Modeling within and between Sub-Genomes Epistasis of Synthetic Hexaploid Wheat for Genome-Enabled Prediction of Diseases.

Common wheat (Triticum aestivum) is a hexaploid crop comprising three diploid sub-genomes labeled A, B, and D. The objective of this study is to investigate whether there is a discernible influence pattern from the D sub-genome with epistasis in genomic models for wheat diseases. Four genomic statistical models were employed; two models considered the linear genomic relationship of the lines. The first model (G) utilized all molecular markers, while the second model (ABD) utilized three matrices representing the A, B, and D sub-genomes. The remaining two models incorporated epistasis, one (GI) using all markers and the other (ABDI) considering markers in sub-genomes A, B, and D, including inter- and intra-sub-genome interactions. The data utilized pertained to three diseases: tan spot (TS), septoria nodorum blotch (SNB), and spot blotch (SB), for synthetic hexaploid wheat (SHW) lines. The results (variance components) indicate that epistasis makes a substantial contribution to explaining genomic variation, accounting for approximately 50% in SNB and SB and only 29% for TS. In this contribution of epistasis, the influence of intra- and inter-sub-genome interactions of the D sub-genome is crucial, being close to 50% in TS and higher in SNB (60%) and SB (60%). This increase in explaining genomic variation is reflected in an enhancement of predictive ability from the G model (additive) to the ABDI model (additive and epistasis) by 9%, 5%, and 1% for SNB, SB, and TS, respectively. These results, in line with other studies, underscore the significance of the D sub-genome in disease traits and suggest a potential application to be explored in the future regarding the selection of parental crosses based on sub-genomes.

Exploring GWAS and genomic prediction to improve Septoria tritici blotch resistance in wheat.

Septoria tritici blotch (STB) is a destructive foliar diseases threatening wheat grain yield. Wheat breeding for STB disease resistance has been identified as the most sustainable and environment-friendly approach. In this work, a panel of 316 winter wheat breeding lines from a commercial breeding program were evaluated for STB resistance at the seedling stage under controlled conditions followed by genome-wide association study (GWAS) and genomic prediction (GP). The study revealed a significant genotypic variation for STB seedling resistance, while disease severity scores exhibited a normal frequency distribution. Moreover, we calculated a broad-sense heritability of 0.62 for the trait. Nine single- and multi-locus GWAS models identified 24 marker-trait associations grouped into 20 quantitative trait loci (QTLs) for STB seedling-stage resistance. The seven QTLs located on chromosomes 1B, 2A, 2B, 5B (two), 7A, and 7D are reported for the first time and could potentially be novel. The GP cross-validation analysis in the RR-BLUP model estimated the genomic-estimated breeding values (GEBVs) of STB resistance with a prediction accuracy of 0.49. Meanwhile, the GWAS assisted wRR-BLUP model improved the accuracy to 0.58. The identified QTLs can be used for marker-assisted backcrossing against STB in winter wheat. Moreover, the higher prediction accuracy recorded from the GWAS-assisted GP analysis implies its power to successfully select superior candidate lines based on their GEBVs for STB resistance.

Nonsmoker COPD represents a clinically Distinct Phenotype: A Prospective Observational Study.

BACKGROUND: Chronic obstructive lung disease (COPD) has been characterized as a smoker's disease, which has resulted in the usual exclusion of never-smokers from COPD studies. It is now recognized that never-smokers account for nearly one-fourth of all COPD cases, and thus airflow limitation in never-smokers needs further evaluation. Our study aims to elucidate the clinical and physiological aspects of COPD in nonsmokers and to compare smokers and nonsmokers with COPD. MATERIALS AND METHODS: A total of 200 naïve sequential patients with COPD were recruited. The severity of airflow limitation in COPD patients was defined as per Global Initiative for COPD (GOLD) 2019 criteria, and the severity of breathlessness was assessed by the modified Medical Research Council (MRC) dyspnea scale. Data was collected using a patient pro forma, including risk factors for COPD and detailed clinical history. Phenotypic differences along with biomass exposure between never-smokers and smokers were analyzed. RESULTS: Compared to smokers, never-smokers presented at a younger age (55.69 ± 11.5 years; p < 0.001), with a longer duration of dyspnea (5.05 ± 4.96 vs 7.35 ± 6.98 years, p < 0.01). Chest radiographs revealed hyperinflation in a higher number of smokers as compared to never-smokers (82.9 vs 64.6%, p < 0.05). On spirometry evaluation, smokers were found to have significantly poorer lung function [forced expiratory volume in first second (FEV1) 40.36 ± 17.76%; forced vital capacity (FVC): 58.16 ± 17.02%] as compared to never-smokers (FEV1: 47.1 ± 16.47%; FVC: 67.38 ± 17.02%) with p < 0.05. With respect to severity at presentation, most (45.8%) never-smokers presented with stage 2 COPD as compared to the majority of smokers (46.7%) who presented with stage 3 COPD (p-value of <0.05). Absolute eosinophil count (AEC) and eosinophil proportion in total leucocyte count (TLC) was significantly higher in never-smokers as compared to the smokers (232 ± 204.2 vs 309 ± 238.8, p < 0.05). Risk factor analysis showed mean biomass exposure index was significantly higher in never-smokers as compared to smokers (56.02 vs 6.28; p-value of <0.001). CONCLUSION: Compared to smokers, COPD in never-smokers presents at a younger age, with a longer duration of dyspnea and higher eosinophil count. Biomass exposure is one of the major contributors to etiologies for COPD in nonsmokers.

Haplotype-tagged SNPs improve genomic prediction accuracy for Fusarium head blight resistance and yield-related traits in wheat.

KEY MESSAGE: Linkage disequilibrium (LD)-based haplotyping with subsequent SNP tagging improved the genomic prediction accuracy up to 0.07 and 0.092 for Fusarium head blight resistance and spike width, respectively, across six different models. Genomic prediction is a powerful tool to enhance genetic gain in plant breeding. However, the method is accompanied by various complications leading to low prediction accuracy. One of the major challenges arises from the complex dimensionality of marker data. To overcome this issue, we applied two pre-selection methods for SNP markers viz. LD-based haplotype-tagging and GWAS-based trait-linked marker identification. Six different models were tested with preselected SNPs to predict the genomic estimated breeding values (GEBVs) of four traits measured in 419 winter wheat genotypes. Ten different sets of haplotype-tagged SNPs were selected by adjusting the level of LD thresholds. In addition, various sets of trait-linked SNPs were identified with different scenarios from the training-test combined and only from the training populations. The BRR and RR-BLUP models developed from haplotype-tagged SNPs had a higher prediction accuracy for FHB and SPW by 0.07 and 0.092, respectively, compared to the corresponding models developed without marker pre-selection. The highest prediction accuracy for SPW and FHB was achieved with tagged SNPs pruned at weak LD thresholds (r2 < 0.5), while stringent LD was required for spike length (SPL) and flag leaf area (FLA). Trait-linked SNPs identified only from training populations failed to improve the prediction accuracy of the four studied traits. Pre-selection of SNPs via LD-based haplotype-tagging could play a vital role in optimizing genomic selection and reducing genotyping costs. Furthermore, the method could pave the way for developing low-cost genotyping methods through customized genotyping platforms targeting key SNP markers tagged to essential haplotype blocks.

Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction-based approaches.

Acinetobacter baumannii is one of the major pathogenic ESKAPE bacterium, which is responsible for about more than 722,000 cases in a year, globally. Despite the alarming increase in multidrug resistance, a safe and effective vaccine for Acinetobacter infections is still not available. Hence in the current study, a multiepitope vaccine construct was developed using linear B cell, cytotoxic T cell, and helper T cell epitopes from the antigenic and well-conserved lipopolysaccharide assembly proteins employing systematic immunoinformatics and structural vaccinology strategies. The multi-peptide vaccine was predicted to be highly antigenic, non-allergenic, non-toxic, and cover maximum population coverage worldwide. Further, the vaccine construct was modeled along with adjuvant and peptide linkers and validated to achieve a high-quality three-dimensional structure which was subsequently utilized for cytokine prediction, disulfide engineering, and docking analyses with Toll-like receptor (TLR4). Ramachandran plot showed 98.3% of the residues were located in the most favorable and permitted regions, thereby corroborating the feasibility of the modeled vaccine construct. Molecular dynamics simulation for a 100 ns timeframe further confirmed the stability of the binding vaccine-receptor complex. Finally, in silico cloning and codon adaptation were also performed with the pET28a (+) plasmid vector to determine the efficiency of expression and translation of the vaccine. Immune simulation studies demonstrated that the vaccine could trigger both B and T cell responses and can elicit strong primary, secondary, and tertiary immune responses. The designed multi-peptide subunit vaccine would certainly expedite the experimental approach for the development of a vaccine against A. baumannii infection.

Managing spot blotch disease in wheat: Conventional to molecular aspects.

Spot blotch (SB) caused by Bipolaris sorokiniana (teleomorph Cochliobolus sativus) is one of the devastating diseases of wheat in the warm and humid growing areas around the world. B. sorokiniana can infect leaves, stem, roots, rachis and seeds, and is able to produce toxins like helminthosporol and sorokinianin. No wheat variety is immune to SB; hence, an integrated disease management strategy is indispensable in disease prone areas. A range of fungicides, especially the triazole group, have shown good effects in reducing the disease, and crop-rotation, tillage and early sowing are among the favorable cultural management methods. Resistance is mostly quantitative, being governed by QTLs with minor effects, mapped on all the wheat chromosomes. Only four QTLs with major effects have been designated as Sb1 through Sb4. Despite, marker assisted breeding for SB resistance in wheat is scarce. Better understanding of wheat genome assemblies, functional genomics and cloning of resistance genes will further accelerate breeding for SB resistance in wheat.

The paradigm of prophylactic viral outbreaks measures by microbial biosurfactants.

The recent emergence and outbreak of the COVID-19 pandemic confirmed the incompetence of countries across the world to deal with a global public health emergency. Although the recent advent of vaccines is an important prophylactic measure, effective clinical therapy for SARS-Cov-2 is yet to be discovered. With the increasing mortality rate, research has been focused on understanding the pathogenic mechanism and clinical parameters to comprehend COVID-19 infection and propose new avenues for naturally occurring molecules with novel therapeutic properties to alleviate the current situation. In accordance with recent clinical studies and SARS-CoV-2 infection markers, cytokine storm and oxidative stress are entwined pathogenic processes in COVID-19 progression. Lately, Biosurfactants (BSs) have been studied as one of the most advanced biomolecules of microbial origin with anti-inflammatory, antioxidant, antiviral properties, antiadhesive, and antimicrobial properties. Therefore, this review inspects available literature and proposes biosurfactants with these properties to be encouraged for their extensive study in dealing with the current pandemic as new pharmaceutics in the prevention and control of viral spread, treating the symptoms developed after the incubation period through different therapeutic approaches and playing a potential drug delivery model.

Genetic sources and loci for Fusarium head blight resistance in bread wheat.

Fusarium head blight (FHB) of wheat is an important disease worldwide, affecting the yield, end-use quality and threatening food safety. Genetic resources or stable loci for FHB resistance are still limited in breeding programs. A panel of 265 bread wheat accessions from China, CIMMYT-Mexico and other countries was screened for FHB resistance under 5 field experiments in Mexico and China, and a genome-wide association analysis was performed to identify QTLs associated with FHB resistance. The major locus Fhb1 was significantly associated with FHB severity and Deoxynivalenol content in grains. FHB screening experiments in multiple environments showed that Fhb1-harbouring accessions Sumai3, Sumai5, Ningmai9, Yangmai18 and Tokai66 had low FHB index, disease severity and DON content in grains in response to different Fusarium species and ecological conditions in Mexico and China. Accessions Klein Don Enrique, Chuko and Yumai34 did not have Fhb1 but still showed good FHB resistance and low mycotoxin accumulation. Sixteen loci associated with FHB resistance or DON content in grains were identified on chromosomes 1A, 1B, 2B, 3A, 3D, 4B, 4D, 5A, 5B, 7A, and 7B in multiple environments, explaining phenotypic variation of 4.43-10.49%. The sources with good FHB resistance reported here could be used in breeding programs for resistance improvement in Mexico and China, and the significant loci could be further studied and introgressed for resistance improvement against FHB and mycotoxin accumulation in grains.

Genome-Wide Association Study for Spot Blotch Resistance in Synthetic Hexaploid Wheat.

Spot blotch (SB) caused by Bipolaris sorokiniana (Sacc.) Shoem is a destructive fungal disease affecting wheat and many other crops. Synthetic hexaploid wheat (SHW) offers opportunities to explore new resistance genes for SB for introgression into elite bread wheat. The objectives of our study were to evaluate a collection of 441 SHWs for resistance to SB and to identify potential new genomic regions associated with the disease. The panel exhibited high SB resistance, with 250 accessions showing resistance and 161 showing moderate resistance reactions. A genome-wide association study (GWAS) revealed a total of 41 significant marker-trait associations for resistance to SB, being located on chromosomes 1B, 1D, 2A, 2B, 2D, 3A, 3B, 3D, 4A, 4D, 5A, 5D, 6D, 7A, and 7D; yet none of them exhibited a major phenotypic effect. In addition, a partial least squares regression was conducted to validate the marker-trait associations, and 15 markers were found to be most important for SB resistance in the panel. To our knowledge, this is the first GWAS to investigate SB resistance in SHW that identified markers and resistant SHW lines to be utilized in wheat breeding.

Left Adrenal Gland Sampling Through Transesophageal Bronchoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-B FNA): A New Route and a New Challenge.

Metastasis to adrenal glands from primary pulmonary carcinoma is quite a common occurrence. In most cases, the diagnosis is made based on an imaging evaluation done because of chronic non-specific pulmonary symptoms. Further evaluation to determine the type of carcinoma is done using histopathological evaluation of the primary lung lesion. Here, we have described a case of a 60-year-old man who presented with chest pain and was incidentally detected with a lower lung mass and a bulky left adrenal gland in the upper abdominal cuts on a CT of the thorax. As the evaluation of the fine needle aspiration (FNA) sample from lung lesion couldn't be successfully performed, sampling from the left adrenal gland was attempted under the guidance of conventional endoscopic ultrasound using an endobronchial ultrasound probe (EUS-B). When the technique failed to localise the left adrenal gland, a modification was made and the gland was localised using the spleen as a marker. This case further presented a challenge, when due to the unfolding of rugae, the FNA needle wasn't able to reach up to the left adrenal gland. Further adjustment was made and the maximum depth of the gland from the margin was measured and the needle was fully freed. Multiple jabs were made and sampling was successfully done. Cellblock confirmed the presence of adenocarcinoma of pulmonary origin, positive for thyroid transcription factor 1 (TTF-1). The patient remained stable and did not present with any early or late post-procedural complications. The patient was started on appropriate chemotherapy for the disease. He has received three cycles of carboplatin and pemetrexed till now and is doing well.

A Rare Etiology of Cystic Lung Disease.

Metastases presenting in the form of cystic lung disease are a very rare occurrence. Even rarer is the association of such metastases with primary pancreatic carcinoma. Here we have described the case of a 60-year-old man who presented with a six-month history of worsening shortness of breath and dry cough associated with loss of weight and appetite. At the time of admission, his oxygen saturation on room air was found to be 82% and the respiratory rate was 28/minute. Apart from bilateral diffuse coarse crackles, the rest of the physical examination was largely unremarkable. All his blood tests were found to be normal except for raised levels of alkaline phosphatase (268 IU/L). The levels of cancer antigen (CA) 19-9 were also found to be elevated (238.8 IU/ml). CT of the chest and abdomen revealed the presence of multiple cystic lesions with predominance in the lower lobes of the lungs and an enlarged head of pancreas. The patient underwent side-view esophagogastroduodenoscopy and multiple biopsies taken from the lesion in the head of pancreas revealed the presence of multiple atypical cells with glandular formation suggestive of adenocarcinoma. We were not able to directly demonstrate the tumor cells in lung tissue, as the patient was not fit for bronchoscopic procedures due to high oxygen requirements. However, the temporal course of the development of symptoms, and cysts do correlate suggesting metastasis as the etiology of cystic lesions found in his lung.

Identification of Genomic Regions and Sources for Wheat Blast Resistance through GWAS in Indian Wheat Genotypes.

Wheat blast (WB) is a devastating fungal disease that has recently spread to Bangladesh and poses a threat to the wheat production in India, which is the second-largest wheat producing country in the world. In this study, 350 Indian wheat genotypes were evaluated for WB resistance in 12 field experiments in three different locations, namely Jashore in Bangladesh and Quirusillas and Okinawa in Bolivia. Single nucleotide polymorphisms (SNPs) across the genome were obtained using DArTseq® technology, and 7554 filtered SNP markers were selected for a genome-wide association study (GWAS). All the three GWAS approaches used identified the 2NS translocation as the only major source of resistance, explaining up to 32% of the phenotypic variation. Additional marker-trait associations were located on chromosomes 2B, 3B, 4D, 5A and 7A, and the combined effect of three SNPs (2B_180938790, 7A_752501634 and 5A_618682953) showed better resistance, indicating their additive effects on WB resistance. Among the 298 bread wheat genotypes, 89 (29.9%) carried the 2NS translocation, the majority of which (60 genotypes) were CIMMYT introductions, and 29 were from India. The 2NS carriers with a grand mean WB index of 6.6 showed higher blast resistance compared to the non-2NS genotypes with a mean index of 46.5. Of the 52 durum wheats, only one genotype, HI 8819, had the 2NS translocation and was the most resistant, with a grand mean WB index of 0.93. Our study suggests that the 2NS translocation is the only major resistance source in the Indian wheat panel analysed and emphasizes the urgent need to identify novel non-2NS resistance sources and genomic regions.

Genomic selection for spot blotch in bread wheat breeding panels, full-sibs and half-sibs and index-based selection for spot blotch, heading and plant height.

KEY MESSAGE: Genomic selection is a promising tool to select for spot blotch resistance and index-based selection can simultaneously select for spot blotch resistance, heading and plant height. A major biotic stress challenging bread wheat production in regions characterized by humid and warm weather is spot blotch caused by the fungus Bipolaris sorokiniana. Since genomic selection (GS) is a promising selection tool, we evaluated its potential for spot blotch in seven breeding panels comprising 6736 advanced lines from the International Maize and Wheat Improvement Center. Our results indicated moderately high mean genomic prediction accuracies of 0.53 and 0.40 within and across breeding panels, respectively which were on average 177.6% and 60.4% higher than the mean accuracies from fixed effects models using selected spot blotch loci. Genomic prediction was also evaluated in full-sibs and half-sibs panels and sibs were predicted with the highest mean accuracy (0.63) from a composite training population with random full-sibs and half-sibs. The mean accuracies when full-sibs were predicted from other full-sibs within families and when full-sibs panels were predicted from other half-sibs panels were 0.47 and 0.44, respectively. Comparison of GS with phenotypic selection (PS) of the top 10% of resistant lines suggested that GS could be an ideal tool to discard susceptible lines, as greater than 90% of the susceptible lines discarded by PS were also discarded by GS. We have also reported the evaluation of selection indices to simultaneously select non-late and non-tall genotypes with low spot blotch phenotypic values and genomic-estimated breeding values. Overall, this study demonstrates the potential of integrating GS and index-based selection for improving spot blotch resistance in bread wheat.

Perception of healthcare workers towards ethical aspects of responsiveness of COVID 19 outbreak: A cross-sectional study.

Introduction: COVID-19 has spread all over the world and most of the countries are still grappled with the Pandemic. Health-care-workers (HCWs) being the frontlines during such pandemics have different beliefs and faiths with regards to ethical aspects of preparations. Methodology: In order to study the perception of HCW about ethical aspects of COVID-19, a cross-sectional study was done in a tertiary-care-teaching hospital. A pretested questionnaire was circulated among the participants on a digital platform. Results: The HCWs were divided over many statements, like if COVID-19 was more hype than reality (45.77% disagreed and 43.25% agreed). 57.44% of participants either agreed or strongly agreed that the treatment of non-COVID-19 cases suffered due to arrangements made for COVID-19 cases. When the responses received against individual statements were compared with various other socio-demographic variables as a denominator, various interesting results were revealed. There was a significant difference of opinion among the participating HCWs (P < 0.05). Conclusion: Differences of the opinions had their relationships to demographic characteristics of the subjects as well as related to perceived knowledge of COVID-19.

Genome-Wide Association Mapping Indicates Quantitative Genetic Control of Spot Blotch Resistance in Bread Wheat and the Favorable Effects of Some Spot Blotch Loci on Grain Yield.

Spot blotch caused by the fungus Bipolaris sorokiniana poses a serious threat to bread wheat production in warm and humid wheat-growing regions of the world. Hence, the major objective of this study was to identify consistent genotyping-by-sequencing (GBS) markers associated with spot blotch resistance using genome-wide association mapping on a large set of 6,736 advanced bread wheat breeding lines from the International Maize and Wheat Improvement Center. These lines were phenotyped as seven panels at Agua Fria, Mexico between the 2013-2014 and 2019-2020 crop cycles. We identified 214 significant spot blotch associated GBS markers in all the panels, among which only 96 were significant in more than one panel, indicating a strong environmental effect on the trait and highlights the need for multiple phenotypic evaluations to identify lines with stable spot blotch resistance. The 96 consistent GBS markers were on chromosomes 1A, 1B, 1D, 2A, 3B, 4A, 5B, 5D, 6B, 7A, 7B, and 7D, including markers possibly linked to the Lr46, Sb1, Sb2 and Sb3 genes. We also report the association of the 2NS translocation from Aegilops ventricosa with spot blotch resistance in some environments. Moreover, the spot blotch favorable alleles at the 2NS translocation and two markers on chromosome 3BS (3B_2280114 and 3B_5601689) were associated with increased grain yield evaluated at several environments in Mexico and India, implying that selection for favorable alleles at these loci could enable simultaneous improvement for high grain yield and spot blotch resistance. Furthermore, a significant relationship between the percentage of favorable alleles in the lines and their spot blotch response was observed, which taken together with the multiple minor effect loci identified to be associated with spot blotch in this study, indicate quantitative genetic control of resistance. Overall, the results presented here have extended our knowledge on the genetic basis of spot blotch resistance in bread wheat and further efforts to improve genetic resistance to the disease are needed for reducing current and future losses under climate change.

Genome-Wide Association Study for Resistance to Tan Spot in Synthetic Hexaploid Wheat.

Synthetic hexaploid wheat (SHW) has shown effective resistance to a diversity of diseases and insects, including tan spot, which is caused by Pyrenophora tritici-repentis, being an important foliar disease that can attack all types of wheat and several grasses. In this study, 443 SHW plants were evaluated for their resistance to tan spot under controlled environmental conditions. Additionally, a genome-wide association study was conducted by genotyping all entries with the DArTSeq technology to identify marker-trait associations for tan spot resistance. Of the 443 SHW plants, 233 showed resistant and 183 moderately resistant reactions, and only 27 were moderately susceptible or susceptible to tan spot. Durum wheat (DW) parents of the SHW showed moderately susceptible to susceptible reactions. A total of 30 significant marker-trait associations were found on chromosomes 1B (4 markers), 1D (1 marker), 2A (1 marker), 2D (2 markers), 3A (4 markers), 3D (3 markers), 4B (1 marker), 5A (4 markers), 6A (6 markers), 6B (1 marker) and 7D (3 markers). Increased resistance in the SHW in comparison to the DW parents, along with the significant association of resistance with the A and B genome, supported the concept of activating epistasis interaction across the three wheat genomes. Candidate genes coding for F-box and cytochrome P450 proteins that play significant roles in biotic stress resistance were identified for the significant markers. The identified resistant SHW lines can be deployed in wheat breeding for tan spot resistance.

An Unusual Case of Pancytopenia: The Lessons Learnt.

Pancytopenia is a common hematological abnormality encountered in clinical practice. We here report a 36-year-old male who presented to emergency department with complaints of weakness of bilateral lower limbs, burning sensation in all four limbs with history of loose stools, and vomiting 5 days back. The complete blood count of patient showed pancytopenia with no circulating atypical cells. Bone marrow examination performed showed nonspecific but characteristic findings. After excluding the possibility of infective etiology, a possibility of heavy metal toxicity was suspected in multidisciplinary meeting. The urine and blood levels of arsenic done came out very high, and a diagnosis of arsenic poisoning was made. Patient had multisystemic involvement with features characteristic of arsenic poisoning. The present case was a diagnostic challenge in face of nonforthcoming history. This case beautifully highlighted the importance of multidepartmental approach in such cases to arrive at unerring diagnosis and the unique bone marrow findings, although nonspecific were sufficient enough to indicate the possibility of acute insult to the hematopoiesis. How to cite this article: Nair RR, Singh PK, Sharma J, Gambhir I, Khanna S, Jain AK, et al. An Unusual Case of Pancytopenia: The Lessons Learnt. Indian J Crit Care Med 2022;26(1):141-144.

Genetic dissection for head blast resistance in wheat using two mapping populations.

Wheat head blast is a dangerous fungal disease in South America and has recently spread to Bangladesh and Zambia, threatening wheat production in those regions. Host resistance as an economical and environment-friendly management strategy has been heavily relied on, and understanding the resistance loci in the wheat genome is very helpful to resistance breeding. In the current study, two recombinant inbred line (RIL) populations, Alondra/Milan (with 296 RILs) and Caninde#2/Milan-S (with 254 RILs and Milan-S being a susceptible variant of Milan), were used for mapping QTL associated with head blast resistance in field experiments. Phenotyping was conducted in Quirusillas and Okinawa, Bolivia, and in Jashore, Bangladesh, during the 2017-18 and 2018-19 cropping cycles. The DArTseq® technology was employed to genotype the lines, along with four STS markers in the 2NS region. A QTL with consistent major effects was mapped on the 2NS/2AS translocation region in both populations, explaining phenotypic variation from 16.7 to 79.4% across experiments. Additional QTL were detected on chromosomes 2DL, 7AL, and 7DS in the Alondra/Milan population, and 2BS, 4AL, 5AS, 5DL, 7AS, and 7AL in the Caninde#2/Milan-S population, all showing phenotypic effects <10%. The results corroborated the important role of the 2NS/2AS translocation on WB resistance and identified a few novel QTL for possible deployment in wheat breeding. The low phenotypic effects of the non-2NS QTL warrantee further investigation for novel QTL with higher and more stable effects against WB, to alleviate the heavy reliance on 2NS-based resistance.

Tofacitinib Associated with Reduced Intubation Rates in the Management of Severe COVID-19 Pneumonia: A Preliminary Experience.

BACKGROUND: The second wave of COVID-19 pandemic was not only associated with a rapid and severe surge in the number of cases but also limited availability of recommended medicines. Baricitinib has been known to reduce recovery time in COVID-19 pneumonia in association with remdesivir. Tofacitinib, with limited evidence, was used in severe COVID-19 pneumonia based on its similarity of action with baricitinib. METHODS: Data of all patients admitted to the COVID-19 intensive care unit in the month of April were accessed and analyzed. Data of patients who were on other immunomodulators, invasive ventilation, or suffering from end-stage organ diseases were excluded from the analysis. RESULTS: Out of 73 patients, data of 50 were analyzed. Twenty-five received tofacitinib and the other 25 were managed with standard of care. Age, comorbidities, and gender distribution between the two groups were similar. On day 7 of admission, the change in SpO2/FiO2 ratio was 1.26 ± 1 and 0.72 ± 1 in the tofacitinib group and control group, respectively. Similarly, a higher number of subjects in the control group showed worsening in the World Health Organization (WHO) ordinal scale (36 vs 12%, p = 0.01). The clinical objective improvement was similar in the two groups. The intubation rates in the tofacitinib group were significantly lower than that in the control group (32% vs 8%, p = 0.034). CONCLUSION: Tofacitinib, in this retrospective single-center experience, was found to be associated with reduced intubation rates and reduced worsening in the WHO ordinal scale. There was no difference in mortality in the two groups. HOW TO CITE THIS ARTICLE: Singh PK, Lalwani LK, Govindagoudar MB, Aggarwal R, Chaudhry D, Kumar P, et al. Tofacitinib Associated with Reduced Intubation Rates in the Management of Severe COVID-19 Pneumonia: A Preliminary Experience. Indian J Crit Care Med 2021;25(10):1108-1112.

New Genotypes and Genomic Regions for Resistance to Wheat Blast in South Asian Germplasm.

Wheat blast (WB) disease, since its first identification in Bangladesh in 2016, is now an established serious threat to wheat production in South Asia. There is a need for sound knowledge about resistance sources and associated genomic regions to assist breeding programs. Hence, a panel of genotypes from India and Bangladesh was evaluated for wheat blast resistance and a genome-wide association study (GWAS) was performed. Disease evaluation was done during five crop seasons-at precision phenotyping platform (PPPs) for wheat blast disease at Jashore (2018-19), Quirusillas (2018-19 and 2019-20) and Okinawa (2019 and 2020). Single nucleotide polymorphisms (SNP) across the genome were obtained using DArTseq genotyping-by-sequencing platform, and in total 5713 filtered markers were used. GWAS revealed 40 significant markers associated with WB resistance, of which 33 (82.5%) were in the 2NS/2AS chromosome segment and one each on seven chromosomes (3B, 3D, 4A, 5A, 5D, 6A and 6B). The 2NS markers contributed significantly in most of the environments, explaining an average of 33.4% of the phenotypic variation. Overall, 22.4% of the germplasm carried 2NS/2AS segment. So far, 2NS translocation is the only effective WB resistance source being used in the breeding programs of South Asia. Nevertheless, the identification of non-2NS/2AS genomic regions for WB resistance provides a hope to broaden and diversify resistance for this disease in years to come.