tbuckley/cabot-search huggingface dataset:
FRI0593 Association of thymoma with autoimmune diseases in a series of 83 cases
Authors: A González García, WA Sifuentes Giraldo, JL Morell Hita, JL Patier de la Peña
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Thymoma is the most common neoplasm originated from the thymus gland and accounting for 50% of anterior mediastinal tumors. Within its clinical manifestations are included the loss of self-tolerance and the development of autoimmunity. <h3>Objectives</h3> To study the frequency of autoimmune diseases (AD) in patients with thymoma and to describe their clinical characteristics and outcome. <h3>Methods</h3> We performed a retrospective observational study of a cohort of patients diagnosed with thymoma and followed-up in our center between January 1985 and September 2016. The variables evaluated included demographics, thymoma characteristics, clinical and analytical manifestations of autoimmunity, treatment and outcome. <h3>Results</h3> A total of 83 patients were included, 56.6% of them women, with a mean age at diagnosis of the thymoma of 58.4±15.8 years (range: 16–94), 31.3% of which corresponded to type I The classification of Masaoka, 39.1% to II, 17.2% to III and 10.9% to IV. There were one or more AD associated in 41 cases (49.4%). The most frequent diagnoses were myasthenia gravis (19), systemic lupus erythematosus (SLE) (4), subacute cutaneous lupus erythematosus (1), Sjögren9s syndrome (1), rheumatoid arthritis (1), spondyloarthritis (1), sarcoidosis (1), hemolytic anemia (2), pernicious anemia (1), aplastic anemia (1), cutaneous limited systemic sclerosis (1), urticaria-vasculitis, erythroblastopenia (1), recurrent pericarditis (1), thyroid disease (2) and lichen planus (1). The diagnosis of AD preceded to thymoma in 38.2% of cases and was later in the remaining cases. In 4 cases there was also a concomitant primary immunodeficiency (variable common immunodeficiency 3, CD4 immunodeficiency 1). The most frequently identified autoantibodies were anti-acetylcholine receptor (14/41, 34.1%), anti-striated muscle (3/41, 7.3%), ANA (11/41, 26.8%), (3/41, 7.3%), rheumatoid factor (3/41, 7.3%), anti-thyroid (3/41, 7.3%), antiphospholipids (2/41, 9%) and anticentromere (1/41, 2.4%). In the comparison of patients with and without associated AD, no significant differences were found regarding age, sex or Masaoka classification. There were 6 deaths, 4 in group with associated AD and 2 in the group without AD, but without significant difference (p=0.3797). <h3>Conclusions</h3> In the analyzed population of patients with thymoma of our center, almost half of them developed AD, which in a major group preceded the diagnosis of neoplasia. The spectrum of autoimmunity associated with thymoma was quite broad, including organ-specific AD such as myasthenia gravis (which is most frequently described in the literature) and autoimmune cytopenias, but also to systemic AD, the most common being SLE. The autoimmunity study should be included in the assessment of the patient with thymoma as it could contribute to the early diagnosis of associated AD. <h3>Disclosure of Interest</h3> None declared
New Hope for a Gonorrhea Vaccine
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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
Now is the Time for a Postracial Medicine: Biomedical Research, the National Institutes of Health, and the Perpetuation of Scientific Racism
Authors: Javier Perez-Rodriguez, Alejandro de la Fuente
Journal: The American Journal of Bioethics (2017)

The consideration of racial differences in the biology of disease and treatment options is a hallmark of modern medicine. However, this time-honored medical tradition has no scientific basis, and the premise itself, that is, the existence of biological differences between the commonly known races, is false inasmuch as races are only sociocultural constructions. It is time to rid medical research of the highly damaging exercise of searching for supposed racial differences in the biological manifestations of disease. The practice not only condoned but required by the National Institutes of Health (NIH) of utilizing racial identification as a demographic characteristic with assumed biological implications is at best badly flawed, and at worst unintentionally contributes to perpetuating the fallacy of natural differences between persons of different skin color, which has been used in the past to advance the cause of racial discrimination.
ドラッグデリバリーのための定義されたマイクロまたはナノ構造をもつ導電性重合体【Powered by NICT】
Authors: Uppalapati Dedeepya, J Boyd Ben, Garg Sanjay, Travas-Sejdic Jadranka, Svirskis Darren
Journal: Biomaterials (2016)
Parallel Evolution of Chromatin Structure Underlying Metabolic Adaptation
Authors: Jian Cheng, Xiaoxian Guo, Pengli Cai, Xiaozhi Cheng, Jure Piškur, Yanhe Ma, Huifeng Jiang, Zhenglong Gu
Journal: Molecular Biology and Evolution (2017)

Parallel evolution occurs when a similar trait emerges in independent evolutionary lineages. Although changes in protein coding and gene transcription have been investigated as underlying mechanisms for parallel evolution, parallel changes in chromatin structure have never been reported. Here, Saccharomyces cerevisiae and a distantly related yeast species, Dekkera bruxellensis, are investigated because both species have independently evolved the capacity of aerobic fermentation. By profiling and comparing genome sequences, transcriptomic landscapes, and chromatin structures, we revealed that parallel changes in nucleosome occupancy in the promoter regions of mitochondria-localized genes led to concerted suppression of mitochondrial functions by glucose, which can explain the metabolic convergence in these two independent yeast species. Further investigation indicated that similar mutational processes in the promoter regions of these genes in the two independent evolutionary lineages underlay the parallel changes in chromatin structure. Our results indicate that, despite several hundred million years of separation, parallel changes in chromatin structure, can be an important adaptation mechanism for different organisms. Due to the important role of chromatin structure changes in regulating gene expression and organism phenotypes, the novel mechanism revealed in this study could be a general phenomenon contributing to parallel adaptation in nature.
Exercise Therapy Offers Modest Benefits for Chronic Fatigue
Authors: Anita Slomski
Journal: JAMA (2017)

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
Abstract 177: Insulin Resistance and Mechanisms of Heart Failure
Authors: Shaodong Guo, Yajuan Qi, Qinglei Zhu, Zihui Xu, Candice Thomas, Rajesh Kumar, Hao Feng, David Dostal, Morris White, Kenneth Baker
Journal: Circulation Research (2013)

A major cause of death in patients with type 2 diabetes is cardiac failure and the molecular mechanism that links diabetes to cardiomyopathy remains unclear. Insulin resistance is a hallmark of type 2 diabetes and intensive insulin therapy on the patients with type 2 diabetes increases the risks of cardiovascular dysfunction. Thus, understanding the mechanisms of insulin actions and resistance, related to cardiac dysfunction, will be critical for development of new strategies treating heart failure in type 2 diabetes. Insulin receptor substrate 1, &amp; 2 (IRS1, IRS2) are major components in insulin signaling pathway regulating metabolism and survival. Here we hypothesized that (1) loss of IRS1 and IRS2 causes heart failure; (2) hyperinsulinemia contributes to loss of IRS1 and IRS2 in type 2 diabetes and promotes cardiac dysfunction; and (3) underlying mechanisms are involved in protein kinase activation. H-DKO mice (Heart Double IRS1 and IRS2 Knock-Out) and L(Liver)-DKO mice were generated using Cre/Loxp system. Cardiac function and ATP content were measured by echocardiograms and ATP assay kit. Protein and gene expressions were detected through western-blot and Q-PCR. Primary cultures of neonatal rat ventricular cardiomyocytes (NRVMs) were prepared from Sprague-Dawley rats with enzymatic method. H-DKO mice reduced ventricular mass, developed cardiac fibrosis and failure, and diminished Akt→Foxo1 signaling accompanied by impaired cardiac metabolic gene expression patterns and reduced ATP content. L-DKO mice decreased cardiac expression of IRS1 and IRS2 proteins with insulin resistance, disrupting cardiac energy metabolism, leading to heart failure and activation of p38α MAPK (p38). Using NRVMs, we demonstrated that hyperinsulinemia degraded IRS1 and IRS2, resulting in insulin resistance and impaired insulin action through activation of p38. In conclusion, myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38 during Insulin resistance, revealing a fundamental mechanism of heart failure during insulin resistance and/or type 2 Diabetes Mellitus.
合成高密度リポ蛋白質様ナノ粒子はリポ多糖類結合Toll様受容体4により誘導される炎症性メディエーターの細胞シグナル伝達と産生を強力に阻害する【Powered by NICT】
Authors: Foit Linda, Thaxton C. Shad
Journal: Biomaterials (2016)
Prolonged human neural stem cell maturation supports recovery in injured rodent CNS
Authors: Paul Lu, Steven Ceto, Yaozhi Wang, Lori Graham, Di Wu, Hiromi Kumamaru, Eileen Staufenberg, Mark H. Tuszynski
Journal: Journal of Clinical Investigation (2017)

Neural stem cells (NSCs) differentiate into both neurons and glia, and strategies using human NSCs have the potential to restore function following spinal cord injury (SCI). However, the time period of maturation for human NSCs in adult injured CNS is not well defined, posing fundamental questions about the design and implementation of NSC-based therapies. This work assessed human H9 NSCs that were implanted into sites of SCI in immunodeficient rats over a period of 1.5 years. Notably, grafts showed evidence of continued maturation over the entire assessment period. Markers of neuronal maturity were first expressed 3 months after grafting. However, neurogenesis, neuronal pruning, and neuronal enlargement continued over the next year, while total graft size remained stable over time. Axons emerged early from grafts in very high numbers, and half of these projections persisted by 1.5 years. Mature astrocyte markers first appeared after 6 months, while more mature oligodendrocyte markers were not present until 1 year after grafting. Astrocytes slowly migrated from grafts. Notably, functional recovery began more than 1 year after grafting. Thus, human NSCs retain an intrinsic human rate of maturation, despite implantation into the injured rodent spinal cord, yet they support delayed functional recovery, a finding of great importance in planning human clinical trials.
Scheduled rituximab maintenance reduces relapse rate in eosinophilic granulomatosis with polyangiitis
Authors: Giacomo Emmi, Giovanni M Rossi, Maria L Urban, Elena Silvestri, Domenico Prisco, Matteo Goldoni, Augusto Vaglio
Journal: Annals of the Rheumatic Diseases (2017)

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with a frequently relapsing/refractory course.1 2 Rituximab (RTX) is an established treatment in the other ANCA-associated vasculitides, but data on EGPA are scarce.3 4 Mohammad5 reported that RTX can be effective in EGPA, particularly in ANCA-positive patients.

We report the outcomes of 21 patients with EGPA who received RTX-induction (1 g 2 weeks apart, on top of ongoing immunosuppression) for refractory/relapsing disease in 2011–2017 (table 1). Starting from 2014, we scheduled RTX-maintenance (500 mg/6 months)6 7 in patients responding to RTX-induction. Nine patients received RTX-maintenance, the others received RTX only for relapses (a single, 1g infusion). Complete remission was defined as Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone ≤7.5 mg/day,3 partial remission as >50% BVAS reduction and prednisone ≤15 mg/day. Refractory disease was defined as failure to achieve remission, relapse as the recurrence/new onset of clinical manifestations requiring intensification of immunosuppression or increase in glucocorticoid dose >50%.8 All patients signed informed consent; the study …
Comparison of pyoderma gangrenosum and Martorell hypertensive ischaemic leg ulcer in a Swiss cohort
Authors: A.G.A. Kolios, J. Hafner, C. Luder, E. Guenova, K. Kerl, W. Kempf, J. Nilsson, L.E. French, A. Cozzio
Journal: British Journal of Dermatology (2017)

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis presenting with painful and sterile skin ulcerations (1).Its aetiology remains largely unknown although an autoinflammatory background seems possible.Several comorbidities as well as triggering factors such as surgery, trauma or pharmacological therapies have been associated with the development of PG (2).Different topical and systemic treatments are recommended for PG, most commonly topical steroids or calcineurin inhibitors as well as systemic steroids, dapsone, infliximab and others, as well as by our group and others canakinumab and ustekinumab (3, 4).
Direct detection of early-stage cancers using circulating tumor DNA
Authors: Jillian Phallen, Mark Sausen, Vilmos Adleff, Alessandro Leal, Carolyn Hruban, James White, Valsamo Anagnostou, Jacob Fiksel, Stephen Cristiano, Eniko Papp, Savannah Speir, Thomas Reinert, Mai-Britt Worm Orntoft, Brian D. Woodward, Derek Murphy, Sonya Parpart-Li, David Riley, Monica Nesselbush, Naomi Sengamalay, Andrew Georgiadis, Qing Kay Li, Mogens Rørbæk Madsen, Frank Viborg Mortensen, Joost Huiskens, Cornelis Punt, Nicole van Grieken, Remond Fijneman, Gerrit Meijer, Hatim Husain, Robert B. Scharpf, Luis A. Diaz, Siân Jones, Sam Angiuoli, Torben Ørntoft, Hans Jørgen Nielsen, Claus Lindbjerg Andersen, Victor E. Velculescu
Journal: Science Translational Medicine (2017)

Noninvasive liquid biopsy analysis of circulating tumor DNA permits direct detection of early-stage cancers.
Domains of generality
Authors: Andrew Buskell, Marta Halina
Journal: Behavioral and Brain Sciences (2017)

Abstract We argue that general intelligence, as presented in the target article, generates multiple distinct and non-equivalent characterisations. Clarifying this central concept is necessary for assessing Burkart et al.'s proposal that the cultural intelligence hypothesis is the best explanation for the evolution of general intelligence. We assess this claim by considering two characterisations of general intelligence presented in the article.
機械的ストレスは血液脳関門の柔軟性3次元モデルにおける輸送を調節する【Powered by NICT】
Authors: P Partyka Paul, A Godsey George, R Galie John, C Kosciuk Mary, K Acharya Nimish, G Nagele Robert, A Galie Peter
Journal: Biomaterials (2017)
Sunitinib dosing, toxicity, and outcomes in first-line advanced renal cell carcinoma (aRCC): A U.S. Oncology Network (USON) retrospective study.
Authors: Ian D. Schnadig, Thomas E. Hutson, Hsingwen Chung, Rahul Dhanda, Melissa Halm, Michael T. Forsyth, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2012)

e15089 Background: Sunitinib is a first-line therapy for patients (pts) with aRCC. As a multitargeted tyrosine kinase inhibitor (TKI), it is associated with toxicities that may impact dosing; dose reductions may result in inferior clinical outcomes (Motzer, 2011 ASCO GU, abstract LBA308). This retrospective study was initiated by USON to evaluate dosing patterns of first-line sunitinib, and its association with toxicities and outcomes in community practices. Methods: Pts with aRCC who started first-line sunitinib between June 1, 2007 and May 31, 2011 at 17 USON practices were identified; clinical data were extracted by chart review from iKnowMed electronic medical records that were linked to USON retail pharmacy database. Pts who were enrolled in clinical trials or receiving care for other primary tumors were excluded. Results: Pt characteristics: N=134; median age = 64 years (range 41–87); ECOG PS 0/1 = 85%; clear cell RCC = 81%; and nephrectomy = 61%. Objective response rate was 16%. Overall survival (OS) was 15.4 months (95% confidence interval 11.9–20.8). Median treatment duration was 4 cycles (range 1–19): 27 pts (20.1%) received only 1 cycle of sunitinib (23 at full dose [50 mg] and 4 at &lt;full dose); 107 pts (79.9%) received &gt;1 cycle of sunitinib (53 received full dose; 35 started at full dose but were dose-reduced; 14 always received &lt;full dose; 5 started at &lt;full dose but were dose-increased to 50 mg). Overall, 45 pts were dose-reduced, principally (93%) due to toxicities; 67% of all dose reductions occurred in the first 3 cycles. 121 pts discontinued sunitinib after completing at least 1 cycle, mostly due to disease progression (PD; 44%) or toxicities (17%); 74% of all discontinuations occurred within the first 5 cycles. Conclusions: RCC pts in community practices commonly undergo sunitinib dose reductions in the first 3 cycles due to toxicities, and discontinue therapy within the first 5 cycles due to PD. The median number of cycles and OS were lower than those reported in clinical trials (Motzer JCO 2009;27:3584–3590). More selective TKIs are needed to reduce toxicities, optimize dosing, and potentially improve outcomes. Funded by a grant from AVEO Pharmaceuticals, Inc.
Abstract 11682: Prognostic Impact of Periodic Leg Movements in Hospitalized Heart Failure Patients
Authors: Yuki Kanno, Akiomi Yoshihisa, Mai Takiguchi, Shunsuke Miura, Akihiko Sato, Takeshi Shimizu, Yuichi Nakamura, Hiroyuki Yamauchi, Takashi Owada, Satoshi Abe, Satoshi Suzuki, Masayoshi Oikawa, Nobuo Sakamoto, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2015)

Background: Periodic leg movements during sleep (PLMs) are the disorder characterized by regularly recurring movements of the legs during sleep. Recently, it has been reported that PLMs have a critical association with cardiovascular mortality and morbidity. However, the prevalence and impact of PLMs on cardiac and all-cause mortality still remain unclear in patients with heart failure (HF). Methods and Results: Consecutive 114 patients admitted for treatment of HF and underwent polysomnography were divided into two groups based on PLM index: moderate-severe PLMs group (PLM index ≥ 20/h, n = 24) and non-mild PLMs group (PLM index &lt; 20/h, n = 90). We compared patient characteristics, findings of echocardiography and cardio-pulmonary exercise test between the two groups. Furthermore, we prospectively followed cardiac events including cardiac death and all-cause mortality. The moderate-severe PLMs group, as compared to non-mild PLMs groups, had lower levels of estimated GFR (46.8 vs. 59.5 ml/min/1.73cm 2 , P = 0.032) and tended to have lower peak VO 2 (14.5 vs. 16.3 ml/min/kg, P = 0.09). In contrast, age, body mass index, systolic blood pressure, B-type natriuretic peptide, hemoglobin, sodium, C-reactive protein and left ventricular ejection fraction were similar between the two groups. Importantly, cardiac mortality (log-rank P = 0.005) and all-cause mortality (P = 0.028) were higher in moderate-severe PLMs group than in non-mild PLMs group (Figure). In the multivariable Cox proportional hazard analyses, after adjusting for potential confounding factors, PLM index was an independent predictor of cardiac (HR 1.024, 95% CI 1.006-1.042, P = 0.009) and all-cause mortality (HR 1.016, 95% CI 1.001-1.031, P = 0.045) in HF patients. Conclusions: The PLM index was a novel predictor of cardiac and all-cause mortality in HF patients.
Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation
Authors: Brigitte T. Hofmeister, Kevin Lee, Nicholas A. Rohr, David W. Hall, Robert J. Schmitz
Journal: Genome biology (2017)

Differences in DNA methylation can arise as epialleles, which are loci that differ in chromatin state and are inherited over generations. Epialleles offer an additional source of variation that can affect phenotypic diversity beyond changes to nucleotide sequence. Previous research has looked at the rate at which spontaneous epialleles arise but it is currently unknown how they are maintained across generations.We used two Arabidopsis thaliana mutation accumulation (MA) lines and determined that over 99.998% of the methylated regions in the genome are stably inherited across each generation indicating that spontaneous epialleles are rare. We also developed a novel procedure that determines genotypes for offspring of genetically identical parents using only DNA methylation data. The resulting epigenotype maps are highly accurate and strongly agree with expected allele frequency and crossover number. Using epigenotype maps, we explore the inheritance of methylation states in regions of differential methylation between the parents of genetic crosses. Over half of the regions show methylation levels consistent with cis inheritance, whereas the other half show evidence of trans-chromosomal methylation and demethylation as well as other possibilities.DNA methylation is stably inherited by offspring and spontaneous epialleles are rare. The epigenotyping procedure that we describe provides an important first step to epigenetic quantitative trait loci mapping in genetically identical individuals.