Non-suicidal self-injury (NSSI) is a known precursor to suicide, which has the highest global rates among older adults. Yet, NSSI in later life remains poorly understood. This systematic review examined literature on NSSI in individuals aged 60+. Following PRISMA guidelines, we searched six databases (PsycInfo, PsycARTICLES, PubMed, ScienceDirect, Scopus, and Web of Science) on May 25, 2025. Eligible studies were peer-reviewed, English-language, included adults ≥60, and reported on NSSI. Two reviewers independently extracted and appraised articles. Five cross-sectional studies published within the past decade met criteria. None used longitudinal designs or informant perspectives; most relied on retrospective data or single-item measures. Samples varied, and none focused exclusively on adults ≥60. Lifetime NSSI prevalence ranged 6.0-9.5%, past-year 1.4-4.1%, and past-month 2.9-6.3%. Some studies suggested declining prevalence with age, though findings were inconsistent across older subgroups. Common behaviours included scratching, punching, and head banging. Assessment methods varied; only one study used a validated NSSI-specific instrument. Overall study quality was moderate to high, with limitations in measurement validity and sample representativeness. NSSI occurs in older adults but remains under-researched. Age-sensitive tools and targeted research are needed to improve identification, understanding, and intervention.
Borderline personality disorder (BPD) and eating disorders (EDs) frequently co-occur and are associated with heightened clinical severity and emotion dysregulation. This systematic review aimed to synthesize empirical evidence on the effectiveness of dialectical behaviour therapy (DBT) in improving eating disorder outcomes among individuals with comorbid BPD and EDs. A systematic literature search was conducted across Wiley, Web of Science, SpringerLink and Scopus databases in accordance with PRISMA 2020 guidelines. Studies were included if they examined DBT-based interventions in samples with comorbid BPD and EDs and reported quantitative outcomes. Eight studies met inclusion criteria. Risk of bias was assessed using Joanna Briggs Institute (JBI) checklists, and a structured narrative synthesis was performed. Across studies, DBT-based interventions were associated with reductions in eating disorder symptom severity, maladaptive eating behaviours (e.g., binge eating and purging) and self-harm. Baseline BPD symptom severity did not consistently predict poorer outcomes and, in some cases, was associated with greater early improvements. However, substantial heterogeneity in study design, sample characteristics and outcome measures was observed, and methodological quality varied across studies. DBT appears to be a clinically relevant and promising transdiagnostic intervention for individuals with comorbid BPD and EDs. Nevertheless, the current evidence base is limited by methodological constraints, highlighting the need for well-designed randomized controlled trials and mechanism-focused research. These findings have important implications for clinical practice, supporting the use of DBT as a transdiagnostic intervention in complex comorbid populations.
The purpose of this study is to systematically compare six deep generative models for predicting long-term anatomic progression of neovascular age-related macular degeneration (nAMD) from pretreatment retinal imaging. We retrospectively analyzed OCT and fundus images from 85 treatment-naïve eyes initiating anti-VEGF therapy for nAMD. Five GAN-based architectures (BiCycleGAN, CycleGAN, Pix2pixHD, CycleGAN-Turbo, Pix2pix-Turbo) and one diffusion-based model (Stable Diffusion Img2Img) were trained separately for each modality to generate synthetic projections at 3, 6, and 12 months. Quantitative performance was assessed using structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), mean squared error (MSE), and root mean squared error (RMSE). Clinical realism was evaluated through a visual Turing test by five blinded expert graders. Pix2pixHD consistently achieved the highest image-quality metrics across all models, modalities, and time points. For OCT, they are SSIM 0.84 and PSNR 27.2 dB (3 months) and SSIM 0.83 and PSNR 25.8 dB (12 months). For fundus photographs, they are SSIM 0.80 and PSNR 26.0 dB (3 months) and SSIM 0.80 and PSNR 24.7 dB (12 months). In the visual Turing test, experts correctly identified synthetic images in 58% of cases (chance level, 50%), with OCT images showing near-chance discriminability (52%) compared to fundus photographs (64%). This study provides the first systematic comparison of multiple generative architectures for long-term nAMD progression prediction. Pix2pixHD achieved the highest fidelity, generating synthetic images whose realism was frequently, though not reliably, distinguished by observers (58%, not significantly different from chance; p = 0.13), particularly for OCT. These findings support the potential of deep generative models for AI-driven decision support in personalized retinal care. This work bridges the gap between computational science and clinical ophthalmology by demonstrating that deep generative models can transform pretreatment retinal images into clinically realistic predictions of disease progression. By enabling visualization of anticipated anatomical outcomes before treatment initiation, these tools have the potential to transition nAMD management from reactive to proactive paradigms, supporting individualized patient counseling, risk stratification, and evidence-based treatment planning at the point of care.
Elevated remnant cholesterol (RC) is implicated in the pathogenesis of atherosclerosis. To assess the prognostic role of RC in atherosclerotic cardiovascular disease. We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from inception to January 18, 2026, for eligible studies. The primary outcome was a composite of major adverse cardiovascular events (MACE). Pooled hazard ratios (HRs) with 95% CIs were calculated using a random-effects model. Twenty-one studies involving 114,592 participants were included. Higher RC levels were significantly associated with an increased risk of MACE (HR: 1.44, P < .001), all-cause mortality (HR: 1.40; P < .001), myocardial infarction (MI) (HR: 1.35; P < .001), stroke (HR: 1.21; P = .004), cardiac death (HR: 1.41; P < .001), and unplanned repeat revascularization (HR: 1.56; P < .001). Furthermore, each 1-SD increment in RC level was associated with an elevated risk of MACE (HR: 1.22; P < .001), all-cause mortality (HR: 1.16; P = .010), MI (HR: 1.11; P < .001), and unplanned repeat revascularization (HR: 1.31; P = .007). The association between RC levels and MACE risk was potentially modified by geographic region, body mass index, current smoking status, adjustment for traditional lipid parameters, and study quality. Elevated RC is associated with a worse prognosis in patients with established coronary artery disease. This association persisted after adjustment for traditional cardiovascular risk factors in the included studies, although residual confounding cannot be excluded. These findings suggest that RC assessment may have potential value within secondary prevention strategies for coronary artery disease.
Chalcones (1,3-diphenyl-2-propen-1-one) are open-chain flavonoids recognized for their structural diversity and broad pharmacological activities. Electrophilic α,β-unsaturated carbonyl systems and versatile substitution patterns on aromatic rings have positioned the chalcones as privileged structures in medicinal chemistry. This review highlights the contributions of Brazilian investigations to the advances of chemistry and bioactivity of natural and synthetic chalcones over the last 40 years. A systematic search of PubMed, Scopus, Embase, and Web of Science up to February 2026 identified 661 publications, revealing a growing interest since the early 2000s and reflecting the consolidation of chalcone as a central subject of research groups. Brazilian investigations have shown chalcones as antibacterial, antifungal, antiparasitic, anticancer, and anti-inflammatory agents, affording pivotal insights into structure-activity relationships and mechanisms of action at the molecular level. In addition, we submitted the most active chalcones to in silico evaluations, using SwissADME web tool, allowing a comparative analysis of their physicochemical, pharmacokinetics, and drug-likeness properties. The results indicated the majority of these compounds demonstrated an appropriate drug-like behavior. Collectively, the set of findings has positioned Brazil as an important research powerhouse of chemistry and pharmacology of chalcone and its derivatives, which may impact the discovery of innovative therapeutic agents.
Objective: To evaluate the efficacy and safety of a novel silicone hydrogel multifocal soft contact lens for presbyopia correction, and to verify its non-inferiority compared with a conventional hydrogel multifocal contact lens. Methods: This was a prospective, randomized, open-label, parallel-group, multicenter non-inferiority clinical trial. From October 2024 to July 2025, 195 presbyopic subjects aged ≥40 years with near add power of +0.75 to +2.50 D were screened at 5 centers (Eye Hospital of Wenzhou Medical University, Eye & ENT Hospital of Fudan University, and Shenzhen Eye Hospital, Qingdao Eye Hospital of Shandong First Medical University, and Shanxi Eye Hospital Affiliated to Shanxi Medical University), and 180 were enrolled and randomized (computer-generated random number method) 1∶1 to the test group (samfilcon A silicone hydrogel multifocal soft contact lens, n=90) or the control group (polymacon hydrogel multifocal soft contact lens, n=90). Both type of lenses were monthly disposable for daily wear. Binocular corrected distance visual acuity (5 m) and near visual acuity (40 cm) were measured at each visit using a standard logarithmic visual acuity chart (5-point recording method). Subjective wearing experience was assessed by a validated acceptability questionnaire, and ocular surface status was evaluated via tear break-up time (TBUT) and corneal fluorescein staining. The primary endpoint was the wearing success rate at 1 week, defined as binocular corrected distance visual acuity ≥4.9 and near visual acuity ≥4.7. Missing values were imputed using the worst observation carried forward method. Rate differences and 95% confidence intervals (CI) were calculated by the Newcombe-Wilson method. Between-group comparisons were performed using Fisher exact test, independent-samples t test, or Wilcoxon rank-sum test. Sensitivity analysis was performed using the Cochran-Mantel-Haenszel method stratified by center. The non-inferiority margin was prespecified as -10%. Results: The full analysis set comprised 177 subjects (87 in the test group, 90 in the control group), with a mean age of (47.1±4.7) years, including 33 males and 144 females. After the data imputation, the wearing success rate at 1 week was 100.0% in both groups, with a rate difference of 0.00% (95%CI:-4.23% to 4.09%), meeting the non-inferiority criterion. Sensitivity analysis of raw data showed success rates of 96.6% and 96.7% in the test and control groups, respectively (adjusted rate difference -0.00%, P=0.991), consistent with the primary analysis. At all visits, binocular corrected visual acuities were within normal ranges in both groups, with no significant between-group differences (all P>0.05). Contact lens-corrected visual acuity was slightly lower than best spectacle-corrected visual acuity in both groups, with mean differences of approximately 0.03 to 0.06. The test group had a higher proportion of"excellent"subjective distance vision ratings at 1 week (50.0% vs. 36.8%, P=0.047), better comfort at 1 week and 1 month (both P<0.05), and better lens cleanliness at dispensing and 1 week (both P<0.05). Subjects with low add power had better total subjective scores at 1 week [2.0 (0.0, 4.0) vs. 4.0 (2.0, 5.0), P=0.004], with no significant difference at 3 months. At 1 month, the test group showed a smaller decrease in TBUT from baseline (P<0.05) and a higher proportion of grade 0 corneal fluorescein staining at 1 week and 1 month (both P<0.05); these differences disappeared by 3 months. No device-related serious adverse events occurred, and the incidence of adverse events did not differ significantly between groups. Conclusions: The novel silicone hydrogel multifocal soft contact lens is non-inferior to the conventional hydrogel lens in presbyopia correction, with a comparable safety profile and superior comfort, subjective experience, and short-term ocular surface protection. It can serve as an effective correction option for presbyopic populations. 目的： 评价新型硅水凝胶多焦点软性接触镜矫正老视的有效性与安全性，验证其相对于传统水凝胶多焦点接触镜的非劣效性。 方法： 本研究为前瞻性、随机、开放、平行对照、多中心非劣效临床试验。2024年10月至2025年7月于5家中心（温州医科大学附属眼视光医院、复旦大学附属眼耳鼻喉科医院、深圳市眼科医院、山东第一医科大学附属青岛眼科医院和山西省眼科医院）筛选195名年龄≥40岁、近附加+0.75~+2.50 D的老视受试者，纳入180名，按1∶1随机（计算机生成随机数字法）分配至试验组（samfilcon A硅水凝胶多焦点软性接触镜，90名）和对照组（polymacon水凝胶多焦点软性接触镜，90名），均为月抛型日戴。采用标准对数视力表（5分记录法）测量各访视点双眼接触镜矫正远视力（5 m）和近视力（40 cm），通过主观可接受性问卷评估配戴体验，以泪膜破裂时间和角膜荧光素染色评估眼表状态。主要终点为戴镜1周时双眼矫正远视力≥4.9且近视力≥4.7的戴镜有效率。缺失值采用最差观测值结转法（WOCF）填补，率差及95%置信区间（CI）采用Newcombe-Wilson法，组间比较采用Fisher确切概率法、成组t检验或秩和检验，敏感性分析采用考虑中心因素的CMH法；非劣效界值为-10%。 结果： 全分析集177名（试验组87名、对照组90名），年龄（47.1±4.66）岁，其中男性33名，女性144名。戴镜1周WOCF填补后，两组戴镜有效率均为100.0%，率差为0.00%（95%CI：-4.23%~4.09%），非劣效成立；敏感性分析两组有效率分别为96.6%与96.7%，CMH校正率差-0.00%（P=0.991），结论一致。各访视点两组双眼矫正视力均在正常范围，差异无统计学意义（均P>0.05）；两组接触镜矫正视力较框架镜略低，差值约0.03~0.06。试验组戴镜1周主观中远视力“极佳”评级比例优于对照组（50.0%和36.8%，P=0.047），舒适度在戴镜1周和1个月时优于对照组（均P<0.05），镜片清洁度在戴镜当天和1周时优于对照组（均P<0.05）。低近附加受试者戴镜1周总主观评分优于高近附加者［2.0（0.0，4.0）和4.0（2.0，5.0），P=0.004］，3个月时差异消失。戴镜1个月时试验组泪膜破裂时间下降幅度小于对照组（P<0.05），戴镜1周和1个月时角膜荧光素染色0级比例均高于对照组（均P<0.05），3个月时差异消失。未发生器械相关严重不良事件，两组不良事件发生率差异无统计学意义。 结论： 新型硅水凝胶多焦点软性接触镜矫正老视的有效性不劣于传统水凝胶镜片，安全性良好，且在配戴舒适度、主观体验及短期眼表保护方面优于对照镜片，可作为老视人群的有效矫正选择。.
Maintaining a balanced immunity between pathogen defense and tolerance to environmental antigens in neonates is essential for survival and the establishment of life-long immune homeostasis. Instructed by environmental signals, type 1 conventional dendritic cells (cDC1) contribute to both processes but how the balance may be achieved is unclear. Here, we uncover an interferon (IFN)γ-driven regulatory circuit in early life that relays dietary cues to spleen cDC1. IFNγ-mediated STAT1-signaling induces an immunogenic maturation program in spleen cDC1 that enables them to shape the effector differentiation of antigen-experienced effector memory CD8⁺ T cells. This cDC1 program emerges during the transition from breastfeeding to solid food at weaning, occurs in germ-free mice, and remains operative to dietary intervention in adult mice. At weaning, this IFNγ signal enables spleen cDC1 to shape the effector phenotype of food-antigen-specific CD8+ T cells in a feedforward manner, thereby recalibrating the developing T cell pool. Our findings identify diet as a modifiable cue that can tune systemic cDC1-mediated immunity, opening new opportunities to steer immune responses during early life and beyond.
Objective: To evaluate the changes of binocular visual function and patient satisfaction after small-incision lenticule extraction (SMILE) with micro-monovision in myopic patients with presbyopia. Methods: This was a single-arm clinical trial. Myopic patients with presbyopia who underwent micro-monovision SMILE at Beijing Tongren Hospital, Capital Medical University, from January 2019 to March 2021 were enrolled. The surgical design principle was full correction of the dominant eye for distance vision, with the non-dominant eye undercorrected by -1.50 D to -0.50 D for near vision. Best corrected distance visual acuity and best corrected near visual acuity (CNVA) for the dominant eye, non-dominant eye, and both eyes were measured before surgery. Uncorrected distance and near visual acuity (UDVA, UNVA), CDVA, and CNVA for the dominant eye, non-dominant eye, and both eyes were measured at 1, 3, 6 months, 3 years, and 5 years after surgery. Accommodative function parameters were measured preoperatively and at each postoperative follow-up visit, including binocular accommodative amplitude (AMP) measured by the push-up method, accommodative response (BCC) measured by the binocular cross-cylinder method, negative relative accommodation (NRA), and positive relative accommodation (PRA), as well as distance and near stereopsis and Worth 4-dot tests. A visual satisfaction questionnaire was administered after surgery. Results: A total of 51 patients (102 eyes) with myopia and presbyopia were included, comprising 19 males and 32 females, aged (41.68±2.47) years. Sixteen patients (32 eyes) completed the 5-year follow-up. The binocular UDVA and UNVA were (-0.02±0.06) logMAR and (0.01±0.09) logMAR at 5 years after surgery, respectively. The spherical equivalent of the dominant and non-dominant eyes was (-0.24±0.22) D and (-0.80±0.37) D, respectively. The binocular AMP decreased from (5.66±0.28) D before surgery to (4.36±0.19) D at 1 month after surgery, and returned to the preoperative level at 3 months after surgery; The PRA decreased from (-1.93±0.17) D before surgery to (-1.33±0.13) D at 1 month after surgery, and returned to the preoperative level at 6 months after surgery. The BCC increased at 1 month after surgery and returned to the preoperative level at 6 months after surgery (differences across time points were all statistically significant, P<0.05). These indicators slightly decreased at 3 and 5 years postoperatively compared with their respective recovered levels. There were no statistically significant differences in NRA and near stereopsis at any postoperative follow-up time point compared with preoperative values. All patients achieved 60″ distance and near stereopsis at each postoperative follow-up visit point, and the Worth 4-dot tests showed both central and peripheral fusion function in both eyes. The subjective satisfaction score was (9.06±1.18) (out of 10) at 5 years after surgery, with a satisfaction rate of 15/16. Conclusions: SMILE with micro-monovision had an impact on accommodative function in the early postoperative stage. The AMP, PRA, and BCC returned to preoperative levels at 3 and 6 months postoperatively, with a slight decrease at 3 to 5 years. The procedure did not affect binocular visual functions such as fusion and stereopsis. At 5 years after surgery, patients exhibited good distance and near vision, maintained binocular visual functions, and reported high subjective satisfaction. 目的： 评估近视伴老视患者行微单眼视设计的飞秒激光小切口角膜基质透镜取出术（SMILE）后双眼视功能变化及患者满意度。 方法： 单臂临床试验。纳入2019年1月至2021年3月在首都医科大学附属北京同仁医院接受微单眼视设计的SMILE矫正近视伴老视的患者。手术设计原则为优势眼足矫看远，非优势眼预留-1.50~-0.50 D看近。术前测量优势眼、非优势眼、双眼最佳矫正远视力（CDVA）、最佳矫正近视力（CNVA）；分别于术后1个月、3个月、6个月、3年、5年时测量优势眼、非优势眼、双眼的裸眼远视力（UDVA）、裸眼近视力（UNVA）及CDVA、CNVA；分别于术前及术后各时间点测量调节功能参数，包括移近法测量双眼调节幅度（AMP）、交叉柱镜法测量双眼调节反应（BCC）、负相对调节（NRA）及正相对调节（PRA），以及远、近立体视和Worth四点灯检查；术后进行视觉满意度问卷调查。 结果： 共纳入近视伴老视患者51例（102只眼），其中男性19例、女性32例，年龄（41.68±2.47）岁，术后5年完成随访16例（32只眼）。术后5年双眼UDVA和UNVA分别为-0.02±0.06和0.01±0.09，优势眼和非优势眼等效球镜度数分别为（-0.24±0.22）D和（-0.80±0.37）D。双眼调节幅度由术前（5.66±0.28）D降至术后1个月（4.36±0.19）D，术后3个月恢复至术前水平；PRA由术前（-1.93±0.17）D降至术后1个月（-1.33±0.13）D，术后6个月恢复至术前水平；调节反应术后1个月升高，术后6个月恢复至术前水平（不同时间点间差异均有统计学意义，均P<0.05）；术后3年和5年上述指标较恢复期略有下降。NRA和近立体视在术后各时间点与术前比较差异均无统计学意义；所有患者术后各时间点远、近立体视均可达到60″，Worth四点灯检查均显示双眼中心及周边融合功能。术后5年主观满意度评分为（9.06±1.18）分，满意率为15/16。 结论： 微单眼视设计的SMILE术后早期对调节功能有影响，调节幅度、PRA和调节反应分别于术后3个月和6个月恢复到术前水平，术后3~5年略有下降。微单眼视设计的SMILE不影响融合和立体视等双眼视功能。术后5年表现出较好的远近视力、双眼视功能维持和较高的主观满意度。.
Presbyopia is one of the most common visual functional problems in middle-aged and older adults. With the increasing availability of correction options, presbyopia care has evolved from traditional near-vision compensation to comprehensive clinical decision-making that integrates visual quality, risk control, and long-term eye health management. However, the traditional single-specialty model is becoming insufficient to comprehensively address key aspects of presbyopia care, including assessment of visual needs, screening of ocular conditions, identification of systemic risk factors, selection of correction strategies, perioperative management, and long-term follow-up. This article discusses the limitations of the single-specialty model in presbyopia correction and the necessity of strengthening multispecialty management, aiming to provide a reference for individualized, precise, and standardized implementation of presbyopia care. 老视是中老年人群最常见的视觉功能问题之一。随着矫正方法不断丰富，老视矫正已由传统近用补偿逐步转向兼顾视觉质量、风险控制与长期眼健康管理的综合临床决策。然而，传统由单一专科主导的诊疗模式，已难以全面覆盖个体视觉需求评估、眼部条件筛查、全身风险识别、矫正方案选择、围手术期管理及长期随访等关键环节。本文针对老视矫正中单一专科诊疗模式面临的局限，阐述加强多专科管理的必要性，旨在为老视诊疗的个性化、精准化及规范化实施提供参考。.
Patients with chronic inflammatory disorders, including inflammatory bowel disease (IBD), carry an increased risk of cardiovascular disease. The 2022 ORAL Surveillance study reported that the pan-selective Janus kinase inhibitor (JAKi) tofacitinib was associated with increased risk of major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis compared to anti-tumor necrosis factor (anti-TNF) therapy. This prompted guideline changes regarding the use of all JAKis, including upadacitinib, a JAK1-selective drug approved for use in chronic inflammatory conditions, including IBD. However, the mechanism underlying JAKi-related MACE outcomes and the significance of JAK selectivity relative to TNF inhibition remain unclear. Microvascular dysfunction (MVD) is a predictor of MACE. Flow-mediated dilation (FMD) is a measure of MVD. Using an established ex vivo model of resistance arterioles isolated from adipose tissue, we performed the first mechanistic comparison of anti-tumor necrosis factor (anti-TNF; infliximab), pan-JAK inhibitor (tofacitinib), and JAK1-selective (upadacitinib) therapies on human microvascular endothelial function. Arterioles were obtained from low-cardiovascular-risk subjects of both sexes. Isolated microvessels were incubated with drugs of interest. Flow-mediated dilation (FMD), an assessment of MVD, was measured before and after nitric oxide (NO) synthase inhibition or hydrogen peroxide (H₂O₂) scavenging. No therapy statistically altered FMD magnitude, yet underlying mechanisms differed. Control and infliximab-treated vessels maintained physiologic NO-mediated dilation. Tofacitinib induced a shift toward pathologic H₂O₂-mediated dilation. Upadacitinib impaired NO-dependent dilation without evidence of compensatory H₂O₂ signaling. In summary, anti-TNF therapy and selective versus non-selective JAKi differentially modulate endothelial mechanisms of vasodilation, suggesting unique microvascular phenotypes with potential implications for cardiovascular risk.
Understanding dengue dynamics from a spatiotemporal perspective has become increasingly relevant in recent years, as it allows the identification of factors influencing disease transmission, including climatic conditions, human behavior, and the distribution of Aedes aegypti, the primary vector responsible for dengue virus transmission in tropical and subtropical regions. This knowledge is essential for supporting public health decision-making and reducing the impact of dengue on vulnerable populations. This study proposes a spatio-temporal deep learning framework based on the U-Net++ architecture to generate high-resolution dengue risk maps in Colombia. The model integrates climatic, environmental, demographic, and socioeconomic information derived from satellite and census sources. Two spatial approaches were evaluated: a high-dimensional geography (HDG) approach at the national scale and a low-dimensional geography (LDG) approach applied to five departments with high dengue incidence. The model integrating climatic, social, and environmental information achieved the best performance in both approaches. In the HDG configuration, the best model (M9) reached a test mIoU of 0.6646 (validation mIoU = 0.7361). In the LDG configuration, the corresponding model achieved an average test mIoU of approximately 0.73 across departments. These results highlight the potential of integrating heterogeneous climatic, environmental, and socioeconomic data within a spatiotemporal deep learning framework to characterize dengue risk patterns and support high-resolution surveillance.
Platinum resistance remains a major therapeutic challenge in ovarian cancer (OC) and is one of the main causes leading to disease relapse and mortality. Although PARP inhibitors have improved outcomes for a subset of patients, most women continue to rely on platinum-taxol based chemotherapy and ultimately develop recurrent, treatment-resistant disease with limited further therapy options. Therefore, there is a critical need to identify actionable, patient-specific vulnerabilities that would help as an alternative for chemoresistant patients. To identify such therapeutic opportunities, we established 35 patient-derived models from 22 OC patients, representing seven OC subtypes and preserving key molecular features of individual patients. High-throughput drug profiling across a library of 528 oncology-focused compounds generated over 29,000 drug response measurements, revealing inter-patient heterogeneity and sensitivity patterns. Among these, a subset of models exhibited a pronounced dependency on the anti-apoptotic protein Bcl-xL with minimal effects observed on patient-derived fibroblasts and healthy bone marrow, suggesting a therapeutic window. Proteomics-based comparison of Bcl-xL-sensitive and -resistant subclones identified activation of NOTCH signaling as a determinant to reduced response to Bcl-xL inhibition. Blocking of NOTCH signaling with gamma-secretase inhibitors restored sensitivity to Bcl-xL targeting and resensitized resistant cells to Carboplatin, resulting in sustained cytotoxicity in long-term washout assays and ex vivo cultures. Similar effects were observed with both Bcl-xL protein degrader and small molecule inhibitor, supporting robust targeting of Bcl-xL through different modalities. Together, these findings define a NOTCH-modulated Bcl-xL survival axis as a therapeutic vulnerability in platinum resistant OC. More broadly, this study demonstrates how translational drug profiling of physiologically relevant disease models can generate insights with clinical potential and provide precision oncology framework for identifying rational combination strategies to overcome chemoresistance.
This systematic review with functional meta-synthesis and exploratory meta-analysis evaluated the clinical utility of molecular testing in ameloblastoma, focusing on diagnostic, genotype-phenotype, prognostic, liquid-biopsy, and precision-therapy implications. PubMed/MEDLINE, Scopus, and Embase were searched from inception to April 2026. Eligible studies were full original articles evaluating direct molecular or molecularly interpretable testing in human ameloblastoma. Data were synthesized using functional meta-synthesis. Exploratory random-effects meta-analyses were performed when sufficient study-level data were available. Twenty-nine studies met the inclusion criteria. Molecular testing was most consistently informative for defining the molecular landscape and supporting diagnosis. BRAF V600E was the dominant alteration across the evidence base, but additional alterations in SMO, FGFR2, RAS-family genes, CTNNB1, PIK3CA, EGFR, and ROS1 were reported, particularly in selected or BRAF-wild-type tumors. Exploratory meta-analysis of 19 studies showed a pooled BRAF V600E prevalence of 69.1% (95% CI: 62.1%-75.3%; I2 = 80.3%). Four studies provided complete site-specific data, showing strong enrichment of BRAF V600E in mandibular versus maxillary tumors (OR = 20.13; 95% CI: 7.65-52.95; I2 = 0.0%). BRAF VE1 immunohistochemistry showed high exploratory pooled sensitivity (96.6%; 95% CI: 84.1%-99.4%) and specificity (89.8%; 95% CI: 71.5%-96.8%) when compared with molecular reference methods. Prognostic evidence was inconsistent: BRAF V600E was not a reliable stand-alone recurrence marker, although VEGF mRNA and broader molecular profiles may have prognostic relevance. Plasma cfDNA testing did not reliably detect tissue-positive BRAF V600E. Targeted therapy evidence suggested radiologic response and organ-preservation potential in selected BRAF V600E-mutated tumors, but remained limited to non-randomized series. Molecular testing provides clinically relevant diagnostic and genotype-phenotype information in ameloblastoma and may guide targeted therapy in selected cases. Prognostic and liquid-biopsy applications remain insufficiently validated.
The occurrence, taxonomic identity, drug resistance pattern and virulence traits of cultivable environmental Leptospira inhabiting the Indian subcontinent remain largely unexplored. Here, we describe the isolation and characterization of six novel strains of Leptospira from environmental samples and decode their drug resistance and virulence traits using in silico and in vitro approaches. Among six new isolates of Leptospira, two strains were identified to represent L. interrogans (SA-L3 and SA-L4), originating from sewage that flows proximal to a wildlife enclosure in Mangalore. We also found a strain each of L. levettii (SA-E5), L. kmetyi (SA-E7), L. koniambonensis (SA-E9) and Leptospira sp. (SA-E8, a putative L. andrefontaineae-like new species of Leptospira) within a ~ 5000 sq. ft. farmland area at Halageri, Uttara Kannada District, India. All isolates exhibited hemolysis and harbored genes encoding diverse sphingomyelinases. All strains were resistant to vancomycin, rifamycin, aztreonam, lincomycin, nalidixic acid, minocycline and troleandomycin and carried genes for a multitude of proteins conferring drug-resistant mechanisms. Leptospira sp. SA-E8 exhibited superior virulence traits and significant biofilm formation in vitro. Comparative genomics revealed remarkable interspecies variations in genome size (4.0‒4.8 Mbp), GC content (35.1‒44.8), coding sequences (3823‒5296) and RNA (39‒43). All strains exhibited the oxidation of diverse organic acids and were equipped with genetic machinery for ketone body oxidation. Our study demonstrated the occurrence of genetically distant Leptospira in environmental samples collected from India and provided evidence for conserved multidrug resistance and virulence, offering new dimensions to the theranostics of Leptospirosis. We suggest the inclusion of L. levettii SA-E5, L. kmetyi SA-E7, L. koniambonensis SA-E9 and Leptospira sp. SA-E8 in the array of leptospiral antigens being used in sero-epidemiological studies to establish their seroprevalence in humans, rodents and livestock.
This study aimed at assessing the inter-procedural reliability (compared to the in-office consultation) and the diagnostic accuracy (compared to the reference standard) of the telemedicine consultation to guide the diagnostic workup of adults and children when complaint of excessive daytime sleepiness, possibly due to narcolepsy, is suspected. A cross-sectional diagnostic study was initiated in 2019 and completed in 2023. Consecutive people of any age referred for excessive daytime sleepiness complaint to the Clinic for Narcolepsy in Bologna were eligible for inclusion. The telemedicine consultation was conducted via tablet for the patient and via equipped personal computer in another room for the physician (interviewer). Interviewers expressed diagnostic orientation indicating narcolepsy as 'probable', 'possible' and 'excluded'. The final diagnosis was established by applying the International Classification of Sleep Disorders criteria. Inter-procedural reliability and diagnostic accuracy measures were calculated. Two hundred and twenty-one participants were included in the reliability study, 198 in the diagnostic accuracy study. The agreement between the two consultation modalities on diagnostic orientation was 'substantial' (Kappa 0.74, 95% CI 0.66-0.82). Agreement on the presence of narcoleptic pentad symptoms was 'substantial' (excessive daytime sleepiness, hypnagogic hallucinations, disrupted nocturnal sleep) or 'almost perfect' (cataplexy, sleep paralysis). In children reliability for excessive daytime sleepiness, cataplexy and hypnagogic hallucinations was lower. Telemedicine and in-office consultation had identical sensitivity (100%, 95% CI 94-100) and similar specificity (43%, 95% CI 35-52, vs. 40%, 95% CI 32-49). Telemedicine consultation is a reliable diagnostic triage procedure when excessive daytime sleepiness possibly due to narcolepsy is suspected, in particular to exclude people who do not suffer from narcolepsy without the risk of false negatives.
Lymphedema is a chronic and progressive condition that significantly affects functional outcomes and quality of life. Social determinants of health (SDOH) contribute substantially to health disparities; however, their association with lymphedema severity and treatment adherence remains underexplored. This study aimed to evaluate the association between SDOH and both lymphedema severity and adherence to therapy. A retrospective chart review was conducted on 300 patients diagnosed with lymphedema (ICD-10: I89.0) who received care at the Georgia Cancer Center between March 2019 and December 2023. SDOH variables were categorized across five domains: economic stability, education, healthcare access, neighborhood environment, and social/community context. Lymphedema severity was assessed using the International Society of Lymphology staging system and dichotomized as moderate or less versus severe. Treatment adherence was measured as a composite score (0-100%) based on four components of complete decongestive therapy and categorized as low (< 50%) or high (≥ 50%). Multivariable logistic regression was used to examine associations. Among 295 eligible patients included in the final analysis, transportation access, ethnicity, and gender were significantly associated with both lymphedema severity and treatment adherence (p < 0.05). Limited transportation access and lower socioeconomic indicators were associated with higher odds of severe lymphedema and lower adherence. African American ethnicity and male gender were also associated with worse outcomes. SDOH significantly influences lymphedema severity and treatment adherence. Addressing barriers such as transportation and socioeconomic disparities is critical to improving outcomes and reducing inequities in lymphedema care.
Magnetic resonance imaging (MRI) is regarded as the clinical diagnostic gold standard. However, its lengthy scan times introduce motion artifacts, which can severely compromise diagnostic accuracy. K-space undersampling is a fundamental strategy to address this issue, but undersampling inevitably introduces quality degradation in reconstructed images. To tackle the challenges in accelerated MRI reconstruction, this paper proposes a Multi-Feature Guided Progressive Divide-and-Conquer reconstruction network (MFG-PDAC). It achieves synergistic optimization through three novel modules. The Multi-Frequency Gated Attention (MFGA) module enhances feature propagation, the Edge Enhanced Feature Modulation (EEFM) module reinforces anatomical boundaries, and the Frequency-Aware Data Consistency (FREDC) module optimizes spectral reconstruction. These three modules form a closed-loop mechanism consisting of feature selection, spatial optimization, and frequency-domain correction. The MFGA enables dynamic fusion of multi-frequency features at U-Net skip connections, providing structural priors for gradient modulation. The gradient modulation amplifies edge response in the image domain, improving high-frequency reconstruction quality. The FREDC dynamically weights constraints based on frequency band errors, creating a feedback mechanism for MFGA refinement. Evaluated on the fast MRI knee dataset, MFG-PDAC achieved a peak signal-to-noise ratio of 37.28 dB and structural similarity index measurement of 0.909 under 8× acceleration, outperforming the current mainstream methods. The network particularly can achieve better reconstruction in key diagnostic regions such as bone-soft tissue interfaces and ligament textures. This study provides an accurate and efficient solution for clinical rapid MRI scanning, demonstrating significant potential for clinical translation.
Tubular epithelial cell (TEC)-macrophage crosstalk contributes to aldosterone (Aldo)-dependent renal fibrosis in hypertension. Extracellular ATP (eATP) can act as a mediator of TEC-macrophage crosstalk. However, whether and how eATP functions in Aldo-induced renal injury remain unknown. A deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mouse model and a primary mouse renal tubular epithelial cell (mTEC)-bone marrow-derived macrophage (BMDM) coculture model were developed. To investigate the relationship between Aldo/MR and eATP signaling in TEC-macrophage crosstalk, specific inhibitors, adeno-associated virus (AAV)-shRNA and small interfering RNA (siRNA) were used. scRNA-seq analysis of kidneys from DOCA-salt mice was performed for verification. Urinary ATP levels and renal pannexin1 (PANX1, an ATP efflux channel) expression increased significantly in DOCA-salt mice, whereas the selective mineralocorticoid receptor (MR) antagonist finerenone treatment reduced urinary ATP levels, PANX1 expression, tubular injury, and macrophage-related inflammation. Inhibiting PANX1-eATP-P2X7 signaling with the PANX1 inhibitor probenecid, specifically knocking down tubular PANX1, or using the eATP ectonucleotidase apyrase or the P2X7 blocker AZ10606120 mitigated renal tubular damage and NLRP3-mediated pyroptosis in the renal cortex of DOCA-salt mice. Similarly, in mTECs, finerenone suppressed Aldo-induced ATP release and PANX1 upregulation. A luciferase assay confirmed the binding site of MR to the PANX1 transcription promoter. Coculture of BMDMs with mTECs under Aldo stimulation significantly increased NLRP3-mediated BMDM pyroptosis and migration. However, these effects were reversed by treating the mTECs with MR or PANX1 siRNA. Similar results were observed after treatment with apyrase or AZ10606120 in the coculture system. scRNA-seq analysis further identified the activation of P2X7/NLRP3-related pyroptosis pathway in macrophages from DOCA-salt mice. In conclusion, TECs play a critical role in macrophage pyroptosis in Aldo-induced renal injury. eATP is a key messenger involved in TEC-macrophage crosstalk. PANX1-eATP-P2X7 signaling mediates TEC‒macrophage interactions to exacerbate Aldo-driven renal inflammation in hypertension. Mechanism through which Aldo/MR-induced PANX1-eATP-P2X7 signaling activation promotes macrophage pyroptosis in hypertensive renal injury.
Accurate and reliable brain tumor diagnosis from magnetic resonance imaging (MRI) remains a challenging task, particularly in multi-class settings where inter-class ambiguity and miscalibration may degrade predictive performance. In this work, we propose a Class-wise Quantum Relational Calibration Network (CQRCNet), a hybrid quantum-classical framework that integrates quantum relational modeling into a classical convolutional neural network backbone. Our approach employs a parameter-shared and low-qubit quantum circuit to explicitly model pairwise interactions between class-specific evidences, serving as a calibration mechanism for logit refinement. Unlike conventional post-hoc calibration methods, the proposed mechanism operates by refining inter-class relational representations prior to softmax normalization. Empirical studies are conducted on a publicly available brain tumor MRI dataset covering four tumor categories, and the proposed method demonstrates favorable performance compared with several reported classical deep learning baselines and representative hybrid quantum-classical models. Noise-aware quantum simulations under depolarizing noise and finite-shot sampling further indicate that the proposed quantum relational calibration maintains stable performance under simulated realistic quantum conditions, suggesting its potential applicability to near-term quantum computing scenarios. In addition, ablation studies, including comparisons with temperature scaling and analyses of different quantum circuit depths, provide further insights into the role of quantum relational modeling in the proposed framework.