tbuckley/cabot-search huggingface dataset:
Bicuspid Aortopathy
Authors: María Martín, Rebeca Lorca, César Morís
Journal: JAMA Cardiology (2017)

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Abstract 165: Chronic Ethanol Consumption Impacts Post-Myocardial Infarction Cardiac Function and Modulates Gene Expression in Cardiac Cell Types through Alteration of Histone 3 Lysine 79 Methylation
Authors: Alexander R Mackie, Erin E Vaughan, Suresh K Verma, Prasanna Krishnamurthy, Veronica Ramirez, Aiko Ito, Tatiana V Abramova, Sol Misener, Raj Kishore
Journal: Circulation Research (2013)

The beliefs surrounding the cardiac effects of chronic ethanol (EtOH) consumption in humans are known to be dictated by the frequency of ingestion. Studies have established that moderate consumption (i.e. 1-2 drinks/day) imparts a cardiac benefit to patients by reducing the frequency of adverse cardiovascular events (ACE). EtOH consumption beyond moderate levels (i.e. &gt;2 drinks per day) is associated with a significant increase in ACEs. Despite this knowledge, little is known regarding the functional impact of chronic EtOH consumption on post-myocardial infarct repair or the cellular mechanisms involved in this process. Therefore, we investigated the post-AMI functional consequences of chronic ethanol consumption in mice. Mice received chronic ethanol via the Lieber-DeCarli paradigm and each group of mice received either: 0%, 1% (moderate) or 5% (high) ethanol v/v in an isocaloric fashion for 8 weeks. After 8 weeks, mice then underwent a 60 minute ischemic/reperfusion injury and the subsequent assessment of their cardiac function at 1, 2 and 4 weeks after AMI. As early as two weeks post-AMI, mice fed the 1% EtOH displayed significant improvements in ejection fraction, systolic ventricular volumes and infarct size as compared to control mice. Conversely, mice that consumed the 5% EtOH diet displayed diminished ejection fraction and increased systolic chamber volume and infarct size. To investigate the mechanistic basis behind these changes, isolated murine cardiac fibroblasts (CFBs) were exposed to EtOH using a “chronic” 5 day treatment paradigm in which media ± EtOH was replaced daily. CFB lysates were then harvested and several epigenetic histone marks were assessed via western blotting. Specifically, methylation of histone 3 lysine 79 (H3K79) was significantly increased at the moderate dose (0.1% v/v) and severely diminished at the high dose (0.5% v/v). H3K79 is exclusively methylated by the methyl-transferase Dot1, suggesting that chronic ethanol may have biphasic dose effects on the regulation of genes influenced by H3K79 methylation. This data represents the first indication that chronic EtOH may affect cells of the post-ischemic heart by influencing their gene expression profiles through manipulation of their epigenetic fingerprint.
Impaired interleukin-10 signaling and ovarian cancer growth in the peritoneal cavity.
Authors: Jill Alldredge, Dallas Flies, Tomoe Higuchi, Thomas Ma, Sarah Foster Adams
Journal: Journal of Clinical Oncology (2014)

e22094 Background: A spontaneous immune response to ovarian cancer improves survival, but tolerant features of the peritoneal (IP) cavity contribute to local immune suppression and tumor immune escape. Interleukin-10 (IL10) is produced by intestinal regulatory T cells (Treg) and peritoneal B1 cells, and is responsible for non-specific suppression of Th1 responses. Ovarian cancer cells also produce IL10, and high IL10 levels in ascites have been associated with a poor prognosis. We hypothesize that IL10 blockade will enhance cytotoxic T cell function in the peritoneal cavity and restrict tumor spread. Methods: We compared peritoneal T cell populations and ovarian cancer growth in IL10 knockout (IL10KO) mice and wild type controls inoculated IP with 5x10^6 ID8 ovarian tumor cells. Mice were euthanized after 9 weeks, and both ascites volume and tumor burden were quantified. Peritoneal leukocytes and splenocytes were harvested and subjected to flow cytometric analysis. Results: The average weight of the animals in both groups was similar. 4/5 wild-type mice had disseminated IP tumor, with large volume ascites (mean 5.2cc, range 0-12 cc), omental caking, mesenteric and peritoneal implants, while 2/5 IL10KO mice had only small volume ascites (mean 0.8cc, range 0-3cc), and none had grossly evident solid tumor. More T cells was found in IP samples from animals with tumor or ascites, however these cells had a predominantly naïve phenotype compared with T cells in tumor-free animals. Peritoneal samples from IL10KO mice had a higher proportion of both CD4 and CD8 cells that were CD44+ memory cells, and an increase in the fraction of T cells that produced both interferon-gamma and tumor necrosis factor-alpha. No significant differences in splenocyte populations were seen. Conclusions: Impaired IL10 signaling limited the establishment of IP ovarian cancer implants in a mouse model. This was associated with increased activation of IP T cell populations and a greater proportion of effector memory cells in the peritoneal cavity, suggesting a role for IL10 in tumor immune escape. We conclude that therapeutic IL10 blockade deserves further study in the design of immunotherapeutic protocols for the treatment of women with ovarian cancer.
A New Formulation of Random Genetic Drift and Its Application to the Evolution of Cell Populations
Authors: Yuxin Chen, Ding Tong, Chung-I Wu
Journal: Molecular Biology and Evolution (2017)

Random genetic drift, or stochastic change in gene frequency, is a fundamental evolutionary force that is usually defined within the ideal Wright-Fisher (WF) population. However, as the theory is increasingly applied to populations that deviate strongly from the ideal model, a paradox of random drift has emerged. When drift is defined by the WF model, it becomes stronger as the population size, N, decreases. However, the intensity of competition decreases when N decreases and, hence, drift might become weaker. To resolve the paradox, we propose that random drift be defined by the variance of "individual output", V(k) [k being the progeny number of each individual with the mean of E(k)], rather than by the WF sampling. If the distribution of k is known for any population, its strength of drift relative to a WF population of the same size, N, can be calculated. Generally, E(k) and V(k) should be density dependent but their relationships are different with or without competition, leading to opposite predictions on the efficiency of random drift as N changes. We apply the "individual output" model to asexual cell populations that are either unregulated (such as tumors) or negatively density-dependent (e.g., bacteria). In such populations, the efficiency of drift could be as low as <10% of that in WF populations. Interestingly, when N is below the carrying capacity, random drift could in fact increase as N increases. Growing asexual populations, especially tumors, may therefore be genetically even more heterogeneous than the high diversity estimated by some conventional models.
Low Dose Secondary/Tertiary Prophylaxis Is Feasible and Effective in Resource Limited Setting in South India for Children with Hemophilia
Authors: Neeraj Sidharthan, Vijayakumar Narayana Pillai, Sheena Mathew, Remya Sudevan, Dinkar Viswam, Cilla Joseph, Sumi Soman, Archana Vijay, Adrienne Lee, Man-Chiu Poon
Journal: Blood (2016)
Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research
Authors: Ahamed H. Idris, Lance B. Becker, Joseph P. Ornato, Jerris R. Hedges, Nicholas G. Bircher, Nisha C. Chandra, Richard O. Cummins, Wolfgang Dick, Uwe Ebmeyer, Henry R. Halperin, Mary Fran Hazinski, Richard E. Kerber, Karl B. Kern, Peter Safar, Petter A. Steen, M. Michael Swindle, Joshua E. Tsitlik, Irene von Planta, Martin von Planta, Robert L. Wears, Max H. Weil
Journal: Circulation (1996)

HomeCirculationVol. 94, No. 9Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research
Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop
Authors: Evan M. Cale, Jason Gorman, Nathan A. Radakovich, Ema T. Crooks, Keiko Osawa, Tommy Tong, Jiaqi Li, Raju Nagarajan, Gabriel Ozorowski, David R. Ambrozak, Mangai Asokan, Robert T. Bailer, Anthony K. Bennici, Xuejun Chen, Nicole A. Doria-Rose, Aliaksandr Druz, Yu Feng, M. Gordon Joyce, Mark K. Louder, Sijy O’Dell, Courtney Oliver, Marie Pancera, Mark Connors, Thomas J. Hope, Thomas B. Kepler, Richard T. Wyatt, Andrew B. Ward, Ivelin S. Georgiev, Peter D. Kwong, John R. Mascola, James M. Binley
Journal: Immunity (2017)
A climate of confusion
Authors: Anne Campbell
Journal: Behavioral and Brain Sciences (2017)

Abstract I identify two confusions and omissions in the target article. Confusion arises from failure to distinguish between a genetically transmitted adaptation and a conditional response to the environment, and from the elision of individual and societal adaptations. Despite points of similarity, there is no mention of Rushton's controversial theory of the climatic basis of race differences in violent crime. Sex differences are also ignored.
Prothrombin gene 20210 G-A mutation in the Turkish population
Authors: Nejat Akar, Müge Misirlioglu, Ece Akar, Ferit Avcu, Atilla Yalçin, Ayşe Sözüöz
Journal: American Journal of Hematology (1998)

The letter published in the November 1997 issue, regarding simultaneous occurrence of lupus anticoagulant (LA) and factor VIII inhibitors [1,2], is very interesting.We agree with Dr. D.A. Triplett that it is of critical importance to differentiate an LA from a factor VIII inhibitor.Strict observance of the criteria recommended by the SSC Subcommittee on Lupus Anticoagulant/Phospholipid-Dependent Antibodies [3] is essential for this purpose.More than one test, with different assay principles, is necessary to screen for an LA, mainly in patients with other simultaneous coagulation defects, such as a neutralizing inhibitor or a factor deficiency.In a recently published study of 170 consecutive hemophilia A patients, we found 36 hemophiliacs who fulfilled the criteria for the diagnosis of LA, 18 of them with a time-dependent effect.It is possible that subjects with a strong time-dependent effect may have both a factor VIII inhibitor and an LA (n ‫ס‬ 12) [4].LAs were diagnosed based mainly on diluted Russell viper venom time (dRVVT).The activated partial thromboplastin time (APTT) is affected by factor VIII inhibitors; however, the platelet neutralization procedure of the APTT showed similar results to those obtained for dRVVT, except in three patients with positive dRVVT, for whom the shortening of the PNP was not sufficient to be considered positive.In our study, the StaclotLA results agreed with those from dRVVT; 8/8 were positive on LAs and 3/3 were negative on factor VIII inhibitors.We believe that factor VIII inhibitors could be masked by LA and the misdiagnosis could delay the prescription of the appropriate therapy [5].The above evidence stresses the need to develop a specific test to identify factor VIII inhibitors without interference of LA, and vice versa.
Cancer risk and survival in <i>path_MMR</i> carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database
Authors: Pål Møller, Toni T Seppälä, Inge Bernstein, Elke Holinski-Feder, Paulo Sala, D Gareth Evans, Annika Lindblom, Finlay Macrae, Ignacio Blanco, Rolf H Sijmons, Jacqueline Jeffries, Hans F A Vasen, John Burn, Sigve Nakken, Eivind Hovig, Einar Andreas Rødland, Kukatharmini Tharmaratnam, Wouter H de Vos tot Nederveen Cappel, James Hill, Juul T Wijnen, Mark A Jenkins, Kate Green, Fiona Lalloo, Lone Sunde, Miriam Mints, Lucio Bertario, Marta Pineda, Matilde Navarro, Monika Morak, Laura Renkonen-Sinisalo, Mev Dominguez Valentin, Ian M Frayling, John-Paul Plazzer, Kirsi Pylvanainen, Maurizio Genuardi, Jukka-Pekka Mecklin, Gabriela Moeslein, Julian R Sampson, Gabriel Capella
Journal: Gut (2017)

Background Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. Objective and design This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. Results 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_ MLH1 , path_ MSH2 and path_ MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer. Conclusion Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.
Lung function parameters in omalizumab responder patients: An interesting tool?
Authors: F. Paganin, G. Mangiapan, A. Proust, A. Prudhomme, J. Attia, S. Marchand‐Adam, F. Pellet, F. Milhe, B. Melloni, A. Bernady, C. Raspaud, C. Nocent, P. Berger, L. Guilleminault
Journal: Allergy (2017)

Abstract Background Omalizumab, an anti‐IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real‐life study was to compare the changes in forced expiratory volume in 1 second ( FEV 1) of omalizumab responders and nonresponders at 6 months. Methods A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity ( FVC ), pre‐ and postbronchodilator FEV 1, residual volume ( RV ), and total lung capacity ( TLC ) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6‐month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. Results Mean prebronchodilator FEV 1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and −0.1±0.4 L, respectively, P &lt;.01). After an improvement at 6 months, pre‐ and postbronchodilator FEV 1 remained stable at 12, 18, and 24 months. The FEV 1/ FVC remained unchanged over time, but the proportion of patients with an FEV 1/ FVC ratio &lt;0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P &lt;.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months ( P &lt;.05). Residual volume/total lung capacity ( RV / TLC ) ratio decreased at 6 months and remained unchanged at 24 months. Conclusion After omalizumab initiation, FEV 1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV / TLC improved at 6 months.
The Impact of Social Contagion on Physician Adoption of Advanced Imaging Tests in Breast Cancer
Authors: Craig E. Pollack, Pamela R. Soulos, Jeph Herrin, Xiao Xu, Nicholas A. Christakis, Howard P. Forman, James B. Yu, Brigid K. Killelea, Shi-Yi Wang, Cary P. Gross
Journal: JNCI Journal of the National Cancer Institute (2017)

Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans are widely used in breast cancer practice despite unproven benefits. We examined the extent to which social contagion is associated with adoption of these imaging modalities.We used Surveillance, Epidemiology, and End Results-Medicare to construct peer groups of physicians who shared patients during a baseline period when these imaging modalities were starting to disseminate into practice (2004-2006) and determined the potential impact of these peer groups during a follow-up period (2007-2009). For non-early-adopting surgeons (whose patients did not receive MRI/PET during baseline), we used hierarchical logistic regression models to examine the effect of their peer group's baseline use on their use of MRI/PET during the follow-up period, adjusting for patient characteristics and hospital MRI/PET use.For MRI, there were 6424 women diagnosed in the follow-up period assigned to 986 non-early-adopting surgeons. During baseline, 9.3% of women received an MRI, varying across peer groups from 0% to 81%. Women assigned to surgeons whose peers had the highest rate of baseline MRI use were more likely to receive MRI compared with women whose surgeons' peers did not use MRI (24.9% vs 10.1%, adjusted odds ratio [OR] = 2.47, 95% confidence interval [CI] = 1.39 to 4.39). Physician peers were associated with uptake of PET imaging (OR for highest vs lowest baseline peer group PET use = 2.04, 95% CI = 1.24 to 3.36).The phenomenon of social contagion may offer opportunities to better understand how new approaches to cancer care disseminate into clinical practice.
Online abortion service is safe and effective way to end pregnancy, finds study
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Online telemedicine provides a safe and effective method to end pregnancy, a study published in The BMJ has found.1

Rates of adverse events among 1000 women in Ireland who used such a service were low, and women were able to identify potentially serious complications and seek medical attention when advised.

The results provide the best safety evidence to date for self sourced medical abortion through telemedicine and have important implications for millions of women worldwide, said the researchers.

About a quarter …
David Oliver: The NHS’s understaffing is its Achilles’ heel
Authors: David Oliver
Journal: BMJ (2017)

I’ve long stopped believing any soundbites about NHS staffing or funding if they come from the Department of Health or Number 10. I’d like to see a truly independent body for all NHS statistics.

The House of Lords’ April report on the NHS’s future1 criticised serial government claims that “4000 new doctors and 9000 new nurses” have been recruited, without these mantras being grounded in coherent planning about how many are needed or acknowledging those who leave or go part time.23 The Lords’ report was also highly critical of the UK’s track record in …
Coexistent Superscan and Lincoln Sign on Bone Scintigraphy
Authors: Mukta Kulkarni, Atul Soni, Shubhangi Shetkar, Momin Amer, Amruta Mulavekar, Prathamesh Joshi
Journal: Clinical Nuclear Medicine (2017)

A 70-year-old man underwent 99mTc–methylene diphosphonate scintigraphy for staging of adenocarcinoma prostate. Scintigraphy revealed diffuse increased tracer uptake in skeletal system along with faint renal visualization, a pattern compatible with metastatic superscan. The scintigraphy also revealed increased radiotracer uptake in the body of the mandible—Lincoln sign or black beard sign. Radiological imaging revealed sclerotic lesions throughout the skeleton including the mandible, confirming widespread skeletal metastases. Lincoln sign is previously described in monostotic Paget disease of the mandible and in contiguous spread of oral malignancy. We describe this pattern in distant metastatic involvement from carcinoma prostate with coexistent superscan pattern.
Effect of early supplemental parenteral nutrition in the paediatric ICU: a preplanned observational study of post-randomisation treatments in the PEPaNIC trial
Authors: Ilse Vanhorebeek, Sascha Verbruggen, Michaël P Casaer, Jan Gunst, Pieter J Wouters, Jan Hanot, Gonzalo Garcia Guerra, Dirk Vlasselaers, Koen Joosten, Greet Van den Berghe
Journal: The Lancet Respiratory Medicine (2017)
Increased T-cell Infiltration Elicited by <i>Erk5</i> Deletion in a <i>Pten</i>-Deficient Mouse Model of Prostate Carcinogenesis
Authors: Carolyn J. Loveridge, Ernest J. Mui, Rachana Patel, Ee Hong Tan, Imran Ahmad, Michelle Welsh, Julie Galbraith, Ann Hedley, Colin Nixon, Karen Blyth, Owen Sansom, Hing Y. Leung
Journal: Cancer Research (2017)

Abstract Prostate cancer does not appear to respond to immune checkpoint therapies where T-cell infiltration may be a key limiting factor. Here, we report evidence that ablating the growth regulatory kinase Erk5 can increase T-cell infiltration in an established Pten-deficient mouse model of human prostate cancer. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared with control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression. A comparative transcriptomic analysis revealed upregulation in prostate DKO mice of the chemokines Ccl5 and Cxcl10, two potent chemoattractants for T lymphocytes. Consistent with this effect, we observed a relative increase in a predominantly CD4+ T-cell infiltrate in the prostate epithelial and stroma of tumors from DKO mice. Collectively, our results offer a preclinical proof of concept for ERK5 as a target to enhance T-cell infiltrates in prostate cancer, with possible implications for leveraging immune therapy in this disease. Cancer Res; 77(12); 3158–68. ©2017 AACR.
Prognostic potential of midregional pro‐adrenomedullin following decompensation for systolic heart failure: comparison with cardiac natriuretic peptides
Authors: Caroline Morbach, Almuth Marx, Mathias Kaspar, Gülmisal Güder, Susanne Brenner, Carolin Feldmann, Stefan Störk, Jörn O. Vollert, Georg Ertl, Christiane E. Angermann
Journal: European Journal of Heart Failure (2017)