tbuckley/cabot-search huggingface dataset:
The clinical significance of SPHK1 expression in human astrocytomas progression and overall patient survival
Authors: Jie Yuan, Jun Li, Hong-Yu Guan, Li-Yun Gong, Li-Bing Song, Nu Zhang, Jueheng Wu, Mengfeng Li
Journal: Cancer Research (2008)

5539  Previous studies have suggested that the sphingosine kinase 1 (SPHK1) gene can act as an oncogene, mediating various cellular functions such as cell proliferation, apoptosis inhibition and cell transformation and migration. The current study was conducted to investigate the expression of SPHK1 in human astrocytomas and to characterize its association with the clinical progression of astrocytomas. Our results of Western blotting and RT-PCR showed that SPHK1 mRNA and protein were upregulated in astrocytoma cell lines, as well as in astrocytoma tissues when compared with paired adjacent non-cancerous tissues from the same patients. In addition, 243 paraffin-embedded archival astrocytoma tissues were examined with immunohistochemical staining, among which 227 paraffin-embedded archival astrocytomas biopsies displayed moderate to strong cytoplasmic staining of SPHK1 in astrocytomas cells, whereas no significant staining of SPHK1 was detected in the adjacent non-cancerous epithelial cells. These data supported the notion that SPHK1 might play a role in the development and progression of astrocytomas. Quantitative SPHK1 immunohistochemical staining demonstrated that the SPHK1 expression level increased in parallel with the development and progression of astrocytomas. Further analysis of the relationship between SPHK1 staining and the clinical characteristics of patients showed a significant correlation of SPHK1 expression with the clinocopathological staging, while it was not correlated to the age and gender in astrocytomas patients, strongly suggesting that SPHK1 might be useful as an independent marker to identify subsets of astrocytomas patients with more aggressive disease. Furthermore, patients with high SPHK1 expression revealed a cumulative 3-year survival rate of 10.3% (n=100, 95% confidence interval, 0.041-0.165), as compared with the 57.7% (95% confidence interval, 0.517-0.637) cumulative 3-year survival rate in the low SPHK1 group (n =143), suggesting the possibility to use SPHK1 as a predictor for patient prognosis and survival. It is also noteworthy that the predictive significance of SPHK1 expression for poorer prognosis was identified in both relatively early- (grade I and II) and late-stage (grade III and IV) patient subgroups. Taken together, our data strongly suggest the usefulness of SPHK1 expression as a prognostic marker for astrocytoma patients.
The epidemiology of malignant melanoma, squamous cell carcinoma and basal cell carcinoma in the UK from 2004 to 2014: a population‐based cohort analysis using the Clinical Practice Research Datalink
Authors: F.N. Mirza, S. Yumeen, F.M. Walter
Journal: British Journal of Dermatology (2020)

Table 1.Stratified incidence and mortality model for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) in the UK (2004-2014) using the European Standard Population in 5-year age categories.
Association of Race/Ethnicity With Overall Survival Among Patients With Colorectal Liver Metastasis
Authors: Lucas W. Thornblade, Susanne Warner, Laleh Melstrom, Gagandeep Singh, Yuman Fong, Mustafa Raoof
Journal: JAMA Network Open (2020)

This cohort study assesses the association of race/ethnicity with overall survival among patients with colorectal liver metastasis overall and among those undergoing liver resection.
Modeling Resistance and Recurrence Patterns of Combined Targeted–Chemoradiotherapy Predicts Benefit of Shorter Induction Period
Authors: David M. McClatchy, Henning Willers, Aaron N. Hata, Zofia Piotrowska, Lecia V. Sequist, Harald Paganetti, Clemens Grassberger
Journal: Cancer Research (2020)

Optimal integration of molecularly targeted therapies, such as tyrosine kinase inhibitors (TKI), with concurrent chemotherapy and radiation (CRT) to improve outcomes in genotype-defined cancers remains a current challenge in clinical settings. Important questions regarding optimal scheduling and length of induction period for neoadjuvant use of targeted agents remain unsolved and vary among clinical trial protocols. Here, we develop and validate a biomathematical framework encompassing drug resistance and radiobiology to simulate patterns of local versus distant recurrences in a non-small cell lung cancer (NSCLC) population with mutated EGFR receiving TKIs and CRT. Our model predicted that targeted induction before CRT, an approach currently being tested in clinical trials, may render adjuvant targeted therapy less effective due to proliferation of drug-resistant cancer cells when using very long induction periods. Furthermore, simulations not only demonstrated the competing effects of drug-resistant cell expansion versus overall tumor regression as a function of induction length, but also directly estimated the probability of observing an improvement in progression-free survival at a given cohort size. We thus demonstrate that such stochastic biological simulations have the potential to quantitatively inform the design of multimodality clinical trials in genotype-defined cancers. SIGNIFICANCE: A biomathematical framework based on fundamental principles of evolution and radiobiology for in silico clinical trial design allows clinicians to optimize administration of TKIs before chemoradiotherapy in oncogene-driven NSCLC.
Metalign: efficient alignment-based metagenomic profiling via containment min hash
Authors: Nathan LaPierre, Mohammed Alser, Eleazar Eskin, David Koslicki, Serghei Mangul
Journal: Genome biology (2020)

Metagenomic profiling, predicting the presence and relative abundances of microbes in a sample, is a critical first step in microbiome analysis. Alignment-based approaches are often considered accurate yet computationally infeasible. Here, we present a novel method, Metalign, that performs efficient and accurate alignment-based metagenomic profiling. We use a novel containment min hash approach to pre-filter the reference database prior to alignment and then process both uniquely aligned and multi-aligned reads to produce accurate abundance estimates. In performance evaluations on both real and simulated datasets, Metalign is the only method evaluated that maintained high performance and competitive running time across all datasets.
Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function
Authors: Kathryn A. Helmin, Luisa Morales-Nebreda, Manuel A. Torres Acosta, Kishore R. Anekalla, Shang-Yang Chen, Hiam Abdala-Valencia, Yuliya Politanska, Paul Cheresh, Mahzad Akbarpour, Elizabeth M. Steinert, Samuel E. Weinberg, Benjamin D. Singer
Journal: Journal of Clinical Investigation (2020)

Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Tregs persist as a self-renewing population that regulates immune system activation. Whether maintenance DNA methylation is required for Treg lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator ubiquitin-like with plant homeodomain and RING finger domains 1 (Uhrf1) is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet nonuniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg genome for both lineage establishment and stability of identity and suppressive function.
Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics
Authors: David Dolivo, Pamela Weathers, Tanja Dominko
Journal: Acta Pharmaceutica Sinica B (2020)

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis, and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to fibrosis. To consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis, we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable doses. It is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases.
Frequent Mental Distress Among Adults, by Disability Status, Disability Type, and Selected Characteristics — United States, 2018
Authors: Robyn A. Cree, Catherine A. Okoro, Matthew M. Zack, Eric Carbone
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Frequent mental distress, defined as 14 or more self-reported mentally unhealthy days in the past 30 days,* is associated with adverse health behaviors, increased use of health services, mental disorders (e.g., diagnosis of major depressive disorder), chronic diseases, and functional limitations (1). Adults with disabilities more often report depression and anxiety (2), reduced health care access (3), and health-related risk behaviors (4) than do adults without disabilities. CDC analyzed 2018 Behavioral Risk Factor Surveillance System (BRFSS) data to compare the prevalence of frequent mental distress among adults with disabilities with that among adults without disabilities and to identify factors associated with mental distress among those with disabilities. Nationwide, an estimated 17.4 million adults with disabilities reported frequent mental distress; the prevalence of reported mental distress among those with disabilities (32.9%) was 4.6 times that of those without disabilities (7.2%). Among adults with disabilities, those with both cognitive and mobility disabilities most frequently reported mental distress (55.6%). Adults with disabilities who reported adverse health-related characteristics (e.g., cigarette smoking, physical inactivity, insufficient sleep, obesity, or depressive disorders) or an unmet health care need because of cost also reported experiencing more mental distress than did those with disabilities who did not have these characteristics. Adults living below the federal poverty level reported mental distress 70% more often than did adults in higher income households. Among states, age-adjusted prevalence of mental distress among adults with disabilities ranged from 25.2% (Alaska) to 42.9% (New Hampshire). Understanding the prevalence of mental distress among adults with disabilities could help health care providers, public health professionals, and policy makers target interventions and inform programs and policies to ensure receipt of mental health screening, care, and support services to reduce mental distress among adults with disabilities.
A Transcriptome-Wide Association Study Identifies Candidate Susceptibility Genes for Pancreatic Cancer Risk
Authors: Duo Liu, Dan Zhou, Yanfa Sun, Jingjing Zhu, Dalia Ghoneim, Chong Wu, Qizhi Yao, Eric R. Gamazon, Nancy J. Cox, Lang Wu
Journal: Cancer Research (2020)

Abstract Pancreatic cancer is among the most well-characterized cancer types, yet a large proportion of the heritability of pancreatic cancer risk remains unclear. Here, we performed a large transcriptome-wide association study to systematically investigate associations between genetically predicted gene expression in normal pancreas tissue and pancreatic cancer risk. Using data from 305 subjects of mostly European descent in the Genotype-Tissue Expression Project, we built comprehensive genetic models to predict normal pancreas tissue gene expression, modifying the UTMOST (unified test for molecular signatures). These prediction models were applied to the genetic data of 8,275 pancreatic cancer cases and 6,723 controls of European ancestry. Thirteen genes showed an association of genetically predicted expression with pancreatic cancer risk at an FDR ≤ 0.05, including seven previously reported genes (INHBA, SMC2, ABO, PDX1, RCCD1, CFDP1, and PGAP3) and six novel genes not yet reported for pancreatic cancer risk [6q27: SFT2D1 OR (95% confidence interval (CI), 1.54 (1.25–1.89); 13q12.13: MTMR6 OR (95% CI), 0.78 (0.70–0.88); 14q24.3: ACOT2 OR (95% CI), 1.35 (1.17–1.56); 17q12: STARD3 OR (95% CI), 6.49 (2.96–14.27); 17q21.1: GSDMB OR (95% CI), 1.94 (1.45–2.58); and 20p13: ADAM33 OR (95% CI): 1.41 (1.20–1.66)]. The associations for 10 of these genes (SFT2D1, MTMR6, ACOT2, STARD3, GSDMB, ADAM33, SMC2, RCCD1, CFDP1, and PGAP3) remained statistically significant even after adjusting for risk SNPs identified in previous genome-wide association study. Collectively, this analysis identified novel candidate susceptibility genes for pancreatic cancer that warrant further investigation. Significance: A transcriptome-wide association analysis identified seven previously reported and six novel candidate susceptibility genes for pancreatic cancer risk.
Safety of Anti–PD-L1 Inhibition in HIV-1–Infected Patients With Cancer—Reply
Authors: Maria Gonzalez-Cao, Javier Martinez-Picado, Rafael Rosell
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Prevalence and Risk Factors Associated With Attention-Deficit/Hyperactivity Disorder Among US Black Individuals
Authors: Jude Mary Cénat, Camille Blais-Rochette, Catherine Morse, Marie-Pier Vandette, Pari-Gole Noorishad, Cary Kogan, Assumpta Ndengeyingoma, Patrick R. Labelle
Journal: JAMA Psychiatry (2020)

As stated in the DSM-5, it is generally reported that the prevalence of attention-deficit/hyperactivity disorder (ADHD) is lower among Black individuals compared with the general population. However, Black individuals living in countries where they are considered a minority population group (eg, in Northern America and Europe) are underrepresented in studies evaluating ADHD.To estimate the pooled prevalence of ADHD and identify associated risk factors among US Black individuals.This systematic review and meta-analysis identified peer-reviewed studies published until October 18, 2019, using the APA PsycInfo, MEDLINE, Embase, Cochrane CENTRAL, CINAHL, ERIC, and Education Source databases.Eligible trials were published in French or English, had empirical data on the prevalence of ADHD in samples or subsamples of Black people, and were conducted in countries with Black minority populations. All studies were assessed and passed quality evaluation.The PRISMA guideline was used for extracting and reporting data. Random-effects meta-analyses were generated to estimate the prevalence of ADHD among Black individuals using the metafor package in R.Prevalence and risk factors associated with ADHD among Black individuals were identified.A total of 24 independent samples and subsamples from 21 studies published between 1979 and 2020 (154 818 Black participants) were included in this systematic review and meta-analysis. All included studies were conducted in the US. Two studies were conducted assessing adults (aged 18 years or older), 8 assessing children (0-12 years), 1 assessing adolescents (aged 13-17 years), and 13 assessing both children and adolescents. The pooled prevalence of ADHD was 14.54% (95% CI, 10.64%-19.56%). In a narrative review of the studies in this analysis, some studies found risk factors associated with ADHD, such as sociodemographic characteristics (age, sex, race, and socioeconomic status), familial factors, environmental factors, and risk behaviors, but the data did not permit a moderation analysis to assess these findings in this study.Contrary to what is stated in the DSM-5, the results of this systematic review and meta-analysis suggest that Black individuals are at higher risk for ADHD diagnoses than the general US population. These results highlight a need to increase ADHD assessment and monitoring among Black individuals from different social backgrounds. They also higlight the importance of establishing accurate diagnoses and culturally appropriate care.
Is Oxytocin “Nature’s Medicine”?
Authors: C. Sue Carter, William M. Kenkel, Evan L. MacLean, Steven R. Wilson, Allison M. Perkeybile, Jason R. Yee, Craig F. Ferris, Hossein P. Nazarloo, Stephen W. Porges, John M. Davis, Jessica J. Connelly, Marcy A. Kingsbury
Journal: Pharmacological Reviews (2020)

Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein–coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. <h3>Significance Statement</h3> Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.
Mortality from malaria in France, 2005 to 2014
Authors: Eric Kendjo, Marc Thellier, Harold Noël, Stéphane Jauréguiberry, Alexandra Septfons, Oussama Mouri, Frédérick Gay, Ilhame Tantaoui, Eric Caumes, Sandrine Houzé, Renaud Piarroux
Journal: Eurosurveillance (2020)

IntroductionMalaria is a notifiable disease in all European Union and European Economic Area countries except Belgium and France, where only autochthonous malaria is notifiable. Although morbidity caused by malaria has been assessed, little is known about mortality incidence.ObjectiveOur aim was to estimate the number of imported malaria-related deaths in hospital in metropolitan France.MethodsWe matched individual deaths reported between 1 January 2005 and 31 December 2014 to the French National Reference Centre for malaria (FNRCm) with malaria-related deaths from two other sources: the French National Registry on medical causes of death and the French national hospital discharge database. A capture-recapture method with log-linear modelling was used. Age, sex and place of death stratification were applied to remove heterogeneity.ResultsThe estimated malaria-related deaths in metropolitan France during the study period were 205 (95% confidence interval (CI): 191-219). The annual mean number of malaria-related deaths was estimated at 21 (95% CI: 19-22). The FNRCm malaria-related deaths surveillance had a 38% sensitivity (95% CI: 32-44). Among 161 in-hospital individual malaria-related deaths reported from three data sources, the sex ratio (male to female) was 2.6. Median age of the patients was 57 years, ranging from 1 to 89 years.ConclusionThe pertinent finding of this report is that malaria-related death records were significantly less complete [corrected] than case records. Therefore, data comparison of imported malaria morbidity and mortality between countries should imperatively be assessed using standard indicators weighted according to the completeness of health surveillance systems.