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GH30 xylobiohydrolases, an expanding enzyme category, need deeper insights for optimal use. The primary aim of this study was to characterize a new xylobiohydrolase, AcGH30A of GH30 family from Acetivibrio clariflavus. The gene encoding AcGH30A was cloned using pET28a(+) vector and expressed in E. coli BL21(DE3) cells. AcGH30A was purified by immobilized metal-ion affinity chromatography. SDS-PAGE analysis of AcGH30A showed molecular mass of ~58 kDa. AcGH30A showed optimum temperature 80 °C and optimum pH 7.0. AcGH30A was stable (maintaining >80 % of control activity) in pH range, 4-7 and temperature range, 30 °C -70 °C when incubated for 90 min. AcGH30A displayed melting temperature, 72 °C and half-life, 21 days at 4 °C. The enzyme activity of AcGH30A was enhanced by 10 mM Ca 2+ and Mg 2+ ions by 25 % and 21 %, respectively, whereas 10 mM Co 2+ , Zn 2+ , Fe 2+ , and Cu 2+ ions significantly reduced it. AcGH30A showed activity against various xylan polysaccharides displaying highest V max , 139 U.mg -1 and K M , 0.71 mg.ml -1 against 4-O-methyl glucuronoxylan under optimum conditions. TLC, HPLC and LC-MS analyses of AcGH30A hydrolyzed products from xylan substrates revealed the release of sole product, xylobiose, confirming it as an obligate xylobiohydrolase. AcGH30A being a highly thermostable enzyme can be potentially utlilized in various biotechnological applications., Competing Interests: Declaration of competing interest CMGAF is a financial beneficiary of the company that sells the enzyme that is described in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Upregulation of MYC is a hallmark of cancer, wherein MYC drives oncogenic gene expression and elevates total RNA synthesis across cancer cell transcriptomes. Although this transcriptional anabolism fuels cancer growth and survival, the consequences and metabolic stresses induced by excess cellular RNA are poorly understood. Herein, we discover that RNA degradation and downstream ribonucleotide catabolism is a novel mechanism of MYC-induced cancer cell death. Combining genetics and metabolomics, we find that MYC increases RNA decay through the cytoplasmic exosome, resulting in the accumulation of cytotoxic RNA catabolites and reactive oxygen species. Notably, tumor-derived exosome mutations abrogate MYC-induced cell death, suggesting excess RNA decay may be toxic to human cancers. In agreement, purine salvage acts as a compensatory pathway that mitigates MYC-induced ribonucleotide catabolism, and inhibitors of purine salvage impair MYC+ tumor progression. Together, these data suggest that MYC-induced RNA decay is an oncogenic stress that can be exploited therapeutically. Significance: MYC is the most common oncogenic driver of poor-prognosis cancers but has been recalcitrant to therapeutic inhibition. We discovered a new vulnerability in MYC+ cancer where MYC induces cell death through excess RNA decay. Therapeutics that exacerbate downstream ribonucleotide catabolism provide a therapeutically tractable approach to TNBC (Triple-negative Breast Cancer) and other MYC-driven cancers., (©2024 The Authors; Published by the American Association for Cancer Research.)

Tuberous sclerosis (TSC) is an autosomal dominant neurocutaneous disorder. This case highlights rare isolated neurologic finding in a TSC patient emphasizing the need for heightened suspicion even in the absence of any cutaneous findings and family history., Competing Interests: Authors declare no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Rabies is a neglected disease primarily related to dog-mediated transmission to humans. Accurate dog demographic and dynamic data are essential for effectively planning and evaluating population management strategies when designing interventions to prevent rabies. However, in Thailand, longitudinal survey data regarding dog population size are scarce. A school-based participatory research (SBPR) approach was conducted to survey owned dogs for one year in four high-risk provinces (Chiang Rai, Surin, Chonburi, and Songkhla) of Thailand, aiming to understand dog population dynamics and raise awareness about rabies. 'Pupify' mobile application was developed to collect data on dog population and observe the long-term population dynamics in this study. At the end of the data collection period, telephone interviews were conducted to gain insight into contextual perceptions and awareness regarding both animal and human rabies, as well as the social responsibility of dog owners in disease prevention and control. Among 303 high school students who registered in our study, 218 students reported at least one update of their dog information throughout the one-year period. Of 322 owned dogs from our survey, the updates of dog status over one year showed approximately 7.5 newborns per 100-dog-year, while deaths and missing dogs were 6.2 and 2.7 per 100-dog-year, respectively. The male to female ratio was approximately 1.8:1. Twenty-three students (10%) voluntarily participated and were interviewed in the qualitative study. The levels of rabies awareness and precautions among high-school students were relatively low. The high dropout rate of the survey was due to discontinuity in communication between the researcher and the students over the year. In conclusion, this study focused on using the SBPR approach via mobile application to collect data informing dog population dynamics and raising awareness regarding rabies in Thailand Other engaging platforms (e.g. Facebook, Instagram, Twitter, and other popular applications) is necessary to enhance communication and engagement, thereby sustaining and maintaining data collection. Further health education on rabies vaccination and animal-care practices via social media platforms would be highly beneficial. For sustainable disease control, engaging communities to raise awareness of rabies and increase dog owners' understanding of their responsibilities should be encouraged., (© 2024. The Author(s).)

Coronary obstruction (CO) is a potential pitfall for transcatheter aortic valve replacement (TAVR), especially in valve in valve procedures into degenerated surgical or transcatheter prostheses. Bioprosthetic leaflet modification techniques that incorporate electrosurgery are evolving as the preferred strategy to mitigate the risk of CO in high CO risk settings. The UNICORN method is proposed as a more predictable leaflet modification strategy than the earlier described BASILICA approach, but its proponents have hitherto mandated the use of a balloon-expandable valve (BEV) prosthesis. Many patients have small prostheses and therein face a significant risk of patient prosthesis mismatch with BEV in this setting. This risk may be curtailed if a self-expanding valve (SEV) prosthesis could be used. Herein described is a modified approach to allow for the utilization of SEV systems in this setting., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Understanding and characterizing the intrinsic properties of charge carrier transport across the interfaces in van der Waals heterostructures is critical to their applications in modern electronics, thermoelectrics, and optoelectronics. However, there are very few published cross-plane resistivity measurements of thin samples because these inherently 2-probe measurements must be corrected for contact and lead resistances. Here, we present a method to extract contact resistances and metal lead resistances by fitting the width dependence of the contact end voltages of top and bottom electrodes of different contact widths to a model based on current crowding. These contributions are then subtracted from the total 2-probe cross-plane resistance to obtain the cross-plane resistance of the material itself without needing multiple devices and/or etching steps. This approach was used to measure cross-plane resistivities of a (PbSe) 1 (VSe 2 ) 1 heterostructure containing alternating layers of PbSe and VSe 2 with random in-plane rotational disorder. Several samples measured exhibited a 4 order of magnitude difference between cross-plane and in-plane resistivities over the 6-300 K temperature range. We also reported the observation of charge density wave transition in the cross-plane transport of the (PbSe) 1 (VSe 2 ) 1 heterostructure. The device fabrication process is fully liftoff compatible, and the method developed enables the straightforward measurement of the resistivity anisotropy of most thin film materials with nm thicknesses.

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20 mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-mo treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20 mg/kg open label. Therefore, only results from the 2, 8, and 20 mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular volumetric bone mineral density (vBMD) from baseline at month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro-finite element (microFE)-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12 mo, there was a significant increase in mean (SE) failure load in the 20 mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20 mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p>05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20 mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Introduction: Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis., Methods: This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20 kg., Results: All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival., Conclusion: This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To assess the visual and clinical outcomes after bilateral implantation of the novel extended depth of focus (EDOF) (AcrySof IQ Vivity) intraocular lens (IOL) using a micromonovision strategy., Methods: This was a prospective interventional study at a tertiary care center. Twenty patients (40 eyes) underwent bilateral implantation of AcrySof IQ Vivity IOL. Twelve weeks postoperatively, both uncorrected vision and corrected vision were assessed. Uniocular and binocular defocus curves with and without correction were noted subjectively as well as objectively on I-trace. Contrast sensitivity was assessed with a FACT (Functional Acuity Contrast Testing) machine, and objective parameters like modulation transfer function and Strehl ratio were also measured on I-Trace. Subjective quality of vision using a subjective questionnaire was also evaluated., Results: The mean binocular postoperative uncorrected distance visual acuity in LogMAR was -0.03 ± 0.09, the uncorrected intermediate visual acuity was 0.03 ± 0.09, and the uncorrected near visual acuity was 0.28 ± 0.18. All defocus curves were smooth and broad with the uncorrected defocus curve (with the micromonovision strategy) better than the corrected defocus curve. The subjective depth of focus (DOF = 3.73) was more than objective DOF (1.93) (P < 0.05). Photopic contrast was better than mesopic at all frequencies. All aberrations increased at 5 mm pupil size compared to 3 mm pupil size and were statistically significant, except for the total eye spherical aberration, which shows no significant difference at 3 mm and 5 mm pupil size (P = 0.27). Spectacle independence for distance, intermediate, and near was achieved in 100%, 94.7%, and 94.7% cases in this study, respectively., Conclusions: Using the micromonovision strategy, the visual performance of this novel EDOF IOL was outstanding both subjectively and objectively., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT. Participants enrolled in the OPRA trial who underwent restaging MRI were eligible for inclusion in the present study. Radiologists classified participants as having clinical complete response (cCR), near-complete clinical response (nCR), or incomplete clinical response (iCR) based on restaging MRI at a mean of 8 weeks ± 4 (SD) after treatment. Oncologic outcomes according to MRI response category were assessed using Kaplan-Meier curves. Logistic regression analysis was performed to identify imaging characteristics associated with RD. Results A total of 277 participants (median age, 58 years [IQR, 17 years]; 179 male) who were randomized in the OPRA trial had restaging MRI forms completed. The median follow-up duration was 4.1 years. Participants with cCR had higher rates of organ preservation compared with those with nCR (65.3% vs 41.6%, log-rank P < .001). Five-year disease-free survival for participants with cCR, nCR, and iCR was 81.8%, 67.6%, and 49.6%, respectively (log-rank P < .001). The MRI response category also predicted overall survival (log-rank P < .001), distant recurrence-free survival (log-rank P = .005), and local regrowth (log-rank P = .02). Among the 266 participants with at least 2 years of follow-up, 129 (48.5%) had RD. At multivariable analysis, the presence of restricted diffusion (odds ratio, 2.50; 95% CI: 1.22, 5.24) and abnormal nodal morphologic features (odds ratio, 5.04; 95% CI: 1.43, 23.9) remained independently associated with RD. Conclusion The MRI response category was predictive of organ preservation and survival. Restricted diffusion and abnormal nodal morphologic features on restaging MRI scans were associated with increased likelihood of residual tumor. ClinicalTrials.gov identifier: NCT02008656 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Milot in this issue.

Nephroureterectomy is currently the criterion-standard treatment for high-grade upper tract urothelial carcinoma (UTUC). Current guidelines and expert opinions propose some exceptions to this approach based on patient characteristics, disease status, and function of the contralateral kidney. We present a rare case of a patient with horseshoe kidney, bilateral large nephrolithiasis, high-grade UTUC in one moiety, and relative parenchymal thinning of the contralateral side. The patient was treated with a percutaneous, minimally invasive, nephron sparing approach. The patient also had intracollecting system instillations of gemcitabine and docetaxel. Minimally invasive percutaneous resection of high-grade UTUC is a safe procedure in select cases. Current guidelines may not apply to all patients; unique scenarios with UTUC may require personalized decision-making and treatment at specialized centers., Competing Interests: No conflict of interest has been declared by the authors., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Diabetic mellitus (DM) is characterized by hyperglycaemia and defective macromolecular metabolism, arising from insulin resistance or lack of insulin production. The present study investigates the potential of artemisinin, a sesquiterpene lactone isolated from Artemisia annua , to exert anti-diabetic and antioxidant effects through modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway. Our computational analyses demonstrated a high binding affinity of artemisinin with proteins belonging to the PI3K/AKT signalling cascade. α-Amylase and α-glucosidase studies revealed a notable increase in inhibition percentages with artemisinin treatment across concentrations ranging from 10 to 160 µM. A similar significant ( p  < 0.05) dose-dependent inhibition of free radicals was observed for the in vitro anti-oxidant assays. Further, toxicological profiling of artemisinin in the in vivo zebrafish embryo-larvae model from 4 to 96 h post-fertilization (hpf) did not exhibit any harmful repercussions. In addition, gene expression investigations confirmed artemisinin's potential mechanism in modulating hyperglycaemia and oxidative stress through the regulation of the PI3K/AKT pathway. Overall, our investigation suggests that artemisinin can be used as a therapeutic intervention for diabetes and oxidative stress, opening up opportunities for future investigation in clinical settings., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04050-2., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: To report on adverse events during magnetic resonance imaging (MRI) in patients with external fixators., Methods:  ., Design: Retrospective case series., Setting: Two Level 1 trauma centers., Patient Selection Criteria: Patients with external fixators on the appendicular skeleton or pelvis undergoing MRI between January 2005 and September 2023., Outcome Measures and Comparisons: Adverse events, defined as any undesirable event associated with the external fixator being inside or outside the MRI bore during imaging, including (subjective) heating, displacement or pullout of the external fixator, or early MRI termination for any reason., Results: A total of 97 patients with 110 external fixators underwent at least one MRI scan with an external fixator inside or outside of the MRI bore. The median age was 51 years (interquartile range: 39-63) and 56 (58%) were male. The most common external fixator locations were the ankle (24%), knee (21%), femur (21%), and pelvis (19%). The median duration of the MRI was 40 minutes (interquartile range: 26-58), 86% was performed using 1.5-Tesla MRI, and 14% was performed using 3.0-Tesla MRI. Ninety-five percent of MRI was performed for the cervical spine/head. Two MRI scans (1.6%), one of the shoulder and one of the head and cervical spine, with the external fixator outside of the bore were terminated early because of patient discomfort. There were no documented events of displacement or pullout of the external fixator., Conclusions: These findings suggest that MRI scans of the (cervical) spine and head can be safely obtained in patients with external fixators on the appendicular skeleton or pelvis. Given the low numbers of MRI scans performed with the external fixator inside the bore, additional studies are necessitated to determine the safety of this procedure. The results from this study can aid orthopaedic surgeons, radiologists, and other stakeholders in developing local institutional guidelines on MRI scanning with external fixators in situ., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: T. V. Ly reports honoraria from the Arbeitsgemeinschaft fur Osteosynthesefragen foundation and consulting fees from DePuy Synthes (Warsaw, Indiana). A. Aneja reports honoraria from the Arbeitsgemeinschaft fur Osteosynthesefragen foundation and research support from the Orthopaedic Trauma Association, American Orthopaedic Foot and Ankle Society, and United States Department of Defense. The remaining authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The endoplasmic reticulum (ER) regulates protein folding and maintains proteostasis in cells. We observed that the ER transcriptome is impaired during chronic reductive stress (RS) in cardiomyocytes. Here, we hypothesized that a prolonged moderate treadmill exercise mitigates the RS-induced ER dysfunction and cardiac remodeling in cardiac-specific constitutively active Nrf2 mice (CaNrf2-TG). RNA sequencing showed notable alterations in the ER transcriptome of TG hearts at 4, 12, and 24 weeks (16, 28, and 35 genes, respectively). Notably, the downregulation of ER genes was significant at 12 weeks, and further pronounced at 24 weeks, at which the cardiac pathology is evident. We also observed increased levels of ubiquitinated proteins in CaNrf2-TG hearts across all ages, along with VCP, a marker of ERAD function, at 24 weeks. These findings indicate that constitutive Nrf2 activation and RS impair protein-folding activity and augments ERAD function over time. Exercise intervention for 20 weeks (beginning at 6 weeks of age), reduced cardiomyocyte hypertrophy (from 448 μm 2 to 280 μm 2 ) in TG mice, through adaptive remodeling, and preserved the cardiac function. However, while exercise did not influence antioxidants or ER stress protein levels, it significantly improved ERAD function and autophagy flux (LC-I to LC-II) in the TG-EXE hearts. Collectively, our findings underscore the prophylactic potential of exercise in mitigating RS-associated pathology, highlighting its essential role in maintaining cellular proteostasis through ER-independent mechanisms., Competing Interests: Declaration of competing interest Authors declare that we have no financial or personal relationships with any individuals or organizations that could potentially influence the work presented in this manuscript. Also confirms that there are no conflicts of interest related to the research, data analysis, interpretation, or publication of this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Research on disease detection by leveraging machine learning techniques has been under significant focus. The use of machine learning techniques is important to detect critical diseases promptly and provide the appropriate treatment. Disease detection is a vital and sensitive task and while machine learning models may provide a robust solution, they can come across as complex and unintuitive. Therefore, it is important to gauge a better understanding of the predictions and trust the results. This paper takes up the crucial task of skin disease detection and introduces a hybrid machine learning model combining SVM and XGBoost for the detection task. The proposed model outperformed the existing machine learning models - Support Vector Machine (SVM), decision tree, and XGBoost with an accuracy of 99.26%. The increased accuracy is essential for detecting skin disease due to the similarity in the symptoms which make it challenging to differentiate between the different conditions. In order to foster trust and gain insights into the results we turn to the promising field of Explainable Artificial Intelligence (XAI). We explore two such frameworks for local as well as global explanations for these machine learning models namely, SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME)., 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 article presents the development of the Equity, Diversity, Inclusivity, and Accessibility (EDIA) Cross-Cutting Theme Project within the Team Primary Care (TPC) initiative, aimed at addressing systemic inequities through innovative educational strategies. Grounded in the social accountability of health professions framework, this project aims to equip primary care teams with the knowledge, skills, and attitudes necessary to promote health equity. The EDIA Integrated Educational Experience (IEE) model includes a self-assessment tool, digital learning space, and national mentorship network, providing a comprehensive approach for primary care teams to promote health equity. The IEE model utilizes a layered micro, meso, and macro approach to support cultural transformation within highly complex healthcare environments. Key lessons learned involve trust- and relationship-building processes to help dismantle historical silos and encourage open dialogue. Future efforts focus on implementation, ensuring adaptability, scalability, and sustainability, positioning the model as a catalyst for equitable primary care delivery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: With the global epidemic of obesity, the importance of metabolic and bariatric surgery (MBS) is greater than ever before. Performing these surgeries requires academic training and the completion of a dedicated fellowship training program. This study aimed to develop guidelines based on expert consensus using a modified Delphi method to create the criteria for metabolic and bariatric surgeons that must be mastered before obtaining privileges to perform MBS., Methods: Eighty-nine recognized MBS surgeons from 42 countries participated in the Modified Delphi consensus to vote on 30 statements in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was regarded to indicate a consensus., Results: Consensus was reached on 29 out of 30 statements. Most experts agreed that before getting privileges to perform MBS, surgeons must hold a general surgery degree and complete or have completed a dedicated fellowship training program. The experts agreed that the learning curves for the various operative procedures are approximately 25-50 operations for the LSG, 50-75 for the OAGB, and 75-100 for the RYGB. 93.1% of experts agreed that MBS surgeons should diligently record patients' data in their National or Global database., Conclusion: MBS surgeons should have a degree in general surgery and have been enrolled in a dedicated fellowship training program with a structured curriculum. The learning curve of MBS procedures is procedure dependent. MBS surgeons must demonstrate proficiency in managing postoperative complications, collaborate within a multidisciplinary team, commit to a minimum 2-year patient follow-up, and actively engage in national and international MBS societies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To compare outcomes of nonoperative and percutaneous fixation of geriatric fragility lateral compression 1 (LC1) pelvic ring fractures., Design: Retrospective., Setting: Two level 1 trauma centers., Patient Selection Criteria: Included were patients who were 60 years or older with an isolated LC1 pelvic ring fracture managed nonoperatively or those who failed mobilization and were managed operatively with percutaneous sacral fixation. Patients with high-energy mechanisms of injury or polytrauma were excluded., Outcome Measures and Comparisons: The primary outcome was pain as measured by using the visual analog scale (VAS) after treatment. Secondary outcomes included length of stay, discharge disposition, mortality, readmission rates, and complications., Results: In total, 231 patients were included with a mean age of 79.5 years (range 60-100). One hundred eighty-five (80.0%) patients were female. Sixty-two (26.8%) patients received percutaneous sacral fixation after failed mobilization, and 169 (73.2%) were managed nonoperatively. In the operative group, the median time to surgery was hospital day 4. Nonoperative patients were older (81.5 ± 10.0 years vs. 74.2 ± 9.4 years, P < 0.01) and had a shorter hospital length of stay (4.8 ± 6.2 days) than the operative group (10.6 ± 9.5 days, P < 0.01). Patients in the operative group had more pain (VAS 7.9 ± 3.0) than those in the nonoperative group (VAS 6.6 ± 3.0) ( P = 0.01) on admission but had similar pain control postoperatively (VAS 4.4 ± 3.0) compared with the nonoperative group (VAS 4.5 ± 3.6) on the equivalent hospital day ( P = 0.91). Thus, patients in the operative group experienced more improvement in pain (VAS 3.3 ± 2.7) compared with the nonoperative group (VAS 1.9 ± 3.9) after treatment ( P = 0.02). Ninety-day mortality ( P = 0.21) and readmission rates ( P = 0.27) were similar for both groups. Two patients in the operative cohort sustained nerve injuries, whereas 1 patient in the nonoperative group had a nonunion and underwent surgery., Conclusions: Patients who undergo percutaneous surgical fixation for low-energy LC1 injuries have similar discharge disposition, mortality, complication rates, and readmission rates compared with patients treated nonoperatively. Percutaneous surgical fixation may provide significant pain relief for patients who failed conservative management., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To examine the effect of local aqueous tobramycin injection adjunct to perioperative intravenous (IV) antibiotic prophylaxis in reducing fracture-related infections (FRIs) following reduction and internal fixation of open fractures., Design: Retrospective cohort study., Setting: Single academic Level I trauma center., Patients Selection Criteria: Patients with open extremity fractures treated with reduction and internal fixation with (intervention group) or without (control group) 80 mg of local aqueous (2 mg/mL) tobramycin injected during closure at the time of definitive fixation were identified from December 2018 to August 2021 based on population-matched demographic and injury characteristics., Outcome Measures and Comparisons: The primary outcome was FRI within 6 months of definitive fixation. Secondary outcomes consisted of fracture nonunion and bacterial speciation. Differences in outcomes between the 2 groups were assessed and logistic regression models were created to assess the difference in infection rates between groups, with and without controlling for potential confounding variables, such as sex, fracture location, and Gustilo-Anderson classification., Results: An analysis of 157 patients was performed with 78 patients in the intervention group and 79 patients in the control group. In the intervention group, 30 (38.5%) patients were women with a mean age of 47.1 years. In the control group, 42 (53.2%) patients were women with a mean age of 46.4 years. The FRI rate was 11.5% in the intervention group compared with 25.3% in the control group ( P = 0.026). After controlling for sex, Gustilo-Anderson classification, and fracture location, the difference in FRI rates between groups remained significantly different ( P = 0.014)., Conclusions: Local aqueous tobramycin injection at the time of definitive internal fixation of open extremity fractures was associated with a significant reduction in FRI rates when administered as an adjunct to intravenous antibiotics, even after controlling for potential confounding variables., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer ® low-dose enteric-coated aspirin 81 mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore ® low-dose phospholipid-aspirin liquid-filled 81 mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU)., Methods: Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer ® LD EC-ASA daily for 14 days, with a washout period of 28 days, followed by Vazalore ® LD PL-ASA daily for 14 days, again followed by ARU testing., Results: Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer ® LD EC-ASA vs. Vazalore ® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer ® LD EC-ASA ARU value (p value 0.788) or Vazalore ® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events., Conclusions: There were no significant differences in aspirin resistance between Bayer ® LD EC-ASA and Vazalore ® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings., Trial Registration: ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024., (© 2024. The Author(s).)

Background/objectives: Weight loss outcomes vary individually. Magnetic resonance imaging (MRI)-based evaluation of adipose tissue (AT) might help to identify AT characteristics that predict AT loss. This study aimed to assess the impact of an 8-week low-calorie diet (LCD) on different AT depots and to identify predictors of short-term AT loss using MRI in adults with obesity., Methods: Eighty-one adults with obesity (mean BMI 34.08 ± 2.75 kg/m², mean age 46.3 ± 10.97 years, 49 females) prospectively underwent baseline MRI (liver dome to femoral head) and anthropometric measurements (BMI, waist-to-hip-ratio, body fat), followed by a post-LCD-examination. Visceral and subcutaneous AT (VAT and SAT) volumes and AT fat fraction were extracted from the MRI data. Apparent lipid volumes based on MRI were calculated as approximation for the lipid contained in the AT. SAT and VAT volumes were subdivided into equidistant thirds along the craniocaudal axis and normalized by length of the segmentation. T-tests compared baseline and follow-up measurements and sex differences. Effect sizes on subdivided AT volumes were compared. Spearman Rank correlation explored associations between baseline parameters and AT loss. Multiple regression analysis identified baseline predictors for AT loss., Results: Following the LCD, participants exhibited significant weight loss (11.61 ± 3.07 kg, p < 0.01) and reductions in all MRI-based AT parameters (p < 0.01). Absolute SAT loss exceeded VAT loss, while relative apparent lipid loss was higher in VAT (both p < 0.01). The lower abdominopelvic third showed the most significant SAT and VAT reduction. The predictor of most AT and apparent lipid losses was the normalized baseline SAT volume in the lower abdominopelvic third, with smaller volumes favoring greater AT loss (p < 0.01 for SAT and VAT loss and SAT apparent lipid volume loss)., Conclusions: The LCD primarily reduces lower abdominopelvic SAT and VAT. Furthermore, lower abdominopelvic SAT volume was detected as a potential predictor for short-term AT loss in persons with obesity., (© 2024. The Author(s).)

Purpose of Review: This review focuses on latest developments in managing antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a systemic autoimmune condition characterized by inflammation and necrosis of small blood vessels due to circulating autoantibodies that target neutrophilic granules., Recent Findings: Our understanding of AAV pathogenesis has evolved in the past decades highlighting the central pathogenic roles of autoantibodies and complement activation. In parallel, the appreciation for glucocorticoid toxicity has led the research on crucial steroid-sparing therapeutic alternatives. Complement inhibitors (like avacopan) that have emerged are associated with better preservation of kidney function in AAV patients with severe kidney impairment. The role of plasma-exchange (PLEX) was revisited in updated guidelines that recommended its potential use in the context of diffuse alveolar hemorrhage associated hypoxia and severe kidney involvement, particularly with a serum creatinine level above 3.4 mg/dl. The ANCA Kidney Risk Score risk prediction and Glucocorticoid Toxicity Index score aid in identifying high-risk patients and individualizing management plans., Summary: Kidney involvement in AAV requires prompt diagnosis and initiation of immunosuppression to prevent irreversible nephron loss. Newer therapeutic targets are on the horizon and offer hope for personalized treatment strategies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In kidney transplantation, pairing recipients with the highest longevity with low-risk allografts to optimize graft-donor survival is a complex challenge. Current risk prediction models exhibit limited discriminative and calibration capabilities and have not been compared to modern decision-assisting tools. We aimed to develop a highly accurate risk-stratification index using artificial intelligence (AI) techniques. Using data from the UNOS database (156,749 deceased kidney transplants, 2007-2021), we randomly divided transplants into training (80%) and validation (20%) sets. The primary measure was death-censored graft survival. Four machine learning models were assessed for calibration (integrated Brier score [IBS]) and discrimination (time-dependent concordance [CTD] index), compared with existing models. We conducted decision curve analysis and external validation using UK Transplant data. The Deep Cox mixture model showed the best discriminative performance (area under the curve [AUC] = 0.66, 0.67, and 0.68 at 6, 9, and 12 years post-transplant), with CTD at 0.66. Calibration was adequate (IBS = 0.12), while the kidney donor profile index (KDPI) model had lower CTD (0.59) and AUC (0.60). AI-based D-TOP outperformed the KDPI in evaluating transplant pairs based on graft survival, potentially enhancing deceased donor selection. Advanced computing is poised to influence kidney allocation schemes., Competing Interests: Disclosure: T.F. is a current employee of the United States Veterans Health Administration. However, the views and opinions expressed herewith do not reflect the official views or opinions of and are not endorsed by the United States Veteran Health Administration. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT)., Materials and Methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function., Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively ( P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months ( P  = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively ( P -0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients ( P -0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively ( P -<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis., Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Global usage of pharmaceuticals has led to the proliferation of bacteria that are resistant to antimicrobial treatments, creating a substantial public health challenge. Here, we investigate the emergence of sulfonamide resistance genes in groundwater and surface water in Patna, a rapidly developing city in Bihar, India. We report the first quantification of three sulfonamide resistance genes (sulI, sulII and sulIII) in groundwater (12-107 m in depth) in India. The mean relative abundance of gene copies was found to be sulI (2.4 × 10 -2 copies/16S rRNA gene) > sulII (5.4 × 10 -3 copies/16S rRNA gene) > sulIII (2.4 × 10 -3 copies/16S rRNA gene) in groundwater (n = 15) and surface water (n = 3). A comparison between antimicrobial resistance (AMR) genes and wastewater indicators, particularly tryptophan:fulvic-like fluorescence, suggests that wastewater was associated with AMR gene prevalence. Urban drainage channels, containing hospital and domestic wastes, are likely a substantial source of antimicrobial resistance in groundwater and surface water, including the Ganges (Ganga) River. This study is a reference point for decision-makers in the fight against antimicrobial resistance because it quantifies and determines potential sources of AMR genes in Indian groundwater., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The NO dioxygenation reaction catalyzed by heme-containing globin proteins is a crucial aerobic detoxification pathway. Accordingly, the second order reaction of NO with oxymyoglobin and oxyhemoglobin has been the focus of a large number of kinetic and spectroscopic studies. Stopped-flow and rapid-freeze-quench (RFQ) measurements have provided evidence for the formation of a Fe(III)-nitrato complex with millisecond lifetime prior to release of the nitrate product, but the temporal resolution of these techniques is insufficient for the characterization of precursor species. Most mechanistic models assume the formation of an initial Fe(III)-peroxynitrite species prior to homolytic cleavage of the OO bond and recombination of the resulting NO 2 and Fe(IV)=O species. Here we report vibrational spectroscopy measurements for the reaction of oxymyoglobin with a photolabile caged NO donor at cryogenic temperatures. We show that this approach offers efficient formation and trapping of the Fe(III)-nitrato, enzyme-product, complex at 180 K. Resonance Raman spectra of the Fe(III)-nitrato complex trapped via RFQ in the liquid phase and photolabile NO release at cryogenic temperatures are indistinguishable, demonstrating the complementarity of these approaches. Caged NO is released by irradiation <180 K but diffusion into the heme pocket is fully inhibited. Our data provide no evidence for Fe(III)-peroxynitrite of Fe(IV)=O species, supporting low activation energies for the NO to nitrate conversion at the oxymyoglobin reaction site. Photorelease of NO at cryogenic temperatures allows monitoring of the reaction by transmittance FTIR which provides valuable quantitative information and promising prospects for the detection of protein sidechain reorganization events in NO-reacting metalloenzymes., 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 © 2023. Published by Elsevier Inc.)

Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care. The study was conducted at a single tertiary hospital in Northern India. We analyzed 70 children with an illness requiring intensive care and obtained a precise molecular diagnosis in 32 of 70 probands (45.3%) using diverse sequencing techniques such as clinical exome, whole exome, and whole genome. A significant change in clinical outcome was observed in 13 of 32 (40.6%) diagnosed probands with a change in medication in 11 subjects and redirection to palliative care in two subjects. Additional benefits included specific dietary management (three cases), avoidance of a major procedure (one case) and better reproductive counseling. Dramatic therapeutic responses were observed in three cases with SCN1A, SCN2A and KCNQ2-related epileptic encephalopathy. A delayed turn-around for sequencing results was perceived as a major limiting factor in the study, as rapid and ultra-rapid sequencing was not available. Achieving a precise molecular diagnosis has great utility in managing critically ill patients with suspected genetic disorders in developing countries., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis., Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics., Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly., Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Moiré superlattices have emerged as a new platform for studying strongly correlated quantum phenomena, but these systems have been largely limited to van der Waals layer two-dimensional materials. Here we introduce moiré superlattices leveraging ultrathin, ligand-free halide perovskites, facilitated by ionic interactions. Square moiré superlattices with varying periodic lengths are clearly visualized through high-resolution transmission electron microscopy. Twist-angle-dependent transient photoluminescence microscopy and electrical characterizations indicate the emergence of localized bright excitons and trapped charge carriers near a twist angle of ~10°. The localized excitons are accompanied by enhanced exciton emission, attributed to an increased oscillator strength by a theoretically predicted flat band. This research showcases the promise of two-dimensional perovskites as unique room-temperature moiré materials., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Gallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC., Methods: Fresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting, respectively, in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 were analysed for predicting overall survival (OS), disease-free survival (DFS) and response to chemotherapy using Kaplan-Meier log-rank test and Cox regression multivariate analysis., Results: The mean age of the cohort was 50 ± 13.2 with 26 (48.1%) in patients having early stage gallbladder cancer (GBC). Over-expression of ABCB1 and ABCG2 was noted in 32/54 (59%) and 40/54 (74%) cases, respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases, respectively. The mean OS and DFS was 20.7 ± 11.5 and 19.3 ± 12.2 months at median follow-up of 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidences of late death and recurrence among over-expression and down-expression. Sub-group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC., Conclusion: Altered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: There exist few maximal oxygen uptake (VO 2max ) non-exercise-based prediction equations, fewer using machine learning (ML), and none specifically for older adults. Since direct measurement of VO 2max is infeasible in large epidemiologic cohort studies, we sought to develop, validate, compare, and assess the transportability of several ML VO 2max prediction algorithms., Methods: The Baltimore Longitudinal Study of Aging (BLSA) participants with valid VO 2max tests were included (n = 1080). Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine (SVM) algorithms were trained to predict VO 2max values. We developed these algorithms for: (a) the overall BLSA, (b) by sex, (c) using all BLSA variables, and (d) variables common in aging cohorts. Finally, we quantified the associations between measured and predicted VO 2max and mortality., Results: The age was 69.0 ± 10.4 years (mean ± SD) and the measured VO 2max was 21.6 ± 5.9 mL/kg/min. Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine yielded root mean squared errors of 3.4 mL/kg/min, 3.6 mL/kg/min, 3.4 mL/kg/min, 3.6 mL/kg/min, and 3.5 mL/kg/min, respectively. Incremental quartiles of measured VO 2max showed an inverse gradient in mortality risk. Predicted VO 2max variables yielded similar effect estimates but were not robust to adjustment., Conclusion: Measured VO 2max is a strong predictor of mortality. Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment. Future studies should seek to reproduce these results so that VO 2max , an important vital sign, can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Purpose: Postmenopausal women experience augmented aortic hemodynamic responses to isometric handgrip (IHG) exercise and metaboreflex activation post-exercise muscle ischemia (PEMI). Relationships between endothelial function brachial artery flow-mediated dilation (FMD) and aortic stiffness carotid-femoral pulse wave velocity (cfPWV) with aortic pulsatile hemodynamics during IHG and PEMI have not been determined. The relationships between aortic hemodynamic responses to PEMI were evaluated., Methods: Aortic blood pressure (BP), wave reflection, and pressure of forward (Pf) and backward (Pb) waves were measured using arterial tonometry at rest, IHG at 30% maximal force, and PEMI in 30 (15/group) postmenopausal women with low (≤ 4.5%) and normal (≥ 5.5%) FMD. Hemodynamic responses were analyzed as the change (Δ) from rest to the last minute of IHG and PEMI., Results: Brachial and aortic systolic BP (SBP) responses to IHG were higher in the low vs normal FMD group (P < 0.05). Aortic SBP (Δ20 ± 8 vs Δ11 ± 7 mmHg), pulse pressure (PP) (Δ12 ± 8 vs Δ6 ± 4 mmHg), augmented pressure (AP) (Δ5 ± 3 vs Δ2 ± 2 mmHg), and Pb (Δ6 ± 4 vs Δ3 ± 2 mmHg) responses to PEMI were greater (P < 0.05) in women with low vs. normal FMD. FMD was negatively correlated with aortic SBP, PP, AP, and Pb (P < 0.05) responses to PEMI. cfPWV was not correlated with responses to PEMI., Conclusion: Endothelial dysfunction relates to augmented aortic pulsatile load during metaboreflex activation, which may increase cardiovascular risk in postmenopausal women., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transition metal (TM) distribution through the phloem is an essential part of plant metabolism and is required for systemic signaling and balancing source-to-sink relationships. Due to their reactivity, TMs are expected to occur in complexes within the phloem sap; however, metal speciation in the phloem sap remains largely unexplored. Here, we isolated phloem sap from Brassica napus and analyzed it via size exclusion chromatography (SEC) coupled online to sector-field ICP-MS. Our data identified known TM binding proteins and molecules including metallothioneins (MT), glutathione, and nicotianamine. While the main peak of all metals was low MW (∼1.5 kD), additional peaks ∼10-15 kD containing Cu, Fe, S and Zn were also found. Further physicochemical analyses of MTs with and without affinity tags corroborated that MTs can form complexes of diverse molecular weights. We also identified and characterized potential artifacts in the TM-biding ability of B. napus MTs between tagged and non-tagged MTs. That is, the native BnMT2 binds Zn, Cu and Fe, while MT3a and MT3b only bind Cu and Zn. In contrast, his-tagged MTs bind less Cu and were found to bind Co and Mn and aggregated to oligomeric forms to a greater extent compared to the phloem sap. Our data indicates that TM chemistry in the phloem sap is more complex than previously anticipated and that more systematic analyses are needed to establish the precise speciation of TM and TM-ligand complexes within the phloem sap., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

There has been an intense surge in interest in the search for alternative sources of petroleum fuels in the modern world as a result of the inflation of fuel prices and the historic supply gap. When compared to petroleum fuels, biodiesel is becoming an increasingly valuable option due to the fact that it produces less emissions and provides the almost same amount of energy. In point of fact, the prime aim of this work is to explore the possibility of utilizing biodiesel derived from lemongrass oil and including dibutyl ether as an additive for the test diesel engine operating on varied compression ratios. The findings showed that the best operating settings are a 17.5 compression ratio with a blend of 30% biodiesel and 70% diesel fuel. At greater loads, brake thermal efficiency is lower than that of diesel engines. Lower loads result in lower specific fuel usage. Mechanical efficiency at higher loads is highest in the B30 blend, but emission metrics such as CO, CO 2 , HC, and NOx were reduced with the inclusion of an additive, though HC rose with higher loads of lemongrass oil biodiesel blends. When compared to the B30 biodiesel blend with various composition additives, the B30 + 4% additive has the highest efficiency at the fourth load in terms of both brake power and mechanical efficiency., (© 2024. The Author(s).)

Dyshormonogenetic goiter (DG) is a rare cause of congenital hypothyroidism (CH) occurring due to the lack of enzymes necessary for thyroid hormone synthesis. If left untreated, it impairs hormone production leading to developmental and metabolic complications. Morphologically, it is characterized by architectural and cellular pleomorphism that may mimic thyroid malignancy causing difficulties in diagnosis. Thus, accurate histopathological evaluation is crucial in distinguishing DG from malignancy. We report a case of a 13-year-old female diagnosed with hypothyroidism at the age of six. Over time, she exhibited slow development of a multinodular goiter and began experiencing dyspnea in the supine position. Ultrasonography confirmed an enlarged thyroid gland with solid hypoechoic nodules devoid of calcifications, so a total thyroidectomy was performed. Gross examination revealed that the gland was notably enlarged with a grey-tan nodular appearance with few cystic hemorrhagic areas and had a firm rubbery texture. Microscopy identified microfollicular cells with significant hyperplasia and cytologic atypia along with scant colloid, indicative of DG. Histopathological literature has been essential to prevent overdiagnosis of malignancy. Additionally, the authors suggest that it is crucial to include DG in the differential diagnosis when evaluating potential causes of CH., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. 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 © 2024, Dekhne et al.)

Objective: Two-tiered preference signaling has been implemented in the radiology residency application system to reduce congestion in the setting of high-volume applications. Signals are an indicator of strong interest that an applicant can transmit to a limited number of programs. This study assessed the impact of program signaling on interview invitations, how applicants strategically used signals based on their application's competitiveness, and applicants' attitudes toward the current signaling system., Methods: A survey was sent to radiology residency applicants registered with TheRadRoom during the 2024 application cycle. We queried the applicant's background, applications, signal distribution, and interview outcome depending on the type of signal sent. We also asked whether respondents received an interview invitation from a hypothetical "comparator non-signaled program" if they had one additional signal to use. Group differences were assessed using nonparametric Wilcoxon signed rank test., Results: A total of 202 applicants completed the survey (28% response rate). Most applied to diagnostic radiology (81%). Nearly all respondents utilized all 6 gold (98%) and 6 silver (96.5%) signals. Interview invitation rates were significantly higher for signaled programs (59.8%±27.4%) than non-signaled (8.5%±8.5%); the invitation rate at the comparator non-signaled programs was 37%. Gold signaled programs had significantly higher interview rates (67.8%±29.3) than silver (51.8%±31.3%). Respondents used 49.2%(±21.7%) of their signals for "likely to match" programs, 33.1%(±20.9%) for "aspirational" programs, and 17.6%(±15.8%) for "safety" programs. Most respondents (146;76%) supported continuing the signaling system for future cycles., Conclusion: Signaling programs significantly enhanced interview invitation rates, with gold signals being more effective than silver. The applicants used about 6 total signals for "likely-to-match" programs, 2 for "aspirational" programs, and about 4 for "safety" programs., (Copyright © 2024. Published by Elsevier Inc.)

Background: Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy., Results: We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma vimentin level at 70 h post-MRSA inoculation was on average twofold higher compared to pre-infection (0 h) level in the same animal. Anti-vimentin antibody effectively reduced fibrin formation ex vivo and increased porosity in the fibrin clot structure generated from septic piglet plasma. In contrast to plasma at 0 h, the size-exclusion chromatography revealed that phosphorylated vimentin was in-complex with fibrinogen in septic piglet plasma., Conclusions: Thus, our swine model of sepsis-induced coagulopathy, reproduced increased extracellular circulating vimentin and subsequent potentiation of fibrin formation, often observed in septic patient. These outcomes validate the use of large animal models to investigate the dysregulated host immune response to infection leading to coagulopathy, and to develop new therapies for sepsis-induced disseminated microvascular thrombosis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Neurons are highly specialised cells that need to relay information over long distances and integrate signals from thousands of synaptic inputs. The complexity of neuronal function is evident in the morphology of their plasma membrane (PM), by far the most intricate of all cell types. Yet, within the neuron lies an organelle whose architecture adds another level to this morphological sophistication - the endoplasmic reticulum (ER). Neuronal ER is abundant in the cell body and extends to distant axonal terminals and postsynaptic dendritic spines. It also adopts specialised structures like the spine apparatus in the postsynapse and the cisternal organelle in the axon initial segment. At membrane contact sites (MCSs) between the ER and the PM, the two membranes come in close proximity to create hubs of lipid exchange and Ca2+ signalling called ER-PM junctions. The development of electron and light microscopy techniques extended our knowledge on the physiological relevance of ER-PM MCSs. Equally important was the identification of ER and PM partners that interact in these junctions, most notably the STIM-ORAI and VAP-Kv2.1 pairs. The physiological functions of ER-PM junctions in neurons are being increasingly explored, but their molecular composition and the role in the dynamics of Ca2+ signalling are less clear. This review aims to outline the current state of research on the topic of neuronal ER-PM contacts. Specifically, we will summarise the involvement of different classes of Ca2+ channels in these junctions, discuss their role in neuronal development and neuropathology and propose directions for further research., (© 2024 The Author(s).)

Photocatalytic water splitting is an efficient and sustainable technology to produce high-purity hydrogen gas for clean energy using solar energy. Despite the tremendous success of halide perovskites as absorbers in solar cells, their utility for water splitting applications has not been systematically explored. A band gap greater than 1.23 eV, high solar absorption coefficients, efficient separation of charge carriers, and adequate overpotentials for water redox reaction are crucial for a high solar to hydrogen (STH) efficiency. In this work, we present a data-driven approach to identify novel lead-free halide perovskites with high STH efficiency ( η > 20%), building upon our recently published computational data and machine learning (ML) models. Our multi-fidelity density functional theory (DFT) dataset comprises decomposition energies and band gaps of nearly 1000 pure and alloyed perovskite halides using both the GGA-PBE and HSE06 functionals. Using rigorously optimized composition-based ML regression models, we performed screening across a chemical space of 150 000+ halide perovskites to yield hundreds of stable compounds with suitable band gaps and edges for photocatalytic water splitting. A handful of the best candidates were investigated with in-depth DFT computations to validate their properties. This work presents a framework for accelerating the navigation of a massive chemical space of halide perovskite alloys and understanding their potential utility for water splitting and motivates future efforts towards the synthesis and characterization of the most promising materials.STH > 20%), building upon our recently published computational data and machine learning (ML) models. Our multi-fidelity density functional theory (DFT) dataset comprises decomposition energies and band gaps of nearly 1000 pure and alloyed perovskite halides using both the GGA-PBE and HSE06 functionals. Using rigorously optimized composition-based ML regression models, we performed screening across a chemical space of 150 000+ halide perovskites to yield hundreds of stable compounds with suitable band gaps and edges for photocatalytic water splitting. A handful of the best candidates were investigated with in-depth DFT computations to validate their properties. This work presents a framework for accelerating the navigation of a massive chemical space of halide perovskite alloys and understanding their potential utility for water splitting and motivates future efforts towards the synthesis and characterization of the most promising materials.

First heterogeneous catalytic system, having a covalently linked hybrid bidentate organotellurium ligand [ i.e. , PhTe-CH 2 -CH 2 -NH 2 ] on the surface of graphene oxide, has been synthesized with immobilized and stabilized Pd(0) nanoparticles. To the best of our knowledge, it is the first such catalytic system in which a heterogenized organotellurium ligand has been used. It has been well-characterized using different physicochemical characterization techniques viz. P-XRD, XPS, HR-TEM, EELS, FE-SEM, EDX, TGA, BET surface area analysis, FT-IR spectroscopy, and Raman spectroscopy. The Pd content of the final system has been quantified using ICP-OES. Its applications have been explored in Suzuki-Miyaura C-C cross coupling and C-O cross coupling reactions. Hot filtration experiments corroborate the heterogeneous nature of the catalysis. It is recyclable for up to five reaction cycles in Suzuki-Miyaura and C-O cross coupling with marginal loss in performance. It also catalyzes the reactions of chloroarenes such as chlorobenzene, 4-chloroaniline, 1-chloro-4-nitrobenzene, 4-chloroacetophenone, 4-chlorobenzophenone for Suzuki coupling, and 1-chloro-4-nitrobenzene, 4-chlorobenzonitrile, chlorobenzene, and 4-chlorotoluene for C-O coupling. P-XRD, FE-SEM, and EDX study reveals that the catalytic system retains its structural originality and functionality after recycling., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To compile and evaluate the heritability and inheritance patterns of lower urinary tract symptoms (LUTS) in adult cohorts., Methods: Searches of five databases (PubMed, Embase, APA PsycInfo, Global Health, and OVID Medline) commenced on 6 July 2024, resulting in 736 articles retrieved after deduplication. Studies evaluating heritability patterns, gene frequencies, and familial aggregation of symptoms were included for review. Screening and predefined eligibility criteria produced 34 studies for final review. A descriptive analysis of synthesised data was performed, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool and the Johanna Briggs Institute checklist were used to evaluate these studies., Results: Ten of the 34 studies (29%) described general LUTS, 14 (41%) described symptoms due to benign prostatic enlargement (BPE), nine (26%) described urinary incontinence (UI; urge UI [UUI], stress UI [SUI] and mixed UI [MUI]), four (12%) described nocturia alone, two (6%) described overactive bladder (OAB), and four (13%) described other specific symptoms (frequency, postvoid residual urine volume). BPE symptoms, UI (MUI and UUI), nocturia alone, and frequency alone were associated with genetic predisposition, whilst OAB and SUI had more modest inheritance., Conclusion: The pathogenetic and pharmacological mechanisms fundamental to LUTS manifestation are highly heterogeneous. Further work is required to evaluate the inheritance patterns of LUTS more extensively., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)