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The stomach is responsible for physically and chemically processing the ingested meal before controlled emptying into the duodenum through the pyloric sphincter. An incompetent pylorus allows reflux from the duodenum back into the stomach, and if the amount of reflux is large enough, it could alter the low pH environment of the stomach and erode the mucosal lining of the lumen. In some cases, the regurgitated contents can also reach the esophagus leading to additional complications. In this work, "StomachSim", an in-silico model of the fluid dynamics of the stomach, is used to study the mechanism of duodenogastric reflux. The effects of variations in food properties and motility disorders on reflux are investigated. The simulations show that the primary driver of reflux is the relaxation of the antrum after a stomach contraction terminates near the pylorus. The region of the stomach walls exposed to the regurgitated contents depends significantly on the density of the stomach contents. For stomach contents of higher viscosity, the increased pressure required to maintain gastric emptying reduces the amount of duodenogastric reflux. Concomitant stomach motility disorders that weaken the relaxation of the walls also affect the amount of reflux. The study illustrates the utility of in-silico models in analyzing the factors at play in gastrointestinal diseases.

Wildland firefighting is a niche specialization in the fire service - inherently dangerous with unique risks. Over the past decade, fatalities amongst all firefighters have decreased; however, wildland firefighter fatalities have increased. This subject has only been described in the grey literature, and a paucity of medical literature exists. The United States Fire Administration's online fatality database was queried for on duty mortality between 1990 and 2022. The year 2001 was excluded due to the 340 deaths that occurred on September 11th. Data collected included demographics, incident characteristics, and nature of fatality and was compared between the decades using a Fisher's exact test. From 1990-2000 to the decade of 2013-2022, there has been a significant increase in wildland fatalities, from 2% to 10% of total fatalities (p < 0.00001). Despite the recent wave of 2023 wildfires across North America, the average annual number of wildfires has decreased 23% (from 79,829 to 61,377) between 1990-2000 and 2013-2022. Burn related fatalities have increased over time, from 9% of fatalities to 27% (p < 0.01), while trauma related injuries decreased significantly between the second and third decade (p <0.01). MI accounted for 16% of total fatalities, with no significant change over time. Although wildfires have become less common over the past decade, there was a 5-fold increase in wildland firefighter fatalities with burn related fatalities also increasing. Further investigation, including analysis of 2023 data, is required to augment development of health and safety measures for these heroes., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

CO2 ablative fractional laser (CO2 AFL) therapy is a safe and effective procedure when used in the treatment of hypertrophic scars for burn patients. It has a high patient satisfaction rate and a minimal side effect profile, typically consisting of postoperative pain, irritation, surgical site inflammation, and, in rare cases, infection. Although prophylactic antibiotics have historically been recommended, there is a paucity of literature on the topic and recent studies indicate that they may be unnecessary in routine cases. In this retrospective, single-center descriptive study, 230 cases in patients with hypertrophic burn scars treated with CO2 AFL therapy were compared. 28 cases were with the use of prophylactic antibiotics and 201 cases were without the use of prophylactic antibiotics. We found that there was no significant association between the use of antibiotics and the prevention of topical skin infection in cases treated with CO2 AFL therapy (P = 1). Therefore, we conclude that the omission of prophylactic antibiotics is not associated with an increased risk of infection and recommend that prophylactic antibiotics should not be indicated in the setting of routine CO2 AFL therapy for patients with hypertrophic burn scars., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Type 1 Diabetes (T1D) is a progressive autoimmune disease often identified in childhood or adolescence, with early stages detectable through pre-diabetic markers such as autoantibodies and subclinical beta-cell dysfunction. The identification of the pre-T1D stage is critical for preventing complications, such as diabetic ketoacidosis, and for enabling timely interventions that may alter disease progression. This review examines the multifaceted approach to managing T1D risk in adolescents and teens, emphasizing early detection, nutritional interventions, beta-cell preservation strategies, and psychosocial support. Screening for T1D-associated autoantibodies offers predictive insight into disease risk, particularly when combined with education and family resources that promote lifestyle adjustments. Although nutritional interventions alone are not capable of preventing T1D, certain lifestyle interventions, such as weight management and specific nutritional choices, have shown the potential to preserve insulin sensitivity, reduce inflammation, and mitigate metabolic strain. Pharmacological strategies, including immune-modulating drugs like teplizumab, alongside emerging regenerative and cell-based therapies, offer the potential to delay disease onset by protecting beta-cell function. The social and psychological impacts of a T1D risk diagnosis are also significant, affecting adolescents' quality of life, family dynamics, and mental health. Supportive interventions, including counseling, cognitive-behavioral therapy (CBT), and group support, are recommended for managing the emotional burden of pre-diabetes. Future directions call for integrating universal or targeted screening programs within schools or primary care, advancing research into nutrition and psychosocial support, and promoting policies that enhance access to preventive resources. Advocacy for the insurance coverage of screening, nutritional counseling, and mental health services is also crucial to support families in managing T1D risk. By addressing these areas, healthcare systems can promote early intervention, improve beta-cell preservation, and support the overall well-being of adolescents at risk of T1D.

Triple-negative breast cancer (TNBC) constitutes for 10-15% of all breast cancer cases. Tumor heterogeneity, high invasiveness, distant metastasis, lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 expression contribute to TNBC associated with poor overall survival outcomes amongst diseased individuals. The disparity in clinico-pathological and metastatic patterns to distant sites has substantially enhanced the incidences of tumor recurrence. Survival outcomes amongst metastatic TNBC patients are worse in comparison to non-metastatic TNBC counterparts. MicroRNAs (miRNAs) have emerged as significant drivers to function either as oncogene or tumor suppressors by exerting modulating effects on the expression of target genes in the TNBC tumor microenvironment. The pleiotropic nature of miRNAs expands their preclinical and clinical utility in combating both metastatic and non-metastatic TNBC cases and thereby improves their survival outcomes. The present review article aims to highlight the varying survival outcomes in metastatic and non-metastatic TNBC cases. The present review article emphasizes the therapeutic and prognostic potential of miRNAs in TNBC to improve survival outcomes by retarding distant metastasis to lung, bone, brain, and lymph nodes., 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.)

Background: Metastatic colon cancer (MCC) is a debilitating condition with a poor prognosis. Currently, there is limited data that investigates MCC in relation to mismatch repair (MMR) status. The aims of this study are to compare sociodemographic and clinicopathologic features and mortality between patients with MMR-proficient (MMR-P) and MMR-deficient (MMR-D) MCC., Methods: We performed an 8-year retrospective review of the National Cancer Database (NCDB) to identify patients age ≥18 years with MCC and reported MMR status. Data collection included sociodemographic characteristics, primary tumor sites and histopathologic features, and treatment modalities. Outcomes included 90-day, 180-day, 1-year, and 2-year overall mortality. Bivariate logistic regression and multivariate Cox regression identified differences between MMR-P and MMR-D and identified predictors of mortality, respectively., Results: A total of 10,922 MCC cases were identified; 8,796 (80.53%) were MMR-P and 2,126 (19.47%) were MMR-D. MMR-D was independently associated with older age at diagnosis, female sex, mucinous adenocarcinoma, medullary carcinoma, and lymph-vascular invasion. MMR-P was independently associated with perineural invasion and left-sided colonic primary tumor predominance. When adjusted for demographics, histology, and treatment modalities, MMR-D was associated with mortality at 180 days, 1 year, and 2 years., Conclusions: Our study identified several key sociodemographic and clinicopathologic features of MMR-D MCC. MMR-D appears to confer increased overall mortality at 180 days, 1 year, and 2 years after diagnosis in MCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-387/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Influenza is highly prevalent in children under five years, particularly those under two, accounting for 5-10% of acute respiratory infections (ARIs) in India. This study was conducted to compare the immunogenicity and safety of two tetravalent inactivated influenza vaccines in healthy children aged 6-35 months. The dose recommendation for this group increased from 0.25 mL to 0.5 mL to ensure adequate immune response, as per the Advisory Committee on Immunization Practices. This Phase III, randomized, single-blind, active-controlled, multicentre study was conducted from May to October 2022 across five centers in India. A total of 346 subjects were randomized to receive two doses of either the test vaccine (Vaxiflu-4, Zydus Lifesciences Limited; n  = 174) or the reference vaccine (Fluarix Tetra, GlaxoSmithKline; n  = 172). The primary objective was to compare immunogenicity using seroprotection rate, seroconversion rate, and geometric mean titers (GMTs) against four vaccine strains. Safety profiles were also compared. Both vaccines demonstrated non-inferiority, with seroprotection rates over 95%, seroconversion rates above 90%, and significant GMT increases. Adverse events (AEs) were similar for both vaccines, including pain at the injection site, erythema, swelling, and pyrexia. The test vaccine, Vaxiflu-4, showed non-inferiority in terms of immunogenicity and safety when compared with reference vaccine, Fluarix Tetra (Clinical trial registry number: CTRI/2022/05/042514).

Purpose: Fluorine-18 prostate-specific membrane antigen-1007 positron emission tomography/computed tomography ( 18 F-PSMA-1007 PET/CT) has been shown to be superior to multiparametric magnetic resonance imaging (MRI) for the locoregional staging of intermediate-risk and high-risk prostate tumors. This study aims to evaluate whether it is also superior in estimating tumor parameters, such as three-dimensional spatial localization and volume., Methods: 134 participants underwent 18 F-PSMA-1007 PET/CT and MRI prior to radical prostatectomy as part of the validating paired-cohort Next Generation Trial (NCT05141760). MRI, 18 F-PSMA-1007 PET/CT, and final pathology were independently assessed by blinded radiologists, nuclear medicine physicians, and pathologists, respectively. Individual tumor nodules were measured in three dimensions and cognitively registered to 38 segment prostate diagrams as per PI-RADSv2.1. Correct spatial localization was compared using McNemar test and estimation of tumor volumes were compared using linear regression and partial F-test., Results: 286 tumor nodules were identified by final histopathology. 18 F-PSMA-1007 PET/CT was superior to MRI for correct localization (186 [65.0%] vs 134 [46.9%], p < 0.001) and tumor volume estimation (R 2  = 0.545 vs 0.431, p < 0.001). Larger tumors and higher Gleason Grade Group (GGG) were associated with correct localization by 18 F-PSMA-1007 PET/CT (OR = 2.05, p < 0.001 for tumor volume and OR = 4.92, p < 0.01 for ≥ GGG3) and MRI (OR = 1.81, p < 0.001 for tumor volume and OR = 11.67, p < 0.001 for ≥ GGG3)., Conclusion: 18 F-PSMA-1007 PET/CT outperforms MRI for determination of three-dimensional spatial localization and volume of prostate tumors. These findings support the use of 18 F-PSMA-1007 PET/CT prior to definitive treatment of localized prostate cancers., Competing Interests: Declarations. Ethics approval: The trial (NCT05141760) received regional Human Research Ethics approval under protocol HREBA.CC-21–0073 and was monitored by the Northern Alberta Clinical Trials and Research Centre. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants included in the study. Competing interest: There was no conflict of interest relevant to this article., (© 2024. The Author(s).)

Pulmonary valves do not display a fibrous annulus as do other valves in the heart; thus, pulmonary valves can be implanted at multiple orientations and locations within the right ventricular outflow tract (RVOT). This gives surgeons more freedom when implanting the valve but it also results in uncertainties regarding placement, particularly with respect to valve orientation. We investigate the pulmonary artery hemodynamics and valve leaflet dynamics of pulmonary valve replacements (PVRs) with various orientations via fluid-structure interaction (FSI) models. A canonical model of the branching pulmonary artery is coupled with a dynamic model of a pulmonary valve, and from this we quantify the effect of valve implant orientation on the postvalvular hemodynamics and leaflet dynamics. Metrics such as turbulent kinetic energy (TKE), branch pulmonary artery flow distributions, projected valve opening area (PVOA), and pressure differentials across the valve leaflets are analyzed. Our results indicate that off-axis orientation results in higher pressure forces and flow and energy asymmetry, which potentially have implications for long-term durability of implanted bioprosthetic valves., (Copyright © 2024 by ASME.)

Introduction: Bisphosphonates have become the standard drugs for the medical management of patients with moderate-to-severe forms of osteogenesis imperfecta (OI). This study was undertaken to study the effect of parenteral pamidronate or oral alendronate therapy, on bone healing after osteotomies in patients with moderately severe forms (Sillence type 4) of OI., Materials and Methodology: We retrospectively evaluated the effects of bisphosphonate therapy on the healing of seven osteotomies in five patients of OI (Sillence type 4) who underwent Sofield Millar procedure for deformity correction and non-union of long bone fractures., Results: The patients were evaluated clinically and radiologically for the time taken for osteotomy healing and the radiological pattern of osteotomy healing. The minimum clinico-radiological follow-up period was 2 years and the mean follow-up period was 3.9 years (range 2-7 years). The mean time taken for the osteotomy to heal in the patients receiving bisphosphonates was 10.4 months (range 8-12 months) and the union was achieved without the typical exuberant callus formation. Periosteal new bone formation was uniquely absent., Conclusion: We infer from our findings that bisphosphonate therapy in OI patients is associated with a different pattern of osteotomy healing and delay in healing of osteotomy., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Introduction: Preterm delivery is a grave and demanding problem that accounts for the major cause of neonatal deaths and long-term morbidities. It remains an unresolved health issue of global dimensions. Cervical elastography is evolving as a useful diagnostic tool for its timely prediction so that individualised management can be done., Aim: To assess the diagnostic accuracy of transvaginal strain cervical elastography in prediction of preterm delivery., Methods: This prospective observational study was conducted from June 2021 to August 2022 in a tertiary care institute of North India. A total of 75 low-risk asymptomatic women were included. Transvaginal ultrasound was performed for the cervical length in the second and third trimesters. In addition, we collected strain elastography data such as colour codes from six regions of the cervix, that is, at the anterior and posterior lips of internal os, middle one-third of the cervix and the external os, and the strain ratios from these three cervical levels were also calculated. Then these parameters were compared with cervical length, second and third trimester groups and also with preterm and term delivery groups., Result: The red colour (soft colour) at the anterior lip of internal os was the best predictor of preterm delivery in our study with a sensitivity and specificity of 63.64% and 96.87%, respectively. The elastography strain ratio of >2 at the internal os and cervical length ⩽2.8 cm were the additional predictors for the same., Conclusion: Cervical elastography can serve as a potential and reliable predictor for preterm delivery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Alpha cells in the pancreas, traditionally known for their role in secreting glucagon to regulate blood glucose levels, are gaining recognition for their involvement in the pathophysiology of type 1 diabetes (T1D). In T1D, autoimmune destruction of beta cells results in insulin deficiency, which in turn may dysregulate alpha cell function, leading to elevated glucagon levels and impaired glucose homeostasis. This dysfunction is characterized by inappropriate glucagon secretion, augmenting the risk of life-threatening hypoglycemia. Moreover, insulin deficiency and autoimmunity alter alpha cell physiological responses, further exacerbating T1D pathophysiology. Recent studies suggest that alpha cells undergo transdifferentiation and interact with beta cells through mechanisms involving gamma-aminobutyric acid (GABA) signaling. Despite these advances, the exact pathways and interactions remain poorly understood and are often debated. Understanding the precise role of alpha cells in T1D is crucial, as it opens up avenues for developing new therapeutic strategies for T1D. Potential strategies include targeting alpha cells to normalize glucagon secretion, utilizing glucagon receptor antagonists, enhancing GABA signaling, and employing glucagon-like peptide-1 (GLP-1) receptor agonists. These approaches aim to improve glycemic control and reduce the risk of hypoglycemic events in individuals with T1D. This review provides an overview of alpha cell function in T1D, highlighting the emerging focus on alpha cell dysfunction in the context of historically well-developed beta cell research.

The discovery of insulin by Frederick G Banting and his colleagues in 1921 marked a pivotal moment in medical history. Born in Ontario, Canada, in 1891, Banting's childhood was impacted by the death of his closest friend, Jane, who died of diabetes mellitus at a young age. This personal tragedy profoundly influenced him to choose a career in medicine and fueled his determination to find a cure for diabetes. This journey led to the discovery of Insulin with the help of Charles H Best and John JR Macleod, resulting in a Nobel Prize for this work. Their discoveries set the stage for advancements in clinical medicine and biotechnology, including developing recombinant insulin over 50 years later., Competing Interests: 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, Sharma et al.)

Metal nanoparticles and nanoclusters are pivotal in nanomaterial science, each offering unique properties for diverse applications. Nanoclusters, typically smaller than 2 nm, exhibit distinct optical and electronic characteristics due to quantum confinement, resulting in fluorescence emission. In contrast, metal nanoparticles, sized between 2 and 100 nm, exhibit absorption spectra. Both are synthesized by reducing metal precursors in the presence of a suitable stabilizing agent. While nanoparticles have been the historical research focus, recent attention has shifted to nanoclusters for their exceptional properties and their synthesis has evolved significantly over the past few decades. This review discusses the selective synthesis of nanoclusters over nanoparticles, emphasizing the role of various factors such as ligand concentration (metal-to-ligand ratio), reducing agents, pH, reaction time and temperature, solvents, and assistant reagents. Higher ligand concentrations stabilize smaller nanoclusters by preventing aggregation, while lower concentrations lead to larger nanoparticles. Stronger reducing agents produce smaller, more uniform particles, whereas weaker reducing agents yield larger ones. pH affects nanocluster size and emission properties. Solvents and assistant reagents influence reaction kinetics and material properties. Temperature and reaction time also play critical roles in controlling nanocluster size and properties. These insights guide the optimized synthesis of metal nanoclusters, for their specific applications., Competing Interests: Declarations Ethical approval The authors declare that they have no conflict of interest. The results/data/figures in this manuscript have not been published elsewhere nor are they under consideration by another publisher. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

India is at the cusp of an impending epidemic of cardiovascular diseases (CVD). It has been triggered by rapid urbanization, industrialization, and globalization. Coronary artery disease (CAD) and ischemic heart disease (IHD) clinically present as angina pectoris (chest pain and discomfort). Despite advances in treatment options for CAD, a lack of awareness of risk factors and disease, access to healthcare, and affordability are the primary concerns in low- and middle-income countries. In India, CAD results in >7 million deaths annually. There is a need for active collaboration between patients, physicians, and healthcare providers to identify the early and adequate use of lifestyle, pharmacological, and primary and secondary preventive measures. Antianginal treatment options are categorized as first line (calcium channel blockers (CCBs), β-blockers, and short-acting nitrates) and second line (ivabradine, nicorandil, ranolazine, and trimetazidine) drugs. This review discusses different CCBs (dihydropyridines (DHPs) or nondihydropyridines) for the management of angina pectoris., (© Journal of the Association of Physicians of India 2024.)

The bluetongue virus (BTV), transmitted by biting midges, poses a significant threat to livestock globally. This orbivirus induces bluetongue disease, leading to substantial economic losses in the agricultural sector. The current control measures have limitations, necessitating the development of novel, efficient vaccines. In this study, an immunoinformatics approach is employed to design a multi-epitope subunit vaccine for Ovis aries targeting six BTV serotypes. Focusing on the VP2 capsid protein, the vaccine incorporates B-cell, helper-T lymphocytes (HTL), and cytotoxic T-cell lymphocytes (CTL) epitopes. Molecular docking reveals stable interactions with TLR2 and TLR4 receptors, suggesting the stability of the complex, indicating the potential viability of the multi-epitope vaccine. The computational approach offers a rapid and tailored strategy for vaccine development, highlighting potential efficacy and safety against BTV outbreaks. This work contributes to understanding BTV and presents a promising avenue for effective control.

Background: Lisfranc injuries are often managed surgically with primary arthrodesis (PA) or open reduction and internal fixation (ORIF); however, neither approach has been shown to be superior. This systematic review and meta-analysis assessed randomized controlled trials (RCTs) to compare the functional and surgical outcomes of PA and ORIF in the treatment of Lisfranc injuries., Methods: This study was performed as per the PRISMA protocol. Database searches were conducted on Cochrane, Embase, and PubMed libraries. Five RCTs were identified for inclusion involving 241 patients, of which 121 underwent PA and 120 underwent ORIF., Results: Statistically significant differences in visual analog scale pain score at 2 years (mean difference 0.89, 95% CI 0.18-1.59), patient satisfaction (OR 10.04, 95% CI 1.78-56.76), and all-cause return to surgery (OR 27.31, 95% CI 12.72-58.63) were observed, all favoring PA. There were no statistically significant differences between PA and ORIF with regard to American Orthopaedic Foot & Ankle Society midfoot scores at 2 years, 36-Item Short Form Health Survey (SF-36) scores, and unplanned return to surgery., Conclusion: This study showed significant improvement in pain at 2 years, patient satisfaction, and all-cause return to surgery favoring PA in all instances. Given ORIF often necessitates a second operation for hardware removal, it is to be expected that all-cause return to surgery is higher in ORIF groups. Overall, these results do not have the power to confer an advantage to a particular approach because of significant heterogeneity. Further studies should focus on larger patient cohorts and longer follow-up, or analysis stratified by patient demographics and injury presentation. In the absence of clinically significant differences, cost-benefit analyses should be considered to answer the question of whether to "fix or fuse" for Lisfranc injuries., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

Alois Alzheimer was a German psychologist and neuropathologist who significantly advanced the study of dementia with his discovery of Alzheimer's disease (AD). Based on his assessment of a 51-year-old female patient with symptoms of presenile dementia and after conducting a postmortem autopsy of her brain, Alzheimer distinguished two neurological substances - senile plaques and neurofibrillary tangles - as unique markers of what was later deemed as AD. He recognized that dementia is not a natural consequence of age but rather a recognizable neurocognitive disorder. Despite the long-lasting criticism of his findings, Alzheimer's discovery fundamentally altered the landscape of neuropathological studies by establishing that AD was a clinically identifiable disease with distinct markers that could be targeted for treatment. Today, modern research on AD continues to build on the foundation laid by Alzheimer's discovery., Competing Interests: 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, Thakor et al.)

Background: The risk of biochemical recurrence (BCR) after radiotherapy for localized prostate cancer (PCa) varies widely within standard risk groups. There is a need for low-cost tools to more robustly predict recurrence and personalize therapy. Radiomic features from pretreatment MRI show potential as noninvasive biomarkers for BCR prediction. However, previous research has not fully combined radiomics with clinical and pathological data to predict BCR in PCa patients following radiotherapy.&#xD;Purpose: This study aims to predict 5-year BCR using radiomics from pretreatment T2W MRI and clinical-pathological data in PCa patients treated with radiation therapy, and to develop a unified model compatible with both 1.5T and 3T MRI scanners.&#xD;Methods: A total of 150 T2W scans and clinical parameters were preprocessed. Of these, 120 cases were used for training and validation, and 30 for testing. Four distinct machine learning models were developed: Model 1 used radiomics, Model 2 used clinical and pathological data, and Model 3 combined these using late fusion. Model 4 integrated radiomic and clinical-pathological data using early fusion.&#xD;Results: Model 1 achieved an AUC of 0.73, while Model 2 had an AUC of 0.64 for predicting outcomes in 30 new test cases. Model 3, using late fusion, had an AUC of 0.69. Early fusion models showed strong potential, with Model 4 reaching an AUC of 0.84, highlighting the effectiveness of the early fusion model.&#xD;Conclusions: This study is the first to use a fusion technique for predicting BCR in PCa patients following radiotherapy, utilizing pre-treatment T2W MRI images and clinical-pathological data. The methodology improves predictive accuracy by fusing radiomics with clinical-pathological information, even with a relatively small dataset, and introduces the first unified model for both 1.5T and 3T MRI images., (Creative Commons Attribution license.)

Late recurrence of hepatocellular carcinoma (HCC) following orthotopic liver transplant (OLT) is infrequently reported, and among cases, those isolated to the spine are rare. Prognoses are poor for this patient population, and no work has been undertaken to create uniform guidelines for management. Here, we report two cases of late recurrent HCC to the spine after OLT and favorable survival outcomes following intervention., 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.)

Objectives: Fatty atrophy and fatty infiltration have been considered as limiting factors for rotator cuff repair. The metabolic activity of the muscle can be measured noninvasively by PET. In our study, we aim to compare the metabolic activity between the shoulders with rotator cuff tears and normal shoulders., Methods: All the patients with unilateral full-thickness rotator cuff tears were included. The patients were divided into two groups based on fatty atrophy and the metabolic activities of the rotator cuff muscles, trapezius, and deltoid were calculated using an 18 F-2-deoxy- d -glucose PET-computed tomography scan for comparison., Results: A total of 17 patients were included. The standardized uptake values were compared between the affected shoulder and the normal shoulders. There was a significant increase in uptake in the insertion sites and musculotendinous junctions in the rotator cuff torn group. The standardized uptake values showed no significant difference between the low-grade and high-grade groups., Conclusion: Our first hypothesis was also proven wrong; when we found that there was no statistically significant difference in the metabolic activity in muscle bellies of normal shoulders and those with rotator cuff tears. Our second hypothesis was proven wrong when found that there was no statistically significant difference in the metabolic activities of rotator cuff muscles between high-grade and low-grade fatty atrophy groups. The metabolic activities of the middle deltoid and trapezius are inversely related. Based on the findings of our study, fatty atrophy or fatty infiltration alone cannot be considered a limiting factor for rotator cuff repair., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Retinoblastoma (RB) is an intraocular malignancy initiated by loss of RB1 function and/or dysregulation of MYCN oncogene. RB is primarily treated with chemotherapy; however, systemic toxicity and long-term adverse effects remain a significant challenge necessitating the identification of specific molecular targets. Aurora kinase A (AURKA), a critical cell cycle regulator, contributes to cancer pathogenesis, especially in RB1-deficient and MYCN-dysregulated tumors. The current immunohistochemistry study in patient specimens (n = 67) indicated that AURKA is overexpressed in RB, and this elevated expression correlates with one or more histopathologic high-risk factors, such as tumor involvement of the optic nerve, choroid, sclera, and/or anterior segment. More specifically, AURKA is ubiquitously expressed in most advanced-stage RB tumors that show a suboptimal response to chemotherapy. shRNA-mediated depletion/pharmacologic inhibition studies in cell lines, patient-derived cells, in vivo xenografts, and enucleated patient specimens confirmed that RB cells are highly sensitive to a lack of functional AURKA. In addition, AURKA and N-myc proto-oncogene protein (MYCN) associate with each other to regulate their levels in RB cells. Overall, these results demonstrate a previously unknown up-regulation of AURKA in RB, facilitated by its crosstalk with MYCN. The elevated levels of this kinase may indicate unfavorable prognosis in tumors refractory to chemotherapy. This study provides a rationale and confirms that therapeutic targeting of elevated AURKA in RB could be a potential treatment approach., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

In this work, L-Histidine-protected copper nanoclusters synthesized by changing the pH levels of precursor solution have been shown to display different emission wavelengths and intensities. As determined by mass spectrometry, nanoclusters Cu 3 L 2 synthesized at acidic pH have 3 atoms in their core and emit in the greenish-yellow region, and nanoclusters Cu 2 L 2 , synthesized in the basic conditions have 2 atoms in their core and emit in the blue-green region. They are expected to have coordination through the carboxylate group and nitrogen of the imidazole ring of histidine ligand, respectively. Metal ions Mg 2+ , Mn 2+ , Zn 2+ , and Pb 2+ selectively enhance the interaction between carboxylate - copper metal core and increase the emission intensity of Cu 3 L 2 . These metal ions weaken the interaction between imidazole nitrogen and copper metal core and quench the emission intensity of Cu 2 L 2 . As synthesized, nanoclusters exhibit good water solubility and photostability, they can act as fluorescent probes to sense the metal ions, therefore, they were utilized for the optical sensing of the mentioned metal ions. Fluorescent nanoclusters were found to sense even a very low concentration of metal ions with a limit of detection (3 σ/slope) in nanomolar range., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Loose bodies in the knee joint are relatively common and the common causes are transchondral fractures, synovial chondromatosis, osteochondritis dissecans, meniscal injury, and osteoarthritis. Neoplastic growths from synovium have been reported to have presentations mimicking loose bodies or meniscus tears., Case Report: We report the case of an unusual cause of loose body in the knee joint of a 35-year-old male who reported for follow-up 3 years after the surgical management of giant cell tumor (GCT) of the distal femur. He had symptoms of loose bodies in the joint without any complaint specific to the operative site. Imaging revealed loose bodies within the joint which were removed arthroscopically. Histopathology showed the loose bodies as GCT. The patient had relief of symptoms after removal and the patient has no evidence of recurrence at the primary site or in the knee joint., Conclusion: GCTs should be considered a cause of loose bodies in the joint when there is a neighboring bone affected by GCT and all such loose bodies removed should undergo histopathological examination., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

This work reports the synthesis of nickel ferrite (NiFe) nanoparticles, N-doped mesoporous carbon nanoflakes (NCF) and novel nickel ferrite-carbon nanoflakes (NiFe@NCF) nanocomposite using solvothermal method. NCF was derived from a cyanobacterial consortium consisting of Anabaena, Lyngbya and Weistiellopsis, rich in carbon and nitrogen. The synthesized nanoparticles were used as heterogeneous photocatalyst for degradation of two harmful water pollutants, ciprofloxacin (CIP) and levofloxacin (LEV). 99.91% LEV and 98.86% CIP were degraded within 50 and 70 min of visible light irradiation using NiFe@NCF following pseudo first order kinetics. This improved efficiency of the nanocomposite may be attributed to its higher surface area, reduction of band gap (from 2.42 to 2.19 eV), more active sites as well as charge carrier mobility with decreasing agglomeration tendency of the magnetic nickel nanoparticles upon being embedded on NCF. N-doping improves light harvesting property, retards charge recombination and extends as well as delocalises ᴨ-conjugated system resulting in enhanced photocatalytic activity. The scavenging experiments and EPR analysis reveal that O 2 -• and •OH are the main active species taking part in the degradation process. The material performs well within a wide range of pH and can be effectively used up to 5 repetitive cycles. A feasible photocatalytic degradation mechanism of the antibiotics against NiFe@NCF nanocomposite is also put forwarded along with their possible degradation pathways from LCMS studies., 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.)

Objective(s): The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before the start of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT., Methods: Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals., Results: One hundred and fifty patients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66., Conclusion: Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colours of India is an annual cultural phenomenon that transcends the boundaries of professional conferences, uniting endocrinologists through the universal language of music and dance. Since its inception in 2016, this vibrant event has brought together teams from across India and other participating countries, showcasing diverse dance forms while fostering friendships, promoting wellness, and celebrating cultural diversity within the medical community., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Endocrinology and Metabolism.)

Autism is a neurodevelopmental disorder that manifests in individuals during childhood and has enduring consequences for their social interactions and communication. The prediction of Autism Spectrum Disorder (ASD) in individuals based on the differences in brain networks and activities have been studied extensively in the recent past, however, with lower accuracies. Therefore in this research, identification at the early stage through computer-aided algorithms to differentiate between ASD and TD patients is proposed. In order to identify features, a Multi-Layer Perceptron (MLP) model is developed which utilizes logistic regression on characteristics extracted from connectivity matrices of subjects derived from fMRI images. The features that significantly contribute to the classification of individuals as having Autism Spectrum Disorder (ASD) or typically developing (TD) are identified by the logistic regression model. To enhance emphasis on essential attributes, an AND operation is integrated. This involves selecting features demonstrating statistical significance across diverse logistic regression analyses conducted on various random distributions. The iterative approach contributes to a comprehensive understanding of relevant features for accurate classification. By implementing this methodology, the estimation of feature importance became more dependable, and the potential for overfitting is moderated through the evaluation of model performance on various subsets of data. It is observed from the experimentation that the highly correlated Left Lateral Occipital Cortex and Right Lateral Occipital Cortex ROIs are only found in ASD. Also, it is noticed that the highly correlated Left Cerebellum Tonsil and Right Cerebellum Tonsil are only found in TD participants. Among the MLP classifier, a recall of 82.61 % is achieved followed by Logistic Regression with an accuracy of 72.46 %. MLP also stands out with a commendable accuracy of 83.57 % and AUC of 0.978., 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. Published by Elsevier B.V.)

A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25-100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25-100 µl), and Pseudomonas spp. inoculums (50-150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC-MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8 th day. From LC-MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 10 6 and 210 × 10 6  CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties., (© 2024. The Author(s).)

Diabetic Peripheral Neuropathy (DPN) is a prevalent and debilitating complication of diabetes, affecting a significant proportion of the diabetic population. Neuromodulation, an emerging therapeutic approach, has shown promise in the management of DPN symptoms. This systematic review aims to synthesize and analyze the current advancements in neuromodulation techniques for the treatment of DPN utilizing studies with preclinical animal models. A comprehensive search was conducted across multiple databases, including PubMed, Scopus, and Web of Science. Inclusion criteria were focused on studies utilizing preclinical animal models for DPN that investigated the efficacy of various neuromodulation techniques, such as spinal cord stimulation, transcranial magnetic stimulation, and peripheral nerve stimulation. The findings suggest that neuromodulation significantly alleviated pain symptoms associated with DPN. Moreover, some studies reported improvements in nerve conduction velocity and reduction in nerve damage. The mechanisms underlying these effects appeared to involve modulation of pain pathways and enhancement of neurotrophic factors. However, the review also highlights the variability in methodology and stimulation parameters across studies, highlighting the need for standardization in future research. Additionally, while the results are promising, the translation of these findings from animal models to human clinical practice requires careful consideration. This review concludes that neuromodulation presents a potentially effective therapeutic strategy for DPN, but further research is necessary to optimize protocols and understand the underlying molecular mechanisms. It also emphasizes the importance of bridging the gap between preclinical findings and clinical applications to improve the management of DPN in diabetic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mittal 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.)

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited., Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers., Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023., Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy., Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion., Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07)., Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

(1) Background: Antibiotic surveillance data are crucial to map out strategies to promote their optimal use at hospital and community levels. We conducted a comprehensive analysis of longitudinal trends in antibiotic consumption over 7 years at a core "National Antimicrobial Consumption Network" site in North India. (2) Methods: In-patient antibiotic consumption data (2017-2023) were obtained from the hospital's central drug store and organised as follows: defined daily dose per 100 bed-days; antibiotic consumption as per the WHO access, watch and reserve classification; trends in overall and different antibiotic classes' consumption; paediatric formulations of antibiotics; and hospital's annual expenditure on antibiotics. (3) Results: During the 7-year study period, no significant trend could be observed in the overall antibiotic consumption (average annual percent change, AAPC: 9.22; 95% CI: -16.46, 34.9) and cost (AAPC: 13.55; -13.2, 40.3). There was a higher proportion of the consumption of antibiotics in the "reserve" group from 2021 onwards compared to previous years, but the overall trend over 7 years was not significant (AAPC: 319.75; -137.6, 777.1). Antibiotic combinations, classified under the WHO "not recommended" category, comprised a significant proportion of antibiotics consumed. A remarkably increased consumption of azithromycin and doxycycline was recorded during 2020 and 2021, coinciding with the COVID-19 pandemic. (4) Conclusions: Some recommendations to optimise antibiotic use are promoting the use of narrow spectrum "access" group agents; linking antimicrobial resistance and consumption data to formulate effective therapeutic and prophylactic antibiotic use guidelines; and the adoption of restrictive antibiotic policy.

Objectives: The aim of this systematic review article is to evaluate the relationship between diabetes mellitus (DM) and sensorineural hearing loss (SNHL) utilizing preclinical animal models. The review focused on studies assessing SNHL in diabetic animal models, elucidating the mechanisms of DM-associated SNHL, and exploring the response of diabetic animal models to noise overexposure. We also discussed studies investigating the efficacy of potential therapeutic strategies for amelioration of DM-associated SNHL in the animal models., Methods: A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42023439961). We conducted a comprehensive search on PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. A minimum of three reviewers independently screened, selected, and extracted data. The risk of bias assessment of eligible studies was conducted using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool., Results: Following the screening of 238 studies, twelve original articles were included in this systematic review. The studies revealed that hyperglycemia significantly affects auditory function, with various pathological mechanisms contributing to DM-induced hearing impairment, including cochlear synaptopathy, microangiopathy, neuropathy, oxidative stress, mitochondrial abnormalities, and apoptosis-mediated cell death. Emerging interventions, such as Asiaticoside, Trigonelline, Chlorogenic acid, and Huotanquyu granules, demonstrated efficacy in providing otoprotection for preserving cochlear hair cells and hearing function., Conclusions: Our systematic review delves into the intricate relationship between DM and hearing impairment in animal models. Future research should focus on targeted therapies to enhance cochlear mitochondrial function, alleviate oxidative stress, and regulate apoptosis. The association between SNHL and social isolation as well as cognitive decline underscores the necessity for innovative therapeutic modalities addressing yet undiscovered mechanisms. Translating findings from animal models to human studies will validate these findings, offering a synergistic approach to effectively manage DM-associated co-morbidities such as hearing impairment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mittal 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.)

The sensitivity of ferroelectric domain walls to external stimuli makes them functional entities in nanoelectronic devices. Specifically, optically driven domain reconfiguration with in-plane polarization is advantageous and thus is highly sought. Here, we show the existence of in-plane polarized subdomains imitating a single domain state and reversible optical control of its domain wall movement in a single-crystal of ferroelectric BaTiO 3 . Similar optical control in the domain configuration of nonpolar ferroelastic material indicates that long-range ferroelectric polarization is not essential for the optical control of domain wall movement. Instead, flexoelectricity is found to be an essential ingredient for the optical control of the domain configuration, and hence, ferroelastic materials would be another possible candidate for nanoelectronic device applications.

Purpose: Lung cancer is the second most common cancer and the leading cause of cancer death globally. Low dose computed tomography (LDCT) is the recommended imaging screening tool for the early detection of lung cancer. A fully automated computer-aided detection method for LDCT will greatly improve the existing clinical workflow. Most of the existing methods for lung detection are designed for high-dose CTs (HDCTs), and those methods cannot be directly applied to LDCTs due to domain shifts and inferior quality of LDCT images. In this work, we describe a semi-automated transfer learning-based approach for the early detection of lung nodules using LDCTs., Approach: In this work, we developed an algorithm based on the object detection model, you only look once (YOLO) to detect lung nodules. The YOLO model was first trained on CTs, and the pre-trained weights were used as initial weights during the retraining of the model on LDCTs using a medical-to-medical transfer learning approach. The dataset for this study was from a screening trial consisting of LDCTs acquired from 50 biopsy-confirmed lung cancer patients obtained over 3 consecutive years (T1, T2, and T3). About 60 lung cancer patients' HDCTs were obtained from a public dataset. The developed model was evaluated using a hold-out test set comprising 15 patient cases (93 slices with cancerous nodules) using precision, specificity, recall, and F1-score. The evaluation metrics were reported patient-wise on a per-year basis and averaged for 3 years. For comparative analysis, the proposed detection model was trained using pre-trained weights from the COCO dataset as the initial weights. A paired t-test and chi-squared test with an alpha value of 0.05 were used for statistical significance testing., Results: The results were reported by comparing the proposed model developed using HDCT pre-trained weights with COCO pre-trained weights. The former approach versus the latter approach obtained a precision of 0.982 versus 0.93 in detecting cancerous nodules, specificity of 0.923 versus 0.849 in identifying slices with no cancerous nodules, recall of 0.87 versus 0.886, and F1-score of 0.924 versus 0.903. As the nodule progressed, the former approach achieved a precision of 1, specificity of 0.92, and sensitivity of 0.930. The statistical analysis performed in the comparative study resulted in a p -value of 0.0054 for precision and a p -value of 0.00034 for specificity., Conclusions: In this study, a semi-automated method was developed to detect lung nodules in LDCTs using HDCT pre-trained weights as the initial weights and retraining the model. Further, the results were compared by replacing HDCT pre-trained weights in the above approach with COCO pre-trained weights. The proposed method may identify early lung nodules during the screening program, reduce overdiagnosis and follow-ups due to misdiagnosis in LDCTs, start treatment options in the affected patients, and lower the mortality rate., (© 2024 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: Diabetic foot ulcers (DFUs) are a challenging complication of diabetes mellitus, often leading to poor clinical outcomes and significant socioeconomic burdens. We evaluated the effectiveness of a definitive single-stage protocolized surgical management pathway, including the use of local antibiotic bone graft substitute, for the treatment of infected DFUs with associated osteomyelitis., Methods: A retrospective cohort study was conducted. Medical records were extracted (from January 2017 to December 2020) to establish a database consisting of patients who underwent surgical intervention for the treatment of an infected DFU with osteomyelitis. Patients were divided into conventional (control) and protocolized (intervention) surgical groups depending on the treatment received. Clinical outcomes were assessed over a 12-month follow-up period., Results: A total of 136 consecutive patients were included (conventional = 33, protocolized = 103). The protocolized group demonstrated a statistically significant reduction in the mean number of operations performed per patient (1.2 vs. 3.5) (P < 0.001) and a shorter accumulative hospital length of stay (12.6 vs. 25.1 days) (P < 0.001) compared to the conventional group. Major amputation rates were significantly lower in the protocolized group (2% vs. 18%) (P < 0.001). Within 12 months of surgical intervention, the protocolized group exhibited an ulcer healing rate of 89%, with a low rate of recurrence (3%)., Conclusion: The protocolized surgical pathway, including local antibiotic bone graft substitute use, demonstrated superior outcomes compared to conventional management for the treatment of infected DFUs with osteomyelitis. Further research is needed to evaluate the cost-effectiveness and generalizability of this approach., (© 2024 Royal Australasian College of Surgeons.)

Background: Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient's quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer., Methods: Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline., Results: Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from Withania somnifera justified the Lipinski's Rule of 5., Conclusion: Viscosalactone obtained from W. somnifera may act as promising drug candidate to fight against metastatic breast cancer., Competing Interests: Conflict of interest: Authors declared no conflict of interest., (© the Author(s).)

Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies., (© 2024. The Author(s).)

Background : Vestibular schwannoma (VS) is a benign tumor of the eighth cranial nerve formed from neoplastic Schwann cells. Although VS can cause a variety of symptoms, tinnitus is one of the most distressing symptoms for patients and can greatly impact quality of life. The objective of this systematic review is to comprehensively examine and compare the outcomes related to tinnitus in patients undergoing treatment for VS. Specifically, it evaluates patient experiences with tinnitus following the removal of VS using the various surgical approaches of traditional surgical resection and gamma knife radiosurgery (GKS). By delving into various aspects such as the severity of tinnitus post-treatment, the duration of symptom relief, patient quality of life, new onset of tinnitus after VS treatment, and any potential complications or side effects, this review aims to provide a detailed analysis of VS treatment on tinnitus outcomes. Methods : Following PRISMA guidelines, articles were included from PubMed, Science Direct, Scopus, and EMBASE. Quality assessment and risk of bias analysis were performed using a ROBINS-I tool. Results : Although VS-associated tinnitus is variable in its intensity and persistence post-resection, there was a trend towards a decreased tinnitus burden in patients. Irrespective of the surgical approach or the treatment with GKS, there were cases of persistent or worsened tinnitus within the studied cohorts. Conclusion : The findings of this systematic review highlight the complex relationship between VS resection and tinnitus outcomes. These findings underscore the need for individualized patient counseling and tailored treatment approaches in managing VS-associated tinnitus. The findings of this systematic review may help in guiding clinicians towards making more informed and personalized healthcare decisions. Further studies must be completed to fill gaps in the current literature.

Background: Dermatophytosis, a major cause of superficial fungal infections, requires topical and systemic antifungals. Amorolfine, a morpholine derivative, is a new topical antifungal available in cream and lotion formulations., Objective: To evaluate the efficacy and safety of amorolfine lotion 0.25% compared to amorolfine cream 0.25% in patients with dermatophytosis., Methods: A multi-center randomized, two-arm, active-controlled, parallel, non-inferiority phase III clinical trial involving 284 dermatophytosis patients was conducted, with the test arm using amorolfine lotion and the reference arm using amorolfine cream. The study drugs were applied once daily in the evening for four weeks and patients were followed up for another two weeks. The primary endpoint was clinical cure, while secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Safety and tolerability were assessed., Results: Amongst the enrolled patients, 69.9% and 68.1% of patients had tinea corporis, while 30.1% and 31.9% had tinea cruris. The majority of patients in both groups (99.3% test and 97% reference) achieved a clinical cure at the end of treatment. Mycological cure was achieved by 98.6% and 96.3% respectively. A composite cure was achieved by 98.6% in the test arm versus 96.3% in the reference arm. A total of two AEs were reported in two (1.4%) patients in the test group and three AEs were reported in three (2.1%) patients in the reference group, all of the AEs were mild and resolved within three days without supportive medication. No severe adverse effects were reported in any of the study subjects., Conclusion: Amorolfine lotion 0.25% w/v showed a non-inferior clinical, mycological, and composite cure in dermatophytosis patients, was well-tolerated, and had a similar safety profile to amorolfine cream 0.25% w/w., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Rao et al.)

Background: Hypertensive disorders in pregnancy account for 15%-20% maternal and 20%-25% perinatal mortality. There is interest in predicting preeclampsia (PE) early in pregnancy to reduce PE and its subsequent complications. There is no cheap and easily available, reliable predictor for PE. Some studies have shown that the lateral location of placenta is associated with adverse pregnancy outcomes due to PE. The lateral placenta is yet to be proven as a strong predictor of PE to initiate preventive measures. Placental localization can be easily done on routine ultrasonography during pregnancy. In the light of these observations, a prospective study was done to study any association between PE and placental location by ultrasound in third trimester. Research Question: Is there any association between placental location on ultrasound and preeclampsia in third trimester? The objective is to study association between location of placenta and preeclampsia and compare placental location in normotensive pregnancies with that in PE in third trimester., Methods: A prospective comparative, case-control, observational study was conducted in the Department of Obstetrics and Gynecology at North DMC Medical College and Hindu Rao Hospital, Delhi, India, from August 2019 to April 2020. The study population included 200 pregnant women with singleton pregnancy in third trimester, without any medical disorders such as diabetes mellitus, hypertension, renal disease, cardiac disease, and coagulation disorder or smoking. One hundred women had preeclampsia and 100 were normotensive controls. Ultrasound was done after filling F form as per the Government of India guidelines to rule out sex determination, and placenta was localized by ultrasound. Placenta was classified as central when it was equally distributed between the right and left sides of the uterus irrespective of anterior, posterior, or fundal position and lateral when 75% or more of the placental mass was on one side of the midline. Placental location was compared in hypertensive and normotensive pregnancies., Results: Out of the total 200 women, 152 (76%) had central and 48 (24%) had lateral placenta. Ninety-two percent of controls and 60% of cases had central placenta. Forty percent of cases and only 8% normotensive women had lateral placenta. Lateral placenta was five times more frequent in presence of PE as compared to normotensive controls. Out of 152 women with central placenta, 92 (60.5%) women were normotensive but with lateral placenta, only 8 (16.7%) had normal blood pressure. PE was present in 83% of women with lateral placenta and in only 39.47% with central placenta. This difference was statistically significant as P < 0.0001 as per Chi-square test. This reflects a significant association between lateral position of placenta and occurrence of PE. As per odds ratio (0.1304) patients without lateral placenta had 90% protection against preeclampsia., Conclusion: Central placenta is more common than lateral placenta. Lateral placenta is seen five times more frequently among hypertensive women and this difference is statistically significant. The absence of lateral placenta provides 90% protection against PE but the severity of PE was not affected by placental location.., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Medical Ultrasound.)

About 10 million people are diagnosed with cancer each year. Globally, it is the second leading cause of death after heart disease, and by 2035, the death toll could reach 14.6 million. Several drugs and treatments are available to treat cancer, but survival rates remain low. Many studies in recent years have shown that plant-derived monoterpenes, particularly geraniol and citral, are effective against various cancers, including breast, liver, melanoma, endometrial, colon, prostate, and skin cancers. This trend has opened new possibilities for the development of new therapeutics or adjuvants in the field of cancer therapy. These monoterpenes can improve the efficacy of chemotherapy by modulating many signaling molecules and pathways within tumors. Analysis of reports on the anticancer effects published in the past 5 years provided an overview of the most important results of these and related properties. Also, the molecular mechanisms by which they exert their anticancer effects in cell and animal studies have been explained. Therefore, this review aims to highlight the scope of geraniol and citral as complementary or alternative treatment options in cancer therapy., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Bicuspid aortic valve (BAV) is the most common cardiac congenital abnormality with a high rate of concomitant aortic valve and ascending aorta (AAo) pathologic changes throughout the patient's lifetime. The etiology of BAV-related aortopathy was historically believed to be genetic. However, recent studies theorize that adverse hemodynamics secondary to BAVs also contribute to aortopathy, but their precise role, specifically, that of wall shear stress (WSS) magnitude and directionality remains controversial. Moreover, the primary therapeutic option for BAV patients is aortic valve replacement (AVR), but the role of improved post-AVR hemodynamics on aortopathy progression is also not well-understood. To address these issues, this study employs a computational fluid dynamics model to simulate personalized AAo hemodynamics before and after TAVR for a small cohort of 6 Left-Right fused BAV patients. Regional distributions of five hemodynamic metrics, namely, time-averaged wall shear stress (TAWSS) and oscillating shear index (OSI), divergence of wall shear (DWSS), helicity flux integral & endothelial cell activation potential (ECAP), which are hypothesized to be associated with potential aortic injury are computed in the root, proximal and distal ascending aorta. BAVs are characterized by strong, eccentric jets, with peak velocities exceeding 4 m/s and axially circulating flow away from the jets. Such conditions result in focused WSS loading along jet attachment regions on the lumen boundary and weaker, oscillating WSS on other regions. The jet attachment regions also show alternating streaks of positive and negative DWSS, which may increase risk for local tissue stretching. Large WSS magnitudes, strong helical flows and circumferential WSS have been previously implicated in the progression of BAV aortopathy. Post-intervention hemodynamics exhibit weaker, less eccentric jets. Significant reductions are observed in flow helicity, TAWSS and DWSS in localized regions of the proximal AAo. On the other hand, OSI increases post-intervention and ECAP is observed to be low in both pre- and post-intervention scenarios, although significant increases are also observed in this ECAP. These results indicate a significant alleviation of pathological hemodynamics post AVR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bailoor 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.)

Computational models are used to examine the effect of schooling on flow generated noise from fish swimming using their caudal fins. We simulate the flow as well as the far-field hydrodynamic sound generated by the time-varying pressure loading on these carangiform swimmers. The effect of the number of swimmers in the school, the relative phase of fin flapping of the swimmers, and their spatial arrangement is examined. The simulations indicate that the phase of the fin flapping is a dominant factor in the total sound radiated into the far-field by a group of swimmers. For small schools, a suitable choice of relative phase between the swimmers can significantly reduce the overall intensity of the sound radiated to the far-field. The relative positioning of the swimmers is also shown to have an impact on the total radiated noise. For a larger school, even highly uncorrelated phases of fin movement between the swimmers in the school are very effective in significantly reducing the overall intensity of sound radiated into the far-field. The implications of these findings for fish ethology as well as the design and operation of bioinspired vehicles are discussed., (Creative Commons Attribution license.)

In India, around 234 million adults (one in three) suffer from hypertension (HTN). An average of 10% of these cases are likely to be resistant hypertension (RH). This load of 23 million patients is expected to expand further with revisions in diagnostic criteria. The treatment and control rates of hypertension in India average around 30% and 15%, respectively. Pharmacological management involves a stepwise approach starting with optimizing the A-C-D (angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide-like diuretics) triple-drug combination, followed by substitution with a thiazide-like diuretic and use of spironolactone as a next step (fourth drug). The subsequent steps are suggestions based on expert input and must be individualized. These include using a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when target blood pressure (BP) values are not achieved. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are likely to be helpful in managing RH due to their renal and cardiovascular protection as well as mortality benefits. SGLT2i lowers BP independent of the dosage and concomitant anti-hypertensive medications. Patient education and tools to monitor BP and treatment compliance will improve outcomes with these medications. In addition to therapeutic intervention, a preventive approach for RH mandates a need to identify patients at risk and use appropriate preventive and optimal therapy to prevent uncontrolled hypertension in patients with cardiovascular disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mittal et al.)

Background : Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Recent research has increasingly focused on the genetic underpinnings of ASD, with the Neurexin 1 ( NRXN1 ) gene emerging as a key player. This comprehensive systematic review elucidates the contribution of NRXN1 gene variants in the pathophysiology of ASD. Methods : The protocol for this systematic review was designed a priori and was registered in the PROSPERO database (CRD42023450418). A risk of bias analysis was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool. We examined various studies that link NRXN1 gene disruptions with ASD, discussing both the genotypic variability and the resulting phenotypic expressions. Results : Within this review, there was marked heterogeneity observed in ASD genotypic and phenotypic manifestations among individuals with NRXN1 mutations. The presence of NRXN1 mutations in this population emphasizes the gene's role in synaptic function and neural connectivity. Conclusion : This review not only highlights the role of NRXN1 in the pathophysiology of ASD but also highlights the need for further research to unravel the complex genetic underpinnings of the disorder. A better knowledge about the multifaceted role of NRXN1 in ASD can provide crucial insights into the neurobiological foundations of autism and pave the way for novel therapeutic strategies.

Hydatid disease is endemic in some regions of the world. Even in endemic regions, splenic hydatid cysts are rare, especially in pregnancy. The most serious presentation is intra peritoneal rupture, which is a surgical emergency. Exploration with splenectomy is the favoured management. We present a case of splenic hydatid cyst, detected late in pregnancy, with intraperitoneal rupture in the postpartum period. Cystic lesions located anywhere in the body in endemic regions could be hydatid cysts. Prompt treatment should be planned immediately on detection in order to prevent potentially serious complications like rupture., Competing Interests: Conflict of Interest Non-declared., (© 2024 Ashraf et al. Published by Tehran University of Medical Sciences.)

Point of Care Diagnostics (POCD) is quintessential in hospitals and the healthcare sector as the secants uplift the quality of medical care and the life of a patient by facilitating quick identification of the underlying pathological condition. Nanotechnology can provide opportunities and has potential in the development of new-age sensing/diagnostic tools. Owing to extraordinary features (e.g., higher density, effective catalysis, good conduction, biocompatibility, inertness, and greater surface-to-volume ratio), gold nanoparticles (AuNPs) are frequently employed in POCT (Point-of-Care-Testing). Gold nanoparticles-based colorimetric methods are widely used in the rapid, sensitive, and selective detection of analytes/target molecules. AuNPs description is critical for their possible utility in prophylaxis, diagnostics, and treatment of an ailment. AuNPs interact with organic/inorganic target molecules to generate colorimetric shift that enables the accurate, precise, and subtle recognition of biologicals (e.g., microorganisms, cellular components, and proteins) and metal ions. This review focused on the need for AuNPs-based colorimetric application in prophylaxis, diagnostics, and treatment in healthcare and reviewed the future outlook of these AuNPs for biological applications. Different synthesis methods of AuNPs, their morphology, and characterization, including their surface functionalization, will be discussed in detail. AuNPs are very much preferable nanomaterials owing to exclusive optical, electrical, and photothermal features. AuNPs-based colorimetric biosensors are simple and possess great utility, yet these offer a robust technique to enable visual, quantitative analysis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)