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Severe aplastic anemia (SAA) is a rare bone marrow failure syndrome that results in a high risk of bleeding, infections, and impaired tissue repair. Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is a curative treatment option for eligible transplant patients and may be the only life-saving treatment option in patients with SAA with concurrent treatment-resistant infections (Bacigalupo, 2017). The following case study highlights a successful Allo-HSCT in a patient with SAA with multiple treatment-resistant infections secondary to a large non-healing perianal wound. The discussion focuses on the creative approach that was guided by specialized point-of-care oncology nurses, a specialized oncology wound care nurse, and oncology nurse practitioners in collaboration with the multidisciplinary team.

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD. This document will provide comprehensive and practical guidance that can be applied across Canada by healthcare professionals caring for patients with cGvHD. Hopefully, this guideline, based on input from GvHD treaters across the country, will aid in standardizing cGvHD care and facilitate access to much-needed novel therapies. This consensus paper aims to discuss the optimal approach to the initial assessment of cGvHD, review the severity scoring and global grading system, discuss systemic and topical treatments, as well as supportive therapies, and propose a therapeutic algorithm for frontline and subsequent lines of cGvHD treatment in adults and pediatric patients. Finally, we will make suggestions about the future direction of cGvHD treatment development such as (1) a mode-of-action-based cGvHD drug selection, according to the pathogenesis of cGvHD, (2) a combination strategy with the introduction of newer targeted drugs, (3) a steroid-free regimen, particularly for front line therapy for cGvHD treatment, and (4) a pre-emptive approach which can prevent the progression of cGvHD in high-risk patients destined to develop severe and highly morbid forms of cGvHD.

Triboelectric Nanogenerators (TENGs), renowned for converting mechanical energy into electrical energy, have evolved significantly since their inception. This paper focuses on enhancing TENG performance, specifically in the contact-separation (CSM) mode paired-electrode configuration. A nanograting of varying periods is introduced on the electrodes, and the corresponding impact on device performance is evaluated. The performance is compared with the conventional planer structure. The analytical results exhibit a notable increase in open-circuit voltage (Voc) by up to 148% and charge during short-circuit condition (Qsc) improvement of up to 200%, compared to a planar structure of similar dimensions at 200 nm grating period. Interestingly, a direct correlation between grating period and voltage generation is observed, emphasizing the critical role of material and design choices. Furthermore, the impact of metallic gratings on TENG performance is found to be minimal. These results emphasize TENGs' potential in minute displacement sensors and highlight the importance of meticulous design considerations to optimize efficiency.

Severe aplastic anemia (SAA) is a life-threatening type of aplastic anemia for which allogeneic stem cell transplantation or immunosuppressive therapy are the principal treatment modalities. Only about 25–30% of patients have a matched sibling donor, and finding an unrelated donor in ethnic minorities is a challenge. The use of related haploidentical donor transplants in severe aplastic anemia is uncommon. We would like to report our experience with the first four patients who underwent haploidentical transplants for severe aplastic anemia. This is a retrospective study. We collected data from our transplant database of all haploidentical hematopoietic stem cell transplants for SAA from 1 January 2020 to 31 December 2021. The transplant protocol used was the Hopkins’ protocol. There were three patients who underwent haploidentical transplants as primary therapy for SAA. A fourth patient received a haploidentical transplant after immunosuppressive therapy failure. The median age of the patients at transplant was 24 y (range 20–29). All patients were engrafted. Neutrophil engraftment occurred at a median of 21 days (range 17–22). Any active infections resolved with the recovery of blood counts. The median hospitalization time was 27 days (range 22–41). Only one patient had grade 2 acute GVHD involving the skin. There was no chronic GVHD. All patients had complete lymphoid and myeloid donor chimerism on day 60. Based on our experience and the emerging literature, haplo-identical transplantation should be considered for select young patients with SAA who have low chances of responding to immunosuppressive therapy.

VLSI physical design is a domain of work as old as more than five decades. Even then, as technology progresses, there are several challenging issues from the perspective of theoretical computer science as well as the high-performance requirements of the chip to be designed. Crosstalk is a threat to achieving routing solutions in high-performance VLSI circuits. As fabrication technology advances, closeness occurs among the devices and their interconnecting wires, the size of the devices and chips reduces, and circuits’ operational frequencies increase. These result in crosstalk, a kind of electrical hazard, which over stresses wire segments that are placed sideways. In this paper, it has been proved that the bottleneck crosstalk minimisation problems in the reserved two- and three-layer Manhattan channel routing are NP-complete. It has also been established that the hardness proclaims in approximating all allied crosstalk minimisation problems. As a natural consequence, heuristics have been devised to realise two- and three-layer bottleneck crosstalk routing solutions for different predefined bottleneck values employed over already computed channel routing solutions. Exhaustive experimentation has been performed and promising experimental results have been accomplished often sacrificing a bit more channel area.

Abstract The most common denture material used for dentistry is poly-methyl-methacrylate (PMMA). Usually, the polymeric PMMA material has numerous biological, mechanical and cost-effective shortcomings. Hence, to resolve such types of drawbacks, attempts have been made to investigate fillers of the PMMA like alumina (Al2O3), silica (SiO2), zirconia (ZrO2) etc. For the enhancement of the PMMA properties a suitable additive is required for its orthopedic applications. Herein, the main motive of this study was to synthesize a magnesium oxide (MgO) reinforced polymer-based hybrid nano-composites by using heat cure method with superior optical, biological and mechanical characteristics. For the structural and vibrational studies of the composites, XRD and FT-IR were carried out. Herein, the percentage of crystallinity for all the fabricated composites were also calculated and found to be 14.79–30.31. Various physical and optical parameters such as density, band gap, Urbach energy, cutoff energy, cutoff wavelength, steepness parameter, electron–phonon interaction, refractive index, and optical dielectric constant were also studied and their values are found to be in the range of 1.21–1.394 g/cm3, 5.44–5.48 eV, 0.167–0.027 eV, 5.68 eV, 218 nm, 0.156–0.962, 4.273–0.693, 1.937–1.932, and 3.752–3.731 respectively. To evaluate the mechanical properties like compressive strength, flexural strength, and fracture toughness of the composites a Universal Testing Machine (UTM) was used and their values were 60.3 and 101 MPa, 78 and 40.3 MPa, 5.85 and 9.8 MPa-m1/2 respectively. Tribological tests of the composites were also carried out. In order to check the toxicity, MTT assay was also carried out for the PM0 and PM15 [(x)MgO + (100 − x) (C5O2H8)n] (x = 0 and 15) composites. This study provides a comprehensive insight into the structural, physical, optical, and biological features of the fabricated PMMA-MgO composites, highlighting the potential of the PM15 composite with its enhanced density, mechanical strength, and excellent biocompatibility for denture applications.

The onset of SARS-CoV-2 infection in 2019 sparked a global COVID-19 pandemic. This infection is marked by a significant rise in both viral and host kinase activity. Our primary objective was to identify a pivotal host kinase essential for COVID-19 infection and the associated phenomenon of the cytokine storm, which may lead to long-term COVID-19 complications irrespective of viral genetic variations. To achieve this, our study tracked kinase phosphorylation dynamics in RAW264.7 macrophages following SPIKE transfection over time. Among the kinases surveyed, p70S6K (RPS6KB1) exhibited a 3.5-fold increase in phosphorylation at S418. This significant change prompted the selection of p70S6K for in silico investigation, utilizing its structure bound to M2698 (PDB: 7N93). M2698, an oral dual Akt/p70S6K inhibitor with an IC50 of 1.1 nM, exhibited psychosis side effects in phase I clinical trials, potentially linked to its interaction with Akt2. Our secondary objective was to discover a small-molecule analogue of M2698 that exhibits a distinct binding preference for p70S6K over Akt2 through computational modeling and analysis. The in silico part of our project began with validating the prediction accuracy of the docking algorithm, followed by an OCA analysis pinpointing specific atoms on M2698 that could be modified to enhance selectivity. Subsequently, our investigation led to the identification of an analog of M2698, designated as S34, that showed a superior docking score towards p70S6K compared to Akt2. To further assess the stability of S34 in its protein–ligand (PL) complexes with p70S6K and Akt2, MD simulations were conducted. These simulations suggest that S34, on average, forms two hydrogen bond interactions with p70S6K, whereas it only forms one hydrogen bond interaction with Akt2. This difference in hydrogen bond interactions likely contributed to the observed larger root mean square deviation (RMSD) of 0.3 nm in the S34-Akt2 complex, compared to 0.1 nm in the S34-p70S6K complex. Additionally, we calculated free binding energy to predict the strength of the binding interactions of S34 to p70S6K and Akt2, which showed ~2-fold favorable binding affinity of S34 in the p70S6K binding pocket compared to that in the Akt2 binding pocket. These observations may suggest that the S34-p70S6K complex is more stable than the S34-Akt2 complex. Our work focused on identifying a host kinase target and predicting the binding affinity of a novel small molecule to accelerate the development of effective treatments. The wet bench results specifically highlight p70S6K as a compelling anti-COVID-19 target. Meanwhile, our in silico investigations address the known off-target effects associated with M2698 by identifying a close analog called S34. In conclusion, this study presents novel and intriguing findings that could potentially lead to clinical applications with further investigations.

Abstract Anti-Microbial Peptide Database version 1 (AMPDB v1) is a meticulously curated resource that aims to address the limitations of existing databases in the field of antimicrobial research. We have utilized the latest technology and put our best efforts into adding all relevant tools to cater to the needs of our users. AMPDB v1 is a derived database, built upon information gathered from the available resources and boasts a significant size of 59,122 entries which are classified into 88 classes. All the information in this resource was curated manually. Sequence alignment and protein feature calculation tools were integrated into the database in the form of web applications, to make them easy to use, quick, and responsive in real-time. We have included multiple types of browsing and searching options to enhance the user experience, from simple text search to a completely customizable advanced search page with intuitive options that let the user combine multiple options together to make a powerful search query. The database is accessible by a web browser at https://bblserver.org.in/ampdb/ .

With the advancement of clinical research and the increased burden on laboratory services, there is an unmet need for guidelines regarding proper laboratory functioning and reliable data generation. Several organizations from all over the world have published guidelines for these clinical and research laboratories. Good Clinical Laboratory Practices (GCLP) are stepwise procedures aimed at strengthening the quality of test results produced by all clinical laboratories engaged in human sample analysis. In this article, we attempt a comparison of the GCLP guidelines recently issued by the Indian Council of Medical Research with the guidelines released by the World Health Organization and the European Medicines Agency. Also, we have included and discussed several suggestions that, if included, will lead to the strengthening of the laboratory practices used for both research and patient care for overall improvement in the Indian healthcare system.

This paper shows a comprehensive review on various maximum power point tracking (MPPT) techniques of the solar photovoltaic (PV) cell. It is well understood that power from a solar PV array is sometimes not sufficient, so it is required to extract the maximum power to meet the load demand. In this regard, different techniques were used for comparative analysis like perturb and observe (P & O), fuzzy logic control (FLC), incremental conductance (IC), ripple correction control (RCC), artificial neural network (ANN), particle swarm optimization (PSO), lyapunov control scheme (LCS), and fisher discrimination dictionary learning (FDDL). The performance of MPPT is also examined under the conditions like effect of shading, irradiance, etc. After reviewing the literature, it has been observed that maximum power at different sets of irradiations is extracted with ANN in comparison to other techniques. Subsequently, the least deviations about maximum power point are attained with IC while comparing with other techniques and FDDL has been found the best technique for attaining the minimum total harmonic distortion (THD). In addition to this, it is also detected that the least switching losses are attained with PSO in comparison to others. To this end, it has been concluded that each method has its significance for the extraction of maximum power from the source and dominance over other methods for smart energy systems. The researchers may find this critical review to be a valuable resource in choosing an appropriate soft computing method for the given parameters.

ABSTRACTIntroduction Allogeneic hematopoietic stem cell transplant (HSCT) and gene therapy (GT) are two potentially curative approaches for sickle cell disease (SCD), but they have never been compared in clinical trials.Objective To compare the safety and efficacy of HSCT and GT to assist clinicians and patients in making informed treatment decisions.Methods Phase I-III clinical trials and case reports/series were included. Regimens included HSCT from all stem cell sources, lentiviral gene therapy, and gene editing, with any conditioning regimen. We searched Medline and EMBASE databases as of 1st June 2020 for studies reporting HSCT and GT outcomes in SCD. The Newcastle-Ottawa scale was used to assess the risk of bias. Descriptive statistics and post-hoc imputation for standard deviations of mean change in FEV1 and FVC were performed.Results In total, 56 studies (HSCT, n = 53; GT, n = 3) representing 1,198 patients met inclusion criteria (HSCT, n = 1,158; GT, n = 40). Length of follow-up was 3,881.5 and 58.7 patient-years for HSCT and GT, respectively. Overall quality of evidence was low, with no randomized controlled trials identified. Two-year overall survival for HSCT was 91%; mortality was 2.5% for GT. Acute chest syndrome and vaso-occlusive episodes were reduced post-HSCT and GT. Meta-analysis was not possible due to lack of comparator and heterogeneity in outcome measures reporting. Very few studies reported post-transplant end-organ function. Six secondary malignancies (5 post-HSCT, 1 post-GT) were reported.Discussion Reporting of SCD-related complications and patient-important outcomes is lacking for both strategies. We advocate for standardized reporting to better compare outcomes within and between treatment groups.

Introduction: Open nephrectomy poses a challenge for the anaesthesiologist due to its large subcostal incision and association with both somatic and visceral pain. While various methods exist for postoperative pain management, a single modality approach remains largely ineffective in adequate pain management. Epidural analgesia, intravenous Patient Controlled analgesia pumps, and ultrasound-guided peripheral nerve blocks are commonly used. Aim: To evaluate the efficacy of ultrasound-guided Erector Spinae Plane Block (ESPB) as a part of multimodal analgesia for postoperative pain in patients undergoing open nephrectomy, to enhance recovery after surgery. Materials and Methods: This randomised controlled study was conducted at Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India, on 48 patients undergoing open nephrectomy. They were randomly assigned to two groups: Group I received ultrasound-guided ESPB, while Group II did not receive a block before anaesthesia reversal. In the Post-Anaesthesia Care Unit (PACU), all patients were kept on intravenous Patient Controlled Analgesia (PCA) morphine, and pain was assessed using the Numeric Rating Scale (NRS) scoring. The time of first analgesic requirement and the total morphine consumption in the first 24 hours were recorded. Patient satisfaction and quality of sleep at night were evaluated using a Likert scale. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25.0. Categorical data were assessed using the Chi-square test, while the Independent t-test/Mann-Whitney test was used to determine the association between continuous data. A p-value of

Background: Acute cholecystitis was initially thought to be a contraindication for laparoscopic cholecystectomy. Now, as the experience is increasing, laparoscopic surgeons are gradually undertaking laparoscopic cholecystectomy as the preferred procedure even in an acute setting. Early surgery in acute presentation has better surgical outcome with lesser and cheaper hospital stay and predictive of better quality of life as compared to delayed treatment. Aims and Objectives: The objectives of this study were to study the perioperative complications during early laparoscopic cholecystectomy. Materials and Methods: One hundred and five patients with acute calculus cholecystitis visiting Fortis Escorts Hospital, Faridabad from June 2017 to November 2018 were studied. All patients underwent laparoscopic cholecystectomy and subsequently compared for the following intraoperative parameters: Presence of adhesions, calot’s anatomy, need for decompression of gallbladder, difficulty in dissecting the gallbladder from liver bed, retrieval of gallbladder, time taken to complete surgery, need of placement of drain, and need for conversion to open cholecystectomy. Complications studied were massive bleed, bile spillage during dissection, stone spillage, duodenal injury, and common bile duct [CBD] injury. Results: Decompression of the acute inflamed gallbladder facilitates laparoscopic cholecystectomy in acute cholecystitis with low conversion rate of 2.86%. Bleeding, CBD injury and duodenal injury are uncommon complications but major factors for conversion. Conclusion: Most common reasons for difficulty in laparoscopic cholecystectomy for acute cholecystitis were found to be adhesions in Calot’s triangle and adhesion of gallbladder with surrounding structures (duodenum/transverse colon).

Image segmentation is an application area of computer vision and digital image processing that partitions a digital image into multiple image regions or segments. This process involves extracting a set of contours from the input digital image so that pixels belonging to a region share some common characteristics or computed properties, such as color, texture, or intensity. The application domain of image segmentation is widespread and includes video surveillance, object detection, traffic control system, and medical imaging. The application of image segmentation techniques in the field of medical imaging can be further subcategorized into virtual surgery simulation, diagnosis, a study of anatomical structures, measurement of tissue volumes, location of tumours, and other pathologies. In this study, we have proposed two new Convolutional Neural Network (CNN)-based models: (a) S-Net and (b) SA-Net (S-Net with attention mechanism) to perform image segmentation tasks in the field of medical imaging, especially to generate segmentation masks for brain tumours if present in brain Medical Resonance Imaging (MRI) scans. Both proposed models were developed by considering U-Net as the base architecture. The newly proposed models have leveraged the concept of ‘Merge Block’ to infuse both the local and global context and ‘Attention Block’ to focus on the region of interest having a specific object. Additionally, it uses techniques, such as data augmentation to utilize the available annotated samples more efficiently. The proposed models achieved a Dice Similarity Coefficient (DSC) measures of 0.78 and 0.81 for the High-Grade Glioma (HGG) and Low-Grade Glioma (LGG) datasets, respectively.

Sudoku is a complicated multidimensional mathematical structure with several applications in various computer science domains. 3D Sudoku, compared to 2D, has one more dimension that can potentially provide an extra edge in the field of different application areas. Several researchers have developed various types of 2D Sudoku solvers using different methodologies. However, there is very limited research in the area of developing 3D Sudoku solvers. Thus, two different solvers for solving 3D Sudoku puzzles of size $9\times 9 \times 9$ are proposed in this work. Both solvers provide all possible solutions for solving a 3D Sudoku puzzle. 2D Sudoku puzzles are applied in different research domains with different purposes. Recently, 3D structure of Sudoku has been applied in several areas to achieve more effectiveness compared to 2D Sudoku. Additionally, it can also be used to solve problems in 3D space. Again, solving an NP-complete puzzle by considering its 3D structure is a challenging job. Thus, we endeavoured to achieve all probable solutions for a 3D Sudoku instance in this work. In the first version of our proposed algorithm, all possible values for each blank cell are computed and stored. Subsequently, a few elimination-based methods are used to reduce the number of probable values (if possible) for each blank cell. Finally, the solutions are computed using the backtracking method. In the second version of our proposed algorithm, the nine 2D Sudoku puzzles, lying in the $xz$ -plane one above the other, which form the 3D puzzle are fed as the input. All possible solutions are obtained for each of the nine puzzles. Then, the obtained solutions are mapped to achieve one or more solutions for the 3D Sudoku instance. Thus, our proposed techniques provide a new approach for solving 3D Sudoku. In addition, applying the obtained solutions provides us with an advantage over 2D Sudoku, in solving problems in the 3D space and where more data is required.

The globalization of the Integrated Circuits supply chain has increased threats from untrusted entities involved in the process. Several mechanisms, such as logic locking, watermarking and split manufacturing, are widely used to ensure hardware security. This study describes a novel method for creating hardware watermarks inspired by finite-state machines. It makes use of the unique physical property of magnetic tunnel junctions that are based on spin-orbit torque. The design strategy is described in detail, including the use of an EDA tool to analyze and take advantage of the unique switching properties of MTJ, their non-volatility, and their reliance on an external magnetic field to direct information through a predetermined order of states in a manner akin to an FSM. Furthermore, the performance prospects are analyzed using Monte Carlo simulations. For the 5% and 10% of process variation in the key MTJ parameters, the accuracy of 100% and 99.80%, respectively, are achieved. In control signal voltage variation, a tolerance of 9% (0.91V) is observed. The required state transition is not altered, demonstrating a tolerable sensitivity to temperature variation from 250K to 350K. The security aspects and methodology for the approach are explained to ensure a more robust and practical application, and finally, a comparison is made with other FSM-based watermarks.

The Yamuna khadar or the floodplains of the river Yamuna in Delhi is a deeply contested agrarian space. While thousands have been involved in farming these floodplains for decades, contestations over their legality, compensation, land use, displacement, and impact on the river, soil, and city have been significant public concerns over the last few decades. In this paper, I focus on one aspect of this agrarian landscape—the toxicity associated with river water due to the pesticides and fertilizers used in agriculture. I examine how toxicity is perceived, discursively constructed, and dealt with by differently located stakeholders in this landscape. The differently located stakeholders associated with the toxic agrarian landscape of Yamuna khadar are not experiencing pollution as a homogenous community, i.e., neither all of them see themselves as suffering from pollution nor do they see themselves as contributing to the toxicity of the landscape in a similar way.

A 5-day-old male presented with bilious vomiting, a grossly distended abdomen, and passage of a small amount of stool. The anal opening was at a normal position. X-ray abdomen showed a large bowel loop with a single air-fluid level occupying more than half of the abdominal width. On laparotomy, the ascending colon was dilated to form a pouch-like structure, and the ileum and appendix were opening into it. Colon distal to pouch was present as microcolon. Histopathology of the dilated segment was suggestive of congenital segmental dilatation (CSD). In CSD, the distal bowel is of normal caliber. This is a rare case of CSD of ascending colon with distal microcolon.

Abstract A 17‐gene stemness (LSC17) score determines risk in acute myeloid leukaemia patients treated with standard chemotherapy regimens. The present study further analysed the impact of the LSC17 score at diagnosis on outcomes following allogeneic haematopoietic cell transplantation (HCT). Out of 452 patients with available LSC17 score, 123 patients received allogeneic HCT. Transplant outcomes, including overall (OS), leukaemia‐free survival (LFS), relapse incidence (RI) and non‐relapse mortality (NRM), were compared according to the LSC17 scored group. The patients with a low LSC17 score had higher OS (56.2%) and LFS (54.4%) at 2 years compared to patients with high LSC17 score (47.2%, p = 0.0237 for OS and 46.0%, p = 0.0181 for LFS). The low LSC17 score group also had a lower relapse rate at 2 years (12.7%) compared to 25.3% in the high LSC17 score group (p = 0.017), but no difference in NRM (p = 0.674). Worse outcomes in the high LSC17 score group for OS, LFS and relapse were consistently observed across all stratified sub‐groups. The use of more intensive conditioning did not improve outcomes for either group. In contrast, chronic graft‐versus‐host‐disease was associated with more favourable outcomes in both groups. The 17‐gene stemness score is highly prognostic for survival and relapse risk following allogeneic HCT.

Background: Cholelithiasis is 7 times more frequent in North India, with an overall incidence of about 2–29%. The number and different morphology of gallstones can cause alterations in the gallbladder (GB) mucosa. GB mucosal change depends on the duration of cholelithiasis, size, number, type of stone, and the gender of the patient. The coexistence of gallstones with cholecystitis, hyperplasia, intestinal metaplasia, and carcinoma is well known in the literature. Incidental gallbladder (GB) carcinoma is revealed in 1% of all cholecystectomies done for benign conditions. The pathological stage of the disease decides the prognosis of the disease. Aims and Objectives: Gallstones are known to produce various histopathological changes in the GB. We aim to correlate gallstone characteristics such as (number and morphological type) with the type of mucosal response in the GB (inflammation, hyperplasia, metaplasia, and carcinoma). Materials and Methods: A study of gallstones was done in 184 cases of open cholecystectomies based on the histological changes. One hundred and sixty-five (89.95%) were associated with gallstones, and the rest 19 cases (10.05%) were of acalculous cholecystitis. The changes in the mucosa of the calculous GB (165 cases) were studied, and the correlation between the mucosal changes and the number and type of stones was evaluated. Tissue sections for histopathological studies were taken from the fundus, body, neck, and abnormal-looking areas of the GB. Results: A gender study revealed a higher incidence of inflammatory changes in males, while GB hyperplasia, intestinal metaplasia, and cancer were found only in females. Conclusion: Correlation of mucosal changes with a number, duration of disease, and morphological type of stones has suggested that there could be an association with the various GB mucosal changes such as inflammation, hyperplasia, metaplasia, and carcinoma of the GB.

The utilization of lignocellulosic biomass as an alternative energy source presents a promising opportunity to achieve a future energy system that is clean and free from CO2 emissions. To realize this potential, it is crucial to develop effective techniques for converting biomass and organic solid waste into secondary energy sources. Among the available options, hydrogen production stands out due to its numerous advantages, including its cleanliness, versatility in conversion and utilization technologies, high energy efficiency, and dense energy content per unit weight. This article offers a comprehensive overview of different conversion pathways and important technologies for generating hydrogen from biomass and organic solid waste. It specifically focuses on the thermochemical conversion process, which shows promise as an economically viable approach. While certain thermochemical conversion processes are still in the developmental phase, utilizing organic biomass for hydrogen production is widely recommended due to its ability to yield higher amounts of end products and its compatibility with existing facilities. However, it should be noted that this method necessitates a substantial amount of energy due to its endothermic nature. This article also explores alternative hydrogen conversion technologies and their potential for utilizing organic biomass as a feedstock, while addressing the challenges and limitations associated with these methods.

Abstract Background Patients with tunneled central venous lines (CVL) may develop bloodstream infections which at times are difficult to control without line removal. Concomitant severe thrombocytopenia with platelet transfusion refractoriness is often considered a major contraindication to any procedure involving a major blood vessel. There is very little literature on the clinical risks of tunneled central line removal in febrile pancytopenia patients. Procedure We analyzed complications and outcomes in all our patients, a total of 52, who underwent CVL removal with platelets

The article presents the design and development of invasive weed optimization (IWO) for the sensor less speed control of doubly fed induction generator (DFIG) under balanced and unbalanced conditions. A healthy condition represents the balanced condition while unbalancing condition is characterized by unhealthy conditions like three-phase fault, single line to ground fault, the line-to-line fault, and double line to ground fault. The DFIG is driven by wind and integrated with the grid. The advantages associated with IWO technique are a simple mathematical approach and less data computation. Normally, DFIG consists of two back-to-back converters namely grid side converter (GSC) and rotor side converter (RSC). The GSC is an uncontrolled converter while the RSC is a controlled converter. The existing methods have poor performance parameters like settling time, peak overshoot for balanced conditions, and poor power quality parameters like total harmonic distortion (THD) for unbalanced conditions. An IWO technique has been applied to overcome such limitations. The effectiveness of the sensor less speed control is also analyzed with other techniques like Adaptive Neuro-Fuzzy Interference System (AN-FIS) & artificial neural network (ANN). The design of ANN is based on the feed-forward method using back propagation delay and the design of ANFIS is based on adaptive control and state space control strategy. It is observed that performance parameters like peak overshoot and settling time for the sensor less speed of DFIG are found to be more profound with IWO in comparison to ANFIS, ANN, and other existing techniques for balanced conditions. Similarly in the unbalanced condition, faulty current approaches are quite closer to their healthy state with the IWO method in comparison to other methods. In addition to this, minimum distortion (%THD) for the grid current under unbalanced conditions is also attained with IWO in comparison to ANFIS, ANN, and other existing techniques. Such application of IWO makes the system highly efficient and robust.

The increasing threat of security attacks on hardware security applications has driven research towards exploring beyond CMOS devices as an alternative. Spintronic devices offer advantages like low power, non-volatility, inherent spatial and temporal randomness, simplicity of integration with a silicon substrate, etc., making them a potential candidate for next-generation hardware security systems. In this work, we explore the Giant Spin Hall effect driven spin-orbit torque magnetic tunnel junction implementing physically unclonable function. The effect of process variation is considered in key MTJ parameters like TMR ratio, free and oxide layer thickness following Gaussian distribution, and Monte-Carlo simulations to determine the effect of the process variations. A unique challenge-response pair is obtained utilizing the inherent variations in magnetization dynamics of the free layer due to process variations.

The purpose of this study is to conduct a comprehensive evaluation and analysis of the most recent studies on the implications of keystroke dynamics (KD) patterns in user authentication, identification, and the determination of useful information. Another aim is to provide an extensive and up-to-date survey of the recent literature and potential research directions to understand the present state-of-the-art methodologies in this particular domain that are expected to be beneficial for the KD research community. From January 1st, 2017 to March 13th, 2022, the popular six electronic databases have been searched using a search criterion (“keystroke dynamics” OR “typing pattern”) AND (“authentication” OR “verification” OR “identification”). With this criterion, a total of nine thousand three hundred forty-eight results, including duplicates, were produced. However, one thousand five hundred forty-seven articles have been chosen after removing duplicates and preliminary screening. Due to insufficient information, only one hundred twenty-seven high-quality quantitative research articles have been included in the article selection process. We compared and summarised several factors with multiple tables to comprehend the various methodologies, experimental settings, and findings. In this study, we have identified six unique KD-based designs and presented the status of findings toward an effective solution in authentication, identification, and prediction. We have also discovered considerable heterogeneity across studies in each KD-based design for desktops and smartphones separately. Finally, this paper found a few open research challenges and provided some indications for a deeper understanding of the issues and further study.

With the advancement of beyond CMOS devices, a new approach to utilize the inherent physics of such emerging structures for various applications is of great interest in recent research. Spintronics-based devices offer key advantages like ease of fabrication with Si-substrate, non-volatile memory, low operational voltage, and non-linear device characteristics, which have shown potential for several emerging fields of study. Hardware security is one of the key interest areas which heavily relies on CMOS-based ICs, and the defense and attack mechanism is mostly based on CMOS-based structures. This work explores several emerging structures based on 2T/3T magnetic tunnel junctions (MTJ) for possible logic locking applications in hardware security systems. We demonstrate the effect of MTJ-based devices to implement logic locking even in the presence of process variations, and its ability of robustness to device imperfections has been evaluated using monte carlo simulations for practical applications.

The increasing trends toward the accurate identification of power quality disturbances (PQD) via power quality (PQ) monitoring require an appropriate digital signal processing (DSP) technique and a robust classifier. To this end, Stockwell transform (ST), one of the most efficient feature extraction DSP tools, and its several variants play an utmost role in PQ assessment framework. Its time-varying spectral characteristics generally extract the local instantaneous frequency spectrum from the global temporary behavior of PQD signal. However, the Standard ST suffers from the poor time-frequency resolution because of its frequency-dependent Gaussian window (GW). While the analysis of the statistically time-varying signals requires a suitable balance between time and frequency resolution. To this end, this paper provides a comprehensive literature review on several modified versions of Standard ST for the first time to reduce the computational complexity of the algorithm as well as maximize the energy concentration of the time-frequency plane. A comparative analysis of all the modified STs has been presented in tabular form to provide the key characteristics of each technique. Additionally, a case study has been presented to substantiate the highest accuracy of the proposed algorithm over the other ST variants. Apart from the PQD classification, miscellaneous applications of Standard ST and its modified variants have been indicated. This review paper may provide a valuable resource to the researchers for further improvement of the time-frequency resolution of ST not only in classifying PQD but also for its other wide applications.

Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HSCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HSCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 33 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other acute myeloid leukemia-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (P=0.969), relapse incidence (P=0.600) or non-relapse mortality (P=0.570). Donor CHIP did not impair neutrophil (P=0.460) or platelet (P=0.250) engraftment, the rates of acute (P=0.490), or chronic graft-versus-host disease (P=0.220). No significant difference was noted for secondary malignancy following HSCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HSCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pretransplant evaluation of donors prior to stem cell donation.

BackgroundAllogeneic blood and marrow transplantation (alloBMT) is a curative treatment for blood cancers associated with various treatment-related adverse events and morbidities. Current rehabilitation programs are limited for patients undergoing alloBMT and research is urgently needed to test the acceptability and effectiveness of these programs. In response, we developed a 6-month multidimensional longitudinal rehabilitation program that spans from pre transplant to 3 months post transplant discharge (CaRE-4-alloBMT).MethodsThis study is a phase II randomized controlled trial (RCT) conducted at the Princess Margaret Cancer Centre in patients undergoing alloBMT. A total of 80 patients stratified by frailty score will be randomized to receive usual care (n = 40) or CaRE-4-alloBMT plus usual care (n = 40). The CaRE-4-alloBMT program includes individualized exercise prescriptions, access to online education through a dedicated self-management platform, wearable technology for remote monitoring, and remote tailored clinical support. Feasibility will be assessed by examining the recruitment and retention rates and adherence to the intervention. Safety events will be monitored. Acceptability of the intervention will be assessed through qualitative interviews. Secondary clinical outcomes will be collected through questionnaires and physiological assessments at baseline (T0, 2-6 weeks pre-transplant), transplant hospital admission (T1), hospital discharge (T2), and 3 months post-discharge (T3).ConclusionThis pilot RCT study will determine the feasibility and acceptability of the intervention and study design and will inform full-scale RCT planning.

A. baumannii is a ubiquitously found gram-negative, multi-drug resistant bacterial species from the ESKAPE family of pathogens known to be the causative agent for hospital-acquired infections such as pneumonia, meningitis, endocarditis, septicaemia and urinary tract infections. A. baumannii is implicated as a contributor to bloodstream infections in approximately 2% of all worldwide infections. Hence, exploring novel therapeutic agents against the bacterium is essential. LpxA or UDP-N-acetylglucosamine acetyltransferase is an essential enzyme important in Lipid A biosynthesis which catalyses the reversible transfer of an acetyl group on the glucosamine 3-OH of the UDP-GlcNAc which is a crucial step in the biosynthesis of the protective Lipopolysaccharides (LPS) layer of the bacteria which upon disruption can lead to the elimination of the bacterium which delineates LpxA as an appreciable drug target from A. baumannii. The present study performs high throughput virtual screening of LpxA against the enamine-HTSC-large-molecule library and performs toxicity and ADME screening to identify the three promising lead molecules subjected to molecular dynamics simulations. Global and essential dynamics analysis of LpxA and its complexes along with FEL and MM/PBSA based binding free energy delineate Z367461724 and Z219244584 as potential inhibitors against LpxA from A. baumannii.

Background: Urinary retention remains a frequent postoperative complication, associated with patient discomfort and delayed discharge following general thoracic surgery (GTS). We aimed to develop and prospectively validate a predictive model of postoperative urinary retention (POUR) among GTS patients. Methods: We retrospectively developed a predictive model using data from the Society of Thoracic Surgeons GTS Database at our institution. The patient study cohort included adults undergoing elective in-patient surgical procedures without a history of renal failure or Foley catheter on entry to the recovery suite (August 2013 to March 2017). Multivariable logistic regression models identified factors associated with urinary retention, and a nomogram to aid medical decision making was developed. The predictive model was validated in a cohort of GTS patients between April 2017 and November 2018 using receiver operating characteristic (ROC) analysis. Results: The predictive model was developed from 1484 GTS patients, 284 of whom (19%) experienced postoperative urinary retention within 24 hours of the operation. Risk factors for POUR included older age, male sex, higher preoperative creatinine, chronic obstructive pulmonary disease, primary diagnosis, primary procedure, and use of postoperative patient-controlled analgesia. A logistic nomogram for estimating the risk of POUR was created and validated in 646 patients, 65 of whom (10%) had urinary retention. The ROC curves of development and validation models had similar favorable c-statistics (0.77 vs 0.72; P > .05). Conclusions: Postoperative urinary retention occurs in nearly 20% of patients undergoing major GTS. Using a validated predictive model may help by targeting certain patients with prophylactic measures to prevent this complication.

A public shaming frenzy has spread through social media (SM) following the instigation of lockdown policies as a way to counter the spread of COVID-19. On SM, individuals shun the idea of self-promotion and shame others who do not follow the COVID-19 guidelines. When it comes to the crime of not taking a pandemic seriously, perhaps the ultimate penalty is online shaming. The study proposes the black swan theory from the human-computer interaction lens and examines the toxic combination of online shaming and self-promotion in SM to discern whether pointing the finger of blame is a productive way of changing rule-breaking behaviour. A quantitative methodology is applied to survey data, acquired from 375 respondents. The findings reveal that the adverse effect of online shaming results in self-destructive behaviour. Change in behaviour of individuals shamed online is higher for females over males and is higher for adults over middle-aged and older-aged.

Heavy metal toxicity in water is a serious problem that may have harmful effects on human health and the ecosystem. Lead [Pb(II)] and cadmium [Cd(II)] are two such heavy metal ions, present in water, whose severity is well-known and well-studied. In the current research, magnetic biochar composite (MBC) is studied as an adsorbent material for the effective removal of lead and cadmium ions from water solutions. Magnetite (Fe3O4) nanoparticles and pine-needle-derived ultrasonicated magnetic biochar were used in different weight ratios to prepare APTES (3-aminopropyl triethoxysilane)-functionalized MBC (FMBC). An average crystalline size of ~10 nm for magnetite NPs was obtained via XRD analysis. The adsorption characteristics of both Pb(II) and Cd(II) ions were investigated in a batch experiment. The FTIR spectra of raw biochar, MBC, FMBC, and metal-loaded FMBC were obtained at different stages. The decrease in the intensity of the –NH2 functional group in the FTIR spectra of the residue confirmed the successful adsorption of heavy metal ions. The SEM-EDX spectra of the residue showed the uniform adsorption of Pb(II) and Cd(II) heavy metal ions onto the surface of the adsorbent. Magnetic biochar composite (MBC) was found to be a very effective adsorbent at basic pH, as a maximum of 97% instantaneous heavy metal removal was observed for both ions in synthetic water solutions. The Langmuir isotherm model predicted the monolayer adsorption and good affinity between the metal ions and adsorbent. The prepared MBC is low-cost, environmentally friendly, and it has shown good adsorption performance. Therefore, our study suggests that the magnetic biochar composite under study is an effective adsorbent for lead and cadmium metal ion removal from aqueous solutions at normal room temperature. Only a few hundred milligrams of the adsorbent dose is sufficient to remove higher concentrations (~100 ppm) of lead and cadmium at basic pH conditions of aqueous solutions.

The present work evaluates the techno-economic feasibility of a rhamnolipids production process that utilizes digestate from anaerobic digestion (AD) of food waste. Technical feasibility, profitability and extent of investment risks between fermenter scale and its operating strategy for rhamnolipids production was investigated in the present study. Three scenarios were generated and compared: production using a single large fermenter (Scenario I), using two small fermenters operated alternately (Scenario II) or simultaneously (Scenario III). It was found that all the scenarios were economically feasible, and Scenario III was the most profitable since it allowed the most optimum fermenter operation with utilization of multiple small-scale equipment to reduce the downtime of each equipment and increase the production capacity and overall productivity. It had the highest net present value, internal rate of return and shortest payback time at a discount rate of 7%. Finally, a sensitivity analysis was conducted to indicate how the variation in factors such as feedstock (digestate) cost, rhamnolipids selling price, extractant recyclability and process capacity influenced the process economics. The work provides important insights on techno-economic performance of a food waste digestate valorization process which would be useful to guide its sustainable scale-up.

Application-Specific Networks-on-Chips (ASNoCs) are suitable communication platforms for meeting current application requirements. Interconnection links are the primary components involved in communication between the cores of an ASNoC design. The integration density in ASNoC increases with continuous scaling down of the transistor size. Excessive integration density in ASNoC can result in the formation of thermal hotspots, which can cause a system to fail permanently. As a result, fault-tolerant techniques are required to address the permanent faults in interconnection links of an ASNoC design. By taking into account link faults in the topology, this paper introduces a fault-tolerant application-specific topology-based NoC design and its prototype on an FPGA. To place spare links in the ASNoC topology, a meta-heuristic algorithm based on Particle Swarm Optimization (PSO) is proposed. By taking link faults into account in ASNoC design, we also propose an application mapping heuristic and a table-based fault-tolerant routing algorithm. Experiments are carried out for a specific link and any link fault in fault-tolerant topologies generated by our approach and approaches reported in the literature. For the experimentation, we used the multi-media applications Picture-in-Picture (PiP), Moving Pictures Expert Group (MPEG) - 4, MP3Encoder, and Video Object Plane Decoder (VOPD). Experiments are run on software and hardware platforms. The static performance metric communication cost and the dynamic performance metrics network latency, throughput, and router power consumption are examined using software platform. In the hardware platform, the Field Programmable Gate Array (FPGA) is used to validate proposed fault-tolerant topologies and analyze performance metrics such as application runtime, resource utilization, and power consumption. The results are compared with the existing approaches, specifically Ring topology and its modified versions on both software and hardware platforms. The experimental results obtained from software and hardware platforms for a specific link and any link fault show significant improvements in performance metrics using our approach when compared with the related works in the literature.

Abstract Background The COVID-19 pandemic caused by SARS-CoV-2 has shown an exponential trend of infected people across the planet. Crediting its virulent nature, it becomes imperative to identify potential therapeutic agents against the deadly virus. The 3-chymotrypsin-like protease (3CLpro) is a cysteine protease which causes the proteolysis of the replicase polyproteins to generate functional proteins, which is a crucial step for viral replication and infection. Computational methods have been applied in recent studies to identify promising inhibitors against 3CLpro to inhibit the viral activity. Main body of the abstract This review provides an overview of promising drug/lead candidates identified so far against 3CLpro through various in silico approaches such as structure-based virtual screening (SBVS), ligand-based virtual screening (LBVS) and drug-repurposing/drug-reprofiling/drug-retasking. Further, the drugs have been classified according to their chemical structures or biological activity into flavonoids, peptides, terpenes, quinolines, nucleoside and nucleotide analogues, protease inhibitors, phenalene and antibiotic derivatives. These are then individually discussed based on the various structural parameters namely estimated free energy of binding (ΔG), key interacting residues, types of intermolecular interactions and structural stability of 3CLpro-ligand complexes obtained from the results of molecular dynamics (MD) simulations. Conclusion The review provides comprehensive information of potential inhibitors identified through several computational methods thus far against 3CLpro from SARS-CoV-2 and provides a better understanding of their interaction patterns and dynamic states of free and ligand-bound 3CLpro structures.

Abstract Background The World Health Organization (WHO) report stated that Acinetobacter baumannii had been classified as one of the most important pathogenic bacteria causing nosocomial infection in hospital patients due to multi-drug resistance (MDR). It is vital to find out new bacterial drug targets and annotated their structure and function for the exploration of new anti-bacterial agents. The present study utilized a systematic route to prioritize the potential drug targets that belong to Mur family of Acinetobacter baumannii and identify their homologous proteins using a computational approach such as sequence similarity search, multiple sequence alignment, phylogenetic analysis, protein sequence, and protein structure analysis. Results From the results of protein sequence analysis of eight Mur family proteins, they divided into three main enzymatic classes namely transferases (MurG, MurA and MraY), ligases (MurC, MurD, MurE, and MurF), and oxidoreductase (MurB). Based on the results of intra-comparative protein sequence analysis and enzymatic classification, we have chosen MurB, MurE, and MurG as the prioritized drug targets from A. baumannii and subjected them for further detailed studies of inter-species comparison. This inter-species comparison help us to explore the sequential and structural properties of homologous proteins in other species and hence, opens a gateway for new target identification and using common inhibitor for different bacterial species caused by various diseases. The pairwise sequence alignment results between A. baumannii’s MurB with A. calcoaceticus’s MurB, A. baumannii’s MurE with A. seifertii’s MurE, and A. baumannii’s MurG with A. pittii’s MurG showed that every group of the proteins are highly similar with each other and they showed sequence identity of 95.7% and sequence similarity of 97.2%. Conclusion Together with the results of secondary and three-dimensional structure predictions explained that three selected proteins (MurB, MurE, and MurG) from A. baumannii and their related proteins (AcMurB, AsMurE, and ApMurG) belong to mixed αβ class and they are very similar.

An inguinal hernia is quite frequent in surgical praxis. One of the rare entities sliding type of inguinal hernia with an incidence of 2%–5%, which is difficult to diagnose preoperatively, most of the time, its diagnosis is made on the operational table. We report a rare case of pantaloon-type hernia with sliding components in either side of the hernia: the appendix, ascending colon onto the lateral, indirect hernia sac, and the urinary bladder onto the medial, direct sac, respectively. The two hernia sacs were saddled on either side of the inferior epigastric vessels. A 77-year-old presented with a right inguinoscrotal swelling for 5 years and increased frequency of micturition for 8 months. The indirect sac was opened very cautiously and was found to contain an appendix, the part of urinary bladder medially and ascending colon laterally forming the sliding component, small bowel, omentum are the contents of sliding hernia. The contents were attenuated and the sac was sealed cautiously. The posterior wall of the right inguinal canal was opened in total, contents were reduced, and neo posterior wall is formed by strengthening, and reinforcement did with prolene mesh. This entity is a diagnostic dispute due to its rarity and defined clinical presentation. Pantaloons hernia with two sliding components is uncommon. The hernia consisted of two parts: a laterally-located indirect sac containing the appendix and sliding ascending colon, and a medially-located direct hernia of sliding urinary bladder. A hernia of long duration in old patients should raise a suspicion of a pantaloon-type hernia. One should be very careful to identify the contents of the hernia to avoid inadvertent injury to the structures.

Abstract A contemporary and decisive optimization algorithm is developed for inverting gravity anomalies due to listric faults. The cross‐section of listric faults are generally concave up, and the dip of the fault plane gradually decreases with depth. Quadratic Bezier curves are utilized to represent the curvature of the fault plane. The densities of sediment deposition are assumed to be known and can take any linear or non‐linear functional form of depth. By constraining the density, a global optimization algorithm is adopted to estimate the fault structure by inverting control point parameters of Bezier curves. The presented algorithm is implemented in two different synthetic models having fixed and depth varying density contrasts. The robustness of the algorithm is authenticated by incorporating white Gaussian noise into synthetic gravity anomalies. A detailed uncertainty appraisal is also performed to justify the reliability of the algorithm. Finally, a real structure is reconstructed using observed gravity anomalies, and the estimated structure is verified with the structure obtained in previously published literature. Furthermore, a Matlab based GUI is developed such that any user can estimate real listric fault structure without any computational difficulties.

Three-dimensional printing (3DP) is predicted to be one of the most progressive innovations within the pharmacy. Nowadays, the use of 3D printing technologies in drug delivery systems has exponentially expanded, due to its potential advantages over customizing drugs in individually adjusted doses. 3DP empowers the precise deposition of medicaments and excipients, which might cause a change in perspective in drug configuration, production, and use. It can span the medication improvement measure, from the preclinical turn of events and clinical preliminaries to frontline medical care. Though 3DP technology represents the clinical and financial advantages, some specialized and administrative challenges limit its utilization of pharmaceutical products. Accordingly, there's a prerequisite for constant development and refinement in 3DP methods to beat current limits and work with patients' particular medical services with the utilization of customized drugs in the future. This article presents a few 3DP technologies appropriate for drug fabrications with their applications in the improvement of the drug dose structures, demonstrating the feasibility of this innovation in regular commercial production with regulatory assessment.

Sickle cell disease is a major public health problem in India. Lack of rapid and reliable diagnostic methods result in many avoidable deaths in affected population. Current diagnostic tools are laboratory based, expensive and need trained manpower. Here, we evaluated the performance of a microchip-based cellulose acetate electrophoresis test, “Gazelle” in the tribal-dominated Indian states of Chhattisgarh and Madhya Pradesh. A total of 1,050 patients were screened by sickle cell solubility, hemoglobin (cellulose acetate) electrophoresis, high-performance liquid chromatography (HPLC) and Gazelle. Of the total 1,027 test results obtained, 960 tests were “Valid” (93.5%) and included in the analysis. Gazelle identified all patients with disease (HbSS and Thalassemia Major) with 100% accuracy. Gazelle demonstrated 100% sensitivity when comparing sickle cell disease (SCD) vs. sickle cell trait and SCD vs. normal. Specificity was 98.9% and 99.5% when comparing SCD vs. trait and trait vs. normal, respectively. Specificity was 99.8% when comparing SCD vs. normal and sensitivity was 99.3% when comparing trait vs. normal. Overall, Gazelle yielded a high accuracy (99.0%) compared to reference standard tests (hemoglobin electrophoresis and HPLC). Gazelle is a low-cost, rapid diagnostic test with high accuracy for detecting SCD both quantitatively and qualitatively. Gazelle can be a potential screening tool for the rapid diagnosis in resource limited settings and developing countries with high burden of hemoglobin disorders.

Epigenetic modifications act as an important bridge to regulate the complex network of gene-environment interactions. As these mechanisms determine the gene-expression patterns via regulating the transcriptomic machinery, environmental stress induced epigenetic modifications may interrupt distinct cellular functions resulting into generation of diseased phenotypes. In the present study, we used a multi-city approach to compare the epigenomic signatures of individuals living in two tiers of Indian cities categorized as low-risk and high-risk air pollution zones. The high-risk group reported marked changes in the expression levels of epigenetic modifiers (DNMT1, DNMT3a, EZH2, EHMT2 and HAT), that maintains the levels of specific epigenetic marks essential for appropriate gene functioning. These results also coincided with the observed alterations in the levels of DNA methylation (LINE-1 and % 5mC), and histone modifications (H3 and H4), among the high-risk group. In addition, higher degree of changes reported in the expression profile of a selected miRNA panel in the high-risk group indicated the probability of deregulated transcriptional machinery. This was further confirmed by the analysis of a target gene panel involved in various signalling pathways, which revealed differential expression of the gene transcripts regulating cell cycle, inflammation, cell survival, apoptosis and cell adhesion. Together, our results provide first insights of epigenetic modifications among individuals living in different high and low levels of air pollution zones of India. However, further steps to develop a point-of-care epigenomic assay for human bio-monitoring may be immensely beneficial to reduce the health burden of air pollution especially in low and-middle-income countries.