Accuracy of Femoral Component External Rotation with all Burr Robotic Assisted Total Knee Arthroplasty.

Introduction: External rotation of femoral component is controversial in Total knee arthroplasty (TKA). The aim of our study is to assess the precision of femoral component external rotation in Robotic Assisted All Burr TKA. Materials and methods: This is a prospective study of 30 cases who underwent All Burr Robotic Assisted TKA at our institute, RNH hospital. Inclusion criteria were primary and secondary osteoarthritis of the knee and exclusion criteria were revision and partial knee replacement. On Navio robotic system femoral external rotation was planned as per medio-lateral flexion gap balancing and executed with burr. Post-operative CT scan was done in all patients to assess intra-operative planned femoral external rotation. Results: Out of 30 cases, 20 were female and 10 were male. Mean age was 66.06±7.43 years. On Navio the planned external rotation of femoral component was 2.86±1.16. Average of femoral component external rotation on postoperative CT scan was 3.11±1.16. The mean deviation of achieved femoral component external rotation from planned external rotation was -0.24 to ±0.28. Only 37% patients required 3° external rotation. Correlation between planned and achieved femoral component external rotation was significant, positive and very strong as indicated by r=0.97 and p=0.0001. Conclusion: All Burr Robotic Assisted TKA provides near accurate femoral component external rotation as planned on Navio with deviation of less than 0.3° between planned and achieved external rotation.

Novel insights into drought-induced regulation of ribosomal genes through DNA methylation in chickpea.

Modifications within the epigenome of an organism in response to external environmental conditions allow it to withstand the hostile stress factors. Drought in chickpea is a severely limiting abiotic stress factor which is known to cause huge yield loss. To analyse the methylome of chickpea in response to drought stress conditions and how it affects gene expression, we performed whole-genome bisulfite sequencing (WGBS) and RNA-seq of two chickpea genotypes which contrast for drought tolerance. It was observed that the mCHH was most variable under drought stress and the drought tolerant (DT) genotype exhibited substantial genome-wide hypomethylation as compared to the drought sensitive (DS) genotype. Specifically, there was substantial difference in gene expression and methylation for the ribosomal genes for the tolerant and sensitive genotypes. The differential expression of these genes was in complete agreement with earlier reported transcriptomes in chickpea. Many of these genes were hypomethylated (q < 0.01) and downregulated under drought stress (p < 0.01) in the sensitive genotype. The gene RPS6 (ribosomal protein small subunit) was found to be downregulated and hypomethylated in the drought sensitive genotype which could possibly lead to reduced ribosomal biosynthesis. This study provides novel insights into regulation of drought-responsive genes in chickpea.

DNA methylation: an emerging paradigm of gene regulation under drought stress in plants.

Drought is an enormous threat to global crop production. In order to ensure food security for the burgeoning population, we must develop drought tolerant crop varieties. This necessitates the identification of drought-responsive genes and understanding the mechanisms involved in their regulation. DNA methylation is a widely studied mechanism of epigenetic regulation of gene expression, which is known to play vital role in conferring tolerance to various biotic and abiotic stress factors. The recent advances in next-generation sequencing (NGS) technologies, has allowed unprecedented access to genome-wide methylation marks, with single base resolution. The most important roles of DNA methylation have been studied in terms of gene body methylation (gbM), which is associated with regulation of both transcript abundance and its stability. The availability of mutants for the various genes encoding enzymes involved in methylation of DNA has allowed ascertainment of the biological significance of methylation. Even though a vast number of reports have emerged in the recent past, where both genome-wide methylation landscape and locus specific changes in DNA methylation have been studied, a conclusive picture with regards to the biological role of DNA methylation is still lacking. Compounding this, is the lack of sufficient evidence supporting the heritability of these epigenetic changes. Amongst the various epigenetic variations, the DNA methylation changes are observed to be the most stable. This review describes the drought-induced changes in DNA methylation identified across different plant species. We also briefly describe the stress memory contributed by these changes. The identification of heritable, drought-induced methylation marks would broaden the scope of crop improvement in the future.

Evidence of a Hardening in the Cosmic Ray Proton Spectrum at around 166 TeV Observed by the GRAPES-3 Experiment.

We present the measurement of the cosmic ray proton spectrum from 50 TeV to 1.3 PeV using 7.81×10^{6} extensive air shower events recorded by the ground-based GRAPES-3 experiment between 1 January 2014 and 26 October 2015 with a live time of 460 day. Our measurements provide an overlap with direct observations by satellite and balloon-based experiments. The electromagnetic and muon components in the shower were measured by a dense array of plastic scintillator detectors and a tracking muon telescope, respectively. The relative composition of the proton primary from the air shower data containing all primary particles was extracted using the multiplicity distribution of muons which is a sensitive observable for mass composition. The observed proton spectrum suggests a spectral hardening at ∼166 TeV and disfavors a single power law description of the spectrum up to the Knee energy (∼3 PeV).

Anther-derived microspore embryogenesis in pepper hybrids orobelle and Bomby.

BACKGROUND: Traditional breeding methods have long been employed worldwide for the evaluation and development of pepper cultivars. However, these methods necessitate multiple generations of screening, line development, evaluation, recognition, and crossing to obtain highly homozygous lines. In contrast, in vitro anther-derived microspore culture represents a rapid method to generate homozygous lines within a single generation. In the present study, we have optimized a protocol for microspore embryogenesis from anther cultures of pepper hybrids Orobelle and Bomby. RESULTS: We achieved early and successful embryo formation from both genotypes by subjecting the buds to a cold pretreatment at 4 °C for 4 days. Our optimized culture medium, comprised of MS medium supplemented with 4 mg/L NAA, 1 mg/L BAP, 0.25% activated charcoal, 2.6 g/L gelrite, 30 g/L sucrose, and 15 mg/L silver nitrate, exhibited the highest efficiency in embryo formation (1.85% and 1.46%) for Orobelle and Bomby, respectively. Furthermore, successful plant regeneration from the anther derived microspore embryos was accomplished using half-strength MS medium fortified with 2% sucrose and 0.1 mg/L 6-benzylaminopurine (BA), solidified with 2.6 g/L gelrite. The ploidy status of the microspore-derived plantlets was analyzed using flow cytometry technique. Notably, the haploid plants exhibited distinct characteristics such as reduced plant height, leaf length, leaf width, and shorter internode length when compared to their diploid counterparts derived from seeds. CONCLUSION: Our findings highlight the potential of anther culture and microspore embryogenesis as an advanced method for accelerating pepper breeding programs, enabling the rapid production of superior homozygous lines.

Growth Assessment of Under-Five Children of Employed and Unemployed Mothers of Etawah District, Uttar Pradesh: A Cross-Sectional Study.

Introduction The under-five age group is crucial because the health profile of this age group will have a huge effect on the future development of the nation. Early infancy is marked by several distinct developmental characteristics. Progress in each domain of childhood development is used to track a child's development. Objectives The objectives of the present study were to assess and compare the growth of under-five children of employed and unemployed mothers in the Etawah District of Uttar Pradesh, India. Material and methods A community-based cross-sectional survey was carried out in Etawah district's urban and rural areas between January 2021 and June 2022. A total of 200 mothers with children under the age of five were recruited using the purposive sampling method. To gather pertinent information, a semi-structured, pre-tested, interviewer-administered questionnaire was used. Results In the present study on the comparison of the growth of children among employed and unemployed mothers, it shows that 48 children (50.5%) with a weight between 10.5 and 15 kg were of employed mothers, while 52 children weighing less than 10.5kg were of unemployed mothers (p<0.001). Forty-four children (57.1%) with a chest circumference of more than 48 cm were of employed mothers, while 26 children (78.8%) with a chest circumference of less than 45 cm were of unemployed mothers (p = 0.001). Conclusion The present study indicates that statistically significant differences were found in age-appropriate gain in weight and chest circumference, which was higher among the children of employed mothers in comparison to children of unemployed mothers. There was no statistically significant difference in age-appropriate gain in height, head circumference, or mid-upper arm circumference among the children of employed mothers and unemployed mothers.

Unravelling the due importance of pseudogenes and their resurrection in plants.

The complexities of a genome are underpinned to the vast expanses of the intergenic region, which constitutes ∼97-98% of the genome. This region is essentially composed of what is colloquially referred to as the "junk DNA" and is composed of various elements like transposons, repeats, pseudogenes, etc. The latter have long been considered as dead elements merely contributing to transcriptional noise in the genome. Many studies now describe the previously unknown regulatory functions of these genes. Recent advances in the Next-generation sequencing (NGS) technologies have allowed unprecedented access to these regions. With the availability of whole genome sequences of more than 788 different plant species in past 20 years, genome annotation has become feasible like never before. Different bioinformatic pipelines are available for the identification of pseudogenes. However, still little is known about their biological functions. The functional validation of these genes remains challenging and research in this area is still in infancy, particularly in plants. CRISPR/Cas-based genome editing could provide solutions to understand the biological roles of these genes by allowing creation of precise edits within these genes. The possibility of pseudogene reactivation or resurrection as has been demonstrated in a few studies might open new avenues of genetic manipulation to yield a desirable phenotype. This review aims at comprehensively summarizing the progress made with regards to the identification of pseudogenes and understanding their biological functions in plants.

Genetic mapping of quantitative trait loci associated with drought tolerance in chickpea (Cicer arietinum L.).

Elucidation of the genetic basis of drought tolerance is vital for genomics-assisted breeding of drought tolerant crop varieties. Here, we used genotyping-by-sequencing (GBS) to identify single nucleotide polymorphisms (SNPs) in recombinant inbred lines (RILs) derived from a cross between a drought tolerant chickpea variety, Pusa 362 and a drought sensitive variety, SBD 377. The GBS identified a total of 35,502 SNPs and subsequent filtering of these resulted in 3237 high-quality SNPs included in the eight linkage groups. Fifty-one percent of these SNPs were located in the genic regions distributed throughout the genome. The high density linkage map has total map length of 1069 cm with an average marker interval of 0.33 cm. The linkage map was used to identify 9 robust and consistent QTLs for four drought related traits viz. membrane stability index, relative water content, seed weight and yield under drought, with percent variance explained within the range of 6.29%-90.68% and LOD scores of 2.64 to 6.38, which were located on five of the eight linkage groups. A genomic region on LG 7 harbors quantitative trait loci (QTLs) explaining > 90% phenotypic variance for membrane stability index, and > 10% PVE for yield. This study also provides the first report of major QTLs for physiological traits such as membrane stability index and relative water content for drought stress in chickpea. A total of 369 putative candidate genes were identified in the 6.6 Mb genomic region spanning these QTLs. In-silico expression profiling based on the available transcriptome data revealed that 326 of these genes were differentially expressed under drought stress. KEGG analysis resulted in reduction of candidate genes from 369 to 99, revealing enrichment in various signaling pathways. Haplotype analysis confirmed 5 QTLs among the initially identified 9 QTLs. Two QTLs, qRWC1.1 and qYLD7.1, were chosen based on high SNP density. Candidate gene-based analysis revealed distinct haplotypes in qYLD7.1 associated with significant phenotypic differences, potentially linked to pathways for secondary metabolite biosynthesis. These identified candidate genes bolster defenses through flavonoids and phenylalanine-derived compounds, aiding UV protection, pathogen resistance, and plant structure.The study provides novel genomic regions and candidate genes which can be utilized in genomics-assisted breeding of superior drought tolerant chickpea cultivars.

Enhanced Thermoelectric Efficiency in P-Type Mg3Sb2: Role of Monovalent Atoms Codoping at Mg sites.

Due to natural abundance, low cost, and compatibility with sustainable green technology, Mg3Sb2-based Zintl compounds are comprehensively explored as potential thermoelectric materials for near-room temperature applications. The effective use of these materials in thermoelectric devices requires both p and n-type Mg3Sb2 having comparable thermoelectric efficiency. However, p-type Mg3Sb2 has inferior thermoelectric efficiency efficiency compared to its n-type counterpart due to low electrical conductivity (∼103Sm-1). Here, we show that codoping of monovalent atoms (Li-Ag, and Na-Ag) at the Mg site of Mg3Sb2 produces a synergistic effect and boosts the electrical conductivity, which enhances the thermoelectric properties of p-type Mg3Sb2. While, Ag prefers to occupy the Mg2 site, Li and Na are favorable at the Mg1 site of Mg3Sb2 lattice. Compared to Li-Ag codoping, Na-Ag codoping in Mg3Sb2 is found to be more effective for increasing the charge carrier concentration and significantly augmenting the electrical conductivity. The dominance of the three-phonon scattering mechanism in Li and Li-Ag doped Mg3Sb2 and the four-phonon scattering process for the Na and Na-Ag doped Mg3Sb2 are confirmed. Due to the simultaneous increase in electrical conductivity and decrease in thermal conductivity, the zT value ∼0.8 at 675 K achieved for Mg2.975Na0.02Ag0.005Sb2 is the highest value among p-type Mg3Sb2. Our work shows a constructive approach to enhance the zT of p-type Mg3Sb2 via monovalent atoms codoping at the Mg sites.

Validation of satisfaction questionnaire for services provided in the labour rooms of government health facilities.

INTRODUCTION AND OBJECTIVES: Using the assessment of satisfaction of patients of labour room services, the caregiver or policymakers can identify the gaps in the implemented programmes and health policies. This study was aimed to design a valid and reliable satisfaction questionnaire that will help in identifying the aspects of gaps that need improvement. METHODS: A facility and community-based observational cross-sectional study was conducted in the district of western Uttar Pradesh (India) between January 2019 and August 2020. Validation of the structured questionnaire with 34 dichotomous questions categorized under five subscales was performed by evaluating its validity and reliability. A total of 380 beneficiaries were selected from 48 government health facilities. RESULTS: The calculated Content validity index was calculated to be 9.5 which was adequate as per the guidelines. The reliability analysis of the questionnaire showed that the internal consistency was high with an overall Cronbach's alpha of 0.710. The variation in Cronbach's alpha on the elimination of any question from the questionnaire ranged from 0.676 to 0.767. The mean patient satisfaction score in the total surveyed population was 24.39±4.684 (total score=34) and there was a greater variation in the satisfaction score of infrastructure when compared with other subscales. CONCLUSION: The findings from this study support the reliability and validity of the patient satisfaction questionnaire as it is capable of evaluating the satisfaction in terms of delivery services provided in labour rooms as a whole.

Genome-wide identification, in silico characterization and expression analysis of the RNA helicase gene family in chickpea (C. arietinum L.).

The RNA helicases are an important class of enzymes which are known to influence almost every aspect of RNA metabolism. The majority of RNA helicases belong to the SF2 (superfamily 2) superfamily, members of which are further categorized into three separate subfamilies i.e., the DEAD, DEAH and DExD/H-box subfamilies. In chickpea, these RNA helicases have not been characterized until now. A genome-wide analysis across the chickpea genome led to the identification of a total of 150 RNA helicase genes which included 50 DEAD, 33 DEAH and 67 DExD/H-box genes. These were distributed across all the eight chromosomes, with highest number on chromosome 4 (26) and least on chromosome 8 (8). Gene duplication analysis resulted in identification of 15 paralogous gene pairs with Ka/Ks values < 1, indicating towards the genes being under purifying selection during the course of evolution. The promoter regions of the RNA helicase genes were enriched in cis-acting elements like the light and ABA-responsive elements. The drought responsiveness of the genes was analysed by studying the expression profiles of few of these genes, in two different genotypes, the cultivated variety ICC 8261 (kabuli, C. arietinum) and the wild accession ILWC 292 (C. reticulatum), through qRT-PCR. These genotypes were selected based on their drought responsiveness in a field experiment, where it was observed that the percentage (%) reduction in relative water content (RWC) and membrane stability index (MSI) for the drought stressed plants after withholding water for 24 days, over the control or well-watered plants, was least for both the genotypes. The genes CaDEAD50 and CaDExD/H66 were identified as drought-responsive RNA helicase genes in chickpea. The protein encoded by the CaDExD/H66 gene shares a high degree of homology with one of the CLSY (CLASSY) proteins of A. thaliana. We hypothesize that this gene could possibly be involved in regulation of DNA methylation levels in chickpea by regulating siRNA production, in conjunction with other proteins like the Argonaute, RNA dependent RNA polymerases and Dicer-like proteins.

Genome-wide identification and expression analysis of the GRAS gene family in response to drought stress in chickpea (Cicer arietinum L.).

The GRAS (gibberellic acid insensitive, repressor of GAI and scarecrow) transcription factors (TFs) regulate diverse biological processes involved in plant growth and development. These TFs are also known to regulate gene expression in response to various abiotic stress factors like cold, drought, etc. In chickpea one of the most devastating abiotic stress factors is terminal drought. The GRAS TF family has not been characterized in chickpea (Cicer arietinum L.) until now. In this study, we report 46 GRAS TF genes (CaGRAS genes) in the chickpea genome. The CaGRAS proteins were categorized into nine subfamilies based on their phylogenetic relationship with known GRAS members of Arabidopsis and soybean. The PAT subfamily was the largest consisting of ten CaGRAS members whereas the LAS subfamily was the smallest with only one member. Gene duplication analysis revealed that segmental duplication was the primary reason for the expansion of this gene family within the chickpea genome. The gene expression levels of CaGRAS genes were analysed using two different chickpea varieties contrasting for drought tolerance trait, i.e., ICC 4958 (drought tolerant) and ICC 1882 (drought sensitive). On exposure to drought stress, the two chickpea genotypes, exhibited differential drought response, which was quantified and estimated in terms of differences in leaf relative water content (RWC). The well-watered or control plants of the drought tolerant variety were able to maintain a higher leaf RWC by the end of the drought stress period, whereas the control plants of the drought sensitive variety continued to show a decline in leaf RWC. The two genotypes also differed in their root morphologies, under well-watered and drought stress conditions. The gene expression analysis revealed a potential role of PAT, SCR, SCL3 and SHR GRAS members in the regulation of differential response to drought, in the root tissues, for both the genotypes. CaGRAS 12 (SCR) was identified as a drought-responsive GRAS TF gene, which could serve as a potential candidate gene for utilization in developing chickpea varieties with improved drought tolerance. This study demonstrates the drought-responsive expression of CaGRAS genes in chickpea and also describes the morpho-physiological response of chickpea plants to drought stress conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03104-z.

Nivolumab induced pulmonary sarcoid-like granulomas with a concurrent pleural schwannoma: A pathologic-radiologic correlation of a rare condition mimicking metastatic melanoma.

Nivolumab is an anti-PD-1 antibody. The mechanism of action of nivolumab is inhibition of binding between PD-1 and PD-1 ligand. This causes activation of antigen-specific T cells that were previously unresponsive to cancer cells. This unique mechanism of action attributes the widespread use of nivolumab for the treatment of a variety of neoplastic conditions. On the other hand, this mode of action is associated with adverse effects as well. Schwannoma, also called neurilemmoma, is a benign peripheral nerve sheath tumor. Pleural schwannomas are very rare and very few cases have been reported in the medical English literature so far. Herein, we report a very rare case of concurrent presence of Nivolumab induced pulmonary sarcoid-like granulomas along with primary benign pleural schwannoma in a 49-year-old male. He was diagnosed with malignant melanoma of the right upper arm for which he underwent surgery and was receiving adjuvant chemotherapy. He developed pneumonitis during chemotherapy, and on imaging multiple reticular and nodular interstitial infiltrates were seen along with an incidental pleural mass with a high suspicion for metastasis. Wedge biopsy of the interstitial infiltrates was done and they were found to be pulmonary granulomas related to the nivolumab therapy he was receiving. The patient underwent excision of the pleural mass which showed histopathological and immunohistochemical features of schwannoma. The two conditions are unrelated and rarely encountered simultaneously. The radiologic and pathologic correlation along with differential diagnosis of these conditions are discussed.

Feasibility of a truncated surveillance schedule for patients following curative intent treatment for carcinoma of the oral cavity.

The purpose of this study was to determine whether a regular follow-up schedule with examination by clinicians results in a better detection rate of disease recurrence and eventual better clinical outcomes when compared to patients who present with symptoms to the clinic and are subsequently detected to have a recurrence of oral squamous cell carcinoma. Retrospective data from 642 patients who underwent treatment for oral squamous cell carcinoma at a tertiary level cancer centre were analysed. Of the 642 patients, 197 had recurrences of which 108 were detected on regular follow-up and 87 were detected in patients presenting out of schedule with symptoms; two patients were detected to have recurrence at another centre, but their mode of detection could not be ascertained. There was no difference in the loco-regional recurrence-free survival or disease-free survival between the two groups. A strict follow-up schedule in the first year followed by a more flexible symptom-based schedule in the subsequent years, with supplementation of imaging if clinically indicated, should be an adequate surveillance plan for oral cancer patients.

Cardiovascular adverse events are associated with usage of immune checkpoint inhibitors in real-world clinical data across the United States.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause life-threatening cardiovascular adverse events (CVAEs) that may not be attributed to therapy. The outcomes of clinical trials may underestimate treatment-related adverse events due to restrictive eligibility, limited sample size, and failure to anticipate selected toxicities. We evaluated the incidence and clinical determinants of CVAEs in real-world population on ICI therapy. PATIENTS AND METHODS: Among 2 687 301 patients diagnosed with cancer from 2011 to 2018, 16 574 received ICIs for any cancer. Patients in the ICI and non-ICI cohorts were matched in a 1 : 1 ratio according to age, sex, National Cancer Institute comorbidity score, and primary cancer. The non-ICI cohort was stratified into patients who received chemotherapy (N = 2875) or targeted agents (N = 4611). All CVAEs, non-cardiac immune-related adverse events occurring after treatment initiation, baseline comorbidities, and treatment details were identified and analyzed using diagnosis and billing codes. RESULTS: Median age was 61 and 65 years in the ICI and non-ICI cohorts, respectively (P < 0.001). ICI patients were predominantly male (P < 0.001). Lung cancer (43.1%), melanoma (30.4%), and renal cell carcinoma (9.9%) were the most common cancer types. CVAE diagnoses in our dataset by incidence proportion (ICI cohort) were stroke (4.6%), heart failure (3.5%), atrial fibrillation (2.1%), conduction disorders (1.5%), myocardial infarction (0.9%), myocarditis (0.05%), vasculitis (0.05%), and pericarditis (0.2%). Anti-cytotoxic T-lymphocyte-associated protein 4 increased the risk of heart failure [versus anti-programmed cell death protein 1; hazard ratio (HR), 1.9; 95% confidence interval (CI) 1.27-2.84] and stroke (HR, 1.7; 95% CI 1.3-2.22). Pneumonitis was associated with heart failure (HR, 2.61; 95% CI 1.23-5.52) and encephalitis with conduction disorders (HR, 4.35; 95% CI 1.6-11.87) in patients on ICIs. Advanced age, primary cancer, nephritis, and anti-cytotoxic T-lymphocyte-associated protein 4 therapy were commonly associated with CVAEs in the adjusted Cox proportional hazards model. CONCLUSIONS: Our findings underscore the importance of risk stratification and cardiovascular monitoring for patients on ICI therapy.