Splicing factor ESRP1 controls ER-positive breast cancer by altering metabolic pathways

The epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) control the epithelial-to-mesenchymal transition (EMT) splicing program in cancer. However, their role in breast cancer recurrence is unclear. In this study, we report that high levels of ESRP1, but not ESRP2, are associated with poor prognosis in estrogen receptor positive (ER+) breast tumors. Knockdown of ESRP1 in endocrine-resistant breast cancer models decreases growth significantly and alters the EMT splicing signature, which we confirm using TCGA SpliceSeq data of ER+ BRCA tumors. However, these changes are not accompanied by the development of a mesenchymal phenotype or a change in key EMT-transcription factors. In tamoxifen-resistant cells, knockdown of ESRP1 affects lipid metabolism and oxidoreductase processes, resulting in the decreased expression of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), and phosphoglycerate dehydrogenase (PHGDH) at both the mRNA and protein levels. Furthermore, ESRP1 knockdown increases the basal respiration and spare respiration capacity. This study reports a novel role for ESRP1 that could form the basis for the prevention of tamoxifen resistance in ER+ breast cancer

A framework for automated anomaly detection in high frequency water-quality data from in situ sensors

River water-quality monitoring is increasingly conducted using automated in situ sensors, enabling timelier identification of unexpected values. However, anomalies caused by technical issues confound these data, while the volume and velocity of data prevent manual detection. We present a framework for automated anomaly detection in high-frequency water-quality data from in situ sensors, using turbidity, conductivity and river level data. After identifying end-user needs and defining anomalies, we ranked their importance and selected suitable detection methods. High priority anomalies included sudden isolated spikes and level shifts, most of which were classified correctly by regression-based methods such as autoregressive integrated moving average models. However, using other water-quality variables as covariates reduced performance due to complex relationships among variables. Classification of drift and periods of anomalously low or high variability improved when we applied replaced anomalous measurements with forecasts, but this inflated false positive rates. Feature-based methods also performed well on high priority anomalies, but were also less proficient at detecting lower priority anomalies, resulting in high false negative rates. Unlike regression-based methods, all feature-based methods produced low false positive rates, but did not and require training or optimization. Rule-based methods successfully detected impossible values and missing observations. Thus, we recommend using a combination of methods to improve anomaly detection performance, whilst minimizing false detection rates. Furthermore, our framework emphasizes the importance of communication between end-users and analysts for optimal outcomes with respect to both detection performance and end-user needs. Our framework is applicable to other types of high frequency time-series data and anomaly detection applications

Whole Genome Characterization of a Few EMS-Induced Mutants of Upland Rice Variety Nagina 22 Reveals a Staggeringly High Frequency of SNPs Which Show High Phenotypic Plasticity Towards the Wild-Type

The Indian initiative, in creating mutant resources for the functional genomics in rice, has been instrumental in the development of 87,000 ethylmethanesulfonate (EMS)-induced mutants, of which 7,000 are in advanced generations. The mutants have been created in the background of Nagina 22, a popular drought- and heat-tolerant upland cultivar. As it is a pregreen revolution cultivar, as many as 573 dwarf mutants identified from this resource could be useful as an alternate source of dwarfing. A total of 541 mutants, including the macromutants and the trait-specific ones, obtained after appropriate screening, are being maintained in the mutant garden. Here, we report on the detailed characterizations of the 541 mutants based on the distinctness, uniformity, and stability (DUS) descriptors at two different locations. About 90% of the mutants were found to be similar to the wild type (WT) with high similarity index (>0.6) at both the locations. All 541 mutants were characterized for chlorophyll and epicuticular wax contents, while a subset of 84 mutants were characterized for their ionomes, namely, phosphorous, silicon, and chloride contents. Genotyping of these mutants with 54 genomewide simple sequence repeat (SSR) markers revealed 93% of the mutants to be either completely identical to WT or nearly identical with just one polymorphic locus. Whole genome resequencing (WGS) of four mutants, which have minimal differences in the SSR fingerprint pattern and DUS characters from the WT, revealed a staggeringly high number of single nucleotide polymorphisms (SNPs) on an average (16,453 per mutant) in the genic sequences. Of these, nearly 50% of the SNPs led to non-synonymous codons, while 30% resulted in synonymous codons. The number of insertions and deletions (InDels) varied from 898 to 2,595, with more than 80% of them being 1–2 bp long. Such a high number of SNPs could pose a serious challenge in identifying gene(s) governing the mutant phenotype by next generation sequencing-based mapping approaches such as Mutmap. From the WGS data of the WT and the mutants, we developed a genic resource of the WT with a novel analysis pipeline. The entire information about this resource along with the panicle architecture of the 493 mutants is made available in a mutant database EMSgardeN22 (http://14.139.229.201/EMSgardeN22)

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

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Not AvailableWild introgressions play a crucial role in improving the genetic diversity of a cultivated varieties and also act as an important source for novel alleles for crop improvement. High-yielding stable backcross introgression lines identified from inter-specific crosses of Swarna cv. Oryza sativa with Oryza nivara were crossed among each other and also with parent Swarna. The F2 populations generated from 5 crosses, viz. Swarna x 166S (C1), 166S x 14S (C2), 166S x 148S (C3), 65S x 248S (C4) and 166-2S x Swarna (C5), were evaluated for 7 phenotypic traits in field conditions. Phenotypic data were analysed for genetic variability and trait association in each population individually. Descriptive statistics and correlation of yield traits in the population and the comparison among all five populations were estimated. Among the populations, C2 showed the highest average trait values for single plant yield, tiller numbers, productive tillers and harvest index. Highest range of phenotypic variation for single plant yield was also observed in C2 followed by C5; however, wide range of variation for plant height and biomass was observed in C3 and C5. Single plant yield showed significant association with all the 7 traits consistently across the populations. Plant height and biomass also showed significant variation in trait association with other traits under study. Development of mapping populations by crossing among backcross introgression lines is a useful strategy to pyramid multiple traits of interest with minimum donor introgressions.ICA

Contralateral Axillary Metastasis in Breast Carcinoma: Case Report and Review of Literature

The clinical dilemma of management of isolated contralateral axillary metastasis (CAM) in carcinoma breast remains unsolved. We report a case of metachronous contralateral left axillary metastasis in a 54-year-old postmenopausal woman, its management, and review of literature. After ruling out distant metastasis and occult primary in the opposite breast, curative treatment was planned. She underwent left axillary lymph node dissection which on histopathology showed metastatic carcinoma. Management of CAM with curative or palliative intent and whether to consider them as locoregional or distant metastasis remains controversial. CAM may occur due to the locoregional spread of disease, and hence, curative intent of treatment should be offered to these patients

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Not AvailableWild introgressions play a crucial role in crop improvement by transferring important novel alleles and broadening allelic diversity of cultivated germplasm. In this study, two stable backcross alien introgression lines 166s and 14s derived from Swarn/Oryza nivara IRGC81848 were used as parents to generate populations to map quantitative trait loci (QTLs) for yield-related traits. Field evaluation of yield-related traits in F2, F3, and F4 population was carried out in normal irrigated conditions during the wet season of 2015 and dry seasons of 2016 and 2018, respectively. Plant height, tiller number, productive tiller number, total dry matter, and harvest index showed a highly significant association to single plant yield in F2, F3, and F4. In all, 21, 30, and 17 QTLs were identified in F2, F2:3, and F2:4, respectively, for yield-related traits. QTLs qPH6.1 with 12.54% phenotypic variance (PV) in F2, qPH1.1 with 13.01% PV, qTN6.1 with 10.08% PV in F2:3, and qTGW6.1 with 15.19% PV in F2:4 were identified as major effect QTLs. QTLs qSPY4.1 and qSPY6.1 were detected for grain yield in F2 and F2:3 with PV 8.5 and 6.7%, respectively. The trait enhancing alleles of QTLs qSPY4.1, qSPY6.1, qPH1.1, qTGW6.1, qTGW8.1, qGN4.1, and qTDM5.1 were from O. nivara. QTLs of the yield contributing traits were found clustered in the same chromosomal region. qTGW8.1 was identified in a 2.6 Mb region between RM3480 and RM3452 in all three generations with PV 6.1 to 9.8%. This stable and consistent qTGW8.1 allele from O. nivara can be fine mapped for identification of causal genes. From this population, lines C212, C2124, C2128, and C2143 were identified with significantly higher SPY and C2103, C2116, and C2117 had consistently higher thousand-grain weight values than both the parents and Swarna across the generations and are useful in gene discovery for target traits and further crop improvement.Not Availabl