This study retrospectively characterized the laboratory features of direct antiglobulin test (DAT)-positive anemia in newly diagnosed multiple myeloma (MM) and explored associated immunologic alterations to better understand MM-related immune dysregulation. We enrolled 77 patients with newly diagnosed MM admitted to our hospital between 2021 and 2025. Based on DAT results, patients were assigned to a DAT-positive group (n = 52) or a DAT-negative group (n = 25). Clinical characteristics, laboratory parameters, and peripheral blood T-cell subsets were compared between groups. Monoclonal immunoglobulin (M protein) isotype distribution was statistically significantly different between groups (P < .001), with immunoglobulin G predominating in the DAT-positive group (88.46%). Compared with the DAT-negative group, DAT-positive patients had lower albumin, sodium, and potassium levels as well as a lower albumin to globulin ratio but higher levels of globulin and ferritin as well as higher absolute lymphocyte counts (all P < .05). Flow cytometric analysis showed increased T-cell-related parameters, particularly CD8-positive T cells, in the DAT-positive group, whereas reduced natural killer-cell and B-cell counts were more common in the DAT-negative group. The observed laboratory profile suggested a more pronounced state of inflammatory or immune activation and electrolyte disturbances, highlighting the need for improved clinical recognition and detection of potential immune-mediated red blood cell injury, hemolytic predisposition, and related immune abnormalities.
Critical limits represent quantitative boundaries of life-threatening diagnostic results that demand urgent clinician notification and potentially, lifesaving intervention. To document 35-year changes in glucose critical limits, characterize decision thresholds at independent and network hospitals, identify US geographic risk differences, report point-of-care testing results, and align critical notifications, pathophysiological risk, and consensus recommendations to improve outcomes. We gathered critical limit notification lists from 417 hospitals comprising university, trauma, and heart centers, and network and community hospitals in all 50 states and Washington, District of Columbia, then extracted glucose critical limits for adults and newborns. All hospitals listed low and high glucose critical limits. Between 1990 and 2025, low glucose critical limits increased significantly (P < .001) with medians of 45 (range, 30-70) versus 50 (range, 35-60) mg/dL, respectively. Histograms documented striking inconsistencies. Matched pairs (N = 73) of laboratory versus point-of-care low glucose critical limits at the same hospitals did not differ significantly. A US risk level map identified geographic discrepancies relative to the neuroglycopenic impaired awareness threshold of 54 mg/dL. There were statistically significant changes in newborn low and high distributions with 2025 medians of 40 (range, 20-55) and 200 (range, 120-500) mg/dL, respectively. An increased median low critical limit of 50 mg/dL does not match the 54 mg/dL threshold for neuroglycopenic loss of awareness that places patients at risk. The median high critical limit of 450 mg/dL at network hospitals decreases the risks of extreme hyperglycemia. The risk map revealed geographic inconsistencies, lack of harmonization, and poor alignment with consensus clinical recommendations.
The goal of quantitative photoacoustic imaging (qPAI) is to determine absolute chromophore concentrations from multispectral photoacoustic images. Achieving this goal would enable bias-free molecular photoacoustic imaging and the derivation of functional tissue biomarkers, such as local blood oxygenation, with numerous clinical implications. To deliver qPAI, two inverse problems must be solved: the acoustic inverse problem of reconstructing the initial pressure distribution from measured signals, and the optical inverse problem of reconstructing spatial images of optical absorption from the initial pressure. Unfortunately, these inverse problems are difficult to solve in practice. The validation of proposed qPAI algorithms is particularly challenging due to the lack of experimentally measured ground truth of the optical and acoustic tissue properties. With OpenQPAIData, we present a dataset of 30 tissue-mimicking phantoms imaged using three different photoacoustic systems: the Multispectral Optoacoustic Tomography (MSOT) InVision commercially produced system from iThera Medical GmbH, and the custom-built Transmission Reflection Optoacoustic and Ultrasound (TROPUS) and Spiral Volumetric Optoacoustic Tomography (SVOT) imaging systems developed by Prof. Daniel Razansky's group. The dataset includes raw measurements, reconstructed images, manually segmented reference annotations, and matched optical property maps derived from double-integrating-sphere (DIS) measurements. By providing these multi-device imaging data with reference optical properties, we believe that OpenQPAIData enables the benchmarking of both acoustic and optical inverse solvers and supports the development of image quality assessment metrics for photoacoustic imaging.
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。.
To estimate the causal effect of increased schooling arising from national policy reforms on HIV/AIDS infection and testing, along with associated indicators of risk across a wide range of settings in sub-Saharan Africa. Multicountry quasi-experimental analysis using two-stage least squares (instrumental variable) analysis with national schooling reforms as the instrument for years of schooling. A pooled sample from 23 sub-Saharan African countries with historical peak HIV-prevalence rates ranging from under 1% to over 20%, surveyed from 2003 to 2019. A sample of 191 128 cases with linked HIV test results was obtained from nationally representative Demographic and Health Surveys and AIDS Indicator Surveys (and a related survey in Botswana), restricted to adults aged 18-49 years in birth cohorts spanning 1955-1998. Primary outcomes were HIV test positivity and ever having been tested for HIV. Secondary outcomes were comprehensive HIV knowledge, age at first intercourse, condom use at last intercourse, number of sexual partners in the preceding 12 months and lifetime number of sexual partners. Exposure to an education reform increased mean schooling by 0.45 years (95% CI 0.28 to 0.63). Pooled instrumental variable analysis found no significant effect of an additional year of schooling on HIV test positivity (-0.5 percentage points, coefficient -0.005, 95% CI -0.018 to 0.008). One additional year of schooling was associated with a 4.6 percentage point increase in ever having been tested for HIV, significant at the 10% level (coefficient 0.046, 95% CI -0.001 to 0.094). Effects on secondary behavioural outcomes were limited to specific subgroups: women showed a small delay in age at first intercourse while men and urban residents showed increased condom use. No significant effect on comprehensive HIV knowledge was identified in the pooled sample. Across a wide range of African settings, policies expanding access to schooling appear to increase HIV testing but do not directly reduce HIV infection. Policymakers should look beyond education alone as an HIV prevention strategy, with realistic expectations of schooling expansion as a strategy on its own.
Background Carpal tunnel syndrome (CTS) frequently requires surgical release, but optimal postoperative rehabilitation strategies remain poorly standardized. Innovative, task-oriented approaches may improve functional recovery and patient engagement. This study aimed to determine whether a structured rehabilitation program using plastic building-block toys improves outcomes after carpal tunnel release (CTR). Specifically, we asked: (1) does this program enhance sensory recovery, (2) does it improve patient-reported functional outcomes, and (3) are these effects observable early after surgery? Hypothesis We hypothesized that the BRICKS rehabilitation program would result in superior sensory and functional recovery compared with non-formal therapy. Patients and Methods This single-centre prospective study included adult patients with severe CTS (grade 4-6) undergoing CTR between 2022 and 2025. Postoperatively, patients received either non-formal therapy (NFT group) or a structured home-based rehabilitation program using plastic building-block toys (BRICKS group). The primary endpoint was the comparison of sensory discrimination (Weber test) at 3 months postoperatively. Secondary endpoints included comparison of Boston Carpal Tunnel Questionnaire Symptom Severity Scale [BCTQ-SS] and Functional Form [BCTQ-FF] results at 3 months postoperatively as well as as all outcome measurements obtained at 1 month postoperatively. A total of 40 patients were included (20 per group). Results Both groups showed significant improvements in Weber test, BCTQ-SS, and BCTQ-FF scores between preoperative and postoperative assessments (1 and 3 months). At 1 month, the Weber test was significantly lower in the BRICKS group compared with the NFT group (3.4 ± 1.0 vs 4.5 ± 1.2), with no between-group differences in BCTQ scores. At 3 months, the BRICKS group demonstrated significantly better outcomes for all endpoints, with lower Weber test values (2.8 ± 0.6 vs 4.1 ± 1.2), BCTQ-SS scores (13.3 ± 1.8 vs 16.6 ± 3.0), and BCTQ-FF scores (9.5 ± 1.7 vs 12.0 ± 3.3) compared with the NFT group. Discussion A structured, task-oriented rehabilitation program using building-block activities improved sensory discrimination and functional outcomes following CTR, with effects becoming significant at 3 months. These findings support the integration of engaging, home-based rehabilitation strategies to enhance postoperative recovery in severe CTS, in line with growing evidence favoring active, task-specific rehabilitation approaches. LEVEL OF EVIDENCE: III; Therapeutic.
The aim of this in vitro study was to evaluate cuspal deflection and marginal adaptation in premolars restored with conventional and low-shrinkage resin composites (RCs). Fifty-six maxillary first premolars with standardized MOD cavities were randomly assigned to four groups (n = 14): Clearfil Majesty Posterior (CMP), Charisma Diamond (CHD), Beautifil II LS (BL), and Filtek Z550 (FZ). Cuspal deflection was measured using a digital micrometer as the linear distance between two reference points at baseline, 5 minutes, and 24 hours after restoration. Deflection values were calculated relative to the baseline. Three samples per group were evaluated using scanning electron microscopy to assess marginal adaptation. Data were analyzed using IBM SPSS Statistics V23.0. Data distribution was evaluated using the Shapiro-Wilk test. Kruskal-Wallis and one-way ANOVA tests were used according to data distribution, followed by appropriate post hoc tests. The significance level was set at p < 0.05. The amount of cuspal deflection at 5 minutes was greater than that observed at 24 hours in all groups. CMP, CHD, and BL showed lower cuspal deflection compared with FZ at all time intervals (p < 0.001). CMP exhibited the lowest cuspal deflection values, although no significant differences were found among the low-shrinkage RCs. Modifications in the organic matrix or material formulation of the RCs can contribute positively to the control of cuspal deflection and support improved marginal adaptation. The reduced cuspal movement produced by low-shrinkage RCs may increase the likelihood of clinical success by helping preserve restoration integrity.
Confirming the underlying molecular etiology of hereditary hypophosphatemia (HH) to provide recurrence risk counseling is highly important. Our aims were to describe the detected variants and their distribution across Argentina and to contrast them with published data. Patients with HH prospectively referred to a hypophosphatemia program for genetic testing were included. Saliva samples were evaluated by next-generation sequencing with a panel of 13 genes associated with HH. In patients with no variants detected in the HH rickets related gene panel, multiplex ligation-dependent probe amplification was performed for the PHEX gene. Cascade genetic testing was recommended for at-risk relatives of index cases (IC). One hundred and sixty participants were enrolled, including 129 ICs with suspected HH (80.62%). Among them, 114 had a positive molecular test (88.37%); 93% were variations in the PHEX gene, predominantly single-nucleotide variants. Distribution of variant types was consistent with international databases. In our sample, 12% of subjects had undetectable variants in the gene panel, highlighting the importance of complete genome sequencing. Ours is the first study in Latin America to analyze PHEX variants, which is considered crucial for the generation of regional evidence to understand the genetic variability of HH and for leading specific targeted treatment.
To examine the effectiveness of virtual reality-assisted neuromuscular training interventions on agility performance and injury prevention indicators in basketball athletes compared to conventional training approaches. A 12-week controlled laboratory experiment was conducted with 70 university-level basketball athletes (age 20.95 ± 1.5 years) randomly allocated to VR-assisted neuromuscular training (n = 35) or conventional training control groups (n = 35). Comprehensive assessments included agility tests (T-test, 5-10-5 shuttle), functional movement screening, biomechanical analysis, and neuromuscular function parameters measured at baseline, mid-intervention, and post-intervention. The VR training group demonstrated 7-10% greater pre-to-post improvements in agility performance compared with the control group across multiple agility measures (p < 0.001, Cohen's d = 0.89-1.34). Neuromuscular function parameters showed 15-30% greater pre-to-post improvements in the VR group relative to controls, including enhanced dynamic balance (pre-VR: 2.34 ± 0.41, post-VR: 1.67 ± 0.28; pre-control: 2.31 ± 0.38, post-control: 2.02 ± 0.35; between-group difference: - 0.35, 95% CI [- 0.52, - 0.18], effect size = 1.24, p < 0.001), improved joint position sense (23.4 vs. 11.8% improvement, 95% CI for difference [8.2%, 15.0%], p = 0.002), reduced dynamic knee valgus angles (18.7 vs. 8.2% reduction, 95% CI for difference [6.1%, 14.9%], p < 0.001), and increased reactive strength index (27.2 vs. 12.3% increase, 95% CI for difference [9.5%, 20.3%], p < 0.001). Movement quality scores and biomechanical injury risk markers consistently favored the VR intervention. Virtual reality-assisted neuromuscular training yields superior improvements in both agility performance and biomechanical injury risk markers compared to conventional training approaches in basketball athletes, supporting its integration into comprehensive athletic development programs.
Accurate assessment of osteoarthritis-related pain in dogs requires validated, language-specific clinical metrology instruments. The absence of a Korean version of the widely used Canine Brief Pain Inventory (CBPI) limits standardized pain assessment and outcome evaluation in Korean-speaking clinical and research settings. This study aimed to develop and perform an initial psychometric evaluation of the Korean version of the CBPI. This observational cross-sectional study included 56 dogs with osteoarthritis and 22 healthy controls. Construct validity was assessed using exploratory and confirmatory factor analyses. Convergent validity was assessed using Spearman correlations between CBPI scores and the owner-reported quality-of-life item. Discriminant validity was evaluated through group comparisons between dogs with osteoarthritis and healthy controls. Internal consistency was evaluated using Cronbach's α. Exploratory analysis identified a dominant general pain factor (eigenvalue = 8.04; 80.4% variance). Confirmatory factor analysis demonstrated superior relative fit for the two-factor model (χ²/df = 2.94, comparative fit index [CFI] = 0.917, root mean square error of approximation [RMSEA] = 0.186, standardized root mean square residual = 0.044) compared with the one-factor model (χ²/df = 4.13, CFI = 0.861, RMSEA = 0.236). CBPI scores showed significant negative correlations with quality of life in dogs with osteoarthritis (ρ = -0.516 to -0.485; corresponding 95% confidence intervals ranged from -0.710 to -0.248; p < 0.001). Dogs with osteoarthritis had higher CBPI total scores than healthy controls (median, 18.0 vs. 0; p < 0.001). Cronbach's α coefficients ranged from 0.951 to 0.968. The Korean CBPI demonstrated excellent internal consistency and preliminary evidence of construct validity for assessing osteoarthritis-related pain in dogs, supporting its use as an owner-reported outcome measure in Korean-speaking clinical and research settings. Future longitudinal studies should evaluate its test-retest reliability and responsiveness to treatment.
This randomized clinical trial aimed to assess the relation of insertion torque value (ITV) and implant stability quotient (ISQ) between bone-level (BL) and tissue-level (TL) dental implants (ISQ recorded immediately and 3 months after implant placement). A total of 90 dental implants (44 BL, 46 TL; BioHorizons Camlog, Iberica) were placed in 21 patients. ITV was recorded at placement. ISQ (Penguin device, Klockner) was measured horizontally (ISQ-H) and vertically (ISQ-V) at baseline and at the 90-day follow-up. The Mann-Whitney U test and Spearman's correlation tests (α = 0.05) were used for the analyses. No significant difference in ITV was found between the BL (36.0 ± 11.5 Ncm) and TL (38.0 ± 11.5 Ncm) groups (p = 0.381). Similarly, no significant differences were observed in baseline ISQ-H (p = 0.928) or ISQ-V (p = 0.874). At 90 days, ISQ-H values were marginally higher in the TL group (66.5 ± 20.9) compared to the BL group (57.1 ± 18.9; p = 0.029). A significant positive correlation was found between ITV and baseline ISQ (r = 0.493, p < 0.001), but not with 90-day ISQ values. Implant design (BL vs. TL) did not significantly influence ITV or ISQ. The finding of greater horizontal stability for TL implants at 90 days, while marginal, suggests a potential long-term biomechanical difference warranting further study. The dissociation between insertion torque and 90-day stability indicates that secondary stability is governed by factors beyond initial mechanical engagement.
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.
Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3,234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC <LLN and FEV1/FVC ≥70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC ≥70%) and symptoms (COPD Assessment Test [CAT] score ≥10). The 1,888 participants with spirometry were a mean (±SD) age of 68.2±9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0±0.8 years. The mean FEV1 was 2.14±0.60 L, FVC 2.74±0.74 L, FEV1/FVC 78.4±6.4%, mean BMI was 32.4±6.7 kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.
This study presents the fabrication of a novel, sustainable, and cost-effective hybrid composite (SAC-PANI) derived from sewage sludge calcined at 600 °C, activated carbon, and polyaniline through in situ oxidative polymerization. Comprehensive Characterization using FTIR, XRD, SEM, BET, and TGA confirmed the successful formation of the composite and its enhanced physicochemical properties. BET analysis revealed a substantial increase in surface area (90 m²/g) compared to raw calcined sludge (58 m²/g), indicating improved porosity. Process optimization was performed using Response Surface Methodology (RSM) based on a Central Composite Design (CCD). The developed quadratic model (R² = 0.984) adequately described the system and revealed significant interactions among pH, adsorbent dosage, and initial metal concentration, with optimum removal achieved at pH 6.0. Adsorption equilibrium data were best described by the Langmuir isotherm (R² = 0.995 and 0.992 for Pb(II) and Cd(II), respectively), yielding maximum adsorption capacities of 128.5 ± 2.3 mg/g for Pb(II) and 115.7 ± 2.1 mg/g for Cd(II). Kinetic studies were well fitted by the pseudo-second-order model (R² = 0.998 for Pb(II) and 0.997 for Cd(II)), with rate constants of k₂ = 0.035 ± 0.001 g/mg·min for Pb(II) and k₂ = 0.029 ± 0.001 g/mg·min for Cd(II), indicating that chemisorption is the dominant adsorption mechanism owing to interactions between the metal ions and the nitrogen-containing functional groups of PANI. Thermodynamic analysis demonstrated that the adsorption process is spontaneous (ΔG° = -19.8 kJ/mol for Pb(II) and - 17.6 kJ/mol for Cd(II) at 298 K), endothermic (ΔH° = +33.5 kJ/mol for Pb(II) and + 25.3 kJ/mol for Cd(II)), and characterized by increased entropy (ΔS° = +132 J/mol·K for Pb(II) and + 98 J/mol·K for Cd(II)), indicating chemisorption-driven metal uptake. The composite also exhibited good stability, retaining more than 82% of its removal efficiency after five adsorption-desorption cycles for both Pb(II) and Cd(II).). Environmental safety assessment via the TCLP leaching test demonstrated that the spent adsorbent is non-hazardous, with Pb and Cd leachate concentrations (0.58 and 0.18 mg/L, respectively) well below EPA regulatory limits (5.0 mg/L for Pb and 1.0 mg/L for Cd). Importantly, the SAC-PANI composite was successfully tested on real electroplating wastewater, achieving Pb(II) and Cd(II) removal efficiencies of 75.0 ± 1.5% and 72.6 ± 1.4%, respectively, in the presence of competing ions and complex matrix effects. Overall, SAC-PANI demonstrates considerable potential as an efficient, sustainable, and low-cost adsorbent for the removal of heavy metals from wastewater.
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.
For most people living with Human immunodeficiency virus (HIV), virus control and sufficient immune function can be achieved with polypharmacotherapy. A minority is intolerant to thereto, and drug-resistant mutants are emerging. Additionally, people living with HIV (PLWH) have significantly higher risk of cardiovascular morbidity and malignant diseases. HIV is in principle immunogenic. If T-cell depletion could be avoided immunological HIV eradication should be achievable. The "Berlin patient" in whom allogeneic stem cell transplantation from a CCR5Δ32/Δ32 donor induced long-term remission without antiviral therapy raised the hope that stem cell gene therapy with CCR5-deleted autologous stem cells could provide a cure, but the strategy did not live up to expectations. We propose to test an alternative strategy, namely expression of a designer recombinase which specifically excises HIV provirus from the genome under a Tat-inducible promoter so that expression is restricted to infected cells. A cGMP-compliant manufacturing protocol and quality control strategy for this investigational medicinal product was developed, validated, and a manufacturing authorization obtained. A First-in-Human-clinical trial, testing engraftment, repopulation of peripheral specific immunity, and ability to control HIV infection without antiviral medication is in preparation. Protocols can be adapted to other stem cell gene therapies by transferring alternative lentviral cargo.
This article aims to compare the flexural properties, fracture toughness, and fracture resistance of 3D-printed hybrid material (Varseosmile Crown plus, VS) at various build orientations versus milled hybrid materials (Cerasmart 270, CS, and Vita Enamic, E). Specimens of 3D-printed material (VS) were fabricated at four build orientations (30, 45, 60, and 90 degrees; n = 10). Two milled hybrid ceramics (CS and E) served as comparative groups (n = 10). Flexural properties and fracture toughness were assessed on standardized bar specimens following ISO 6872:2024. Fracture resistance was tested on cemented crowns (n = 10). Statistical analysis was performed using Welch's ANOVA with Dunnett T3 post hoc comparison at α = 0.05. CS exhibited the highest flexural strength (230.19 ± 13.59 MPa), fracture toughness (1.88 ± 0.07 MPa·m1/2), and fracture resistance (4,161.75 ± 597.50 N). E demonstrated the highest flexural modulus (26.79 ± 1.36 GPa). VS had lower values in all test parameters of this study compared to CS and E. Among VS specimens, building orientation significantly influenced flexural properties and fracture toughness, with a 90-degree building orientation yielding optimal results (flexural strength: 111.49 ± 4.15 MPa, flexural modulus: 2.32 ± 0.10 GPa, fracture toughness: 1.05 ± 0.05 MPa·m1/2, and fracture resistance: 2,296.52 ± 282.81 N). However, building orientation did not significantly affect the fracture resistance of the cemented crown. Milled hybrid ceramics demonstrated superior strengths to the 3D-printed specimens. While 90-degree orientation optimized strength in standardized specimens, this benefit did not translate to a significant improvement in the fracture resistance of cemented crowns, suggesting that clinical geometry and cementation may affect the effects of build anisotropy.
Equine Rotavirus A (ERVA) is a major cause of acute diarrhea in neonatal foals, leading to significant economic losses. Genetic variation and global transmission complicate disease control efforts. To analyze the complete genome of an ERVA strain from Jeju Island, Korea, and assess its genetic and phylogenetic relationships with global ERVA strains. Twenty-five fecal and swab samples were collected from diarrheic horses in Jeju during spring and summer 2025. Samples were screened using antigen testing and RT-PCR. One PCR-positive, antigen-test-positive sample was selected for whole-genome sequencing. All 11 segments were amplified using segment-specific primers and sequenced by the Sanger method. The Jeju isolate exhibited a G14-P[12]-I2-R2-C2-M3-A10-N2-T3-E2-H7 genome constellation, matching the globally prevalent ERVA genotypes. Most segments showed > 99% identity to a South African strain (SA1), while the VP4 segment showed higher similarity to a Japanese BI strain, suggesting a reassortment event. Phylogenetic analysis grouped the Jeju strain with isolates from South Africa and Ireland, but distinct from recent Japanese strains, indicating independent transmission patterns. This is the first full-genome report of ERVA from Korea. The findings confirm the presence of globally related ERVA in Korean horses and suggest complex, international transmission dynamics. Continuous molecular surveillance is essential to support effective prevention and vaccine strategies.
Microplastics (MPs) have established complex bidirectional interactions with bacteria, encompassing both mutualism and antagonism. This review advances a unified 'Stress-Habitat-Degradation' triangular model that systematically integrates three interconnected dimensions: (1) MPs-induced biotoxic stress on bacterial communities in water, soil, guts and plant tissues; (2) the plastisphere as a colonisation substrate that enriches pathogens and facilitates ARG spread; and (3) enzymatic biodegradation by functional taxa like Pseudomonas via specific enzymatic pathways. This framework explicitly links microbial community dynamics to functional outcomes, demonstrating that the same MPs-bacteria interplay simultaneously drives toxicity/pathogen enrichment and beneficial degradation. Environmental factors (temperature, oxygen, soil organic matter) profoundly shape these interactions by regulating gene expression and community succession. Crucially, we identify and resolve apparent contradictions-such as differential Gram-positive/Gram-negative responses and conflicting diversity trends-by attributing them to variations in polymer type, particle size, concentration, exposure time, host species and test conditions. Overall, this synthesis provides a critical integration of MPs-bacterial interactions and proposes a novel pollution control strategy centred on these interactions, redefining environmental risk assessment and bioremediation approaches.