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The National Cancer Institute (NCI) supports numerous research consortia that rely on imaging technologies to study cancerous tissues. To foster collaboration and innovation in this field, the Image Analysis Working Group (IAWG) was created in 2019. As multiplexed imaging techniques grow in scale and complexity, more advanced computational methods are required beyond traditional approaches like segmentation and pixel intensity quantification. In 2022, the IAWG held a virtual hackathon focused on addressing challenges in analyzing complex, high-dimensional datasets from fixed cancer tissues. The hackathon addressed key challenges in three areas: (1) cell type classification and assessment, (2) spatial data visualization and translation, and (3) scaling image analysis for large, multi-terabyte datasets. Participants explored the limitations of current automated analysis tools, developed potential solutions, and made significant progress during the hackathon. Here we provide a summary of the efforts and resultant resources and highlight remaining challenges facing the research community as emerging technologies are integrated into diverse imaging modalities and data analysis platforms., (© 2025 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Pharmaceutical contaminants (PCs), including antibiotics, analgesics, and other medications, pose a growing threat to aquatic ecosystems and human health due to their persistence and bioaccumulation potential. Biochar, a carbonaceous material derived from biomass pyrolysis, has emerged as a sustainable adsorbent for removing PCs from wastewater. Biochar is reported to remove PCs from water with an average range of 58 to 91 %, depending on the nature of feedstock, pyrolysis conditions, and characteristics of the pharmaceuticals. Biochar's effectiveness is attributed to its unique properties, including high porosity, large surface area and diverse functional groups, which enable the adsorption of various pharmaceutical compounds through physical and chemical interactions. Common PCs such as tetracycline, ciprofloxacin, ibuprofen, paracetamol, sulfamethoxazole, and cephalexin can be effectively removed using biochar. The adsorption process involves different mechanisms such as Van der Waals forces, electrostatic interactions, hydrogen bonding, and surface complexation. This review summarizes the current state of knowledge on biochar-based adsorption mechanisms, highlights successful applications in wastewater treatment, and identifies areas for future research. While promising, a deeper understanding of adsorption mechanisms, optimization of biochar production, and the development of effective regeneration methods are crucial for maximizing biochar's efficacy and ensuring its sustainable implementation in wastewater treatment systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Introduction: Data about impact of switch to dolutegravir (DTG)-based antiretroviral therapy (ART) on estimated glomerular filtration rate (eGFR) in Asians are scarce. RV254/SEARCH010 is a prospective observational cohort in Bangkok, Thailand with ART initiation during acute HIV infection (AHI) where participants switched to DTG-based ART., Methods: Participants started Efavirenz (EFV)-based ART during AHI (n = 214) and switched to DTG-based ART after a median of 97 weeks (IQR 61-145). GFR was estimated by serum creatinine (eGFR cre ) every 24 weeks before and after switch. Estimated GFR by cystatin C (eGFR cystC ) was ordered at clinician's discretion for decreased eGFR cre after switch. Random-effect linear regression model was used to assess changes in eGFR cre over 96 weeks from starting ART, and from switching to DTG., Results: At study entry, 20 participants (9.3%) had eGFR cre  < 90 ml/min/1.73 m 2 . During EFV-based ART, an additional 17 (8%) developed eGFR cre  < 90 ml/min/1.73 m 2 , nearly all transient, while mean eGFR cre remained stable and within normal range. At switch to DTG, 21 (9.8%) had eGFR cre  < 90 ml/min/1.73 m 2 but an additional 116 (54%) developed eGFR cre  < 90 ml/min/1.73 m 2 during follow-up with eGFR cre decrease being mostly persistent. Mean eGFR cre decreased 20.8% from 117.0 to 92.4 ml/min/1.73 m 2 (p < 0.001). Among 20 post-switch participants with eGFR cystC measured within 4 weeks of eGFR cre  < 90 mL/min/1.73 m 2 , 13 (65%) had normal kidney function by eGFR cystC ., Conclusions: Persistent eGFR cre decrease to < 90 ml/min/1.73 m 2 after switch to DTG was common in this Thai population. eGFR cystC was helpful to identify individuals with clinically significant decrease in kidney function and obviate unnecessary ART modifications. Trial registration Clinical Trials Registry Number: ClininicalTrials.gov NCT00796146., Competing Interests: Declarations. Ethics approval and consent to participate: All participants signed written informed consent and participated in protocols approved by Thai (Chulalongkorn University, Faculty of Medicine, OHRP IRB00001607) and US (Walter Reed Army Institute of Research, OHRP IRB00000794) Institute Review Boards. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell lymphoma characterized by malignant proliferation of T cells with epidermotropism in the skin. MF has an indolent course, presents as erythematous scaly patches or plaques, and may progress to generalized erythroderma, cutaneous tumors, or extracutaneous invasion. MF is often misdiagnosed at early stages due to nonspecific clinical findings. Patients with MF are at high risk for developing secondary malignancies, including hematological malignancies. We hereby report a case of MF misdiagnosed and associated with underlying diffuse large B-cell lymphoma., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Human papillomavirus (HPV) vaccines provide excellent protection from infection and disease. The minimum number of doses needed for long-term protection and the potential need for boosters are areas of continuing interest. Studies on the durability of vaccines have focused on antibodies, fewer have analyzed memory immune cells that could provide protection even when antibody levels are low. In this study, subjects who had participated in one of two trials comparing two and three doses (2D, 3D), were given an additional vaccine dose (Gardasil®9, 9vHPV) several years after the initial vaccine doses, and the magnitude of immune responses were compared. Both trials had 2D children who received doses at 0 and 6 months (G1a), 3D children 9-13 (08-001) or 9-14 (V503-010) years old at enrollment in the original trial (G2) and 3D women (age 16-26) (G3). Trial V503-010 had a second 2D group of children vaccinated at 0 and 12 months (G1b). Changes in numbers of HPV specific memory B cells (Bmem) (N = 6 per group, both studies) at 1 month and plasmablasts (PB) (08-001: N = 6 per group, V503-010: G1a N = 12, G1b N = 8, G2 N = 6, G3 N = 28) at 1 week, relative to baseline at the additional dose, were compared among groups. Changes in the geometric mean titers (GMTs) of HPV specific antibodies relative to baseline were compared (N = same as PB). Statistically significant (p < 0.05) increases in the numbers of PB, Bmem and antibody levels (GMT) were seen among subjects receiving an extra vaccine dose relative to baseline. Increases in the number of PB and Bmem were not significantly different among subjects receiving two or three doses. Thus, robust immune responses were observed and did not differ significantly among subjects vaccinated with two or three doses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Denise Galloway reports financial support was provided by Merck Sharp and Dohme Pharmaceuticals. Denise Galloway reports a relationship with Merck Sharp and Dohme Pharmaceuticals that includes: consulting or advisory and funding grants. Honoraria paid from Merck to Erin M. Scherer for lectures/seminars delivered, Manish Sadarangani has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer and Sanofi-Pasteur. All funds have been paid to his institute, and he has not received any personal payments. Sandhya Sankaranarayanan, Alain Luxembourg and are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Chlorpyrifos contamination is a currently on-going issue with significant environmental impacts. As such, rapid and effective techniques that remove chlorpyrifos from the environment are urgently required. Here, a strain of Pseudomonas nitroreducens W-7 exhibited exceptional degradation ability towards both chlorpyrifos and its major metabolite 3,5,6-trichloro-2-pyridinol (TCP). W-7 can effectively reduce the toxicity of chlorpyrifos and TCP towards a variety of sensitive organisms through its superior degradation capacity. W-7 demonstrated efficient soil bioremediation by removing over 50 % of chlorpyrifos (25 mg/kg) from both sterile and non-sterile soils within 5 days, with significantly reduced half-lives. Additionally, 16S rDNA high-throughput sequencing of the soil revealed that the introduction of W-7 had no significant impact on the soil microbial community. A pivotal hydrolase Oph2876 containing conserved motif (HxHxDH) and a bimetallic catalytic center was identified from W-7. Oph2876 was a heat- and alkali-resistant enzyme with low sequence similarity (< 44 %) with other reported organophosphorus hydrolases, with a better substrate affinity for hydrolysis of chlorpyrifos to TCP. The molecular docking and site-directed mutagenesis studies indicated that the amino acid residues Asp235, His214, and His282, which were associated with the conserved sequence "HxHxDH", were crucial for the activity of Oph2876. These findings contribute to a better understanding of the biodegradation mechanism of chlorpyrifos and present useful agents for the development of effective chlorpyrifos bioremediation strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Platysma prominence (PP) is a sign of aging in the lower face and neck characterized primarily by a blunting of the jawline and the presence of vertical banding along the anterior and posterior margins of the muscle on one or both sides of the neck. The aim of this review was to combine findings from the literature on topics relevant to PP with expert perspective to help guide clinical decision-making in assessment and treatment., Methods: A review of the literature focusing on platysma muscle anatomy and function; PP signs, characteristics, causes, clinical severity, and aesthetic and psychosocial effects; and treatment options for PP was performed and summarized. Expert clinical perspectives of these findings elucidated from the authors' experience were used to develop considerations for the evaluation and treatment of PP., Results: PP is an aesthetically undesirable condition that is bothersome to affected individuals and has negative effects on quality of life and psychological and emotional well-being. Knowledge of platysma muscle anatomy, proper patient assessment, and considerations in the use of onabotulinumtoxinA for the treatment of PP, including selection of the appropriate candidates and careful dosing and injection techniques, can produce consistent results with limited adverse events, potentially enhancing the patient's quality of life., Conclusions: PP is a bothersome condition with a detrimental impact on patient quality of life and psychological and emotional well-being. OnabotulinumtoxinA is a nonsurgical treatment option with a record of safe, consistent results in treating PP., Competing Interests: Dr. Bertossi is an investigator for Allergan Aesthetics, an AbbVie Company. Dr. Braz is a speaker, advisor, and investigator for Allergan Aesthetics, an AbbVie Company. Dr. Carruthers is a consultant and researcher for Alastin, Appiell, Allergan Aesthetics, an AbbVie Company, Avari, Bonti (Allergan Aesthetics/AbbVie), Evolus, Fount Bio, InMode, Inverse Genomic Ltd, Jeune Aesthetics, Merz, Revance Biopharma, and Object Pharma, is an author and an editor for Elsevier, an author for “Up to Date” on neuromodulators and fillers, an assistant editor for Dermatologic Surgery, and a reviewer for Aesthetic Surgery Journal, Ophthalmic Plastic and Reconstructive Surgery, and Plastic and Reconstructive Surgery. Dr. De Boulle is a key opinion leader and speaker for Allergan Aesthetics, an AbbVie Company, and has received grants and honoraria from AbbVie. Drs. Dimitrijevic, Shimoga, and Hopfinger are full-time employees of AbbVie. Dr. Trindade de Almeida is a speaker, consultant, and researcher for Allergan/AbbVie and Merz and a consultant for Galderma. The other author has no financial interest to declare in relation to the content of this article. Allergan Aesthetics, an AbbVie Company, funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis datasets), as well as other information (eg, protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan, and execution of a Data Sharing Agreement. Data requests can be submitted at any time after approval in the United States and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: https://vivli.org/ourmember/abbvie/ then select “Home.”, (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Mytella strigata, a potentially invasive species native to South America, is rapidly spreading across various aquatic ecosystems around the globe, posing a threat to native mussels. This study presents the first comprehensive de novo transcriptome assembly of M. strigata. We generated 254 million reads, which were processed and assembled using the Trinity assembler, resulting in 60362 transcripts with an N50 of 1,578 bp and over 93-98% completeness, as confirmed by BUSCO analysis with multiple ortho-datasets. A number of databases were used for functional annotation, including UniProt, KEGG, Reactome, InterPro, and eggNOG. Gene Ontology and pathway analyses identified transcripts associated with key biological processes, including those associated with cell signalling, metabolism, stress responses, cancer pathways, and immune regulation. This dataset enriches the bivalve database by advancing the understanding of the adaptive success and evolutionary resilience of this invasive species. The present study provides a fundamental framework for future research on the ecological and evolutionary impacts of this invasive species., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype. Expression of H3E50K is sufficient to transform human cells as evidenced by an increase in cell migration and invasion, and an increase in proliferation and clonogenicity. H3E50K also increases the invasive phenotype in the context of co-occurring BRAF mutations, which are present in patient tumors characterized by H3E50K. H3E50 lies on the globular domain surface in a region that contacts H4 within the nucleosome. We find that H3E50K selectively increases chromatin accessibility and perturbs proximal H3 post-translational modifications including H3K27me3; together these changes to chromatin dynamics dysregulate gene expression to support the epithelial-to-mesenchymal transition. Functional studies using Saccharomyces cerevisiae reveal that, while yeast cells that express H3E50K as the sole copy of histone H3 show sensitivity to cellular stressors, including caffeine, H3E50K cells display some genetic interactions that are distinct from the characterized H3K36M oncohistone yeast model. Taken together, these data suggest that additional H3 mutations have the potential to support oncogenic activity and function through distinct mechanisms that dysregulate gene expression., Competing Interests: None declared., (© The Author(s) 2025. Published by Oxford University Press on behalf of NAR Cancer.)

Background: Platysma prominence (PP) refers to the undesirable effects that may occur with platysma muscle contraction., Objective: Evaluate safety and efficacy of onabotulinumtoxinA for improving Moderate (Grade 3) to Severe (Grade 4) PP in adults., Methods: Participants were randomized 1:1 to receive a total dose of onabotulinumtoxinA 26, 31, or 36 U or placebo on Day 1 and monitored for 120 days. Dosage was administered via superficial intramuscular injections into the platysma muscle based on baseline PP severity., Results: At Day 14, 32.3% of onabotulinumtoxinA-treated participants in the intent-to-treat population versus 1.9% who received placebo achieved investigator- and participant-rated Grade 1 or 2 (Minimal or Mild) and ≥2-grade improvement from baseline in PP severity, while 56.9% and 51.7% achieved Grade 1 or 2 on investigator's and participant's assessments, respectively (all P < .0001). OnabotulinumtoxinA-treated participants reported higher satisfaction, less bother from jawline and vertical neck band appearance, and reduced psychosocial impact versus placebo (all P < .0001). Adverse event incidence was similar between onabotulinumtoxinA and placebo. No events of dysphagia or muscular weakness were reported., Limitations: A single onabotulinumtoxinA treatment was evaluated., Conclusion: OnabotulinumtoxinA showed favorable tolerability and significantly improved PP severity and patient-reported outcomes in participants with moderate-to-severe PP., Competing Interests: Conflicts of interest Financial arrangements of the authors with companies whose products may be related to the present report are listed as declared by the authors. Dr Fabi is a consultant/speaker for AbbVie, Galderma, Merz Aesthetics, Revance, CROMA, and Ortho Dermatologics; has received research support from AbbVie, Galderma, Merz, Revance, CROMA, and Raziel; and holds stock in AbbVie and Revance Therapeutics. Drs Biesman and George are speakers, consultants, investigators, and advisory board members for Allergan Aesthetics, an AbbVie company. Dr Humphrey is a speaker, consultant, and/or investigator for Allergan Aesthetics, an AbbVie company, Galderma, Merz, and Revance. Drs LaTowsky and Weiss are speakers, consultants, investigators, and advisory board members for Allergan Aesthetics, an AbbVie company, and Galderma. Drs Park and Shimoga are employees of AbbVie and may own AbbVie stock. Ms Lee, Mr Jierjian, Mr Tong, and Ms Hopfinger are employees of Allergan Aesthetics, an AbbVie company, and may own AbbVie stock., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with metastatic triple-negative breast cancer (mTNBC) who received ≥2 prior systemic therapies (≥1 in metastatic setting). Exposure-response (E-R) relationships between SG exposure and efficacy and safety outcomes were characterized in 277 patients with mTNBC using data from the phase I/II IMMU-132-01 and phase III ASCENT (IMMU-132-05) studies. Evaluated endpoints included complete response (CR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety endpoints (individual first worst grade of select adverse events (AEs)). E-R analyses were also conducted for time to first dose reduction or delay. Patients received SG at 8 or 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle. Average SG-related serum exposure over the treatment duration (until the event) was consistently the most significant exposure metric correlated with efficacy and safety endpoints. Higher average concentration over the treatment duration for SG (CAVG SG ) was the best predictor of CR and ORR. The model-predicted proportions of patients with CR and ORR at 10 mg/kg were 4.26% and 32.6%, respectively. Higher CAVG for total antibody was the best predictor of OS and PFS. The model-predicted probability of OS at 12 months at median lactate dehydrogenase (227 IU/L) was 53%. The probability of grade ≥1 evaluated AEs and the risk of dose reductions and delays significantly increased with increasing CAVG SG . The model-predicted proportions of patients with any-grade AEs were 35.9%, 67.4%, 64.7%, and 67.1% for vomiting, diarrhea, nausea, and neutropenia, respectively (10 mg/kg dose group). Neutropenia was the only evaluated AE for which CAVG SG was significantly associated with grade ≥3 events. The clinically meaningful efficacy and manageable safety achieved with SG 10 mg/kg on days 1 and 8 of every 21-day cycle dosing regimen supports the appropriateness of this clinical dosage in patients with mTNBC., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Breast cancer classification plays a crucial role in healthcare, especially in the diagnosis and monitoring of patients. Traditional methods for classifying breast cancer based on histopathological images often suffer from limited accuracy, which can hinder early detection and treatment. Hence, this paper devises a novel Internet of Things (IoT) based healthcare system using SqueezeNet&#95;Fractional Dung Beetle Optimization (Squeeze&#95;FDBO) for breast cancer detection. Initially, IoT network is simulated, and routing of the histopathological images to the Base Station (BS) is established utilizing FDBO, which is obtained by combining Dung Beetle Optimizer (DBO), and the Fractional Calculus (FC). At BS, breast cancer classification is done, where input is first processed by a bilateral filter. Then, blood cell segmentation is effectuated using LadderNet, and then, feature extraction is performed. Finally, the multigrade classification of breast cancer is executed utilizing SqueezeNet tuned by FDBO. The efficiency of Squeeze&#95;FDBO is validated using various performance measures, and it is found to record an accuracy of 0.919, sensitivity of 0.913, specificity of 0.923, Negative Predictive Value (NPV) of 0.920, and Positive Predictive Value (PPV) of 0.908, and a better routing performance with energy of 0.405 J, distance of 6.901 m, and delay of 0.650mS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This is a descriptive study based on National Family Health Survey- Round 5 (2020-21) dataset, comparing two groups of Indian women: "stay-behind pregnant women" and "women who are living with their husbands." We applied z-test analyzing health status and healthcare access between the two groups. The result shows both health status (D Mean Hemoglobin  = -2.02, p  = .002; DMean Sys BP  = -2.48, p  = .001; D Mean Dias BP  = -1.53, p  = .003; D Anemic  = 0.04, p = .006) and healthcare access (D Access to public healthcare  = -4.6 percent, p = .005; D Access to private healthcare  = 10.4 percent, p  = .002, D Others  = -9.3 percent, p  = .001) are significantly lower among "stay-behind pregnant women." The intake of nutritious food among stay-behind pregnant women is relatively low (D Pulses  = -7.9 percent, p  = .003; D Veg  = -3.4 percent, p  = .002; D Fruits = -5.5 percent, 0.005; D Eggs  = -3.8 percent, p  = .004; D Meat  = -3.4 percent, p = .002) which contributes to their poor health status. Overall, it is concluded that the health status and healthcare access of "stay-behind pregnant women" are poorer than others. Future studies can explore the role of empowerment of "stay-behind pregnant women" in ensuring their better health and healthcare access.

Background: Talquetamab is approved for treatment of triple-class exposed (TCE) patients with relapsed/refractory multiple myeloma (RRMM). We evaluated the comparative effectiveness of talquetamab in the MonumenTAL-1 study versus real-world physician's choice (RW) treatment., Materials and Methods: An external control arm for MonumenTAL-1 was created from patients in the Flatiron Health database who satisfied MonumenTAL-1 eligibility criteria (n = 629 with 1169 eligible lines of therapy). Patient-level data from MonumenTAL-1 were included for patients who received subcutaneous talquetamab 0.4 mg/kg QW (n = 143) and 0.8 mg/kg Q2W (n = 145). After adjusting for baseline covariate imbalances, comparative effectiveness was assessed for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS)., Results: Baseline covariates were comparable across cohorts after adjustment. Talquetamab 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts, respectively, showed significant improvement in PFS (HR, 0.55 [95% CI, 0.44-0.69; P < .0001; median, 7.5 vs. 4.0 months] and 0.40 [95% CI, 0.31-0.53; P < .0001; median, 14.2 vs. 4.0 months]), TTNT (HR, 0.59 [95% CI, 0.47-0.74; P < .0001; median, 9.1 vs. 5.1 months] and 0.45 [95% CI, 0.35-0.59; P < .0001; median, 13.3 vs. 5.1 months]), and OS (HR, 0.56 [95% CI, 0.40-0.78; P = .0007; median, NR vs. 16.5 months] and 0.48 [95% CI, 0.33-0.70; P = 0.0002; median NR vs. 15.9 months]) versus RW treatment., Conclusion: Both talquetamab schedules demonstrated superior effectiveness over RW treatment for all outcomes assessed. These data suggest talquetamab as an effective immunotherapy option in patients with TCE RRMM., Competing Interests: Disclosure The authors declare the following conflicts of interest: JCY has served in a consulting/advisory role for BMS and Janssen; has received honoraria from BMS and Janssen Scientific Affairs; and has received research funding from Celgene, Genmab, GSK, MingSight, Novartis, Pfizer, and Regeneron. NB has served in a board membership/advisory role for Amgen, BMS, GSK, Janssen, Karyopharm, Pfizer, Sanofi, and Takeda; has received honoraria from AbbVie, BMS, Janssen, Sanofi, and Takeda; has received research funding from Amgen, BMS, Janssen, Karyopharm, and Merck; has divested equity in Genomic Testing Cooperative; and has a spouse who is an employee of Boehringer Ingelheim. SN, XL, KQ, AL, EA, TR, CK, TP, KG, and SP are employees of Janssen and may own stock in Janssen/Johnson & Johnson. LJC has served in a consulting role for AbbVie, Amgen, BMS, Pfizer, and Sanofi; has received grants or contracts from AbbVie, Amgen, and BMS; and has received research funding from Janssen., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: This study investigated the characteristics and trends of pediatric exposures to caffeine energy products reported to US poison centers METHODS: National Poison Data System data for caffeine energy product single-substance exposures during 2011-2023 among individuals < 20 years old were analyzed., Results: There were 32,482 caffeine energy product exposures reported to US poison centers with a 17.3% exposure rate increase during 2011-2023. Most exposures were among < 6-year-olds (69.6%), males (56.7%), or involved liquid formulations (57.5%). Most (80.7%) were not treated in a healthcare facility; however, 1.6% were medically admitted. Teenagers 13-19 years old were more likely to be medically admitted (OR = 12.74, 95% CI: 10.40-15.60) or have a serious medical outcome (OR = 18.83, 95% CI: 16.88-21.01) than children < 13 years old. Solid energy product formulations were more likely to be associated with a serious medical outcome (OR = 1.98, 95% CI: 1.81-2.17) or medical admission (OR = 5.23, 95% CI: 4.31-6.36) than other types of formulations. During the study period, exposure rates increased for liquid (34.5%) and powder/granules (632.9%) product formulations but decreased for solids (-51.5%). Among liquid formulation subcategories, the exposure rate for beverages increased (46.5%) and that for shots decreased (-86.1%)., Conclusions: Although most pediatric exposures to caffeine energy products reported to US poison centers were associated with no or minimal clinical effects, serious medical outcomes and medical admissions occurred. The product formulations that drove the 17% increase in the exposure rate changed during the study period. Opportunities exist to reduce the adverse effects of caffeine energy products among the pediatric population., Competing Interests: Declarations. Previous Presentation of Data: Not applicable. Conflicts of Interest: The authors declare that they have no conflicts of interest., (© 2025. The Author(s).)

Ameloblastic fibroma is an uncommon, benign, mixed odontogenic tumor characterized by the presence of both epithelial and mesenchymal components, without the formation of hard tissue. It constitutes approximately 1.5%-4.5% of all odontogenic tumors and predominantly affects the posterior mandible. Most cases are observed in individuals under 22 years of age, with a slight predilection for males. The initial presentation typically involves a painless, slow-growing mass, often discovered incidentally during routine radiographic examinations. This lesion carries a risk of recurrence and potential for malignant transformation. We present a case of an 8-year-old female child who presented with a painless swelling in the right posterior mandibular region for 6 months, which was histologically characterized by dentinoid formation., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Oral furosemide postpartum improves the time to hypertension resolution in randomized control trials. Further investigation is needed to determine the impact of furosemide in routine clinical practice., Objective: Real world study to assess impact of furosemide on rates of postpartum hypertension and readmissions for patients with hypertensive disorders of pregnancy., Study Design: A prospective cohort study of postpartum patients with hypertensive disorders of pregnancy at a single institution between October 2021 and April 2022. Patients were enrolled in the remote postpartum blood pressure monitoring program (RPM) as standard of care. Use of oral furosemide for 5 days postpartum was implemented per protocol for all patients with gestational hypertension and preeclampsia. Data was obtained until six weeks postpartum. Exclusion criteria included age less than 18 years old, patients with chronic hypertension alone without superimposed preeclampsia, and patients who did not provide consent for data collection. The primary outcome was hospital readmission within six weeks postpartum. The secondary outcome was blood pressure values across those six weeks. Hypertension was defined as any blood pressure value with SBP ≥ 140 mmHg or DBP ≥ 90 mmHg., Results: Overall, 545 patients were enrolled in the RPM program during the study period, 306 of them consented to data collection and 258 patients were ultimately included after meeting all inclusion criteria with no exclusions. Of these, 203 patients received furosemide. Overall, 47.7 % of patients had gestational hypertension, 40.3 % of patients had preeclampsia with or without severe features, and 12.0 % of patients had superimposed preeclampsia with or without severe features. In total, 24.2 % of patients were discharged home on an antihypertensive medication in addition to furosemide. The overall rate of readmission was 13.2 %. There was no difference between patients who received oral furosemide versus those who did not (12.8 % vs 14.6 %, p = 0.74). Rates of hypertension at the one-week postpartum visit between those two groups did not differ significantly (32.8 % [oral furosemide] vs 36.2 % [no furosemide], p = 0.66). Diastolic blood pressures at the six-week follow-up visit were lower in the furosemide group (74 [69,81] vs 82 [76,89]; p = 0.02) among patients registered to care who completed the six-week visit., Conclusion: The addition of furosemide did not result in improved blood pressure control by the first week postpartum or fewer hospital readmissions. However, diastolic blood pressure trended lower at the six-week visit in patients who received furosemide., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SR reports serving as a consultant for Roche Diagnostics, Thermo Fisher, Beckman Coulter, Siemens and has received research funding from Roche Diagnostics and Siemens for work related to angiogenic biomarkers unrelated to the submitted work. All other authors report no conflict of interests., (Copyright © 2025 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

The generation of spectral libraries using hyperspectral data allows for the capture of detailed spectral signatures, uncovering subtle variations in plant physiology, biochemistry, and growth stages, marking a significant advancement over traditional land cover classification methods. These spectral libraries enable improved forest classification accuracy and more precise differentiation of plant species and plant functional types (PFTs), thereby establishing hyperspectral sensing as a critical tool for PFT classification. This study aims to advance the classification and monitoring of PFTs in Shoolpaneshwar wildlife sanctuary, Gujarat, India using Airborne Visible/Infrared Imaging Spectrometer-Next Generation (AVIRIS-NG) and machine learning techniques. A comprehensive spectral library was developed, encompassing data from 130 plant species, with a focus on their spectral features to support precise PFT classification. The spectral data were collected using AVIRIS-NG hyperspectral imaging and ASD Handheld Spectroradiometer, capturing a wide range of wavelengths (400-1600 nm) to encompass the key physiological and biochemical traits of the plants. Plant species were grouped into five distinct PFTs using Fuzzy C-means clustering. Key spectral features, including band reflectance, vegetation indices, and derivative/continuum properties, were identified through a combination of ISODATA clustering and Jeffries-Matusita (JM) distance analysis, enabling effective feature selection for classification. To assess the utility of the spectral library, three advanced machine learning classifiers-Parzen Window (PW), Gradient Boosted Machine (GBM), and Stochastic Gradient Descent (SGD)-were rigorously evaluated. The GBM classifier achieved the highest accuracy, with an overall accuracy (OAA) of 0.94 and a Kappa coefficient of 0.93 across five PFTs., (© 2025 John Wiley & Sons Ltd.)

Cutaneous neoplasms are relatively rare in children. Most commonly, skin cancers arise through environmental factors, particularly ultraviolet radiation; thus, age is the most predictive factor in developing cutaneous carcinomas. However, children born with certain genodermatoses are significantly more likely to develop malignancies and must be carefully monitored and treated. Most published data are based mainly on signs and symptoms present in White patients. Therefore, we aim to highlight the cutaneous presentations and relative differences of these genodermatoses among patients with skin of colour, who are underrepresented in medicine. We conducted a literature review of 504 patients presented in 236 published articles. Manuscripts with accessible case reports for children aged ≤ 17 years were included. Patients with skin of colour often present with fewer classical findings and have higher incidences of scarring and dyspigmentation. There is also a higher incidence of consanguinity in affected patients. Providers who are able to recognize nonclassical signs can provide proper management and treatment regimens, potentially bringing outcomes for patients with skin of colour more in line with those of White children., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Under stress conditions, cells reprogram their molecular machineries to mitigate damage and promote survival. Ubiquitin signaling is globally increased during oxidative stress, controlling protein fate and supporting stress defenses at several subcellular compartments. However, the rules driving subcellular ubiquitin localization to promote concerted response mechanisms remain understudied. Here, we show that K63-linked polyubiquitin chains, known to promote proteasome-independent pathways, accumulate primarily in non-cytosolic compartments during oxidative stress induced by sodium arsenite in mammalian cells. Our subcellular ubiquitin proteomic analyses of non-cytosolic compartments expanded 2.5-fold the pool of proteins (2,494) and provided a comprehensive number of sites (10,157) known to be ubiquitinated during arsenite stress, suggesting their involvement in a myriad of cellular pathways. Moreover, subcellular proteome analyses revealed proteins that are recruited to non-cytosolic compartments under stress, including a significant enrichment of helper ubiquitin-binding adaptors of the ATPase VCP that processes ubiquitinated substrates for downstream signaling. We further show that VCP recruitment to non-cytosolic compartments under arsenite stress occurs in a ubiquitin-dependent manner mediated by its adaptor NPLOC4. Additionally, we show that VCP and NPLOC4 activities are critical to sustain low levels of non-cytosolic K63-linked ubiquitin chains, supporting a cyclical model of ubiquitin conjugation and removal that is disrupted by reactive oxygen species. This work deepens our understanding of the role of localized ubiquitin and VCP signaling in the basic mechanisms of stress response and highlights new pathways and molecular players that are essential to reshape the composition and function of the human subcellular proteome under dynamic environments., Competing Interests: COMPETING INTERESTS The authors declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alpha-mannosidosis is a rare lysosomal storage disorder caused by deficiency of the lysosomal enzyme alpha-mannosidase, which leads to the accumulation of mannose-rich oligosaccharides. Serum oligosaccharides are useful biomarkers for the therapeutic monitoring of patients with alpha-mannosidosis. In this study, we have developed a ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for thetrue quantitation of GlcNAc(Man) 2 , and semi-quantitation of GlcNAc(Man) 3-6 ., Results: In plasma samples from 16 untreated alpha-mannosidosis patients, GlcNAc(Man) 2-6 levels were significantly higher than in controls, demonstrating 100 % sensitivity. In plasma samples from patients with other glycoproteinosis disorders, GlcNAc(Man) 2-6 levels were within the normal range, other than mild elevations observed in some Mucolipidosis II/III patients, demonstrating high specificity. We have evaluated if these biomarkers can be used for therapeutic monitoring of alpha-mannosidosis by testing plasma samples from 4 patients who had received hematopoietic stem cell transplantation (HSCT). All oligosaccharide species were largely reduced in treated patients., Conclusions: This study indicates that the analysis of serum/plasma oligosaccharides by UPLC-MS/MS is a feasible and valuable tool for diagnosis, and treatment monitoring of patients with alpha-mannosidosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zackary (Ari) M. Herbst is a member of GelbChem, LLC., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Mussels, particularly Perna viridis, are vital sentinel species for toxicology and biomonitoring in environmental health. This species plays a crucial role in aquaculture and significantly impacts the fisheries sector. Despite the ecological and economic importance of this species, its omics resources are still scarce. We generated a gill-specific reference transcriptome for Perna viridis using 292 million short Illumina reads from eight pooled gill tissue samples isolated from twenty-four individuals. The Trinity assembler generated 438,842 transcripts with an N50 of 1,958 bp. Several databases were employed in the annotation process. This dataset greatly expands the omics resources of bivalve databases and advances our knowledge of transcriptomics, molecular biology, environmental toxicology, and cancer research., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Lenacapavir is a potent, long-acting HIV-1 capsid inhibitor used in combination with other antiretrovirals to treat HIV-1 infection. The pharmacokinetics of orally administered drugs may be affected by food intake or coadministration of acid-reducing agents (ARA). Two Phase 1 studies were conducted on healthy participants to evaluate the effect of food and the impact of the histamine H 2 -receptor antagonist famotidine in parallel cohorts. In Study 1, oral lenacapavir (300 mg) was administered under fasting conditions, after a standardized high-fat meal, and after a low-fat meal (n = 8/cohort). In Study 2, lenacapavir 300 mg was administered alone (n = 27) and 2 hours after famotidine (40 mg; n = 25), each under fasting conditions. For the high-fat meal versus fasted comparison, the percentage geometric least-squares mean (%GLSM) ratios for the lenacapavir area under the curve to infinity (AUC inf ) and maximum concentration (C max ) were 115.2 and 145.2, respectively. For the low-fat meal, the %GLSM ratios for lenacapavir AUC inf  and C max were 98.6 and 115.8, respectively, versus the fasted state. In the famotidine study, the %GLSM ratio for lenacapavir AUC from time zero to the last quantifiable concentration was 137.4, and for C max was 100.6. Based on available clinical safety data, the exposure increases observed in these studies were not expected to be clinically relevant. Overall, these data support the dosing of oral lenacapavir without regard to food intake or coadministration with ARAs., (© 2025, The American College of Clinical Pharmacology.)

Purpose of Review: WHO defines SCD as sudden unexpected death either within 1 h of symptom onset (witnessed) or within 24 h of having been observed alive and symptom-free (unwitnessed). Sudden cardiac arrest is a major cause of mortality worldwide, with survival to hospital discharge for hospital cardiac arrest and in-hospital cardiac arrest being only 9.3 % and 21.2 %, respectively, despite treatment highlighting the importance of effectively predicting and preventing cardiac arrest. This literature review aims to explore the role and application of AI (Artificial Intelligence) in predicting and preventing sudden cardiac arrest., Material and Methods: Eligible studies were searched from PubMed and Web of Science. The inclusion criteria were fulfilled if sudden cardiac death prediction and prevention, artificial intelligence, machine learning, and deep learning were included., Conclusions: Artificial intelligence, machine learning, and deep learning have shown remarkable prospects in SCA risk stratification, which can improve the survival rate from SCA. Nonetheless, they have not been adequately trained and tested, necessitating further studies with explainable techniques, larger sample sizes, external validation, more diverse patient samples, multimodal tools, ethics, and bias mitigation to unlock their full potential., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Aim: We aimed to understand the host and microbe interactions at the time of infection and inflammatory response in amoebic liver abscess (ALA) patients based on toll-like receptor (TLR) expression (mRNA), cytokine and IgG subtypes levels., Methods and Results: Liver aspirates from 100 ALA patients and 11 liver autopsy samples were used as negative controls. Blood samples from 100 ALA and 41 healthy individuals were collected. mRNA expression of TLR 1 to 9 genes was measured using reverse transcriptase polymerase chain reaction (RT-PCR). Serum cytokines level was quantified by flow cytometry. In-house ELISA for the analysis of IgG and its subtypes in the serum samples was performed. A total of 7 TLR genes (TLR1, TLR2, TLR4, TLR6, TLR7, TLR8 and TLR9) and 6 TLR genes (TLR1, TLR2, TLR3, TLR4, TLR5 and TLR8) were found to be elevated in liver aspirates and PBMCs respectively. Increased serum cytokine levels were observed in ALA patients vs. healthy controls. Interestingly, a significant increase in IgG and its subtypes (IgG1, IgG3 and IgG4) was found in the serum of ALA patients., Conclusion: Increased levels of TLR, pro- and anti-inflammatory cytokines, IgG and its subtypes, are possibly linked with early-stage infection in ALA patients., Impact Statement: The role of TLRs in association with ALA might provide insights into new therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier GmbH.)

Background: Subjective cognitive decline (SCD) is the early predementia syndrome. that occurs even before the development of objective cognitive decline. SCD plus refers to an additional set of criteria that increases the likelihood of developing mild cognitive impairment and further progressing to Alzheimer's disease (AD). Studying the progression of SCD-plus participants will help in understanding the importance of diagnosing this condition at an early stage and delaying its onset., Objective: The present tries to examine neurocognitive changes in individuals who met the criteria of SCD-plus patients. The study also investigated the imaging correlates of these individuals in both cohorts., Methods: This study included 94 participants from Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) and Tata Longitudinal Study of Aging (TLSA) cohorts who satisfy the criteria of SCD plus. Mann-Whitney U test was used to compare the SCD plus participants and healthy controls. Regression analysis was performed to find the association between SCD plus and cognition., Results: The SCD-plus group performed poorer than the healthy group in episodic memory delayed recall (p = 0.049), name face recognition (p = 0.023), and letter fluency (p = 0.004) tasks. The generalized linear model revealed that the SCD-plus group had lower left cerebellar cortex (p = 0.010) and right inferior occipital cortex (p = 0.016) volumes than the healthy control group., Conclusions: The participants in the SCD-plus group performed poorly on memory and language-related tasks, and the volumes of the associated brain regions decreased. This study suggested that the SCD-plus group had characteristics similar to AD group and can help in identifying AD at the earliest., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Automatic Sign Language Recognition Systems (ASLR) offers smooth communication between hearing-impaired and normal-hearing individuals, enhancing educational opportunities for impaired. However, it struggles with "curse of dimensionality" due to excessive features resulting in prolonged training time and exhaustive computational demand. This paper proposes technique that integrates machine learning and swarm intelligence to effectively address this issue. The proposed technique, initially, extracts features using histrogram of gradient (HOG) approach and then reduces dimensions of extracted features using unsupervised autoencoder and subsequently refining the feature set with an improved GWO algorithm. A handcrafted artificial neural network serves as the classifier within this integrated framework, denoted as AEGWO-Net. Exhaustive experimentations were conducted on six different datasets namely ASL, ASL MNIST, ISL, ArSL, MNIST Digits, and IEEE-ISL containing gestures of different languages to demonstrate the performance of AEGWO-Net. The AEGWO-Net demonstrates superior performance improving accuracy and F1 score by 6% and 4% respectively compared to PCA-IGWO and KPCA-IGWO algorithms. Achieving high accuracy (98.40%), F1-score (96.59%), MCC (97.14%), and AUC (96.21%) indicates the robustness and generalizability of the AEGWO-Net method even with reduced dimensionality. Furthermore, a comparison between AEGWO-Net with other existing swarm intelligence techniques is also made to demonstrate its superiority., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The widespread use of zinc oxide nanoparticles (ZnO NPs) in various products raises significant ecological concerns due to their potential toxic effects in aquatic environments. This study employed the Asian green mussel (Perna viridis) as a model to explore the molecular and ecological risks of ZnO NP exposure using transcriptomics. Mussels exposed to ZnO NPs (5, 10, and 15 mg/L) for 28 days showed significant gene expression changes in gill tissues, affecting immune response, calcium homeostasis, and cellular stress. Disrupted pathways such as FOXO, Wnt, and TGFβ reveal complex toxicity mechanisms. These findings provide crucial insights into the environmental impact of nanoparticle pollution, emphasizing the need for stringent regulations. Furthermore, the shared molecular pathways suggest that similar mechanisms may occur in humans, highlighting potential health risks associated with nanoparticle exposure., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that could influence the work reported in this paper. All authors have approved the manuscript and the data presented., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Platysma prominence (PP) describes the noticeable appearance of the platysma muscle upon contraction, causing a less defined jawline contour and vertical neck bands., Objectives: The objective of this study was to assess the safety and efficacy of onabotulinumtoxinA for improvement of PP in adults., Methods: Participants with moderate to severe (Grade 3 to 4) PP at maximum contraction received onabotulinumtoxinA or placebo on Day 1 and were monitored for 120 days. OnabotulinumtoxinA dosage (26, 31, or 36 U) was customized based on baseline PP severity on each side of the neck., Results: Efficacy analyses were conducted in the intent-to-treat (ITT) population (all randomized participants), and modified ITT population (mITT; psychosocially impacted by PP appearance). Results from ITT and mITT populations were comparable. As assessed by investigators, 76.7% of onabotulinumtoxinA mITT participants achieved ≥1-grade improvement vs 21.2% in the placebo group, and 41.0% vs 2.2% (P < .0001) achieved ≥2-grade improvement at Day 14. As assessed by participants, 79.9% of onabotulinumtoxinA mITT participants vs 21.8% in the placebo group and 40.8% vs 3.9% (P < .0001) achieved ≥1- or ≥2-grade improvement, respectively, at Day 14. OnabotulinumtoxinA responder rates remained higher than placebo through Day 120, gradually declining over time. OnabotulinumtoxinA participants reported significantly higher satisfaction with treatment effect, less bother from jawline and vertical neck bands, and lower psychosocial impact from PP than placebo at Day 14 (P < .0001). OnabotulinumtoxinA effectively improved self-perceived jawline definition and was well tolerated., Conclusions: OnabotulinumtoxinA was well tolerated and effective at improving moderate to severe PP, including neck bands and jawline definition., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

The advancement in the arena of bone tissue engineering persuades us to develop novel nanocomposite scaffolds in order to improve antibacterial, osteogenic, and angiogenic properties that show resemblance to natural bone extracellular matrix. Here, we focused on the development of novel zinc-doped hydroxyapatite (ZnHAP) nanoparticles (1, 2 and 3 wt%; size: 50-60 nm) incorporated chitosan-gelatin (CG) nanocomposite scaffold, with an interconnected porous structure. The addition of ZnHAP nanoparticles decreases the pore size (∼30 µm) of the CG scaffolds. It was observed that with the increase in the concentration of ZnHAP nanoparticles (3 wt%) in CG scaffolds, the swelling ratio (1760% ± 2.0%), porosity (71% ± 0.98%) and degradation rate (35%) decreased, whereas mechanical property (1 MPa) increased, which was better as compared to control (CG) samples. Similarly, the high deposition of apatite crystals especially CG-ZnHAP 3 nanocomposite scaffold revealed the excellent osteoconductive potential among all other scaffolds. MC3T3-E1 osteoblastic cells seeded with CG-ZnHAP nanocomposite scaffolds depicted better cell adhesion, proliferation and differentiation to osteogenic lineages. Finally, the chorioallantoic membrane (CAM) assay revealed better angiogenesis of ZnHAP nanoparticles (3 wt%) loaded CG scaffolds supporting vascularization after 7th day incubation in the CAM area. Overall, the results showed that the CG-ZnHAP 3 nanocomposite scaffold could be a potential candidate for bone defect repair., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Heterozygous variants in SOX10 cause congenital syndromes affecting pigmentation, digestion, hearing, and neural development, primarily attributable to failed differentiation or loss of non-skeletal neural crest derivatives. We report here an additional, previously undescribed requirement for Sox10 in bone mineralization. Neither crest- nor mesoderm-derived bones initiate mineralization on time in zebrafish sox10 mutants, despite normal osteoblast differentiation and matrix production. Mutants are deficient in the Trpv6+ ionocytes that take up calcium from the environment, resulting in severe calcium deficiency. As these ionocytes derive from ectoderm, not crest, we hypothesized that the primary defect resides in a separate organ that systemically regulates ionocyte numbers. RNA sequencing revealed significantly elevated stanniocalcin (Stc1a), an anti-hypercalcemic hormone, in sox10 mutants. Stc1a inhibits calcium uptake in fish by repressing trpv6 expression and Trpv6+ ionocyte proliferation. Epistasis assays confirm excess Stc1a as the proximate cause of the calcium deficit. The pronephros-derived glands that synthesize Stc1a interact with sox10+ cells, but these cells are missing in mutants. We conclude that sox10+ crest-derived cells non-autonomously limit Stc1a production to allow the inaugural wave of calcium uptake necessary to initiate bone mineralization., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2025. Published by The Company of Biologists.)

Among new antimalarials discovered over the past decade are multiple chemical scaffolds that target Plasmodium falciparum P-type ATPase ( Pf ATP4). This essential protein is a Na + pump responsible for the maintenance of Na + homeostasis. Pf ATP4 belongs to the type two-dimensional (2D) subfamily of P-type ATPases, for which no structures have been determined. To gain better insight into the structure/function relationship of this validated drug target, we generated a homology model of Pf ATP4 based on sarco/endoplasmic reticulum Ca 2+ ATPase, a P2A-type ATPase, and refined the model using molecular dynamics in its explicit membrane environment. This model predicted several residues in Pf ATP4 critical for its function, as well as those that impart resistance to various Pf ATP4 inhibitors. To validate our model, we developed a genetic system involving merodiploid states of Pf ATP4 in which the endogenous gene was conditionally expressed, and the second allele was mutated to assess its effect on the parasite. Our model predicted residues involved in Na + coordination as well as the phosphorylation cycle of Pf ATP4. Phenotypic characterization of these mutants involved assessment of parasite growth, localization of mutated Pf ATP4, response to treatment with known Pf ATP4 inhibitors, and evaluation of the downstream consequences of Na + influx. Our results were consistent with modeled predictions of the essentiality of the critical residues. Additionally, our approach confirmed the phenotypic consequences of resistance-associated mutations as well as a potential structural basis for the fitness cost associated with some mutations. Taken together, our approach provides a means to explore the structure/function relationship of essential genes in haploid organisms., Competing Interests: Competing interests statement:The authors declare no competing interest.

A new species of eight-gilled hagfish genus Eptatretus (Myxinidae) is described based on five specimens trawled on the upper continental slope off Kollam, Kerala, India, northern Indian Ocean. Eptatretus gopali sp. nov. can be diagnosed by the presence of eight-gill pouches and gill apertures, 10-11 pre-brachial, 7 branchial, 50-55 trunk, 9-10 tail slime pores, 77-82 total pores, 3/2 multicusp teeth pattern, 40-44 total cusps, absence of nasal-sinus papillae, and a light brown body color. Detailed morphological comparisons with all known eight-gilled species of Eptatretus showed that the new species was distinct from all others by having 40-44 total cusps, characteristic body proportions, and the shortest tail length. E. gopali formed a district clade in the phylogenetic tree and exhibited a genetic distance of 3.6%-11.6% in Cytochrome C oxidase I (COI) sequences and 2.0%-4.9% in 16S rRNA sequences between the congeners. An identification key is also provided for the species of Eptatretus from the Indian Ocean., (© 2025 Fisheries Society of the British Isles.)

Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)). We show that individual macrophages can take up both SPIONs and drug-loaded NPs efficiently, thereby generating drug-loaded cells susceptible to AMF-induced cell death. Macrophages co-loaded with SPIONs and drug-containing IOH-NPs spontaneously released the drugs at similar rates irrespective of the application of an AMF. Notably, while the spontaneous drug release from macrophages co-loaded with SPIONs and drug-associated MSNs was low, AMF exposure accelerated the drug release. Thus, AMF exposure of SPION/drug-MSN coloaded macrophages provides a simple strategy for trigger-controlled drug release since it does not require any chemical modification of NPs or drugs. Thus, we assume that the coloading of different types of NPs will expand the potential of macrophages for drug delivery., Competing Interests: Declarations. Ethics approval and consent to participate: The study involved primary cells which were isolated from euthanized mice. According to German law, no licence is required for euthanasia of untreated mice for research purposes. Consent for publication: Not applicable. Competing interests: The authors declare that there are no competing interests., (© 2025. The Author(s).)

Introduction: Cash bail reforms that end pretrial detention owing to the inability to afford bail have been highly debated across the U.S. A major concern cited by bail reform opponents is that reducing pretrial detention will increase community violence, particularly violence against women. The objective of this study was to assess whether New Jersey's cash bail reform was associated with changes in rates of fatal violence against women., Methods: This study used synthetic control methods to evaluate the impact of bail reform on the rates of fatal violence against women in New Jersey compared with that in a weighted combination of 21 control states with no bail reform from 2015-2019. Outcome data were from the National Violent Death Reporting System and included intimate partner violence-related homicides, pregnancy-associated homicides, and overall homicides of adult women. Outcomes were measured for all adult women and within racialized groups. Analyses were performed in 2024., Results: There were no significant changes in the rates of intimate partner violence-related homicide (average treatment effect on the treated= -0.11 deaths per 100,000 women, p=0.1), pregnancy-associated homicide (0.28 deaths per 100,000 births, p=0.8), and overall homicide (-0.03 deaths per 100,000, p=0.1) during the postpolicy period. There were also no significant changes within racialized groups., Conclusion: Violence against women and mass incarceration are urgent and interconnected public health crises. These findings demonstrate the potential for policies to reduce the number of people incarcerated before trial without increasing fatal violence against women. Addressing these public health crises requires holistic structural interventions, such as housing and economic support, that reduce violence without criminalization., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Lactoferrin (Lf), a multifunctional glycoprotein known for its roles in immune modulation, iron metabolism, and antimicrobial activity, has limited therapeutic efficacy due to poor bioavailability. Liposomal encapsulation of lactoferrin (LLf) offers a potential solution by improving its stability, absorption, and sustained release, making it a promising candidate for various clinical applications. This study aims to compare the effectiveness of LLf and plain Lf in cellular uptake, proliferation, and wound healing using HEK-293T and Caco-2 cell lines., Methods: Cell uptake, proliferation, and wound healing assays were conducted using HEK-293T and Caco-2 cells to evaluate the bioavailability and therapeutic efficacy of LLf compared to plain Lf. The cellular uptake was assessed over a 24-h period using an indirect ELISA method. Cell proliferation was measured using the MTT assay, while wound healing was evaluated using a scratch assay to observe cell migration over 48 h., Results: LLf demonstrated significantly higher cellular uptake in both HEK-293T and Caco-2 cells, with peak internalization at 4 h, compared to plain Lf. In proliferation studies, LLf showed a dose-dependent increase in cell growth, achieving a 71% proliferation rate at 75 µg/mL, while plain Lf reached only 53%. LLf also accelerated wound healing, with nearly complete closure by 48 h, compared to 51.3% closure with plain Lf., Conclusion: The results indicate that liposomal encapsulation significantly enhances lactoferrin's bioavailability, proliferation-inducing capacity, and wound healing efficacy. LLf's superior performance in these key areas suggests its potential for broader therapeutic applications, particularly in wound care, immune modulation, and tissue regeneration. Future clinical studies are warranted to validate the therapeutic benefits of LLf in vivo .

Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. Toll-like receptors (TLRs) are present on gingival epithelial cells and recognize pathogen-associated molecular patterns (PAMPs) on pathogenic bacteria, induce the secretion of proinflammatory cytokines, and initiate innate and adaptive antigen-specific immune responses to eradicate the invading microbes. Since PD is a chronic inflammatory disease, TLR2/TLR4 plays a vital role in disease pathogenesis and maintaining the periodontium during health. Many factors modulate the TLR-mediated signaling pathway, including specific miRNAs. The present study was designed to characterize the function of TLR2/4 signaling to the miRNA profile after polybacterial infection with Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia in C57BL6/J wild-type, TLR2 -/- , and TLR4 -/- mice (n=16/group) using RT-qPCR. The selection of 15 dominant miRNAs for RT-qPCR analysis was based on prior NanoString global miRNA expression profiling in response to polymicrobial and monobacterial infection. Polybacterial infections established gingival colonization in wild-type, TLR2 -/- and TLR4 -/- mice with induction of bacterial-specific IgG. A significant reduction in alveolar bone resorption (ABR) and gingival inflammation was observed in the mandibles of TLR2/4 -/- mice compared to C57BL6/J wild-type mice ( p <0.0001). Periodontal bacteria disseminated from gingival tissue to the multiple organs in wild-type and TLR2 -/- mice (heart, lungs, brain, kidney) and limited to heart ( F. nucleatum ), lungs ( P. gingivalis ), kidney ( T. forsythia ) in TLR4 -/- mice. The diagnostic potential of miRNAs was assessed by receiver operating characteristic (ROC) curves. Among 15 miRNAs, three were upregulated in C57BL6/J wild-type mice, two in TLR2 -/- , and seven in TLR4 -/- mice. Notably, the anti-inflammatory miR-146a-5p was consistently upregulated in all the mice. Additionally, miR-15a-5p was upregulated in wild-type and TLR2 -/- mice. let-7c-5p was upregulated in TLR4 -/- mice and downregulated in the wild-type mice. Multi-species oral bacterial infection alters the TLR2/4 signaling pathways by modulating the expression of several potential biomarker miRNAs in periodontium., Importance: Periodontitis is the most prevalent chronic immuno-infectious multispecies dysbiotic disease of the oral cavity. The Toll-like receptors (TLR) provide the first line of defense, one of the best-characterized pathogens-detection systems and play a vital role in recognizing multiple microbial products. Multispecies infection with periodontal bacteria S. gordonii, F. nucleatum, P. gingivalis, T. denticola, and T. forsythia induced gingival inflammation, alveolar bone resorption (ABR) and miRNA expression in the C57BL6/J wild-type mice and whereas infection did not increase significant ABR in the TLR2/4 deficient mice. Among the 15 miRNAs investigated, miR-146a - 5p, miR-15a-5p were upregulated in wild-type and TLR2 -/- mice and miR-146a-5p, miR-30c-5p, let-7c-5p were upregulated in the TLR4 -/- mice compared to sham-infected controls. Notably, inflammatory miRNA miR-146a-5p was upregulated uniquely among the three different infection groups. The upregulated miRNAs (miR-146a, miR-15-a-5p, let-7c-5p) and downregulated miRNAs could be markers for TLRs-mediated induction of periodontitis.

Noncoding small RNAs are essential for modulating bacterial gene expression, especially under carbon and nutrient-limited conditions. In this study, by employing both in silico and molecular hybridization tools, we identified a carbon source responsive small RNA in A. baumannii DS002. Expression of corresponding gene, abcR200, located at the intergenic region of omt (O-methyltransferase) and orf72 genes, is under the transcriptional control of a global transcriptional factor, Leucine Responsive Regulatory Protein (Lrp). A sequence motif that serves as a target for Lrp was found overlapping the abcR200 promoter (P abcR200 ). Chromatin immunoprecipitation (ChIP) demonstrated that Lrp oligomers, formed under low leucine conditions, strongly interacted to the P abcR200 . However, the observed interactions were disrupted in the presence of leucine, as leucine promoted dissociation of Lrp to monomers and dimers, the conformation unfavourable to interact with P abcR200. The abcR200 promoter activity increased with increase of exogenous leucine concentrations, and at 2 mM maximum promoter activity was observed. The AbcR200 target mRNAs were identified by analysing the transcriptome of abcR200 negative strain of A. baumannii. Intriguingly, in abcR200 negative background, expression of lut (lactate utilization) mRNA has increased, suggesting that lut mRNA as one of the mRNA targets for AbcR200. Consistent of this observation, there existed extensive sequence complementarity between AbcR200 and lut mRNA, especially in the regions coding LutP, LutE and LutR. In support of the observed sequence complementarity, the levels of lut mRNA encoded proteins got elevated in abcR200 negative HS002 strains suggesting a role for AbcR200 in translational inhibition of lut mRNA., Competing Interests: Conflict of Interest Statement The authors of this paper declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported herein. This encompasses any financial arrangements, affiliations, or involvements with organizations that may have influenced the research process, analysis, or interpretation of results. Additionally, the authors affirm that they have not received any financial support or other benefits from entities with an interest in the subject matter discussed in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Sex as a biological variable (SABV) may help to account for the differential development and expression of post-traumatic stress disorder (PTSD) symptoms among trauma-exposed males and females. Here, we investigate the impact of SABV on PTSD-related neural alterations in resting-state functional connectivity (rsFC) within three core intrinsic connectivity networks (ICNs): the salience network (SN), central executive network (CEN), and default mode network (DMN)., Methods: Using an independent component analysis (ICA), we compared rsFC of the SN, CEN, and DMN between males and females, with and without PTSD (n = 47 females with PTSD, n = 34 males with PTSD, n = 36 healthy control females, n = 20 healthy control males) via full factorial ANCOVAs. Additionally, linear regression analyses were conducted with clinical variables (i.e., PTSD and depression symptoms, childhood trauma scores) in order to determine intrinsic network connectivity characteristics specific to SABV. Furthermore, we utilized machine learning classification models to predict the biological sex and PTSD diagnosis of individual participants based on intrinsic network activity patterns., Results: Our findings revealed differential network connectivity patterns based on SABV and PTSD diagnosis. Males with PTSD exhibited increased intra-SN (i.e., SN-anterior insula) rsFC and increased DMN-right superior parietal lobule/precuneus/superior occipital gyrus rsFC as compared to females with PTSD. There were also differential network connectivity patterns for comparisons between the PTSD and healthy control groups for males and females, separately. We did not observe significant correlations between clinical measures of interest and brain region clusters which displayed significant between group differences as a function of biological sex, thus further reinforcing that SABV analyses are likely not confounded by these variables. Furthermore, machine learning classification models accurately predicted biological sex and PTSD diagnosis among novel/unseen participants based on ICN activation patterns., Conclusion: This study reveals groundbreaking insights surrounding the impact of SABV on PTSD-related ICN alterations using data-driven methods. Our discoveries contribute to further defining neurobiological markers of PTSD among females and males and may offer guidance for differential sex-related treatment needs., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The Indian scad, Decapterus russelli is one of the most exploited pelagic resources of India. Population genetic analyses using mitochondrial and nuclear markers indicated a lack of genetic structuring among populations from Indian waters. As this species is highly migratory, it is also important to establish the environmental influence on its population structure. In the present study, the whole sagittal otolith composition was analysed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) to assess spatial distribution of D. russelli collected from 4 sites along the Indian coast. Elemental ratios (Ba/Ca, Fe/Ca, K/Ca, Mg/Ca, Na/Ca, Sr/Ca and Zn/Ca) were analysed using univariate and multivariate statistics to determine whether this chemical signature can provide insight into the adaptive patterns. All element/Ca ratios are found to be significantly different between the four sampling locations (ANOVA, p < 0.05; MANOVA, p < 0.05). Five of the element/Ca ratios were found to be significantly different when the data was analysed coastwise (ANOVA, p < 0.05; MANOVA, p < 0.05). The LDA plot also showed the spatial heterogeneity of Element/Ca ratios between the four sampling sites, but some overlaps were also observed, reflecting the migratory ability of the species. This basic information on spatial ecology is required for formulating effective management and conservation strategies for the species., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Acne vulgaris is an inflammatory skin disease that shows chronic effects in adolescents and young adults. Its impact on quality of life (QoL) often extends beyond the physical symptoms, influencing social interactions and reducing self-confidence. Although these impacts are widely acknowledged, they are seldom given sufficient attention or assessed in depth with standardized measures like the Dermatology Life Quality Index (DLQI). This study aimed to evaluate the extent to which acne interferes with QoL in young adults using DLQI scores and its associations with demographic and clinical factors., Methods: This hospital-based, cross-sectional study was conducted between October 2023 and December 2023 at Gayatri Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam, India. The study population comprised 200 participants aged 16-28 diagnosed with acne. Data collected included demographic factors (age, sex), clinical features (acne grade, duration, site, scars, hyperpigmentation, and skin type), and DLQI scores. Acne severity was classified from grade I to IV, and the relationships between DLQI scores and clinical/demographic variables were analyzed using chi-squared tests, with statistical significance set at p<0.05. Data analysis was performed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States)., Results: The mean age of participants was 19.6 years, with women comprising 68.5% of the study population. Acne grade II was the most common, and the average DLQI score was 11.14, indicating a noticeable impact on QoL. Nearly half of the participants (48%) reported a "very large" effect on QoL. Highly significant associations were found between duration of acne, post-acne hyperpigmentation, and grade of acne with DLQI scores (all p<0.001), showing that longer duration, hyperpigmentation, and higher grades of acne significantly worsened QoL. Significant associations were also observed for site of acne and acne scars (both p<0.05), with multiple acne sites and severe scarring linked to greater negative impacts on DLQI scores. Grade III-IV acne were especially tied to bigger hits on QoL. Additionally, site of acne and acne scars were highly associated with acne grade (p<0.001). Factors such as having acne for over two years, oily skin, acne across multiple sites (face, chest, and back), and post-acne hyperpigmentation contributed to higher DLQI scores., Conclusion: Acne vulgaris has a marked impact on QoL in young adults, especially those with severe, persistent, and extensive cases. Focusing on both the physical and mental aspects of acne in treatment could make a difference. Further multi-center studies with larger samples are recommended to generalize these findings and help create targeted interventions., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee of Gayatri Vidya Parishad Institute of Health Care and Medical Technology issued approval GVPIHCMT/IEC/20231031/03. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was funded by the Undergraduate Student Research Scholarship (UGSRS) from Dr. NTR University of Health Sciences, Vijayawada. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Veldi et al.)

Asthma is considered severe if it remains uncontrolled despite optimal conventional therapy, characterised by poor symptom control, frequent exacerbations and increased exposure to systemic corticosteroids. This has a significant impact on morbidity, mortality and healthcare resource utilisation. Recent advances in the understanding of asthma heterogeneity and immunopathogenesis have helped delineate precise disease pathways. The discovery of these pivotal pathways has led to the development of highly effective biologic therapies. Currently available asthma biologics target immunoglobulin E, interleukin (IL)-5/IL-5Rα, IL-4Rα and thymic stromal lymphopoietin. Identification of specific asthma phenotypes, utilising easily measurable biomarkers, has paved the way towards personalised and precision asthma management. Biologic therapies play a significant role in reducing exacerbations, hospitalisations and the need for maintenance systemic steroids, while also improving the quality of life in patients with severe asthma. The evidence for their clinical efficacy comes from randomised controlled trials (RCTs), extension studies, metanalyses and real-world data. This review synthesises findings from early, pivotal RCTs and subsequent studies following the approval of biologics for severe asthma. The safety and efficacy data from these studies, completed in a variety of settings, provide practical perspectives on their application and enhance their generalisability., Competing Interests: Conflict of interest: All authors report no conflicts of interest associated with the publication of this manuscript and there is no financial support for this work. Outside of this work: B. Gyawali has nothing to disclose. S.N. Georas reports research grants from NIH, consulting fees from AstraZeneca, ARS Pharma, Chiesi inc, Amarin Pharma and GH Research, payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Exchange CME, and acts as Chair of PreciSE Asthma Network steering committee (NIH/NHLBI) and Chair of DSMB for COPDGene study (NIH/NHLBI). S. Khurana reports research grants from the American Lung Association, royalties from Springer Nature, CME honoraria from CHEST/ACCP, European Respiratory Society, Healio, NYU, Cleveland Clinic, Thai Asthma Council, Eastern Pulmonary Conference, and serves as Regent-at-large for CHEST and Chair of DSMB for an NIH study., (Copyright ©The authors 2025.)

Mobile Ad Hoc Networks (MANETs) are increasingly replacing conventional communication systems due to their decentralized and dynamic nature. However, their wireless architecture makes them highly vulnerable to flooding attacks, which can disrupt communication, deplete energy resources, and degrade network performance. This study presents a novel hybrid deep learning approach integrating Convolutional Neural Networks (CNN) with Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) architectures to effectively detect and mitigate flooding attacks in MANETs. To optimize the model's efficiency, a unique DECEHGS algorithm combining Differential Evolution and Evolutionary Population Dynamics techniques is employed, enhancing both convergence and performance. The proposed model demonstrates significant improvements over existing methods, achieving an accuracy of 95%, a 12% increase in packet delivery ratio, and a 20% reduction in routing overhead compared to traditional techniques. These advancements underline the model's superiority in detecting malicious nodes, conserving energy, and ensuring reliable network performance. The comprehensive evaluation using MATLAB R2023a validates the proposed approach as an effective and energy-efficient solution for enhancing MANET security., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The submitted work is original and has not been published elsewhere in any form or language., (© 2024. The Author(s).)

Background: Telemedicine may help improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied., Methods: This was a single-centre randomised clinical trial of unselected adult surgical patients. Patients were randomised to receive usual care or decision support from a telemedicine service, which provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews and physiological alerts. ORs were randomised 1:1. The co-primary outcomes were 30-day all-cause mortality, respiratory failure, acute kidney injury, and delirium in the intensive care unit, analysed by intention to treat., Results: Between July 1, 2019, and January 31, 2023, a total of 35,302 patients were randomised to receive telemedicine support, with 36,625 receiving usual care. Telemedicine clinicians provided review in 11,812/35,302 cases, with alerts delivered to 2044/35,302 patients. Telemedicine support had no effect on any of the co-primary outcomes. Within 30 days, 630/35,302 (1.8%) patients randomised to telemedicine died within 30 days, compared with 649/36,625 (1.8%) receiving usual care (relative risk [RR]1.01, 95% confidence interval [CI] 0.87-1.16, P=0.98). Telemedicine support did not alter postoperative respiratory failure [telemedicine 1071/33,996 (3.2%) vs usual care 1130/35,236 (3.2%), RR 0.98, 95% CI 0.88-1.09, P=0.98], acute kidney injury [telemedicine 2316/33 251 (7.0%) vs usual care 2432/34,441 (7.1%); RR 0.99, 95% CI 0.92-1.06, P=0.98], or delirium [telemedicine 1264/3873 (32.6%) vs usual care 1298/4044 (32.1%), RR 1.02, 95% CI 0.94-1.10, P=0.98]., Conclusions: In this large randomised clinical trial, intraoperative telemedicine decision support using real-time alerts and case reviews had no impact on adverse postoperative outcomes., Clinical Trial Registration: NCT03923699., Competing Interests: Declaration of interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)