tbuckley/cabot-search huggingface dataset:
Validation and Utility Testing of Clinical Prediction Models
Authors: Amin Adibi, Mohsen Sadatsafavi, John P. A. Ioannidis
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Targeted Apoptosis of Ductular Reactive Cells Reduces Hepatic Fibrosis in a Mouse Model of Cholestasis
Authors: Adiba I. Azad, Anuradha Krishnan, Leia Troop, Ying Li, Tomohiro Katsumi, Kevin Pavelko, Enis Kostallari, Maria Eugenia Guicciardi, Gregory J. Gores
Journal: Hepatology (2020)

In cholestatic liver diseases, ductular reactive (DR) cells extend into the hepatic parenchyma and promote inflammation and fibrosis. We have previously observed that multidrug-resistant 2 (Mdr2-/- ) double knockout (DKO) mice lacking tumor necrosis factor-related apoptosis-inducing ligand receptor (Tr-/- ) display a more extensive ductular reaction and hepatic fibrosis compared to Mdr2-/- mice. This observation suggests that the magnitude of the DR-cell population may be regulated by apoptosis.To examine this concept, we cultured epithelial cell adhesion molecule-positive reactive cholangioids (ERCs) obtained from wild-type (WT), Tr-/- , Mdr2-/- and DKO mice. Single-cell transcriptomics and immunostaining of both WT and DKO ERCs confirmed their DR-cell phenotype. Moreover, DKO ERCs displayed a unique translational cluster with expression of chemokines, indicating a reactive state. Incubation with the myeloid cell leukemia 1 (MCL1) inhibitor S63845, a proapoptotic BH3-mimetic therapy, significantly decreased DKO and Mdr2-/- ERC viability compared to WT. Intravenous administration of S63845 significantly reduced the DR-cell population and markers of inflammation and liver fibrosis in Mdr2-/- and DKO mice. Furthermore, DKO mice treated with S63845 displayed a significant decrease in hepatic B lymphocytes compared to untreated mice as assessed by high-definition mass cytometry by time-of-flight. Coculture of bone marrow-derived macrophages with ERCs from DKO mouse livers up-regulated expression of the B cell-directed chemokine (C-C motif) ligand 5. Finally, DR cells were noted to be primed for apoptosis with Bcl-2 homologous antagonist/killer activation in vitro and in vivo in primary sclerosing cholangitis liver specimens.DR cells appear to play a key role in recruiting immune cells to the liver to actively create an inflammatory and profibrogenic microenvironment. Pharmacologic targeting of MCL1 in a mouse model of chronic cholestasis reduces DR-cell and B-cell populations and hepatic fibrosis.
Abstract P490: Subclinical Thyroid Disorders and Triglyceride-rich Lipoprotein Particles Concentration. ELSA-Brasil Cohort
Authors: Carolina Janovsky, Marcio S Bittencourt, Alessandra C Goulart, Raul Santos, Michael J Blaha, Steven R Jones, Peter P Toth, Isabela M Bensenor, Paulo A LOTUFO
Journal: Circulation (2020)

Background: Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. Subclinical hypothyroidism is associated with higher levels of total cholesterol and Low-density lipoprotein cholesterol as well as high levels of triglycerides and low levels of high-density lipoprotein cholesterol. Triglyceride-rich Lipoprotein Particles concentration (TRLP) have recently emerged as a causal factor for atherogenesis. Aim: To evaluate the relationship between Subclinical Hypothyroidism and Subclinical Hyperthyroidism and Triglyceride-rich Lipoprotein Particles. Methods: Participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were classified according to the baseline thyroid function as Subclinical Hypothyroidism, Euthyroidism, and Subclinical Hyperthyroidism. Conventional lipid concentrations (total, HDL cholesterol, and triglycerides were determined by a nonprecipitated colorimetric method. The TRLP subfractions were analyzed through Nuclear Magnetic Resonance spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted a multivariate linear regression model adjusted for demographic characteristics (race, gender, and educational level), body-mass index, diabetes, smoking status, and alcoholic beverages intake. Results: Of 3,550 individuals free of cardiovascular or thyroid diseases (54%, women; median age 51 years; 51% White, and 53% with at least college education) 92%of them were euthyroid, 6.8% had subclinical hypothyroidism, and 1.2% had subclinical hyperthyroidism. No differences were observed concern the levels of total, HDL, and LDL-cholesterol, but triglycerides were higher for people with Subclinical Hypothyroidism. After adjustment by the covariates described above and using subjects with normal thyroid function as the reference group, for people with Subclinical hypothyroidism a difference of means ( and 95% Confidence Interval) for Total TRLP levels (in ng/L) obtained was 0.06 (-0.00 to 0.13), and for the TRLP subfractions elevated for Very-Small [0.16 (0.02 to 0.28)] and Very-Large [0.21 (0.05 to 0.36)], and similar values for Small [-0.01 (-0.13 to 0.12)]; Medium [0.05 (-0.08 to 0.17)] and Large [0.16 (-0.06 to 0.38)] subfractions. In Subclinical Hyperthyroidism, there was a reduction in Total TRLP (-0.24 (-0.40 - -0.08)), seemingly driven by reduced Very Small-TRLP (0.23 (-0.11 - 0.57). Conclusion: This study suggests that subclinical hypothyroidism is associated with high levels of Very-Small and Very-Large TRLP, which are related to an unfavorable atherogenic profile. Subclinical Hyperthyroidism is associated with low concentrations of Very-Small TRLP.
Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets
Authors: Jason K. Karimy, Benjamin C. Reeves, Eyiyemisi Damisah, Phan Q. Duy, Prince Antwi, Wyatt David, Kevin Wang, Steven J. Schiff, David D. Limbrick, Seth L. Alper, Benjamin C. Warf, Maiken Nedergaard, J. Marc Simard, Kristopher T. Kahle
Journal: Nature Reviews Neurology (2020)
Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine
Authors: Connor J Liu, Maximilian Schaettler, Dylan T Blaha, Jay A Bowman-Kirigin, Dale K Kobayashi, Alexandra J Livingstone, Diane Bender, Christopher A Miller, David M Kranz, Tanner M Johanns, Gavin P Dunn
Journal: Neuro-Oncology (2020)

Although clinical trials testing immunotherapies in glioblastoma (GBM) have yielded mixed results, new strategies targeting tumor-specific somatic coding mutations, termed "neoantigens," represent promising therapeutic approaches. We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination.Flow cytometric analysis was performed on intracranial CT2A and GL261 tumor-infiltrating lymphocytes (TILs). Whole-exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations. Predicted neoantigens were identified using the pVAC-seq software suite, and top-ranking candidates were screened for reactivity by interferon-gamma enzyme linked immunospot assays. Survival analysis was performed comparing neoantigen vaccination, anti-programmed cell death ligand 1 (αPD-L1), or combination therapy.Compared with the GL261 model, CT2A exhibited immunologic features consistent with human GBM including reduced αPD-L1 sensitivity and hypofunctional TILs. Of the 29 CT2A neoantigens screened, we identified neoantigen-specific CD8+ T-cell responses in the intracranial TIL and draining lymph nodes to two H2-Kb restricted (Epb4H471L and Pomgnt1R497L) and one H2-Db restricted neoantigen (Plin2G332R). Survival analysis showed that therapeutic neoantigen vaccination with Epb4H471L, Pomgnt1R497L, and Plin2G332R, in combination with αPD-L1 treatment was superior to αPD-L1 alone.We identified endogenous neoantigen specific CD8+ T cells within an αPD-L1 resistant murine GBM and show that neoantigen vaccination significantly augments survival benefit in combination with αPD-L1 treatment. These observations provide important preclinical correlates for GBM immunotherapy trials and support further investigation into the effects of multimodal immunotherapeutic interventions on antiglioma immunity.1. Neoantigen vaccines combined with checkpoint blockade may be promising treatments.2. CT2A tumors exhibit features of human GBM microenvironments.3. Differential scanning fluorimetry assays may complement in silico neoantigen prediction tools.
Streamlining radioembolization in UNOS T1/T2 hepatocellular carcinoma by eliminating lung shunt estimation
Authors: Ahmed Gabr, Srirajkumar Ranganathan, Samdeep K. Mouli, Ahsun Riaz, Vanessa L. Gates, Laura Kulik, Daniel Ganger, Haripriya Maddur, Christopher Moore, Elias Hohlastos, Nitin Katariya, Juan Carlos Caicedo, Aparna Kalyan, Robert J. Lewandowski, Riad Salem
Journal: Journal of Hepatology (2020)
Characterization of novel LncRNA P14AS as a protector of ANRIL through AUF1 binding in human cells
Authors: Wanru Ma, Juanli Qiao, Jing Zhou, Liankun Gu, Dajun Deng
Journal: Molecular Cancer (2020)

The CDKN2A/B locus contains crucial tumor suppressors and a lncRNA gene ANRIL. However, the mechanisms that coordinately regulate their expression levels are not clear. Novel RNAs transcribed from the CDKN2A gene were screened by CDKN2A-specific RNA capture deep-sequencing and confirmed by Northern blotting and clone-sequencing. Long non-coding RNA (lncRNA) binding proteins were characterized by RNA pull-down combined with mass spectrometry and RNA immunoprecipitation. LncRNA functions in human cells were studied using a set of biological assays in vitro and in vivo. We characterized a novel lncRNA, P14AS with its promoter in the antisense strand of the fragment near CDKN2A exon 1b in human cells. The mature P14AS is a three-exon linear cytoplasmic lncRNA (1043-nt), including an AU-rich element (ARE) in exon 1. P14AS decreases AUF1-ANRIL/P16 RNA interaction and then increases ANRIL/P16 expression by competitively binding to AUF1 P37 and P40 isoforms. Interestingly, P14AS significantly promoted the proliferation of cancer cells and tumor formation in NOD-SCID mice in a P16-independent pattern. Moreover, in human colon cancer tissues, the expression levels of P14AS and ANRIL lncRNAs were significantly upregulated compared with the paired normal tissues. A novel lncRNA, P14AS, transcribed from the antisense strand of the CDKN2A/P14 gene, promotes colon cancer development by cis upregulating the expression of oncogenic ANRIL.
Lobbying Expenditures, Campaign Contributions, and Health Care—Follow the Money
Authors: Robert Steinbrook
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Abstract P363: Regional And Racial Variation In The Prevalence Of Concomitant Diabetes And Peripheral Artery Disease
Authors: J Aaron Barnes, Mark A Eid, Zachary J Wanken, Richard J Powell, David H Stone, Bjoern D Suckow, Barbara Gladders, Mark A Creager, Philip P Goodney
Journal: Circulation (2020)

Introduction and Objectives: Prior research has demonstrated regional and racial variation in the prevalence of concomitant diabetes and peripheral artery disease (PAD). However, trends in prevalence of diabetes and PAD across races has not been well explored in recent patient cohorts. Methods: Using data from the Centers for Medicare and Medicaid Services from 2003-2016, we identified patients concurrently diagnosed with both diabetes and PAD (n=10,506,254). Overall prevalence of concomitant diabetes and PAD was determined. Regional variation at the state and hospital referral region (HRR) level was then identified using zip code data. Racial demographics within Medicare data were used to stratify prevalence by race. Results: The overall prevalence of diabetes and PAD across the entire cohort was 15.3 per 1,000 Medicare patients. When stratified by HRR, prevalence of patients with concomitant diabetes and PAD varied by nearly 7-fold with a low of 5.0 and a high of 33.2 per 1,000 Medicare patients. When stratified by race, the number of new patients concomitantly diagnosed with diabetes and PAD decreased across all races, with the greatest decline seen in the Hispanic population (absolute decrease 1.84%, relative reduction 63%). The number of new black patients decreased as well (absolute decrease 1.40%, relative reduction 52%), but blacks continue to comprise the highest proportion of newly diagnosed patients at 1.29% (Figure 1). Conclusion: Significant regional and racial variation exists in the prevalence of concomitant diabetes and PAD diagnoses among Medicare patients with black patients remaining disproportionately affected. Efforts to improve prevention and care management should target these endemic regions and populations.
Abstract P486: Association Of Psychiatric History With Hypertension Among Adults Who Presented For Bariatric Surgery
Authors: Gabriel S Tajeu, Jingwei Wu, Colleen Tewksbury, Jacqueline C Spitzer, Crystal A Gadegbeku, David Sarwer
Journal: Circulation (2020)

Introduction: Poor psychological health is common among adults with extreme obesity (body mass index (BMI) &gt; 40 kg/m 2 ). While prior studies report an association between psychological conditions (i.e., depression) and risk of hypertension, less is known about this association among adults with extreme obesity. Additionally, the association between other forms of poor psychological health (i.e., anxiety) and hypertension among this population have yet to be studied. Methods: Participants (n=281) were recruited from a large academic medical center in an urban environment who were scheduled for bariatric surgery. Informed consent was obtained from all participants. Hypertension diagnosis (yes/no) was identified from the electronic medical record of the participants within eight weeks of psychological assessment. Psychiatric diagnoses were assessed by structured clinical interview and included major depression, bipolar disorder, alcohol use disorder, substance use disorder, post-traumatic stress syndrome (PTSD), anxiety, and eating disorders. Prevalence of hypertension by psychiatric diagnosis was compared using chi-square tests. Multivariable adjusted odds ratios (aOR) for the association between poor psychological health and hypertension were calculated using logistic regression. Regression models were adjusted for age, BMI, gender, race, marital status, education, and employment status. In order to avoid collinearity, each psychiatric diagnosis was included in its own model. Results: The mean age of participants was 41.5 (SD=11.0) and BMI was 45.9 kg/m 2 (SD=6.2). The majority (61.2%) of participants were black and 86.5% were women. Across the sample, 42.6% of participants were married, 75.5% had more than a high school education, and 77.9% were employed. Hypertension prevalence was 44.8%. Approximately 64.4% of participants had at least one lifetime psychiatric diagnosis. Prevalence of individual lifetime diagnosis was 41.6% for major depressive disorder, 41.0% for affective/bipolar disorder, 23.2% for alcohol use disorder, 16.8% for substance use disorder, 13.6% for PTSD, 10.4% for anxiety, and 3.2% for eating disorders. Unadjusted prevalence of hypertension was higher among participants with a diagnosis of anxiety (65.4% vs. 43.3%; p=0.03) compared to those without diagnosis. Multivariable adjusted odds of hypertension were higher among participants with a diagnosis of anxiety (aOR=6.28; 95% CI: 2.07-19.04; p-value=0.001) compared to those without. Conclusions: Among a diverse sample of patients with extreme obesity who presented for bariatric surgery, a lifetime diagnosis of anxiety, but not other commonly seen psychiatric diagnoses, was associated with increased odds of hypertension.
Exceptional Response to Olaparib in a Patient With Recurrent Ovarian Cancer and an Entire BRCA1 Germline Gene Deletion
Authors: Megan Randall, Kelly Burgess, Lela Buckingham, Lydia Usha
Journal: Journal of the National Comprehensive Cancer Network (2020)

PARP inhibitors are known to be effective in patients with ovarian cancer (OC) and germline mutations in BRCA1 and BRCA2 genes ( BRCA mutations). Little is known, however, about any correlation between the deletion size and location of the BRCA mutation and the response to PARP inhibitors. Women with OC commonly undergo genetic testing because the presence of a germline BRCA mutation impacts therapeutic decisions and is important for cancer surveillance in patients and their family members. This report presents a case of a rare entire germline BRCA1 gene deletion and an exceptional response to a PARP inhibitor, olaparib, in a heavily pretreated patient with OC. Her disease course was also remarkable for complete responses to platinum-based chemotherapy and long chemotherapy-free intervals. Interestingly, the deletion of the entire BRCA1 gene was found after previously negative BRCA test results and is associated with a deletion of 6 adjacent genes without known clinical significance. She has remained progression-free and asymptomatic for &gt;3 years on olaparib, with an overall survival of &gt;12 years. We postulate that this unusually favorable response and prolonged overall survival is related to the cancer cells’ inability to reverse the entire gene deletion to wild-type (a common mechanism of resistance to PARP inhibition). This case shows the value of genetic testing for patients with OC and highlights the utility of additional testing with previously negative results and limited genetic testing. It also provides insight into a potential mechanism of an exceptional response to PARP inhibition.
Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas
Authors: Jerome Fortin, Ruxiao Tian, Ida Zarrabi, Graham Hill, Eleanor Williams, Gonzalo Sanchez-Duffhues, Midory Thorikay, Parameswaran Ramachandran, Robert Siddaway, Jong Fu Wong, Annette Wu, Lorraine N. Apuzzo, Jillian Haight, Annick You-Ten, Bryan E. Snow, Andrew Wakeham, David J. Goldhamer, Daniel Schramek, Alex N. Bullock, Peter ten Dijke, Cynthia Hawkins, Tak W. Mak
Journal: Cancer Cell (2020)

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors for which there is currently no effective treatment. Some of these tumors combine gain-of-function mutations in ACVR1, PIK3CA, and histone H3-encoding genes. The oncogenic mechanisms of action of ACVR1 mutations are currently unknown. Using mouse models, we demonstrate that Acvr1
Abstract P123: Metabolic Syndrome Risk Factors' Aggregation Within the Seven Countries' Study: 45 Years Follow Up Results
Authors: Biljana Parapid, Nicolas Danchin, Olga Nedeljkovic-Arsenovic, Bratislav Kircanski, Dragana Bubanja, Milos Stojanovic, Henry Blackburn, David Jacobs, Joanna Moschandreas, Hisashi Adachi, Aulikki Nissinen, Daan Kromhout, Alessandro Menotti, Miodrag C Ostojic, Vladimir Kanjuh
Journal: Circulation (2020)

Introduction: Components of the metabolic syndrome (MetSy) have gone through myriad of changes ever since the initial cluster was defined. The Seven Countries Study taught us the basics of classical risk factors for atherosclerotic artery disease and their influence on both cardiovascular and cerebrovascular morbidity and mortality. Material and Methods: In a 3-continent, 7-country (USA, Japan, Greece, the Netherlands, Finland, Italy, and former Yugoslavia then, now Croatia and Serbia) sample of 12,763 participants -- all healthy men over 40 at entry -- systematic, quinquennial checkups were conducted over 4 decades and MetSy was defined using the IDF definition. ResultS: A total of 9,09% of participants were identified to have MetSy, while the detailed description of risk factors' combination is shown in Table 1 and Figure 1, below. Conclusion: The leading combination was hypertension (HTA), diabetes (DM) and dyslipidemia (HLP), while hypertension was the hallmark risk factor irrelevant of presence or absence of MetSy. The results of this study call for a contemporary comprehensive research involving both sexes that could elucidate better real life risk factors' relationships in aforementioned countries.