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Abstract LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90–120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90–120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.

Background: Despite documented correlation between glioma grades and dynamic contrast-enhanced (DCE) magnetic resonance (MR) perfusion-derived parameters, and its inherent advantages over dynamic susceptibility contrast (DSC) perfusion, the former remains underutilized in clinical practice. Given the inherent spatial heterogeneity in high-grade diffuse glioma (HGG) and assessment of different perfusion parameters by DCE (extravascular extracellular space volume [Ve] and volume transfer constant in unit time [k-trans]) and DSC (rCBV), integration of the two into a protocol could provide a holistic assessment. Considering therapeutic and prognostic implications of differentiating WHO grade 3 from 4, we analyzed the two grades based on a combined DCE and DSC perfusion.

Abstract Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E−04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.

Abstract Succinic acid (SA) is one of the top platform chemicals with huge applications in diverse sectors. The presence of two carboxylic acid groups on the terminal carbon atoms makes SA a highly functional molecule that can be derivatized into a wide range of products. The biological route for SA production is a cleaner, greener, and promising technological option with huge potential to sequester the potent greenhouse gas, carbon dioxide. The recycling of renewable carbon of biomass (an indirect form of CO2), along with fixing CO2 in the form of SA, offers a carbon-negative SA manufacturing route to reduce atmospheric CO2 load. These attractive attributes compel a paradigm shift from fossil-based to microbial SA manufacturing, as evidenced by several commercial-scale bio-SA production in the last decade. The current review article scrutinizes the existing knowledge and covers SA production by the most efficient SA producers, including several bacteria and yeast strains. The review starts with the biochemistry of the major pathways accumulating SA as an end product. It discusses the SA production from a variety of pure and crude renewable sources by native as well as engineered strains with details of pathway/metabolic, evolutionary, and process engineering approaches for enhancing TYP (titer, yield, and productivity) metrics. The review is then extended to recent progress on separation technologies to recover SA from fermentation broth. Thereafter, SA derivatization opportunities via chemo-catalysis are discussed for various high-value products, which are only a few steps away. The last two sections are devoted to the current scenario of industrial production of bio-SA and associated challenges, along with the author's perspective.

Rationale Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications.Aim The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD.Sample size Using 80% power and an alpha error of 5 %, presuming a 10%–15% drop-out rate, a total of 2200 patients will be recruited for the study.Methodology This is a prospective, randomised, double-blind, placebo controlled trial.Study outcomes The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase.Discussion The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.

Rationale Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy.Aim The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO.Sample size estimates Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study.Methods and design This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design.Study outcomes The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH.Discussion This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK.Trial registration number CTRI/2022/01/039473.

Background: Pain in the shoulder is the third-most prevalent musculoskeletal pain type. Most frequently involved in tendinopathy/tendon tears is the supraspinatus tendon, followed by a combination of the supraspinatus and infraspinatus tendon. At present, gray-scale ultrasound and MRI are used to determine the tear size, gross morphology, and postsurgical tendon repair. However, they are unable to determine the material characteristics of the muscle or tendon. Aims and Objectives: The aim of this study is to assess the role of ultrasound elastography in the evaluation of the rotator cuff tendon and to compare gray scale ultrasound and shear wave elastography (SWE) findings of the supraspinatus tendon with MRI in patients with shoulder pain. Materials and Methods: This prospective observational study included 50 patients. They were examined using a 1.5-T MRI machine and the ACUSON S3000 (Siemens Medical Solution) machine. The radiologist performing the ultrasound was blinded by the results of the MRI. Results: Age varied from 19 to 75 years. The majority (34%) were in the range of 31–40 years. Males were predominately affected. In MRI, the most common type of injury was mild tendinosis (34%), followed by moderate/severe tendinosis (26%). About 30% were diagnosed with moderate/severe tendinosis, 24% with mild tendinosis, 22% with partial tears, and 18% with full-thickness tears in gray-scale ultrasound. When SWE was combined, 32% were diagnosed with moderate/severe tendinosis, 28% with mild tendinosis, 20% with a partial tear, and 14% with a full-thickness tear. Conclusion: SWE showed better diagnostic performance than gray-scale ultrasound in the detection of supraspinatus tendinopathy.

Alcohol use is a risk factor for death and disability and is attributed to almost one-third of injury deaths globally. This highlights the need for interventions aimed at alcohol reduction, especially in areas with high rates of injury with concurrent alcohol use, such as Tanzania. The aim of this study is to create a culturally appropriate text messages as a booster to a brief negotiational intervention (BNI), to in the Emergency Department of the Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Creation of text message boosters for an ED-based intervention expands the window of opportunity for alcohol use reduction in this high-risk population. The study followed a two-step approach to create the text message content in English and then translate and culturally adapt to Tanzanian Swahili. The culturalization process followed the World Health Organization's process of translation and adaptation of instruments. Translation, back translation, and qualitative focus groups were used for quality control to ensure text message content accuracy and cultural appropriateness. In total, nearly 50 text messages were initially developed in English, yet only 29 text messages were successfully translated and adapted; they were focused on the themes of Self-awareness, Goal setting and Motivation. We developed culturally appropriate text message boosters in Swahili for injury patients in Tanzania coupled with a BNI for alcohol use reduction. We found it important to evaluate content validation for interventions and measurement tools because the intended text message can often be lost in translation. The process of culturalization is critical in order to create interventions that are applicable and beneficial to the target population. Trial registration: Clinical Trials Registration Number: NCT02828267, NCT04535011.

BackgroundPeople experiencing homelessness co-occurring with substance use or offending ('severe and multiple disadvantage' SMD) often have high levels of poor oral health and related health behaviours (particularly, substance use, smoking, poor diet). This systematic review aimed to assess the effectiveness and cost-effectiveness of interventions in adults experiencing SMD to improve oral health and related health behaviours.Methods and findingsFrom inception to February 2023, five bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus) and grey literature were searched. Two researchers independently screened the search results. Randomized controlled trials (RCTs), comparative studies and economic evaluations were included that reported outcomes on oral health and the related health behaviours. Risk of bias was assessed and results narratively synthesized. Meta-analyses were performed where appropriate. This review was registered with PROSPERO (reg. no: CRD42020202416). Thirty-eight studies were included (published between 1991 and 2023) with 34 studies reporting about effectiveness. Most studies reported on substance use (n = 30). Interventions with a combination of housing support with substance use and mental health support such as contingent work therapy appeared to show some reduction in substance use in SMD groups. However, meta-analyses showed no statistically significant results. Most studies had short periods of follow-up and high attrition rates. Only one study reported on oral health; none reported on diet. Three RCTs reported on smoking, of which one comprising nicotine replacement with contingency management showed improved smoking abstinence at 4 weeks compared to control. Five studies with economic evaluations provided some evidence that interventions such as Housing First and enhanced support could be cost-effective in reducing substance use.ConclusionThis review found that services such as housing combined with other healthcare services could be effective in improving health behaviours, particularly substance use, among SMD groups. Gaps in evidence also remain on oral health improvement, smoking, and diet. High quality studies on effectiveness with adequate power and retention are needed to address these significant health challenges in SMD populations.

Objectives Among people experiencing severe and multiple disadvantage (SMD), poor oral health is common and linked to smoking, substance use and high sugar intake. Studies have explored interventions addressing oral health and related behaviours; however, factors related to the implementation of these interventions remain unclear. This mixed-methods systematic review aimed to synthesise evidence on the implementation and sustainability of interventions to improve oral health and related health behaviours among adults experiencing SMD.Methods Bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature were searched from inception to February 2023. Studies meeting the inclusion criteria were screened and extracted independently by two researchers. Quality appraisal was undertaken, and results were synthesised using narrative and thematic analyses.Results Seventeen papers were included (published between 1995 and 2022). Studies were mostly of moderate quality and included views from SMD groups and service providers. From the qualitative synthesis, most findings were related to aspects such as trust, resources and motivation levels of SMD groups and service providers. None of the studies reported on diet and none included repeated offending (one of the aspects of SMD). From the quantitative synthesis, no difference was observed in programme attendance between the interventions and usual care, although there was some indication of sustained improvements in participation in the intervention group.Conclusion This review provides some evidence that trust, adequate resources and motivation levels are potentially important in implementing interventions to improve oral health and substance use among SMD groups. Further research is needed from high quality studies and focusing on diet in this population.PROSPERO registration number CRD42020202416.

ABSTRACT The extremely radiation-resistant bacterium, Deinococcus radiodurans, is a microbe of importance, both, for studying stress tolerance mechanisms and as a chassis for industrial biotechnology. However, the molecular tools available for use in this organism continue to be limiting, with its multiploid genome presenting an additional challenge. In view of this, the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas tools provide a large repertoire of applications for gene manipulation. We show the utility of the type I-E Cascade system for knocking down gene expression in this organism. A single-vector system was designed for the expression of the Cascade components as well as the crRNA. The type I-E Cascade system was better tolerated than the type II-A dCas9 system in D. radiodurans. An assayable acid phosphatase gene, phoN integrated into the genome of this organism could be knocked down to 10% of its activity using the Cascade system. Cascade-based knockdown of ssb, a gene important for radiation resistance resulted in poor recovery post-irradiation. Targeting the Radiation and Desiccation Response Motif (RDRM), upstream of the ssb, prevented de-repression of its expression upon radiation exposure. In addition to this, multi-locus targeting was demonstrated on the deinococcal genome, by knocking down both phoN and ssb expression simultaneously. The programmable CRISPR interference tool developed in this study will facilitate the study of essential genes, hypothetical genes, and cis-elements involved in radiation response as well as enable metabolic engineering in this organism. Further, the tool can be extended for implementing high-throughput approaches in such studies. IMPORTANCE Deinococcus radiodurans is a microbe that exhibits a very high degree of radiation resistance. In addition, it is also identified as an organism of industrial importance. We report the development of a gene-knockdown system in this organism by engineering a type I-E clustered regularly interspaced short palindromic repeat (CRISPR)-Cascade system. We used this system to silence an assayable acid phosphatase gene, phoN to 10% of its activity. The study further shows the application of the Cascade system to target an essential gene ssb, that caused poor recovery from radiation. We demonstrate the utility of CRISPR-Cascade to study the role of a regulatory cis-element in radiation response as well as for multi-gene silencing. This easy-to-implement CRISPR interference system would provide an effective tool for better understanding of complex phenomena such as radiation response in D. radiodurans and may also enhance the potential of this microbe for industrial application.

Introduction: In order to reduce the oral health disparities among school children in rural areas and provide a sustainable program, a pilot project using community health workers was planned. Aim and Objectives: The objectives of the study were to implement and evaluate community participatory oral health promotion and prevention program in school children from select rural population in Deshmukhwadi, Pune district, and also carry out knowledge, attitude and practice survey among health workers and school teachers about oral health. Materials and Methods: One hundred and thirty-nine students, aged 6–13 years, constituted the sample size. The program consisted of oral health education, atraumatic restorative treatment, scaling of teeth with hand scalers, and fortnightly fluoride mouth rinsing. The health workers who were commissioned into medical department by Tata Motors from the same village, after proper training and calibration performed the above-mentioned preventive procedures on children. Results: There was a significant improvement in gingival status (P < 0.001), caries status (P = 0.003), and incipient lesion (P = 0.01) after the program. In the present study, the health workers were successfully trained to provide basic oral care services in rural areas. Furthermore, the knowledge, attitude, and practice regarding oral health which was assessed among the health workers and school teachers improved after 16 months of the program. Conclusions: The community participatory oral health promotion and prevention program showed a significant improvement in the filled and initial lesion surfaces in the primary and permanent dentition and the bleeding sextants. Health workers and school teachers showed improvement in knowledge and practice after the program.

Background: Stress, anxiety and depression are common nowadays with having debilitating effects on the affected person. Doctors face a lot of stress owing to various reasons. This stress affects them on a personal level and a professional level too. Methods: Fifty one faculty members willingly participated in the study. A self-reported depression anxiety stress scale (DASS)-42 along with a semi-structured pro forma was distributed amongst the faculty members of a medical college and hospital at Rajpura. Results: Most of the participants were female (60.8%) and married (86.3%). Majority were from the age group of 30–39 years (49%). Half of the faculty experience mild (25.5%)-to-moderate (25.5%) levels of depressive symptoms, about one-third reported moderate (33.3%) anxiety symptoms and about 43.1% reported mild stress symptoms. Conclusions: High extent of depression, anxiety and stress is present in faculty of a medical college. The contributory factors related to this stress, anxiety and depression need to be studied further. Mental health and working environment of the faculty need to be addressed.

Abstract Background Coronavirus disease (COVID-19) predisposes patients to both arterial and venous thrombosis due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Therefore, therapeutic anticoagulant therapy has been an integral part for management in patients with moderate to severe COVID-19 disease. We shall here discuss the concerns of starting anticoagulants in patients with COVID-19 disease who are already on antiplatelets, an unexplored area. Case presentation We herein report a case of 61-year-old patient with hypertension and diabetes mellitus type 2 with COVID-19 disease. Patient also had coronary artery disease and underwent CABG 4 years ago and was on aspirin 75-mg HS, clopidogrel 75-mg OD, and tab atorvastatin 40-mg HS. Patient was hemodynamically stable and was maintaining a saturation of 66% on room air and a saturation of 96% on 02 by high FiO2 partial rebreathing face mask. On auscultation, crepitations were present in bilateral lower lung fields. The patient was admitted under moderate category of COVID-19 SARS in the intensive care unit (ICU). Despite of standard care and treatment, in next 2 days, the oxygenation deteriorated Pa02/Fi02

This paper investigates the differential binary modulation for decode-and-forward (DF) based relay-assisted free space optical (FSO) network under the effect of strong atmospheric turbulence together with misalignment error (ME). The atmospheric fading links experience K-distributed turbulence. First we derive novel closed form expression for average bit error rate (BER) and outage probability (OP) in terms of Meijer’s G function. Further, the OP of differential DF-FSO system with multiple relays is derived. We also analyze the asymptotic performance for the sake of getting the order of diversity and the coding gain. The power allotment term is utilized to examine the effect of different power allotment techniques on BER and OP. The simulation results have been used to validate the derived analytical results.

Abstract The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Human pluripotent stem cells serve as a robust model system to study disease pathogenesis in a dish and search for various targeted therapeutics. Collection of control lines from healthy individuals are essential for any study. Therefore, we have generated hiPSC line from a healthy male donor after episomal reprogramming of PBMCs. The generated line is pluripotent, had normal karyotype and has a potential of tri-lineage differentiation. The generated line would serve as control line of Asian origin from Indian population.

The study examines the market efficiency, multi-dimensions of liquidity, and their interconnectedness for the Emerging Indian Stock Market. In contrast to the extant literature, the current study involves testing the market liquidity considering multi-dimensions such as depth, breadth, immediacy, tightness, and resiliency. Second, the study used a battery of tests to determine efficiency, including the Ljung and Box, runs test, Bartel test, Variance ratio, and BDS tests. Furthermore, using five quintiles classified by market depth, the linkage of market efficiency and liquidity is also being investigated. The findings show that during the pandemic, the Indian stock market has been proven to be efficient, suggesting that there are no abnormal returns. Moreover, the research demonstrates that during the COVID-19 pandemic, large volumes of securities are traded quickly and at a lower price effect, but with higher trading costs for completing a market transaction. However, it is worth noting that increased liquidity equates to greater efficiency, while lower liquidity equates to inefficiency.

Background: Ozone oil has both antimicrobial and antiinflammatory properties. This study was undertaken to compare the efficacy of ozone oil with chlorhexidine gluconate 1.0% w/w gel for the treatment of gingivitis. Methods: A triple-blind, controlled trial with parallel design was conducted for 28 days as a pilot study. Thirty participants aged 14–17 years were recruited. After baseline data collection involving gingival index (GI) and plaque index (PI), the products were distributed, scaling of teeth was done, and oral hygiene instructions were given. The participants were asked to apply the gel and oil topically and followed up on days 7 and 28. Results: A statistically significant difference (P < 0.01) was seen within the ozone and chlorhexidine groups at the end of 28 days, showing a reduction in the plaque and gingival scores. At day 28, the reduction in plaque and gingival score was significant for the chlorhexidine group. It was found that chlorhexidine gel showed a greater reduction in the clinical parameters than the ozone oil, which was statistically significant but clinically similar. Both the products showed a substantial reduction in plaque scores. The participants from both the groups showed an improvement, having mild gingivitis post intervention. Conclusion: Ozone oil showed a significant reduction in the clinical parameters of PI and GI similar to chlorhexidine gel, thereby signifying its antimicrobial and antiinflammatory effects on the gingival tissues without any adverse effects, implicating the possession of properties required by a chemotherapeutic agent.

Introduction: Despite advancements in cross-sectional aging techniques, ultrasonography continues to remain the first-line imaging modality for the preoperative assessment of pelvic adnexal masses. Ultrasound strain elastography is a novel technique that can characterise adnexal lesions based on their tissue stiffness and when used in conjunction with conventional USG, it may increase the precision of diagnosis and can act as a cost-effective viable ancillary tool. Aim: To assess the role of strain sonoelastography in characterising the adnexal lesion as benign or malignant. Materials and Methods: This cross-sectional study was conducted in the Department of Radiodiagnosis, Teerthankar Mahaveer Medical College and Research Centre (TMMC&RC), Moradabad, Uttar Pradesh, India, for a period of 18 months (January 2020 to June 2021) and consisted of 110 patients with clinical suspicion of adnexal mass, who were evaluated on SIEMENS Acuson S 3000 scanner (from the total of 130 cases). Various morphological features of mass (size, laterality, consistency, echogenicity and internal contents) were assessed on Gray scale and vascularity was assessed on colour doppler Ultrasonography (USG). Subsequently, real time strain elastography (eSie touch) was performed to assess the tissue stiffness. Elasticity was indicated on a colour-coded elastogram map, with blue areas denoting hard tissue, green areas suggesting intermediate tissue, and red portions denoting soft tissues. The sonographic findings were compared with histopathological diagnosis. Sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were calculated for Gray scale sonography in combination with Doppler (conventional ultrasound techniques) and in conjunction with elastography. The Chi-square test was applied for comparing the frequency and p-value less than 0.05 was considered to be significant. Results: The mean age of study population was 36.35±14.82 years. On histopathology out of 110 patients, 95 (86.36%) had benign adnexal lesions and 15 (13.64%) had malignant adnexal lesions. The youngest patient was 16-year-old and eldest was 70 years and the mean age of the study population was 36.35 years. When conventional ultrasound technique was used alone for differentiating benign and malignant adnexal masses the sensitivity was 96.7%, specificity was 83%, PPV was 96.7% and NPV was 83% while on addition of sonoelastography the sensitivity increased to 98.9%, specificity increased to 93%, PPV increased to 98.9% and NPV increased to 93.7%. Conclusion: Conventional ultrasound techniques should be combined with sonoelastography in a diagnostic system to achieve better characterisation and differentiation of benign and malignant adnexal masses.

Summary: Background: There is a high burden of stroke, including recurrent stroke, in India. We aimed to assess the effect of a structured semi-interactive stroke prevention package in patients with subacute stroke to reduce recurrent strokes, myocardial infarction, and death. Methods: This was a multicentre, randomised, clinical trial conducted in 31 centres of the Indian Stroke Clinical Trial Network (INSTRuCT). Adult patients with first stroke and access to a mobile cellular device were randomly allocated (1:1) to intervention and control groups by the research coordinators at each centre using a central, in-house, web-based randomisation system. The participants and research coordinators at each centre were not masked to group assignment. The intervention group received regular short SMS messages and videos that promoted risk factor control and medication adherence and an educational workbook, in one of 12 languages, and the control group received standard care. The primary outcome was a composite of recurrent stroke, high-risk transient ischaemic attack, acute coronary syndrome, and death at 1 year. The outcome and safety analyses were done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03228979 and Clinical Trials Registry-India (CTRI/2017/09/009600) and was stopped for futility after interim analysis. Findings: Between April 28, 2018, and Nov 30, 2021, 5640 patients were assessed for eligibility. 4298 patients were randomised to the intervention group (n=2148) or control group (n=2150). 620 patients were not followed up at 6 months and a further 595 patients were not followed up at 1 year because the trial was stopped for futility after interim analysis. 45 patients were lost to follow-up before 1 year. Acknowledgment of receipt of the SMS messages and videos by the intervention group patients was low (17%). The primary outcome occurred in 119 (5·5%) of 2148 patients in the intervention group and 106 (4·9%) of 2150 patients in the control group (adjusted odds ratio 1·12; 95% CI 0·85–1·47; p=0·370). Among the secondary outcome measures, alcohol cessation and smoking cessation were higher in the intervention group than in the control group (alcohol cessation 231 [85%] of 272 in the intervention group vs 255 [78%] of 326 in the control group; p=0·036; smoking cessation 202 [83%] vs 206 [75%]; p=0·035). Medication compliance was better in the intervention group than in the control group (1406 [93·6%] of 1502 vs 1379 [89·8%] of 1536; p

Introduction: We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus platinum-based chemotherapy (pembrolizumab-combination) for NSCLC among patients in the phase 3 KEYNOTE-189 (ClinicalTrials.gov, NCT02578680; nonsquamous) and KEYNOTE-407 (ClinicalTrials.gov, NCT02775435; squamous) trials. Methods: This retrospective exploratory analysis evaluated prevalence of high tTMB and STK11, KEAP1, and KRAS mutations in patients enrolled in KEYNOTE-189 and KEYNOTE-407 and the relationship between these potential biomarkers and clinical outcomes. tTMB and STK11, KEAP1, and KRAS mutation status was assessed using whole-exome sequencing in patients with available tumor and matched normal DNA. The clinical utility of tTMB was assessed using a prespecified cutpoint of 175 mutations/exome. Results: Among patients with evaluable data from whole-exome sequencing for evaluation of tTMB (KEYNOTE-189, n = 293; KEYNOTE-407, n = 312) and matched normal DNA, no association was found between continuous tTMB score and overall survival (OS) or progression-free survival for pembrolizumab-combination (Wald test, one-sided p > 0.05) or placebo-combination (Wald test, two-sided p > 0.05) in patients with squamous or nonsquamous histology. Pembrolizumab-combination improved outcomes for patients with tTMB greater than or equal to 175 compared with tTMB less than 175 mutations/exome in KEYNOTE-189 (OS, hazard ratio = 0.64 [95% confidence interval (CI): 0.38‒1.07] and 0.64 [95% CI: 0.42‒0.97], respectively) and KEYNOTE-407 (OS, hazard ratio = 0.74 [95% CI: 0.50‒1.08 and 0.86 [95% CI: 0.57‒1.28], respectively) versus placebo-combination. Treatment outcomes were similar regardless of KEAP1, STK11, or KRAS mutation status. Conclusions: These findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the utility of tTMB, STK11, KEAP1, or KRAS mutation status as a biomarker for this regimen.

Abstract Reprogramming somatic cells to pluripotent stem cells has revolutionized the biomedical field by providing enormous hopes and opportunities for the regeneration of tissues and organs for transplantation. Using a small molecule cocktail of epigenetic modifiers and cell signalling inhibitors, a chemical-based easy and controllable technique for converting human somatic cells into chemically induced pluripotent stem cells was recently reported (Guan, Nature 605:325–31, 2022). This novel approach offers well-defined, safe, simple, easy, and clinical-grade manufacturing strategies for modifying the fate of human cells required for regenerative therapeutics.

Background: The salivary gland lesions constitute around 3–6% of all head-and-neck lesions and have always posed a diagnostic riddle for the cytopathologists around the world. Since the majority of these lesions need surgical excision, it is, therefore, important to diagnose these lesions with utmost precision to prevent over or under stage procedures. The recent adaption of Milan system of reporting aims to establish a uniform, accurate, and consensual reporting system which bridges the communication between the pathologists and the clinicians. Aims and Objectives: The current study aims to assess the diagnostic application of Milan system and aims to reclassify the lesions according to it. Materials and Methods: The current study was conducted at our institute during 1 year period. All salivary gland swellings presenting to the fine-needle aspiration cytology (FNAC) section during this period were included in the study. Along with this, records and slides of cases of salivary gland lesions were retrospectively assessed. All relevant data and radiologic findings were retrieved from the case records. FNAC was done using 23 G needle. The slides were stained with both Leishman and Papanicolaou stain wherever possible. Quantitative data were expressed as mean and standard deviation and percentages. All the 83 lesions were reclassified as per the Milan system. Histopathology was available in 42 cases. Inclusion criteria: All the samples of the patient having salivary gland lesion(s) whose FNAC were performed in the department of pathology. Statistical Analysis: Data were be entered into Microsoft Excel spreadsheets. For quantitative data, mean and standard deviation were calculated. For qualitative data, percentage and proportion were calculated. Sensitivity, specificity, and spearman correlation between FNAC and histopathology were calculated. P

Abstract Background Evidence for the health benefits of urban green space tends to stem from small, short-term quasi-experimental or cross-sectional observational research, whilst evidence from intervention studies is sparse. The development of an urban greenway (9 km running along 3 rivers) in Northern Ireland provided the opportunity to conduct a natural experiment. This study investigated the public health impact of the urban greenway on a range of physical activity, health, wellbeing, social, and perceptions of the environment outcomes. Methods A repeated cross-sectional household survey of adult residents (aged ≥16 years) who lived ≤1-mile radius of the greenway (intervention sample) and > 1-mile radius of the greenway (control sample) was conducted pre (2010/2011) and 6-months post implementation (2016/2017). We assessed changes in outcomes pre- and post-intervention follow-up including physical activity behaviour (primary outcome measure: Global Physical Activity Questionnaire), quality of life, mental wellbeing, social capital and perceptions of the built environment. Linear regression was used to calculate the mean difference between post-intervention and baseline measures adjusting for age, season, education, car ownership and deprivation. Multi-level models were fitted using a random intercept at the super output area (smallest geographical unit) to account for clustering within areas. The analyses were stratified by distance from the greenway and deprivation. We assessed change in the social patterning of outcomes over time using an ordered logit to make model-based outcome predictions across strata. Results The mean ages of intervention samples were 50.3 (SD 18.9) years at baseline (n = 1037) and 51.7 (SD 19.1) years at follow-up (n = 968). Post-intervention, 65% (adjusted OR 0.60, 95% CI 0.35 to 1.00) of residents who lived closest to the greenway (i.e., ≤400 m) and 60% (adjusted OR, 0.64 95% CI 0.41 to 0.99) who lived furthest from the greenway (i.e.,≥1200 m) met the physical activity guidelines - 68% of the intervention sample met the physical activity guidelines before the intervention. Residents in the most deprived quintiles had a similar reduction in physical activity behaviour as residents in less deprived quintiles. Quality of life at follow-up compared to baseline declined and this decline was significantly less than in the control area (adjusted differences in mean EQ5D: -11.0 (95% CI − 14.5 to − 7.4); − 30.5 (95% CI − 37.9 to − 23.2). Significant change in mental wellbeing was not observed despite improvements in some indicators of social capital. Positive perceptions of the local environment in relation to its attractiveness, traffic and safety increased. Conclusions Our findings illustrate the major challenge of evaluating complex urban interventions and the difficulty of capturing and measuring the network of potential variables that influence or hinder meaningful outcomes. The results indicate at this stage no intervention effect for improvements in population-level physical activity behaviour or mental wellbeing. However, they show some modest improvements for secondary outcomes including positive perceptions of the environment and social capital constructs. The public health impact of urban greenways may take a longer period of time to be realised and there is a need to improve evaluation methodology that captures the complex systems nature of urban regeneration.

Abstract Background: Tuberculosis (TB), a communicable disease, caused by Mycobacterium tuberculosis requires a simple, rapid test, which can be easily carried out in a laboratory. Unfortunately, despite a battery of investigations, no definite test is available till date. Adenosine deaminase (ADA), a biochemical marker has been proposed as a useful surrogate marker for TB as its levels can be measured in body fluids. Methods: A one-and-a-half-year prospective study of 154 cases presenting with lymphadenitis from January 2019 to June 2020 was undertaken. Using cytology, lymphadenitis subjects were divided into two groups: Tubercular (104 patients) as a case group and Reactive (50 patients) as a control group. All cases were followed by serum ADA assay by colorimetric method. Nonparametric tests were performed to compare the two groups. Results: The mean age of the participants was 28.99 ± 13.26 years with a F:M ratio of 1.81:1. Involvement of cervical lymph nodes was most frequent (89.42% cases). The mean S.ADA level for tubercular and reactive lymphadenitis was 41.71 ± 11.53 U/L and 21.16 ± 4.16 U/L, respectively (P-value < 0.05). The cut-off value calculated was 32.6 U/L. The sensitivity, specificity, PPV, NPV, and accuracy were calculated as 79.81%, 100%, 100%, 70.42%, and 86.36%, respectively. Conclusion: A statistically significant increase was found in serum ADA levels in tubercular lymphadenitis cases compared to reactive lymphadenitis. Hence, it can be used as an adjunct to FNAC and is a fairly sensitive and specific test. Since it is difficult to always demonstrate AFB in FNAC smears, ADA can be helpful in establishing a definite diagnosis despite smear negativity.

Abstract Hepatocytes store triglycerides (TGs) in the form of lipid droplets (LDs), which are increased in hepatosteatosis. The regulation of hepatic LDs is poorly understood and new therapies to reduce hepatosteatosis are needed. We performed a siRNA kinase and phosphatase screen in HuH‐7 cells using high‐content automated imaging of LDs. Changes in accumulated lipids were quantified with developed pipeline that measures intensity, area, and number of LDs. Selected “hits,” which reduced lipid accumulation, were further validated with other lipid and expression assays. Among several siRNAs that resulted in significantly reduced LDs, one was targeted to the nuclear adapter protein, transformation/transcription domain‐associated protein (TRRAP). Knockdown of TRRAP reduced triglyceride accumulation in HuH‐7 hepatocytes, in part by reducing C/EBPα‐mediated de novo synthesis of TGs. These findings implicate TRRAP as a novel regulator of hepatic TG metabolism and nominate it as a potential drug target for hepatosteatosis.

Introduction: Metaplastic Carcinoma of Breast (MCB) is a rare heterogeneous neoplasm characterised by a mixture of adenocarcinoma with dominant areas of spindle cells, squamous and other mesenchymal differentiation. The reported incidence is 0.2% of all breast cancers. Aim: To study the clinicopathological presentation, pathologic features and differential diagnosis of MB. Materials and Methods: This retrospective cross-sectional descriptive study included 10 cases of MCB who underwent mastectomy and biopsies at BPS GMC Khanpur Kalan, Sonipat, Haryana, India from March 2013 to February 2020. Data were analysed by Microsoft Office Excel Datasheet 2019. Results: Out of 10 cases, five cases were MCB Not Otherwise Specified (NOS) type, four cases were MCB with mesenchymal differentiation and one case showed rhabdomyosarcomatous differentiation. The right breast was involved in nine cases. The mean size of tumour was 8 cm with range of 3 to 16 cm. Five patients were treated by modified radical mastectomy and axillary dissection, four patients had lumpectomy and one patient underwent mastectomy. Half of the patients were below 40 years with the mean age being 36.8 years and range of 21-60 years. On Immunohistochemistry (IHC), 90% (9/10) cases were triple negative. Conclusion: The MCB, although rare has to be diagnosed and excised at the earliest as the prognosis is predicted to be worse similar to other triple negative breast carcinomas. Ductal Carcinoma in Situ (DCIS) at the tumour periphery and co-expression of vimentin and cytokeratin would help to clinch the diagnosis in difficult situations.

Deficiency of the small Maf proteins Mafg and Mafk cause multiple defects, namely, progressive neuronal degeneration, cataract, thrombocytopenia and mid-gestational/perinatal lethality. Previous data shows Mafg−/−:Mafk+/- compound knockout (KO) mice exhibit cataracts age 4-months onward. Strikingly, Mafg−/−:Mafk−/− double KO mice develop lens defects significantly early in life, during embryogenesis, but the pathobiology of these defects is unknown, and is addressed here. At embryonic day (E)16.5, the epithelium of lens in Mafg−/−:Mafk−/− animals appears abnormally multilayered as demonstrated by E-cadherin and nuclear staining. Additionally, Mafg−/−:Mafk−/− lenses exhibit abnormal distribution of F-actin near the “fulcrum” region where epithelial cells undergo apical constriction prior to elongation and reorientation as early differentiating fiber cells. To identify the underlying molecular changes, we performed high-throughput RNA-sequencing of E16.5 Mafg−/−:Mafk−/− lenses and identified a cohort of differentially expressed genes that were further prioritized using stringent filtering criteria and validated by RT-qPCR. Several key factors associated with the cytoskeleton, cell cycle or extracellular matrix (e.g., Cdk1, Cdkn1c, Camsap1, Col3a1, Map3k12, Sipa1l1) were mis-expressed in Mafg−/−:Mafk−/− lenses. Further, the congenital cataract-linked extracellular matrix peroxidase Pxdn was significantly overexpressed in Mafg−/−:Mafk−/− lenses, which may cause abnormal cell morphology. These data also identified the ephrin signaling receptor Epha5 to be reduced in Mafg−/−:Mafk−/− lenses. This likely contributes to the Mafg−/−:Mafk−/− multilayered lens epithelium pathology, as loss of an ephrin ligand, Efna5 (ephrin-A5), causes similar lens defects. Together, these findings uncover a novel early function of Mafg and Mafk in lens development and identify their new downstream regulatory relationships with key cellular factors.

Large animal studies of long-term ischemia reperfusion are hampered by the use of immunosuppressive drugs to inhibit the influence of the allogeneic response. In small animals, this can be controlled by using inbred strains of the animal. For obvious reasons, this is not possible in large animals such as pigs. Since studies in pigs usually are the last step before first-in-man studies, this remains a problem trying to resemble a clinical situation. In the following short paper, we describe a novel auto kidney transplantation model that can be used for long term ischemia reperfusion studies. We also suggest a control setting to balance out the possible influence of an increased surgical trauma.

Abstract Background: Tuberculosis (TB) is a global health problem and the second most common infectious cause of death. High-resolution computed tomography (HRCT) is far more superior to chest radiography as well as conventional CT for analyzing the pulmonary parenchyma. This study aimed to evaluate the role of HRCT in pulmonary tuberculosis (PTB) with respect to disease activity and complication after anti-tubercular therapy (ATT). Methods: This prospective observational study was conducted in the Department of Radiodiagnosis, Teerthanker Mahaveer Medical College & Research Centre (TMMC&RC) for a period of 1.5 years. A total of 50 cases of newly diagnosed TB were included in the study and a standard six-month ATT was given to the patients. Pulmonary involvement was evaluated by HRCT (128 slice multi-detector PHILIPS INGENUITY CT scanner), twice for each patient (first scan after diagnosis and second after treatment completion). The acquired HRCT images were reconstructed on a high-resolution lung algorithm and parenchymal, bronchial, and extra parenchymal findings were recorded systematically. Results: Out of the 50 patients, 5 died within two months of the initiation of treatment and four were lost to follow-up. Thus, post treatment follow-up sample size was reduced to 41 patients. Ill-defined nodules (96%), tree-in-bud pattern (74%), consolidation (86%), cavitary lesions (98%), and ground glass opacities (58%) were the main imaging features of active cases of TB on HRCT. Resolution to thin-walled cavitary lesions (36.5%), bronchiectasis (41.5%), and fibrotic (parenchymal) bands (66%) were common complications or sequelae which were observed after completion of treatment. Conclusion: HRCT thorax is a sensitive modality for evaluation of parenchymal and airway manifestations in cases of PTB and can aid in differentiation of active disease from healed disease. It allows early identification of post-treatment complications and sequelae in patients of PTB.

The genetic basis of cataract is not well understood. Here, the authors perform a genome-wide association multiethnic meta-analysis of cataract, finding 37 new loci and replicating known and new loci. They additionally perform sex-specific analyses, identifying new associations specific to women.

Defects in the development of the ocular lens can cause congenital cataracts. To understand the various etiologies of congenital cataracts, it is important to characterize the genes linked to this developmental defect and to define their downstream pathways that are relevant to lens biology and pathology. Deficiency or alteration of several RNA-binding proteins, including the conserved RBP Celf1 (CUGBP Elav-like family member 1), has been described to cause lens defects and early onset cataracts in animal models and/or humans. Celf1 is involved in various aspects of post-transcriptional gene expression control, including regulation of mRNA stability/decay, alternative splicing and translation. Celf1 germline knockout mice and lens conditional knockout (Celf1cKO) mice develop fully penetrant cataracts in early postnatal stages. To define the genome-level changes in RNA transcripts that result from Celf1 deficiency, we performed high-throughput RNA-sequencing of Celf1cKO mouse lenses at postnatal day (P) 0. Celf1cKO lenses exhibit 987 differentially expressed genes (DEGs) at cut-offs of >1.0 log2 counts per million (CPM), ≥±0.58 log2 fold-change and Celf1cKO lenses. The DEGs were subjected to various downstream analyses including iSyTE lens enriched-expression, presence in Cat-map, and gene ontology (GO) and representation of regulatory pathways. Further, a comparative analysis was done with previously generated microarray datasets on Celf1cKO lenses P0 and P6. Together, these analyses validated and prioritized several key genes mis-expressed in Celf1cKO lenses that are relevant to lens biology, including known cataract-linked genes (e.g., Cryab, Cryba2, Cryba4, Crybb1, Crybb2, Cryga, Crygb, Crygc, Crygd, Cryge, Crygf, Dnase2b, Bfsp1, Gja3, Pxdn, Sparc, Tdrd7, etc.) as well as novel candidates (e.g., Ell2 and Prdm16). Together, these data have defined the alterations in lens transcriptome caused by Celf1 deficiency, in turn uncovering downstream genes and pathways (e.g., structural constituents of eye lenses, lens fiber cell differentiation, etc.) associated with lens development and early-onset cataracts.

World of technology provides everyone with a great outlet to give their opinion, using social media like Twitter and other platforms. This paper employs machine learning methods for text analysis to obtain sentiments of reviews by the people on twitter. Sentiment analysis of the text uses Natural language processing, a machine learning technique to tell the orientation of opinion of a piece of text. This system extracts attributes from the piece of writing such as a) The polarity of text, whether the speaker is criticizing or appreciating, b) The topic of discussion, subject of the text. A comparison of the work done so far on sentiment analysis on tweets has been shown. A detailed discussion on feature extraction and feature representation is provided. Comparison of six classifiers: Naïve Bayes, Decision Tree, Logistic Regression, Support Vector Machine, XGBoost and Random Forest, based on their accuracy depending upon type of feature, is shown. Moreover, this paper also provides sentiment analysis of political views and public opinion on lockdown in India. Tweets with ‘#lockdown’ are analysed for their sentiment categorically and a schematic analysis is shown.

Introduction: The pandemic of coronavirus disease 19 (COVID-19) has engulfed most of the world and has constrained already overburdened health care systems, especially in developing countries. There is an urgent need of a rapid investigation to assess disease severity in suspected patients and the baseline chest radiograph may serve as a triage tool. The aim is to correlate chest radiographic findings and coagulation abnormality with disease severity in COVID-19 positive patients. Materials and Methods: This was a retrospective observational study which comprised 100 reverse transcription-polymerase chain reaction positive COVID-19 cases which were clinically stratified into three groups based on clinical parameters. Baseline chest radiograph and serum D-dimer levels at the time of admission for all the patients were reviewed. A radiographic severity score (Radiographic Assessment of Lung Edema [RALE]) was determined for all four quadrants of both lungs. The scores of each quadrant were added to yield the final severity score. Results: Baseline chest radiograph was abnormal in 75% of patients, whereas 25% of patients had normal chest radiograph. Most frequent radiographic abnormality was ground-glass opacity (GGO) (n = 31, 41.3%) followed by lung consolidation (n = 19, 25.3%), while 7 patients (9.3%) had both GGO and consolidation. The most common pattern of disease distribution was bilateral 34 (57.7%) and peripheral in 58 (69%). The optimal cut-off RALE score for identifying symptomatic patients was ≥3 (area under the curve [AUC] 0.760) and for identifying severe cases was ≥7 (AUC 0.870). Similarly, the optimal cut-off D-Dimer value for identifying symptomatic patients was ≥567 ng/ml (AUC 0.836) and for diagnosing severe disease was ≥1200 ng/ml (AUC 0.99). Conclusions: Radiographic RALE score and elevated serum D-Dimer levels correlate strongly with disease severity in COVID-19 patients and can be utilized for early identification of high-risk cases which can ultimately reduce mortality and morbidity.

In this paper, we aim to study the interrelationship between social spending, economic growth, and income inequality in developing countries from the year 1990 to 2013. We observed that all the categories of social spending produced a significant reduction in income inequality. Further, the impact of health and education spending on economic growth is significant, and that of social protection is insignificant. This indicates that both health and education spending can break the trade-off between equity and efficiency, that is, it can lead to both growth and progressive distributional change. However, given the importance of social welfare measures in reducing income inequality, developing countries need to focus on active social spending like labor market reforms that can increase gross domestic product growth rate and simultaneously reduce income inequality.

This paper fundamentally looks at the novel concept of Smart Beta investing in constructing a more efficient and well-diversified alternative investment. Smart beta has been a popular investment philosophy, although emerging countries have been slower to adopt and execute it. In this way, the study investigates the existence, performance, and robustness of smart beta strategies in a divergent financial market. Moreover, it is an initial attempt to integrate the framework of stock selection and stock weighting to construct and test smart beta strategies against the traditional Indian market benchmark (S&P BSE 500). The findings show that smart beta investing results in a better risk-return profile on an absolute and risk-adjusted basis. Furthermore, the results demonstrate the consistency and robustness of smart beta strategies in different market conditions and display their outperformance even in bearish market conditions.

Background and aims Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India (SPRINT India) is a complex intervention delivered across 30 centres in 16 Indian states. The study delivers intervention in 12 languages in the form of workbook, videos and short messaging using cellular device and internet as a tool. Objectives of process evaluation are to assess whether trial was implemented as planned (fidelity and dose); whether, how and why the intervention is effective by looking at the stakeholders’ experiences (effectiveness); to assess reach of intervention in population (reach); how intervention fits into treatment plan to cause behavioural change when adopted (adoption); usefulness for target population and bring behaviour change (maintenance). Methods SPRINT India process evaluation is a prospective, multicentre study conducted with mixed-methods approach. Sample size of centres and stakeholders will be selected by maximum variance purposive sampling strategy. Centres will be stratified primarily for representing the 11 regional language in which the intervention is delivered. Qualitative data will comprise of interviews of patients, care givers and health professionals at these centres using semi structured interview guide. Quantitative data will comprise of all the randomised patients. Process evaluation framework is based on Realist and RE-AIM evaluation models presented according to Medical Research Council’s guidance. The four sections of the framework are context, trial implementation, mechanisms of impact and trial outcomes. Results Interviews of approximately 100 stakeholders and focus group interviews of health professionals and SPRINT India study central coordinating staff will be conducted. Analysis will be done using triangulation methodology. It will incorporate use of both quantitative and qualitative data, data collection techniques, data sources, evaluation models, stakeholders and researchers. Conclusions Process evaluation will identify efficacious factors in intervention package and consolidate use of secondary stroke semi-interactive stroke prevention package into practice and policy to prevent recurrent stroke.

During the past decade, novel Deep Learning (DL) algorithms, workloads and hardware have been developed to tackle a wide range of problems. Despite the advances in workload and hardware ecosystems, the programming methodology of DL systems is stagnant. DL workloads leverage either highly-optimized, yet platform-specific and inflexible kernels from DL libraries, or in the case of novel operators, reference implementations are built via DL framework primitives with underwhelming performance. This work introduces the Tensor Processing Primitives (TPP), a programming abstraction striving for efficient, portable implementation of DL workloads with high-productivity. TPPs define a compact, yet versatile set of 2D-tensor operators [or a virtual Tensor Instruction Set Architecture (ISA)], which subsequently can be utilized as building-blocks to construct complex operators on high-dimensional tensors. The TPP specification is platform-agnostic, thus, code expressed via TPPs is portable, whereas the TPP implementation is highly-optimized and platform-specific. We demonstrate the efficacy and viability of our approach using standalone kernels and end-to-end DL & High Performance Computing (HPC) workloads expressed entirely via TPPs that outperform state-of-the-art implementations on multiple platforms.

Introduction: Identification of the nature of lymph nodes is one of the most important parameters for diagnosis in any oncological setting. The lymph nodes help in staging and this directly affects the prognostic outcome and treatment decision. Ultrasound is the preferred imaging method for distinguishing between benign and malignant superficial lymph nodes given ease of availability and its low cost. However, there is no reliable and definitive sonographic criterion in ultrasound to categorise lymph nodes as benign or malignant. Aim: To evaluate the role of sonography and sonoelastography in characterisation of cervical lymphadenopathy and to associate the imaging findings with cytopathology. Materials and Methods: This was a prospective cohort study, conducted over a period of one year in Teerthanker Mahaveer Medical College and Research Centre, Moradabad, Uttar Pradesh, India, constituting a total of 60 patients with enlarged cervical lymph nodes and evaluated on B-mode ultrasound and elastography in the present study. The ultrasonography was performed using either Acuson S3000 ultrasound system (Siemens Medical Solutions, Mountain View, CA) with a 4 to 9 MHz linear transducer for conventional sonography and Acoustic Radiation Force Impulse (ARFI) imaging. Results of radiological findings were tabulated, evaluated and collated with pathological findings. Results: ARFI imaging displayed a sensitivity and specificity of 80% and 97.5% respectively with a Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 94.1% and 90.7% respectively in distinguishing malignant from benign cervical lymphadenopathy with the diagnostic accuracy being 91.67%. Using Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.925, a cut-off value for shear wave velocity of 2.98 m/s was obtained. Conclusion: ARFI is a novel technique which can be used to characterise the nature of cervical lymph nodes. Present study demonstrated high diagnostic accuracy (91.67%) in comparison with histopathological findings, ARFI elastography may help in distinction of benign from malignant nodes in adjunct to the gray scale.