Citations

Wastewater treatment is evolving rapidly with the advent of advanced deep-learning AI, graph-based, and physics-informed approaches. This study integrates graph neural networks, physics-informed neural networks, and multi-agent reinforcement learning within a hybrid digital-twin framework, evaluated on multi-scale real-world datasets. The developed models achieved over 90% dissolved organic carbon removal and reduced aeration energy by up to 22% while maintaining process stability. The results demonstrate that graph–physics synergies not only boost operational efficiency but also reveal critical trade-offs between energy savings and hydraulic performance. Our findings establish a new benchmark for resilient, low-carbon wastewater treatment, highlighting the transformative role of data-driven system design.

Clean water security demands autonomous systems that sense, reason, and act at scale. We introduce AquaSurveil, a unified multi-agent platform coupling mobile robots, fixed IoT nodes, and privacy-preserving machine learning for continent-scale water health surveillance. The architecture blends Gaussian-process mapping with distributed particle filtering, multi-agent deep-reinforcement Voronoi coverage, GAN/LSTM anomaly detection, and sheaf-theoretic data fusion; components are tuned by Bayesian optimization and governed by Age-of-Information-aware power control. Evaluated on a 2.82-million-record dataset (1940–2023; five countries), AquaSurveil achieves up to 96% spatial-coverage efficiency, an ROC-AUC of 0.96 for anomaly detection, ≈95% state-estimation accuracy, and reduced energy consumption versus randomized patrols. These results demonstrate scalable, robust, and energy-aware water quality surveillance that unifies robotics, the IoT, and modern AI.

Abstract Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL who were treated with the B-cell maturation antigen–directed chimeric antigen receptor T-cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients; 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression-free survival (mPFS) was 9.0 months (95% confidence interval [CI], 4-15) and the median overall survival (mOS) was 13.0 months (95% CI, 8 to not estimable [NE]). The 1-year cumulative incidence of progression or death was 72%, and the 1-year cumulative incidence of death was 47%. Patients who received cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months [NE] vs 9.0 months) when compared with those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI, 17.4-68.5) with cilta-cel, whereas all patients treated with ide-cel progressed or died within 12 months of infusion. The rates of hematologic and nonhematologic toxicities were similar between patients treated with cilta-cel and those treated with ide-cel and were consistent with those reported in patients with MM. In this first multicenter study that evaluated patients with PCL who were treated with standard-of-care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes when compared with historic standards.

Abstract Objective: We investigated differences in cognition between variants of progressive supranuclear palsy (PSP) including PSP-Richardson (PSP-RS) and subcortical and cortical variants using updated diagnostic criteria and comprehensive neuropsychological assessment. Method: We recruited 140 participants with PSP (age = 71.3 ± 6.9 years; education = 15.0 ± 2.8 years; 49.3% female) who completed neurological and neuropsychological assessment. Participants received diagnoses of PSP clinical variants at their evaluation (or retrospectively if evaluated before 2017) according to the Movement Disorder Society PSP criteria. We grouped variants as PSP-RS (62 participants), PSP-Cortical (25 with PSP-speech/language and 9 with PSP-corticobasal syndrome), and PSP-Subcortical (27 with PSP-parkinsonism, 11 with PSP-progressive gait freezing, and 6 with PSP-postural instability). Analysis of covariance adjusted for age assessed for differences in neuropsychological performance between variants across cognitive domains. Results: PSP-Cortical participants performed worst on measures of visual attention/working memory (Spatial Span Forward/Backward/Total), executive function (Frontal Assessment Battery), and language (Letter Fluency). PSP-RS participants performed worst on verbal memory (Camden Words). There were no significant group differences for the MoCA or indices of visuospatial function. There were no sex or education differences between PSP groups; however, there were differences in age at visit and disease duration. Conclusions: In a large sample of participants with PSP, there were differences in cognition across PSP-RS, PSP-Subcortical, and PSP-Cortical variants, with PSP-Cortical and, to a lesser extent, PSP-RS, performing worse on tests of attention and executive function. These findings suggest cognitive distinctions among PSP clinical variants and highlight the value of neuropsychological assessment in differential diagnosis of PSP subtypes for more accurate and timely clinical classification.

Abstract INTRODUCTION We investigated associations of plasma proteins with blood‐based amyloid/tau/neurodegeneration/inflammation (A/T/N/I) biomarkers for Alzheimer's disease (AD). METHODS Plasma proteomics and clinical data from the Indiana AD Research Center ( N = 498) were used. Association analysis of plasma proteins with blood A/T/N/I biomarkers as well as diagnosis was performed, followed by replication in an independent cohort ( N = 323), network analysis, pathway enrichment, and machine learning classification to identify proteins and pathways related to AD risk. RESULTS We identified 35 proteins associated with AD, 20 of which were replicated in the independent cohort. We identified 150, 448, and 219 proteins associated with T/N/I biomarkers, respectively, revealing biomarker‐specific pathways. Network analysis identified two modules associated with T/N/I biomarkers, preserved in cerebrospinal fluid (CSF), and their enriched pathways. The classification model of proteins effectively differentiated AD (area under the curve [AUC] = 0.930). CONCLUSION Our findings suggest dysregulated plasma proteins and pathways in AD, enhancing our understanding of molecular mechanisms and diagnostic strategies for AD. Highlights Plasma proteins were identified as being associated with Alzheimer's disease (AD) and plasma biomarkers. The identified proteins were replicated in both plasma and cerebrospinal fluid (CSF) proteomics. The identified proteins were associated with AD biomarker‐specific pathways. The identified proteins improved the performance of the AD classification. Protein network analysis identified network modules and their enriched pathways.

Abstract The link between regional tau load and clinical manifestation of Alzheimer’s disease (AD) highlights the importance of characterizing spatial tau distribution across disease variants. In typical (memory-predominant) AD, the spatial progression of tau pathology mirrors the functional connections from temporal lobe epicentres. However, given the limited spatial heterogeneity of tau in typical AD, atypical (non-amnestic-predominant) AD variants with distinct tau patterns provide a key opportunity to investigate the universality of connectivity as a scaffold for tau progression. In this large-scale, multicentre study across 14 international sites, we included cross-sectional tau-PET data from 320 individuals with atypical AD (n = 139 posterior cortical atrophy/PCA-AD; n = 103 logopenic variant primary progressive aphasia/lvPPA-AD; n = 35 behavioural variant AD/bvAD; n = 43 corticobasal syndrome/CBS-AD), with a subset of individuals (n = 78) having longitudinal tau-PET data. Additionally, as an independent sample, we included regional post-mortem tau stainings from 93 atypical AD patients from two sites (n = 19 PCA-AD, n = 32 lvPPA-AD, n = 23 bvAD, n = 19 CBS-AD). Gaussian mixture modelling was used to harmonize different tau-PET tracers by transforming tau-PET standardized uptake value ratios to tau positivity probabilities (a uniform scale ranging from 0% to 100%). Using linear regression, we assessed whether brain regions with stronger resting-state functional MRI-based functional connectivity, derived from healthy elderly controls in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showed greater covariance in cross-sectional and longitudinal tau-PET and post-mortem tau pathology. Furthermore, we examined whether functional connectivity of tau-PET epicentres (i.e. the top 5% of regions with the highest baseline tau load) and tau-PET accumulation epicentres (i.e. the top 5% of regions with the highest tau accumulation rates) was associated with cross-sectional and longitudinal tau patterns. Our findings show that tau-PET epicentres aligned with clinical variants, e.g. a visual network predominant pattern in PCA-AD (‘visual AD’) and left-hemispheric temporal predominance, particularly within the language network, in lvPPA-AD (‘language AD’). Moreover, more strongly functionally connected regions showed correlated concurrent tau-PET levels (confirmed with post-mortem data) and tau-PET accumulation rates. The functional connectivity profile of tau-PET epicentres and accumulation epicentres corresponded to tau-PET progression patterns, with higher tau-PET levels and accumulation rates in functionally close regions, and lower tau-PET levels and accumulation rates in functionally distant regions. Our data are consistent with the hypothesis that tau propagation occurs along functional connections originating from local epicentres, across all AD clinical variants. Since tau proteinopathy is a major driver of neurodegeneration and cognitive decline, this finding may advance personalized medicine and participant-specific end points in clinical trials.

BACKGROUND Approximately 10% of patients report penicillin allergy. Based on historical guidelines, patients with a penicillin allergy should receive an alternative to cephalexin for prophylaxis in dermatologic surgery. OBJECTIVE To determine, based on evidence, if cephalexin should be used as a first-line prophylactic antibiotic in dermatologic surgery for patients with penicillin allergy. METHODS Systematic review of the literature was performed with defined search terms. RESULTS Less than 5% of those with penicillin allergy labels have a true penicillin allergy. For patients with true, persistent penicillin allergy, there is an overall low cross-reactivity with cephalosporins, especially with cephalosporins that do not share identical R1 side chain. The first-generation cephalosporins, including cephalexin, have a slightly higher risk of cross-reactivity in patients with reported allergy to amino-penicillins (amoxicillin, ampicillin) but not other penicillins. The risk of severe cross-reactivity of cephalosporins in patients with low-risk penicillin allergies is extremely low. Cephalexin has a superior side effect profile and efficacy compared to alternatives. CONCLUSION Cephalexin should be used as the first-line prophylactic antibiotic in dermatologic surgery for patients with documented penicillin allergy, including anaphylaxis. There may be a higher risk of cross-reactivity with cephalexin in patients with a confirmed amino-penicillin allergy.

Abstract Objective Novel subcutaneous electroencephalography (sqEEG) systems enable prolonged, near‐continuous cerebral monitoring in real‐world conditions. Nevertheless, the feasibility, acceptability and overall clinical utility of these systems remain unclear. We report on the longest observational study using ultra‐long‐term sqEEG to date. Methods We conducted a 15‐month prospective, observational study including 10 adult people with treatment‐resistant epilepsy. After device implantation, patients were asked to record sqEEG, to use an electronic seizure diary, and to complete acceptability and usability questionnaires. sqEEG seizures were annotated visually, aided by automated detection. Individualized temporal patterns of seizure occurrence were assessed via circadian circular statistics and via Fano factor analysis. Results Over a median duration of 438 days, 10 patients recorded a median 18.8 h/day, totaling 71 984 h of real‐world sqEEG data. Adherence and acceptability remained high throughout the study. Although 754 sqEEG seizures were recorded across patients, more than half (52%) of these were not reported in the patient diary. Of the 140 (27%) diary reports not associated with an identifiable sqEEG seizure, the majority (68%) were reported as seizures with preserved awareness. The sqEEG to diary F1 agreement score was highly variable, ranging from .06 to .97. Patient‐specific patterns of circadian seizure occurrence and seizure clustering were found, including several relevant discrepancies between sqEEG and diary. Significance We demonstrate feasibility and high acceptability of ultra‐long‐term (months–years) sqEEG monitoring. These systems help provide real‐world, more objective seizure counting compared to patient diaries. It is possible to objectively monitor individual temporal fluctuations of seizure occurrence.

Background: Injuries of the medial ulnar collateral ligament (MUCL) among baseball pitchers are increasing. Surgical treatment is evolving to optimize outcomes. Purpose/Hypothesis: This study’s purpose was to highlight trends in MUCL repair and reconstruction in professional pitchers, describe outcomes such as return to any level of play (RTP), and identify factors impacting these outcomes. It was hypothesized that primary and revision MUCL surgery is increasing, with revision surgery requiring greater RTP time. Study Design: Case series; Level of evidence, 4. Methods: The Major League Baseball (MLB) Health and Injury Tracking System database was used to procure data during the study period (2010-2023). All professional pitchers who underwent MUCL surgery during this period were included. RTP was defined as a pitcher returning to at least 1 professional game after index surgery. Return to the same level of play (RTSL) was defined as return to at least 1 game in the same league of play as before surgery. Because of the coronavirus pandemic, the year 2020 was considered an outlier and omitted from time-trend analysis. Results: A total of 2281 pitchers who underwent MUCL surgery during the study period were included for analysis. The number of MUCL surgeries for pitchers increased yearly ( R 2 = 0.821; P < .001), as did the number of reconstructions with internal brace augmentation ( R 2 = 0.896; P < .001). The RTP rate for MLB pitchers was significantly higher than the RTSL rate (93% vs 71%; P < .001). This difference was not observed in Minor League Baseball (MiLB) pitchers (RTP 76% vs RTSL 74%; P = .142). RTP rates after revision surgery were lower than those after primary surgery (71% vs 80%; P = .020). The mean time to RTP was shorter (470 ± 135 days) than the mean time to RTSL (499 ± 153 days; P < .001). Conclusion: The incidence of MUCL surgery and revision surgery is increasing among professional pitchers. Overall, 79% of pitchers returned to any level of play at a mean of 470 days, while 74% returned to the same level of play at a mean of 499 days, but this varied based on level of play. This study will guide athlete expectations and surgeon decision-making.