal thinning. In MOG+ patients, monoclonal antibody therapy reduced the ARR (n = 21; 2 [1-3] vs. 0 [0-2], p = 0.024), primarily driven by tocilizumab (n = 11; 2 [1-3] vs. 0 [0-1], p = 0.023). In MOG-patients, rituximab and azathioprine showed a trend toward ARR reduction. ConclusionCRION represents a heterogeneous syndrome encompassing distinct subgroups. MOG+ patients demonstrate higher disease activity but respond favorably to tocilizumab. Serological testing is critical for treatment stratification and preventing relapses.

Non-invasive glucose monitoring (NIGM) has been pursued for decades, yet no device has achieved regulatory approval despite numerous studies reporting high accuracy. This systematic review and meta-analysis of 32 studies (38 cohorts: 20 NIGM, 18 iCGM; N = 1,693) investigated methodological factors underlying this accuracy-regulatory gap. The pooled Mean Absolute Relative Difference (MARD) for NIGM (10.21%; 95% CI: 8.73-11.69%) showed no significant difference from iCGM (11.82%; 95% CI: 10.36-13.29%; p = 0.13), with extreme heterogeneity (I^2 = 95.2%). Meta-regression revealed that study duration was the strongest predictor of NIGM accuracy ({beta} = 3.94, p < 0.001), with MARD degrading from 8.7% in short-term to 15.2% in long-term studies, while iCGM accuracy remained stable. Only 15% of NIGM cohorts validated in the hypoglycemia range, compared to 89% of iCGM studies (p < 0.001). These findings suggest that reported NIGM accuracy is substantially influenced by methodological asymmetries.

There is an ongoing Oropouche Fever (OF) outbreak in Brazil since 2024. There are dengue and chikungunya prediction models available, but none to help discriminate dengue, chikungunya, and OF. Objective: This study aims to develop and validate clinical prediction models for dengue, chikungunya, OF. Methods: This study uses surveillance data from Espirito Santo state / Brazil, from 2023-2025. Epidemiological investigations and biological samples were used to conclude cases as either (a) clinical-epidemiologically confirmed, (b) laboratory confirmed, or (c) discarded. The predictors were all data related to signs, symptoms, and comorbidities available in the notification forms. The analysis was performed using random forest regression models, one for each outcome, in development and validation datasets. Results: A total of 465,280 observations were analyzed, 261,691 dengue cases (56.6%), 18,676 chikungunya cases (4.0%), 12,174 OF cases (2.6%), and 179,115 discarded cases (38.6%). All three models had good discrimination and moderate to good calibration after scaling prediction. The models retained from 26 to 16 predictors each. Leukopenia and vomiting were the most discriminatory predictors for dengue, arthritis, arthralgia, and rash were the most discriminatory for chikungunya, and epidemiological features were the most relevant for OF. The dengue, chikungunya, and OF models had ROC AUC of 0.726, 0.851, and 0.896 in the validation set, respectively. Conclusion: This research identified predictors most discriminative between dengue, chikungunya, and OF. We developed and validated predictive models, one for each condition, with moderate to very good performance available at https://pedrobrasil.shinyapps.io/INDWELL/. One may use them in diagnostic work-up and arbovirus surveillance.

PURPOSE: Bispecific antibodies (BsAbs) represent a major advancement in the management of relapsed/refractory multiple myeloma (RRMM), offering high response rates even in heavily pretreated patients. However, their use presents operational, safety, and supportive care complexities that require coordinated care teams, and evolving infrastructure. This manuscript summarizes best practice recommendations for adverse event (AE) management, outpatient operational models, referral pathways, and emerging strategies to optimize long-term tolerability. METHODS: Medlive, A PlatformQ Health Brand, conducted qualitative interviews of academic and community-based clinicians. Discussions focused on BsAb implementation, patient selection and counseling, and AE management. Experts provided recommendations on team-based protocols, transitions of care, and inpatient versus outpatient considerations. RESULTS: Ten hematologists/oncologists (academic n=4; community n=6) described practice patterns, barriers, and perspectives on BsAb use. BsAbs were consistently regarded as highly effective across multiple lines of therapy, particularly for patients without alternatives. Cytokine release syndrome (CRS) was the most common acute toxicity, generally low grade and managed effectively with early tocilizumab, including prophylactic use in outpatient settings. Immune effector cell-associated neurotoxicity syndrome (ICANS) was rare, mild, and best mitigated through early recognition and caregiver support. Infections, largely from BCMA-associated hypogammaglobulinemia, frequently interrupted therapy, necessitating antiviral prophylaxis, pneumocystis jirovecii pneumonia (PJP) prophylaxis, and intravenous immunoglobulin (IVIG). Outpatient step-up dosing is expanding, supported by prophylactic strategies and academic-community collaboration. Timely referral was emphasized to preserving eligibility. Major outpatient challenges included sequencing, infrastructure readiness, and standardized caregiver and staff education. CONCLUSION: Effective community implementation of BsAbs requires multidisciplinary coordination, standardized AE protocols, infection prevention, and infrastructure to support monitoring, referrals, and equitable access. These measures are critical to ensure safe, sustainable integration of bispecific therapies and to optimize patient outcomes.

Purpose: We evaluated healthcare resource utilization (HCRU) and costs in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients with newly diagnosed EGPA (2017--2021), [&ge;]12 months' pre-diagnosis health plan enrollment, and [&ge;]1 inpatient or [&ge;]2 outpatient claims with an EGPA diagnosis were included. Follow-up was from EGPA diagnosis until disenrollment or database end. HCRU and health insurer payment costs during follow-up were compared with those for matched cohorts of general insured patients without EGPA (comparison A) and without EGPA but with severe uncontrolled asthma (SUA; comparison B). Results: In comparison A, all-cause HCRU was higher in the EGPA cohort (n = 213) versus matched patients (n = 779) for all clinical encounters/pharmacy claim types; annualized, mean total all-cause costs were 16-fold higher ($117,563/patient) versus matched patients ($7,520/patient). In comparison B, all-cause HCRU was higher for the EGPA cohort (n = 182) versus the matched SUA cohort (n = 640) for all clinical encounters/pharmacy claim types, with 5-fold higher mean total all-cause costs ($118,127/patient vs $22,286/patient). In both EGPA cohorts, HCRU and associated costs increased between the baseline and follow-up periods. Conclusions: These findings highlight the need for more effective treatments to reduce the clinical and economic burden of EGPA.

Abstract Objective: To compare the safety and efficacy of bridging intravenous thrombolysis (IVT) plus endovascular thrombectomy (EVT) versus direct EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO) treated within the 6- to 24-hour time window. Methods: This is a retrospective analysis of prospective EVT registry from 10 comprehensive stroke centers in China and Singapore between 2019 and 2024. Eligible patients had anterior circulation LVO, underwent EVT within 6-24 hours of onset, had ASPECTS 6, NIHSS 6, and pre-stroke mRS 2. Patients were stratified into bridging IVT + EVT (IVT group) versus direct EVT alone (non-IVT group). Propensity score matching (1:2 ratio) was performed to balance baseline covariates. The primary outcome was 3-month favorable functional outcome (mRS 0-2). Secondary outcomes included successful recanalization (mTICI 2b-3), symptomatic intracranial hemorrhage (sICH), hemorrhagic transformation (HT) and 3-month mortality. In the matched cohort, binary outcomes were compared using the Cochran-Mantel-Haenszel test. Results: Of 772 included patients, 110 (14.2%) received bridging IVT and 662 (85.8%) received direct EVT. After propensity score matching, 202 non-IVT patients were matched to 101 IVT patients, with all covariates well-balanced (absolute SMD <0.10). In the matched cohort, bridging IVT was not associated with a significant difference in 3-month favorable outcome (44.55% vs. 47.03%; common OR 0.91; 95% CI 0.56-1.46), successful recanalization (91.09% vs. 90.10%; OR 1.11; 0.51-2.44), sICH (5.94% vs. 9.41%; OR 0.61; 0.24-1.58), HT (23.76% vs. 23.27%; OR 1.03; 0.57-1.85), or 3-month mortality (15.84% vs. 13.37%; OR 1.22; 0.62-2.37). Conclusion: In this large multicenter propensity score-matched analysis, bridging intravenous thrombolysis before endovascular thrombectomy in the 6- to 24-hour time window was not significantly associated with improved efficacy or increased safety risks compared with direct endovascular therapy alone.

Purpose To evaluate patient satisfaction and preferences for portable versus table-mounted visual field (VF) devices in a rural telemedicine setting and identify influencing factors. Methods We conducted a sequential explanatory mixed methods study at three Federally Qualified Health Centers (FQHCs) within the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine (AL-SIGHT) study. Participants completed VF testing with table-mounted Humphrey Field Analyzer (HFA), tablet-based Melbourne Rapid Fields (MRF), and virtual reality (VR)-based VisuALL perimeters. Participants rated satisfaction, comfort, ease of use, and future testing preference. Chi-square tests assessed differences in device preferences. Twelve participants completed semi-structured interviews to explore reasons underlying preferences. Qualitative data were analyzed in NVivo 14 using reflexive thematic analysis. Results Among 271 respondents (mean age 60.4 years; 62.4% women), 50.6% preferred VR-based, 35.1% tablet-based, and 14.4% table-mounted for future testing ({chi}2 (2) = 53.52, p<0.001, Cramers V = 0.31). Satisfaction was highest for VR-based (56.9% very satisfied), followed by tablet-based (49.4%), and HFA (38.0%). VR-based perimeter was most frequently selected as the most comfortable (55.7%; {chi}2 (2) = 63.33, p<0.001, V = 0.34) and easiest to use (54.6%; {chi}2 (2) = 71.96, p<0.001, V = 0.36). Preferences did not vary significantly across demographic variables (all p>0.05). Qualitative themes identified four key drivers: comfort and physical experience, visual experience, ease of use and interaction, and psychological and motivational factors. Portability and community suitability were valued. Conclusion Rural underserved patients strongly preferred portable visual field devices, particularly VR-based, over table-mounted HFA. Comfort, ergonomic flexibility, immersive visual experience, and simplicity of interaction were central determinants of preference. Portable perimetry may enhance patient-centered glaucoma monitoring within telemedicine programs and access in resource-limited settings.

Carnivorous plants have been the subject of fascination and research ever since Darwin codified the subject in his 1875 book Insectivorous Plants. The origin of complex trapping mechanisms from structures adapted for photosynthesis is of particular interest. While Darwin proposed a plausible scenario for the origin of the snap traps of the Venus flytrap from simpler adhesive traps, the origin of the tiny and complex bladder traps of the genus Utricularia mystified Darwin and many subsequent workers, despite Utricularia being the most diverse genus of carnivorous plants. In this study, we test the "pitcher hypothesis," which proposes that Utricularia bladder traps evolved gradually from an adhesive trap ancestor, via an extinct pitcher trap intermediate. To overcome the lack of any fossil evidence for this scenario, we constructed a variety of continuous-time Markov chain (CTMC) models, each of which consists of a transition matrix allowing or disallowing certain transitions between 11 types of traps. We assembled available phylogenetic trees for 436 carnivorous plant species and noncarnivorous outgroups, classified each species by trap type, and statistically compared the fit of 18 CTMC models using Maximum Likelihood and statistical model comparison with Akaike Information Criterion. The best-fitting model (PH-7R-AAI), consistent with our pitcher hypothesis, had an AIC weight of 60%, with two similar models accounting for the remaining 40%. These results support a circuitous stepwise evolutionary pathway to the bladder trap, and demonstrate how a detailed stepwise evolutionary scenario may be statistically tested even without direct fossil evidence of key intermediate stages.

BackgroundTransposable elements (TEs) are repetitive genetic elements that can jump to new loci causing genome expansions, structural rearrangements, and can, ultimately, propel the evolution of genomes. Despite their significance, the role of TEs in the evolution of genomes and phylogenetic groups remains largely understudied in early diverging lineages. Further, the extent to which TE content varies across species is still an open question. Medusozoa, a group within Cnidaria encompassing jellyfish and hydroids, exhibits an exceptional diversity of life history strategies, body plans, and physiological capabilities. These characteristics, along with its early-diverging phylogenetic position, establish Medusozoa as an ideal system for investigating the composition and evolutionary history of TEs within the group. ResultsWe generated a custom repeat library built from annotations of 25 Medusozoan genomes and used it to characterize TEs, aiming to identify lineage-specific TE content and activity that may correlate with the diversity observed within the group. We found that repetitive element percentage and genome size varied considerably, with Hydrozoa exhibiting the most variation among classes in both respects. DNA transposons were the most prevalent TE classification in all but two genomes, averaging 28% of all genomes. Intra-genus comparisons revealed a surprising degree of differences in TE content. In the genus Aurelia, the expansion of a single DNA transposon superfamily accounted for much of the difference in repetitive element percentage between two species, whereas in the genus Turritopsis, a similar divergence resulted from the proliferation of multiple superfamilies. Interestingly, most genomes showed evidence of recent TE expansions, suggesting ongoing activity in many medusozoan species. ConclusionWe present the first comparative analysis of TEs across all medusozoan classes. Our results reveal class-specific TE dynamics and highlight cases of TE proliferations as lineages diverge. This research provides data on TE activity and diversity that can be used as a resource for future study and fills important gaps in our understanding of TEs in early diverging animal lineages.