Novel resistance loci for quantitative resistance to Septoria tritici blotch in Asian wheat (Triticum aestivum) via genome-wide association study.

BACKGROUND: Septoria tritici blotch (STB) disease causes yield losses of up to 50 per cent in susceptible wheat cultivars and can reduce wheat production. In this study, genomic architecture for adult-plant STB resistance in a Septoria Association Mapping Panel (SAMP) having 181 accessions and genomic regions governing STB resistance in a South Asian wheat panel were looked for. RESULTS: Field experiments during the period from 2019 to 2021 revealed those certain accessions, namely BGD52 (CHIR7/ANB//CHIR1), BGD54 (CHIR7/ANB//CHIR1), IND92 (WH 1218), IND8 (DBW 168), and IND75 (PBW 800), exhibited a high level of resistance. Genetic analysis revealed the presence of 21 stable quantitative trait nucleotides (QTNs) associated with resistance to STB (Septoria tritici blotch) on all wheat chromosomes, except for 2D, 3A, 3D, 4A, 4D, 5D, 6B, 6D, and 7A. These QTNs were predominantly located in chromosome regions previously identified as associated with STB resistance. Three Quantitative Trait Loci (QTNs) were found to have significant phenotypic effects in field evaluations. These QTNs are Q.STB.5A.1, Q.STB.5B.1, and Q.STB.5B.3. Furthermore, it is possible that the QTNs located on chromosomes 1A (Q.STB.1A.1), 2A (Q.STB_DH.2A.1, Q.STB.2A.3), 2B (Q.STB.2B.4), 5A (Q.STB.5A.1, Q.STB.5A.2), and 7B (Q.STB.7B.2) could potentially be new genetic regions associated with resistance. CONCLUSION: Our findings demonstrate the importance of Asian bread wheat as a source of STB resistance alleles and novel stable QTNs for wheat breeding programs aiming to develop long-lasting and wide-ranging resistance to Zymoseptoria tritici in wheat cultivars.

HyEpiSeiD: a hybrid convolutional neural network and gated recurrent unit model for epileptic seizure detection from electroencephalogram signals.

Epileptic seizure (ES) detection is an active research area, that aims at patient-specific ES detection with high accuracy from electroencephalogram (EEG) signals. The early detection of seizure is crucial for timely medical intervention and prevention of further injuries of the patients. This work proposes a robust deep learning framework called HyEpiSeiD that extracts self-trained features from the pre-processed EEG signals using a hybrid combination of convolutional neural network followed by two gated recurrent unit layers and performs prediction based on those extracted features. The proposed HyEpiSeiD framework is evaluated on two public datasets, the UCI Epilepsy and Mendeley datasets. The proposed HyEpiSeiD model achieved 99.01% and 97.50% classification accuracy, respectively, outperforming most of the state-of-the-art methods in epilepsy detection domain.

Wheat genetic resources have avoided disease pandemics, improved food security, and reduced environmental footprints: A review of historical impacts and future opportunities.

The use of plant genetic resources (PGR)-wild relatives, landraces, and isolated breeding gene pools-has had substantial impacts on wheat breeding for resistance to biotic and abiotic stresses, while increasing nutritional value, end-use quality, and grain yield. In the Global South, post-Green Revolution genetic yield gains are generally achieved with minimal additional inputs. As a result, production has increased, and millions of hectares of natural ecosystems have been spared. Without PGR-derived disease resistance, fungicide use would have easily doubled, massively increasing selection pressure for fungicide resistance. It is estimated that in wheat, a billion liters of fungicide application have been avoided just since 2000. This review presents examples of successful use of PGR including the relentless battle against wheat rust epidemics/pandemics, defending against diseases that jump species barriers like blast, biofortification giving nutrient-dense varieties and the use of novel genetic variation for improving polygenic traits like climate resilience. Crop breeding genepools urgently need to be diversified to increase yields across a range of environments (>200 Mha globally), under less predictable weather and biotic stress pressure, while increasing input use efficiency. Given that the ~0.8 m PGR in wheat collections worldwide are relatively untapped and massive impacts of the tiny fraction studied, larger scale screenings and introgression promise solutions to emerging challenges, facilitated by advanced phenomic and genomic tools. The first translocations in wheat to modify rhizosphere microbiome interaction (reducing biological nitrification, reducing greenhouse gases, and increasing nitrogen use efficiency) is a landmark proof of concept. Phenomics and next-generation sequencing have already elucidated exotic haplotypes associated with biotic and complex abiotic traits now mainstreamed in breeding. Big data from decades of global yield trials can elucidate the benefits of PGR across environments. This kind of impact cannot be achieved without widescale sharing of germplasm and other breeding technologies through networks and public-private partnerships in a pre-competitive space.

Evaluation of the Treatment Planning and Delivery for Hip Implant Cases on Tomotherapy.

Purpose: The metal present in the implant creates artifacts during the treatment simulation, which impacts the treatment planning and delivery of the prescribed dose to the target and sparing normal tissues. This retrospective study evaluated the uncertainties in the planning and delivery of doses for prosthesis cases with dedicated phantom. Materials and Methods: In this retrospective study, 11 patients with a hip prosthesis having cervix carcinoma were selected. Two treatment plans were generated on treatment planning system (TPS) for each case. Plan_No_Res was without any beam restriction, and Plan_exit_only was the plan with restricted beam entry through the metallic implant. An indigenous phantom was utilized to verify the accuracy of the treatment. In the phantom, some groves were present, which could be filled by implants that mimic the patient's geometries, like left, right and bilateral femur implants. The delivered doses were recorded using optically stimulated luminescence dosimeters (OSLDs), which were placed at different positions in the phantom. The plans were further calculated using megavoltage computed tomography (MVCT) scans acquired during treatment. Results: The patient data showed no significant dose changes between the two planning methods. The treatment time increases from 412.18 ± 86.65 to 427.36 ± 104.80 with P = 0.03 for Plan_No_Res and Plan_exit_only, respectively. The difference between planned and delivered doses of various points across phantom geometries was within ± 9.5% in each case as left, right, and bilateral implant. The variations between OSLDs and MVCT calculated doses were also within ± 10.8%. Conclusion: The study showed the competency of tomotherapy planning for hip prosthesis cases. The phantom measurements demonstrate the errors in dosimetry near the implant material, suggesting the need for precise methods to deal with artifact-related issues.

Screening of CIMMYT and South Asian Bread Wheat Germplasm Reveals Marker-Trait Associations for Seedling Resistance to Septoria Nodorum Blotch.

Wheat (Triticum aestivum L.) production is adversely impacted by Septoria nodorum blotch (SNB), a fungal disease caused by Parastagonospora nodorum. Wheat breeders are constantly up against this biotic challenge as they try to create resistant cultivars. The genome-wide association study (GWAS) has become an efficient tool for identifying molecular markers linked with SNB resistance. This technique is used to acquire an understanding of the genetic basis of resistance and to facilitate marker-assisted selection. In the current study, a total of 174 bread wheat accessions from South Asia and CIMMYT were assessed for SNB reactions at the seedling stage in three greenhouse experiments at CIMMYT, Mexico. The results indicated that 129 genotypes were resistant to SNB, 39 were moderately resistant, and only 6 were moderately susceptible. The Genotyping Illumina Infinium 15K Bead Chip was used, and 11,184 SNP markers were utilized to identify marker-trait associations (MTAs) after filtering. Multiple tests confirmed the existence of significant MTAs on chromosomes 5B, 5A, and 3D, and the ones at Tsn1 on 5B were the most stable and conferred the highest phenotypic variation. The resistant genotypes identified in this study could be cultivated in South Asian countries as a preventative measure against the spread of SNB. This work also identified molecular markers of SNB resistance that could be used in future wheat breeding projects.

Novel quinoline substituted autophagy inhibitors attenuate Zika virus replication in ocular cells.

Zika virus (ZIKV) is a re-emerging RNA virus that is known to cause ocular and neurological abnormalities in infants. ZIKV exploits autophagic processes in infected cells to enhance its replication and spread. Thus, autophagy inhibitors have emerged as a potent therapeutic target to combat RNA viruses, with Hydroxychloroquine (HCQ) being one of the most promising candidates. In this study, we synthesized several novel small-molecule quinoline derivatives, assessed their antiviral activity, and determined the underlying molecular mechanisms. Among the nine synthesized analogs, two lead candidates, labeled GL-287 and GL-382, significantly attenuated ZIKV replication in human ocular cells, primarily by inhibiting autophagy. These two compounds surpassed the antiviral efficacy of HCQ and other existing autophagy inhibitors, such as ROC-325, DC661, and GNS561. Moreover, unlike HCQ, these novel analogs did not exhibit cytotoxicity in the ocular cells. Treatment with compounds GL-287 and GL-382 in ZIKV-infected cells increased the abundance of LC3 puncta, indicating the disruption of the autophagic process. Furthermore, compounds GL-287 and GL-382 effectively inhibited the ZIKV-induced innate inflammatory response in ocular cells. Collectively, our study demonstrates the safe and potent antiviral activity of novel autophagy inhibitors against ZIKV.

Rmg10, a Novel Wheat Blast Resistance Gene Derived from Aegilops tauschii.

Wheat blast, caused by Pyricularia oryzae (syn. Magnaporthe oryzae) pathotype Triticum (MoT), is a devastating disease that can result in up to 100% yield loss in affected fields. To find new resistance genes against wheat blast, we screened 199 accessions of Aegilops tauschii, the D genome progenitor of common wheat (Triticum aestivum), by seedling inoculation assays with Brazilian MoT isolate Br48 and found 14 resistant accessions. A synthetic hexaploid wheat line (Ldn/KU-2097) derived from a cross between the T. turgidum 'Langdon' (Ldn) and resistant A. tauschii accession KU-2097 exhibited resistance in seedlings and spikes against Br48. In an F2 population derived from 'Chinese Spring' × Ldn/KU-2097, resistant and susceptible individuals segregated in a 3:1 ratio, suggesting that the resistance from KU-2097 is controlled by a single dominant gene. We designated this gene Rmg10. Genetic mapping using an F2:3 population from the same cross mapped the RMG10 locus to the short arm of chromosome 2D. Rmg10 was ineffective against Bangladesh isolates but effective against Brazilian isolates. Field tests in Bolivia showed increased spike resistance in a synthetic octaploid wheat line produced from a cross between common wheat cultivar 'Gladius' and KU-2097. These results suggest that Rmg10 would be beneficial in farmers' fields in South America.

Implementing vision transformer for classifying 2D biomedical images.

In recent years, the growth spurt of medical imaging data has led to the development of various machine learning algorithms for various healthcare applications. The MedMNISTv2 dataset, a comprehensive benchmark for 2D biomedical image classification, encompasses diverse medical imaging modalities such as Fundus Camera, Breast Ultrasound, Colon Pathology, Blood Cell Microscope etc. Highly accurate classifications performed on these datasets is crucial for identification of various diseases and determining the course of treatment. This research paper presents a comprehensive analysis of four subsets within the MedMNISTv2 dataset: BloodMNIST, BreastMNIST, PathMNIST and RetinaMNIST. Each of these selected datasets is of diverse data modalities and comes with various sample sizes, and have been selected to analyze the efficiency of the model against diverse data modalities. The study explores the idea of assessing the Vision Transformer Model's ability to capture intricate patterns and features crucial for these medical image classification and thereby transcend the benchmark metrics substantially. The methodology includes pre-processing the input images which is followed by training the ViT-base-patch16-224 model on the mentioned datasets. The performance of the model is assessed using key metrices and by comparing the classification accuracies achieved with the benchmark accuracies. With the assistance of ViT, the new benchmarks achieved for BloodMNIST, BreastMNIST, PathMNIST and RetinaMNIST are 97.90%, 90.38%, 94.62% and 57%, respectively. The study highlights the promise of Vision transformer models in medical image analysis, preparing the way for their adoption and further exploration in healthcare applications, aiming to enhance diagnostic accuracy and assist medical professionals in clinical decision-making.

Genomic prediction of synthetic hexaploid wheat upon tetraploid durum and diploid Aegilops parental pools.

Bread wheat (Triticum aestivum L.) is a globally important food crop, which was domesticated about 8-10,000 years ago. Bread wheat is an allopolyploid, and it evolved from two hybridization events of three species. To widen the genetic base in breeding, bread wheat has been re-synthesized by crossing durum wheat (Triticum turgidum ssp. durum) and goat grass (Aegilops tauschii Coss), leading to so-called synthetic hexaploid wheat (SHW). We applied the quantitative genetics tools of "hybrid prediction"-originally developed for the prediction of wheat hybrids generated from different heterotic groups - to a situation of allopolyploidization. Our use-case predicts the phenotypes of SHW for three quantitatively inherited global wheat diseases, namely tan spot (TS), septoria nodorum blotch (SNB), and spot blotch (SB). Our results revealed prediction abilities comparable to studies in 'traditional' elite or hybrid wheat. Prediction abilities were highest using a marker model and performing random cross-validation, predicting the performance of untested SHW (0.483 for SB to 0.730 for TS). When testing parents not necessarily used in SHW, combination prediction abilities were slightly lower (0.378 for SB to 0.718 for TS), yet still promising. Despite the limited phenotypic data, our results provide a general example for predictive models targeting an allopolyploidization event and a method that can guide the use of genetic resources available in gene banks.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

Selection of reference genes for normalizing gene expression data across seasons in spermatozoa of water buffalo (Bubalus bubalis).

Selection of the most stably expressed reference genes is key to monitoring accurate target gene expression across any tissue or cell type. The mRNA in spermatozoa stores valuable information related to changes in spermatogenesis due to variations in environmental conditions, especially during heat stress, which affects various sperm functions. Semen quality in buffalo bulls is significantly influenced by the seasons. In the study, a panel of nine genes was evaluated to identify the most stably expressed internal control gene (ICG) for the normalization of real-time gene expression data generated across various seasons for Murrah buffalo bulls' spermatozoa. Sperm cells were purified from the semen samples collected during different seasons, with temperature-humidity index (THI) ranging from 80.80 ± 1.47 (hot summer) to 55.88 ± 1.98 (winter), using the BoviPure™ gradient purification method. The RNA isolated from the purified spermatozoa fraction was quality checked prior to reverse transcription and subjected to qPCR (quantitative real-time PCR) based expression analysis. An automated 'endoGene' pipeline was employed to apply the geNorm, NormFinder, and BestKeeper algorithms for data analysis. The result indicated that GAPDH and PP1A were the most stably expressed among the gene panel, whereas ATPSF1 and ACTB were the two least stable expressed reference genes. Further, the most suitable ICGs identified were validated by normalization of real time expression data of heat stress and sperm quality genes, HSFY2 and AKAP4, respectively. The genes identified would help in generating the most reliable results for the expression profiling of the genes dictating sperm quality and heat stress cope-up mechanism in buffalo spermatozoa, collected during different seasons.

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.

Minimal Residual Disease in the Management of B-Cell Acute Lymphoblastic Leukemia: A Systematic Review of Studies from Indian Settings.

Minimal residual disease (MRD) has become an essential tool in the management of B-cell acute lymphoblastic leukemia (B-ALL) and aids in tailoring treatment strategies to suit specific patient needs. Although much progress has been made in this area, there is limited data on the use of MRD in the Indian context. Our objective was to identify relevant literature that discusses the utility of MRD in the management of B-cell ALL in adolescents and young adults (AYA) and adults in Indian settings. A systematic search and screening of articles were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary data source was PubMed followed by Google Scholar for articles and conference proceedings. Of the 254 records screened, 24 records were retained for analysis. MRD monitoring had a significant role in the management of AYA/adult B-cell ALL patients. Variability of results was observed across these studies with respect to methods, techniques, and use. However, these studies evidenced and validated the importance of MRD assessment in risk-adapted management of B-cell ALL and highlighted the need for optimization. The advances in MRD diagnostics and applications are yet to be tested and adopted in Indian settings. Hence, there is a need for in-depth research to develop and optimize approaches for calibrating country-specific management strategies. The potential role of MRD assessments in anticipating relapse or treatment failures warrants more attention for the preemptive positioning of novel strategies involving immunotherapies.

Genome-wide 5'-C-phosphate-G-3' methylation patterns reveal the effect of heat stress on the altered semen quality in Bubalus bubalis.

Semen production and quality are closely correlated with different environmental factors in bovines, particularly for the buffalo (Bubalus bubalis) bulls reared under tropical and sub-tropical conditions. Factors including DNA methylation patterns, an intricate process in sperm cells, have an impact on the production of quality semen in buffalo bulls under abiotic stress conditions. The present study was conducted to identify DNA methylome signatures for semen quality in Murrah buffalo bulls, acclaimed as a major dairy breed globally, under summer heat stress. Based on semen quality parameters that significantly varied between the two groups over the seasons, the breeding bulls were classified into seasonally affected (SA = 6) and seasonally non-affected (SNA = 6) categories. DNA was isolated from purified sperm cells and sequenced using the RRBS (Reduced Representation Bisulfite Sequencing) technique for genome-wide methylome data generation. During the hot summer months, the physiological parameters such as scrotal surface temperature, rectal temperature, and respiration rate for both the SA and SNA bulls were significantly higher in the afternoon than in the morning. Whereas, the global CpG% of SA bulls was positively correlated with the afternoon's scrotal surface and rectal temperature. The RRBS results conveyed differentially methylated cytosines in the promoter region of the genes encoding the channels responsible for Ca2+ exchange, NPTN, Ca2+ activated chloride channels, ANO1, and a few structure-related units such as septins (SEPT4 and SEPT6), SPATA, etc. Additionally, the hypermethylated set of genes in SA was significantly enriched for pathways such as the FOXO signaling pathway and oocyte meiosis. The methylation patterns suggest promoter methylation in the genes regulating the sperm structure as well as surface transporters, which could contribute to the reduced semen quality in the Murrah buffalo bulls during the season-related heat stress.

Laparoscopic subtotal cholecystectomy in difficult gallbladder: Our experience in a tertiary care center.

Backgrounds/Aims: Open cholecystectomy is becoming obsolete and laparoscopic cholecystectomy has become the treatment of choice in gallstone diseases. Difficult gallbladders are encountered whenever there is a frozen calot's triangle, obliterated cystic plate, or both. Rather than converting to open procedure, there has been a growing preference for laparoscopic subtotal cholecystectomy (LSC) during difficult gallbladders. This study aimed to assess the advantages, indications, and viability of LSC in difficult gallbladders. Methods: The study included patients undergoing laparoscopic cholecystectomy in NIMS Hospital, Jaipur, from January 2021 to January 2023. Data of the patients who underwent LSC for difficult gallbladders included demographics, comorbidities, operative time, conversion to open cholecystectomy, length of hospital stay, and complications. LSC was classified into three types depending on the part of the gallbladder remnant. Results: A total of 728 patients underwent laparoscopic cholecystectomy. Among them, 41 patients (5.6%) were attempted for LSC. However, one patient was converted to an open procedure and the rest 40 underwent LSC. LSC was divided into 3 types, 4 patients underwent LSC type I, 34 patients underwent type II, and 2 patients type III. The average operating time and postoperative length of hospital stay were 86.2 minutes and 2.1 days, respectively. Two patients had surgical site infection. No patient had a bile leak and none required intensive care unit care. Conclusions: LSC is a safe and feasible option for use in difficult gallbladders.

Novel technique for laparoscopic common bile duct exploration using flexible videobronchoscope to study on clinical outcomes of single-stage (laparoscopic cholecystectomy and laparoscopic common bile duct exploration) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis - Prospective study in a tertiary care centre (BRACE study - BRonchoscope Assisted Common bile duct Exploration Study).

INTRODUCTION: This study aimed to study on clinical outcomes of single-stage (laparoscopic cholecystectomy [LC] and laparoscopic common bile duct [CBD] exploration using flexible videobronchoscope) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis-prospective study in a tertiary care centre (BRACE STUDY-Bronchoscope-Assisted CBD Exploration [CBDE] Study). PATIENTS AND METHODS: Between April 2022 and April 2023, patients who underwent LC with laparoscopic CBDE and endoscopic retrograde cholangiopancreatography (ERCP) followed by LC participated in this single-centre prospective research. The Institute Ethics Committee granted its approval after receiving an ethical review. The primary endpoint of the proposed research was the removal of the gall bladder and CBD stones. The secondary outcomes studied were complications using the Clavien-Dindo score, cost-effectiveness, patient satisfaction score and post-procedure duration of hospital stay. RESULTS: A total of 168 patients were included in the study. The success rate of LC with laparoscopic CBD exploration using a flexible videobronchoscope (Group 1) was significantly higher as compared to ERCP f/b LC (Group 2) (96.4% vs. 84.5%, P value = 0.02). Out of the 84 patients in Group 1, direct choledochotomies were performed on 83 of them. Group 1 had a considerably shorter hospital stay (4.6 ± 2.4 vs. 5.3 ± 6.2 days; P = 0.03). Both the cost ( P = 0.002) and the number of procedures per patient ( P < 0.001) were considerably higher in Group 2. Major complications (Clavien-Dindo grade 3 and above) were significantly higher in Group 2 ( P = 0.04). Patient satisfaction in Group 1 scored more favourably than those in Group 2 (2.26 ± 0.3 vs. 1.92 ± 0.7; P = 0.006). CONCLUSION: For concurrent gall bladder and CBD stones, single-stage management by LCBDE using a flexible videobronchoscope has a significantly better primary outcome and lower major complications than dual-stage management. The single-stage strategy also has advantages in terms of a shorter hospital stay, the need for fewer procedures, cost efficiency and patient satisfaction.

Genome-wide association mapping for field spot blotch resistance in South Asian spring wheat genotypes.

Spot blotch caused by Bipolaris sorokiniana ((Sacc.) Shoemaker) (teleomorph: Cochliobolus sativus [Ito and Kuribayashi] Drechsler ex Dastur) is an economically important disease of warm and humid regions. The present study focused on identifying resistant genotypes and single-nucleotide polymorphism (SNP) markers associated with spot blotch resistance in a panel of 174 bread spring wheat lines using field screening and genome-wide association mapping strategies. Field experiments were conducted in Agua Fria, Mexico, during the 2019-2020 and 2020-2021 cropping seasons. A wide range of phenotypic variation was observed among genotypes tested during both years. Twenty SNP markers showed significant association with spot blotch resistance on 15 chromosomes, namely, 1A, 1B, 2A, 2B, 2D, 3A, 3B, 4B, 4D, 5A, 5B, 6A, 6B, 7A, and 7B. Of these, two consistently significant SNPs on 5A, TA003225-0566 and TA003225-1427, may represent a new resistance quantitative trait loci. Further, in the proximity of Tsn1 on 5B, AX-94435238 was the most stable and consistent in both years. The identified genomic regions could be deployed to develop spot blotch-resistant genotypes, particularly in the spot blotch-vulnerable wheat growing areas.

Perioperative Treatment Strategies in EGFR-Mutant Early-Stage NSCLC: Current Evidence and Future Challenges.

Treatment with 3 years of adjuvant osimertinib is considered a new standard in patients with completely resected stage I to IIIA NSCLC harboring a common sensitizing EGFR mutation. This therapeutic approach significantly prolonged the disease-free survival and the overall survival versus placebo and revealed a significant role in preventing the occurrence of brain metastases. However, many unanswered questions remain, including the optimal duration of this therapy, whether all patients benefit from adjuvant osimertinib, and the role of adjuvant chemotherapy in this population. Indeed, there is a renewed interest in neoadjuvant strategies with targeted therapies in resectable NSCLC harboring oncogenic drivers. In light of these considerations, we discuss the past and current treatment options, and the clinical challenges that should be addressed to optimize the treatment outcomes in this patient population.

Rapid mini-chromosome divergence among fungal isolates causing wheat blast outbreaks in Bangladesh and Zambia.

The fungal pathogen, Magnaporthe oryzae Triticum pathotype, causing wheat blast disease was first identified in South America and recently spread across continents to South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Magnaporthe oryzae strains closely related to a South American field isolate B71 were found to have caused the wheat blast outbreaks in South Asia and Africa. Genomic variation among isolates from the three continents was examined using an improved B71 reference genome and whole-genome sequences. We found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates, although they were all close to B71 and, therefore, collectively referred to as the B71 branch. In addition, B71 branch strains carried at least one supernumerary mini-chromosome. Genome assembly of a Zambian strain revealed that its mini-chromosome was similar to the B71 mini-chromosome but with a high level of structural variation. Our findings show that while core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome and rapid genomic changes suggest the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.