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Summary: In mammalian cells, the Golgi exists in ribbon architecture—individual stacks laterally linked to each other by tubular structures. Golgi architecture changes dynamically to cater to cellular needs. Loss of architecture is linked with pathological conditions like cancer and neurodegeneration. Not much is known about the regulators of Golgi dynamics. Here, we demonstrate that CARP2 (caspase-8- and caspase-10-associated RING-containing protein 2), an endosomal ubiquitin ligase and a known regulator of cell migration, modulates Golgi dynamics. Epidermal growth factor (EGF) treatment modestly increases CARP2 protein and disperses Golgi. An exogenous supply of CARP2 also leads to Golgi dispersal. Conversely, Golgi remains intact in CARP2 knockout (KO) cells upon EGF treatment. CARP2 variants defective in either endosomal association or ligase activity are unable to affect Golgi dispersal. Importantly, CARP2 targets Golgin45 for ubiquitination and degradation in EGF-stimulated cells. Collectively, our findings unravel the existence of crosstalk between endosomal ubiquitin signaling and Golgi dynamics.

Diabetes is a chronic disease that affects millions of humans worldwide. This review article provides an analysis of the recent advancements in non-invasive blood glucose monitoring, detailing methods and techniques, with a special focus on Electromagnetic wave microwave glucose sensors. While optical, thermal, and electromagnetic techniques have been discussed, the primary emphasis is focussed on microwave frequency sensors due to their distinct advantages. Microwave sensors exhibit rapid response times, require minimal user intervention, and hold potential for continuous monitoring, renders them extremely potential for real-world applications. Additionally, their reduced susceptibility to physiological interferences further enhances their appeal. This review critically assesses the performance of microwave glucose sensors by considering factors such as accuracy, sensitivity, specificity, and user comfort. Moreover, it sheds light on the challenges and upcoming directions in the growth of microwave sensors, including the need for reduction and integration with wearable platforms. By concentrating on microwave sensors within the broader context of non-invasive glucose monitoring, this article aims to offer significant enlightenment that may drive further innovation in diabetes care.

The present study illustrates the mechanical and wear behaviour of Al-MWCNT composites by varying MWCNTs concentration (0 %,0.25 %, 0.50 % & 1 %) by weight in composites. These composites were synthesized through sintering in the muffle furnace after mechanical alloying which involved flattening and welding particles to form flake-shaped lamellar particles. The presence of MWCNT lamellas restricted grain growth, creating a 2D aluminium layer between the MWCNTs during sintering. Increasing the MWCNT content in aluminum refined the interlayer thickness of the composites. The compressive strength of Al is increased exponentially with the addition of CNTs. By adding CNTs to aluminium, the maximum strength was reached at 460 MPa in 1% samples, and the compression strength of the aluminium increased by 84 % as well. The sintered composites exhibited higher hardness and its value increased significantly when CNTs were added to the Al composite. The wear resistance of aluminium is substantially increased when CNTs are added, and the maximum wear resistance is achieved when CNTs are added at 0.5 wt%. The addition of CNTs reduced wear resistance, which could be attributed to the decrease in interface adhesion and agglomeration effects of CNTs.

Abstract Background Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. Methods We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. Results Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. Conclusion The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.

Background: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular condition characterized by the formation of blood clots in the cerebral venous sinuses, which are responsible for draining blood and cerebrospinal fluid from the brain. CVST represents a significant cause of stroke in young individuals, with a mortality rate ranging from 6% to 15%. Methods: Common clinical presentations include symptoms like headaches, seizures, altered mental state, and focal neurological deficits. In India, a noteworthy occurrence of CVST is observed among postpartum women, while alcoholism poses a significant risk factor for males. Results: This study identifies headaches as the most prevalent initial symptom of CVST, followed by seizures and focal neurological deficits. The superior sagittal sinus is the most frequently affected in these patients. Notably, 83.3% of patients in this study achieved a favorable outcome. However, a midline shift exceeding 10mm was identified as a predictive factor for an unfavorable outcome in this series. Conclusions: Contrary to previous perceptions, CVST is not uncommon in males. The early diagnosis and prompt intervention have a positive impact on overall patient outcomes. This research sheds light on the importance of recognizing CVST in a broader demographic, its common symptoms, and the critical role of timely intervention for improved patient prognosis.

Macrophages are integral part of the body's defense against pathogens and serve as vital regulators of inflammation. Adaptor molecules, featuring diverse domains, intricately orchestrate the recruitment and transmission of inflammatory responses through signaling cascades. Key domains involved in macrophage polarization include Toll-like receptors (TLRs), Src Homology2 (SH2) and other small domains, alongside receptor tyrosine kinases, crucial for pathway activation. This review aims to elucidate the enigmatic role of macrophage adaptor molecules in modulating macrophage activation, emphasizing their diverse roles and potential therapeutic and investigative avenues for further exploration.

Background Ni-kshay Poshan Yojana (NPY), a direct benefit transfer scheme under the National Tuberculosis Elimination Program (NTEP) in India, provides a monthly benefit of INR500 for nutritional support of persons with TB (PwTB). Objectives To determine the proportion of PwTB receiving at least one NPY instalment and pattern of utilisation; to ascertain factors associated with NPY non-receipt and association of NPY receipt with TB treatment outcome. Methods In our cross-sectional study, we used multi-stage sampling to select PwTB whose treatment outcome was declared between May 2022 and February 2023. A cluster-adjusted, generalized linear model was used to identify factors associated with the non-receipt of NPY and determine association between NPY receipt and TB treatment outcome. Results Among 3201 PwTB, 2888 (92.7%; 95% CI 89.8%, 94.8%) had received at least one NPY instalment, and 1903 (64.2%; 95% CI 58.9%, 69.2%) self-reported receipt of benefit. The median (IQR) time to receipt of first instalment was 105 (60,174) days. Non-receipt was significantly higher among PwTB from states with low TB score (aPR = 2.34; 95%CI 1.51, 3.62), who do not have bank account (aPR = 2.48; 95%CI 1.93, 3.19) and with unknown/missing diabetic status (aPR = 1.69; 95%CI 1.11, 2.55). Unfavorable treatment outcomes were associated with non-receipt of NPY (aPR 4.93; 95%CI 3.61,6.75) after adjusting for potential confounders. Conclusion Majority of the PwTB received at least one NPY instalment, but they experience significant delays. Most of the recipients utilised NPY for nutrition. Longitudinal follow-up studies are required to study the impact of NPY on treatment outcomes.

Engineering transition metal dichalcogenides-based semiconducting two-dimensional (2D) layered materials for photo(electro)chemical (PEC) hydrogen evolution reaction (HER) by water splitting is an enduring challenge. Here, alloy-assisted photoconductivity and photoresponse from CVD-grown MoS2(1-x)Se2x (MSSE) 2D ternary atomic layered alloy-based photodetector device is presented for the realization of PEC HER. The explicit role of ‘S–Se’ and ‘Se2’ atomic alloy sites including chalcogen-induced vacancy defects on the photoconductivity/photoresponse and PEC HER performance of MSSE 2D alloy is investigated. Alloy formation, atomic site-by-site ‘Se’ composition and atomic structure are characterized using Raman/Photoluminescence (PL) spectroscopy, high-angle annular dark field (HAADF)- scanning transmission electron microscopy (STEM) extensively and supported with Auger Electron Spectroscopy (AES) mapping. Further, the local density and concentration of S–Se, Se2 atomic sites and defects were quantitatively estimated using HAADF-STEM image analysis in correlation with AES and it is found between the range of ∼15–20 % in MSSE alloy. A 10-fold high photoresponsivity in the case of MSSE concerning as-grown MS having fast photocurrent growth time and the prolonged decay time originates from the ‘Se’ and this alloy assisted states to enhance the PEC performance of MSSE alloy. The enhanced PEC HER activity of MSSE alloy was identified in terms of overpotential and current density. In addition, increased density of states as a function of ‘Se’ alloying, shifts in a p-band centre and lowers ΔGH* according to density functional theory calculations, which makes MSSE alloy an efficient HER activity. Further, the PEC stability and presence of the ‘S–Se’ and ‘Se2’ alloying and their role towards HER have been correlated by the spectral line shape analysis of PL and Raman spectra from post-PEC HER catalysts. These experimental and theoretical findings establish the role of chalcogen, and transition metal-based 2D alloy, leading to the design of new PECs of engineered 2D atomic layer interfaces.

Abstract This article reports the development of a microscopy imaging system that gives feasibility for studying spatio-temporal dynamics of physiological activities of alive biological specimens (over entire volume not only for a particular section, i.e., in 4D). The imaging technology facilitates to obtain two image frames of a section of the larger specimen ( $$\sim \text {mm}$$ ∼ mm ) with different FOVs at different resolutions or magnifications simultaneously in real-time (in addition to recovery of 3D (volume) information). Again, this imaging system addresses the longstanding challenges of housing multiple light sources (6 at the maximum till date) in microscopy (in general) and light sheet fluorescence microscopy (LSFM) (in particular), by using a tuneable pulsed laser source (with an operating wavelength in the range $$\sim 420$$ ∼ 420 –670 nm) in contrast to the conventional CW laser source being adopted for inducing photo-excitation of tagged fluorophores. In the present study, we employ four wavelengths ( $$\sim$$ ∼ 488 nm, 585 nm, 590 nm, and 594 nm). Our study also demonstrates quantitative characterization of spatio-temporal dynamics (velocity—both amplitude and direction) of organelles (mitochondria) and their mutual correlationships. Mitochondria close to the nucleus (or in clustered cells) are observed to possess a lower degree of freedom in comparison to that at the cellular periphery (or isolated cells). In addition, the study demonstrates real-time observation and recording of the development and growth of all tracheal branches during the entire period ( $$\sim 95$$ ∼ 95 min) of embryonic development (Drosophila). The experimental results—with experiments being conducted in various and diversified biological specimens (Drosophila melanogaster, mouse embryo, and HeLa cells)—demonstrate that the study is of great scientific impact both from the aspects of technology and biological sciences.

Numerical association rule mining (NARM) is an extended version of association rule mining that determines association rules in numerical data items through distribution, discretization, and optimization methods. In the optimization techniques domain, numerous evolutionary and swarm intelligence-based algorithms have been proposed to extract association rules from numerical datasets. However, there is still a lack of comprehensive understanding regarding the performance of swarm intelligence-based algorithms, particularly for NARM. Presently, in state-of-the-art, various swarm intelligence-based optimization algorithms are claimed to be better based on their arbitrary comparisons with different algorithms in different classes, e.g., swarm intelligence-based algorithms are compared with genetic algorithms. Consequently, it becomes challenging to select the most suitable swarm intelligence-based algorithm for NARM. This article specifically aims to address this gap by conducting an exhaustive multi-aspect analysis of four popular swarm intelligence-based optimization algorithms (MOPAR, MOCANAR, ACO-R, and MOB-ARM) using four real-world datasets and six key metrics: performance time, the number of rules, support, confidence, comprehensibility, and interestingness, aiming to demonstrate the efficiencies of the SI-based algorithms in addressing the NARM problem. The achieved outcomes are also compared with the Apriori algorithm, which is one of the classical algorithms for association rule mining. In our analysis, MOPAR shows low rule count with high confidence, comprehensibility, and interestingness. MOCANAR consistently performs well across all parameters and datasets. ACO-R generates high-quality rules but may need parameter adjustments for large datasets. MOB-ARM is slower compared to others, and Apriori underperforms in support and time but excels in confidence.

To address the challenges posed by a large number of disaster-waiver-affected users and the complexities of scaling centralized algorithms for rapidly restoring emergency communication services, the paper proposes a distributed intent-based optimization architecture based on multi-agent reinforcement learning. This approach aims to mitigate service discrepancies and dynamics among users. In the network feature layer, a distributed K-sums clustering algorithm considers variations in user services. Each UAV base station autonomously and minimally adjusts the local network structure based on user requirements. It selects user features from the cluster center as input states for the multi-agent reinforcement learning neural network. In the trajectory regulation layer, the paper introduces a multi-agent maximum entropy reinforcement learning (MASAC) algorithm. The UAV base station, acting as an intelligent node, governs its flight trajectory within the framework of “distributed training – distributed execution.” The paper incorporates techniques such as integrated learning and curriculum learning to enhance training stability and convergence speed. Simulation results demonstrate the effectiveness of our distributed K-sums clustering algorithm in terms of load efficiency and cluster balance, outperforming the traditional K-means algorithm. Additionally, the UAV base station trajectory control algorithm based on MASAC significantly reduces communication interruptions, enhances network spectral efficiency, and surpasses existing reinforcement learning methods.

Mobile smart contracts (MSCs) are essential to facilitate quick, safe, and decentralized transactions on mobile blockchain networks. Scalable blockchain solutions facilitate the establishment of a mobile blockchain ecosystem characterized by enhanced resilience and adaptability. This encourages an increase in the number of users and, thus, spreads the adoption of blockchain technology in the mobile domain. With the inception of blockchain technology, a wide range of applications use smart contracts due to their high customizability. However, problems with scalability and resource-intensive consensus procedures prevent their general use. Therefore, this work seeks to identify and analyze these constraints by conducting a systematic survey using Kitchenham’s guidelines for available scalable blockchains and consensus methods. Out of a preliminary pool of 2,073 publications, our study, which consists of 25 selected studies, identifies 12 consensus mechanisms and 13 scalable blockchain systems. Our investigation shows that, despite the wide range of techniques, no blockchain solution provides the scalability and lightweight operating requirements to implement smart contracts on mobile devices. This realization draws attention to a significant gap in academic and industry-driven blockchain research that may have implications for creating MSCs. Our findings encourage academics to explore scalable and energy-efficient blockchain technology, targeting creating more approachable smart contracts designed with mobile devices in mind.

Abstract Background Women’s health is usually looked upon in terms of their reproductive health. However, cardio-vascular diseases are one of the leading causes of death and disability among women, globally as well as in India. Risk factors of today can be disease of tomorrow. Gradience in level of epidemiological transition is observed across different states. The study aims to estimate the national and regional prevalence, and sociodemographic determinants of biological and behavioural risk factors for cardiovascular diseases. Materials and methods The present study was conducted among women in the age group of 15 to 49 years using nationally representative sample from fifth round National Family Health Survey in India. The data analysis in the current study included 7,24,115 women in the age group of 15 to 49 years. SPSS version 20 was used for the purpose of analysis. Weighted prevalence was computed for the studied behavioral and biological (dependent variable) risk factors using women specific weights as provided in the dataset. Binary logistic regression model was employed to calculate the adjusted odds ratio (OR) with the corresponding 95% confidence interval (CI) to study the sociodemographic determinants (independent variables) of these risk factors. Results Highest prevalent risk factor for cardiovascular diseases was reported to be central obesity (78.2%), followed by overweight/obesity (23.9%), oral contraceptive use (13.4%), raised blood pressure (11.8%), raised blood sugar (8.6%), tobacco use (4.0%), and alcohol use (0.7%). Higher odds of all the studied risk factors were reported with increasing age. All of the studied risk factors, except for alcohol consumption [OR (95%CI): 0.9 (0.8–0.96)], had higher odds in rural areas compared to urban areas. Compared to other castes, the odds of tobacco [OR (95% CI): 2.01 (1.91–2.08)] and alcohol consumption [OR (95% CI): 5.76 (5.12–6.28)], and raised blood pressure [OR (95% CI): 1.07(1.04–1.11)] was significantly higher among the people belonging to schedule tribe. Conclusion and recommendation The present study highlights the state-wise disparities in the burden and predictors of risk factors for cardio-vascular diseases among women of reproductive age. The study provides insights to these disparities, and focuses on the need of tailoring the disease prevention and control measures suiting to the local needs.

Abstract Background Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. Methods In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. Results Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. Conclusions The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.

This work aims to simplify the characterization process of coded-apertures for computational imaging (CI) at microwave frequencies. A major benefit of the presented technique is the minimization of the processing time needed to calculate the system sensing matrix for microwave CI-based compressive sensing applications. To achieve this, a deep learning-based approach which is capable of generating the sensing matrix using features learned directly from the coded-aperture distribution is proposed. To avoid the vanishing gradient problem, the proposed deep learning network contains skip connections. Using a dataset of 1,000 testing samples, the average normalized mean-squared-error (NMSE) calculated between the sensing matrix generated by the conventional method and that predicted by the proposed network is 0.0036. Moreover, the average mean-squared-error (MSE) calculated between the images reconstructed using the conventional and the predicted sensing matrix is 0.00297. In addition to providing high-fidelity estimations with minimized error, we demonstrate that using the trained network, the prediction of the sensing matrix can be achieved in 0.212 s, corresponding to a 65% reduction in the computation time needed to calculate the sensing matrix. This has significant outcomes in achieving real-time operation of CI-based microwave imaging systems.

This paper proposes a new integrated control scheme for large-scale wind turbine generators (WTG) incorporated with a battery energy storage system (BESS). The primary goal is to improve the dispatchability of wind power over a wide range. The proposed controller consists of switching feedback controllers for WTG equipped with BESS management and is developed to systematically govern both systems for optimal regulation while ensuring safe operation within defined limits. A scenario-based switching logic is recommended to coordinate the hybrid systems, and a three-layer WTG controller is devised using a gain-scheduled control method. The suggested controller’s performance is evaluated through simulation case studies, particularly in dealing with wind forecast errors (WFE) in the short-term dispatch scheme. To assess the proposed controller’s effectiveness, a comparison is made against a baseline controller in three criteria: standard deviation (STD), mean ( $\bar {X}$ ) and an integral absolute error (IAE). These criteria help to evaluate the energy mismatch concerning the reference power command. The results are presented to elucidate the effectiveness of the proposed controller in regulating WTG-BESS throughout the entire operating region using a real wind profile from a wind farm in Australia. The findings show that the proposed approach has significant potential to enhance performance, leading to vastly improved wind power dispatch compared to the baseline approach.

ABSTRACT: Objectives: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. Methods: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. Results: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. Conclusions: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.

Summary: Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

Summary: NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language texts, special characters in drug SMILES have specific meanings and cannot be ignored. We introduce a novel NLP-based method that extracts interpretable sequences and essential features from drug SMILES notation using N-grams. Our method compares these features to Morgan fingerprint bit-vectors using UMAP-based embedding, and we validate its effectiveness through two personalized drug screening (PSD) case studies. Our NLP-based features are sparse and, when combined with gene expressions and disease phenotype features, produce better ML models for PSD. This approach provides a new way to analyze drug molecule structures represented as SMILES notation, which can help accelerate drug discovery efforts. We have also made our method accessible through a Python library.

Abstract Legionella pneumophila (LP) secretes more than 300 effectors into the host cytosol to facilitate intracellular replication. One of these effectors, SidH, 253 kDa in size with no sequence similarity to proteins of known function is toxic when overexpressed in host cells. SidH is regulated by the LP metaeffector LubX which targets SidH for degradation in a temporal manner during LP infection. The mechanism underlying the toxicity of SidH and its role in LP infection are unknown. Here, we determined the cryo-EM structure of SidH at 2.7 Å revealing a unique alpha helical arrangement with no overall similarity to known protein structures. Surprisingly, purified SidH came bound to a E. coli EF-Tu/t-RNA/GTP ternary complex which could be modeled into the cryo-EM density. Mutation of residues disrupting the SidH-tRNA interface and SidH-EF-Tu interface abolish the toxicity of overexpressed SidH in human cells, a phenotype confirmed in infection of Acanthamoeba castellani. We also present the cryo-EM structure of SidH in complex with a U-box domain containing ubiquitin ligase LubX delineating the mechanism of regulation of SidH. Our data provide the basis for the toxicity of SidH and into its regulation by the metaeffector LubX.

In Wire Arc Additive Manufacturing (WAAM), variable layer heights enable the non-parallel or non-planar slicing of parts. In researching variable layer heights, this paper documents printing strategies for a reference geometry whose key features are non-orthogonal growth and unsupported overhangs. The complexity of 3D printing with welding requires parameter optimization to control the deposition of molten material. Thus, 3D printing with welding requires the precise deposition of molten material. Currently, there is no standard solution for the customization of process parameters and intelligent collection of data from sensors. To address this gap in technology, this research develops an Internet of Things (IoT)-enabled, distributed communication protocol to control process parameters, synchronize commands, and integrate device data. To intelligently collect sensor information, this research creates a query-able database during pre-planning and production. This contributes to fundamental research in WAAM by documenting strategies for printing variable layer heights, the customization of control parameters, and the collection of data through a WAAM Information Model (WIM).

Macrophages play a central role in initiating, maintaining, and terminating inflammation. For that, macrophages respond to various external stimuli in changing environments through signaling pathways that are tightly regulated and interconnected. This process involves, among others, autoregulatory loops that activate and deactivate macrophages through various cytokines, stimulants, and other chemical mediators. Adaptor proteins play an indispensable role in facilitating various inflammatory signals. These proteins are dynamic and flexible modulators of immune cell signaling and act as molecular bridges between cell surface receptors and intracellular effector molecules. They are involved in regulating physiological inflammation and also contribute significantly to the development of chronic inflammatory processes. This is at least partly due to their involvement in the activation and deactivation of macrophages, leading to changes in the macrophages’ activation/phenotype. This review provides a comprehensive overview of the 20 adaptor molecules and proteins that act as negative regulators of inflammation in macrophages and effectively suppress inflammatory signaling pathways. We emphasize the functional role of adaptors in signal transduction in macrophages and their influence on the phenotypic transition of macrophages from pro-inflammatory M1-like states to anti-inflammatory M2-like phenotypes. This endeavor mainly aims at highlighting and orchestrating the intricate dynamics of adaptor molecules by elucidating the associated key roles along with respective domains and opening avenues for therapeutic and investigative purposes in clinical practice.

The paper aims to utilize an integral transform, specifically the Khalouta transform, an abstraction of various integral transforms, to address fractional differential equations using both Riemann-Liouville and Caputo fractional derivative. We discuss some results and the existence of this integral transform. In addition, we also discuss the duality between Shehu transform and Khalouta transform. The numerical examples are provided to confirm the applicability and correctness of the proposed method for solving fractional differential equations.2010 Mathematics ClassificationPrimary 92B05, 92C60; Secondary 26A33.

Abstract100141: The conducting polymers and metal oxide-based nanocomposites (NCs) reported in the literature are non-biodegradable. We have synthesized cellulose/polyaniline/ternary metal oxide-based NCs which are environment-friendly and show multifunctional applications. Cellulose is a natural polymer. Polyaniline (PANI) is a synthetic polymer. Both natural and synthetic polymers were blended with ternary metal oxide NCs of Zn/Ni/CuO (ZNC). Epoxy-modified cellulose (EMC) was prepared. Sol-gel was used for producing ternary metal NCs, and a chemical oxidative process was used for PANI. Structural evaluation of EMC, PANI, and ZNC NCs was carried out by SEM, PXRD, Raman, FTIR, and UV–visible spectroscopy techniques. Photocatalytic, anticorrosive, electrical, and magnetic properties of PANI/EMC/ZNC NCs were investigated. The NCs show 85% degradation of Methyl Red dye in 180 min. PANI/EMC/ZNC NCs show 83.9% corrosion prevention efficiency for MS in 1.0 M H2SO4. The NCs show magnetic susceptibility (χ = 0.0714) in the paramagnetic region and an optical band gap of 2.3 eV. The PANI/EMC/ZNC NCs were proved to be very good photocatalytic, magnetic, electrical, and anticorrosive agents.

In 2022, the Food and Drug Administration approved a second mitral transcatheter edge-to-edge repair device for the treatment of primary mitral regurgitation (PASCAL Precision Transcatheter Valve Repair System, Edwards Lifesciences, Irvine, CA). The PASCAL Precision system consists of a guide sheath, implant system, and accessories. The implant system consists of a steerable catheter, an implant catheter, and the implant (PASCAL or PASCAL Ace). The guide sheath and steerable catheter move and flex independently from each other and are not keyed, allowing for freedom of rotation in three dimensions. This manuscript provides an overview of the PASCAL Precision system and describes the basic and advanced steering maneuvers to facilitate effective and safe mitral transcatheter edge-to-edge repair.

Abstract Background Addition of adjuvants to routinely used intrathecal drugs is cornerstone in safe and effective prolongation of single shot spinal block for gynecological surgery. In resource deficient countries, where epidural anesthesia is usually not used because of cost factor, adjuvants are routinely used to prolong the effect of regional anesthesia. Alpha 2 agonists are considered best drugs as adjuvants, but there is inconclusive data in literature about the block characteristic, dose at which to be used and side effect after use of these drugs. Methods Clonidine 30 µgm or dexmedetomidine 5 µgm was used intrathecally as an adjuvant with 15 mg bupivacaine 0.5% in 90 female patients undergoing gynecological surgery in this randomized, prospective, single blind study. Results The mean time to onset of sensory block a (T6 level) and time to attain maximum sensory height were significantly early in group D over group C (124.44 ± 20.64 s, 175.09 ± 68.01 s, p 0.05). Conclusions We recommend clonidine 30 µg over dexmedetomidine 5 µg as an adjuvant to intrathecal bupivacaine, to effectively and safely prolong the effect of single shot spinal anesthesia.

Abstract Background The importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings. Methods MEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE’s risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol. Discussion Our systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews. Systematic review registration PROSPERO CRD42022367726.

Objectives This article assesses the treatment outcomes in the patients diagnosed with arteriovenous malformations (AVMs) treated with stereotactic radiosurgery. Materials and Methods We retrospectively analyzed 30 patients diagnosed with AVM treated between 2010 and 2018.The median age at presentation was 30 years (range: 14–60 years). The median planning target volume (PTV) was 6.8 mL (range: 0.9–54 mL). The median dose prescribed was 18 Gy (range: 16–24 Gy). Modified radiosurgery-based AVM grading score was calculated for all the patients. Results The median follow-up of the entire cohort was 60 months (range: 24–96 months). The obliteration rates for patients followed up for 3 and 5 years were 75 and 86.1%, respectively. Age (< 35 years; p = 0.007) and PTV (< 7 mL; p = 0.04), had better obliteration rates. Three patients had hemorrhage, from the AVM after irradiation. None of them were fatal. Conclusion Stereotactic radiosurgery is a preferred noninvasive treatment modality with acceptable morbidity.

Background: Severe eosinophilic asthma (SEA), one of the phenotypes of asthma that is characterized by elevated blood eosinophil counts, is a common cause of uncontrolled asthma. Patients with SEA often experience severe persistent symptoms and have frequent exacerbations despite optimal inhaler therapy. They also have poor lung function and quality of life (QoL). Benralizumab (Fasenra), a monoclonal antibody, has been approved for managing cases of SEA. This series of six cases, the first of its kind from India, aims to add to the real-world evidence of benralizumab in India. Methods: Benralizumab 30 mg (once in four weeks for the first three doses followed by a dose every eight weeks for two years) was administered in six patients with symptoms of cough, breathlessness on exertion, and wheezing, diagnosed with SEA. The following were the endpoints assessed: (i) overlap between high immunoglobulin E (IgE) and eosinophilic asthma; (ii) reduction of exacerbations; (iii) withdrawal of oral corticosteroids; and (iv) improvement in lung function and QoL. Results: In all cases, management with benralizumab resulted in optimal clinical and functional improvement, a decline in systemic steroid use, and improved QoL. Conclusions: The cases presented here are the first of their kind in the Indian asthmatic population with all SEA patients demonstrating significant improvement in symptoms with the use of benralizumab.

Introduction Although many programmes have been developed to address elder mistreatment, high-quality, rigorous evaluations to assess their impact are lacking. This is partly due to challenges in conducting programme evaluation for such a complex phenomenon. We describe here the development of a protocol to mitigate these challenges and rigorously evaluate a first-of-its-kind emergency department/hospital-based elder mistreatment intervention, the Vulnerable Elder Protection Team (VEPT).Methods and analysis We used a multistep process to develop an evaluation protocol for VEPT: (1) creation of a logic model to describe programme activities and relevant short-term and long-term outcomes, (2) operationalisation of these outcome measures, (3) development of a combined outcome and (4) design of a protocol using telephone follow-up at multiple time points to obtain information about older adults served by VEPT. This protocol, which is informing an ongoing evaluation of VEPT, may help researchers and health system leaders design evaluations for similar elder mistreatment programmes.Ethics and dissemination This project has been reviewed and approved by the Weill Cornell Medicine Institutional Review Board, protocol #20-02021422. We aim to disseminate our results in peer-reviewed journals at national and international conferences and among interested patient groups and the public.

Introduction: Percutaneous Nephrolithotomy (PCNL) is the preferred method for treating large or complex renal calculi. Despite positive results and apparent benefits over the prone position, there are few randomised trials comparing the supine and prone positions. Aim: To evaluate the effectiveness of PCNL in prone and supine positions in terms of operative time, stone-free rate, hospital stay, postoperative complications, and the level of haemoglobin drop. Materials and Methods: The study was conducted from December 2020 to December 2022, at the Department of Urology, Mamata Medical College in Khammam, Telangana, India. Patients with renal stones diagnosed by Non-Contrast Computed Tomography (NCCT) Kidney Ureter Bladder (KUB) and meeting the inclusion criteria were enrolled. Patient demographic data, operative time, stone-free rate, haemoglobin level drop, postoperative fever, and hospital stay in prone and supine positions were recorded. Statistical tests like chi-square or Fisher-exact test were used to compare proportions, and the student t-test was used to compare means. Results: The overall operative time was 79.50 minutes in the prone group and 66.78 minutes in the supine group (p=0.0213). The average hospital stay was 2.68 days in the prone group and 2.72 days in the supine group (p=0.2432). Fall in haemoglobin levels, size of stones extracted, and stone-free rate at three months between the two groups (p>0.05) showed insignificant relation. Furthermore, there was no significant difference in complications between the two groups (p>0.05). Conclusion: PCNL performed with the patient in the supine position requires significantly less time during surgery. There was no significant difference in terms of stone-free rate, hospital stay, fall in haemoglobin levels, and complications between the supine and prone groups.

Background: Severe eosinophilic asthma (SEA), one of the phenotypes of asthma that is characterized by elevated blood eosinophil counts, is a common cause of uncontrolled asthma. Patients with SEA often experience severe persistent symptoms and have frequent exacerbations despite optimal inhaler therapy. They also have poor lung function and quality of life (QoL). Benralizumab (Fasenra), a monoclonal antibody, has been approved for managing cases of SEA. This series of six cases, the first of its kind from India, aims to add to the real-world evidence of benralizumab in India. Methods: Benralizumab 30 mg (once in four weeks for the first three doses followed by a dose every eight weeks for two years) was administered in six patients with symptoms of cough, breathlessness on exertion, and wheezing, diagnosed with SEA. The following were the endpoints assessed: (i) overlap between high immunoglobulin E (IgE) and eosinophilic asthma; (ii) reduction of exacerbations; (iii) withdrawal of oral corticosteroids; and (iv) improvement in lung function and QoL. Results: In all cases, management with benralizumab resulted in optimal clinical and functional improvement, a decline in systemic steroid use, and improved QoL. Conclusions: The cases presented here are the first of their kind in the Indian asthmatic population with all SEA patients demonstrating significant improvement in symptoms with the use of benralizumab.

Ventriculo-peritoneal (VP) shunt is a universally accepted, most commonly performed cerebrospinal fluid (CSF) diversion procedure for hydrocephalus. However, the procedure is associated with wide variety of complications. Trans-anal extrusion of VP shunt is rare but a well known entity. This is a case report of transanal migration of ventriculoperitoneal shunt in an eight year old male child.