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Abstract Background Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains. Method In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI. Result Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI. Conclusion Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI. Graphical abstract

The development of rotary files and other endodontic instrument techniques have revolutionised treatment by enhancing canal preparation and producing rounder, smoother canals that are constructed of Nickel-Titanium (NiTi) alloy. There are two types of movements in these instruments: rotary continuous and reciprocating. Rotary continuous movements involve torsion and flexion, and can cause instrument fractures. An alternative approach to avoid the issue is proposed, which involves reciprocating movement. The present literature review compares the incidence of dentinal crack formation in root canal walls when using stainless steel and NiTi rotary systems. It highlights the potential complications, such as tooth fracture and increased bacterial susceptibility due to contact between instruments and dentinal walls.

Abstract Cd(II) is a potentially toxic heavy metal having carcinogenic activity. It is becoming widespread in the soil and groundwater by various natural and anthropological activities. This is inviting its immediate removal. The present study is aimed at developing a Cd(II) resistant strain isolated from contaminated water body and testing its potency in biological remediation of Cd(II) from aqueous environment. The developed resistant strain was characterized by SEM, FESEM, TEM, EDAX, FT-IR, Raman Spectral, XRD and XPS analysis. The results depict considerable morphological changes had taken place on the cell surface and interaction of Cd(II) with the surface exposed functional groups along with intracellular accumulation. Molecular contribution of critical cell wall component has been evaluated. The developed resistant strain had undergone Cd(II) biosorption study by employing adsorption isotherms and kinetic modeling. Langmuir model best fitted the Cd(II) biosorption data compared to the Freundlich one. Cd(II) biosorption by the strain followed a pseudo second order kinetics. The physical parameters affecting biosorption were also optimized by employing response surface methodology using central composite design. The results depict remarkable removal capacity 75.682 ± 0.002% of Cd(II) by the developed resistant strain from contaminated aqueous medium using 500 ppm of Cd(II). Quantitatively, biosorption for Cd(II) by the newly developed resistant strain has been increased significantly (p

Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature.

Introduction: This study aimed to assess the knowledge, attitudes, and practices related to coronavirus disease 2019 (COVID-19) among adolescents in India, recognizing the vital role this demographic plays in pandemic control. Materials and Methods: Conducted at the Medical College, Kolkata COVID-19 vaccination center from June to August 2022, this web-based prospective cross-sectional study included individuals aged 13–19 years. Data collection involved a structured questionnaire in multiple languages, ensuring broad accessibility. Ethical standards were upheld with online informed consent and rigorous data confidentiality measures. Results: The study revealed balanced gender representation among participants, with most enrolled in the 10th or 12th standard. Parents' educational backgrounds varied, but a significant proportion had family members employed in the health-care sector (66.7%). Knowledge about COVID-19 in India was surprisingly limited: only 3.7% knew about oxygen saturation and its utility. 18.75% considered depression as a comorbidity of COVID-19. 73.8% of the participants relied on social media for information about COVID-19. A majority (66.25%) of the participants believed 2 doses of the vaccine would protect them from the disease. Twice as many women believed in the protection offered by vaccines. Conclusion: This research, distinct from conventional scoring-based studies, emphasized uncovering misconceptions and knowledge gaps. Importantly, many adolescents lacked awareness of the true COVID-19 situation in India, potentially undermining the pandemic gravity perception and preventive measures. Although participants showed awareness of common COVID-19 symptoms and preventive measures, knowledge about comorbidities' influence on mortality rates was limited.

Abstract Background A water-soluble ingredient of mature leaves of the tropical mahogany ‘Neem’ (Azadirachta indica), was identified as glycoprotein, thus being named as ‘Neem Leaf Glycoprotein’ (NLGP). This non-toxic leaf-component regressed cancerous murine tumors (melanoma, carcinoma, sarcoma) recurrently in different experimental circumstances by boosting prime antitumor immune attributes. Such antitumor immunomodulation, aid cytotoxic T cell (Tc)-based annihilation of tumor cells. This study focused on identifying and characterizing the signaling gateway that initiate this systemic immunomodulation. In search of this gateway, antigen-presenting cells (APCs) were explored, which activate and induce the cytotoxic thrust in Tc cells. Methods Six glycoprotein-binding C-type lectins found on APCs, namely, MBR, Dectin-1, Dectin-2, DC-SIGN, DEC205 and DNGR-1 were screened on bone marrow-derived dendritic cells from C57BL/6 J mice. Fluorescence microscopy, RT-PCR, flow cytometry and ELISA revealed Dectin-1 as the NLGP-binding receptor, followed by verifications through RNAi. Following detection of β-Glucans in NLGP, their interactions with Dectin-1 were explored in silico. Roles of second messengers and transcription factors in the downstream signal were studied by co-immunoprecipitation, western blotting, and chromatin-immunoprecipitation. Intracellularization of FITC-coupled NLGP was observed by processing confocal micrographs of DCs. Results Considering extents of hindrance in NLGP-driven transcription rates of the cytokines IL-10 and IL-12p35 by receptor-neutralization, Dectin-1 receptors on dendritic cells were found to bind NLGP through the ligand’s peripheral β-Glucan chains. The resulting signal phosphorylates PKCδ, forming a trimolecular complex of CARD9, Bcl10 and MALT1, which in turn activates the canonical NFκB-pathway of transcription-regulation. Consequently, the NFκB-heterodimer p65:p50 enhances Il12a transcription and the p50:p50 homodimer represses Il10 transcription, bringing about a cytokine-based systemic-bias towards type-1 immune environment. Further, NLGP gets engulfed within dendritic cells, possibly through endocytic activities of Dectin-1. Conclusion NLGP’s binding to Dectin-1 receptors on murine dendritic cells, followed by the intracellular signal, lead to NFκB-mediated contrasting regulation of cytokine-transcriptions, initiating a pro-inflammatory immunopolarization, which amplifies further by the responding immune cells including Tc cells, alongside their enhanced cytotoxicity. These insights into the initiation of mammalian systemic immunomodulation by NLGP at cellular and molecular levels, may help uncovering its mode of action as a novel immunomodulator against human cancers, following clinical trials.

Abstract Glioblastoma is a highly heterogeneous disease, with variations observed at both phenotypical and molecular levels. Personalized therapies would be facilitated by non-invasive in vivo approaches for characterizing this heterogeneity. In this study, we developed unsupervised joint machine learning between radiomic and genomic data, thereby identifying distinct glioblastoma subtypes. A retrospective cohort of 571 IDH-wildtype glioblastoma patients were included in the study, and pre-operative multi-parametric MRI scans and targeted next-generation sequencing (NGS) data were collected. L21-norm minimization was used to select a subset of 12 radiomic features from the MRI scans, and 13 key driver genes from the five main signal pathways most affected in glioblastoma were selected from the genomic data. Subtypes were identified using a joint learning approach called Anchor-based Partial Multi-modal Clustering on both radiomic and genomic modalities. Kaplan–Meier analysis identified three distinct glioblastoma subtypes: high-risk, medium-risk, and low-risk, based on overall survival outcome (p

Abstract The present work explores the potential for observing multiple reentrant localization behavior in a double-stranded helical (DSH) system, extending beyond the conventional nearest-neighbor hopping (NNH) interaction. The DSH system is considered to have hopping dimerization in each strand, while also being subjected to a transverse electric field. The inclusion of an electric field serves the dual purpose of inducing quasi-periodic disorder and strand-wise staggered site energies. Two reentrant localization regions are identified: one exhibiting true extended behavior in the thermodynamic limit, while the second region shows quasi-extended characteristics with partial spreading within the helix. The DSH system exhibits three distinct single-particle mobility edges linked to localization transitions present in the system. The analysis in this study involves examining various parameters such as the single-particle energy spectrum, inverse participation ratio, local probability amplitude, and more. Our proposal, combining achievable hopping dimerization and induced correlated disorder, presents a unique opportunity to study phenomenon of reentrant localization, generating significant research interest.

Introduction: Very Low Birth Weight (VLBW) babies are those with a birth weight of less than 1500 gm and require special care, attention, and resources. However, despite all efforts, their mortality rate remains high. Proper assessment of these neonates is crucial to identify high-risk cases and take early steps to reduce mortality. In addition to technical advances in neonatal care, severity scores have been developed to predict neonatal mortality. Richardson developed the Score for Neonatal Acute Physiology (SNAP-II) and SNAP with Perinatal Extension (SNAPPE-II) as scoring systems for predicting mortality in the Neonatal Intensive Care Unit (NICU). Aim: To assess the usefulness of SNAP-II and SNAPPE-II as predictors of mortality in VLBW neonates. Materials and Methods: This was an observational cross-sectional study involving 145 VLBW neonates admitted to the NICU of North Bengal Medical College and Hospital (NBMCH) from May 2019 to April 2020. Relevant data were collected to assess the mortality risk scores SNAP-II and SNAPPE-II. The outcome of discharge or death was recorded. Data entry was performed using MS excel and analysed using Statistical Package for Social Sciences (SPSS) version 20.0. The relationship between newborn survival and SNAP-II or SNAPPE-II final scores was determined using the Mann-Whitney U test, and the relationship between survival and various SNAP-II and SNAPPE-II score categories was determined using Fisher’s-Exact Test. A p-value of less than 0.05 was considered statistically significant. An ROC curve was generated to determine the best cutoff score for predicting mortality. Results: The mean scores of SNAP-II and SNAPPE-II were higher in babies who expired compared to those who survived. The mean (±SD) SNAP-II scores were 8.96 (±13.865) for survived newborns and 41.08 (±23.174) for expired newborns. The mean (±SD) SNAPPE-II scores were 20.01 (±14.54) for survived newborns and 48.85 (±25.02) for expired newborns. The optimal cutoff values for SNAP-II and SNAPPE-II in predicting mortality were 31.5 and 36, respectively. The sensitivity and specificity of SNAP-II were 83.0% and 89.1%, while for SNAPPE-II they were 69.8% and 89.1%, respectively. Conclusion: The mean SNAP-II and SNAPPE-II scores were higher among expired VLBW neonates compared to those who survived. A SNAP-II score of 31.5 and SNAPPE-II score of 36 were associated with higher mortality, indicating that both scores are effective predictors of mortality regardless of Gestational Ages (GA) and birth weight.

Abstract We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of $$\sim$$ ∼ 4.2 M veterans. The ensembles rely on nonlinear base models trained using a matched retrospective nested case-control (Rcc) study cohort and show good calibration across a diversity of subgroups, including risk strata, age, sex, race, and level of healthcare utilization. In addition, a linear Rcc base model provided a rich set of biological predictors, including indicators of suicide, substance use disorder, mental health diagnoses and treatments, hypoxia and vascular damage, and demographics.

Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster, internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b, is expressed exclusively in a pair of GRNs activated by high salt. Using a two-way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co-receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt.

High Serum Ascites Albumin Gradient (SAAG) ascites in severe rheumatic mitral stenosis is very uncommon. Hereby, the authors present a similar case with this rare combination. The present case report describes a 42-year-old male with no history of hypertension or diabetes, but occasional alcohol consumption, who presented to department with complaints of recurrent anasarca over the past five years. The electrocardiogram showed an irregular R-R interval with no P waves, indicating atrial fibrillation. Ascitic fluid analysis revealed a high serum ascites albumin gradient with low ascitic protein levels. The patient responded well to treatment and was discharged with appropriate medications. He was referred to a higher centre with cardiothoracic surgical facilities for mitral valve replacement and tricuspid annuloplasty. The present case report highlights the uniqueness of the combination of severe rheumatic mitral stenosis and ascites.

Abstract In this paper, we consider the problem of batch classification and propose a novel framework for achieving fairness in such settings. The problem of batch classification involves selection of a set of individuals, often encountered in real-world scenarios such as job recruitment, college admissions etc. This is in contrast to a typical classification problem, where each candidate in the test set is considered separately and independently. In such scenarios, achieving the same acceptance rate (i.e., probability of the classifier assigning positive class) for each group (membership determined by the value of sensitive attributes such as gender, race etc.) is often not desirable, and the regulatory body specifies a different acceptance rate for each group. The existing fairness enhancing methods do not allow for such specifications and hence are unsuited for such scenarios. In this paper, we define a configuration model whereby the acceptance rate of each group can be regulated and further introduce a novel batch-wise fairness post-processing framework using the classifier confidence-scores. We deploy our framework across four real-world datasets and two popular notions of fairness, namely demographic parity and equalized odds. In addition to consistent performance improvements over the competing baselines, the proposed framework allows flexibility and significant speed-up. It can also seamlessly incorporate multiple overlapping sensitive attributes. To further demonstrate the generalizability of our framework, we deploy it to the problem of fair gerrymandering where it achieves a better fairness-accuracy trade-off than the existing baseline method.

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 plays any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension upon chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the ‘outside-in’ signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.

Abstract In this work, we discuss the development of H.O.S.T., a novel hemoglobin microbubble-based electrochemical biosensor for label-free detection of Hydrogen peroxide (H2O2) towards oxidative stress and cancer diagnostic applications. The novelty of the constructed sensor lies in the use of a sonochemically prepared hemoglobin microbubble capture probe, which allowed for an extended dynamic range, lower detection limit, and enhanced resolution compared to the native hemoglobin based H2O2 biosensors. The size of the prepared particles Hemoglobin microbubbles was characterized using Coulter Counter analysis and was found to be 4.4 microns, and the morphology of these spherical microbubbles was shown using Brightfield microscopy. The binding chemistry of the sensor stack elements of HbMbs’ and P.A.N.H.S. crosslinker was characterized using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy and UV–Vis Spectroscopy. The electrochemical biosensor calibration (R2 > 0.95) was done using Electrochemical Impedance Spectroscopy, Cyclic Voltammetry, and Square Wave Voltammetry. The electrochemical biosensor calibration (R2 > 0.95) was done using Electrochemical Impedance Spectroscopy, Cyclic Voltammetry, and Square Wave Voltammetry. The specificity of the sensor for H2O2 was analyzed using cross-reactivity studies using ascorbic acid and glucose as interferents (p

Abstract This work explores the potential for achieving correlated disorder in electrical circuits by utilizing reactive elements. By establishing a direct correspondence between the tight-binding Hamiltonian and the admittance matrix of the circuit, a novel approach is presented. The localization phenomena within the circuit are investigated through the analysis of the two-port impedance. To introduce correlated disorder, the Aubry–André–Harper (AAH) model is employed. Both one-dimensional and quasi-one-dimensional AAH structures are examined and effectively mapped to their tight-binding counterparts. Notably, transitions from a high-conducting phase to a low-conducting phase are observed in these circuits, highlighting the impact of correlated disorder.

Abstract Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML). However, MRD cannot be detected in many patients using current methods. We developed a highly sensitive 5-hydroxymethylcytosine (5hmC) signature in cell-free DNA by analyzing 115 AML patients and 86 controls. The 5hmC method detected MRD in 20 of 29 patients with negative MRD by multiparameter flow cytometry and 11 of 14 patients with negative MRD by molecular methods. MRD detection by the 5hmC method was significantly associated with relapse-free survival. This novel method can be used in most AML patients and may significantly impact AML patient management.

Abstract Cadmium is one of the most dreadful heavy metals and is becoming a major toxicant in ground water with increasing concentration above the WHO Guidelines in drinking water (0.003 mg/L). The potential sources of cadmium include sewage sludge, phosphate fertilizers and ingredients like Ni–Cd batteries, pigments, plating and plastics. Cadmium levels are increased in water owing to the use and disposal of cadmium containing ingredients. Water draining from a landfill may contain higher cadmium levels. The authors have tried to evaluate the optimized nutritional conditions for the optimal growth and Cd(II) remediation capacity for a developed Cd(II) resistant yeast strain named Candida tropicalis XTA 1874 isolated from contaminated water-body in West Bengal. By analyzing the optimization conditions, a synthetic medium was developed and the composition has been given in the main text. The strain showed much better Cd(II) adsorption capacity under the optimized nutritional conditions (Mean removal = 88.077 ± 0.097%).

Immune checkpoint (IC) therapy has brought a huge revolution in the field of lung cancer treatment over the past decade. It has also revolutionised treatment paradigm and has tremendously improved patient prognosis. IC inhibitors (ICIs) targeting Programmed Cell Death Protein 1/Programmed cell death Ligand 1 (PD1/PD-L1) have shown remarkable success and are now being used as first-line therapies in metastatic disease, adjuvant therapy following surgical resection and chemotherapy in resectable disease. Despite this remarkable success, only a subset of patients obtains complete benefit and most patients do not respond or develop progressive disease during treatment. ICIs are relatively expensive and some patients suffer from significant immune-related adverse toxicities. Hence, the identification and discovery of new predictive and prognostic immunotherapy biomarkers remains the present crucial need for patient selection, stratification and also for guiding therapeutic decisions. Currently established biomarkers such as PD-L1 determined by immunohistochemistry and tumour mutation burden determined by next-generation sequencing are non-specific and possess limitations. At present, several other biomarkers using peripheral blood, liquid biopsies along with gene expression signatures, and tumour infiltrating lymphocytes are being researched globally which have demonstrated predictive potential to characterise ICIs responders. In this review, we provide a comprehensive overview of the current biomarkers, highlighting the main clinical challenges and possible novel potential biomarkers to better predict responders to ICIs.

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (

Abstract As the world grapples with global warming, it becomes imperative to carefully examine the sustainable energy technology choices. Solar is the fastest growing clean energy source but today it contributes little to the electricity generated, so future installations will dwarf the existing installed base. There is a factor of 2–4 decrease in the energy payback time from the dominant crystalline silicon technology to thin film technologies. Essential criteria like use of abundant materials and simple but mature production technology point to amorphous silicon (a-Si) technology. Here we delve into the primary issue impeding adoption of a-Si technology—the Staebler Wronski Effect (SWE), that generates metastable, light induced defects which reduce the performance of a-Si based solar cells. We demonstrate that a simple change leads to a significant reduction in SWE power loss and define a clear path to elimination of SWE, allowing the technology to be widely adopted.

Abstract A P-N junction engineered within a Dirac cone system acts as a gate tunable angular filter based on Klein tunneling. For a 3D topological insulator with a substantial bandgap, such a filter can produce a charge-to-spin conversion due to the dual effects of spin-momentum locking and momentum filtering. We analyze how spins filtered at an in-plane topological insulator PN junction (TIPNJ) interact with a nanomagnet, and argue that the intrinsic charge-to-spin conversion does not translate to an external gain if the nanomagnet also acts as the source contact. Regardless of the nanomagnet’s position, the spin torque generated on the TIPNJ is limited by its surface current density, which in turn is limited by the bulk bandgap. Using quantum kinetic models, we calculated the spatially varying spin potential and quantified the localization of the current versus the applied bias. Additionally, with the magnetodynamic simulation of a soft magnet, we show that the PN junction can offer a critical gate tunability in the switching probability of the nanomagnet, with potential applications in probabilistic neuromorphic computing.

AbstractBackground: Brucellosis is a pervasive zoonotic disease caused by various Brucella species. It mainly affects livestock and wildlife and poses significant public health threats, especially in regions with suboptimal hygiene, food safety, and veterinary care standards. Human contractions occur by consuming contaminated animal products or interacting with infected animals. Objective: This study aims to provide an updated understanding of brucellosis, from its epidemiology and pathogenesis to diagnosis and treatment strategies. It emphasizes the importance of ongoing research, knowledge exchange, and interdisciplinary collaboration for effective disease control and prevention, highlighting its global health implications. Methods: Pathogenesis involves intricate interactions between bacteria and the host immune system, resulting in chronic infections characterized by diverse clinical manifestations. The diagnostic process is arduous owing to non-specific symptomatology and sampling challenges, necessitating a fusion of clinical and laboratory evaluations, including blood cultures, serological assays, and molecular methods. Management typically entails multiple antibiotics, although the rise in antibiotic-resistant Brucella strains poses a problem. Animal vaccination is a potential strategy to curb the spread of infection, particularly within livestock populations. Results: The study provides insights into the complex pathogenesis of brucellosis, the challenges in its diagnosis, and the management strategies involving antibiotic therapy and animal vaccination. It also highlights the emerging issue of antibiotic-resistant Brucella strains. Conclusions: In conclusion, brucellosis is a significant zoonotic disease with implications for public health. Efforts should be directed towards improved diagnostic methods, antibiotic stewardship to combat antibiotic resistance, and developing and implementing effective animal vaccination programs. Interdisciplinary collaboration and ongoing research are crucial for addressing the global health implications of brucellosis.

Abstract Rheumatoid Arthritis is one of the most common autoimmune diseases, causing irreversible joint damage and disability. Methotrexate (MTX) is the gold standard drug for this. The low cost, easy availability and high efficacy makes it the most important and commonly used DMARD in developing and low income countries. However, long term use of MTX is also associated with intolerance including gastrointestinal effects such as nausea, vomiting, abdominal pain and diarrhoea. In addition, anticipatory, associative and behavioural symptoms such as anxiety and irritability are also observed. These adverse effects arise as a conditioned response and are often inadequately managed, leading to discontinuation of treatment. Understanding and assessing the incidence of MTX intolerance across ethnicities and geographical regions would lead to a better treatment compliance. In this review we present a compilation of the available literature on Methotrexate intolerance in Rheumatoid Arthritis and strategies to mitigate this effect.

Abstract In developing a wire-arc directed energy deposition process for superalloys used in high-speed flight environments, Inconel 718 was deposited using a plasma arc process and tested for its high temperature performance. The deposited material was tested in both the as deposited condition and after an age-hardening industry standard heat-treatment for this alloy. Results showed a reduced performance in both deposited conditions, with heat-treated material significantly outperforming as deposited material up to 538 °C. The difference in performance was less significant from 760 to 1000 °C, owing to an in-test aging process which increased the performance of the as deposited material. The microstructure of deposited material showed significant cracking throughout the alloy and formation of secondary phases throughout the matrix, with significantly more precipitation after heat-treating.

Abstract Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets. The 22 cis-regulatory variants predictably alter the binding of 44 transcription factors (TFs) expressed in lung tissue. Interestingly, 6 reported lung cancer-associated variants were found in linkage disequilibrium (LD) with 5 prioritized cis-eQTLs from our study. A case–control study with 3 promoter cis-eQTLs (p

Abstract We report for the first time the phenomenon of flux-driven circular current in an isolated Su–Schrieffer–Heeger (SSH) quantum ring in presence of cosine modulation in the form of the Aubry–André–Harper (AAH) model. The quantum ring is described within a tight-binding framework, where the effect of magnetic flux is incorporated through Peierls substitution. Depending on the arrangements of AAH site potentials we have two different kinds of ring systems that are referred to as staggered and non-staggered AAH SSH rings. The interplay between the hopping dimerization and quasiperiodic modulation leads to several new features in the energy band spectrum and persistent current which we investigate critically. An atypical enhancement of current with increasing AAH modulation strength is obtained that gives a clear signature of transition from a low conducting phase to a high conducting one. The specific roles of AAH phase, magnetic flux, electron filling, intra- and inter-cell hopping integrals, and ring size are discussed thoroughly. We also study the effect of random disorder on persistent current with hopping dimerization to compare the results with the uncorrelated ones. Our analysis can be extended further in studying magnetic responses of similar kinds of other hybrid systems in presence of magnetic flux.

Background: The present study is designed to deal with an indication of various stoma surgery, type of stoma formed, and various ju=of General surgery, RG Kar Medical College and hospital, Kolkata, from June 2020 to May 2021 The study includes patients 12 years and

The use of artificial intelligence (AI) is an emerging technique in the early identification and categorisation of brain tumour. The currently used method, i.e., magnetic resonance image for the detection of tumour is a time–consuming and complex technique. In the newly developing technique using the AI, the magnetic resonance image scans are used as input data, whereas the currently used method reads the magnetic resonance image manually. The purpose of this article is that the use of novel technique seems very promising in the early detection of brain tumour with high sensitivity and specificity. In this article, two disciplines of AI – machine learning and deep learning are extensively discussed. Through the utilisation of AI techniques, the fields of medicine and health care have experienced remarkable advancements, still there is a shortage of knowledge on artificial–based methods for early tumour diagnosis and classification. In addition, the article discusses the future application of AI techniques in clinical studies.

Abstract Moisture recycling in precipitation is an important hydrological process, accounting for ~ 67% globally. North-east India, home to the world's wettest place, boasts vast wetlands and forest-cover. Despite its proximity to the coast, we find locally recycled moisture to be the primary annual source of rainfall (~ 45%). During the pre-monsoon season, the enriched δ18O (~ − 0.7 ‰) and high d-excess (~ 14 ‰) are ascribed to enhanced transpiration, owing to atmospheric instability which causes Nor’westers. During the Monsoon season, oceanic flux provides increased surficial moisture, enabling deep-localised convection via evaporation. Significant localised recycling, even during the Monsoon season is estimated (~ 38%), with predominantly high d-excess in precipitation during latter half of the monsoon with increased moisture contribution from floods in Brahmaputra (high d-excess). The increasing δ18O and d-excess during the post-monsoon season is associated with progressively lesser rainout history and increased localized recycling (~ 67%). In light of the dwindling wetlands and forest-cover, our study highlights their indispensable role in governing regional hydro-meteorology and water availability.

Abstract A standard experimental setup for Inelastic Electron Tunneling Spectroscopy (IETS) performs the measurement of the second derivative of the current with respect to the voltage ( $$d^2I/dV^2$$ d 2 I / d V 2 ) using a small AC signal and a lock-in based second harmonic detection. This avoids noise arising from direct differentiation of the current-voltage characteristics (I–V) by standard numerical methods. Here we demonstrate a noise-filtering algorithm based on Tikhonov Regularization to obtain IET spectra (i.e. $$d^2I/dV^2$$ d 2 I / d V 2 vs. V) from measured DC I–V curves. This leads to a simple and effective numerical method for IETS extraction. We apply the algorithm to I–V data from a molecular junction and a metal-insulator-semiconductor tunneling device, demonstrating that the computed first/second derivatives have a workable match with those obtained from our lock-in measurements; the computed IET spectral peaks also correlate well with reported experimental ones. Finally, we present a scheme for automated tuning of the algorithm parameters well-suited for the use of this numerical protocol in real applications.

Abstract Globally 3 billion people are consuming water with moderately high concentrations of fluoride and arsenic. The development of a simple point of care (PoC) device or home device for the detection of fluoride/arsenic ensures safety before consuming water. Till date, lateral flow assay (LFA) based PoC devices can detect nucleic acids, viruses and diseases. An aluminium complex of rhodamine B functionalized oxacalix[4]arene (L) was designed to execute the LFA-based PoC device. Initially, Al3+ and Fe3+ ions were involved in complexation with the rhodamine B functionalized oxacalix[4]arene (L), resulting C 1 (L-Al3+) and C 2 (L-Fe3+) complexes respectively. The receptor L, as well as the probes (C 1 , C 2 ), were characterized thoroughly using mass spectroscopy, FTIR, NMR, and EA. C 1 and C 2 were further utilized as recyclable probes for the detection of aqueous fluoride (21 ppb) and arsenate (1.92 ppb) respectively. The computational calculation indicates that upon complexation, the spirolactam ring opening at the rhodamine B site leads to optoelectronic changes. The consistency of LFA-based portable sensing device has been tested with water samples, synthetic fluoride standards and dental care products like toothpaste and mouthwash with concentrations ≥ 3 ppm. Moreover, fixed cell imaging experiments were performed to ascertain the in-vitro sensing phenomena.

Abstract Brain-machine interfaces (BMIs) provide a framework for studying how cortical population dynamics evolve over learning in a task in which the mapping between neural activity and behavior is precisely defined. Learning to control a BMI is associated with the emergence of coordinated neural dynamics in populations of neurons whose activity serves as direct input to the BMI decoder (direct subpopulation). While previous work shows differential modification of firing rate modulation in this population relative to a population whose activity was not directly input to the BMI decoder (indirect subpopulation), little is known about how learning-related changes in cortical population dynamics within these groups compare.To investigate this, we monitored both direct and indirect subpopulations as two macaque monkeys learned to control a BMI. We found that while the combined population increased coordinated neural dynamics, this increase in coordination was primarily driven by changes in the direct subpopulation. These findings suggest that motor cortex refines cortical dynamics by increasing neural variance throughout the entire population during learning, with a more pronounced coordination of firing activity in subpopulations that are causally linked to behavior.

Abstract Heated tobacco products (HTP) are novel nicotine delivery products with limited toxicological data. HTP uses heating instead of combustion to generate aerosol (HTP-smoke). Physiologically relevant human bronchial and alveolar lung mucosa models developed at air–liquid interface were exposed to HTP-smoke to assess broad toxicological response (n = 6–7; ISO puffing regimen; compared to sham; non-parametric statistical analysis; significance: p

Abstract Vitiligo is a prevalent depigmentation disorder affecting around 1% of the general population. So far, various Genome Wide Association Studies (GWAS) and Candidate Gene Association Studies (CGAS) have identified several single nucleotide variants (SNVs) as a risk factor for vitiligo. Nonetheless, little has been discerned regarding their direct functional significance to the disease pathogenesis. In this study, we did extensive data mining and downstream analysis using several experimentally validated datasets like GTEx Portal and web tools like rSNPBase, RegulomeDB, HaploReg and STRING to prioritize 13 SNVs from a set of 291SNVs that have been previously reported to be associated with vitiligo. We also prioritized their underlying/target genes and tried annotating their functional contribution to vitiligo pathogenesis. Our analysis revealed genes like FGFR10P, SUOX, CDK5RAP1 and RERE that have never been implicated in vitiligo previously to have strong potentials to contribute to the disease pathogenesis. The study is the first of its kind to prioritize and functionally annotate vitiligo-associated GWAS and CGAS SNVs and their underlying/target genes, based on functional data available in the public domain database.

Abstract Aberrant changes in 5-hydroxymethylcytosine (5hmC) are a unique epigenetic feature in many cancers including acute myeloid leukemia (AML). However, genome-wide analysis of 5hmC in plasma cell-free DNA (cfDNA) remains unexploited in AML patients. We used a highly sensitive and robust nano-5hmC-Seal technology and profiled genome-wide 5hmC distribution in 239 plasma cfDNA samples from 103 AML patients and 81 non-cancer controls. We developed a 5hmC diagnostic model that precisely differentiates AML patients from controls with high sensitivity and specificity. We also developed a 5hmC prognostic model that accurately predicts prognosis in AML patients. High weighted prognostic scores (wp-scores) in AML patients were significantly associated with adverse overall survival (OS) in both training (P = 3.31e−05) and validation (P = 0.000464) sets. The wp-score was also significantly associated with genetic risk stratification and displayed dynamic changes with varied disease burden. Moreover, we found that high wp-scores in a single gene, BMS1 and GEMIN5 predicted OS in AML patients in both the training set (P = 0.023 and 0.031, respectively) and validation set (P = 9.66e−05 and 0.011, respectively). Lastly, our study demonstrated the genome-wide landscape of DNA hydroxymethylation in AML and revealed critical genes and pathways related to AML diagnosis and prognosis. Our data reveal plasma cfDNA 5hmC signatures as sensitive and accurate markers for AML diagnosis and prognosis. Plasma cfDNA 5hmC analysis will be an effective and minimally invasive tool for AML management.

Introduction: Any major surgery like lower uterine Caesarean Section (CS) can be hazardous due to postoperative nosocomial infection. Pregnant mothers are at greater risk during such surgical intervention as compared to vaginal delivery. Prophylactic antibiotic administration is a standard practice across the globe to prevent such anticipated postoperative infection. Aim: To evaluate the prophylactic antimicrobial use with regards to the choice of antimicrobials, dose, route, timing and duration, any possible Adverse Drug Reaction (ADR) as well as to assess the frequency of the postoperative morbidity due to infection (if any). Materials and Methods: A prospective observational data-based study was conducted in the Department of Pharmacology in collaboration with Department of Obstetrics and Gynaecology, Burdwan Medical College and Hospital, Burdwan, West Bengal, India, from February 2016 to October 2017. Study was conducted on 1944 pregnant women of reproductive age group planned or scheduled for elective/emergency lower segment CS, but otherwise healthy and received prophylactic antimicrobials for the surgery. They were prospectively observed regarding the treatment they received with focus on antimicrobial agents from the period of antimicrobial prophylaxis during their stay at hospital to till their discharge. Demographic data, vital signs, indication of CS, postoperative infections and ADR if any were recorded in predesigned proforma. The study population was divided into two groups: group A included 995 mothers, who received ceftriaxone sodium (1 g intravenously) and metronidazole (15 mg/kg) infusion and group B included 949 mothers, who received ampicillin (2 g intravenously), metronidazole (15 mg/kg) infusion and injection gentamycin (5 mg/kg) for 0.5 hour before initiation of CS. The data were statistically analysed by standard statistical software Microsoft Excel 2010 and Statistical Package for the Social Sciences (SPSS) sotware version 27.0 (SPSS Inc., Chicago, IL, USA) expressed as mean and standard deviation and percentage. Independent t- test and Chi-square test were used for analysis. Results: The mean age of group A was 22.36±3.07 years and group B was 22.76±2.47 years. Endomyometritis was documented in 4 (0.4%) from group A and 2 (0.21%) from the group B. Wound infection was present in 3 (0.3%) for group A and five (0.5%) for the group B. Infection related complications like chest infection seen in 7 (0.7%) for group A and in 3 (0.31%) for group B and urinary tract infection was noticed in 6 (0.6%) for group A and 5 (0.52%) for group B. Any incidence of maternal mortality was not evident among the two study groups and statistically insignificant ADR like vomiting and maculopapular rash (p-value=0.324) was observed in both the study groups with the use of above-mentioned antimicrobial therapy. Conclusion: Prophylactic use of ceftriaxone plus metronidazole and combination of triple antimicrobial therapy of ampicillin, metronidazole, and gentamycin therapy at the usual standard dose were commonly used antimicrobials at the present set up and they are safe and equally effective in decreasing considerably the incidence of post caesarean maternal infection thereby reducing their morbidity and mortality.

Introduction: Emergence and subsequent exponential spread of Coronavirus Disease-2019 (COVID-19) infection during 2020 forced the Government to issue countrywide lockdown from March 2020. Diabetic Retinopathy (DR) is one of the debilitating diseases of the eye which requires regular follow-ups and timely intervention to prevent permanent vision loss. The impact of countrywide lockdown on prevalence and progression of DR needs to be evaluated. Aim: To assess the effect of COVID-19 pandemic situation on the prevalence and progression of DR and analyse the possible risk factors for progression of DR in the ongoing pandemic period by comparing retrospective data from immediate prepandemic quarter with post lockdown quarter. Materials and Methods: This retrospective study was conducted in the Department of Opthalmology at Regional Institute of Ophthalmology, Kolkata, West Bengal, India. The study was done during the prepandemic period, from November 2019 to February 2020. In the present study, a cohort of 83 diabetic patients with pre-existing DR was selected from past medical records and compared with post lockdown period during November 2020 to February 2021. Data regarding prevalence of various types of DR, mean Central Macular Thickness (CMT), mean Visual Acuity (VA), proportion of patients requiring >3 doses of monthly anti-Vascular Endothelial Growth Factors (VEGF) and additional laser therapy or vitrectomy, VA improvement and reduction of mean CMT were gathered and compared between those two quarters. The data was analysed using Statistical Package for Social Sciences (SPSS) version 25.0. Results: The prevalence of moderate Non Proliferative Diabetic Retinopathy (NPDR) (13% vs 25%), severe NPDR (19% vs 8%), Proliferative DR (PDR) (18% vs 7%), Advanced Diabetic Eye Disease (ADED) (4.8% vs 1%) and Diabetic Macular Oedema (DME) (62% vs 28%) increased several folds during post lockdown quarter in comparison to prepandemic quarter. There was a statistically significant difference (p-value

Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2‑dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.

Objectives Postoperative outcomes vary considerably across bariatric patients and may be related to psychosocial factors. In this study, we examined whether a patient’s family support predicts postsurgical weight loss and the remission of type 2 diabetes mellitus (T2DM).Design Retrospective cohort study in Singapore.Setting Participants were recruited from a public hospital in Singapore.Participants Between 2008 and 2018, 359 patients completed a presurgical questionnaire before undergoing gastric bypass or sleeve gastrectomy.Outcome measures As part of the questionnaire, patients described their family support in terms of structure (marital status, number of family members in the household) and function (marriage satisfaction, family emotional support, family practical support). Linear mixed-effects and Cox proportional-hazard models were used to examine whether these family support variables predicted percent total weight loss or T2DM remission up to 5 years postsurgery. T2DM remission was defined as glycated haemoglobin (HbA1c)

Abstract Removal of particulate materials that would otherwise cumulate within the airspace and hinder the gas exchange is one of the central processes of maintaining lung homeostasis. While the importance of the particle uptake by alveolar macrophages and their expulsion via the airways mucociliary escalator is well established, very little is known about the alternative route for removing the particles via direct crossing the lung epithelium for transfer into the pulmonary lymph and bloodstream. This study dissected sequential mechanisms involved in nanoparticle transcytosis through the alveolar epithelial cell layer. By a combination of live cell, super resolution, and electron microscopy and RNA interference study, we have dissected temporal steps of nanoparticle transcytosis through alveolar epithelium. Our study revealed that caveolin is essential for the firm adhesion of the silica nanoparticle agglomerates to the apical membrane and their subsequent rapid internalization with the help of macropinocytic elements C-terminal-binding protein1 and Rabankyrin-5 but not dynamin. Actin, but not microtubules, played a major role in nanoparticle uptake and subsequent transportation. The compartments with nanoparticles were tethered to trans-Golgi network to be jointly transported along actin stress fibers across the cytoplasm, employing a myosin-dependent mechanism. The trans-Golgi nanoparticle transport machinery was positive to Rab6A, a marker linked to vesicle exocytosis. Exocytosis was primarily occurring at the basolateral plane of the alveolar epithelial cells. The high-proficiency novel caveolin and Rabankyrin-5 associated uptake and transcellular transport of nanoparticles across the AEC barrier supports its importance in clearance of amorphous silica and other types of non-inflammatory nanoparticles that are rapidly removed from the lungs following their inhalation.

Abstract Multi-omic data, i.e., clinical measures, radiomic, and genetic data, capture multi-faceted tumor characteristics, contributing to a comprehensive patient risk assessment. Here, we investigate the additive value and independent reproducibility of integrated diagnostics in prediction of overall survival (OS) in isocitrate dehydrogenase (IDH)-wildtype GBM patients, by combining conventional and deep learning methods. Conventional radiomics and deep learning features were extracted from pre-operative multi-parametric MRI of 516 GBM patients. Support vector machine (SVM) classifiers were trained on the radiomic features in the discovery cohort (n = 404) to categorize patient groups of high-risk (OS

Abstract The placenta is a heterogeneous organ whose development involves complex interactions of trophoblasts with decidual, vascular, and immune cells at the fetal–maternal interface. It maintains a critical balance between maternal and fetal homeostasis. Placental dysfunction can lead to adverse pregnancy outcomes including intra-uterine growth restriction, pre-eclampsia, or pre-term birth. Exposure to environmental pollutants contributes to the development of placental abnormalities, with poorly understood molecular underpinning. Here we used a mouse (C57BL/6) model of environmental pollutant exposure by administration of a particulate matter (SRM1649b at 300 μg/day/mouse) suspension intra-nasally beginning 2 months before conception and during gestation, in comparison to saline-exposed controls. Placental transcriptomes, at day 19 of gestation, were determined using bulk RNA-seq from whole placentas of exposed (n = 4) and control (n = 4) animals and scRNAseq of three distinct placental layers, followed by flow cytometry analysis of the placental immune cell landscape. Our results indicate a reduction in vascular placental cells, especially cells responsible for structural integrity, and increase in trophoblast proliferation in animals exposed to particulate matter. Pollution-induced inflammation was also evident, especially in the decidual layer. These data indicate that environmental exposure to air pollutants triggers changes in the placental cellular composition, mediating adverse pregnancy outcomes.

Toxoplasma infection can be congenital or acquired. Infection with Toxoplasma gondii can result in multi-organ involvement in immunocompromised patients; whereas in immunocompetent patients, it usually remains asymptomatic. Toxoplasma is a rare cause of isolated lymphadenopathy especially in immunocompetent individuals, though it is a common manifestation of this protozoal infection. We present a 27-year-old male who presented to us with isolated cervical lymphadenopathy. Histopathology and serological studies confirmed the diagnosis of toxoplasma lymphadenopathy. It usually affects the posterior cervical group of lymph nodes, but in our case, it had also affected anterior group and presented without any constitutional symptom. The patient was treated with cotrimoxazole double strength tablet once daily for 1 month and responded well.

DNA has been discussed as a potential medium for data storage. Potentially it could be denser, could consume less energy, and could be more durable than conventional storage media such as hard drives, solid-state storage, and optical media. However, performing computations on the data stored in DNA is a largely unexplored challenge. This paper proposes an integrated circuit (IC) based on microfluidics that can perform complex operations such as artificial neural network (ANN) computation on data stored in DNA. We envision such a system to be suitable for highly dense, throughput-demanding bio-compatible applications such as an intelligent Organ-on-Chip or other biomedical applications that may not be latency-critical. It computes entirely in the molecular domain without converting data to electrical form, making it a form of in-memory computing on DNA. The computation is achieved by topologically modifying DNA strands through the use of enzymes called nickases. A novel scheme is proposed for representing data stochastically through the concentration of the DNA molecules that are nicked at specific sites. The paper provides details of the biochemical design, as well as the design, layout, and operation of the microfluidics device. Benchmarks are reported on the performance of neural network computation.

Introduction: SARS-CoV-2 respiratory infection leads to two-layered pathology in time (a) immediate pathology and recovery or fatal ending and (b) long periods of remission followed by unexplained clinical expressions involving one or more systems with various clinical presentations, even leading to loss of lives. Among the common causative factors affecting nearly all organs and systems, oxygen radicals and oxygen-derived species (ROS) should rank conclusively on top. Objective: This clinical report, part of a community screening of unexplained clinical outcomes in post-COVID presentation, carries findings focusing on ROS production and possible ROS-induced damages. Materials and Methods: Flow cytometry was used to quantify the samples' total ROS, superoxide production, and apoptosis quantification. Results: Observations indicate unexplained nearly uniform enhanced ROS production in all these long COVID subjects, although clinical presentations varied from no complaints to the requirement of advanced interventions. Conclusion: Causative factors leading to raised oxygen-derived toxic intermediaries (ROS) in initiating these variable long COVID presentations are ill-understood yet possibly merit mass screenings and possible intense anti-oxidative therapy given that such antioxidant therapy through oral medications led to rapid lowering of ROS production and improvement of clinical presentations.