Cysteine metabolic circuitries: druggable targets in cancer

xloma.fota13 shared this article with you from Inoreader Cysteine metabolic circuitries: druggable targets in cancer Via Cancer View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tumour‐only sequencing for oncology management: germline‐focused analysis and implications

xloma.fota13 shared this article with you from Inoreader Tumour‐only sequencing for oncology management: germline‐focused analysis and implications Via Genes, Chromosomes and Cancer Abstract As patients are now routinely having large somatic genomic testing panels undertaken as part of routine management, there is the rising likelihood of uncovering the presence of a germline pathogenic variant. This may be found on testing undertaken on plasma (ctDNA) or tissue. This has led to the need for clear guidelines for oncologists about how to manage such results, including which variants require validation, how this should be undertaken, and what potential problems may arise. This requires an understanding of the limits of testing, and the pitfalls that may be encountered. In this review, we assess the frequency of detecting germline variants through tumour‐only sequencing, the necessary considerations for such information to be analysed and the role of the molecular tumour board in considering results. We assess the additional considerations for interpretation of the underlying tumour, use of ctDNA or tissue for testing, clonal haematopoiesis and hypermutation. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysis of Mutational Signatures with YAPSA (Yet Another Package for Signature Analysis)

xloma.fota13 shared this article with you from Inoreader Analysis of Mutational Signatures with YAPSA (Yet Another Package for Signature Analysis) Via Genes, Chromosomes and Cancer Abstract Different mutational processes leave characteristic patterns of somatic mutations in the genome that can be identified as mutational signatures. Determining the contributions of mutational signatures to cancer genomes allows not only to reconstruct the etiology of somatic mutations, but can also be used for improved tumor classification and support therapeutic decisions. We here present the R package YAPSA (Yet Another Package for Signature Analysis) to deconvolute the contributions of mutational signatures to tumor genomes. YAPSA provides in‐built collections from the COSMIC and PCAWG SNV signature sets as well as the PCAWG Indel signatures and employs signature‐specific cutoffs to increase sensitivity and specificity. Furthermore, YAPSA allows to determine 95% confidence intervals for signature exposures, to perform constrained stratified signature analyses to obtain enrichment and depletion patterns of the identified signatures and, when applied to whole exome sequencing da ta, to correct for the triplet content of individual target capture kits. With this functionality, YAPSA has proved to be a valuable tool for analysis of mutational signatures in molecular tumor boards in a precision oncology context. YAPSA is available at R/Bioconductor (http://bioconductor.org/packages/3.12/bioc/html/YAPSA.html). This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Extended cubic B‐spline collocation method for singularly perturbed parabolic differential‐difference equation arising in computational neuroscience

xloma.fota13 shared this article with you from Inoreader Extended cubic B‐spline collocation method for singularly perturbed parabolic differential‐difference equation arising in computational neuroscience Via International Journal for Numerical Methods in Biomedical Engineering Abstract A parameter uniform numerical method is presented for solving singularly perturbed parabolic differential‐difference equations with small shift arguments in the reaction terms arising in computational neuroscience. To approximate the terms with the shift arguments, Taylor's series expansion is used. The resulting singularly perturbed parabolic differential equation is solved by applying the implicit Euler method in temporal direction and extended cubic B‐spline basis functions consisting of a free parameter λ for the resulting system of ordinary differential equations in the spatial direction. The proposed method is shown to be accurate of order by preserving an ε‐uniform convergence. To demonstrate the applicability of the proposed method, two test examples are solved by the method and the numerical results are compared with some existing results. The obtained numerical results agreed with the theoretical results. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Moving the dial on prenatal stress mechanisms of neurodevelopmental vulnerability to mental health problems: A personalized prevention proof of concept

xloma.fota13 shared this article with you from Inoreader Moving the dial on prenatal stress mechanisms of neurodevelopmental vulnerability to mental health problems: A personalized prevention proof of concept Via Developmental Psychobiology Abstract Prenatal stress exposure increases vulnerability to virtually all forms of psychopathology. Based on this robust evidence base, we propose a "Mental Health, Earlier" paradigm shift for prenatal stress research, which moves from the documentation of stress‐related outcomes to their prevention, with a focus on infant neurodevelopmental indicators of vulnerability to subsequent mental health problems. Achieving this requires an expansive team science approach. As an exemplar, we introduce the Promoting Healthy Brain Project (PHBP), a randomized trial testing the impact of the Wellness‐4‐2 personalized prenatal stress‐reduction intervention on stress‐related alterations in infant neurodevelopmental trajectories in the first year of life. Wellness‐4‐2 utilizes bio‐integrated stress monitoring for just‐in‐time adaptive intervention. We highlight unique challenges and opportunities this novel team science approach presents in synergizing expertise across predictiv e analytics, bioengineering, health information technology, prevention science, maternal – fetal medicine, neonatology, pediatrics, and neurodevelopmental science. We discuss how innovations across many areas of study facilitate this personalized preventive approach, using developmentally sensitive brain and behavioral methods to investigate whether altering children's adverse gestational exposures, i.e., maternal stress in the womb, can improve their mental health outlooks. In so doing, we seek to propel developmental SEED research towards preventive applications with the potential to reduce the pernicious effect of prenatal stress on neurodevelopment, mental health, and wellbeing. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Are We Ready for Bariatric Surgery in a Liver Transplant Program? A Meta-Analysis

xloma.fota13 shared this article with you from Inoreader Are We Ready for Bariatric Surgery in a Liver Transplant Program? A Meta-Analysis Via Latest Results for Obesity Surgery Abstract Background Obesity-related non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are two main causes of end-stage liver disease requiring a liver transplantation. Studies exploring bariatric surgery in the liver transplantation setting have increased in recent years; however, a systematic analysis of the topic is lacking to date. This meta-analysis was conducted to explore the perioperative and long-term outcomes of bariatric surgery in obese patients undergoing liver transplantation. Methods Electronic databases were systematically searched for studies reporting bariatric surgery in patients undergoing liver transplantation. The primary outcomes were postoperative complications and mortality. We also extracted data about excess weight loss, body mass index, and improvement of comorbidities after bariatric surgery. Results A total of 96 patients from 8 articles were included. Bariatric surgery–related morbidity and mortality rates were 37% (95% CI 0.27–0.47) and 0.6% (95% CI 0.02–0.13), respectively. Body mass index at 24 months was 31.02 (95% CI 25.96–36.09) with a percentage excess weight loss at 12 and 24 months of 44.08 (95% CI 27.90–60.26) and 49.2 (95% CI 31.89–66.66), respectively. After bariatric surgery, rates of improvement of arterial hypertension and diabetes mellitus were 61% (95% CI 0.45–0.75) and 45% (95% CI 0.25–0.66), respectively. In most patients, bariatric surgery was performed after liver transplant and the most frequent technique was sleeve gastrectomy. Conclusions Bariatric surgery can be performed safely in the setting of liver transplantation resulting in improvement of obesity-related comorbidities. The optimal timing and technique require further studies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Extramedullary Hematopoiesis in Adrenal Incidentaloma: Case Report of an Atypical Histopathological Finding

xloma.fota13 shared this article with you from Inoreader Extramedullary Hematopoiesis in Adrenal Incidentaloma: Case Report of an Atypical Histopathological Finding Via Latest Results for Indian Journal of Surgery Abstract Adrenal gland extramedullary hematopoiesis is extremely rare, and when present, imaging studies may mimic an incidentaloma suspicious of malignancy. We present a 55-year-old woman without a history of hematologic disorder or neoplasms. There was an incidental finding of a 3.2 × 2.4-cm heterogenous adrenal mass and enhanced by contrast abdominal CT scan. Suspicious of malignancy was established, and laparoscopic left adrenalectomy was performed. Histopathological examination and immunohistochemical staining exhibited myeloid and erythroid precursors, as well as megakaryocyte confirming the diagnosis of extramedullary hematopoiesis in the adrenal gland. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacite et innocuite des agents antiviraux contre le SRAS-CoV-2, selon des donnees detudes sur la COVID-19 et dautres infections virales aigues : revue systematique et meta-analyse [Recherche]

xloma.fota13 shared this article with you from Inoreader Efficacite et innocuite des agents antiviraux contre le SRAS-CoV-2, selon des donnees detudes sur la COVID-19 et dautres infections virales aigues : revue systematique et meta-analyse [Recherche] Via Canadian Medical Association Journal current issue View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mortality among patients with frequent emergency department use for alcohol-related reasons

xloma.fota13 shared this article with you from Inoreader Mortality among patients with frequent emergency department use for alcohol-related reasons in Ontario: a population-based cohort study [Research] Via Canadian Medical Association Journal current issue BACKGROUND: Little is known about the risk of death among people who visit emergency departments frequently for alcohol-related reasons, including whether mortality risk increases with increasing frequency of visits. Our primary objective was to describe the sociodemographic and clinical characteristics of this high-risk population and examine their 1-year overall mortality, premature mortality and cause of death as a function of emergency department visit frequency in Ontario, Canada. METHODS: We conducted a population-based retrospective cohort study using linked health administrative data (Jan. 1, 2010, to Dec. 31, 2016) in Ontario for people aged 16–105 years who made at least 2 emergency department visits for mental or behavioural disorders due to alcohol within 1 year. We subdivided the cohort based on visit frequency (2, 3 or 4, or ≥ 5). The primary outcome was 1-year mortality, adjusted for age, sex, income, rural residence and presence of comorbidities. We examined premature mortality using years of potential life lost (YPLL). RESULTS: Of the 25 813 people included in the cohort, 17 020 (65.9%) had 2 emergency department visits within 1 year, 5704 (22.1%) had 3 or 4 visits, and 3089 (12.0%) had 5 or more visits. Males, people aged 45–64 years, and those living in urban centres and lower-income neighbourhoods were more likely to have 3 or 4 visits, or 5 or more visits. The all-cause 1-year mortality rate was 5.4% overall, ranging from 4.7% among patients with 2 visits to 8.8% among those with 5 or more visits. Death due to external causes (e.g., suicide, accidents) was most common. The adjusted mortality rate was 38% higher for patients with 5 or more visits than for those with 2 visits (adjusted hazard ratio 1.38, 95% confidence interval 1.19–1.59). Among 25 298 people aged 16–74 years, this represented 30 607 YPLL. INTERPRETATION: We observed a high mortality rate among relatively young, mostly urban, lower-income people with frequent emergency department visits for alcohol-related reasons. These visits are opportunities for intervention in a high-risk population to reduce a substantial mortality burden. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Genomic Destabilization and its Associated Mutagenesis Increase with Senescence‐Associated Phenotype Expression

xloma.fota13 shared this article with you from Inoreader Genomic Destabilization and its Associated Mutagenesis Increase with Senescence‐Associated Phenotype Expression Via Cancer Science Abstract Cancer develops through multiple rounds of clonal evolution of cells with abrogated defense systems. Such clonal evolution is triggered by genomic destabilization with associated mutagenesis. However, it remains unclear what increases the risk of genomic destabilization. Genomic instability is usually the result of erroneous repair of DNA double‐strand breaks (DSBs); paradoxically, however, most cancers develop with genomic instability but lack mutations in DNA repair systems. In this manuscript, we review current knowledge regarding a cellular state that increases the risk of genomic destabilization, in which cells exhibit phenotypes often observed during senescence. In addition, we also explore the pathways that lead to genomic destabilization and its associated mutagenesis, which ultimately result in cancer. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

NQO1 promotes an aggressive phenotype in hepatocellular carcinoma via amplifying ERK‐NRF2 signaling

xloma.fota13 shared this article with you from Inoreader NQO1 promotes an aggressive phenotype in hepatocellular carcinoma via amplifying ERK‐NRF2 signaling Via Cancer Science Abstract Patients with hepatocellular carcinoma (HCC) are usually diagnosed at the later stages and have poor survival outcomes. New molecules are urgently needed for the prognostic predication and individual treatment. Our study shows that the high levels of NQO1 expression are frequently existed in HCC with obvious cancer‐specific pattern. The patient with NQO1‐high tumors was significantly associated with poor survival outcomes and served as an independent predictor. Functional experiments showed that NQO1 promotes the growth and aggressiveness of HCC in both in vitro and in vivo models, and the underlying mechanism involved NQO1‐derived amplification of ERK/P38‐NRF2 signaling. Combined blockage of ERK and NRF2 signaling generated the stronger growth inhibition than any single blockage, especially for HCC with high‐NQO1. Therefore, NQO1 is a potential biomarker for HCC early diagnosis and prognosis prediction, and also attractive cancer‐specific targets for HCC treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tick species from Africa by migratory birds: a 3-year study in Italy

xlomafota.13 shared this article with you from Inoreader Tick species from Africa by migratory birds: a 3-year study in Italy Via Latest Results for Experimental and Applied Acarology Abstract The role of resident or migratory birds in dispersal of tick species and tick-borne pathogens is still poorly known in Italy. We report here the results of a 3-year project based on sampling ticks from migratory birds, as well as from the vegetation at three stop-over sites for migrants, namely the islands of Ventotene (Latium), Asinara (Sardinia) and Ustica (Sicily). During the spring seasons from 2017–2019, in total 2681 ticks were collected, 2344 of which were sampled from migratory birds and 337 from the vegetation. Ticks were identified by morphology or by molecular tools when necessary. In total, 16 tick species were identified among which the following were exclusively found on birds: Hyalomma rufipes (43.3%), Hy. truncatum (0.1%), Ixodes frontalis (11.8%), Ix. inopinatus (0.2%), Ix. ricinus (3%), Haemaphysalis punctata (0.08%), Hae. erinacei (0.1%), Amblyomma variegatum (0.08%) and Argas vulgaris 0.1%), whereas five species were exclusively collected from the vegetation: Rhipicephalus bursa (10.5%), Rh. turanicus (5.9%), Rh. sanguineus sensu lato (2%), Rh. pusillus (2.4%), Hae. sulcata (0.08%). Hy. marginatum (10.3%) and Ix. ventalloi (9.3%) were found both on birds and on the vegetation on the island Ustica. It is worth noting that the search for ticks on the vegetation did not detect allochthonous tick species. Although we found several interesting local species and allochthonous ticks like Hy. rufipes, Am. variegatum and Ar. vulgaris on birds, further investigations are needed to better define the possible role of migratory birds in the introduction of ticks and tick-borne diseases in Italy, above all after the evidence of imported ticks positive to Crimean Congo hemorrhagic fever (CCHF) virus in several European countries. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.