tbuckley/cabot-search huggingface dataset:
Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia
Authors: Michelle Brasure, Priyanka Desai, Heather Davila, Victoria A. Nelson, Collin Calvert, Eric Jutkowitz, Mary Butler, Howard A. Fink, Edward Ratner, Laura S. Hemmy, J. Riley McCarten, Terry R. Barclay, Robert L. Kane
Journal: Annals of Internal Medicine (2017)

The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems.To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments.Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews.Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls.Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions.Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes.Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence).Agency for Healthcare Research and Quality.
<i>ESR1</i> Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment
Authors: Sophia Mastoraki, Areti Strati, Eleni Tzanikou, Maria Chimonidou, Eleni Politaki, Alexandra Voutsina, Amanda Psyrri, Vassilis Georgoulias, Evi Lianidou
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM+ CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. ESR1 methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER+/HER2− advanced breast cancer receiving everolimus/exemestane. Results: ESR1 methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) EpCAM+ CTC fractions: 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) plasma ctDNA: 8/108 (7.4%) patients and 1/30 (3.3%) HD. ESR1 methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, ESR1 methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment (P = 0.023, Fisher exact test). Conclusions: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. Clin Cancer Res; 24(6); 1500–10. ©2017 AACR.
Association of Uterine Leiomyomas With Central Centrifugal Cicatricial Alopecia
Authors: Yemisi Dina, Ginette A. Okoye, Crystal Aguh
Journal: JAMA Dermatology (2017)

This cohort study examines the risk of uterine leiomyomas in black women with central centrifugal cicatricial alopecia.
Shared cancer neoantigens: Making private matters public
Authors: Christopher A. Klebanoff, Jedd D. Wolchok
Journal: The Journal of Experimental Medicine (2017)

In this issue of JEM, Chheda et al. (https://doi.org/10.1084/jem.20171046) report that a conserved hotspot mutation associated with an aggressive form of brain cancer generates an immunogenic T cell epitope restricted by a common HLA subtype, thereby creating a “public” neoantigen.
Immunotherapy Combinations Proliferating in Immuno-Oncology
Authors: Vicki Brower
Journal: JNCI Journal of the National Cancer Institute (2017)

A recent phase III study in advanced melanoma tested a combination of two immunotherapies, nivolumab and ipilimumab, against each drug alone.The duo improved overall survival and progression-free survival, with the median overall survival not reached at 36 months or more, compared with 37.6 months for nivolumab and 19.9 months for ipilimumab.The drugs are checkpoint inhibitors of the programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), respectively, proteins that block immune responses to cancer (N.Engl.J. Med.
Abstract 16671: Thermodilution Underestimates Cardiac Output During Exercise Leading to Frequent Erroneous Diagnoses of Exercise-induced Pulmonary Hypertension
Authors: Samuel B Brusca, Steven Hsu, Parker S Rhodes, Ryan J Tedford
Journal: Circulation (2016)

Introduction: Recent interest in establishing a definition of exercise-induced pulmonary hypertension (EiPH) has resulted in two potential criteria: mean pulmonary artery pressure/cardiac output (m...
Margaret Machon Platts
Authors: Colin Brown
Journal: BMJ (2017)

Margaret Machon Platts won a scholarship to Sheffield Girls High School at the age of 11. She entered Sheffield medical school in 1942-3 and may have been the only woman in her class. Her initial interest after qualifying was in respiratory physiology, on which she obtained her MD and was appointed to the teaching staff in Sheffield. However, her professional life was to take a very different course. In the mid 1960s the NHS began to fund …
23 Small intestinal bacterial overgrowth in chronic pancreatitis patients with pancreatic exocrine insufficiency; a prospective cohort study
Authors: H Ní Chonchubhair, Y Bashir, M Dobson, B Ryan, S Duggan, K Conlon
Journal: Gut (2017)

Background  Pancreatic exocrine insufficiency (PEI) causes malabsorption and is a major complication of chronic pancreatitis (CP). Small intestinal bacterial overgrowth (SIBO) worsens symptoms and nutritional status in CP, its prevalence is unclear  Aim  We examined SIBO prevalence in CP patients with PEI (defined as faecal elastase-1  Method  34 patients and 25 controls (matched for age/gender/smoking status) underwent hydrogen breath-testing using a glucose substrate. Exclusion criteria included gastric/pancreatic/intestinal surgery, or antibiotic treatment   Results  Patients and controls were well-matched, with 67% and 64% males respectively (p=0.775), a mean (standard deviation) age of 52.4 (10.4) and 53.3 (10.5) year respectively (p=0.919), and 47.1% and 28% smokers respectively (p=0.143). Among patients, there was no association found between the presence of SIBO and gender (p=0.156), or PPI use (p=0.328). There was a significantly positive association found between the presence of SIBO and diabetes (p=0.033), while the positive association between the presence of SIBO and pancreatic enzyme replacement therapy (PERT) use just reached significance (p=0.052)  Conclusions  SIBO prevalence was 15% and not associated with gender, age, or PPI use, but was positively associated with PERT use, and concurrent diabetes. Patients with diabetes may be more likely to suffer from SIBO due to small bowel dysmotility, whilst SIBO and PEI may co-exist, with similar symptoms. We recommend that SIBO should be considered in non-surgical CP patients, if they have gastro-intestinal symptoms that are unresponsive to high-dose PERT, particularly if there is co-existent diabetes. Treatment should be aggressive, and there may be a requirement for repeat therapy.
Abstract 12140: Effect of Hypothermia on the Peripheral and Cerebral Microcirculation in a Rat Model of Cardiac Arrest
Authors: Ziren Tang, Jiangang Wang, Lu Yin, Shen Zhao, Haifang Yu, Xiaobo Wu, Mary A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: Therapeutic hypothermia improves outcomes after cardiac arrest (CA) and is a standard therapy for comatose patients after successful initial resuscitation. Post-resuscitation functional vital organ recovery is largely dependent on microcirculatory function. The effects of hypothermia on the peripheral and cerebral microcirculation following CA are not fully understood. Hypothesis: Hypothermia reduces the peripheral microcirculatory flow. However, the microcirculatory flow of cerebral cortex is preserved during hypothermia in a rat model of CPR. Methods: Twenty-one male Sprague-Dawley rats were randomized into three groups: hypothermic (HT, n=8), normothermic (NT, n=8) or sham-operated group (SO, n=5). Ventricular fibrillation was induced electrically and untreated for 8 mins, followed by 8 mins of precordial compressions and mechanical ventilations. The core temperature was reduced to 33±0.2°C at 5 mins following successful resuscitation and maintained for 8 hrs in the HT group. Normothermic animals were maintained at 37±0.2°C for 8 hrs. Sublingual and cerebral cortex microcirculation was measured by a sidestream dark-field imaging device at baseline, 1, 2, 3, 4, 6 and 8 hrs post-resuscitation. Results: All animals were resuscitated successfully. The sublingual microcirculatory flow index (MFI) was decreased significantly compared to the cerebral cortex MFI in the HT group following resuscitation (P&lt; 0.05) (Figure 1). However, sublingual and cerebral microcirculation were impaired equally in the NT group after resuscitation.(Figure 2) Conclusions: A similar reduction in both sublingual and cerebral cortex microcirculatory flow was observed following resuscitation under conditions of normothermia. Hypothermia preserved the cerebral cortex microcirculation, but not the peripheral microcirculation, after resuscitation.
Abstract 16600: Unraveling Outcomes in Medically Managed Patient With Acute Coronary Syndromes (ACS): The Alberta COntemporary Acute coronary syndrome Patients invasive Treatment Strategies (COAPT) Study
Authors: Robert C Welsh, Kevin R Bainey, Colleen Norris, Merril Knudtson, Dean Traboulsi, Neil Brass, Anamaria Savu, Imtiaz Ali, Blair O'Neill, Paul W Armstrong, Padma Kaul
Journal: Circulation (2015)

Objectives: Limited “real world” data exists on characteristics and outcomes of ACS patients managed without revascularization (REVASC). Accordingly, we assessed an inclusive cohort of ACS patients grouped by catheterization and REVASC status. Methods: ACS pts in Alberta, Canada (n=3.7M) were assessed using population health database linkages (April 2010 - March 2013) and categorized into 3 groups: no CATH, CATH no REVASC and CATH REVASC (excluding pts with previous CATH - 6 m or ACS - 3 m). Baseline characteristics, in-hospital death, one year death and readmission were compared (logistic regression modelling). Results: Of 14, 661 ACS pts, 20.6% were not referred for CATH, 17.7% had CATH no REVASC and 61.7% had CATH REVASC (table). The pts not referred for CATH pts were older had more comorbidities, less frequent STEMI and were more likely admitted to a non-CATH hospital. They had prolonged hospital stay and 11.9% in-hospital death; 4-fold higher comparing no CATH vs. REVASC (adjusted OR 4.37, 95% CI 3.4-5.6). After excluding pts with in-hospital death within 2 days from admission and/or non-obstructive CAD (n=712), pts not referred for CATH had a 3-fold risk of in-hospital death (OR 3.28, 95% CI 2.5-4.4). Compared to REVASC, CATH no REVASC did not have increased in-hospital death (OR 1.2, 95% CI 0.86 - 1.1), however if pts without obstructive CAD were excluded, CATH no REVASC had a trend for increased in-hospital death (OR 1.4, 95% CI 0.99 - 1.96). Cath no REVASC was associated with increased 1 yr death (adjusted OR 1.97 (1.54-2.5)). Conclusion: Patients with ACS managed medically represent a diverse patient population. Once receiving CATH, pts managed medically have similar risk of death as those receiving REVASC. However those not referred for CATH have multiple comorbidities, are more likely managed in non-cardiac CATH hospitals and have a marked increase in both of in-hospital and 1 year death and rehospitalizaiton.This substantial cohort deserves further investigation.
Prognostic impacts and dynamic changes of cohesin complex gene mutations in de novo acute myeloid leukemia
Authors: Cheng-Hong Tsai, Hsin-An Hou, Jih-Luh Tang, Yuan-Yeh Kuo, Yu-Chiao Chiu, Chien-Chin Lin, Chieh-Yu Liu, Mei-Hsuan Tseng, Tzung-Yi Lin, Ming-Chih Liu, Chia-Wen Liu, Liang-In Lin, Ming Yao, Chi-Cheng Li, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Chien-Ting Lin, Shang-Ju Wu, Chien-Yuan Chen, Woei Tsay, Eric Y. Chuang, Wen-Chien Chou, Hwei-Fang Tien
Journal: Blood Cancer Journal (2017)

Cohesin complex is a multimeric protein complex, composed of four core subunits, including SMC1A, SMC3, RAD21, and either STAG1 or STAG2 proteins.They form a ring-shaped structure, and mediate sister chromatid cohesion and segregation during mitosis and meiosis.Recently, the cohesin gene mutations have been reported in myeloid neoplasms [1][2][3][4][5][6][7] , but studies regarding their clinical and prognostic relevance and dynamic changes in de novo acute myeloid leukemia (AML) patients are limited and the findings are controversial.In this study, we aimed to investigate the clinical, biological, and prognostic implications of cohesin gene mutations in a large cohort of de novo AML patients.To evaluate the sequential changes of cohesin and cooccurring gene mutations, serial analyses of gene mutations by targeted next-generation sequencing (NGS) were performed in 386 samples from 116 patients during follow-ups.To the best of our knowledge, this is the first report to address the dynamic changes of cohesin gene mutations during the clinical course in de novo AML.We also investigated the pathophysiological pathways by mRNA expression profiling.A total of 391 consecutive patients with newly diagnosed de novo non-M3 AML, consisting of 217 males and 174 females, were recruited.The coding sequences of cohesin complex genes were screened by Ion Torrent
The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex
Authors: Lorena Verduci, Maria Ferraiuolo, Andrea Sacconi, Federica Ganci, Jlenia Vitale, Teresa Colombo, Paola Paci, Sabrina Strano, Giuseppe Macino, Nikolaus Rajewsky, Giovanni Blandino
Journal: Genome biology (2017)

Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. circPVT1 up- and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines. We show that circPVT1 expression is transcriptionally enhanced by the mut-p53/YAP/TEAD complex. circPVT1 acts as an oncogene modulating the expression of miR-497-5p and genes involved in the control of cell proliferation. This study shows the oncogenic role of circPVT1 in HNSCC, extending current knowledge about the role of circular RNAs in cancer.
Abstract 15976: Comparison of Patients With Variant and Typical Takotsubo Cardiomyopathy
Authors: Sijun Kim, Robert T Palac, Anthony S Gemignani, Daniel J O’Rourke, Harley P Friedman, Scott E Friedman
Journal: Circulation (2015)

Background: Variant, or reverse, Takotsubo cardiomyopathy (TTC) is defined by left ventricular basal and/or mid-ventricular systolic dysfunction with preserved apical function. This condition is increasingly recognized, yet there have been few studies comparing variant and typical TTC. This study aims to contrast the demographic features and clinical outcomes of patients with variant and typical TTC. Methods: All patients at a single academic medical center with a discharge diagnosis of Takotsubo syndrome [ICD-9-CM 429.83] from 2010-2014 were identified. Patients who met the Mayo Clinic criteria for TTC were included and were then grouped into typical or variant TTC categories based on wall motion abnormality patterns. Results: The initial query identified 275 patients with a discharge diagnosis of TTC, of which 145 (52.7%) met diagnostic criteria for TTC. Typical TTC was present in 125 patients (86.2%) and variant TTC in 20 patients (13.8%). The demographic and clinical characteristics of these groups are summarized in table 1. Variant TTC patients were more likely to be male and subject to a physically stressful trigger. Typical TTC patients had lower left ventricular ejection fraction, higher left ventricular end-diastolic pressure, and were more likely to be intubated. Cardiac biomarkers were not significantly different between groups. In-hospital mortality, length of hospital stay, TTC recurrence and follow-up LVEF were similar between groups. Conclusions: There are important differences between patients with variant and typical TTC. Variant TTC is not as strongly associated with female sex, it is more frequently preceded by a physical stressor, and it has a more benign presentation. Long term outcomes are favorable in patients with variant and typical TTC.
Abstract 13261: Relationship Between Circulating CD34+ and CD146+ Cells and Change in Infarct Size in Patients With Acute Coronary Syndrome
Authors: Damien Montange, Siamak Davani, Ségolène Gambert, Marie-France Seronde, Francois Schiele, Nicolas F Meneveau
Journal: Circulation (2015)

Background: The presence of CD34+ and CD146+ cells in the peripheral blood in response to myocardial ischemia has been advocated as a marker of an organism’s regenerative capacity by late and early progenitor cells respectively. The aim of this study was to evaluate the relationship between circulating CD34+ and CD146+ levels and the change in infarct size, as assessed by magnetic resonance imaging (MRI) in patients (pts) with acute coronary syndrome (ACS including ST and non ST elevation myocardial infarction). Methods: Patients &lt;75 years old, admitted with a first ACS within 12 hours of onset of symptoms were enrolled. Peripheral blood samples for cytofluorimetric analysis of CD34+ and CD146+ cells level were drawn at day 0. Initial infarct size was evaluated from peak troponin I levels determined from 5 blood samples over the first 72 hours. MRI measurements of infarct size were performed at day 5 and at 6 months follow-up. Results: In total, 34 patients aged 57±10 years were included. Mean ejection fraction was 62±11%. Log-transformed number of CD 34+ and CD146+ were significantly correlated with the relative change in infarct size between day 5 and 6 month follow-up (p=0.01, r=-0;41 and p=0.001, r=-0.52 respectively) (Figure) Conclusion: The highest CD34+ and CD146+ cell levels were associated with the greatest relative reduction in infarct size 6 months after ACS. These results support the hypothesis that these cells could be considered as a marker of regenerative capacity in patients with acute coronary syndromes.
Abstract 17233: The Preventive Effect of Angiotensin-converting Enzyme Inhibitor on Renal Function in the Late Phase After Percutaneous Coronary Intervention in Patients With Statin
Authors: Daisuke Kanda, Takuro Takumi, Takeshi Sonoda, Ippei Kosedo, Masaaki Miyata, Mitsuru Ohishi
Journal: Circulation (2016)

Introduction: The statin is a pivotal medicine for patients with angina pectoris, and is thought to have a preventive effect on renal function. Depressant medicines of Renin-Angiotensin System (RAS...
Psychiatric symptoms after acute respiratory distress syndrome: a 5-year longitudinal study
Authors: O. Joseph Bienvenu, Lisa Aronson Friedman, Elizabeth Colantuoni, Victor D. Dinglas, Kristin A. Sepulveda, Pedro Mendez-Tellez, Carl Shanholz, Peter J. Pronovost, Dale M. Needham
Journal: Intensive Care Medicine (2017)
Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M4 Muscarinic Receptor
Authors: Mark S. Moehle, Tristano Pancani, Nellie Byun, Samantha E. Yohn, George H. Wilson, Johnathan W. Dickerson, Daniel H. Remke, Zixiu Xiang, Colleen M. Niswender, Jürgen Wess, Carrie K. Jones, Craig W. Lindsley, Jerri M. Rook, P. Jeffrey Conn
Journal: Neuron (2017)
Reduced‐Intensity Chemotherapy in Patients With Advanced‐Stage Hodgkin Lymphoma
Authors: Andreas Engert, Helen Goergen, Jana Markova, Thomas Pabst, Julia Meissner, Josée M. Zijlstra, Zdenek Král, Dennis A. Eichenauer, Martin Soekler, Richard Greil, Stefanie Kreissl, Ruth Scheuvens, Hans Eich, Carsten Kobe, Markus Dietlein, Harald Stein, Michael Fuchs, Volker Diehl, Peter Borchmann
Journal: HemaSphere (2017)

The international, randomized phase 3 HD15 trial established 6xeBEACOPP as standard therapy for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) within the German Hodgkin Study Group (GHSG). We performed a follow-up analysis to assess long-term efficacy and safety of this approach. Between 2003 and 2008, 2182 patients aged 18 to 60 years were recruited and randomized in a 1:1:1 ratio between 8 or 6 cycles of eBEACOPP or 8 cycles of the dose-dense BEACOPP-14 regimen, each followed by 30 Gy radiotherapy in case of positron emission tomography (PET)-positive residual lesions ≥2.5 cm. The study aimed at demonstrating non-inferiority regarding efficacy of the 2 experimental arms on a significance level of 2.5% each. The intention-to-treat analysis comprised 2126 patients with a median follow-up of 102 months. Ten-year progression-free survival was 81% (97.5% CI 77-85) with 8xeBEACOPP, 84% (80-87) with 6xeBEACOPP, and 84% (80-87) with 8xBEACOPP-14; the non-inferiority margin of 1.51 for the hazard ratio (HR) could be excluded for both comparisons (6xeBEACOPP, HR = 0.7, 97.5% CI 0.5-1.0; 8xBEACOPP-14, HR = 0.9, 97.5% CI 0.7-1.2). Overall survival at 10 years was 88% (85-91), 90% (88-93), and 92% (89-94), respectively. A total of 142 second malignancies corresponding to 10-year cumulative incidences of 10%, 7%, and 7% and standardized incidence ratios of 4.3, 2.5, and 2.8 were reported for 8xeBEACOPP, 6xeBEACOPP, and 8xBEACOPP-14, respectively. This updated analysis of the HD15 trial thus confirms the efficacy and reports on the long-term safety of a shortened first-line chemotherapy consisting of 6xeBEACOPP followed by PET-guided radiotherapy in advanced-stage HL.