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Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans

Robot-assisted versus manual percutaneous vascular interventions across vascular territories: a systematic review and meta-analysis.

Robot-assisted percutaneous vascular intervention (R-PVI) has expanded beyond coronary procedures, but previous reviews were largely coronary-focused and observational. Recent randomized controlled trials (RCTs) warrant broader reassessment of R-PVI versus manual percutaneous vascular intervention (M-PVI) across vascular territories. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from database inception to January 31, 2026, following PRISMA guidelines. RCTs and observational studies including &#x2265;10 adult patients in total were eligible. Comparative studies informed primary analyses, while single-arm studies provided supportive evidence. Primary outcomes were clinical success rate and major adverse cardiovascular/cerebrovascular events (MACE) rate. Secondary outcomes included mortality rate, technical success rate, procedural time metrics, contrast volume, and radiation exposure. Random-effects models were used. Forty studies were included: 3 RCTs, 10 comparative observational studies, and 27 single-arm observational studies, comprising 3,870 patients undergoing R-PVI and 1,142 undergoing M-PVI. Comparative analyses showed similar clinical success rates (RR 1.00, P = 0.46), MACE rates (RR 0.72, P = 0.43), and mortality. Single-arm pooled estimates for clinical and technical success were 98.76% and 96.09%, respectively. R-PVI prolonged total procedure time overall (MD 15.92&#xa0;min, P = 0.01), with consistent increases in the neurovascular, RCT, and non-RCT subgroups. Fluoroscopy time was also longer (MD 1.91&#xa0;min, P = 0.04), mainly in the RCT subgroup (MD 2.83&#xa0;min, P = 0.001). In contrast, intravascular intervention time was unchanged overall and in RCTs, but was prolonged in non-RCTs (MD 8.72&#xa0;min, P = 0.006). Operator radiation exposure was markedly reduced (MD -33.97 &#x3bc;Sv, P < 0.001), whereas patient radiation exposure and contrast volume were similar. R-PVI appears feasible and safe across selected vascular procedures. Its clearest benefit is reduced operator radiation exposure, whereas lower whole-procedure efficiency remains its main limitation.

Humans

An Assessment of Reliability Estimation Methods for Binomial Health Care Quality Measures.

We evaluated the performance of commonly used methods for estimating the reliability of binomial health care quality measures using simulated datasets spanning a range of performance score means and variances, numbers of entities, and patient sample sizes. For each simulation, reliability was estimated for all selected methods and compared with the known true reliability derived from the simulation parameters, with methods assessed on their accuracy and precision. Logistic regression with reliability estimated on the outcome scale demonstrated the highest accuracy and precision among all methods evaluated. The widely used Adams beta-binomial method performed poorly, although a modification recommended by Nieser and Harris substantially improved its performance. These approaches are applicable only to binomial measures. Among methods that can be applied to both binomial and continuous measures, permutation resampling of the Spearman rank correlation coefficient was the most accurate and precise, outperforming other commonly used approaches. Overall, for binomial quality measures, logistic regression on the outcome scale is the preferred method for reliability estimation, followed closely by the modified beta-binomial approach, while for non-binomial measures, permutation-based Spearman rank correlation appears to be the most suitable method.

Reproducibility of Results

Hydrodissection-assisted laparoscopic orchiopexy utilizing needle grasper for palpable undescended testes: Clinical efficacy analysis.

OBJECTIVE: Laparoscopic orchiopexy has emerged as a viable alternative for the treatment of palpable undescended testis (UDT). This study aims to evaluate the feasibility and efficacy of needle-grasper hydrodissection-assisted laparoscopic orchiopexy (NHLO) in comparison to conventional laparoscopic orchiopexy (CLO) for palpable UDT. METHODS: A cohort of 96 patients diagnosed with palpable UDT, admitted between January 2020 and April 2024, was included in this study. Among these, 54 patients underwent NHLO, while 42 patients were treated with CLO. In the NHLO procedure, normal saline was injected into the retroperitoneal space to create a hydrodissection barrier, facilitating the separation and protection of the vas deferens and spermatic cord. The vas deferens and spermatic cord were meticulously dissected following the principles of integrity and minimal tissue trauma. Outcome measures included final testicular position, testicular volume growth, testicular atrophy, success rate, and postoperative complications. RESULTS: No significant differences were observed between the NHLO and CLO groups in terms of age, laterality, operative time (NHLO: 38-46 min; CLO: 39-48 min), or complication rates (NHLO: 1.9 %; CLO: 0.0 %). At follow-up, all patients in both groups exhibited palpable testes in satisfactory scrotal positions. Notably, no visible abdominal scarring was observed in the NHLO group, whereas there were two noticeable scars on the abdomen in CLO. CONCLUSION: Needle-grasper hydrodissection-assisted laparoscopic orchiopexy is a safe, effective, and minimally invasive technique that provides optimal protection of the vas deferens and spermatic cord while achieving excellent cosmetic outcomes.

Humans

Robot-assisted bladder diverticulectomy in adults: a systematic review and pooled analysis of perioperative and functional outcomes.

Robot-assisted bladder diverticulectomy (RABD) is used for symptomatic acquired bladder diverticula, but evidence is dispersed across small single-centre series and the only dedicated systematic review dates from 2010. We reviewed contemporary perioperative and functional outcomes of RABD. Following a protocol registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/54CFT ), PubMed, Embase, the Cochrane Library, Scopus and Web of Science were searched from inception to 30 August 2026 (initial search June 2026, re-run and broadened for this version), following PRISMA 2020. Eligible studies were original series of five or more adults undergoing robot-assisted bladder diverticulectomy reporting extractable outcomes. Two reviewers independently screened, extracted data and appraised risk of bias with the Joanna Briggs Institute checklist for case series, with third-reviewer adjudication. Binary outcomes were pooled as proportions with Wilson 95% confidence intervals (CI); continuous outcomes were summarised as patient-number-weighted descriptive values, because mixed median/mean reporting and clinical heterogeneity precluded a formal pooled-effect meta-analysis. Twelve studies (146 patients) were included and all outcomes were extracted from the full-text reports. A transperitoneal route was used throughout. There were no conversions to open surgery (0/129; 95% CI 0-2.9%). Major complications (Clavien-Dindo&#x2009;&#x2265;&#x2009;III) occurred in 3.0% (4/135; 95% CI 1.2-7.4%). Patient-number-weighted descriptive values (combining study-level medians and means, and therefore not a pooled mean) were: operative time 163 min, blood loss 99 mL, length of stay 3.6 days and catheter duration 7.7 days. Symptom scores and post-void residual improved in every reporting series, significantly in five. The single non-randomised comparison with open surgery reported fewer major complications after RABD (5% [1/20] vs. 50% [3/6], p&#x2009;=&#x2009;0.007), but the open arm comprised only six patients and this finding should not be regarded as comparative evidence. Across these series, RABD was feasible with low reported short-term morbidity in selected patients: no conversions to open surgery were recorded in the studies reporting conversion status, the major-complication rate was low, and symptom scores and post-void residual improved in every series that measured them. A minority of patients had an incidentally detected intradiverticular tumour; oncological outcomes were not an endpoint of this review. Evidence remains limited by small, heterogeneous, mostly retrospective series, so these findings should be read as descriptive; prospective comparative data are warranted.

Humans

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584&#xa0;mM (OXD) and 0.1498&#xa0;mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10&#xa0;ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines

Analysis of deep learning techniques in computer-aided diagnosis for meniscus injuries: a systematic literature review.

Meniscus informatics is a growing subject of study in the healthcare industry. One of the major hindrances to the healthcare system's transformation is obtaining knowledge and meaningful information from complicated, high-dimensional and diverse sources. Modern biomedical research, for instance, has seen an increase in the use of complex, dissimilar, poorly documented, and generally unstructured electronic health records, imaging, sensor data and text, even after many current techniques have been used to extract more robust and useful elements from the data for analysis. New efficient standards for building end-to-end learning models from complex data are therefore needed. Therefore, the current study aims to examine the most recent research on the use of deep learning techniques for diagnosing meniscus tears and recommend creating comprehensive and meaningful interpretable structures that might benefit the healthcare industry. We also draw attention to shortcomings and the need for better technique development, and we provide new perspectives about this exciting new development in the field.

Humans

Enhancing Self Care Among Oral Cancer Survivors Using a Digital Approach: The Empowered Survivor Trial.

BACKGROUND: Oral and oropharyngeal cancer survivors experience debilitating physical and psychosocial challenges. Little knowledge exists on the efficacy of interventions to enhance self-efficacy in managing these challenges, increase survivorship preparedness, and improve health-related quality of life (HRQoL). METHODS: Individuals (n&#xa0;=&#xa0;643) diagnosed with oral or oropharyngeal cancer diagnosed within past 3&#xa0;years were randomized to a digital intervention, Empowered Survivor (ES) or a Generic Online Intervention (GO). Primary (self-efficacy, preparedness, HRQoL) and secondary outcomes (self-care activities) were measured at Baseline, 2-months, and 6-months. RESULTS: Participants assigned to ES reported greater self-efficacy and increased self-care activities of oral self-exams, swallowing, and mobility exercises than those assigned to GO (self-efficacy: 2&#xa0;months, p&#xa0;=&#xa0;0.003, 6-months, p&#xa0;<&#xa0;0.001; self-care activities). CONCLUSIONS: The ES enhanced self-efficacy and increased self-care activities. Further examinations of survivorship preparedness and HRQoL in oral and oropharyngeal cancer are warranted. TRIAL REGISTRATION: Registered on clinicaltrials. gov as NCT04713449.

Humans

An AI-assisted Clinical Decision Support System for Green Classification of Cystocele on Dynamic Transperineal Ultrasound.

Green classification of cystocele on dynamic transperineal ultrasound (TPUS) remains operator-dependent because it requires manual frame selection and landmark-based assessment of the Valsalva maneuver. We developed a workflow-oriented AI-assisted clinical decision support system for automated urethrovesical junction localization and dynamic Green classification and prospectively evaluated its standalone and reader-support performance. This diagnostic accuracy and reader study included 881 patients from a tertiary referral hospital, comprising a retrospective development cohort (n&#x2009;=&#x2009;688) and an independent prospective test cohort (n&#x2009;=&#x2009;193). A nested subset of 67 prospective patients was used for a reader study involving two junior and two intermediate radiologists under unaided and AI-assisted conditions. In the complete prospective test cohort, Green-AttGRU achieved a macro-averaged AUC of 0.939 (95% CI, 0.897-0.971) and an overall accuracy of 0.902 (95% CI, 0.860-0.943). In the reader study, overall accuracy increased from 0.761 to 0.821 without AI to 0.851-0.881 with AI, while macro-F1 increased from 0.660 to 0.777 to 0.820-0.860. Overall inter-reader agreement increased from a Fleiss' &#x3ba; of 0.453 to 0.786, and pooled median interpretation time decreased from 26.7&#xa0;s to 9.9&#xa0;s. These findings support the preliminary feasibility of the system as a workflow-oriented decision-support tool for dynamic TPUS interpretation.

Humans

Robotic assistance in total hip arthroplasty: a systematic review and meta-analysis of leg length, cup orientation, and early outcomes.

This review examined whether robotic assistance alters postoperative leg-length discrepancy (LLD), acetabular cup orientation, or early hip-specific outcomes relative to conventional total hip arthroplasty (THA). We searched PubMed and Web of Science through May 2026 for comparative English-language reports. Study eligibility, data extraction, and methodological appraisal were undertaken independently by two reviewers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated in Review Manager 5.4. Model selection was based on the target estimand and anticipated clinical and methodological diversity; leave-one-out and alternative-model sensitivity analyses were undertaken for heterogeneous outcomes. The protocol is registered with PROSPERO (CRD420261454043). The review included seven studies and 968 participants. Compared with conventional THA, robot-assisted THA yielded a smaller postoperative LLD (MD = -2.02, 95% CI -3.46 to -0.58; P = 0.006) and a higher Harris Hip Score (MD = 2.96, 95% CI 1.12 to 4.80; P = 0.002). Mean cup anteversion was lower in the robotic group (MD = -1.52, 95% CI -2.29 to -0.76; P < 0.0001), whereas cup inclination did not differ (MD = -0.71, 95% CI -3.26 to 1.83; P = 0.58). The robotic group also had higher Forgotten Joint Score (MD = 14.68, 95% CI 5.02 to 24.33; P = 0.003) and Oxford Hip Score values (MD = 2.61, 95% CI 0.71 to 4.51; P = 0.007). Robotic assistance was linked to a modest improvement in leg-length restoration and to higher scores on several early functional measures. The limited number of studies, predominance of nonrandomized designs, and marked heterogeneity in some analyses temper the certainty of these findings.

Humans

Immersive virtual reality-assisted anatomy training improves endotracheal intubation performance in simulation: a randomized controlled trial among Chinese non-anesthesiology residents.

INTRODUCTION: This study aimed to compare immersive virtual reality (IVR)-assisted versus conventional anatomy training for teaching endotracheal intubation (ETI) to novice non-anesthesiology residents enrolled in China's Standardized Residency Training program. METHODS: A total of 90 non-anesthesiology residents without prior ETI experience were randomly assigned to either an IVR group receiving IVR-assisted anatomy training (n&#x2009;=&#x2009;45) or a control group receiving conventional anatomy training (n&#x2009;=&#x2009;45). All participants underwent a standardized teaching protocol. The primary endpoint was residents' ETI performance on a simulator, assessed using both the Global Rating Scale (GRS) and a task-specific checklist. The secondary endpoints included changes in written multiple-choice question (MCQ) scores and residents' evaluations of the course. RESULTS: In practical ETI assessments on a manikin, the IVR group achieved significantly higher scores on the task-specific checklist than the control group (90.34&#x2009;&#xb1;&#x2009;2.89 vs. 87.20&#x2009;&#xb1;&#x2009;3.29; p&#x2009;<&#x2009;0.001), whereas GRS scores were comparable between groups. Both groups showed significant post-training improvement in knowledge scores (p&#x2009;<&#x2009;0.001), with the IVR group showing a greater gain in theoretical knowledge (54.0% vs. 36.3%; p&#x2009;<&#x2009;0.001). Participants in the IVR group also expressed a stronger preference for their training method (80.8%) and reported higher levels of motivation, confidence, and enjoyment (all p&#x2009;<&#x2009;0.05). CONCLUSION: IVR-assisted anatomy training enhances the effectiveness of ETI training for novice non-anesthesiology residents, offering an interactive, engaging, and reproducible approach within China's Standardized Residency Training framework.

Humans

Vortex-assisted liquid-liquid microextraction based on natural deep eutectic solvents for the determination of pyrethroid pesticides in urine.

A novel, facile, and environmentally friendly analytical method was developed based on vortex-assisted liquid-liquid microextraction and high-performance liquid chromatography with diode-array detection for detecting pyrethroid pesticides (PPs) in urine. Natural deep eutectic solvents (NADESs) were prepared using plant essential oil-derived monoterpenoids (thymol, carvacrol, and menthol) combined with aromatic primary alcohols (benzyl alcohol, phenethyl alcohol, and phenylpropyl alcohol) as hydrogen bond donors and acceptors. These solvents served as environmentally benign extraction media, thereby avoiding the use of conventional volatile, toxic organic solvents. NADESs are naturally derived, easy to prepare, biodegradable, and environmentally friendly solvents. Hydrophobic and &#x3c0;-&#x3c0; interactions between the NADESs and PPs may contribute to enhancing the affinity of PPs toward the NADESs phase. Vortex technology, accelerating mass transfer between the sample and extractant phases, enables fast extraction of PPs. Under optimized conditions, the method achieved a low detection limit (0.002&#xa0;mg&#xa0;L-1), satisfactory precision with relative standard deviations (0.3%-2.4%), and acceptable recovery (80.7%-86.2%). The method demonstrated excellent performance in urine analysis and was feasible as a facile and green strategy for monitoring the content of PPs in biological matrices and assessing exposure risk.

Liquid Phase Microextraction

Ketamine assisted psychotherapy to reduce chronic neuropathic pain: A mixed-methods randomized pilot trial.

BACKGROUND: Intravenous ketamine can provide short-term analgesia in chronic neuropathic pain but benefits often wane after treatment. We conducted a randomized pilot trial to assess the feasibility of combining ketamine infusions with psychotherapy to inform future efficacy trials. METHODS: In this single-center, randomized, outcome-assessor-blinded pilot trial at a Canadian tertiary pain clinic, adults with moderate-to-severe chronic neuropathic pain were randomly assigned in 1:1:1 ratio to the ketamine, psychotherapy, or combined ketamine plus psychotherapy arm. Ketamine was delivered as three intravenous infusions over 16 weeks; psychotherapy consisted of 16 weekly cognitive behavioral therapy and mindfulness-based meditation sessions. The primary outcome was feasibility, assessed using prespecified progression criteria. Exploratory outcomes included changes in pain interference (PROMIS 6a T-score), pain intensity, mood, and qualitative interview findings at week 20 (ClinicalTrials.gov: NCT05639322). FINDINGS: Between October 23, 2023, and March 31, 2025, 30 participants were randomized, and 26 (87%) completed 20-week follow-up. Most feasibility criteria, including consent, retention, data completeness, and absence of study-related serious adverse events, were met; adherence targets were partially met. Exploratory pain outcomes showed numerical improvement across groups, with clinically meaningful reductions observed for pain interference and pain intensity. Sixty-four adverse events were recorded, mostly mild and in ketamine-containing groups; no serious study-related adverse events occurred. CONCLUSIONS: Combined ketamine and psychotherapy was feasible and acceptably safe in this pilot trial, supporting evaluation in a larger efficacy-powered study. FUNDING: The study was funded by the St. Michael's Hospital Innovation Fund, The Canadian Pain Society Early Investigator Award and the Physician Services Incorporation Early Career Researcher Award.

Humans

Transabdominal lumbar approach (TALA) versus retroperitoneal approach for robot-assisted renal surgery: a prospective randomised controlled trial.

PURPOSE: Common robotic nephrectomy approaches access the kidney via transperitoneal (TP) or retroperitoneal (RP) routes, each with distinct trade-offs. We developed the transabdominal lumbar approach (TALA), combining advantages of both accesses with improved visualisation and strategic trocar placement, and compared it with conventional RP in a prospective randomised controlled trial using technique-oriented intraoperative endpoints. METHODS: In this single-centre, prospective, open-label RCT, 40 patients were randomised to TALA (n&#x2009;=&#x2009;18) or conventional RP (n&#x2009;=&#x2009;22). Eligible patients were &#x2265;&#x2009;18 years with a renal tumour or non-functional kidney requiring robot-assisted total or partial nephrectomy. Exclusions included prior surgery on the affected kidney, renal vein tumour thrombus, and pregnancy. Both groups were followed for 30 days. The primary endpoint was time from first skin incision to renal artery identification. RESULTS: TALA achieved a median time saving of 16&#xa0;min compared to conventional RP (38 vs. 54&#xa0;min, p&#x2009;=&#x2009;0.001). Perioperative safety was comparable between groups, with three patients (7.5%) experiencing Clavien-Dindo grade III-IV complications. CONCLUSIONS: TALA met its primary endpoint with a significantly shorter time to renal artery identification than conventional RP access, and improving perceived surgical exposure and instrument handling.

Humans

A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants.

Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70&#xa0;mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).

Humans

PCa Detection in PI-RADS 4 and 5 Lesions: Comparison of [68Ga]Ga-PSMA-11 PET/CT-Guided Robot-Assisted Biopsy Versus mpMRI Cognitive-Fusion TRUS-Guided Prostate Biopsy.

Lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 4 or greater on multiparametric MRI (mpMRI) indicate a high likelihood of prostate cancer (PCa), and guidelines recommend a targeted biopsy. We aimed to compare the diagnostic performance of robotic arm-assisted [68Ga]Ga-PSMA-11 PET/CT-guided prostate biopsy (PGPB) with mpMRI-directed cognitive-fusion transrectal ultrasound-guided biopsy (MCFB) in biopsy-na&#xef;ve men with clinical findings suggestive of PCa. Methods: This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-na&#xef;ve men age 50-90 y with elevated levels of prostate-specific antigen (&#x2265;4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain. Result: Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% &#xb1; 20%), despite obtaining fewer cores. Conclusion: [68Ga]Ga-PSMA-11 PGPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.

Humans

A cooperative regulatory module between TAGL2 and JMJC1 activates specific defense genes against root-knot nematodes in tomato.

Plant-parasitic nematodes (PPNs) threaten global food security. Although epigenetic modifications are crucial for plant immunity, how histone modifiers contribute to root-knot nematodes (RKNs, Meloidogyne incognita) resistance remains unclear. Here, using genetic, molecular and biochemical approaches, we investigated the epigenetic and transcriptional mechanisms underlying RKN resistance mediated by the histone demethylase (HDM) JMJC1 and the MADS-box transcription factor TAGL2 in tomato (Solanum lycopersicum). We identified JMJC1 as an RKN-induced positive defense regulator targeting H3K9me3 and H3K27me3 histone marks. JMJC1 physically interacts with TAGL2, which also positively regulates RKN resistance. Transcriptomic analysis indicated that TAGL2 regulates multiple layers of the plant defense network, transcriptionally activating representative genes from distinct pathways (including PUB10, bHLH98, CCaMK, and SAUR3), which we validated as positive regulators of RKN resistance via virus-induced gene silencing (VIGS). At the chromatin level, TAGL2 and JMJC1 co-regulate these loci, associating with localized H3K9me3 and H3K27me3 reduction. Furthermore, TAGL2 directly activates JMJC1 transcription, establishing a positive feedback loop that amplifies immune signaling. Our findings reveal a cooperative model wherein a HDM and a transcription factor coordinate at specific loci to fine-tune multiple defense layers at both epigenetic and transcriptional levels, providing insights for breeding durable nematode-resistant plants.

Solanum lycopersicum

An RPA-assisted homogeneous electrochemical DNA sensor for on-site eDNA detection toward early warning of crown-of-thorns starfish outbreaks.

Crown-of-thorns starfish (COTS) outbreaks seriously threaten coral reef ecosystems, while conventional monitoring approaches are time-consuming and often lack sufficient sensitivity for early warning. Existing electrochemical DNA sensors usually require complex electrode-surface immobilization procedures, which can lead to uneven probe distribution, significant steric hindrance, and poor stability. Meanwhile, the low concentration of environmental DNA (eDNA) in marine environments further complicates detection. To overcome these challenges, this study developed a homogeneous electrochemical DNA sensor assisted by recombinase polymerase amplification (RPA) for COTS eDNA detection. Target DNA was first amplified by RPA, and the amplification products were then hybridized in solution with capture probe (CP)-modified magnetic beads (MB) and biotin-labeled signal probe (SP) to form sandwich-structured MB complexes. These complexes were subsequently magnetically enriched and immobilized on the electrode surface for electrochemical signal readout. Under optimized conditions, the sensor displayed a linear response to COTS genomic DNA from 3.77&#xa0;fg/&#x3bc;L to 1&#xa0;ng/&#x3bc;L, with an LOD of 2.02&#xa0;fg/&#x3bc;L and an LOQ of 3.77&#xa0;fg/&#x3bc;L. The sensor was applied to Xisha Islands samples, and the results agreed with droplet digital PCR (ddPCR) (P&#xa0;>&#xa0;0.05), demonstrating its potential for sensitive and reliable on-site COTS eDNA detection.

Animals