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Abstract The World Health Organization (WHO) has declared the monkeypox outbreak a public health emergency, as there is no specific therapeutics for monkeypox virus (MPXV) disease. This study focused on docking various commercial drugs and plant-derived compounds against the E8 envelope protein crucial for MPXV attachment and pathogenesis. The target protein structure was modeled based on the vaccinia virus D8L protein. Notably, maraviroc and punicalagin emerged as potential ligands, with punicalagin exhibiting higher binding affinity (− 9.1 kcal/mol) than maraviroc (− 7.8 kcal/mol). Validation through 100 ns molecular dynamics (MD) simulations demonstrated increased stability of the E8-punicalagin complex, with lower RMSD, RMSF, and Rg compared to maraviroc. Enhanced hydrogen bonding, lower solvent accessibility, and compact motions also attributed to higher binding affinity and stability of the complex. MM-PBSA calculations revealed van der Waals, electrostatic, and non-polar solvation as principal stabilizing energies. The binding energy decomposition per residue favored stable interactions between punicalagin and the protein’s active site residues (Arg20, Phe56, Glu228, Tyr232) compared to maraviroc. Overall study suggests that punicalagin can act as a potent inhibitor against MPXV. Further research and experimental investigations are warranted to validate its efficacy and safety.

Abstract Background Long-acting injectable cabotegravir plus rilpivirine (LAI CAB/RPV) has several potential benefits over daily oral formulations for HIV treatment, including the potential to facilitate long-term adherence and reduce pill fatigue. We aimed to assess facilitators of and barriers to LAI CAB/RPV implementation and delivery through the perspectives of physicians and clinical staff, and the experiences of LAI CAB/RPV use among people living with HIV (PLWH) at a Ryan-White supported safety-net clinic in North Texas. Methods We conducted semi-structured interviews with recruited clinic staff (physicians, nurses, and support staff) involved with LAI CAB/RPV implementation and PLWH who switched to LAI CAB/RPV and consented to participate in individual interviews. Data were collected from July to October 2023. Our interview guide was informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM), and Proctor Implementation Outcomes frameworks. Qualitative data were analyzed using a rapid qualitative analysis approach to summarize key themes. Results We recruited and interviewed 15 PLWH who transitioned to LAI CAB/RPV and 11 clinic staff serving these patients. PLWH conveyed that emotional and informational support from family or a trusted clinician influenced their decision to switch to LAI CAB/RPV. PLWH also reported that injectable treatment was more effective, convenient, and acceptable than oral antiretroviral therapy. Clinic staff and physicians reported that staff training, pharmacist-led medication switches, flexible appointments, refrigeration space and designated room for injection delivery facilitated implementation. Clinic staff cited medication costs, understaffing, insurance prior authorization requirements, and lack of medication access through state drug assistance programs as critical barriers. Conclusions Our study offers insights into real-world experiences with LAI usage from the patient perspective and identifies potential strategies to promote LAI CAB/RPV uptake. The barriers to and facilitators of LAI CAB/RPV program implementation reported by clinic staff in our study may be useful for informing strategies to optimize LAI CAB/RPV programs.

Abstract The geometric features and operational parameters of rotary blades on rotary tillers significantly impact their performance characteristics. The sweepback angle is a geometric feature of the 'L'-shaped rotary blade that has remained unexplored in previous studies. This study aimed to analyze the effect of geometrical and operational parameters on the performance dynamics of the 'L'-shaped rotary blade. The investigation was conducted using the discrete element method (DEM) and further validated through experiments conducted in a soil bin. The simulation experiment was conducted by dividing the particle bed into horizontal particle zones. The effect of the geometrical (sweepback angle) and operational parameters (forward speed, rotational speed, and depth) on the power requirement, disturbance intensity, and mixing index was studied. The novel method was adopted to determine the mixing capability of rotary blades in terms of sub-domain mixing index (SMI) and overall mixing index (OMI). The results revealed that the power requirements for a sweepback angle of 18° were 26.39% and 16.50% lower than those for sweepback angles of 6° and 12°, respectively. The sweepback angle tends to have the least effect on the overall mixing index compared to operational parameters. The average particle velocity decreased by 22.19% and 29.60% with sweepback angles of 12° and 18°, respectively, compared to the sweepback angle of 6°. The relative error during the experiment varied between 1.29% and 13.51%. It was concluded that the sweepback angle was found to be a feasible option for reducing the power requirement with good mixing indices.

Introduction: Although H3N2 outbreaks were once rare, they have become more common in recent years. With a significant toll on health-care resources and the ability to cripple any society, the epidemiological significance of this disease is paramount. While most of the previous studies on influenza outbreaks have reported H1N1 disease, there is a scarcity of literature regarding the H3N2 clinicoradiological profile. Hereby, we present the clinicoradiological profile of a series of H3N2 cases from western India. Materials and Methods: This is a retrospective chart-based review of clinicoradiological profile of a series of cases that were reported to a tertiary care center in western India between February 2023 and March 2023. Results: A total of 10 patients had tested positive for H3N2. All patients had a history of fever lasting an average of 4.7 days, and six had varying degrees of dyspnea. One patient had gastrointestinal symptoms, and six developed tachypnea with hypoxemia requiring oxygen supplementation. One patient with multiple comorbidities required invasive mechanical ventilation and had a complicated course with a superadded bacterial infection. Out of the four patients with radiographic findings, two had atypical pneumonia/acute infective etiology. Conclusion: This study provides valuable insights into the clinical presentation and management of H3N2 infections. The findings highlight the importance of influenza vaccination and early detection of H3N2 infections to prevent severe complications. The successful outcomes of the patients in this study demonstrate the effectiveness of prompt intervention and appropriate treatment in managing H3N2 infections.

Introduction: Regular monitoring of Vitamin B12 (VB12) levels and intake of supplements is crucial since their deficiency may cause serious health conditions including neurological and cardiovascular complications. Medical professionals recommend supplements in the form of oral tablets and parenteral replacement for patients who cannot obtain these nutrients through diet or who are deficient due to other health conditions. This study aimed to compare the efficacy of oral medications and parenteral administrations, especially intramuscular (IM) injections for managing VB12 deficiency. Methods: The patients diagnosed with confirmed VB12 deficiency (

Abstract Point defect qubits in semiconductors have demonstrated their outstanding capabilities for high spatial resolution sensing generating broad multidisciplinary interest. Hexagonal boron nitride (hBN) hosting point defect qubits have recently opened up new horizons for quantum sensing by implementing sensing foils. The sensitivity of point defect sensors in hBN is currently limited by the linewidth of the magnetic resonance signal, which is broadened due to strong hyperfine couplings. Here, we report on a vacancy-related spin qubit with an inherently low symmetry configuration, the VB2 center, giving rise to a reduced magnetic resonance linewidth at zero magnetic fields. The VB2 center is also equipped with a classical memory that can be utilized for storing population information. Using scanning transmission electron microscopy imaging, we confirm the existence of the VB2 configuration in free-standing monolayer hBN.

Abstract We demonstrate a machine learning-based approach which predicts the properties of crystal structures following relaxation based on the unrelaxed structure. Use of crystal graph singular values reduces the number of features required to describe a crystal by more than an order of magnitude compared to the full crystal graph representation. We construct machine learning models using the crystal graph singular value representations in order to predict the volume, enthalpy per atom, and metal versus semiconductor/insulator phase of DFT-relaxed organic salt crystals based on randomly generated unrelaxed crystal structures. Initial base models are trained to relate 89,949 randomly generated structures of salts formed by varying ratios of 1,3,5-triazine and HCl with the corresponding volumes, enthalpies per atom, and phase of the DFT-relaxed structures. We further demonstrate that the base model is able to be extended to related chemical systems (isomers, pyridine, thiophene and piperidine) with the inclusion of 2000 to 10,000 crystal structures from the additional system. After training a single model with a large number of data points, extension can be done at significantly lower cost. The constructed machine learning models can be used to rapidly screen large sets of randomly generated organic salt crystal structures and efficiently downselect the structures most likely to be experimentally realizable. The models can be used as a stand-alone crystal structure predictor, but may serve CSP efforts best as a filtering step in more sophisticated workflows.

Abstract Social influence pervades our everyday lives and lays the foundation for complex social phenomena, such as the spread of misinformation and the polarization of communities. A disconnect appears between psychology approaches, generally performed and tested in controlled lab experiments, and quantitative methods, which are usually data-driven and rely on network and event analysis. The former are slow, expensive to deploy, and typically do not generalize well to topical issues; the latter often oversimplify the complexities of social influence and ignore psychosocial literature. This work bridges this gap by introducing a human-in-the-loop active learning method that empirically quantifies social influence by crowdsourcing pairwise influence comparisons. We develop simulation and fitting tools, allowing us to estimate the required budget based on the design features and the worker’s decision accuracy. We perform a series of pilot studies to quantify the impact of design features on worker accuracy. We deploy our method to estimate the influence ranking of 500 X/Twitter users. We validate our measure by showing that the obtained empirical influence is tightly linked with agency and communion, the Big Two of social cognition, with agency being the most important dimension for influence formation.

Abstract Background Picocyanobacteria from the genera Prochlorococcus, Synechococcus, and Cyanobium are the most widespread photosynthetic organisms in aquatic ecosystems. However, their freshwater populations remain poorly explored, due to uneven and insufficient sampling across diverse inland waterbodies. Results In this study, we present 170 high-quality genomes of freshwater picocyanobacteria from non-axenic cultures collected across Central Europe. In addition, we recovered 33 genomes of their potential symbiotic partners affiliated with four genera, Pseudomonas, Mesorhizobium, Acidovorax, and Hydrogenophaga. The genomic basis of symbiotic interactions involved heterotrophs benefiting from picocyanobacteria-derived nutrients while providing detoxification of ROS. The global abundance patterns of picocyanobacteria revealed ecologically significant ecotypes, associated with trophic status, temperature, and pH as key environmental factors. The adaptation of picocyanobacteria in (hyper-)eutrophic waterbodies could be attributed to their colonial lifestyles and CRISPR-Cas systems. The prevailing CRISPR-Cas subtypes in picocyanobacteria were I-G and I-E, which appear to have been acquired through horizontal gene transfer from other bacterial phyla. Conclusions Our findings provide novel insights into the population diversity, ecology, and evolutionary strategies of the most widespread photoautotrophs within freshwater ecosystems. Video Abstract

Abstract Background Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. This real-world study used patient and physician surveys to describe the clinical characteristics and disease burden of eosinophilic esophagitis—overall and in a subgroup of patients with dysphagia despite treatment. Methods Data analyzed in this study were collected in 2020 from US and EU patients with eosinophilic esophagitis. Eligible patients were aged ≥ 12 years with a diagnosis of eosinophilic esophagitis, had an esophageal count of ≥ 15 eosinophils/high-power field at diagnosis, and were currently prescribed treatment for eosinophilic esophagitis. Results Overall, 1001 patients were included, of whom 356 (36%) had dysphagia despite treatment. Demographics and clinical characteristics were similar in both populations. The severity of eosinophilic esophagitis was mild in more patients overall (69%) versus those with dysphagia despite treatment (48%). Patient disease history was similar in both populations, with some exceptions: common patient-reported symptoms were dysphagia (70% and 86%) and heartburn/acid reflux (55% and 49%), and common physician-reported symptoms were dysphagia (75% and 91%) and food impaction (46% and 52%). Treatment history was similar in both populations; overall, the most common treatments were proton pump inhibitors (83%) and topical corticosteroids (51%). Patients reported slightly more days with symptoms, higher impacts on activities of daily living, and slightly higher anxiety or depression in the dysphagia-despite-treatment population versus the overall population. Conclusions Eosinophilic esophagitis presents severe symptoms and comorbidities that substantially impact patients’ well-being and quality of life. Greater awareness of and novel treatments for eosinophilic esophagitis are needed.

Abstract Introduction Dermatomyositis (DM) is a rare systemic autoimmune disease characterized by a distinctive debilitating skin rash and skeletal muscle weakness. It is unclear if existing clinical outcome assessment (COA) measures include the concepts of priority to patients and those necessary to fully capture improvements in the active cutaneous manifestations of DM. This study aimed to develop the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA), a de novo IGA, for use in clinical trials of adult DM. Methods Eight DM clinical experts participated in 60-min qualitative interviews consisting of concept elicitation and cognitive debriefing methodologies. Concept elicitation comprised open-ended questions with follow-up probes to explore clinicians’ experiences of treating patients with DM, the impact of symptoms on patients’ quality of life, and the severity levels of disease characteristics to explore DM progression. Cognitive debriefing required the clinical experts to perform a review of the CDM-IGA, designed to assess the severity of cutaneous disease activity of DM. After the interviews, a consensus meeting with three clinical experts was held to agree on any outstanding issues relating to the CDM-IGA. Results The CDM-IGA was iteratively developed using the opinions of nine clinical experts. Feedback provided by all clinicians agreed that erythema was the main active cutaneous manifestation of DM and should be the primary characteristic on the CDM-IGA, split by erythema color and extent. To determine cutaneous disease severity, experts suggested adding a metric called secondary changes, which combined erosion/ulceration and lichenification, which could modify the patient’s final score. Three clinical experts suggested that a photo-guide to support assessments of erythema across different skin tones could be beneficial. Conclusions A novel CDM-IGA was developed for use with adult patients with DM in clinical trials, based on an iterative development process that combined qualitative feedback from clinical experts of DM and importantly adult patients living with DM.

The gene therapy approach for retinal disorders has been considered largely over the last decade owing to the favorable outcomes of the US Food and Drug Administration-approved commercial gene therapy, Luxturna. Technological advances in recent years, such as next-generation sequencing, research in molecular pathogenesis of retinal disorders, and precise correlations with their clinical phenotypes, have contributed to the progress of gene therapies for various diseases worldwide, and more recently in India as well. Thus, considerable research is being conducted for the right choice of vectors, transgene engineering, and accessible and cost-effective large-scale vector production. Many retinal disease-specific clinical trials are presently being conducted, thereby necessitating the collation of such information as a ready reference for the scientific and clinical community. In this article, we present an overview of existing gene therapy research, which is derived from an extensive search across PubMed, Google Scholar, and clinicaltrials.gov sources. This contributes to prime the understanding of basic aspects of this cutting-edge technology and information regarding current clinical trials across many different conditions. This information will provide a comprehensive evaluation of therapies in existing use/research for personalized treatment approaches in retinal disorders.

Purpose: To evaluate the prediction accuracy of various intraocular lens (IOL) power calculation formulas on American Society of Cataract and Refractive Surgery (ASCRS) calculator and Barrett True-K total keratometry (TK) in eyes with previous laser refractive surgery for myopia. Methods: This retrospective study included eyes with history of myopic laser refractive surgery, which have undergone clear or cataractous lens extraction by phacoemulsification followed by IOL implantation. Those who underwent uneventful crystalline lens extraction were included. Eyes with any complication of refractive surgery or those with eventful lens extraction procedure and those who were lost to follow-up were excluded. Formulas compared were Wang–Koch–Maloney, Shammas, Haigis-L, Barrett True-K no-history formula, ASCRS average power, ASCRS maximum power on the ASCRS post-refractive calculator and the IOLMaster 700 Barrett True-K TK. Prediction error was calculated as the difference between the implanted IOL power and the predicted power by various formulae available on ASCRS online calculator. Results: Forty post-myopic laser-refractive surgery eyes of 26 patients were included. Friedman’s test revealed that Shammas formula, Barrett True-K, and ASCRS maximum power were significantly different from all other formulas (P < 0.00001 for each). Median absolute error (MedAE) was the least for Shammas and Barrett True-K TK formulas (0.28 [0.14, 0.36] and 0.28 [0.21, 0.39], respectively) and the highest for Wang–Koch–Maloney (1.29 [0.97, 1.61]). Shammas formula had the least variance (0.14), while Wang–Koch–Maloney formula had the maximum variance (2.66). Conclusion: In post-myopic laser refractive surgery eyes, Shammas formula and Barrett True-K TK no-history formula on ASCRS calculator are more accurate in predicting IOL powers.

The term “Pulmonary-renal syndrome” is a clinical syndrome, which encompasses a group of disorders with distinctive clinical and radiological features suggestive of diffuse alveolar hemorrhage and glomerulonephritis. The most common etiologies implicated are antineutrophil cytoplasmic antibody ANCA ANCA-associated vasculitis and Goodpasture syndrome. Early diagnosis and prompt treatment are critical for the management as patients can land up in severe respiratory distress and renal failure. A multi-disciplinary team is required for its management. The mainstay of treatment includes steroids, immunosuppressants, and plasmaphereses, depending on the etiology. Despite optimal management, mortality and morbidity remain high.

Acute kidney injury (AKI) is a common problem in critical care settings and conferred an increased risk of morbidities and mortality. The pendulum has shifted to the increasing number of children with comorbidities exposed to potential kidney damage. AKI is a complex clinical syndrome due to heterogeneous etiology. There has been an evolution in the definition and staging of AKI over the past two decades. However, estimating glomerular filtration rate in rapidly changing kidney function remains challenging. Although biomarkers are promising in AKI identification, timing is crucial in deciding which biomarker to measure. The outcome of AKI is not always recovery, but it is an interconnected syndrome with acute and chronic kidney disease.

Abstract In many Indian regions, paddy wheat is the main crop rotation and facing the problem of straw incorporation for seed bed preparation in short period. The handling of straw in combine harvested paddy fields is a significant issue in the paddy wheat rotation. In order to solve this issue, efforts were carried out to cut paddy straw into small pieces by the newly proposed counter-rotating blades, followed by the simultaneous incorporation of a rotary tiller into the soil. Therefore, a tractor operated chopping cum tilling mixing machine was developed. In the study, three different blades (straw management system (SMS) Serrated, cutter bar and SMS plain) were tested in the terms of torque and required to chop the straw. SMS serrated blade was best suitable for the chopping mechanism as it required minimum cutting torque for the straw bunches. The developed chopping cum tilling mixing machine was tested at three different levels of forward speed (1.77, 2.3, and 3 km h−1), moisture content at three levels (35 ± 3.4, 24 ± 2.2 and 17 ± 2.6%) with fix rotary tiller rotational speed of 810 rev min−1. Optimum operating condition of the machine was obtained at a forward speed of 1.9 km h−1 and a moisture of 24%. At these optimized values, the mixing index (96%), mean weight diameter (7.9 mm), bulk density (1230 g cc−1) and fuel consumption (3 l h−1) were 96%, 7.9 mm, 1230 g cc−1 and 3.0 l h−1 respectively. The developed machine performs three operations i.e., chopping, tilling, and mixing in single pass for effective in-situ straw management.

Abstract Background Accurately assessing corneal structural status is challenging when thickness deviates from the average. Polarization-sensitive optical coherence tomography (PS-OCT) measures tissue-specific polarization changes, providing additional contrast for accurate segmentations and aids in phase retardation (PR) measurements. Previous studies have shown PR's effectiveness in identifying sub-clinical keratoconus (KC) in asymmetric cases. Thus, this study aims to assess PR distribution in thick corneas with and without KC. Methods In this retrospective and cross-sectional study, 45 thick corneas from 30 Asian-Indian subjects, categorized into healthy (n = 26) and KC (n = 19) groups were analyzed. All eyes underwent standard clinical evaluations, tomographic assessments, and corneal biomechanics measurements. PR and individual layer thicknesses were measured using custom-designed ultrahigh-resolution PS-OCT. PR en-face maps were generated. Individual layer thicknesses and PR analysis was conducted across multiple zones, extending up to 8–10 mm in diameter. All eyes in the study had not undergone interventions, received topical medications, or had previous corneal disease history. Results Significant differences were found in spherical and cylindrical powers, keratometry, pachymetry, and biomechanical indices (all P

Abstract The rapid evolution of mass spectrometry-based single-cell proteomics now enables the cataloging of several thousand proteins from single cells. We investigated whether we could discover cellular heterogeneity beyond proteome, encompassing post-translational modifications (PTM), protein-protein interaction, and variants. By optimizing the mass spectrometry data interpretation strategy to enable the detection of PTMs and variants, we have generated a high-definition dataset of single-cell and nuclear proteomic-states. The data demonstrate the heterogeneity of cell-states and signaling dependencies at the single-cell level and reveal epigenetic drug-induced changes in single nuclei. This approach enables the exploration of previously uncharted single-cell and organellar proteomes revealing molecular characteristics that are inaccessible through RNA profiling.

Abstract Current convolutional neural networks (CNNs) are not designed for large scientific images with rich multi-scale features, such as in satellite and microscopy domain. A new phase of development of CNNs especially designed for large images is awaited. However, application-independent high-quality and challenging datasets needed for such development are still missing. We present the ‘UltraMNIST dataset’ and associated benchmarks for this new research problem of ‘training CNNs for large images’. The dataset is simple, representative of wide-ranging challenges in scientific data, and easily customizable for different levels of complexity, smallest and largest features, and sizes of images. Two variants of the problem are discussed: standard version that facilitates the development of novel CNN methods for effective use of the best available GPU resources and the budget-aware version to promote the development of methods that work under constrained GPU memory. Several baselines are presented and the effect of reduced resolution is studied. The presented benchmark dataset and baselines will hopefully trigger the development of new CNN methods for large scientific images.

Abstract Our study aims to validate safety and efficacy of Feroglobin capsule compared with different iron supplementations in adult subjects diagnosed with non-anemic to mild anemic iron deficiency and fatigue. Enrolled 302 participants diagnosed with non-anemic to mild anemic iron deficiency and fatigue. Group A (n = 147) received Feroglobin, Group B (n = 146) received standard of care [Haem Up Gems capsules (Ferrous fumarate) or Fericip tablets (Ferrous ascorbate)]. 293 subjects completed the study with follow-up visits on days 30, 60, and 90. Feroglobin treatment significantly increased hemoglobin levels from mean 12.43 g/dl to 13.24 g/dl in 90 days. Ferritin levels improved significantly by 442.87% compared to the standard care’s 256.67%. Fatigue scale scores reduced by 47.51%, and all presenting health complaints resolved completely. Gastrointestinal symptoms observed were similar in both the groups. Both groups exhibited moderate treatment adherence. Quality of life improved in pain and general health domains, exhibiting a good tolerability. Adverse events were unrelated to the investigational products. Feroglobin serves as an efficacious therapeutic alternative for improving hemoglobin, ferritin, and reducing fatigue with low doses compared to standard of care. However, longer-term effects of low-dose require further investigations in different target groups.

Abstract Background Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. Methods Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. Discussion The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. Trial registration anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Background and Aims: Fully covered self-expandable metal stents are commonly used for managing GI adverse events like perforations, leaks, fistulas, and strictures. Although effective, stent length and migration can be a limitation when dealing with larger defects. Over-the-scope clips and over-the-scope suturing can be used to mitigate migration risk; however, their role is limited for stent-to-stent suturing to create longer stents. We present a novel application of through-the-scope suturing (TTSS) system for creating longer stents to manage larger GI defects. Methods: We demonstrate using a video case series the applicability of TTSS for fixing multiple coaxially placed stents to create a longer stent and simultaneously anchor them to underlying GI wall to mitigate stent migration. Results: We illustrate our success in managing 3 cases of large esophageal and/or gastric pathologies (stenosis and leak) using the TTSS system to create longer stents through stent-in-stent fixation. Conclusions: TTSS is a novel endoscopic suturing platform that is compatible with most endoscopes and can be navigated to challenging narrow and angulated location, giving it an advantage over over-the-scope suturing/over-the-scope clips. Our case series demonstrates that stent-in-stent fixation of multiple fully covered self-expandable metal stents to create longer stents using the TTSS system is an effective technique when managing larger GI defects.

Copper (Cu) is highly sought for its excellent electrical and thermal conductivity. However, its limited mechanical strength hinders its wider application in demanding fields. This work explores the potential of graphene nanoplatelets (GNPs) as a strengthening agent for Cu. Cu-GNP composites with varying GNP content (0.1–1.5 wt%) were fabricated using a combined ball milling and powder metallurgy approach. The microstructure and mechanical properties of the composites were comprehensively analyzed using field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Raman spectroscopy. Compared to pure Cu, the Cu-GNP composites showcased significantly improved mechanical performance. Notably, the Cu-1.0 wt% GNP composite exhibited a remarkable ∼27% and ∼53% enhancement in compressive strength and micro-hardness, respectively. This improvement is attributed to the effective load transfer between Cu and well-dispersed GNPs, which act as reinforcement elements and inhibit dislocation movement. These findings demonstrate the promising potential of Cu-GNP composites for applications requiring high strength.

Large surface full-thickness burns pose a significant clinical challenge to the burn surgeon. Integra® dermal matrix has now been commercially available for more than 3 decades. Over this time, its role continues to evolve, and it remains an important tool in the hands of a burn surgeon. Integra® is now being successfully used in acute burn injury, chronic wounds, and reconstructive surgery. Successful outcomes, however, are predicated on a multitude of factors. This overview serves to provide a history of the device, review data and lessons learned, and provide an algorithm for success based on the experience of the authors.

Abstract This article presents a coherent phenomenon called spontaneously generated coherence (SGC) under the regime of electromagnetically induced transparency (EIT) in a three-coupled multiple quantum wells. We demonstrate that the presence of SGC in these quantum wells lead to intriguing modifications in the transparency window within the absorption spectrum. At the same time, modification of the dispersive nature is also demonstrated which enables the feasibility of the system in diverse applications based on light propagation. The absorption and dispersion responses are found to be varied by the individual strength of the first and second control fields in presence as well as in absence of SGC in the EIT regime. The positional shifting of the transparency window and simultaneous modifications in the dispersive profiles by tuning the control field detunings of both the first and second control fields are also revealed. Some absorption and dispersion contours are illustrated for getting better insights into the modifications of the optical responses via SGC. Finally, by manipulating the strength of the SGC parameter, we observe the changes in the respective position of the transparency window and dispersion curve. It is expected that the current investigations will pave novel ways for innovative applications in quantum communications, and fabrication of advanced photonic devices.

In this paper, the generalized (3+1)-dimensional nonlinear wave equation in fluid with gas bubbles is studied in soliton theory and produced by taking the Hirota bilinear operators. The first- to third rogue wave solutions through numerous rogue wave strategy by Maple typical estimations are recovered. The made conditions for the analyticity and positively of the gotten arrangements can be effectively accomplished by utilizing the specific determinations of the included values. The most merits of this plot are to recoup the Hirota bilinear models and their generalized equivalences. Also, the rational tan(Π(ξ)) technique on the generalized nonlinear wave equation is examined. The perturbed solution of the generalized nonlinear wave equation through the way of Modulational stability is studied. Finally, the graphical reenactments of the precise arrangements are portrayed. By selecting suitable values for the parameters involved in the solutions, 3D graphs, 2D contour graphs and line graphs are presented to provide graphical demonstration of the results. The reported results will be helpful to design new and better optical devices. The findings of this work may also help in problems arising in ocean engineering.

Conventional breeding approaches have played a significant role in meeting the food demand remarkably well until now. However, the increasing population, yield plateaus in certain crops, and limited recombination necessitate using genomic resources for genomics-assisted crop improvement programs. As a result of advancements in the next-generation sequence technology, GABs have developed dramatically to characterize allelic variants and facilitate their rapid and efficient incorporation in crop improvement programs. Genomics-assisted breeding (GAB) has played an important role in harnessing the potential of modern genomic tools, exploiting allelic variation from genetic resources and developing cultivars over the past decade. The availability of pangenomes for major crops has been a significant development, albeit with varying degrees of completeness. Even though adopting these technologies is essentially determined on economic grounds and cost-effective assays, which create a wealth of information that can be successfully used to exploit the latent potential of crops. GAB has been instrumental in harnessing the potential of modern genomic resources and exploiting allelic variation for genetic enhancement and cultivar development. GAB strategies will be indispensable for designing future crops and are expected to play a crucial role in breeding climate-smart crop cultivars with higher nutritional value.

Introduction: Expanding knowledge on tobacco use and quitting outcomes in Chhattisgarh, India, is crucial. Limited data hinder the assessment of tobacco use prevalence and quitting outcomes in the region. This household-based cross-sectional study aimed to assess smokeless tobacco (SLT) use and quit behaviour among village dwellers aged 35–44 and 65–74 years in Jamul, Chhattisgarh. Materials and Methods: A survey was conducted among 450 participants, utilising a pretested questionnaire and data analysis using IBM Statistical Package for the Social Sciences (SPSS) v23. Results: The study revealed that among the survey participants, 61.1% were males and 38.9% were females. The prevalence of SLT use was found to be 67.8%, with 59.1% of current SLT users reporting daily use. Middle-aged individuals predominantly chose gutkha, while khaini was more common among the elderly. Tobacco and paan with tobacco were also commonly used forms. Gudakhu, a popular SLT product for oral hygiene and easy defecation, was reported by 71.34% of participants. Television warnings and SLT packages proved to be successful methods for disseminating information about the dangers of SLT use. However, SLT users who attempted to quit independently reported encountering one or more withdrawal symptoms, which posed significant obstacles to quitting SLT. Conclusion: Community-based awareness programmes are implemented via regional television (TV) channels, coupled with cessation initiatives, including professional counselling, pharmaceutical interventions and support of peer. Changing attitudes against SLT use and promoting tobacco-free environments are prioritized. These strategies will effectively address SLT use and improve quitting outcomes in Jamul, Chhattisgarh, fostering a healthier community.

Background: Pulmonary rehabilitation (PR) can help in improving the exercise capacity and quality of life (QoL) in diffuse parenchymal lung diseases (DPLDs), even in end-stage lung diseases listed for lung transplant. With the paucity of literature from the Indian population, the current study assessed PR’s benefits on the respiratory functions and exercise capacity in DPLD. Methods: This prospective interventional study was conducted over 18 months in patients with diagnosed stable DPLD who were previously not involved in any PR program. All the enrolled patients underwent 12-week in-hospital, supervised PR program, which included exercise training with increasing load, endurance training, resistance training, flexibility training, and stretching. The patients were evaluated for the measures at baseline and after 12 weeks of a rehabilitation program. Results: There was a significant improvement in respiratory capacity forced expiratory volume in 1 s (FEV1), 6-min walk distance (6MWD), Modified Medical Research Council (MMRC), and total St. George’s Respiratory Questionnaire scores (P < 0.05) after the completion of the PR program. Among the outcome parameters, there were no significant differences in the PO2 and FEV1/forced vital capacity ratio (P > 0.05) etiologically; the improvement was significant for all outcome parameters except MMRC and symptom score in the idiopathic pulmonary fibrosis (IPF) group (P = 0.165). In the non-IPF group, the improvement was significant for all outcome parameters except PO2 (P = 0.9). On multivariate linear regression, age was the only independent factor for 6MWD (P = 0.0002; 95% confidence interval [CI]: −5.019–−1.665) and MMRC (P = 0.005; 95% CI: 0.007–0.037). Conclusion: This study reveals that PR is effective for people with DPLD in decreasing the symptoms and improving the exercise capacity and QoL. Clinical improvement is greater in those with non-IPF compared to IPF, but both groups as a whole achieved clinically significant improvements. An adaptation of the PR regimen as per age may be necessary for optimizing the clinical benefits.

The use of posttransplant cyclophosphamide has revolutionized the field of haploidentical hematopoietic stem cell transplant. The impact has been especially enhanced in low- and middle-income countries. Unrelated donor pool in developing nations is often limited due to the lack of large unrelated donor registries. Donor-specific antibodies (DSAs) are preformed immunoglobulin G anti-human leukocyte antigen (HLA) antibodies against HLA antigens that are not shared with the donor. We present successful desensitization in a 13-year-old patient with class III β-thalassemia with very high MFI DSAs with flow crossmatch positivity, persisting after pretransplant immunosuppression.

Background: There is a limited number of studies from India investigating the role of transcranial direct current stimulation (tDCS) in treatment-resistant depression (TRD). This clinic-based study reports on the effectiveness of tDCS as an add-on treatment in individuals suffering from TRD. Materials and Methods: Twenty-six right-handed individuals suffering from major depressive disorder who failed to respond to adequate trials of at least two antidepressant drugs in the current episode received tDCS as an augmenting treatment. Twice daily sessions of conventional tDCS were given providing anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal placement at the right DLPFC. A total of 20 sessions were given over 2 weeks. The outcome was assessed based on changes in scores of the Hamilton Rating Scale for Depression (HAMD) and Montgomery-Asberg Depression Rating Scale (MADRS). Results: There was a significant reduction in outcome assessment after tDCS intervention as compared to baseline, with more than 50% of the participants showing response in both scales, which increased further to approximately 77% by the end of 1 month of the follow-up period. Conclusion: Twice daily tDCS sessions with anodal stimulation of left DLPFC and cathodal stimulation of right DLPFC is an effective add-on treatment strategy in individuals with TRD.

Abstract This data descriptor elaborates the details of a high-resolution digital bathymetric elevation model generated for the region, namely, Adam’s Bridge, which encompasses a chain of shoals between Rameswaram Island, off the southeastern coast of Tamil Nadu, India, and Mannar Island, off the northwestern coast of Sri Lanka. The proposed dataset has taken advantage of the photon penetrability in the shallow waters by the green laser of ICESat-2 LiDAR to derive the seabed topography. Seafloor depths from ~0.2 million geolocated photons of ICESat-2 for the study area were accrued and interpolated to generate a 10 m digital bathymetric elevation model. Adam’s Bridge, an isthmus and submerged reefal assemblage in shallow and super-shallow waters, is a feature of scientific curiosity. Our dataset has the potential to enhance the understanding of Adam’s Bridge structure by providing substantial information to reconstruct its evolution.

Abstract Adam’s Bridge is a submerged ridge connecting India and Sri Lanka, generally regarded as a chain of shoals extending for ~ 29 km from Dhanushkodi on the Indian side to Talaimannar Island of Sri Lanka. A high-resolution digital bathymetric elevation model generated using the seafloor returned photons of ICESat-2 was used to understand the intricate details of Adam’s Bridge structure. Photons emanating from ICESat-2’s green laser have the potential to detect the seafloor up to a depth of ~ 40 m; taking a cue from this potentiality, in our research, we have accrued ~ 0.2 million photons representing the depth information and generated a 10 m resolution bathymetric data for the extent of Adam’s Bridge. Visual interpretations made from this bathymetric data through 3D perspectives with multi-directional lighting effects, and also with the derived parameters like contours, slope, and volumetric analysis, enabled us to recognize the current form of Adam’s Bridge’s physical features. The results from our research confirm that, in its entirety, Adam’s Bridge is a submarine continuation of Dhanushkodi and Talaimannar Island. Throughout the crest line of Adam’s Bridge, approximately 1.5 km on either side is highly undulating within the super-shallow water with occurrences of sudden depths. There is an asymmetry of transverse slopes to the base on both sides of Adam’s Bridge, indicating dominant transgression of material energy from the waters of the Gulf of Mannar compared to the Palk Strait. The volume of Adam’s Bridge computed in our research yielded a value of ~ 1 km3; interestingly, only 0.02 percent of this volume is above the mean sea level, and in general, the same is visible in optical satellite imagery—in total ~ 99.98 percent of the Adam’s Bridge is submerged in shallow and super-shallow waters.

Abstract Background Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as “the interest in establishing and guiding the next generation,” can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU? intervention. Methods In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention. Discussion We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U? intervention. We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL. Trial registration ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.

Abstract Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.

Purpose: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). Design: Prospective, placebo-controlled, double-blind, cross-over study. Methods: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. Results: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture) . A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. Conclusions: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.

Abstract Background Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. Methods In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). Discussion This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. Trial registration ISRCTN ISRCTN14957538. Registered in October 2022.

Abstract This paper describes a comprehensive energy-related dataset, collected from residential electricity households within an energy community in Ireland, as part of StoreNet project. The data includes local weather parameters and per household power (W) and energy (Wh) components for various aspects such as active power consumption, PV generation, grid import and export, charging and discharging, and the state of charge of energy storage. Additionally, it provides weather data for the location at a 1-minute temporal resolution for the year 2020. The dataset has been validated by comparing measurements that should yield identical results to standard load profiles, with no significant inconsistencies discovered. Validation examples have also been given through the published articles where this dataset has been used to analyse peer-to-peer energy trading benefits for the energy community and decision-making support for aggregators. The dataset aids in understanding patterns in electrical load curves and the duty cycle of energy storage within an energy community. Furthermore, it can assist in comprehending the impact on distribution networks caused by distributed energy storage.

Abstract The purpose of the study was to assess the effects of a novel technique involving facial stretching of the unaffected side along with a structured exercise for the affected side on facial symmetry and facial functions as compared to conventional exercise. A hospital-based parallel-group randomized trial was completed among patients with acute Bell’s palsy in Mangalore, India. Participants were randomized to receive facial stretching and a structured exercise program (experimental group) or the conventional exercise regimen (conventional group). Primary outcomes were facial symmetry and voluntary movement; assessed by the Sunnybrook Facial Grading System (SFGS). Both regimens were given for 3 weeks, with baseline, 10th day, and 20th day assessments. Out of 31 participants screened, 24 were eligible and 12 participants each were assigned to experimental and conventional groups. Change scores revealed greater improvement in the SFGS score (p = 0.002) for the experimental group participants. Facial stretching and structured exercise program exhibited promising results in enhancing facial symmetry and function in acute Bell’s palsy when compared to conventional exercise regimen.

Abstract This paper proposes a novel multi-hybrid algorithm named DHPN, using the best-known properties of dwarf mongoose algorithm (DMA), honey badger algorithm (HBA), prairie dog optimizer (PDO), cuckoo search (CS), grey wolf optimizer (GWO) and naked mole rat algorithm (NMRA). It follows an iterative division for extensive exploration and incorporates major parametric enhancements for improved exploitation operation. To counter the local optima problems, a stagnation phase using CS and GWO is added. Six new inertia weight operators have been analyzed to adapt algorithmic parameters, and the best combination of these parameters has been found. An analysis of the suitability of DHPN towards population variations and higher dimensions has been performed. For performance evaluation, the CEC 2005 and CEC 2019 benchmark data sets have been used. A comparison has been performed with differential evolution with active archive (JADE), self-adaptive DE (SaDE), success history based DE (SHADE), LSHADE-SPACMA, extended GWO (GWO-E), jDE100, and others. The DHPN algorithm is also used to solve the image fusion problem for four fusion quality metrics, namely, edge-based similarity index ( $$Q^{AB/F}$$ Q A B / F ), sum of correlation difference (SCD), structural similarity index measure (SSIM), and artifact measure ( $$N^{AB/F}$$ N A B / F ). The average $$Q^{AB/F} = 0.765508$$ Q A B / F = 0.765508 , $$SCD = 1.63185$$ S C D = 1.63185 , $$SSIM = 0.726317$$ S S I M = 0.726317 , and $$N^{AB/F} = 0.006617$$ N A B / F = 0.006617 shows the best combination of results obtained by DHPN with respect to the existing algorithms such as DCH, CBF, GTF, JSR and others. Experimental and statistical Wilcoxon’s and Friedman’s tests show that the proposed DHPN algorithm performs significantly better in comparison to the other algorithms under test.

Protein hydrolysates are composed of peptones and peptides, and their type depends on the biological source and manufacturing process. We studied the survival response of Salmonella enterica in the presence of casein, soy protein, and fish protein hydrolysates at refrigeration and freezing temperatures. Fish protein hydrolysate (FPH) was identified as the only capable hydrolysate of sustaining the viability of S. enterica for 60 days at refrigeration temperatures. None of the three hydrolysates were able to impart cryoprotection to S. enterica under freezing conditions. The survival rate of S. enterica in FPH was further enhanced by growing the inoculum on agar instead of broth. An optimization study using response surface methodology was also conducted to identify suitable concentrations of protein hydrolysates capable of maximizing the survival of S. enterica. The results of this study can be used to manage Salmonella-related food safety incidents by replacing animal-sourced with plant-sourced protein hydrolysates at the recipe development stage, as well as the use of FPH in microbiological growth media and the formulation of secondary reference materials. These results indicate that FPH produced by enzymatic hydrolysis of Stolephorus indicus at lower concentrations (5%) can serve as nutritive agents in culture media, contribute to long-term preservation, and can be used in the formulation of quantitative reference materials for Salmonella.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder that mostly affects old aged people. Its symptoms are initially mild, but they get worse over time. Although this health disease has no cure, its early diagnosis can help to reduce its impacts. A methodology SMOTE‐RF is proposed for AD prediction. Alzheimer's is predicted using machine learning algorithms. Performances of three algorithms decision tree, extreme gradient boosting (XGB), and random forest (RF) are evaluated in prediction. Open Access Series of Imaging Studies longitudinal dataset available on Kaggle is used for experiments. The dataset is balanced using synthetic minority oversampling technique. Experiments are done on both imbalanced and balanced datasets. Decision tree obtained 73.38% accuracy, XGB obtained 83.88% accuracy and RF obtained a maximum of 87.84% accuracy on the imbalanced dataset. Decision tree obtained 83.15% accuracy, XGB obtained 91.05% accuracy and RF obtained maximum 95.03% accuracy on the balanced dataset. A maximum accuracy of 95.03% is achieved with SMOTE‐RF.

Abstract Medical image segmentation has made a significant contribution towards delivering affordable healthcare by facilitating the automatic identification of anatomical structures and other regions of interest. Although convolution neural networks have become prominent in the field of medical image segmentation, they suffer from certain limitations. In this study, we present a reliable framework for producing performant outcomes for the segmentation of pathological structures of 2D medical images. Our framework consists of a novel deep learning architecture, called deep multi-level attention dilated residual neural network (MADR-Net), designed to improve the performance of medical image segmentation. MADR-Net uses a U-Net encoder/decoder backbone in combination with multi-level residual blocks and atrous pyramid scene parsing pooling. To improve the segmentation results, channel-spatial attention blocks were added in the skip connection to capture both the global and local features and superseded the bottleneck layer with an ASPP block. Furthermore, we introduce a hybrid loss function that has an excellent convergence property and enhances the performance of the medical image segmentation task. We extensively validated the proposed MADR-Net on four typical yet challenging medical image segmentation tasks: (1) Left ventricle, left atrium, and myocardial wall segmentation from Echocardiogram images in the CAMUS dataset, (2) Skin cancer segmentation from dermoscopy images in ISIC 2017 dataset, (3) Electron microscopy in FIB-SEM dataset, and (4) Fluid attenuated inversion recovery abnormality from MR images in LGG segmentation dataset. The proposed algorithm yielded significant results when compared to state-of-the-art architectures such as U-Net, Residual U-Net, and Attention U-Net. The proposed MADR-Net consistently outperformed the classical U-Net by 5.43%, 3.43%, and 3.92% relative improvement in terms of dice coefficient, respectively, for electron microscopy, dermoscopy, and MRI. The experimental results demonstrate superior performance on single and multi-class datasets and that the proposed MADR-Net can be utilized as a baseline for the assessment of cross-dataset and segmentation tasks.

Abstract Background Platinum-based chemotherapy regimens are a mainstay in the management of ovarian cancer (OC), but emergence of chemoresistance poses a significant clinical challenge. The persistence of ovarian cancer stem cells (OCSCs) at the end of primary treatment contributes to disease recurrence. Here, we hypothesized that the extracellular matrix protects CSCs during chemotherapy and supports their tumorigenic functions by activating integrin-linked kinase (ILK), a key enzyme in drug resistance. Methods TCGA datasets and OC models were investigated using an integrated proteomic and gene expression analysis and examined ILK for correlations with chemoresistance pathways and clinical outcomes. Canonical Wnt pathway components, pro-survival signaling, and stemness were examined using OC models. To investigate the role of ILK in the OCSC-phenotype, a novel pharmacological inhibitor of ILK in combination with carboplatin was utilized in vitro and in vivo OC models. Results In response to increased fibronectin secretion and integrin β1 clustering, aberrant ILK activation supported the OCSC phenotype, contributing to OC spheroid proliferation and reduced response to platinum treatment. Complexes formed by ILK with the Wnt receptor frizzled 7 (Fzd7) were detected in tumors and correlated with metastatic progression. Moreover, TCGA datasets confirmed that combined expression of ILK and Fzd7 in high grade serous ovarian tumors is correlated with reduced response to chemotherapy and poor patient outcomes. Mechanistically, interaction of ILK with Fzd7 increased the response to Wnt ligands, thereby amplifying the stemness-associated Wnt/β-catenin signaling. Notably, preclinical studies showed that the novel ILK inhibitor compound 22 (cpd-22) alone disrupted ILK interaction with Fzd7 and CSC proliferation as spheroids. Furthermore, when combined with carboplatin, this disruption led to sustained AKT inhibition, apoptotic damage in OCSCs and reduced tumorigenicity in mice. Conclusions This “outside-in” signaling mechanism is potentially actionable, and combined targeting of ILK-Fzd7 may lead to new therapeutic approaches to eradicate OCSCs and improve patient outcomes.

Noise pollution is a significant concern in urban settings, caused by traffic increases, urban expansion, and industrial activity. The transportation sector is a crucial contributor to overall noise pollution, particularly in India, where different vehicles ply the roads, resulting in highly fluctuating noise levels. Consequently, traffic noise modeling is essential for addressing this severe issue. The present study employs the MLR (Multiple Linear Regression) and Artificial Neural Network (ANN) approach to model and predict traffic-induced noise levels. The ANN approach outperforms the MLR technique. The architecture of the ANN model integrates different vehicle categories and average speeds as input, resulting in precise predictions. Evaluation of the model’s performance reveals an average Root Mean Squared Error (RMSE) of 0.204 and a high Coefficient of determination (R2) value of 0.93, emphasizing its accuracy. Similarly, in the case of MLR model the RMSE for the training and testing dataset are 1.55 and 1.69 dBA, respectively with R2 value of 0.84. Subsequently, sensitivity analysis highlights the substantial impact of 2-wheelers, tractors/trailers, and 3-wheelers on noise predictions. This study contributes valuable insights into noise management, urban planning, and sustainable development. It demonstrates the efficiency of the ANN approach in addressing complex noise pollution challenges, offering a path toward quieter and healthier urban environments.

Aim: The aim of the study is to evaluate changes in corneal parameters following the use of the Malyugin ring (MR) and B-Hex ring (BhR) in small pupil phacoemulsification. Methods: A prospective cross-sectional study. 51 eyes with small pupil underwent phacoemulsification with the use of MR and BhR as pupil expansion techniques. Best-corrected visual acuity (BCVA), endothelial cell counts density (ECD), coefficient-of-variation (CV), hexagonality, central corneal thickness (CCT), and intraocular pressure (IOP) were recorded on preoperative day and postoperative day 1 and day 30. Results: Mean age at presentation was 70.9 ± 4.1 years. The most common cause for small pupils was alpha-blockers used in benign prostate hypertrophy, followed by diabetes mellitus and pseudo-exfoliation syndrome. Mean preoperative BCVA (3/60–6/12), IOP (17.12 ± 2.81 mmHg), CCT (530.96 ± 44.47 μ), ECD (2347.96 ± 298.09 cells/mm2), 6A (48.92% ± 6.34%) and CV (39.50 ± 3.49) changed to BCVA (6/9–6/6), IOP (18.69 ± 1.91 mm of Hg), CCT (536.04 ± 37.61 μ), endothelial cell count (2201.15 ± 276.75 cells/mm2), 6A (45.12% ±4.99%), and CV (37.57 ± 3.37) at day 30 postoperatively after use of MR. Similarly, mean preoperative BCVA (3/60–6/12), IOP (16.40 ± 2.42 mmHg), CCT (532.40 ± 36.14 μ), ECD (2433.68 ± 162.01 cells/mm2), 6A (48.84% ± 3.73%), and CV (39.36 ± 3.915) changed to BCVA (6/9–6/6), IOP (17.68 ± 2.75 mmHg), CCT (546.88 ± 31.25 μ), ECD (2322.08 ± 167.97 cells/mm2), 6A (46.36% ± 3.25%) and CV (38.96 ± 4.43) at day 30 post-operatively after use of BhR. The average change was clinically insignificant at day 30. Conclusion: MR and BhRs are safe pupil expansion devices and the corneal parameters are in the acceptable range of any routine phacoemulsification for senile cataracts. Nevertheless, B-hR shows relatively less alteration in corneal parameters, when compared to MR.

Post-intensive care syndrome (PICS) refers to persistent or new onset physical, mental, and neurocognitive complications that can occur following a stay in the intensive care unit. PICS encompasses muscle weakness; neuropathy; cognitive deficits including memory, executive, and attention impairments; post-traumatic stress disorder; and other mood disorders. PICS can last long after hospital admission and can cause significant physical, emotional, and financial stress for patients and their families. Several modifiable risk factors, such as duration of sepsis, delirium, and mechanical ventilation, are associated with PICS. However, due to limited awareness about PICS, these factors are often overlooked. The objective of this paper is to highlight the pathophysiology, clinical features, diagnostic methods, and available preventive and treatment options for PICS.