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Community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strains are increasingly replacing hospital-acquired MRSA (HA-MRSA) strains in hospitalized patients leading to poor clinical outcomes. Hence, this study aimed to characterize clinical isolates of MRSA (HA-MRSA and CA-MRSA) and to understand their clonal origin. A total of 400 consecutive S. aureus clinical isolates were collected from the clinical bacteriology lab of a tertiary care hospital. All the isolates were screened for MRSA by cefoxitin disc diffusion test and mecA PCR, followed by SCCmec typing, antibiotic susceptibility testing, Panton Valentine Leukocidin (PVL) screening, and pulsed field gel electrophoresis (PFGE). Of the total 400 isolates, 134 categorized MRSA by cefoxitin, while 129 as mecA positive by PCR, of which 117 could be characterized into SCCmec types. SCCmecI and II were present in 1 isolate each, SCCmecIII in 36 (31%) representing HA-MRSA, While SCCmecIV in 51 (44%), and SCCmecV in 28 (24%) isolates representing CA-MRSA. Of all SCCmecIII isolates, 70% were multidrug resistant (MDR) while 59% of SCCmecIV and 29% of SCCmecV isolates were MDR. PVL (CA-MRSA virulence factor) positivity in mecIII, IV, V isolates was 9%, 31%, 46% respectively. PFGE typing showed MRSA clones of multiple origins. In conclusion, study showed the evolving epidemiology of HA-MRSA and CA-MRSA. CA-MRSA constituted the majority of clinical isolates amongst both community and hospital MRSA isolates. Various MDR clones of mecIV and mecV were circulating and replacing mecIII in hospital settings. SCCmecIV isolates were predominant and evolved as MDR, however, PVL was significantly associated with CA-MRSA. [ABSTRACT FROM AUTHOR]

The ability to localize hundreds of macromolecules to discrete locations, structures and cell types in a tissue is a powerful approach to understand the cellular and spatial organization of an organ. Spatially resolved transcriptomic technologies enable mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner. The rapid development of spatial transcriptomic technologies has accelerated the pace of discovery in several fields, including nephrology. Its application to preclinical models and human samples has provided spatial information about new cell types discovered by single-cell sequencing and new insights into the cell–cell interactions within neighbourhoods, and has improved our understanding of the changes that occur in response to injury. Integration of spatial transcriptomic technologies with other omics methods, such as proteomics and spatial epigenetics, will further facilitate the generation of comprehensive molecular atlases, and provide insights into the dynamic relationships of molecular components in homeostasis and disease. This Review provides an overview of current and emerging spatial transcriptomic methods, their applications and remaining challenges for the field. Spatially resolved transcriptomic technologies enable the mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner. This Review describes current and emerging spatial transcriptomic methods, their applications of relevance to kidney biology and remaining challenges for the field. Key points: Spatially resolved transcriptomic technologies allow the spatial mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner, and currently include sequencing-based technologies and imaging-based methodologies. Sequencing-based technologies include whole transcriptome-wide in situ capture and region of interest-based spatial RNA analysis platforms; imaging-based technologies include a variety of massively multiplexed in situ hybridization methodologies. Key data outputs from spatial transcriptomic technologies include the anchoring of cell types and states derived from disaggregated single-cell technologies, determination of spatially variable gene expression, and the annotation of functional neighbourhoods. Spatial technologies enable the localization of biologically relevant cellular interactions in the histopathological context and identification of disease-relevant cell signalling pathways associated with morphological and histopathological changes. Spatial technologies are rapidly advancing to provide single-cell signatures at a whole transcriptome level. Further, these technologies are becoming increasingly multiplexed with orthogonal technologies such as spatial proteomics or epigenomics to define gene and protein regulatory patterns. [ABSTRACT FROM AUTHOR]

The most detrimental disease of finger millet (Eleusine coracana) is blast caused by Pyricularia grisea inflicting substantial yield losses. This study evaluated 100 finger millet genotypes from a core collection for disease response to leaf, neck and finger blast. Good phenotypic variability in the genotypes was recorded for blast reactions. None of the accessions was resistant to leaf blast; however, 12 and 27 accessions were resistant to neck and finger blast, respectively. A total of 28 accessions showed resistance to both neck and finger blast. A significant positive correlation was observed between neck and finger blast. Genotyping of 50 accessions differing in disease reactions to neck blast was performed using 30 SSR markers 17 of which proved to be polymorphic. A total of 51 alleles were detected with the mean value of 2.55 alleles per locus. The PIC values of the polymorphic SSR markers ranged from 0.03 to 0.98, and the dendrogram grouped these genotypes in 13 clusters. Cluster I and II comprised of resistant accessions, whereas cluster VIII formed the susceptible group. SSR markers UGEP 76 and UGEP 102 consistently produced bands in neck blast susceptible and highly susceptible germplasms, indicating their probable association with neck blast susceptibility gene(s). Our results showed that the core collection has appreciable diversity for blast reactions both phenotypically and genotypically. [ABSTRACT FROM AUTHOR]

Soil erosion is a major global concern due to its adverse impact on agricultural productivity and dam reservoir storage capacity. Effective land management in large watersheds is difficult, particularly in developing countries, owing to the high cost of soil conservation expenditure. Identifying the most vulnerable areas for erosion and executing remedial measures for those areas is crucial to reduce costs and improve effectiveness. The Soil and Water Assessment Tools model was used to identify weak zones for erosion from hydrologic response units to larger watersheds. The study focused on the Tekeze watershed, divided into 34 subbasins and 158 hydrologic response units, with the model performing within acceptable limits for evaluating erosion and flow. The results showed that the model is within acceptable limits for evaluating erosion and flow in the Tekeze basin, with significant differences in sediment yield across each subbasin. Due to their high sediment yield, six subbasins (viz., 1, 3, 5, 14, 17, and 28) require urgent attention. The findings of this study can guide land managers in developing effective strategies to reduce soil erosion and enhance agricultural productivity. [ABSTRACT FROM AUTHOR]

In the context of the Himalayan region, where glaciers and snow cover area (SCA) critically influence river runoff, monitoring SCA on a spatio-temporal basis is essential for the effective utilization of water resources. This study delves into the complex dynamics of snow cover within the Indus, Ganga, and Brahmaputra basins in the Hindu-Kush Himalayan region (HKH), leveraging the high temporal resolution of the Moderate Resolution Imaging Spectroradiometer (MODIS). The MODIS data, with its reduced cloud cover, offers an enhanced observation capability for these high-elevation regions. Our research focuses on evaluating the annual and seasonal variations in SCA across these basins from 2003 to 2021 and correlates these variations with critical climatic variables such as temperature and precipitation, using data from the fifth-generation European Centre for Medium-Range Weather Forecasts (ECMWF) Atmospheric Reanalysis of the global climate (ERA5). The study presents a comprehensive assessment of SCA, highlighting significant findings that include a range of mean annual SCA from 22.31 to 42.14%, with notable seasonal fluctuations. The data analysis reveals a clear correlation between SCA variability and climatic parameters, particularly temperature, indicating a high sensitivity of snow cover to temperature changes. Notably, the most significant temperature increases and their impacts on SCA were observed in the Ganga and Brahmaputra basins. Furthermore, the study examines how topographical attributes such as elevation, slope, and aspect contribute to the distribution of SCA, revealing the critical role these factors play in determining the varying elevations of the snow line across each basin. These findings underscore the profound influence of climate change on snow cover dynamics in this region. The study's insights into the spatial and temporal variability of SCA, coupled with the observed climatic trends, emphasize the urgent need for adaptive water resource management strategies in these crucial river basins. [ABSTRACT FROM AUTHOR]

Raman spectroscopy discovered by Nobel laureate Sir Chandrasekhara Venkata Raman from India in 1928 changed the history of Oncosurgery and gave a new direction and dimension to the diagnosis, management, screening, and treatment of cancer. The amalgamation of laser and artificial intelligence in spectroscopy made this invention of Raman an extremely useful non-invasive tool in cancer surgery and management. Apart from intraoperative guidance, early detection, and tumor classification, Raman spectroscopy was found to be useful in the assessment of residual disease, therapeutic monitoring of chemotherapy drugs and radiotherapy, biomarker invention, drug delivery monitoring, and cancer screening. While Raman spectroscopy shows great promise in cancer research and diagnosis, it is still a developing field, and further research is needed to fully understand its potential. [ABSTRACT FROM AUTHOR]

Accurate forecast of daily streamflow of the major Himalayan rivers is crucial for understanding changes in their hydrological regimes caused by precipitation variability, as well as their potential implications for hydropower generation and flood management in the downstream region. However, the study pertaining to daily streamflow forecasting in the western Himalayas is lacking, primarily due to the limited availability and accessibility of long-term daily gauged data. In this study, four machine learning (ML) models, namely support vector machine, random forest, deep neural networks, and bi-directional long-short-term memory (BLSTM), were employed to forecast daily streamflow in the Sutlej river basin. The models were trained (11 years) and tested (2 years) using publicly accessible earth observation and reanalysis datasets for a period of 13 hydrological years, grouped into four distinct scenarios, denoted as M1, M2, M3, and M4. In each scenario, feature parameters were generated from the pool of six hydro-meteorological variables namely- precipitation (P), air temperature ( T a ), evapotranspiration (ET), snowfall, snow cover area (SCA), and discharge. The optimal feature combinations (e.g., scenarios) were identified using the time lag cross correlation technique. All of the ML models demonstrated reasonable performance (NSE > 0.82, R > 0.91, and RMSE < 101.2 m3/s) in simulating streamflow during testing period, the BLSTM model showed a slightly superior level of accuracy across all scenarios (NSE = 0.97, R = 0.99 and RMSE = 42.7 m3/s for M4). The BLSTM was further used to reconstruct daily timeseries discharge for the period 2012–2021. The variability in T a , ET, and P exerts a greater influence on streamflow generation in the glacierized catchment in comparison to snowfall. The observed phenomenon can be ascribed to the dampening effect of snowfall on discharge, as their effects become apparent within a timeframe of five to seven days. [ABSTRACT FROM AUTHOR]

Recently, hydrogen gas is becoming the most prominent alternative fuel due to its clean and environment-friendly nature. It only delivers water as a waste product during the operation instead of emitting harmful greenhouse gases. It has a high heating value (142 MJ/kg), over 2.75 times that of other hydrocarbon-based petroleum fuels. Presently, the primary method of producing hydrogen is the steam reforming of fossil fuels, which is not economical and environmentally harmful, and fossil fuels are on the deadline to finish. Hence, alternative methods of hydrogen production are the topic of current research. Biological methods of hydrogen production were found the best for producing green hydrogen because they utilize plentiful available renewable sources as feedstock. The dark fermentation technique is becoming more famous among all biological hydrogen generation methods because of its light autonomous nature and functional ability. It has the facility to convert any type of carbohydrate-rich organic substrates into bio-hydrogen, but pure carbohydrate substances are not economical on a commercial scale. Hence, carbohydrate-rich organic waste can be easily harnessed for bio-hydrogen generation. This method yields hydrogen gas and different high-volatility fatty acids, which could be used for industrial purposes after separation or as a precursor for the bio-methanation process for biogas production. This paper defines mechanism, microbiology, affecting factors, various integration methodologies, and potential and limitations related to the dark fermentation method. [ABSTRACT FROM AUTHOR]

Groundwater is an important resource for a multitude of purposes, and change in groundwater levels is an important factor in determining the increase and decrease of groundwater quantity in aquifers. This study has been carried out for Gomti River basin, where groundwater is the major drinking water source for the entire region. This paper evaluates the behavior of the groundwater levels using Visual MODFLOW under RCP 4.5 and RCP 8.5 scenarios. For modeling of groundwater flow, the entire study area was discretized into 108480 (X-direction) and 207090 (Y-direction) gridal network with each cell size of 1000 m × 1000 m. The model was calibrated for the period 2002 to 2008 and validated for the period 2009 to 2013 using data of 24 observation wells. During the calibration period of Visual MODFLOW, residual mean ranged between 0.658 and 0.268 m, and absolute residual mean ranged between 2.035 and 2.174 m. The calibrated Visual MODFLOW model was employed to evaluate the influence of climate change on future groundwater levels. Future groundwater recharge (2020–2030), obtained after the application of four (MIROC-ESM, MIROC-ESM-CHEM, MIROC MIROC5, and MOHC-HADGEM2-ES) global climate model (GCM) data into prior SWAT model, was applied to Visual MODFLOW. After applying, the projected future (2020–2030) trend in the groundwater levels was found continuously decreasing due to low groundwater recharge and excessive groundwater withdrawal in the basin in future. [ABSTRACT FROM AUTHOR]

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.Application of multiplexed RNA in situ mapping techniques to human tissues remains challenging. Here, the authors report DART-FISH, a padlock probe-based technology capable of profiling large numbers of genes in centimetre-sized human tissue sections. [ABSTRACT FROM AUTHOR]

Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid subtypes. Here we present a hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. Using this platform, we visualize and identify high density lipoprotein particles in human kidney, a high cholesterol to phosphatidylethanolamine ratio inside granule cells of mouse hippocampus, and subcellular distributions of sphingosine and cardiolipin in human brain. Our PRM-SRS displays unique advantages of enhanced chemical specificity, subcellular resolution, and fast data processing in distinguishing lipid subtypes in different organs and species. Spatial imaging methods in lipid research can disrupt tissue integrity and can have limited spatial and spectral resolution. Here, the authors present an SRS-based hyperspectral imaging platform to visualise lipids and lipoproteins in a variety of tissues and animal species. [ABSTRACT FROM AUTHOR]

Conventional heat pipes with one evaporator and one condenser are used to cool only one heat source at a time. In electronics and space applications, where a large number of heat sources are to be cooled with limited space available, a multi branch heat pipe could be the solution. In the present study, a heat pipe (T-shape) with three branches was developed with 20 number of axial grooves in which two branches worked as evaporators and one branch as a condenser. Experimental study was performed by considering four novel types of orientations i.e. (a) horizontal orientation (HO) (b) gravity assisted orientation (GAO) (c) anti-gravity orientation (AGO) and (d) compound orientation (CO). The results are analyzed in terms of start-up characteristics and total heat transfer coefficient at different heat loads. Evaporator and condenser thermal resistances are calculated and analyzed for better understanding. It was found that horizontal orientation resulted in the highest overall heat transfer coefficient (2.72 kW/m2 ℃ at 240 W) and comparatively lower evaporator temperatures (less than 100 ℃ at 240 W) which is suitable condition for electronics cooling. Maximum effective thermal conductivity of 31.82 kW/m ℃ was achieved in horizontal orientation. It also resulted in lowest evaporator resistance (0.157 ℃/W) and lowest condenser resistance (0.114 ℃/W). Phenomena of temperature jump was observed and elaborated for compound orientation. [ABSTRACT FROM AUTHOR]

Background: Distal biceps tears are uncommon injuries, typically leading to significant loss of elbow flexion and supination strength; surgical repairs restore muscular strength and endurance. The aim of this study was to compare the complication rate of early (< 21 days) vs delayed (> 21 days) repair and the effect of types of incision and fixation methods used in the repair. Methods: A total of 86 cases were retrospectively reviewed, and 66 cases were included in the study after exclusion. Different preoperative and intraoperative variables and postoperative outcome measures were recorded. We analysed the effects of early and delayed repair, types of incision and fixation methods on the complications. Results: 31 had an early, and 35 had delayed distal biceps repair. The mean follow-up was 14.92 weeks. 13.6% had major, and 40.9% had minor complications. No significant difference was noted in complications between the two groups (54.8% vs 54.3%). Higher complications were observed when surgery was done using a single anterior incision compared to 2 anterior incisions (68.8% vs 16.7%, p=0.0002). Overall, higher (76.3% vs 25.9%, p=0.0001) complications were noted in patients where fixation was done using a cortical button & interference screw in comparison to the cortical button alone. Conclusion: No significant difference in complication was noted between early and delayed repair. However, more complications were noted in the single anterior incision compared to the two anterior incision technique. Higher complications were also observed with the cortical button and interference screw fixation method compared to the cortical button alone. [ABSTRACT FROM AUTHOR]

The intracellular delivery of the drug to the solid tumor is a major challenge in the treatment of solid tumors. This project aims to increase cytosolic drug delivery using the endosomal escape of drugs. Topotecan (TPT) and capsaicin were used for the treatment of solid tumors. The pH-dependent conversion of active lactone form to inactive carboxylic form is a major problem of TPT that limits its therapeutic use. Liposomal encapsulation of TPT improved the stability of active lactone form and increased the therapeutic efficacy of TPT. Endosomal degradation of liposomes may reduce the content in the target cells. To solve these problems, pH-sensitive liposomes (pSLPs) were developed which improved the intracellular drug delivery by the endosomal escape of drugs. The liposomes (LPs) bearing the drug(s) were prepared using the cast film method and optimized for various formulation and process variables using the Design-Expert 7 software by employing the Box-Behnken design (BBD). The developed hyaluronic acid (HA)–conjugated pSLPs (HA-pSLPs) displayed a vesicle size of 166.5 ± 2.31 nm, zeta potential − 30.53 ± 0.91, and entrapment efficiency of 44.39 ± 1.78%, and 73.48 ± 2.15% for TPT and CAP, respectively. HA-pSLPs displayed better cytotoxicity in comparison to free drugs either single or in combination on the MCF-7 cell line. The apoptosis and cellular uptake of HA-pSLPs were increased ⁓ 4.45-fold and ⁓ 6.95-fold as compared to unconjugated pSLPs, respectively. The pharmacokinetic studies in Balb/c mice demonstrated that HA-pSLPs increased the half-life, MRT, and AUC in comparison to the free drug solution. The HA-pSLPs formulation has shown remarkable tumor regression as compared to PpSLPs, pSLPs, and free drug combinations. These results demonstrated that TPT- and CAP-loaded HA-pSLPs offer a potential platform for targeted drug delivery to solid tumors. [ABSTRACT FROM AUTHOR]

This study examines the proportional contribution of snow/ice melt, rainfall, and groundwater to Sutlej River discharge at various locations. Sutlej River is a major tributary of the Indus River system and an important water supply source for irrigation through the canal network in northwest India. Here, we used hydrograph separation and associated uncertainty and applied the snowmelt runoff model (SNOWMOD) to estimate the contribution from different water sources to the Sutlej River. We used δ18O and electrical conductivity values of different waters for the hydrograph-separation approach. The first-order Gaussian error propagation and Monte-Carlo simulation are used to assess the accuracy. The estimated contribution at Rampur is ~ 62.7% (snow/ice melt), 18.7% (rainfall), and ~ 18.4% (groundwater); for Ropar is 59 ± 2% (snow/ice melt), 23 ± 2% (rainfall), and 18 ± 2% (groundwater); and for Yusufpur, 25 ± 3% (snow/ice melt), 39 ± 3% (rainfall), and 36 ± 2% (groundwater) during July–December 2013. The findings from the hydrograph-separation and SNOWMOD analysis established a fundamental understanding of the hydrological processes in the Sutlej River system, providing valuable baseline data essential for developing sustainable water resource management strategies. [ABSTRACT FROM AUTHOR]

Despite an essential differential diagnosis for fever of unknown origin (FUO) in young adults, adult-onset Still's disease (AOSD) is infrequently considered and remained underdiagnosed in low-middle-income countries. The present study analyzed the clinical, serological, radiological, and pathological characteristics of AOSD presented as FUO in India. A hospital-based retrospective study of patients aged > 13 years admitted with FUO and later diagnosed with AOSD in Postgraduate Institute of Medical Education and Research, Chandigarh (India), was conducted between January 2014 and December 2020. Petersdorf and Beeson's criteria were used to define FUO. The diagnosis of AOSD was made based on Yamaguchi's criteria. Twenty-seven patients (median age 26 years, 14 females) were enrolled. All presented with intermittent fever with a median duration of 10 weeks. The typical features of AOSD at admission were arthralgia (n = 24), hepatosplenomegaly (n = 21), spiking fever ≥ 39 °C (n = 19), lymphadenopathy (n = 18), typical rash (n = 17), and sore throat (n = 11). Leukocytosis (n = 25) and neutrophilia (n = 19) were frequent. Hyperferritinemia was universal (range, 700–145,003 ng/ml; ≥ 2000, n = 23). At admission, AOSD was suspected in only nine FUO cases, while tuberculosis (n = 16), undifferentiated connective tissue disorder (n = 14), and lymphoproliferative disorder (n = 11) were common diagnostic possibilities. Crispin et al. clinical scale detected AOSD in only 15 (55.5%) FUO patients. Whole-body imaging (n = 27), including fluorodeoxyglucose positron emission tomography (n = 12), demonstrated reticuloendothelial organ-system involvement and serositis. Seventeen (63%) patients had macrophage activation syndrome at the time of AOSD diagnosis. AOSD FUO presents with typical but nonspecific features; thus, early differentiation from common causes (e.g., tuberculosis, lymphoma) is difficult. Macrophage activation syndrome is common in AOSD with FUO presentation. [ABSTRACT FROM AUTHOR]

Depression, anxiety, sleep disturbances, and fatigue are inadequately addressed comorbidities in granulomatosis with polyangiitis (GPA). We determined the prevalence, severity, determinants, and the impact of these comorbidities on quality-of-life (QoL) in GPA. This observational study included adult GPA patients; patients with RA and lupus were included as comparators. Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorder 7-item scale for anxiety, Epworth Sleepiness Scale for sleep disturbances, and Fatigue Severity Scale for fatigue were administered prospectively to estimate prevalence and severity. QoL and disability were estimated using PROMIS-HAQ, HAQ-health and HAQ-pain. Correlations among these parameters were assessed. Stepwise regression analyses were performed to identify determinants of depression, anxiety, excessive sleepiness, and fatigue. One hundred eighty-one patients—62 GPA [mean age 43 (13) years], 57 RA and 62 SLE- were included. The prevalence of depression (47%), excessive sleepiness (21%), and fatigue (39%) in GPA were comparable to RA and lupus; anxiety was less prevalent (29% versus 46% and 53%, p = 0.02). Severity was mostly mild-moderate. Younger age [OR = 0.93 (0.89–0.98)], higher BMI [OR = 1.2 (1.0–1.4)], and greater disease damage [OR = 2.0 (1.3–3.3)] independently predicted presence of depression. Higher BMI [OR = 1.3 (1.1–1.5)] and concomitant FMS [OR = 80.9 (5.1–1289.2)] were independently associated with excessive sleepiness. No association with disease activity, duration, or gender was seen. GPA patients with depression, anxiety, excessive sleepiness, and fatigue had worse PROMIS-HAQ, HAQ-pain, and HAQ-health. In conclusion, depression, anxiety, sleep disturbances, and fatigue are common in GPA. Although their severity is mostly mild-moderate, they impair QoL significantly. Potentially modifiable determinants that can form targets for future interventions have been identified. [ABSTRACT FROM AUTHOR]

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers. Kidney stone disease causes significant morbidity and increases in health care utilization. Here, the authors define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human renal papilla and identify associated urinary biomarkers. [ABSTRACT FROM AUTHOR]

The ancillary services are becoming more important due to the increasing integration of non-dispatchable and intermittent renewable energy sources. Such behavior under deregulation necessitates the procurement of these services suitably. This paper presents the multi-objective procurement of voltage control ancillary service in a dynamic pool deregulated system that is contingent to wind and solar power generation uncertainties. The shunt capacitors bid to supply this service and their switchings, although restricted due to life expectancy, depend on locational marginal prices. An improved multi-objective artificial electric field algorithm, which adopts the concept of Pareto-based non-dominated sorting, is presented to co-optimize total cost and voltage deviation. The particle's positions are updated through randomly picked Pareto solution to enhance exploitation capability. The sign and reorder mutation operations are employed to maintain diversity in the population, improve exploration, and evade local optima trap. The performance is investigated for different levels of wind and solar penetration on IEEE 30-bus and IEEE 118-bus test systems. The convergence of presented algorithm is analyzed and compared with other algorithms through statistical metrics and associated boxplots. [ABSTRACT FROM AUTHOR]

To compare the efficacy of methotrexate and apremilast in psoriatic arthritis (PsA). This Single blinded (physician), parallel group, randomized controlled trial was conducted at a single centre between October 2019 and December 2020. Adult PsA patients (age > 18 years), fulfilling CASPAR criteria, not on methotrexate/apremilast in last 3 months and never receiving bDMARDs or, JAK inhibitors, having active articular disease (one or more swollen joint or, having one or more tender entheseal point) were recruited. Primary outcome measure was rate of major cDAPSA response at week 24 and secondary outcome measures were ACR 20 response, change in PASI score, Maastricht enthesitis score, Leeds dactylitis index, and health assessment questionnaire-disability index (HAQ-DI) and number of adverse events at week 24 between methotrexate and apremilast groups. A total of 31 patients were recruited (15 in the apremilast arm and 16 in the methotrexate arm) amongst whom 26 patients completed 24 weeks follow up (13 patients in the apremilast arm and 13 patients in the methotrexate arm). Median cDAPSA score at baseline was 23 (9) in the apremilast group and 20 (21) in the methotrexate group. No difference in major cDAPSA response at week 24 was observed between apremilast and methotrexate arm (20% vs. 37.5%; p = 0.433). In the secondary outcome measures, there was no significant differences between both the groups. Both the drugs were safe without any serious adverse events. There was no significant difference between methotrexate and apremilast in terms of efficacy as measured by cDAPSA and ACR20 responses. [ABSTRACT FROM AUTHOR]

There is little data on long-term persistence/continuation of methotrexate among Indian Rheumatoid arthritis patients. We assembled a retrospective single-center cohort consisting of RA patients (fulfilling 1987 ACR criteria) started on methotrexate as part of three academic studies (including two RCTs) from 2011 to 2016. Oral methotrexate was started at 7.5 or 15 mg per week with a target dose of 25 mg per week. Between August and December 2020, all patients were contacted (telephonically) and data were obtained from clinic files to evaluate self-reported continuation/persistence of methotrexate and reasons for discontinuation. Survival analysis using Kaplan–Meier and cox-regression were used to assess methotrexate continuation rates and factors associated with its discontinuation. This study included 317 patients with rheumatoid arthritis, with mean age and disease duration (at enrollment) of 43 years and 2 years; And positive rheumatoid factor and anti-CCP in 69 and 75%. At follow-up, 16 patients (5%) had died, whereas 103 (32.5%) had discontinued methotrexate. On Kaplan–Meier survival analysis, the mean survival (continuation) time for methotrexate was 7.3 years (95% CI 7–7.6 years). The actuarial continuation/persistence of methotrexate at 3, 5 and 9 years was 92, 81 and 51%, respectively. Among those who discontinued methotrexate, common reasons were remission of disease, symptomatic adverse effects (intolerance), perceived lack of efficacy and socioeconomic reasons. On multivariable cox-regression, symptomatic adverse effects during the first 12–24 weeks (Hazard ratio, 95% CI 1.8 (1.2–2.8)) and anti-CCP positivity (Hazard ratio, 95% CI 0.6 (0.3–1.0)) were significantly associated with hazard of discontinuation. Persistence or continuation of methotrexate was found to be good and comparable to reports in other centers world-wide. Apart from remission, the most important cause of methotrexate discontinuation was symptomatic adverse effects (intolerance). [ABSTRACT FROM AUTHOR]

Glacier-associated hazards are becoming a common and serious challenge to the high mountainous regions of the world. Glacial lake outburst floods (GLOFs) are one of the most serious unanticipated glacier hazards, with the potential to release a huge amount of water and debris in a short span of time, resulting in the loss of lives, property, and severe damage to downstream valleys. The present study used multi-temporal Landsat and Google earth imageries to analyze the spatio-temporal dynamism of the selected glacial lake (moraine-dammed) in the Satluj basin of Western Himalayas. Furthermore, GLOF susceptibility of the lake was assessed using a multi-criteria decision-based method. The results show that the lake area has increased from 0.11 to 0.26 km2 over the past 28 years from 1990 to 2018. The susceptibility index value for the lake was calculated as 0.75, which indicates that the lake is highly susceptible to the GLOF. The depth and volume of the lake were estimated to be 16 m and 57 × 105 m3, respectively, using an empirical formula. HEC-RAS, HECGeo-RAS, and Arc-GIS software were utilized in this study to perform unsteady flow analysis and to determine the GLOF impact on the downstream area. The worst-case GLOF scenario (breach width of 75 m) was revealed during an overtopping failure of the moraine dam, resulted in a peak discharge of 4060 m3/s and releasing a total water volume of 57 × 105 m3. The breach hydrograph has been routed to calculate the spatial and temporal distribution of peak flood, inundation depth, velocity, water surface elevation, and flood peak arrival time along the river channel. The analysis further reveals that the routed flood waves reach the nearest settlement, i.e., Rajpur town, situated at a distance of 102 km in the downstream valley of the lake at 6 h after the beginning of the lake breach event with a peak discharge/flood of 1757 m3/s and maximum flow velocity of 1.5 m/s. With the ongoing climate warming and glacier retreat, moraine-dammed lakes are becoming more hazardous and thus increasing the total threat. Therefore, it is mandatory to monitor and assess such lakes at regular intervals of time to lessen the disastrous impacts of GLOFs on the livelihood and infrastructure in the downstream valleys. The findings of this study will aid in the creation of risk management plans, preparatory tactics, and risk reduction techniques for GLOF hazards in the region. [ABSTRACT FROM AUTHOR]

Background: Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive ciliopathy characterized by early onset retinal dystrophy, renal anomalies, postaxial polydactyly, and cognitive impairment with considerable phenotypic heterogeneity. BBS results from biallelic pathogenic variants in over 20 genes that encode key proteins required for the assembly or primary ciliary functions of the BBSome, a heterooctameric protein complex critical for homeostasis of primary cilia. While variants in BBS1 are most frequently identified in affected individuals, the renal and pulmonary phenotypes associated with BBS1 variants are reportedly less severe than those seen in affected individuals with pathogenic variants in the other BBS-associated genes. Case-Diagnosis: We report an infant with severe renal dysplasia and lethal pulmonary hypoplasia who was homozygous for the most common BBS1 pathogenic variant (c.1169 T > G; p.M390R) and also carried a predicted pathogenic variant in TTC21B (c.1846C > T; p.R616C), a genetic modifier of disease severity of ciliopathies associated with renal dysplasia and pulmonary hypoplasia. Conclusions: This report expands the phenotypic spectrum of BBS with the first infant with lethal neonatal respiratory failure associated with biallelic, pathogenic variants in BBS1 and a monoallelic, predicted pathogenic variant in TTC21B. BBS should be considered among the ciliopathies in the differential diagnosis of neonates with renal dysplasia and severe respiratory failure. [ABSTRACT FROM AUTHOR]

Pretomanid is a nitroimidazole antimicrobial active against drug-resistant Mycobacterium tuberculosis and approved in combination with bedaquiline and linezolid (BPaL) to treat multidrug-resistant (MDR) pulmonary tuberculosis (TB). However, the penetration of these antibiotics into the central nervous system (CNS), and the efficacy of the BPaL regimen for TB meningitis, are not well established. Importantly, there is a lack of efficacious treatments for TB meningitis due to MDR strains, resulting in high mortality. We have developed new methods to synthesize 18F-pretomanid (chemically identical to the antibiotic) and performed cross-species positron emission tomography (PET) imaging to noninvasively measure pretomanid concentration-time profiles. Dynamic PET in mouse and rabbit models of TB meningitis demonstrates excellent CNS penetration of pretomanid but cerebrospinal fluid (CSF) levels does not correlate with those in the brain parenchyma. The bactericidal activity of the BPaL regimen in the mouse model of TB meningitis is substantially inferior to the standard TB regimen, likely due to restricted penetration of bedaquiline and linezolid into the brain parenchyma. Finally, first-in-human dynamic 18F-pretomanid PET in six healthy volunteers demonstrates excellent CNS penetration of pretomanid, with significantly higher levels in the brain parenchyma than in CSF. These data have important implications for developing new antibiotic treatments for TB meningitis. Pretomanid has been approved for use in cases of multi-drug resistant pulmonary tuberculosis, yet the penetration of this antibiotic into other target tissues is not well established. Authors provide insight on pretomanid pharmacokinetics in the central nervous system, using positron emission tomography in animal models, and human studies. [ABSTRACT FROM AUTHOR]

Seventeen international consortia are collaborating on a human reference atlas (HRA), a comprehensive, high-resolution, three-dimensional atlas of all the cells in the healthy human body. Laboratories around the world are collecting tissue specimens from donors varying in sex, age, ethnicity, and body mass index. However, harmonizing tissue data across 25 organs and more than 15 bulk and spatial single-cell assay types poses challenges. Here, we present software tools and user interfaces developed to spatially and semantically annotate ("register") and explore the tissue data and the evolving HRA. A key part of these tools is a common coordinate framework, providing standard terminologies and data structures for describing specimen, biological structure, and spatial data linked to existing ontologies. As of April 22, 2022, the "registration" user interface has been used to harmonize and publish data on 5,909 tissue blocks collected by the Human Biomolecular Atlas Program (HuBMAP), the Stimulating Peripheral Activity to Relieve Conditions program (SPARC), the Human Cell Atlas (HCA), the Kidney Precision Medicine Project (KPMP), and the Genotype Tissue Expression project (GTEx). Further, 5,856 tissue sections were derived from 506 HuBMAP tissue blocks. The second "exploration" user interface enables consortia to evaluate data quality, explore tissue data spatially within the context of the HRA, and guide data acquisition. A companion website is at https://cns-iu.github.io/HRA-supporting-information/. The software tools and user interfaces for the registration and exploration of tissue data for the human reference atlas are presented, providing evaluation metrics for data quality examination and guidance for data acquisition in support of reference atlas construction. [ABSTRACT FROM AUTHOR]

The fusion of visible and infrared (IR) images is considered as one of the most efficient image fusion methods so far, as more valuable information can be obtained from the fused images overcoming the sensor limitations. Even in poor lighting conditions, by utilizing the thermal (IR) radiation information, the details can be obtained from the IR sensors. Visual images provide better spectral, spatial, and texture details. Thus, integrating the IR and visual images will provide more information about an object in a scene, thus enhancing the decision-making process in surveillance applications. The proposed work is aimed to be an object detection framework that utilizes this image fusion technique to identify an object. However, when the query image has more features, the computational complexity for extraction and processing of those features for identification of an object increases. This reduces the detection accuracy of the system. Hence, an optimal set of features ought to be identified before proceeding into the classification and detection processes. To achieve this, the research work has proposed a nature-inspired optimal feature selection methodology using ant colony optimization. Finding the optimal features to reduce the computational complexity and thereby increase the accuracy of detection is the research objective. The fusion of IR and visible images is progressed using pulse-coupled neural network. The rest of the processes such as classification and detection are performed using the convolutional neural network model. Experimental results have been compared with conventional techniques in terms of accuracy and computation time. [ABSTRACT FROM AUTHOR]

The objective of the study is to report the outcomes of COVID-19 in ANCA-associated vasculitis (AAV) patients. This was a registry-based observational study conducted at a tertiary care center in north India. AAV patients with at least one follow-up visit between March 2020 and September 2021 were included. Demographic features, clinical manifestations, disease activity, and treatment details of underlying AAV were noted in all patients. Details of COVID-19 infection including severity, treatment, and outcomes were noted. Predictors of COVID-19 severity were determined using univariate analysis. A total of 33 (18.3%) out of 180 AAV patients contracted COVID-19 infection. Moderate COVID-19 infection was seen in 33.3% and severe or critical infection was seen in 36.3% of patients. Seventeen patients (51.5%) required supplemental oxygen therapy. Nine patients had active disease at the time of COVID-19 infection and three of them died due to COVID-19 infection. The risk of COVID-19 infection and its severity did not differ between patients receiving different immunosuppressants including rituximab induction. Hypothyroidism (p = 0.046) and ocular (p = 0.038) involvement due to AAV predicted the development of moderate to severe/critical COVID-19. Three (9.1%) patients died from COVID-19 and the rate of AAV flare after COVID-19 was similar to that in non-COVID-19 patients (15.3/100 person-year vs. 15.6/100 person-year, p = 0.95). Majority of the patients with AAV had moderate to severe or critical COVID-19 infection. The rate of death due to COVID-19 in AAV is higher than in general population. Use of standard remission induction regimens did not lead to increased risk of COVID-19 infection in our AAV cohort. [ABSTRACT FROM AUTHOR]

A catastrophic debris flow in the Rishiganga and Dhauliganga rivers in Uttarakhand, India, on 7 February 2021 left a trail of disaster. Around 100–150 people lost their lives according to Uttarakhand Chief Secretary statement given to ANI news portal, two hydropower projects were badly damaged and a bridge across the Rishiganga River was washed off in the event. Study shows that the debris flow is caused due to detachment of 0.59 km2 right lobe of a hanging glacier and resultant ice-rock avalanche. This right lobe of the glacier was located over a mountain slope having an average slope of 35° at 4700–5555 m a.s.l. and travelled 12.4 km before hitting the infrastructure projects. Role of precipitation, snow cover, land surface temperature, and permafrost processes were investigated for identifying causes of the event. Since 2012, monsoon precipitation and mean annual land surface temperature (LST) showed significant increasing trend. Snow cover during monsoon months showed increasing trend and September, October and November experienced decreasing trend at glacier elevations. Mean annual LST increased from − 0.3 °C in 2012 to a peak of 0.4 °C in 2016. Central lobe of the glacier advanced during this period and eventually fell off in 2016 suggesting that the LST warming forced reduction of frictional drag at the interface facilitating it advancement and eventual dislodgement. Permafrost modelling suggests warm permafrost below 50 m and conditions favourable for intense frost cracking up to 10–15 m. At ~ 40 m depth, the delayed response of 2012–2016 warming produced peak positive temperature conditions by December and probably facilitated the formation of thin film of water at the deeper layers acting as a lubricant for glacier sliding. It is also suggested that the increase in summer precipitation might have forced thickening of the accumulation area and thereby increasing the shear stress for sliding of the glacier. It is proposed that the recent change in the weather conditions in the region is primarily responsible for this event through geological, glaciological, and permafrost processes. Flood modelling study suggests a flood volume of ~ 10 MCM generating 24.5 m flow depth at the bridge site with 12.7 m/s flow velocity. The event highlighted the need for improved monitoring of the cryosphere areas of the Himalaya to capture the early warning signs for better preparedness. [ABSTRACT FROM AUTHOR]

The objectives of this study were to describe the clinical features and evaluate the utility of immunological features as predictors of organ involvement and disease severity in patients with primary Sjogren's syndrome (pSS). In this single-center observational cross-sectional study, subjects fulfilling the 2012 AECG criteria or 2016 ACR/EULAR criteria for pSS were included. Details of glandular, extra-glandular manifestations, ESSDAI, ESSPRI, ANA, anti-Ro/La antibodies, rheumatoid factor (RF), complement (C3 and C4) levels and hyperglobulinemia were noted. Chi-square and Mann–Whitney U tests were performed for determining associations and relative risk (RR) was calculated. Sixty-four subjects with pSS were included in the study. Females constituted 92% and median age at onset was 37.5 (15–74) years. Ocular or oral sicca was noted in 61 (95.3%) subjects and parotidomegaly was noted in 17 (26.5%) subjects. Extra-glandular manifestations noted were: constitutional (85.9%), articular (65.6%), renal (29.6%), hematological (26.6%), cutaneous (12.5%), peripheral nerves (9.3%) and pulmonary (4.7%). Immunological features noted were: ANA (85.9%), anti-Ro (81.3%), anti-La (60.9%), RF (84.4%), hypocomplementemia (39.1%) and hyperglobulinemia (62.5%). Median ESSDAI was 6 (0–23) and ESSPRI was 7 (0–10). ANA was associated with younger age and renal involvement (RR 1.25). Anti-Ro was associated with younger age, renal involvement (RR 1.36) and high ESSDAI. Anti-La was associated with high renal (RR 3.4) and low articular involvement (RR 2.75). RF was associated with hematological involvement and hyperglobulinemia was associated with younger age. Certain immunological features can help predict the organ involvement in patients with pSS. Larger, prospective follow-up studies are needed to clearly understand these associations. [ABSTRACT FROM AUTHOR]

Purpose: Macrophages represent an essential means of sequestration and immune evasion for Mycobacterium tuberculosis. Pulmonary tuberculosis (TB) is characterized by dense collections of tissue-specific and recruited macrophages, both of which abundantly express CSF1R on their outer surface. 4-Cyano-N-(5-(1-(dimethylglycyl)piperidin-4-yl)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-2-yl)-1H-imidazole-2-carboxamide (JNJ-28312141) is a reported high affinity, CSF1R-selective antagonist. We report the radiosynthesis of 4-cyano-N-(5-(1-(N-methyl-N-([11C]methyl)glycyl)piperidin-4-yl)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-2-yl)-1H-imidazole-2-carboxamide ([11C]JNJ-28312141) and non-invasive detection of granulomatous and diffuse lesions in a mouse model of TB using positron emission tomography (PET). Methods: Nor-methyl-JNJ-28312141 precursor was radiolabeled with [11C]iodomethane to produce [11C]JNJ-28312141. PET/CT imaging was performed in the C3HeB/FeJ murine model of chronic pulmonary TB to co-localize radiotracer uptake with granulomatous lesions observed on CT. Additionally, CSF1R, Iba1 fluorescence immunohistochemistry was performed to co-localize CSF1R target with reactive macrophages in infected and healthy mice. Results: Radiosynthesis of [11C]JNJ-28312141 averaged a non-decay-corrected yield of 18.7 ± 2.1%, radiochemical purity of 99%, and specific activity averaging 658 ± 141 GBq/µmol at the end-of-synthesis. PET/CT imaging in healthy mice showed hepatobiliary [13.39–25.34% ID/g, percentage of injected dose per gram of tissue (ID/g)] and kidney uptake (12.35% ID/g) at 40–50 min post-injection. Infected mice showed focal pulmonary lesion uptake (5.58–12.49% ID/g), hepatobiliary uptake (15.30–40.50% ID/g), cervical node uptake, and renal uptake (11.66–29.33% ID/g). The ratio of infected lesioned lung/healthy lung uptake is 5.91:1, while the ratio of lesion uptake to adjacent infected radiolucent lung is 2.8:1. Pre-administration of 1 mg/kg of unlabeled JNJ-28312141 with [11C]JNJ-28312141 in infected animals resulted in substantial blockade. Fluorescence microscopy of infected and uninfected whole lung sections exclusively co-localized CSF1R staining with abundant Iba1 + macrophages. Healthy lung exhibited no CSF1R staining and very few Iba1 + macrophages. Conclusion: [11C]JNJ-28312141 binds specifically to CSF1R + macrophages and delineates granulomatous foci of disease in a murine model of pulmonary TB. [ABSTRACT FROM AUTHOR]

Several international and national consensus guidelines from professional bodies and expert panels are available for the management of breast cancers. The widely used international guidelines are from the National Comprehensive Cancer Network (NCCN), St. Gallen International Expert Consensus, and the European Society of Medical Oncology (ESMO) and the National Institute for Health and Care Excellence (NICE) of the UK. This article is an update from the Association of Breast Surgeons of India (ABSI) regarding the guidelines to manage breast cancer in India. The earlier version of the same was published in 2016. This article has been updated with the latest research work in the management of breast cancer to date and necessary changes made to the earlier version. [ABSTRACT FROM AUTHOR]

This paper investigates presentations of lamplighter groups using computational models from automata theory. The present work shows that if G can be presented such that the full group operation is recognised by a transducer, then the same is true for the lamplighter group G ≀ Z of G. Furthermore, Cayley presentations, where only multiplications with constants are recognised by transducers, are used to study generalised lamplighter groups of the form G ≀ Z d and G ≀ F d , where F d is the free group over d generators. Additionally, Z k ≀ Z 2 and Z k ≀ F d are shown to be Cayley tree automatic. [ABSTRACT FROM AUTHOR]

The main purpose of this study is to mitigate the flood impact which may be caused by uncertain future extreme high rainfall-runoff events. To accomplish the objective, an integrated hydrologic–hydrodynamic flood modeling has been performed in the Periyar river basin by utilizing the HEC-RTS framework including reservoir simulation, optimization and calibration of modeling parameters. For the reconstruction of historical floods, seven historical extreme high rainfall-runoff events have been identified (2002 to 2018) and the event-based flood modeling and continuous flood modeling were performed. Simulated floods showed a good agreement with reference to observed floods (at Neeleswaram gauge) (where R2 is recorded as 0.80 and 0.67 for flood event 2018 and continuous simulation, respectively). The historical flood event (i.e., July–August 2018) was reconstructed using HEC-RESSIM and the operating rules were modified for Mullaperiyar and Idukki reservoirs. The regulated flood flows were generated for all seven historical extreme events utilizing the daily meteorological time series datasets. The flood frequency analysis (FFA) has been performed to generate the return period floods and probabilistic flood maps. For hydrodynamic flood simulation, one-dimensional (1D) flood routing was performed in the downstream sections. For the accuracy assessment, the computed flood inundation area and depths were compared with the existing reference datasets like (i) Central Water Commission (CWC) flood data, (ii) real-time flood inundation captured in Sentinel satellite data and (iii) flood maps prepared by DARTMOUTH Flood Agency USA, which showed a reliable agreement. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are limited therapeutic options for the prevention and treatment of SARS-CoV-2 infections. We evaluated the antiviral activity of sulforaphane (SFN), the principal biologically active phytochemical derived from glucoraphanin, the naturally occurring precursor present in high concentrations in cruciferous vegetables. SFN inhibited in vitro replication of six strains of SARS-CoV-2, including Delta and Omicron, as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN should be explored as a potential agent for the prevention or treatment of coronavirus infections. Sulforaphane, a chemical found in broccoli, has known antioxidant and antiinflammatory effects. Here, the authors show that it can inhibit SARS-CoV-2 and other coronavirus infections in mammalian cells and can decrease viral load in mice when treated prior to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

In this perspectives paper, I employ the term jugalbandi to describe the ways in which many contemporary Indian organizations engage in innovation. Through a description of three Indian organizations – ISRO, Amul and Aadhaar – I illustrate how this distinctive approach draws both on jugaad – and its emphasis on being frugal, flexible and inclusive – as well as systematic innovation, with its focus on building capabilities, relying on process and advancing technological frontiers. As a homegrown approach, jugalbandi builds on an "Indian" way of doing things while imbibing influences from other modes, and is enabling organizations build their innovation capacities even as they remain relevant to their contexts. In developing this conceptualization, I highlight the need to appreciate the contextual and institutional roots of innovation, suggest that trajectories of development within emerging economies will remain distinctive and provide both practical and policy advice on how actors should pursue innovation in these scenarios. [ABSTRACT FROM AUTHOR]

Arterial involvement, although rare, accounts for significant mortality and morbidity in patients of Behçet's disease (BD). There is paucity of data on arterial BD. The objective of this 5-year retrospective cohort study was to examine the clinical presentation, pattern of arterial involvement, and treatment outcome in Indian arterial BD patients. Data on demography, clinical presentation, radiology, instituted therapy, vascular interventions and treatment outcomes were recorded and analyzed. Ten (16.9%) out of 59 patients with BD had arterial involvement in 13 vascular territories [mean age 30 (8) years, 9 (90%) males]. Pulmonary artery was most commonly involved (46%), followed by abdominal aorta (15%), femoral artery (15%), descending thoracic aorta (8%), common iliac (8%), and dorsalis pedis artery (8%). Two patients had multi-territory involvement. The median interval between disease onset and development of arterial aneurysms was 3 years (3 months–12 years). Concomitant deep vein thrombosis was seen in 60% cases. Prednisolone and cyclophosphamide were the most common immunosuppressive therapy used; one patient who relapsed on cyclophosphamide responded to infliximab. Five surgical or endovascular interventions were performed. Four patients (40%) died due to aneurysm rupture—all had a delayed diagnosis, and three had pulmonary artery involvement, with death due to massive hemoptysis. Based on the present study, we concluded that arterial involvement in BD is seen predominantly in males and has a high mortality. Early detection and aggressive treatment with immunosuppression and surgical or endovascular interventions are essential for good outcomes. [ABSTRACT FROM AUTHOR]

In recent times, video analysis gains more popularity among the researchers, due to its social impact and widespread applications. In this research article, a novel algorithm is proposed to detect the multiple events in the videos. At first, histogram equalization technique is used for contrast enhancement and smoothing of the videos, which are collected from Columbia consumer video, and UCF101 databases. The histogram equalization delivers a better quality of frames without loss of any local information like edges, patches and points. Further, feature extraction is accomplished using gradient local ternary pattern, histogram of oriented gradients, and Tamura features to extract the feature vectors from the enhanced frames that speed up the training process. The extracted feature vectors are high dimension in nature, so an ensemble feature selection algorithm is proposed to select optimal features from the extracted features. The selected optimal feature sub-sets are fed to multi support vector machine classifier to classify the multiple events. Finally, the relevant events are retrieved utilizing Euclidean distance measure and the simulation result showed that the proposed algorithm achieved better performance in multi-event recognition. The proposed algorithm almost showed a maximum of 14.21 % improvement in video event classification by means of accuracy compared to the existing algorithms like two-stage neural network, multi-stream deep learning system, improved two-stream model, Concept wise Power Law Normalization (CPN) with Convolutional Neural Network (CNN), Motion based Shot Boundary Detection (MSBD) algorithm, and motion features with Recurrent Neural Network (RNN). [ABSTRACT FROM AUTHOR]

In this study, a coupled and improved snow-glacier runoff modeling framework has been presented, which aims to separate the snowmelt runoff from glaciated and non-glaciated areas. To fulfil the above objective, the two hydrological models such as the conceptual Glacier-hydrological Model (GSM-SOCONT) and Soil & Water Assessment Tool (SWAT) have been used over the Teesta river Himalayan catchments. The temperature index model (TIM) based degree-day approach (DDA) in GSM-SOCONT model has been modified and radiation components were added. The R2 values computed between observed and modeled discharge (1991–2005) was improved from 0.55 to 0.63 after adding the radiation components. Initially, SWAT model has been used for the simulation, calibration, and optimization of the various snowmelt hydrology parameters. Then, SWAT model based optimized parameters and outcomes were used as inputs to set up the GSM-SOCONT model. After simulating/separating snow melts from glaciated and non-glaciated areas, the optimized snow-glacier parameters from the improved GSM-SOCONT (1991–2005) were re-input to the SWAT for the projection of snowmelt scenarios (2008–2100) utilizing the downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5) Global Circulation Models (GCMs) datasets. The snow water equivalent (SWE) reconstructed for the year 2005 from the MODIS satellite snow covers (i.e. ranges from 80 to 138 mm) found comparable to the SWAT generated SWE (i.e. ranges from 86 to 115 mm). Based on the future projections of snowmelt, the earlier snow-melting or shifts have been observed in extreme high and low elevation areas of the Sikkim Himalaya. [ABSTRACT FROM AUTHOR]

Prioritization of river basin in semi-arid to sub-humid tropical region is important in the context of natural resources conservation and management. In this paper, the Gomti River basin was prioritized for soil–water resource conservation based on analysis of morphometric parameters and land use–land cover with RS and GIS techniques. Gomti River is a monsoon and groundwater-fed river; it is a tributary of Ganga River. The basin has been divided into seventeen sub-basins. ASTER (30 m) Digital Elevation Model data and LANDSAT—8 (30 m) satellite imagery were used to analyze the morphometric parameters and to generate land-use–land-cover data for the basin through supervised image classification technique. The linear, areal, and relief aspects of each sub-basins were determined. Morphometric analysis revealed that the basin is a fifth-order drainage system with a dendritic to sub-dendritic drainage pattern. Drainage patterns indicate that sub-surface materials are homogeneous and lack structural control over topography. The circulatory ratio value indicates the basin is an elongated shape. Low values of morphometric parameters indicate good permeability, infiltration, and coarse drainage texture, low relief, and elongated shape indicated good groundwater potential in the basin. The final prioritization result shows that the sub-basin 12 is at the highest priority with the greatest shortage of groundwater potential, so immediate water conservation measures are needed. Contrary, sub-basin 3 is at low priority that indicates the highest groundwater potential. This study suggests the primary priority to improve the water resource management in semi-arid regions at the basin level. [ABSTRACT FROM AUTHOR]

The 1990 American College of Rheumatology (ACR) criteria for the classification of polyarteritis nodosa (PAN) have many pitfalls and performed poorly when used for diagnostic purposes. Recently, a provisional seven-item diagnostic criteria for PAN was proposed. To validate the provisional seven-item diagnostic criteria for PAN in a cohort of PAN patients from a tertiary care centre in India. Clinical details of patients diagnosed as PAN as per the European Medicines Agency algorithm between 2005 and 2020 were collected retrospectively. Age and sex-matched anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients were included in the non-PAN group. Patients with a deficiency of adenosine deaminase 2 (DADA2) were included as a separate group. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for ACR criteria, the Ministry of Health, Labour and Welfare (MHLW) in Japan diagnostic criteria and the seven-item diagnostic criteria were calculated. Thirty-seven PAN, 14 DADA2 and 37 AAV patients were included in the analysis. The sensitivity, specificity, PPV and NPV of the seven-item criteria were 83.7%, 96.8%, 97.3% and 81.1% respectively. For the ACR criteria, sensitivity was 82.9% and specificity was 79.5%. The sensitivity, specificity for MHLW criteria were 77.3% and 90% respectively. The sensitivity and specificity of seven-item criteria for DADA2 patients were 58.8% and 88.2% respectively. There was very poor agreement between the ACR criteria and the seven-item and MHLW criteria and fair agreement between seven-item and MHLW criteria (κ = 0.279). The provisional seven-item criteria for PAN performed well with high specificity and PPV. [ABSTRACT FROM AUTHOR]

Objectives: To present single centre experience on the efficacy and safety of similar biologic of rituximab in patients with granulomatosis with polyangiitis (GPA). Methods: This was a retrospective study of GPA patients who received similar biologic of rituximab as either remission induction or maintenance agent. Demographic parameters, Birmingham Vasculitis Activity Score (BVAS-v3), vasculitis damage index, relapse and adverse events were retrieved from patient records. Outcomes noted were remission at 6 months in remission induction group and rates of relapses, adverse events, serious infections and mortality in both remission induction and maintenance groups. Results: Seventy-seven GPA patients were enrolled. Sixty received rituximab for induction and 57 for maintenance; 69% were anti PR-3 positive. In the induction group, median BVAS-v3 reduced from 12 (IQR 6–21.5) to 0 (0–1) at 6 months. At 6 months, 60% patients attained remission, 40% in primary induction group and 74% in re-induction group (p = 0.016%). In the maintenance group, seven (12%) patients had relapses with median time to relapse of 12 (6–22) months. Median relapse free survival was 21 (6–22) months on rituximab maintenance. There were 12 deaths (15.6%) and 18 serious infections. Conclusion: Similar biologic of rituximab was an effective agent for remission induction and remission maintenance in patients with GPA. Head to head trials with innovator molecule are needed to confirm these results. Key Points: • Remission was achieved in 60% of GPA patients who received similar biologic of rituximab as remission induction therapy. • Relapse rate during maintenance phase was 12% with similar biologic of rituximab. Serious infections and mortality with similar biologic of rituximab were comparable with that reported previously in AAV trials. [ABSTRACT FROM AUTHOR]

Climate change can adversely affect the elements of water balance in river basins. This paper studies the effects of climate change on hydro-climatological components of the Gomti River basin using SWAT hydrological model. Model performance has been evaluated through sensitivity analysis, calibration, and validation. During calibration and validation time period, the Nash-Sutcliffe efficiency (NSE) and coefficient of determination (R2) values were obtained as 0.86, 0.87, and 0.79, 0.83, respectively. From the sensitivity analysis, it was found that SCS runoff curve number for antecedent moisture condition II (CN2) is the most sensitive parameter, followed by saturated hydraulic conductivity (SOL_K) and then available water capacity of the soil layer (SOL_AWC) etc. To assess the future climate change effects on hydrological variables, MIROC-ESM, MIROC-ESM-CHEM, MIROC_MIROC5, and MOHC_HADGEM2_ES Global Climate Models (GCMs) under RCP 4.5 and RCP 8.5 were applied in the calibrated SWAT model. The following trends were observed after applying the scenarios—the temperature is rising under RCP 4.5 (8.5) scenarios, near-century by + 0.24% (+ 0.65), mid-century by + 2.8% (+ 4.62), and end-century by + 5.25% (+ 10.98), respectively. Precipitation is declining under RCP 4.5 (8.5) by − 29.17% (− 29.65%), − 28.69% (− 28.88%), and − 23.82% (− 20.11%), respectively. Evapotranspiration under RCP 4.5 (RCP 8.5) is increasing by + 3.62% (+ 3.95%), + 4.30% (+ 5.38%), and + 5.49% (+ 6.03%), respectively. Consequently, streamflow under RCP 4.5 (RCP 8.5) is declining by − 31.27% (− 23.99%), − 27.45% (− 28.96%), and − 24.30% (− 18.03%), respectively in near, mid, and end century. The findings will be beneficial for managing future water resources in the Gomti River basin. [ABSTRACT FROM AUTHOR]

Fungal keratitis (FK) is a corneal infection caused by different fungal species. It is treated by the topical application of natamycin (NAT). Nevertheless, this approach faces many limitations like toxic effects, frequent dosing, resistance, and patient discomfort. The present research reports the development of trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes by a modified thin-film hydration method. TMC was synthesized using a one-step carbodiimide method and characterized by 1H-NMR and degree of quaternization (53.74 ± 1.06%). NAT, cholesterol (CHOL), span 60 (Sp60), and dicetyl phosphate (DCP) were used to prepare niosomes which were incubated with TMC to obtain mucoadhesive cationic NAT loaded niosomes (MCNNs). MCNNs showed a spherical shape with 1031.12 ± 14.18 nm size (PDI below 0.3) and 80.23 ± 5.28% entrapment efficiency. In vitro drug release studies showed gradual drug release from TMC coated niosomes as compared to the uncoated niosomes. MIC assay and disk diffusion assay revealed promising in vitro antifungal potential of MCNNs similar to the marketed formulation. For investigating in vivo performance, ocular retention and pharmacokinetics, ocular irritation, and ulcer healing studies were performed using the rabbit model. Mucoadhesive property and prolonged local drug release improved the safety and efficacy of NAT, suggesting that the developed niosomes could be an emerging system for effective treatment of fungal keratitis. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial dysfunction is an uncommon but potentially fatal complication in systemic lupus erythematosus (SLE). We describe the outcome in a small series of Asian Indian patients and examine associated factors. Methods: SLE patients who fulfilled the 2012 SLICC criteria and developed new-onset myocardial dysfunction were included in this retrospective case series. Acute myocardial dysfunction was defined as global hypokinesia and left ventricular ejection fraction (LVEF)<50% on echocardiography (with or without symptoms) in patients with SLE. Survival was assessed using Kaplan-Meier survival analysis and Cox regression. Results: This study included 37 patients with mean age 28.2 ± 11.2 years and median (range) LVEF of 35% (18–48%) at presentation. A majority had active disease, with SLEDAI-2k ≥ 5 in 26 (of 28). All patients received oral corticosteroids and a majority received additional immunosuppression, including pulse methylprednisolone in 28 and cyclophosphamide in 27. Nine patients died during hospitalisation (25%), a majority due to infections. Death was significantly associated with elevated procalcitonin at presentation (p = 0.05), elevated white cell count (p = 0.02) and low complement C3 (p = 0.03). In those who survived, long-term outcomes were good, with complete myocardial recovery in 14 (64%). A higher ejection fraction at presentation was associated with complete recovery. Conclusions: In this small series of patients of SLE with acute myocardial dysfunction, we report a significant in-hospital mortality due to infections. Many of the patients who died had elevated procalcitonin at presentation. A diligent search for infection seems prudent in lupus patients who present with acute myocardial dysfunction. Key Points • In patients of SLE with acute myocardial dysfunction who were treated with immunosuppression, there was significant short-term mortality due to infections. • This mortality was associated with elevated procalcitonin at baseline and may suggest some of them had pre-existing hidden sepsis. • A prudent search for infections in these patients before immunosuppression may help to decrease short-term mortality. [ABSTRACT FROM AUTHOR]

Purpose: Despite recent advances in antimicrobial treatments, tuberculosis (TB) remains a major global health threat. Mycobacterium tuberculosis proliferates in macrophages, preventing apoptosis by inducing anti-apoptotic proteins leading to necrosis of the infected cells. Necrosis then leads to increased tissue destruction, reducing the penetration of antimicrobials and immune cells to the areas where they are needed most. Pro-apoptotic drugs could be used as host-directed therapies in TB to improve antimicrobial treatments and patient outcomes. Procedure: We evaluated [18F]-ICMT-11, a caspase-3/7-specific positron emission tomography (PET) radiotracer, in macrophage cell cultures and in an animal model of pulmonary TB that closely resembles human disease. Results: Cells infected with M. tuberculosis and treated with cisplatin accumulated [18F]-ICMT-11 at significantly higher levels compared with that of controls, which correlated with levels of caspase-3/7 activity. Infected mice treated with cisplatin with increased caspase-3/7 activity also had a higher [18F]-ICMT-11 PET signal compared with that of untreated infected animals. Conclusions: [18F]-ICMT-11 PET could be used as a noninvasive approach to measure intralesional pro-apoptotic responses in situ in pulmonary TB models and support the development of pro-apoptotic host-directed therapies for TB. [ABSTRACT FROM AUTHOR]

This paper presents a novel strategy to indirectly control the peak dc-link voltage (PDV) of grid-connected quasi-Z-source (qZS) inverter supplied with renewable energy sources (RES). The method is directed to indirectly determine and regulate the pulsating PDV through the qZS network capacitor voltages. The small signal model is developed by representing ac- and dc-sides separately. The ac-side control is designed with higher bandwidth to avoid interference from dc-side. The dc-side control utilizes shoot-through duty ratio to PDV transfer function and controller is designed to minimize the effect of its right-half-plane zero (RHPZ) characteristics. The gating signals are realized through maximum constant boost control in conjunction with one-sixth of third harmonic injection. The strategy is implemented through MATLAB/Simulink and is verified experimentally with real-time simulations (RTSs) in OPAL-RT. [ABSTRACT FROM AUTHOR]