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Citrobacter koseri is a significant bacterial cause of community-acquired urinary tract infections in female college students. Given limited previous attention to genomic analysis and molecular epidemiology of this species, whole-genome sequencing was carried out for eight uropathogenic C. koseri clinical isolates. Six complete and two draft assemblies are presented. Genome organization was largely conserved between isolates, and comparative analysis with archived genomes suggests that more than 90% of C. koseri genes are conserved across the species. These isolates contained relatively few mobile genetic elements (plasmids, prophage, transposons and insertion elements) and extensive antiphage defence systems. Other than a single conserved chromosomal β-lactamase gene, little or no acquired antibiotic resistance was observed. Clues to urovirulence were sought among genes conserved in C. koseri but not found in other Citrobacter genomes, suggesting roles for iron acquisition, motility and adhesion.

A self-driving metabolomics laboratory has long been envisioned but remains largely unrealized due to the complexity of analytical method design. As an initial step toward this goal, we developed BAGO, a self-optimizing framework for automated liquid chromatography (LC) gradient design in mass spectrometry-based untargeted metabolomics. BAGO aims to enhance global metabolite detection by improving the separation of all compounds, regardless of whether their identities are known or unknown. It operates through a data-driven Bayesian optimization process that iteratively learns from acquired MS data to propose improved gradients. To support this, we propose a global separation index that quantifies coelution among both annotated and unannotated features, enabling robust and structure-agnostic optimization across diverse sample types. Benchmarking across four metabolomics assays involving diverse sample matrices, column chemistries, and gradient durations, BAGO achieved substantial improvements within only 10 optimization iterations by balancing exploration and exploitation. The optimized gradients led to increased numbers of Gaussian-shaped peaks, higher MS/MS acquisition rates, and more annotated metabolites using both identity and analog search approaches. We further applied BAGO to a sex-differentiated metabolomics study of Drosophila abdominal carcasses, completing the workflow in parallel under both initial and optimized gradients. The optimized method resulted in a 41.9% increase in Gaussian-shaped peaks, a 36.8% increase in MS/MS-acquired peaks, and the identification of 18 additional biologically significant metabolites, including sex-associated compounds such as octopamine and pyroglutamic acid. BAGO (https://github.com/HuanLab/bago) is freely available as an open-source tool and represents a generalizable step toward fully automated, self-optimizing experimental workflows in untargeted metabolomics.

Trofinetide (TROF) became the first approved pharmacologic treatment for Rett syndrome (RTT) in the United States in March 2023; however, real-world evidence comparing TROF-treated and untreated individuals is limited. This study aimed to compare the baseline demographic and clinical profiles of those treated with TROF vs untreated in routine clinical practice. This retrospective cohort study used linked IQVIA Anonymized Patient Level Database medical claims and a specialty pharmacy database. Individuals with ≥1 medical claim for RTT between 01/01/2021 and 09/30/2024 (study period) were identified. Treated individuals had ≥1 TROF prescription during 04/01/2023 to 09/30/2023 (identification period), with first prescription set as index; untreated individuals had no TROF prescription. A risk-set sampling approach was used to assign proxy index dates to untreated individuals to improve comparability and reduce immortal time bias. Individuals with cerebrovascular disease or brain trauma before RTT diagnosis and those without 12 months pre-and post-index enrollment were excluded. Baseline characteristics were assessed during the 12 months pre-index. Of 8047 individuals with RTT identified, 2950 met eligibility criteria; 766 (26.0%) were treated with TROF and 2184 (74.0%) remained untreated. Treated individuals were younger at index (15.4 vs 23.5 years), and a greater proportion were pediatric (≤17 years; 66.6% vs 38.3%). Females predominated in both groups, while males represented a smaller proportion of the treated (4.6% vs 10.8%). Treated individuals more frequently had documented nonspecific developmental delay (31.3% vs 21.6%), autism spectrum disorder (19.1% vs 15.7%), and core RTT-related neurodevelopmental features such as loss of acquired communication skills (23.8% vs 12.9%) and loss of acquired motor skills (11.1% vs 4.9%). Child neurology was the most common prescriber specialty in both groups and was more frequent among treated individuals (50.3% vs 26.8%). Overall comorbidity burden was broadly similar between groups. In this real-world analysis, only one-quarter of eligible individuals with RTT initiated TROF during the early post-approval period. TROF uptake appeared concentrated in younger, specialist-managed individuals with more clearly documented RTT-related features, while three-quarters remained untreated. These findings highlight the need to better understand treatment pathways and barriers to initiation in males and adults in routine RTT care.

Diabetic wounds are often infected with microbes, which perpetuate inflammation, and stall wound healing. The bacterium Group B Streptococcus (GBS) is frequently isolated from diabetic wounds; however, little is known about how GBS adapts to survive in this niche. Previously, we found that GBS acquires stable mutations in the major two-component system CovRS during murine diabetic wound infection that result in increased pigmentation. Here, we further characterize these pigmented variants and determine the consequences on GBS survival. Using a murine model of wound infection, we find that covRS mutants arise specifically in diabetic hosts and are selected for across multiple GBS backgrounds. Whole genome sequencing of pigmented isolates revealed mutations in both covR and covS, with most isolates having a single nucleotide insertion or deletion in the covR promoter region. Phenotypic analysis of murine-acquired mutants reveals enhanced traits associated with virulence, including increased hemolytic activity, host cell cytotoxicity, and elevated nuclease activity. While our previous and current study indicated that engineered covR deletion mutants do not exhibit increased survival in the diabetic wound, we observe that a pigmented isolate survived better than wild-type during co-infection with Enterococcus faecalis, another frequently isolated wound pathogen. Finally, we find that depletion of neutrophils reduces the frequency of covRS mutant variants that arise in the population. Our work highlights the emergence of covRS mutations in GBS, and the consequences of these variations are associated with enhanced virulence and competitive fitness, underscoring the importance of these regulatory changes in the context of diabetic wounds.

Cold agglutinin disease is a rare autoimmune hemolytic anemia, a low-grade lymphoproliferative disease. Our objective was to determine the occurrence of cold agglutinin disease among patients with autoimmune hemolytic anemia and to map its specific characteristics, with a particular focus on thromboembolic complications. In a Hungarian hematology center, we retrospectively studied clinical data, laboratory parameters, and therapy of 84 patients with autoimmune hemolytic anemia. A total of 17% of patients had cold autoimmune hemolytic anemia, with 8 patients fulfilling the criteria for cold agglutinin disease and 7 patients having cold agglutinin syndrome. Most patients were older than 70 years, and the disease was more common in women (49 women, 35 men). Here, 71% of patients with CAD were administered rituximab, while some received additional chemotherapy. The 10-year survival rate was significantly worse in cold-type hemolytic anemia than in warm-type autoimmune hemolytic anemia (66.7% vs. 82.4%). Congenital and acquired causes of thrombophilia were examined in patients with severe hemolysis (hemoglobin <60 g/L, LDH >1.5&#xd7; the upper limit of normal) and in cases with thromboembolic complications. This is the first case series from a country in Central Eastern Europe with a four-season climate, demonstrating the occurrence of cold autoimmune hemolytic anemia. Overall survival was influenced by age, type of hemolytic anemia, and total bilirubin level during presentation. Inherited and acquired thrombophilia risk factors and antiphospholipid antibodies were detected in more patients with cold autoimmune hemolytic anemia than those with warm autoimmune hemolytic anemia.

Pressure injuries contribute substantially to patient morbidity and healthcare costs. However, comprehensive analyses of their burden within the U.S. paediatric population are limited. As a cross-sectional database, the National Inpatient Sample permits estimation of hospitalization-based prevalence rather than true prevalence. We hypothesized that pressure injury burden would increase over time with significant sociodemographic variations. This cross-sectional study used the National Inpatient Sample (2010-2019) to analyse temporal trends in the hospitalization-based prevalence, length of stay, and total inpatient costs for paediatric patients (1-17 years) with a diagnosis of pressure injury. Trends were analysed using Joinpoint regression, and differences across sociodemographic subgroups were examined. Among 2640,461 weighted paediatric admissions, 32,905 cases involved a pressure injury diagnosis. The annual prevalence increased significantly from 0.20% in 2010 to 0.31% in 2019 (annual percentage change = 6.1%; 95% confidence interval 4.6%-7.7%). Mean length of stay significantly increased from 16.42 to 19.25 days (average annual percentage change = 1.54%, 95% confidence interval 0.03%-3.07%). Mean total hospitalization costs (inflation-adjusted to 2019 U.S. dollars) for patients with pressure injury diagnoses rose substantially from $137,609 to $309,776. Variations were observed across sociodemographic groups. The increasing prevalence, length of stay, and total hospitalization costs among hospitalized U.S. paediatric patients aged 1-17 years with pressure injury diagnoses highlight a growing clinical and economic challenge. The observed differences across age, race, and socioeconomic groups warrant further investigation to inform future surveillance and research. Because the National Inpatient Sample does not distinguish hospital-acquired from community-acquired pressure injuries and does not isolate pressure injury-attributable costs from total hospitalization costs, causal inferences and direct policy recommendations require caution.

This article presents a multispectral imaging dataset dedicated to training a machine learning algorithm for the in situ detection of Huanglongbing (HLB). HLB, also known as citrus greening disease, is a major pathology caused by the bacterial pathogen Candidatus Liberibacter asiaticus, particularly in species of the citrus genus. The dataset is constituted of terrestrial images acquired in a commercial sweet orange orchard of the variety Pera Rio (Citrus sinensis (L.) Osbeck). The images describe large portions of canopy, with healthy leaves and sections infected by HLB as well as some confounding factors naturally present in orchards. Multispectral images were acquired with a multi-lens camera within the visible-near-infrared domain, resulting in 14 narrow spectral bands. The image acquisition was conducted during two field campaigns in 2023 and 2024. In total, the dataset contains 2,978 images divided into two classes HLB (1,681) and non-HLB (1,297). Originally, data are stored in TIFF format as 14 monochromatic images, organised by spectra band. Additionally, an HDF5-format version is provided, where images are stored as 3D arrays with spectral bands in ascending order. This format is compatible with various programming languages, enables efficient data handling, and is optimised for machine learning and image processing applications, supporting reproducible and portable analysis. This dataset is a valuable resource for the development and benchmarking of classification models, including deep learning approaches, aimed at the detection of HLB. Phytopathology imaging datasets are scarce yet essential for advancing digital agriculture and the development of robust tools for crop disease detection worldwide.

Lysine cyclodeaminase (LCD) catalyzes the conversion of l-lysine into l-pipecolic acid, a key building block for food additives and pharmaceutical intermediates. Despite its industrial relevance, LCD displays a narrow substrate scope, efficiently converting l-lysine, while bulkier derivatives such as l-lysine ethyl ester fail to undergo productive biotransformation. To elucidate the molecular origin of this selectivity and define the catalytic mechanism, we combined molecular docking, substrate tunnel engineering, classical molecular dynamics, well-tempered metadynamics simulations, and experimental validation. Computational analyses show that both l-lysine and l-lysine ethyl ester can access and bind within the LCD active site, and tunnel engineering produced LCD variants (I61V-I94V-D236C and I61V-I94V-E264T) with improved tunnel properties. However, experimental assays demonstrated that these variants did not acquire catalytic activity toward l-lysine ethyl ester. Mechanistic simulations reveal that the proposed l-lysine iminium intermediate consistently adopts low-energy, cyclization-competent conformations in which the nucleophilic N&#x3b5; and reactive C&#x3b1; atoms achieve near-attack geometries. In contrast, the proposed l-lysine ethyl ester iminium intermediate populates higher-energy states with misaligned geometries and kinetically trapped conformations, suggesting difficult cyclization despite successful binding. These findings suggest that steric and dynamic constraints&#xe5f8;rather than substrate access&#xe5f8;could impact the catalysis of esterified substrates. This work establishes a mechanistic framework linking enzyme dynamics, substrate recognition, and catalytic efficiency, providing a foundation for rational LCD engineering aimed at expanding substrate scope and guiding future industrial applications.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is mainly driven by activating&#xa0;KIT or PDGFRA mutations. Although tyrosine kinase inhibitors (TKIs) improve outcomes, primary and acquired resistance remain major challenges, especially in high-risk and wild-type GIST. Protein O-linked N-acetylgalactosamine (O-GalNAc) glycosylation regulates protein stability and signaling, but its role in GIST remains unclear. Bulk RNA-seq, proteomic, and single-cell RNA-seq data were integrated to identify O-glycosylation-related programs and key glycosyltransferases in GIST. Functional assays in GIST-T1 and GIST-882 cells, together with xenograft models, were performed to assess the effects of GalNAc-transferase 7 (GALNT7). GALNT7-KIT interaction, KIT O-GalNAcylation, and protein stability were examined by co-immunoprecipitation, VVA lectin blotting, confocal microscopy, and cycloheximide chase assays. Benzyl-&#x3b1;-GalNAc was evaluated as an O-glycosylation-targeting strategy&#xa0;in vitro and in vivo. O-glycosylation signatures were enriched in high-risk GIST and correlated with pathological risk. High O-glycosylation scores co-segregated with elevated copy-number variation in a fibroblast-like malignant cell population. GALNT7 was identified as a hub gene, upregulated in GIST, and associated with poor progression-free survival. GALNT7 promoted GIST cell growth, migration, and xenograft formation. Mechanistically, GALNT7 interacted with KIT, catalyzed its Tn-antigen O-GalNAcylation, increased KIT protein stability, and sustained PI3K/AKT and MAPK/ERK1/2 signaling. Benzyl-&#x3b1;-GalNAc reduced KIT O-GalNAcylation and stability, attenuated GALNT7-driven phenotypes, and inhibited xenograft growth. GALNT7-mediated O-GalNAc glycosylation stabilizes KIT and drives GIST progression. GALNT7 may serve as a prognostic biomarker and therapeutic target in GIST.

Ultraviolet (UV) imaging can reveal structural flaws, fluorescent markers, and characteristic signals generated by material changes that are difficult to detect in visible-light imaging and has been applied in numerous fields. However, in traditional UV imaging, it is challenging to simultaneously acquire reflection/transmission and UV-excited fluorescence imaging, often requiring additional optical filters to eliminate interference bands. Here, we demonstrate a dual-mode UV lensless imaging method based on diffuser speckle modulation, which enables direct reconstruction of both reflection/transmission and fluorescence images from a single-shot measurement. Compared with conventional methods, our scheme eliminates the need for optical lenses and filters, enabling an ultra-compact lensless system. This approach can be further integrated with other image post-processing operations or general computer vision tasks for the development of task-oriented intelligent UV cameras.

This work provides a multi-condition, long-duration acoustic dataset for ball bearings, covering five states: normal, cage fracture, inner race pitting, outer race pitting, and compound inner-outer race pitting. These data were acquired separately for each of the combinations of three rotational speeds (800, 1000, and 1200 r/min) and three load levels (0%, 15%, and 30% of the rated torque, where 100% corresponds to 6 Nm). Acoustic signals were synchronously recorded using two B&K 4966 and one CRY333 microphones, with a continuous 50-minute recording for each of the 45 operational conditions at a sampling rate of 32,768 Hz. The raw data are provided in the proprietary .bkc format, with a total duration of 2250 minutes. Files are organized in a hierarchical directory structure (speed-load-fault type) and accompanied by metadata tables. The dataset supports tasks such as feature extraction, pattern recognition, and can serve as a benchmark for developing and validating fault diagnosis algorithms for rotating machinery, particularly for evaluating model performance across varying operating conditions.

Early detection is an essential component in averting preventable higher-stage pressure injuries (PI). However, decades of clinical practice have not yielded the elimination of preventable hospital-acquired PIs, especially in patients with dark skin tones. Late detection of PIs in dark skin tones is a health equity issue. As an equity-informed initiative, an interprofessional team in a large hospital complex developed an enabler for practice to address overreliance on simple visual inspection for detecting early skin and tissue damage. The 4Ts practice enabler provides a nontechnological and practical approach for the early identification of stage 1 PIs in all skin tones by examining skin tone, temperature, texture, and twinge (pain). This equity-informed comprehensive approach will impact early detection of PI, thereby triggering expedited measures for effective prevention.

Remote teleophthalmological examinations can reduce access barriers for nursing home residents; however, it is unclear to what extent an actual ophthalmological aftercare can be realized. The acceptance of the model, aftercare participation rate and the reasons for not contacting a medical specialist when indicated were examined 6 months after a remote ophthalmological first examination during the TOVIS pilot study. Residents in two nursing homes who had participated in the TOVIS pilot study were surveyed in writing 6 months after the first examination. Data were acquired on 1) utilization of a recommended ophthalmological follow-up examination, 2) reasons for not participating in a recommended ophthalmological aftercare, 3) assessment of the remote examination using a Likert scale. Descriptive statistics, &#x3c7;2-tests and t&#x2011;tests were used for the analysis. Of the 86 originally examined residents, 64 (participation rate 74%, mean age 82.6&#x202f;&#xb1;&#x2009;8.8&#xa0;years, 60.9&#x202f;% female) participated in the follow-up survey. The remote ophthalmological examination was broadly accepted, 83.6% assessed it as meaningful (&#x2265;&#x202f;8 on the 10-point Likert scale), 82.5% would participate again and 76.9% would recommend the offer to others. Although 52 residents received the recommendation of an ophthalmological follow-up examination, after 6 months only 14/52 (26.9%) followed this recommendation. Findings that required treatment were in particular vision-relevant cataract (50%), glaucoma (21%) and subretinal or intraretinal fluid (7%), which were predominantly (68.8%) previously unknown to those affected. The major reasons for the 38 residents who did not participate in the aftercare were no complaints (31.6%), no desire for treatment (23.7%) and problems with transport or accompanying persons (10.5%). The remote ophthalmological model study showed a high acceptance among the participants but there was a clear discrepancy between the express recommendation and the actually realized consultation with a medical specialist. Neither the presence of potentially vision-threatening findings nor the urgency of the recommendation significantly increased the compliance for aftercare. Therefore, for the realization of the full benefit of teleophthalmological programs for residents of nursing homes for the aged, supplementary measures are necessary, such as patient-centered clarification, structured appointment management and logistic support for the continuation with a visit to the practice. HINTERGRUND: Teleophthalmologische Untersuchungen k&#xf6;nnen Zugangsbarrieren f&#xfc;r Pflegeheimbewohner verringern, jedoch ist unklar, in welchem Ma&#xdf;e sich daraus eine tats&#xe4;chliche augen&#xe4;rztliche Nachsorge ableiten l&#xe4;sst. Sechs Monate nach einer teleophthalmologischen Erstuntersuchung im Rahmen der TOVIS-Pilotstudie werden Akzeptanz des Modells, Nachsorgeteilnahmequote und Gr&#xfc;nde f&#xfc;r ausbleibende Facharztkontakte untersucht. Bewohner zweier Pflegeheime, die an der TOVIS-Pilotstudie teilgenommen hatten, wurden 6&#xa0;Monate nach der Erstuntersuchung schriftlich befragt. Erhoben wurden (1)&#xa0;Inanspruchnahme einer empfohlenen augen&#xe4;rztlichen Nachsorge, (2)&#xa0;Gr&#xfc;nde f&#xfc;r eine Nichtteilnahme einer empfohlenen augen&#xe4;rztlichen Nachsorge, (3)&#xa0;Bewertung der Teleuntersuchung mittels Likert-Skala. Deskriptive Statistiken, Chi2-Tests und t&#x2011;Tests wurden zur Analyse genutzt. Von den urspr&#xfc;nglich 86&#xa0;untersuchten Bewohner:innen nahmen 64 (Teilnahmequote 74&#x202f;%; mittleres Alter 82,6&#x202f;&#xb1;&#x2009;8,8&#xa0;Jahre; 60,9&#x202f;% weiblich) an der Nachbefragung teil. Die teleophthalmologische Untersuchung stie&#xdf; auf breite Zustimmung: 83,6&#x202f;% bewerteten sie als sinnvoll (&#x2265;&#x202f;8 auf der 10-Punkte-Likert-Skala), 82,5&#x202f;% w&#xfc;rden erneut teilnehmen und 76,9&#x202f;% das Angebot weiterempfehlen. Obwohl 52&#xa0;Bewohner:innen die Empfehlung einer augen&#xe4;rztlichen Nachsorge erhielten, folgten innerhalb von 6&#xa0;Monaten lediglich 14/52 (26,9&#x202f;%) dieser Empfehlung. Behandlungsbed&#xfc;rftige Befunde waren v.&#xa0;a. visusrelevante Katarakt (50&#x202f;%), Glaukom (21&#x202f;%) und sub- bzw. intraretinale Fl&#xfc;ssigkeit (7&#x202f;%), die den Betroffenen zuvor &#xfc;berwiegend (68,8&#x202f;%) nicht bekannt gewesen waren. Hauptgr&#xfc;nde bei den 38&#xa0;Bewohner:innen, die nicht an der Nachsorge teilnahmen, waren fehlende Beschwerden (31,6&#x202f;%), fehlender Behandlungswunsch (23,7&#x202f;%) und Transport- oder Begleitpersonprobleme (10,5&#x202f;%). Die teleophthalmologische Modellstudie zeigt unter den Teilnehmer:innen eine hohe Akzeptanz, jedoch f&#xe4;llt eine deutliche Diskrepanz zwischen ausdr&#xfc;cklicher Empfehlung und tats&#xe4;chlich erfolgter Facharztkonsultation auf. Weder das Vorliegen potenziell visusbedrohlicher Befunde noch die Dringlichkeit der Empfehlung erh&#xf6;hte die Nachsorge-Compliance signifikant. Zur Realisierung des vollen Nutzens teleophthalmologischer Programme bei Bewohner:innen von Seniorenheimen sind daher erg&#xe4;nzende Ma&#xdf;nahmen erforderlich, etwa patientenzentrierte Aufkl&#xe4;rung, strukturiertes Terminmanagement und logistische Unterst&#xfc;tzung f&#xfc;r den weiterf&#xfc;hrenden Praxisbesuch.

Large language models (LLMs) are increasingly deployed as autonomous agents that make choices and use tools on behalf of users. Yet, we have limited evidence about how their decisions are shaped by their environment. We adapt a human decision-making task to test leading LLMs under four forms of choice architecture: defaults, suggestions, information highlighting, and "optimal" nudges derived from a resource-rational model of human choice. We treat human behavior as a baseline for predictable sensitivity to such interventions. Across models and prompting strategies, LLMs often depart substantially from this baseline. They sometimes pay excessive costs to acquire information, sometimes ignore available information, and, most crucially, are far more responsive to nudges than humans, such that weak cues that slightly shift human behavior have larger effects on model choices, toward both better and worse payoff outcomes. Chain-of-thought prompting and in-context human data do not reliably stabilize behavior. Recent reasoning-optimized LLMs can, in some configurations, restore more human-level sensitivity to nudges, but do so inconsistently and at substantial computational cost. These results point to an important and largely neglected safety concern: LLM agents can be behaviorally brittle under subtle changes in choice architecture, even in the absence of adversarial settings.