tbuckley/cabot-search huggingface dataset:
Abstract 12587: Telomere Length Regulates Cellular Fate of Cardiac Progenitor Cells
Authors: Jacqueline Emathinger, Nathalie Nguyen, Pearl Quijada, Donald Bers, Mark Sussman, Nirmala Hariharan
Journal: Circulation (2015)

Myocardial regeneration following injury is severely limited by aging. Understanding the impact of age-associated factors such as telomere shortening is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs), which are currently used in clinical trials. Telomere length (TL) determines the proliferation potential such that short telomeres cause senescence of CPCs, however the impact of TL on regulating the balance between quiescence and differentiation of adult stem cells remains undetermined. We hypothesize that TL regulates the equilibrium between quiescence, proliferation, commitment and senescence, thus determining cellular fate of CPCs. CPCs were isolated from 3 mouse strains with varying TLs- common laboratory mouse strains FVB (TL:70Kb) and C57 (TL:50Kb), as well as a naturally occurring wild mouse strain, Mus musculus castaneus (CAST) possessing critically short telomeres (TL:18Kb) comparable to humans (TL:5-10Kb). CAST CPCs with short TLs have slower proliferation rate (-80% vs FVB, p&lt;0.01), increased population doubling time and exhibit characteristics of senescence such as flattened cell morphology, increased beta-galactosidase activity (p&lt;0.05) and p53 expression (1.7 fold, p&lt;0.05). Interestingly, CAST CPCs also undergo basal differentiation in the absence of commitment cues, as evidenced by increased expression of lineage markers smooth muscle actin (SMA; 16.6 fold, p&lt;0.01), Tie2 (1.7 fold, p&lt;0.05), and sarcomeric actinin (1.75 fold). Acquisition of differentiation and senescence is accompanied by reduced expression of quiescence marker p21 (-33%). Consistent findings of senescence, increased basal differentiation (11.3 and 1.6 fold increase in SMA and Tie2 levels) and loss of quiescence (-26% decrease in p21 levels) are evidenced in CPCs isolated from old FVB mice with short TLs relative to young CPCs. Corroborative findings in adult human failing heart CPCs with short TLs suggests that telomere shortening tips the equilibrium away from quiescence and proliferation into differentiation and senescence leading to exhaustion of CPCs. Understanding mechanistically how TL regulates CPC fate will enable identification of molecular strategies to enhance the therapeutic effects of CPCs.
Frailty affects quality of spirometry : the Rotterdam study
Authors: Lies Lahousse, DW Loth, Vja Verlinden, G Ziere, M Zillikens, AG Uitterlinden, F Rivadeneira, H Tiemeier, M Ikram, A Hofman, Guy Joos, BH Stricker, Guy Brusselle
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Individual and Area-Based Socioeconomic Factors Associated With Dementia Incidence in England
Authors: Dorina Cadar, Camille Lassale, Hilary Davies, David J. Llewellyn, G. David Batty, Andrew Steptoe
Journal: JAMA Psychiatry (2018)

Lower educational attainment is associated with a higher risk of dementia. However, less clear is the extent to which other socioeconomic markers contribute to dementia risk.To examine the relationship of education, wealth, and area-based deprivation with the incidence of dementia over the last decade in England and investigate differences between people born in different periods.Data from the English Longitudinal Study of Ageing, a prospective cohort study that is representative of the English population, were used to investigate the associations between markers of socioeconomic status (wealth quintiles and the index of multiple deprivation) and dementia incidence. To investigate outcomes associated with age cohorts, 2 independent groups were derived using a median split (born between 1902-1925 and 1926-1943).Dementia as determined by physician diagnosis and the Informant Questionnaire on Cognitive Decline in the Elderly.A total of 6220 individuals aged 65 years and older enrolled in the study (median [interquartile range] age at baseline, 73.2 [68.1-78.3] years; 3410 [54.8%] female). Of these, 463 individuals (7.4%) had new cases of dementia ascertained in the 12 years between 2002-2003 and 2014-2015. In the cohort born between 1926 and 1943, the hazard of developing dementia was 1.68 times higher (hazard ratio [HR] = 1.68 [95% CI, 1.05-2.86]) for those in the lowest wealth quintile compared with those in the highest quintile, independent of education, index of multiple deprivation, and health indicators. Higher hazards were also observed for those in the second-highest quintile of index of multiple deprivation (HR = 1.62 [95% CI, 1.06-2.46]) compared with those in the lowest (least deprived) quintile.In an English nationally representative sample, the incidence of dementia appeared to be socioeconomically patterned primarily by the level of wealth. This association was somewhat stronger for participants born in later years.
Implementation of a Population-Based Cirrhosis Identification and Management System
Authors: Fasiha Kanwal, Srikar Mapaskhi, Donna Smith, Tamar Taddei, Khozema Hussain, Stella Madu, Ngoc Duong, Donna White, Yumei Cao, Rajni Mehta, Hashem El-Serag, Steven Asch, Amanda Midboe
Journal: Clinical Gastroenterology and Hepatology (2018)
Chemically Modified Polyaniline for the Detection of Volatile Biomarkers of Minimal Sensitivity to Humidity and Bending
Authors: Yunfeng Deng, Jiaxing Sun, Han Jin, Muhammad Khatib, Xianhui Li, Zongsu Wei, Feng Wang, Yehu David Horev, Weiwei Wu, Hossam Haick
Journal: Advanced Healthcare Materials (2018)

Abstract Flexible sensors can be widely used in future wearable devices to monitor people's health states. However, most of the sensors are sensitive to humidity and bending effects, limiting their application in a real‐world environment. A new strategy is proposed for obtaining flexible sensors with good tolerance to humidity. By integrating a hydrophobic layer on the surface of doped polyaniline, a flexible sensor that can resist water response with a concentration up to 350 ppm is developed. Good resilience against mechanical bending is also achieved in this flexible sensor. These results may trigger a renaissance in flexible sensor applications for disease diagnosing by wearable devices.
The Antifibrotic Effect of A<sub>2B</sub> Adenosine Receptor Antagonism in a Mouse Model of Dermal Fibrosis
Authors: Harry Karmouty‐Quintana, Jose G. Molina, Kemly Philip, Chiara Bellocchi, Brent Gudenkauf, Minghua Wu, Ning‐Yuan Chen, Scott D. Collum, Junsuk Ko, Sandeep K. Agarwal, Shervin Assassi, Hongyan Zhong, Michael R. Blackburn, Tingting Weng
Journal: Arthritis & Rheumatology (2018)

Systemic sclerosis (SSc; scleroderma) is a chronic disease that affects the skin and various internal organs. Dermal fibrosis is a major component of this disease. The mechanisms that promote dermal fibrosis remain elusive. Elevations in tissue adenosine levels and the subsequent engagement of the profibrotic A2B adenosine receptor (ADORA2B) have been shown to regulate fibrosis in multiple organs including the lung, kidney, and penis; however, the role of ADORA2B in dermal fibrosis has not been investigated. We undertook this study to test our hypothesis that elevated expression of ADORA2B in the skin drives the development of dermal fibrosis.We assessed the involvement of ADORA2B in the regulation of dermal fibrosis using a well-established mouse model of dermal fibrosis. Using an orally active ADORA2B antagonist, we demonstrated how inhibition of ADORA2B results in reduced dermal fibrosis in 2 distinct experimental models. Finally, using human dermal fibroblasts, we characterized the expression of adenosine receptors.We demonstrated that levels of ADORA2B were significantly elevated in dermal fibrosis and that the therapeutic blockade of this receptor in vivo using an ADORA2B antagonist could reduce the production of profibrotic mediators in the skin and attenuate dermal fibrosis. Antagonism of ADORA2B resulted in reduced numbers of arginase-expressing macrophages and myofibroblasts and in reduced levels of the extracellular matrix proteins fibronectin, collagen, and hyaluronan.These findings identify ADORA2B as a potential profibrotic regulator in dermal fibrosis and suggest that ADORA2B antagonism may be a useful approach for the treatment of SSc.
Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy
Authors: G. Errico, C. Gagliotti, M. Monaco, L. Masiero, P. Gaibani, S. Ambretti, M.P. Landini, S. D’Arezzo, A. Di Caro, S.G. Parisi, G. Palù, F. Vespasiano, F. Morsillo, M.L. Moro, F. Procaccio, A. Ricci, P.A. Grossi, A. Pantosti, A. Nanni Costa, C. Farina, F. Vailati, G. Gesu, C. Vismara, M. Arghittu, R. Colombo, E. Torresani, L. Rossi, P.G. Conaldi, F. Gona, P. Cambieri, P. Marone, C. Venditti, A. Garcia Fernandez, C. Mancini, M. Cusi, L. Henrici De Angelis, L. Fossati, A.C. Finarelli, C. De Cillia, G. Sangiorgi, A.D. Pinna, F. Stella, P. Viale, M. Colledan, M. Platto, M. Bonizzoli, A. Peris, R. Torelli, S. Vesconi, E. Cibelli, L. De Carlis, A. De Gasperi, M. Ravini, R. Carrinola, E. Coluccio, D. Dondossola, G. Rossi, L. Santambrogio, D. Tosi, G. Feltrin, C. Rago, U. Cillo, A. Da Riva, F. Rea, V. Sparacino, A. Bertani, M. Canzonieri, B. Gridelli, A. Mularoni, M. Spada, E. Carrara, A. Maria D’Armini, P. Paladini, D. Adorno, M. Valeri, M. Caprio, P. Di Ciaccio, F. Puoti, P. Berloco, B. D’Auria, F. Maldarelli, G. Paglialunga, F. Pugliese, M. Rossi, F. Venuta, A. Amoroso, R. Giacometti, M. Rinaldi, M. Salizzoni
Journal: Clinical Microbiology and Infection (2018)
Reply
Authors: Jasmohan S. Bajaj, Tor Savidge, Zain A Kassam, Phillip B. Hylemon, Patrick M. Gillevet
Journal: Hepatology (2018)

Bajaj JS, Savidge T, Kassam ZA, Hylemon PB, Gillevet PM. Reply. Hepatology. 2018;00:000–000. https://doi.org/10.1002/hep.30092BajajJS, SavidgeT, KassamZA, HylemonPB, GillevetPM. Reply. Hepatology. 2018;00:000–000. https://doi.org/10.1002/hep.30092 Dear Editor, We thank Mullish et al. for their comments. They bring out important issues focused on their knowledge of either rodent models or patients without cirrhosis in illustrating their points. Contrary to these experiences, human patients with cirrhosis have underlying deficits in gastrointestinal and immune function that adversely affect microbiota communities. These are also affected by the use of microbiota‐modifying drugs such as proton pump inhibitors and rifaximin.(1) The disruption of secondary bile acid and short‐chain fatty acid production also demonstrates functional alterations. As is established in recurrent C. difficile, it is difficult for microbiota communities to recover in a susceptible host after antibiotics. Antibiotic use in cirrhosis is common and leads to higher fungal abundance and the development of resistant organisms, which can worsen liver disease.(2) As opposed to the older study cited by Mullish et al., there are newer longer‐term experiments that demonstrate how antibiotic‐associated recovery is not spontaneous and does not recover to the baseline, even in healthy individuals.(4) Fecal microbiota transplantation (FMT) studies in other conditions demonstrate how recipients do not completely attain the donor microbiota; therefore, it is not surprising that the post‐FMT microbiota are not identical to the donor. We also note that measuring microbial relative abundance reflects compositional changes and not total bacterial load, which can significantly increase following FMT. In addition, we found not only a restoration of bile acid deconjugation and 7α‐dehydroxylation capacity, but also a continued decrease in desulfation, which improves the post‐FMT microbial functional milieu over and above the antibiotics. The natural history of cirrhosis and hepatic encephalopathy is further hospitalization, until the occurrence of infections with resistant and fungal organisms, death, organ failures, or transplant.(3) Therefore, the chances of this tenuous microbial ecosystem returning to normal or even baseline without the use of a major "reset" in the ecosystem, such as FMT, is highly unlikely. This precedent is already established for recurrent C. difficile. We argue that appropriately regulated precision‐based microbial therapy should be a consideration for other disease indications, including cirrhosis. The beneficial clinical outcomes seen in the main trial are potential evidence that FMT could be promising, but we agree that placebo‐controlled randomized trials are needed.(5) Potential Conflicts of Interest Dr. Kassam consults and advises Open Biome. He is employed by and owns stock in Finch.
Human pegivirus persistence in human blood virome after allogeneic haematopoietic stem-cell transplantation
Authors: D.-L. Vu, S. Cordey, F. Simonetta, F. Brito, M. Docquier, L. Turin, C. van Delden, E. Boely, C. Dantin, A. Pradier, E. Roosnek, Y. Chalandon, E.M. Zdobnov, S. Masouridi-Levrat, L. Kaiser
Journal: Clinical Microbiology and Infection (2018)
Epithelial mesenchymal transition in an advanced BRAF mutation type colorectal cancer.
Authors: Jun-Eul Hwang, Woo Kyun Bae, Hyun-Jeong Shim, Sang-Hee Cho, Ik-Joo Chung
Journal: Journal of Clinical Oncology (2018)

693 Background: BRAF mutation is associated with poor survival in colorectal cancer. We aimed to generate genomic signature associated with BRAF mutation that possibly predict prognosis in colorectal cancer. Methods: A gene expression signature reflecting BRAF mutation was generated in TCGA cohorts (n = 207). The colorectal cancer patients were stratified into two groups according to this signature: BRAF mutation type colorectal cancer or BRAF wild type colorectal cancer. Prognostic significance of BRAF mutation-associated gene signature was tested in three independent cohorts (GSE 17536, GSE 14333, and GSE 39582). Results: The BRAF mutation signature was associated with poor prognosis in two independent cohorts (total n = 522). BRAF mutation type colorectal cancer was associated with poor disease-free survival (median: not reached, P = 0.0303) in GSE14333, and associated with poor overall survival (BRAF mutation vs. wild, P = 0.0355), poor disease-free survival (P = 0.00794), and poor disease-specific survival (P = 0.0341) in GSE 17536. In GSE 39582, BRAF mutation type colorectal cancer demonstrated the trend of poor overall survival according to increase of stage. In a multivariate analysis, BRAF mutation gene signature was independent poor prognostic factor for disease-free survival (hazard ratio 2.7; 95% CI 1.59-2.83: P = 0.001). Gene network analyses suggested epithelial-mesenchymal transition and colon cancer metastasis signaling are the possible explanations for poor prognosis of BRAF mutation type colorectal cancer. Conclusions: BRAF mutation signature is highly associated with poor prognosis in colorectal cancer, especially in advanced stage, and the molecules associated with epithelial-mesenchymal transition can be potential therapeutic targets in BRAF mutation type colorectal cancer.
Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977–2014
Authors: Marie Villumsen, Susana Aznar, Bente Pakkenberg, Tine Jess, Tomasz Brudek
Journal: Gut (2018)

Objective Intestinal inflammation has been suggested to play a role in development of Parkinson’s disease (PD) and multiple system atrophy (MSA). To test the hypothesis that IBD is associated with risk of PD and MSA, we performed a nationwide population-based cohort study. Design The cohort consisted of all individuals diagnosed with IBD in Denmark during 1977–2014 (n=76 477) and non-IBD individuals from the general population, who were comparable in terms of gender, age and vital status (n=7 548 259). All cohort members were followed from IBD diagnosis/index date to occurrence of PD and MSA (according to the Danish National Patient Register). Results Patients with IBD had a 22% increased risk of PD as compared with non-IBD individuals (HR=1.22; 95% CI 1.09 to 1.35). The increased risk was present independently of age at IBD diagnosis, gender or length of follow-up. The overall incidence of MSA was low in our study, and the regression analysis suggested a tendency towards higher risk of developing MSA in patients with IBD as compared with non-IBD individuals (HR=1.41; 95% CI 0.82 to 2.44). Estimates were similar for women and men. The increased risk of parkinsonism was significantly higher among patients with UC (HR=1.35; 95% CI 1.20 to 1.52) and not significantly different among patients with Crohn’s disease (HR=1.12; 95% CI 0.89 to 1.40). Conclusions This nationwide, unselected, cohort study shows a significant association between IBD and later occurrence of PD, which is consistent with recent basic scientific findings of a potential role of GI inflammation in development of parkinsonian disorders.
Framingham at 70: What We’ve Learned About Women and Heart Disease
Authors: Rebecca Voelker
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Bundled Payments Initiative Participation and Retention—Reply
Authors: Karen E. Joynt Maddox, Arnold M. Epstein
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Management of Locoregional Rectal Cancer
Authors: Christopher G. Willett
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">The NCCN Guidelines for Rectal Cancer are now more closely aligned with those for colon cancer. A new MRI-based definition of the rectum has been included and the use of MRI in staging has been elevated in importance. There is a new emphasis on neoadjuvant therapy, especially the concurrent use of chemotherapy and radiotherapy. One of the biggest changes is more acceptance of an observational approach—“watch and wait, nonoperative management”—for select patients experiencing a complete clinical response with no evidence of residual disease after neoadjuvant therapy. </section>
The Loss of a Sense of Control as a Major Contributor to Physician Burnout
Authors: Frederick Seacrest Southwick, Steven Mark Southwick
Journal: JAMA Psychiatry (2018)

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 Psychiatry 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 Psychiatry journal
Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition
Authors: Natividad R. Fuentes, Mohamed Mlih, Rola Barhoumi, Yang-Yi Fan, Paul Hardin, Trevor J. Steele, Spencer Behmer, Ian A. Prior, Jason Karpac, Robert S. Chapkin
Journal: Cancer Research (2018)

Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown. Here, we demonstrate that dietary n-3 PUFA reduce the lateral segregation of cholesterol-dependent and -independent nanoclusters, suppressing phosphatidic acid-dependent oncogenic KRas effector interactions, via their physical incorporation into plasma membrane phospholipids. This results in attenuation of oncogenic Ras-driven colonic hyperproliferation in both Drosophila and murine models. These findings demonstrate the unique properties of dietary n-3 PUFA in the shaping of Ras nanoscale proteolipid complexes and support the emerging role of plasma membrane-targeted therapies.Significance: The influence of dietary long chain n-3 polyunsaturated fatty acids on plasma membrane protein nanoscale organization and KRas signaling supports development of plasma membrane-targeted therapies in colon cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3899/F1.large.jpg Cancer Res; 78(14); 3899-912. ©2018 AACR.