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Nikhil Gopalakrishnan,1 Shankar Prasad Nagaraju,2 Neenu Mariam George,3 Sulatha V Bhandary,4 Yogish S Kamath,4 Sushan Shankar Shetty,4 Soumya S Nair,4 Neetha IR Kuzhuppilly,4 Shailaja S4 1Department of Retina, Narayana Nethralaya, Bangalore, Karnataka, India; 2Department of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India; 3Aravind Eye Hospital, Coimbatore, Tamil Nadu, India; 4Department of Ophthalmology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, IndiaCorrespondence: Shailaja S; Sushan Shankar Shetty, Department of Ophthalmology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, 576104, India, Tel +91 9686125861, Fax +91-820-2571934, Email shailaja.s@manipal.edu; sushan.shetty@manipal.eduPurpose: To correlate the optical coherence tomography (OCT) based morphological patterns of diabetic macular edema (DME) and prognostic biomarkers with severity of anaemia in patients with diabetic kidney disease (DKD).Patients and Methods: Single centre, observational cross sectional study of 42 eyes of 42 patients with DME and DKD. Eyes were divided into 2 groups: Group A (Haemoglobin level above 10 g% and group B with haemoglobin less than 10 g%). The OCT pattern and biomarkers were compared between the two groups.Results: Mean age of the patients was 56.9 ± 8.1 (range 42– 79). Out of 42 participants, 22 patients had hemoglobin level more than 10g%(group A) while 20 patients had hemoglobin less than 10g%(Group B). The most common morphological pattern seen was combination of cystoid macular edema (CME) with diffuse retinal thickening (DRT) in both groups. Disruption of the external limiting membrane (ELM) and ellipsoid zone (EZ) was found to be associated with lower hemoglobin levels (p= 0.0155 and p= 0.0154 respectively). None of the other OCT biomarkers showed correlation with hemoglobin levels.Conclusion: CME with DRT is the most common morphological pattern of macular edema seen in DKD patients with anemia. ELM-EZ disruption can be considered as important biomarker of anaemia in patients with DKD.Keywords: anemia, central foveal thickness, external limiting membrane, cystoid macular edema, ellipsoid zone

Background Severe hemophilia A is managed with factor VIII replacement or hemostatic products that stop or prevent bleeding. Data on gene therapy with hematopoietic stem-cell (HSC)–based expression of factor VIII for the treatment of severe hemophilia A are lacking. Methods We conducted a single-center study involving five participants 22 to 41 years of age with severe hemophilia A without factor VIII inhibitors. Autologous HSCs were transduced with CD68-ET3-LV — a lentiviral vector including a new F8 transgene (ET3) with a myeloid-directed CD68 promoter — either without transduction enhancer (group 1) or with transduction enhancer (group 2). Transduced HSCs were transplanted into recipients after myeloablative conditioning. The treatment was assessed for safety (engraftment and regimen-related toxic effects) and efficacy (factor VIII activity and annualized bleeding rate). Results Participants received CD68-ET3-LV–transduced autologous CD34+ HSCs at doses of 5.0×106 to 6.1×106 per kilogram of body weight. The vector copy numbers in the final drug product were 1.0 and 0.6 copies per cell for the two participants in group 1 and 1.5, 0.6, and 2.2 copies per cell for the three participants in group 2. The duration of severe neutropenia was 7 to 11 days and of severe thrombocytopenia was 1 to 7 days. The median factor VIII activity level, measured with the use of a one-stage assay, after day 28 until the last follow-up visit was 5.2 IU per deciliter (range, 3.0 to 8.7) and 1.7 IU per deciliter (range, 1.0 to 4.0) with a peripheral-blood vector copy number of 0.2 and 0.1 copies per cell, respectively, in the two group 1 participants, and 37.1 IU per deciliter (range, 18.3 to 73.6), 19.3 IU per deciliter (range, 6.6 to 34.5), and 39.9 IU per deciliter (range, 20.6 to 55.1) with a peripheral-blood vector copy number of 4.4, 3.2, and 4.8 copies per cell, respectively, in the three group 2 participants. The annualized bleeding rate was zero for all five participants over a cumulative follow-up of 81 months (median follow-up, 14 months; range, 9 to 27). Conclusions Gene therapy for hemophilia A with the use of lentiviral vector–transduced autologous HSCs resulted in stable factor VIII expression, with factor VIII activity correlating to vector copy number in the peripheral blood. [ABSTRACT FROM AUTHOR]

Objectives: To assess the blood lead level (BLL) of school children in 10 cities of India., Methods: This multi-centric cross-sectional study enrolled participants from randomly selected schools. Data on demographic details, socioeconomic status (SES) and anthropometric indicators was collected. Samples were collected for assessment of lead level in blood. Inductively coupled plasma-optical emission spectrometry technique was used to assess BLL., Results: From April 2019 through February 2020, 2247 participants were recruited from sixty schools (62.6% government schools) with equal gender distribution. The overall median (interquartile range) BLL was 8.8 (4.8, 16.4) µg/dl. The highest median (interquartile range) BLL was in Manipal 30.6 (23.0, 46.7) and lowest in Dibrugarh 4.8 (3.2, 7.0). Overall, 82.5% of participants had BLL above ≤4 µg/dl. Significant negative correlation was observed between BLL and SES (correlation= -0.24, p <0.001), anthropometric indicators (correlation= -0.11, p <0.001), hemoglobin level (correlation= -0.045, p = 0.03) and multivariate regression model showed association with gender, SES and anthropometric indicators., Conclusions: BLL are elevated in urban school going children and there is intercity variation. Hence, urgent focus is needed to reduce exposure to lead in India., Competing Interests: Declarations. Ethical Approval and Consent: This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects/patients were approved by the Institutional Ethics Committees for Sher-i-Kashmir Institute of Medical Sciences [approval reference number (ARN): IEC/SKIMS Protocol # RP 175/2018], PGIMER, Chandigarh (ARN: PGI/IEC/2019/000152), All India Institute of Medical Sciences, Jodhpur (ARN: AIIMS/IEC/2017/765), King George's Medical University (ARN: 9334/Ethics/R.Cell-16), All India Institute of Medical Sciences, Patna (ARN: IEC/AIIMS/PAT/153/2017), Assam Medical College (ARN: AMC/EC/1430), Kalinga Institute of Medical Sciences, Bhubaneswar (ARN: KIMS/KIIT/IEC/112/2016), Kasturba Medical College (ARN: IEC:388/2019), MS Ramaiah Medical College and Hospital, Bangalore (ARN: MSRMC/EC/AP-02/02-2019) and Medical College, Thiruvananthapuram (ARN: HEC.No.04/34/2019/MCT). Written informed consent was obtained from parents of all study participants. The study was prospectively registered with Clinical Trial Registry of India. Registration number is: CTRI/2019/02/017783 [Clinical Trials Registry - India (CTRI)]. Conflict of Interest: None., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Cataract surgery is followed by post-operative eye drops for a duration of 4-6 weeks. The multitude of ocular barriers, coupled with the discomfort experienced by both the patient and their relatives in frequently administering eye drops, significantly undermines patient compliance, ultimately impeding the recovery of the patient. This study aimed to design and develop an ocular drug delivery system as an effort to achieve a drop-free post-operative care after cataract surgery. An implant was prepared containing a biodegradable polymer Poly-lactic-co-glycolic acid (PLGA), Dexamethasone (DEX) as an anti-inflammatory drug, and Moxifloxacin(MOX) as an antibiotic. Implant characterization and drug loading analysis were conducted. In vitro drug release profile showed that the release of the two drugs are correlated with the clinical prescription for post operative eye drops. In vivo study was conducted on New Zealand albino rabbits where one eye underwent cataract surgery, and the drug delivery implant was inserted into the capsular bag after placement of the synthetic intraocular lens (IOL). Borderline increase in the intraocular pressure (IOP) was noted in the test sample group. Slit-lamp observations revealed no significant anterior chamber reaction in all study groups. Histopathology study of the operated eye revealed no significant pathology in the test samples. This work aims at developing the intra ocular drug delivery implant which will replace the post-operative eye drops and help the patient with the post-operative hassle of eye drops., Competing Interests: Declarations. Ethics approval: All institutional and national guidelines for the care and use of laboratory animals were followed. The approval was granted by the Institutional Animal Ethics Committee (AIEC) of Kasturba Medical College, Manipal (IAEC/KMC/36/2018). Consent for publication: All the authors have approved the final manuscript and agreed for its publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The effect of temporary blood flow arrest during endovascular thrombectomy for acute ischemic stroke is uncertain due to the lack of evidence from randomized controlled trials. We aimed to investigate whether temporary blood flow arrest during endovascular thrombectomy using a balloon guide catheter improves intracranial vessel recanalization compared with nonflow arrest., Methods: The ProFATE trial (Proximal Blood Flow Arrest During Endovascular Thrombectomy) was a multicenter, randomized, participant- and outcome-blinded trial at 4 thrombectomy centers in the United Kingdom. Adults with acute ischemic stroke due to anterior circulation large vessel occlusion were randomly assigned (1:1) by a central, Web-based program with a minimization algorithm to undergo thrombectomy with temporary proximal blood flow arrest or nonflow arrest during each attempt. The primary outcome was the proportion of participants achieving near-complete/complete vessel recanalization (expanded Thrombolysis in Cerebral Infarction score of 2c or 3) at the end of the thrombectomy procedure, adjudicated by a blinded independent imaging core laboratory. Analyses were performed on the intention-to-treat population, adjusted for age, IV thrombolysis, onset-to-randomization time, Alberta Stroke Program Early CT Score, occlusion site, randomization site, and National Institutes of Health Stroke Scale., Results: Between October 10, 2021, and June 27, 2023, we recruited 134 participants, of whom 131 participants (mean age, 75 years; 62 [47%] women and 69 [53%] men) were included in the final analysis. Sixty-six participants were allocated to the temporary blood flow arrest group and 65 to the nonflow arrest group. The proportion of participants with an expanded Thrombolysis in Cerebral Infarction 2c/3 score at the end of the endovascular procedure was 74.4% (49/66) in the flow arrest group and 70.8% (46/65) in the nonflow arrest group (adjusted odds ratio, 1.07 [95% CI, 0.45-2.55]; P =0.88). Among the prespecified secondary efficacy outcomes, a lower rate of emboli to a new vascular territory occurred in the blood flow arrest group compared with the nonflow arrest group (1.5% versus 12.3%; adjusted odds ratio, =0.04 [95% CI, 0.01-0.53]; P =0.014) and a higher rate of complete recanalization (expanded Thrombolysis in Cerebral Infarction score, 3) after the first attempt in the flow arrest group versus the nonflow arrest group (33.0% versus 15.3%; adjusted odds ratio, =3.80 [95% CI, 1.40-10.01]; P =0.007). No between-group differences were identified for the remaining procedural or clinical efficacy (modified Rankin Scale at 90 days) or safety outcomes (worsening of the stroke severity at 24 hours, adverse events, symptomatic intracranial hemorrhage, or mortality)., Conclusions: Among patients presenting with anterior circulation large vessel occlusion acute ischemic stroke, temporary proximal blood flow arrest during endovascular thrombectomy, compared with nonflow arrest, did not significantly improve the near-complete/complete vessel recanalization (expanded Thrombolysis in Cerebral Infarction score, 2c-3) at the end of the procedure. Larger randomized controlled trials are warranted to confirm or refute a clinically significant treatment effect of temporary flow arrest on the functional outcome following endovascular thrombectomy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05020795., Competing Interests: Dr Dhillon reports grants from Nottingham University Hospitals National Health Service Trust and The Royal College of Radiologists. Dr Bhogal reported travel support from Perflow; stock options in Perfuze and Toro, stock holdings in Ceroflo, compensation from Cerenovus, Balt USA, LLC, Vesalio, Q’apel, Phenox Inc, and Brainomix for consultant services. Dr Booth reported travel support from Balt, consultant services from Medtronic, and core laboratory services from Microvention. The other authors report no conflicts.

Insects exhibit remarkable adaptability to a wide range of environmental stressors, including temperature fluctuations, pathogens, and changes in diet. This adaptability is often driven by epigenetic processes, which regulate gene expression without altering the underlying DNA sequence. This review provides a comprehensive overview of these epigenetic processes in insect adaptation, highlighting their impact on development, behaviour, and stress resilience. Understanding these mechanisms is essential for pest management and conservation efforts, offering insights into the rapid adaptive capacity of insects. By examining recent studies on epigenetics in insects, we aim to elucidate the molecular underpinnings of their adaptation and suggest future research directions in this evolving field., 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 Inc. All rights reserved.)

Purpose: To describe the use of crescentic autograft as a graft salvage technique for inadvertently undersized donor lenticules in superficial anterior lamellar keratoplasty (SALK)., Methods: A prospective interventional study included 5 eyes of 4 patients who underwent SALK and had an inadvertently undersized donor lenticule. The described technique involves the preparation of a crescent-shaped graft from the host lenticule itself that is matched to fit into the remaining bare recipient stromal bed., Results: At 6-week follow-up, the crescentic autograft was uniformly epithelized along with the donor tissue. There were no incidences of graft dehiscence, rejection, or infection., Conclusions: Crescentic autograft from the host lenticule offers a simple, easy-to perform, and unique technique to manage cases of undersized donor lenticules in SALK with no additional risks., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Osteoarthritis is the prevailing form of inflammatory condition in joints of adults and the aging population, leading to long-term disability and chronic pain. Current therapeutic options have variable therapeutic efficacy and/or several side effects., Methods: A randomized, placebo-controlled, double-blind clinical trial was conducted in 62 participants using a nutraceutical [standardized Boswellia serrata Roxb. gum resin (300 mg) and Apium graveolens L. seed extract (250 mg)], to determine its safety and efficacy for supporting cartilage health and reduction in knee osteoarthritis symptoms. All participants were assessed for physical function and pain with the help of WOMAC, VAS, Physicians' Global Assessment for the six-minute walk test/pain. Knee X-ray, KOOS questionnaire score, and FACIT-F score were assessed. Additionally, inflammatory, cartilage degeneration and regeneration biomarkers in serum and urine were evaluated at baseline and after 90 days of treatment., Results: Oral administration of the nutraceutical resulted in prolonged symptomatic relief with reduced pain, stiffness, and swelling. Inflammatory (serum IL-7, IL-1, IL-6, hs-CRP, TNF-α, ESR) and cartilage degeneration biomarkers (serum CTX-II, COMP, MMP-3 and urinary CTX-II) were decreased in the nutraceutical group compared to baseline and placebo. Furthermore, serum N-propeptide of collagen IIA (PIIANP) and procollagen-type-C propeptide (PIICP) levels were increased in the nutraceutical group, suggesting collagen synthesis contributing to cartilage regeneration. At given doses for 90 days, there were no adverse effects based on the clinical examination, biochemical, hematological, and ECG analysis., Conclusions: Taken together, the combination of Boswellia and celery could be a safe and promising herbal nutraceutical option for managing osteoarthritis and cartilage health effectively., Competing Interests: Declarations. Conflict of Interest: RestorCel™ is marketed by Phytoveda Pvt. Ltd., Mumbai, India which funded this study. CG, AM, DM and SN are employees of Phytoveda Pvt. Ltd., Mumbai, India and Viridis Biopharma Pvt. Ltd., Mumbai, India. However, these authors had no role in the conduct of the trial or analysis of results. The clinical trial was conducted by an external Contract Research Organisation (CRO), MPREX Healthcare Pvt. Ltd., Pune, India, who analyzed the results themselves along with the clinicians conducting the study in this multicentric trial (NV, RA, DGD, HP, GG, DN)., (© 2025. The Author(s).)

Background: Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis., Methods: Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality., Results: 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I 2 =48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P<0.0001, I 2 =20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I 2 =76%) were not significantly different., Conclusion: The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT., Competing Interests: Competing interests: TNN reported research support from Medtronic and SVIN; advisory board with Idorsia. PB reported travel support from Perflow; compensation from Cerenovus, Balt USA, LLC, Vesalio, Phenox Inc, and Brainomix for consultant services. BG has received grants from the French Ministry of Health and is the primary investigator of the TITAN, DIRECT ANGIO, and IA-RESCUE trial, and consulting fees from Air Liquide, MIVI, Medtronic, Boerhinger Ingelheim, Microvention, and Penumbra. JPA is supported, in part, by an NIHR Health and Care Research Scholarship. KK is a recipient of a research fellowship awarded by the Nottingham University Hospitals NHS Trust. There are no other disclosures or competing interests declared by the remaining authors., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Accurate assessment of cardiovascular disease (CVD) risk is crucial for effective prevention and resource allocation. However, few CVD risk estimation tools consider social determinants of health (SDoH), despite their known impact on CVD risk. We aimed to estimate 10-year CVD risk in the Eastern Caribbean Health Outcomes Research Network Cohort Study (ECS) across multiple risk estimation instruments and assess the association between SDoH and CVD risk., Methods: Five widely used CVD risk estimation tools (Framingham and WHO laboratory, both laboratory and non-laboratory-based, and ASCVD) were applied using data from ECS participants aged 40-74 without a history of CVD. SDoH variables included educational attainment, occupational status, household food security, and perceived social status. Multivariable logistic regression models were used to compare differences in the association between selected SDoH and high CVD risk according to the five instruments., Findings: Among 1,777 adult participants, estimated 10-year CVD risk varied substantially across tools. Framingham non-lab and ASCVD demonstrated strong agreement in categorizing participants as high risk. Framingham non-lab categorized the greatest percentage as high risk, followed by Framingham lab, ASCVD, WHO lab, and WHO non-lab. Fifteen times more people were classified as high risk by Framingham non-lab compared with WHO non-lab (31% vs 2%). Mean estimated 10-year risk in the sample was over 2.5 times higher using Framingham non-lab vs WHO non-lab (17.3% vs 6.6%). We found associations between food insecurity, those with the lowest level compared to the highest level of education, and non-professional occupation and increased estimated CVD risk., Interpretation: Our findings highlight significant discrepancies in CVD risk estimation across tools and underscore the potential impact of incorporating SDoH into risk assessment. Further research is needed to validate and refine existing risk tools, particularly in ethnically diverse populations and resource-constrained settings, and to develop race- and ethnicity-free risk estimation models that consider SDoH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Schwartz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Placement of right precordial leads in higher intercostal spaces (EEP-ECG) improves the detection of Brugada Syndrome (BrS). Given the potential difficulty of lead placement and the transient nature of BrS ECG patterns, we developed a model to predict EEP-ECG from a standard 12‑lead ECG., Objective: To create and validate a model that derives EEP-ECG leads from a standard 12‑lead ECG., Methods: We recorded 16 channel ECGs (12 standard leads plus 4 elevated leads in the 2nd and 3rd intercostal spaces) using two identical ECG recorders. A linear regression model was developed from the ECG data in the training group. This model was subsequently used to predict EEP-ECG in the validation group. Accuracy of the model was evaluated by comparing the derived leads to the actually recorded leads. Comparison was done using correlation coefficients and visual assessment by two cardiologists on a scale of 1-3., Results: The study included 42 participants (22 in the training group, 20 in the validation group), including 8 BrS patients. The model showed strong correlation (r > 0.85) between actual and predicted leads for 76 of 80 leads. Visual assessment yielded an average score of 2.44 ± 0.68. The model has been made available as an online tool for automatic derivation of EEP-ECG from a standard 12‑lead ECG (http://eep-ecg.in/)., Conclusion: We developed a linear model to derive elevated ECG leads from standard 12‑lead ECGs. The model predicts EEP-ECG with reasonable accuracy. This model can be useful in diagnosing BrS in new or existing ECGs., Competing Interests: Declaration of competing interest None for any of the authors., (Copyright © 2025. Published by Elsevier Inc.)

Objective: Skeletal muscle fat infiltration (myosteatosis) increases with age and is an emerging risk factor for dementia. We aimed to determine the association between myosteatosis and cognitive decline among middle-aged White and Black Americans., Methods: Data were on men (n=1,080; 41.9% Black) and women (n=1,432; 49.0% Black) from the CARDIA study. CT-measured abdominal intermuscular fat (IMAT) volume was assessed at baseline. Cognition was assessed by Digit Symbol Substitution (DSST), Rey Auditory Verbal Learning (RAVLT), and Stroop Test at baseline and 5-year follow-up. Multivariable linear regression was used to assess associations of IMAT with cognitive change., Results: Participants were aged 50.2 (3.6) years and had IMAT of 2.3 (1.6) cm 3 , 5-year change in DSST of -2.8% (21.8), RAVLT 2.8% (17.5) and Stroop 6.5% (49.5). Greater IMAT was associated with steeper DSST decline (β =-0.52 points per SD, p-value=0.035), but not with Stroop or RAVLT. Stratified by race, greater IMAT predicted DSST decline among White (β =-0.73, p =0.044), but not Black (β =-0.44, p =0.195), participants., Conclusions: Abdominal myosteatosis may be a novel risk factor for decline in psychomotor speed, especially in middle-aged Whites. Further research on mechanisms, including metabolic mediators, is warranted to understand myosteatosis's role in mid-life cognitive decline.

Objective: To assess the association of dietary fatty acids with asthma in Indian school children., Methods: Children aged 6-16 years were enrolled from randomly selected urban schools in 10 cities. The International Study on Asthma and Allergies in Childhood Phase III Questionnaire was used to assess the prevalence of asthma. Three-day dietary intake data was obtained using 24-hr dietary recall method. Intake of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and trans fatty acids (TFA) was calculated using DIETSOFT software., Results: Between April 2019 and February 2020, 2428 participants were recruited (49.8% males) from 60 schools. The prevalence of asthma was 2.4% (95 % CI 1.8, 3.1). The mean (SD) intake of various FA (g per kg) were 0.19 (0.22) for SFA,18 (0.22) for MUFA, 0.17 (0.18) for PUFA and 0.003 (0.005) for TFA. SFA intake in those with asthma was 0.35 (0.34) as compared to 0.18 (0.21) without asthma (P value < 0.001). On unconditional logistic regression, dietary intake of TFA was associated with asthma in children [OR 2.16 (95% CI 1.27, 3.68)]., Conclusion: Dietary intake of SFA and TFA is associated with asthma in children.

To fully evaluate the atomic structure, and associated properties of materials using transmission electron microscopy, examination of samples from three non-collinear orientations is needed. This is particularly challenging for thin films and nanoscale devices built on substrates due to limitations with plan-view sample preparation. In this work, a new method for preparation of high-quality, site-specific, plan-view TEM samples from thin-films grown on substrates, is presented and discussed. It is based on using a dual-beam focused ion beam scanning electron microscope (FIB-SEM) system. To demonstrate the method, the samples were prepared from thin films of perovskite oxide BaSnO 3 grown on a SrTiO 3 substrate and metal oxide IrO 2 on a TiO 2 substrate, ranging from 20-80 nm in thicknesses using molecular beam epitaxy. While the method is optimized for the thin films, it can be extended to other site-specific plan-view samples and devices build on wafers. Aberration-corrected STEM was used to evaluate the quality of the samples and their applicability for atomic-resolution imaging and analysis., 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.)

Background: Verbal autopsy (VA) has been a crucial tool in ascertaining population-level cause of death (COD) estimates, specifically in countries where medical certification of COD is relatively limited. The World Health Organization has released an updated instrument (Verbal Autopsy Instrument 2022) that supports electronic data collection methods along with analytical software for assigning COD. This questionnaire encompasses the primary signs and symptoms associated with prevalent diseases across all age groups. Traditional methods have primarily involved paper-based questionnaires and physician-coded approaches for COD assignment, which is time-consuming and resource-intensive. Although computer-coded algorithms have advanced the COD assignment process, data collection in densely populated countries like India remains a logistical challenge., Objective: This study aimed to develop an Android-based mobile app specifically tailored for streamlining VA data collection by leveraging the existing Indian public health workforce. The app has been designed to integrate real-time data collection by frontline health workers and seamless data transmission and digital reporting of COD by physicians. This process aimed to enhance the efficiency and accuracy of COD assignment through VA., Methods: The app was developed using Android Studio, the primary integrated development environment for developing Android apps using Java. The front-end interface was developed using XML, while SQLite and MySQL were employed to streamline complete data storage on the local and server databases, respectively. The communication between the app and the server was facilitated through a PHP application programming interface to synchronize data from the local to the server database. The complete prototype was specifically built to reduce manual intervention and automate VA data collection., Results: The app was developed to align with the current Indian public health system for district-level COD estimation. By leveraging this mobile app, the average duration required for VA data collection to ascertainment of COD, which typically ranges from 6 to 8 months, is expected to decrease by approximately 80%, reducing it to about 1-2 months. Based on annual caseload projections, the smallest administrative public health unit, health and wellness centers, is anticipated to handle 35-40 VA cases annually, while medical officers at primary health centers are projected to manage 150-200 physician-certified VAs each year. The app's data collection and transmission efficiency were further improved based on feedback from user and subject area experts., Conclusions: The development of a unified mobile app could streamline the VA process, enabling the generation of accurate national and subnational COD estimates. This mobile app can be further piloted and scaled to different regions to integrate the automated VA model into the existing public health system for generating comprehensive mortality statistics in India., (©Harleen Kaur, Stuti Tripathi, Manjeet Singh Chalga, Sudhir K Benara, Amit Dhiman, Shefali Gupta, Saritha Nair, Geetha Menon, B K Gulati, Sandeep Sharma, Saurabh Sharma. Originally published in JMIR Formative Research (https://formative.jmir.org).)

Despite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (TF) binding and chromatin accessibility at context-specific cREs remain elusive. We introduce ChromBPNet, a deep learning DNA sequence model of base-resolution accessibility profiles that detects, learns and deconvolves assay-specific enzyme biases from regulatory sequence determinants of accessibility, enabling robust discovery of compact TF motif lexicons, cooperative motif syntax and precision footprints across assays and sequencing depths. Extensive benchmarks show that ChromBPNet, despite its lightweight design, is competitive with much larger contemporary models at predicting variant effects on chromatin accessibility, pioneer TF binding and reporter activity across assays, cell contexts and ancestry, while providing interpretation of disrupted regulatory syntax. ChromBPNet also helps prioritize and interpret regulatory variants that influence complex traits and rare diseases, thereby providing a powerful lens to decode regulatory DNA and genetic variation., Competing Interests: Competing interests: A.S. was a consultant for MyoKardia. W.J.G. is a consultant and equity holder for 10x Genomics, Nvidia, Guardant Health, Quantapore, and Ultima Genomics, and cofounder of Protillion Biosciences, and is named on patents describing ATAC-seq.. A.S is an employee of Insitro. S.N is an employee of Genentech. A.S.K is an employee of Ultima Genomics. V.R is an employee of Rockefeller University. A.K. is on the scientific advisory board of SerImmune, TensorBio, AINovo, is a consultant with Arcardia Science, Inari, Precede Biosciences, was a consultant with Illumina and PatchBio and has a financial stake in DeepGenomics, Immunai and Freenome.

Central serous chorioretinopathy (CSC) is a known side effect of systemic steroid therapy. The role of intravitreal steroids in causing CSC is controversial. We present two cases of acute CSC that developed after intravitreal steroid injections. One was a case of diabetic macular oedema; another was a case of branch retinal vein occlusion-related macular oedema. Both cases showed complete resolution of cystoid oedema after intravitreal triamcinolone acetonide injection, but there was a progressive increase in neurosensory detachment (NSD), leading to a suspicion of CSC. Fundus fluorescein angiography confirmed the diagnosis. The first case was treated with focal laser, and the second one was treated with oral eplerenone. There was complete resolution of NSD in both cases. This report adds to the evidence that intravitreal steroids can indeed cause acute CSC. A high index of suspicion for CSC should be maintained in cases where NSD increases following intravitreal steroid administration., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site. In vitro data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR in vivo when expressed in Methanosarcina acetivorans , an organism that does not normally possess this PTM. M. acetivorans strains expressing MgmA showed small, but significant, reductions in growth rates and yields on methylotrophic substrates. Structural characterization of the Ni(II) form of Gln-methylated M. acetivorans MCR revealed no significant differences in the protein fold between the modified and unmodified enzyme; however, the purified enzyme contained the heterodisulfide reaction product, as opposed to the free cofactors found in eight prior M. acetivorans MCR structures, suggesting that substrate/product binding is altered in the modified enzyme. Structural characterization of MgmA revealed a fold similar to other B12-dependent rSAMs, with a wide active site cleft capable of binding an McrA peptide in an extended, linear conformation.IMPORTANCEMethane plays a key role in the global carbon cycle and is an important driver of climate change. Because MCR is responsible for nearly all biological methane production and most anoxic methane consumption, it plays a major role in setting the atmospheric levels of this important greenhouse gas. Thus, a detailed understanding of this enzyme is critical for the development of methane mitigation strategies.

Yerba mate (YM, Ilex paraguariensis ) is an economically important crop marketed for the elaboration of mate, the third-most widely consumed caffeine-containing infusion worldwide. Here, we report the first genome assembly of this species, which has a total length of 1.06 Gb and contains 53,390 protein-coding genes. Comparative analyses revealed that the large YM genome size is partly due to a whole-genome duplication (Ip-α) during the early evolutionary history of Ilex , in addition to the hexaploidization event (γ) shared by core eudicots. Characterization of the genome allowed us to clone the genes encoding methyltransferase enzymes that catalyse multiple reactions required for caffeine production. To our surprise, this species has converged upon a different biochemical pathway compared to that of coffee and tea. In order to gain insight into the structural basis for the convergent enzyme activities, we obtained a crystal structure for the terminal enzyme in the pathway that forms caffeine. The structure reveals that convergent solutions have evolved for substrate positioning because different amino acid residues facilitate a different substrate orientation such that efficient methylation occurs in the independently evolved enzymes in YM and coffee. While our results show phylogenomic constraint limits the genes coopted for convergence of caffeine biosynthesis, the X-ray diffraction data suggest structural constraints are minimal for the convergent evolution of individual reactions., Competing Interests: FV, AH, CM, ES, LD, RO, GN, RA, GB, SR, PZ, DM, PS, GO, EC, MS, ND, SN, TB, AT No competing interests declared, (© 2025, Vignale, Hernandez Garcia et al.)

Significance: As the field of artificial intelligence evolves rapidly, these hallmarks are intended to capture fundamental, complementary concepts necessary for the progress and timely adoption of predictive modeling in precision oncology. Through these hallmarks, we hope to establish standards and guidelines that enable the symbiotic development of artificial intelligence and precision oncology., (©2024 American Association for Cancer Research.)

This case report describes an adult man in his 50s with a history of type 2 diabetes and previously well-controlled hypertension, who presented with uncontrolled hypertension, muscle weakness and fatigue. Biochemical testing revealed hypokalaemia. There was no evidence of renal/renovascular disease. Evaluation for primary hyperaldosteronism revealed suppressed renin concentration with low aldosterone levels. Detailed history taking revealed the daily consumption of three to four cups of liquorice root tea for 3 months. Glycyrrhetinic acid, a metabolite of glycyrrhizic acid found in liquorice, inhibits the 11 beta-hydroxysteroid dehydrogenase-2 (11β-HSD2 enzyme present at the renal tubule, leading to cortisol-mediated mineralocorticoid receptor activation. The diagnosis of liquorice-induced pseudohyperaldosteronism was made, and the discontinuation of liquorice with short-term use of mineralocorticoid receptor blockers led to normalisation of blood pressure and serum potassium. This case highlights the importance of considering the possibility of excess use of liquorice in the differential diagnosis of unexplained hypertension, especially in the context of low-renin hypertension., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: The incidence of mortality late in the pandemic, particularly after widespread vaccine availability, is not well understood. Herein, we elucidate the effect of this impact of the COVID pandemic as well as risk factors for mortality during it., Methods: The primary end point was death with a functioning graft with secondary endpoints of mortality rates in subgroups and at different time intervals during the pandemic., Results: Despite widespread vaccination, mortality rates for kidney transplant (KTx) recipients almost doubled during the COVID-19 era (6.40 deaths per 100 person years vs. 3.54 pre-COVID). Mortality increased in all racial/ethnic groups but increased more in Native Americans, Hispanics, and African Americans compared to non-Hispanic Caucasians. The highest mortality rate occurred during the Delta and Omicron time frames. In contrast to the general population, mortality was more evenly spread across age groups in KTx recipients., Conclusions: Mortality rates during the COVID-19 era were extremely high, more than doubling in some racial/ethnic groups. We conclude that the KTx population was a particularly vulnerable group during the COVID-19 era and suggests the need for further research into the management of variants in the future., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We present the case of a patient with a vestibular schwannoma (VS) who developed vascular complications following surgery and discuss the potential mechanisms. Additionally, we systematically searched the literature to identify citations on vascular and brain stem complications following VS surgery. We excluded the articles related to facial and vestibulocochlear nerve-related complications and other complications, such as headache, tinnitus, and ataxia. We also excluded the articles related to recurrent vestibular schwannoma because our article focuses on primary VS surgery-related complications due to vascular injury. We have clearly come a long way in managing vestibular schwannoma (VS) surgery over the past century. In the early twentieth century, VS surgery entailed high morbidity and mortality. The principles of microneurosurgery have improved the outcomes of surgery on VSs to a great extent. The current concept in modern VS surgery is maximal safe resection with minimal complications and minimal cranial nerve deficits. The management of VS has undergone a paradigm shift from reducing mortality to facial nerve preservation and the preservation of hearing. Surgery of the cerebellopontine (CP) angle requires a unique skill set and is a craft in that any iatrogenic damage can have devastating results on the neurovascular structures and brain stem in the vicinity. As with other neurosurgical procedures, the goal of VS surgery is to minimize complications, but complications are always possible, from the positioning of the patient under general anaesthesia to complications during the various steps of VS surgery. In spite of advancements in surgical techniques and better illumination provided by modern high-end microscopes, the surgical removal of large and giant vestibular schwannomas with good preservation of facial nerve function continues to be one of the most challenging operations in modern neurosurgery. The complexity of operating on the vestibular schwannoma is attributable not only to the difficult anatomy in the CP angle but also to the presence of multiple vital neurovascular structures and the brain stem in the vicinity. The various complications arising out of surgery for vestibular schwannomas range from one or more cranial nerve deficits to life-endangering complications associated with vascular and/or brain stem damage. The senior author, who has a personal experience with consecutively operating on 835 such cases of large and giant vestibular schwannoma, describes the clinical course following petrosal vein damage to a patient who underwent a standard retrosigmoid operation for a large vestibular schwannoma. We retrospectively analyse the critical management issues that could have reduced the unexpected morbidity resulting in a prolonged hospital stay., Competing Interests: Conflicts of Interest. None., (© 2025. The Author(s).)

Introduction: Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. The aim of this research was to compare the transcriptomes of common in vitro models of the human placenta compared to bulk human placental tissue., Methods: We performed differential gene expression analysis on publicly available transcriptomic data from 7 in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, Villous Explants, and Trophoblast Stem Cells) and compared to bulk placental tissue from 2 cohort studies (CANDLE and GAPPS) or individual trophoblast cell types derived from bulk placental tissue., Results: All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR<0.01) compared to the CANDLE and GAPPS placentas (Average DEGs = 10,624), and the individual trophoblast cell types (Average DEGs = 5413), indicating that there are vast differences in gene expression. Hierarchical clustering identified 54 gene clusters with distinct expression profiles across placental models, with 23 clusters enriched for specific KEGG pathways. Placental cell lines were classified by fetal sex based on expression of Y-chromosome genes that identified HTR-8/SVneo cells as female origin, while JEG-3, JAR, and BeWo cells are of male origin., Discussion: None of the models were a close approximation of the human bulk placental transcriptome, highlighting the challenges with model selection. To enable appropriate model selection, we adapted our data into a web application: "Comparative Transcriptomic Placental Model Atlas (CTPMA)"., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)