tbuckley/cabot-search huggingface dataset:
Abstract 14242: Clinical Impact of Previous Ischemic or Hemorrhagic Stroke on the Intracranial Event in Japanese Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Yoshimori An, Mitsuru Ishii, Takashi Unoki, Moritake Iguchi, Nobutoyo Masunaga, Hisashi Ogawa, Hiromichi Wada, Koji Hasegawa, Masahiro Esato, Yeong-Hwa Chun, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2015)

Introduction: Little is known about the risk factors for each of ischemic and hemorrhagic stroke in patients with atrial fibrillation (AF). Methods: The Fushimi AF Registry, a community-based survey, was designed to enroll all of the AF patients who visited the participating institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,499 patients by April 2015 (median follow-up period: 849 days). We explored the predictors for each of ischemic and hemorrhagic stroke, especially focusing on previous ischemic or hemorrhagic stroke. Results: The mean age was 73.6±10.9 years. The mean CHADS2, CHA2DS2-VASc and HAS-BLED scores were 2.01, 3.35 and 1.49, respectively. 53.5% of patients received oral anticoagulation (OAC) at baseline. Ischemic stroke occurred in 132 patients (3.8%) and hemorrhagic stroke in 42 (1.2%). On multivariate analysis, the independent predictors for ischemic stroke were as follows: advanced age (≥75 years) (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.63-3.53), sustained (persistent or permanent) AF (HR: 1.51, 95% CI: 1.05-2.23) and previous ischemic stroke (HR: 2.23, 95% CI: 1.54-3.19). As for hemorrhagic stroke, the independent predictor was previous hemorrhagic stroke (HR: 4.96, 95% CI: 1.19-13.8), whereas either of hypertension, previous ischemic stroke or OAC prescription was not. In patients with versus without previous ischemic stroke, the annual incidence of ischemic stroke was higher (3.55% vs. 1.35%; p&lt;0.01), but that of hemorrhagic stroke was similar (0.58% vs. 0.53%; p=0.81). This was also the case with patients with versus without previous hemorrhagic stroke; the incidence of hemorrhagic stroke was higher (2.67% vs. 0.51%; p&lt;0.01), and that of ischemic stroke was similar (1.78% vs. 1.73%; p=0.99) (Figure) . Conclusions: The risk of stroke in patients with AF was dependent on the type of stroke. The history of ischemic or hemorrhagic stroke was a risk of the same type of stroke, but not of the other one.
Abstract 13053: Characteristics, Outcomes, and Predictors in Cardiovascular Shock Patients in Japan: Results From the Japanese Circulation Society Cardiovascular Shock Registry
Authors: Yasushi Ueki, Masahiro Mohri, Tetsuya Matoba, Toshiaki Kadokami, Satoru Suwa, Tsukasa Yagi, Hiroshi Takahashi, Nobuhiro Tanaka, Yohei Hokama, Rei Fukuhara, Eizo Tachibana, Naohiro Yonemoto, Ken Nagao
Journal: Circulation (2015)

Introduction: Despite the advances in the treatment of cardiogenic shock, mortality in these patients remains high. Data on the actual state of cardiovascular shock treatment and outcomes in Japan are scarce. In this study, we aimed to investigate the baseline characteristics and outcomes of patients with cardiovascular shock and identify the predictors of 30-day mortality. Methods: The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multi-center, cohort study. Between May 2012 and June 2014, a total of 980 patients with cardiovascular shock were enrolled from 82 centers in Japan. The median (interquartile range) age of the enrolled patients was 72 (63, 81) years, and 66% of the patients were male. The primary endpoint was all-cause death at 30 days. Results: The causes of shock included acute coronary syndrome (50.6%), non-ischemic arrhythmia (15.9%), aortic disease (14.9%), myocarditis (2.2%), cardiomyopathy (3.4%), pulmonary embolism (4.4%), valvular heart disease (1.3%), infective endocarditis (0.5%) and cardiac tamponade (1.4%). The all-cause mortality was 34.3%. On multivariate analysis, systolic blood pressure (odds ratio [OR], 0.986; 95% confidence interval [CI], 0.98-0.99, p&lt;0.001), neurological status (OR, 1.694; 95% CI, 1.47-1.96, p&lt;0.001), estimated glomerular filtration rate (OR, 0.982; 95% CI, 0.97-0.99, p&lt;0.001), non-ischemic arrhythmia (OR, 0.516; 95% CI, 0.32-0.82, p=0.005), aortic disease (OR, 2.155; 95% CI, 1.41-3.30, p&lt;0.001), and myocarditis (OR, 3.803; 95% CI, 1.41-10.23, p=0.008) were independent predictors of all-cause death at 30 days. Conclusion: Patients with non-ischemic arrhythmia had better prognosis, whereas those with aortic disease and myocarditis had poor prognosis. Blood pressure, neurological status, and renal function were also independent predictors of 30-day mortality.
Melanoma subsequent to natalizumab exposure: A report from the RADAR (Research on Adverse Drug events And Reports) program
Authors: Ryan C. Kelm, Erika L. Hagstrom, Regine J. Mathieu, Kelsey A. Orrell, Linda Serrano, Kelly A. Mueller, Anne E. Laumann, Dennis P. West, Beatrice Nardone
Journal: Journal of the American Academy of Dermatology (2018)
AB1049 Rheumatological manifestations during chronic hepatitis c
Authors: H. Kchir, D. KAFFEL, H. Dabbebi, D. ISSAOUI, H. Sahli, W. Hamdi, M. Elleuch, M.M. Kchir, R. Debbeche, N. Maamouri
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Chronic hepatitis C (CHC) is assimilated to a systemic disease because of his multiple extrahepatic manifestations notably rheumatological. <h3>Objectives</h3> The aim of this study was to determinate the prevalence and the characteristics of rheumatological manifestations (RM) associated with CHC. <h3>Methods</h3> A retrospective study including all patients suffering from CHC followed over a period of 11 years (2002–2012). Were excluded all patients co-infected by hepatitis B virus or by human immunodefficiency virus and those having decompensated cirrhosis. Different RM were collected and analysed according to the epidemiological, clinico-biological, immunological, virological and histological data of the CHC. <h3>Results</h3> Two hundred and four patients affected by CHC were included, meanly aged by 52 years [22–66 years]. The sex-ratio was 0,46. MR were noted in 76 patients (37,25%) dominated by inflammatory polyarthralgia of big joints (88,25%). Non erosive arthritis was observed in a woman and was localised to the proximal interphalangeal articulation of the index. Myalgia were noted in 11 cases (14,47%) among them, 2 appeared under antiviral treatment. Sicca Syndrome was observed in 17 cases (22,36%). RM were associated to other extrahepatic manifestations of CHC in 69,7% of cases, notably to mixed cryoglobulinemia (MC) (60%) and to antinuclear antibodies (21,6%). Anti DNA, anti SSA, anti SSB, rheumatoid factor and anti CCP were absent in all cases. A partial to total amelioration of RM was noted in almost patients under antiviral treatment and sometimes associated to symptomatic measures. In univariate analyse, only feminal sexe and presence of MC were significatly correlated to the presence of MR. <h3>Conclusions</h3> During CHC, MR are frequent, dominated by arthralgia, myalgia and sicca syndrome. Authentic arthritis are rare and constitute a diagnostic problem essentially when they inaugurate the disease. MC is the immunological factor the most associated with RM. Treatment of MR still antiviral. <h3>Disclosure of Interest</h3> None declared
Abstract 15022: Coronary Microvascular Dysfunction in Patients With Acute Coronary Syndromes in the Absence of Obstructive Coronary Atherosclerosis
Authors: Antonio De Vita, Giulio Russo, Priscilla Lamendola, Antonino Di Franco, Angelo Villano, Lina Gentile, Emanuele Ravenna, Gaetano Antonio Lanza, Filippo Crea
Journal: Circulation (2016)

Introduction: About 10% of patients admitted for a non ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NO-CAD) at angiography. Hypothesis: Abnor...
Medical cannabis: “restrictive” guidance lets patients down, say campaigners
Authors: Richard Hurley
Journal: BMJ (2018)

GPs have been advised not to prescribe unlicensed drugs containing naturally occurring cannabinoids but to refer patients at “the appropriate point in their treatment pathway” to specialists registered with the General Medical Council.

The guidance from NHS England advises that patients should not approach GPs to ask for these products.1

Very few patients are expected to benefit from the change in the law that comes into force on 1 November,2 experts have warned. Many patients will continue to take cannabis illegally to manage symptoms, risking criminalisation, they said.

The move to change medicinal products derived from cannabis to schedule 2 of the 2001 Misuse of Drugs Regulations came after advice from England’s chief medical officer, Sally Davies, and the Advisory Council on the Misuse of Drugs, after several recent cases of children …
Management and outcomes of cardiac sarcoidosis: a 20‐year experience in two tertiary care centres
Authors: Lynn A. Fussner, Erin Karlstedt, David O. Hodge, Nowell M. Fine, Sanjay Kalra, Eva M. Carmona, James P. Utz, Debra L. Isaac, Leslie T. Cooper
Journal: European Journal of Heart Failure (2018)
The CDK4/6 Inhibitor Palbociclib Exerts Growth-Inhibitory Effects on Neoplastic Mast Cells and Synergizes with Midostaurin in Producing Growth Arrest
Authors: Mathias A. Schneeweiss, Gabriele Stefanzl, Daniela Berger, Gregor Eisenwort, Mohamad Jawhar, Greiner Georg, Gregor Hoermann, Wolfgang R. Sperr, Michel Arock, Andreas Reiter, Peter Valent, Karoline V. Gleixner
Journal: Blood (2018)
Abstract 15061: Prognostic Value of Post-exercise Heart Rate Recovery in Patients With Acute Decompensated Heart Failure
Authors: Jong-Chan Youn, Namki Hong, Jaewon Oh, Sungha Park, Sang-Hak Lee, Donghoon Choi, Seok-Min Kang
Journal: Circulation (2014)

Background: Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcomes in patients with chronic heart failure. However, its prognostic value i...
Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population based cohort study
Authors: Yash S Khandwala, Valerie L Baker, Gary M Shaw, David K Stevenson, Ying Lu, Michael L Eisenberg
Journal: BMJ (2018)

To evaluate the impact of advanced paternal age on maternal and perinatal outcomes in the United States.Retrospective, population based cohort study.US.40 529 905 documented live births between 2007 and 2016.Primary perinatal outcomes were gestational age, birth weight, Apgar score at five minutes, admission to a neonatal intensive care unit, need for postpartum antibiotics, and seizures. Primary maternal outcomes were gestational diabetes and pre-eclampsia. Secondary outcome was the number of preventable perinatal events.Higher paternal age was associated with an increased risk of premature birth, low birth weight, and low Apgar score. After adjustment for maternal age, infants born to fathers aged 45 years or older had 14% higher odds of premature birth (odds ratio 1.14, 95% confidence interval 1.13 to 1.15), independent of gestational age, and 18% higher odds of seizures (1.18, 0.97 to 1.44) compared with infants of fathers aged 25 to 34 years. The odds of gestational diabetes was 34% higher (1.34, 1.29 to 1.38) in mothers with the oldest partners. 13.2% (95% confidence interval 12.5% to 13.9%) of premature births and 18.2% (17.5% to 18.9%) of gestational diabetes in births associated with older fathers were estimated to be attributable to advanced paternal age.Advanced paternal age is associated with negative effects on both mothers and offspring. Given the relatively low prevalence of advanced paternal age in the US, population level impacts are currently modest. Nevertheless, as advanced paternal age has doubled in the US over the past generation, further investigation is warranted of the impact on birth outcomes and public health.
Unrecognised myocardial infarction and its relationship to outcome in critically ill patients with cardiovascular disease
Authors: Annemarie B. Docherty, Shirjel Alam, Anoop S. Shah, Alastair Moss, David E. Newby, Nicholas L. Mills, Simon J. Stanworth, Nazir I. Lone, Timothy S. Walsh
Journal: Intensive Care Medicine (2018)
Abstract P235: Baseline Demographic Characteristics of the Million Veteran Program: Increasing BMI Seen From 2011-2016 Among US Male Enrollees
Authors: Rachel M Quaden, Xuan-Mai T Nguyen, Rebecca J Song, John Concato, J. Michael Gaziano, Christopher J O’Donnell, David R Gagnon, Luc Djousse, Kelly Cho on behalf of the MVP Investigators
Journal: Circulation (2017)

Background: More than one-third of US adults are obese and the prevalence has remained stable since 2003. In the largest cohort of 515,912 men and women participating in the Million Veteran Program (MVP), we analyzed trends in baseline weight/obesity across the years of enrollment. Objective: The goal of this study is to examine prevalence and trends in baseline characteristics among US Veterans enrolled in MVP between 2011 and 2016. We highlight the trends in BMI over the enrollment period. Methods: BMI was computed for 479,521 Veterans who enrolled in MVP between 2011 to September 2016. Participants reported weight and height on the baseline survey. Missing survey data was supplemented with patient EMR data taken closest to enrollment date and stratified by year of enrollment. Results: Mean age was 61.2 (SD=13.8), 91.6% (391,124/427,187) were men, 73.8% (353,720/479,520) White, 18.8% (90,020/479,520) Black, and 7.4% (35,593/479,520) Hispanic. Overall, mean BMI was 29.7 [range 11.3 to 78.5]. Prevalence of underweight, normal weight, and overweight was 0.7% (3,164/479,521), 19.4% (93,318/479,521), 38.4% (184,625/479,521), respectively, in this cohort. While the prevalence of obesity increased with consecutive years of enrollment in men and overall, we did not observe such trend for other categories of adiposity (Fig). When stratified by race we did not observe any difference in prevalence of underweight and normal weight among White and Black participants. Prevalence of obesity was higher in Blacks, but the rate of obesity among Whites appears to be growing at a faster rate than in Blacks. Compared to the general VHA (Veterans Health Administration) population, prevalence of obesity and the distributions of race, gender, and ethnicity were similar among participants in MVP. Conclusion: Our data show that the prevalence of overweight/obesity is high among US Veterans. Across consecutive years of enrollment, prevalence of obesity but not overweight appears to increase across each ethnic group.
In Situ Forming Injectable Silk Fibroin Hydrogel Promotes Skin Regeneration in Full Thickness Burn Wounds
Authors: Dimple Chouhan, Tshewuzo‐u Lohe, Pavan Kumar Samudrala, Biman B. Mandal
Journal: Advanced Healthcare Materials (2018)

Abstract Full‐thickness skin wounds, associated with deep burns or chronic wounds pose a major clinical problem. Herein, the development of in situ forming hydrogel using a natural silk fibroin (SF) biomaterial for treating burn wounds is reported. Blends of SF solutions isolated from Bombyx mori and Antheraea assama show inherent self‐assembly between silk proteins and lead to irreversible gelation at body temperature. Investigation of the gelation mechanism reveals crosslinking due to formation of β‐sheet structures as examined by X‐ray diffraction and Fourier transform infrared spectroscopy. The SF hydrogel supports proliferation of primary human dermal fibroblasts and migration of keratinocytes comparable to collagen gel (Col) as examined under in vitro conditions. The SF hydrogel also provides an instructive and supportive matrix to the full‐thickness third‐degree burn wounds in vivo. A 3‐week comparative study with Col indicates that SF hydrogel not only promotes wound healing but also shows transitions from inflammation to proliferation stage as observed through the expression of TNF‐α and CD163 genes. Further, deposition and remodeling of collagen type I and III fibers suggests an enhanced overall tissue regeneration. Comparable results with Col demonstrate the SF hydrogel as an effective and inexpensive formulation toward a potential therapeutic approach for burn wound treatment.
Sixty Years of Discovery
Authors: David Baltimore
Journal: Annual Review of Immunology (2018)

Each of us is a story. Mine is a story of doing science for 60 years, and I am honored to be asked to tell it. Even though this autobiography was written for the Annual Review of Immunology, I have chosen to describe my whole career in science because the segment that was immunology is so intertwined with all else I was doing. This article is an elongation and modification of a talk I gave at my 80th birthday celebration at Caltech on March 23, 2018.
Activation of PP2A and Inhibition of mTOR Synergistically Reduce MYC Signaling and Decrease Tumor Growth in Pancreatic Ductal Adenocarcinoma
Authors: Brittany L. Allen-Petersen, Tyler Risom, Zipei Feng, Zhiping Wang, Zina P. Jenny, Mary C. Thoma, Katherine R. Pelz, Jennifer P. Morton, Owen J. Sansom, Charles D. Lopez, Brett Sheppard, Dale J. Christensen, Michael Ohlmeyer, Goutham Narla, Rosalie C. Sears
Journal: Cancer Research (2018)

Abstract In cancer, kinases are often activated and phosphatases suppressed, leading to aberrant activation of signaling pathways driving cellular proliferation, survival, and therapeutic resistance. Although pancreatic ductal adenocarcinoma (PDA) has historically been refractory to kinase inhibition, therapeutic activation of phosphatases is emerging as a promising strategy to restore balance to these hyperactive signaling cascades. In this study, we hypothesized that phosphatase activation combined with kinase inhibition could deplete oncogenic survival signals to reduce tumor growth. We screened PDA cell lines for kinase inhibitors that could synergize with activation of protein phosphatase 2A (PP2A), a tumor suppressor phosphatase, and determined that activation of PP2A and inhibition of mTOR synergistically increase apoptosis and reduce oncogenic phenotypes in vitro and in vivo. This combination treatment resulted in suppression of AKT/mTOR signaling coupled with reduced expression of c-MYC, an oncoprotein implicated in tumor progression and therapeutic resistance. Forced expression of c-MYC or loss of PP2A B56α, the specific PP2A subunit shown to negatively regulate c-MYC, increased resistance to mTOR inhibition. Conversely, decreased c-MYC expression increased the sensitivity of PDA cells to mTOR inhibition. Together, these studies demonstrate that combined targeting of PP2A and mTOR suppresses proliferative signaling and induces cell death and implicates this combination as a promising therapeutic strategy for patients with PDA. Significance: These findings present a combinatorial strategy targeting serine/threonine protein phosphatase PP2A and mTOR in PDA, a cancer for which there are currently no targeted therapeutic options.
Abstract 17863: Is Isolated Nocturnal Hypertension a Reproducible Ambulatory Blood Pressure Phenotype?
Authors: Marwah Abdalla, Jeff Goldsmith, Keith M Diaz, Paul Muntner, Joseph E Schwartz, Daichi Shimbo
Journal: Circulation (2014)

Background: Isolated nocturnal hypertension (INH), defined as nocturnal without daytime hypertension, assessed using ambulatory blood pressure (ABP) monitoring (ABPM), is associated with increased ...
NTA-Co3+-His6 versus NTA-Ni2+-His6 mediated E-Cadherin surface immobilization enhances cellular traction
Authors: Jacopo Di Russo, Jennifer L. Young, Adithya Balakrishnan, Amelie S. Benk, Joachim P. Spatz
Journal: Biomaterials (2018)

Understanding the biological impact of strategies for protein immobilization onto bioactive surfaces is crucial for the design of biomimetic materials. A common strategy used to immobilize or label recombinant proteins is to exploit the Ni2+-mediated interaction of nitrilotriacetic acid (NTA) with the hexahistidine tag (His6-tag) present on recombinant proteins. While this method ensures a controlled orientation and functionality of the protein, the kinetically labile nature of the bond ensures only its weak immobilization onto the surface. Recently, it has been shown that the oxidation of Co2+ to Co3+ greatly stabilizes the bond between NTA and the His6-tagged proteins, making it inert to ligand exchange and resistant to chelators. This approach not only has the potential to improve the quality of biomimetic material functionalization and molecule labeling but could also affect cellular mechanical responses for which the mechanical strength of the protein-surface bond is crucial. Here, we compared gold (Au) nanopatterned polyacrylamide (PAA) hydrogels functionalized with E-cadherin via Co3+ with those functionalized via Ni2+ for studying adhesion-mediated responses in keratinocytes. We show that keratinocytes develop higher and a broader range of adhesion forces, leading to extended cell spreading and colony organization on Co3+ vs. Ni2+. This work uniquely shows that stabilizing the NTA/His6-tag bond via Co3+ for protein immobilization significantly impacts cellular phenotype on biomimetic materials by impacting cell signaling.
Promoting Axon Regeneration in Adult CNS by Targeting Liver Kinase B1
Authors: Yosuke Ohtake, Armin Sami, Xinpei Jiang, Makoto Horiuchi, Kieran Slattery, Lena Ma, George M. Smith, Michael E. Selzer, Shin-ichi Muramatsu, Shuxin Li
Journal: Molecular Therapy (2018)

Liver kinase B1 (LKB1), a downstream effector of cyclic AMP (cAMP)/PKA and phosphatidylinositol 3-kinase (PI3K) pathways, is a determinant for migration and differentiation of many cells, but its role in CNS axon regeneration is unknown. Therefore, LKB1 was overexpressed in sensorimotor cortex of adult mice five days after mid-thoracic spinal cord injury, using an AAV2 vector. Regeneration of corticospinal axons was dramatically enhanced. Next, systemic injection of a mutant-AAV9 vector was used to upregulate LKB1 specifically in neurons. This promoted long-distance regeneration of injured corticospinal fibers into caudal spinal cord in adult mice and regrowth of descending serotonergic and tyrosine hydroxylase immunoreactive axons. Either intracortical or systemic viral delivery of LKB1 significantly improved recovery of locomotor functions in adult mice with spinal cord injury. Moreover, we demonstrated that LKB1 used AMPKα, NUAK1, and ERK as the downstream effectors in the cortex of adult mice. Thus, LKB1 may be a critical factor for enhancing the growth capacity of mature neurons and may be an important molecular target in the treatment of CNS injuries.