tbuckley/cabot-search huggingface dataset:
Opposing Actions of Fibroblast and Cardiomyocyte Smad3 Signaling in the Infarcted Myocardium
Authors: Ping Kong, Arti V. Shinde, Ya Su, Ilaria Russo, Bijun Chen, Amit Saxena, Simon J. Conway, Jonathan M. Graff, Nikolaos G. Frangogiannis
Journal: Circulation (2017)

Transforming growth factor-βs regulate a wide range of cellular responses by activating Smad-dependent and Smad-independent cascades. In the infarcted heart, Smad3 signaling is activated in both cardiomyocytes and interstitial cells. We hypothesized that cell-specific actions of Smad3 regulate repair and remodeling in the infarcted myocardium.To dissect cell-specific Smad3 actions in myocardial infarction, we generated mice with Smad3 loss in activated fibroblasts or cardiomyocytes. Cardiac function was assessed after reperfused or nonreperfused infarction using echocardiography. The effects of cell-specific Smad3 loss on the infarcted heart were studied using histological studies, assessment of protein, and gene expression levels. In vitro, we studied Smad-dependent and Smad-independent actions in isolated cardiac fibroblasts.Mice with fibroblast-specific Smad3 loss had accentuated adverse remodeling after reperfused infarction and exhibited an increased incidence of late rupture after nonreperfused infarction. The consequences of fibroblast-specific Smad3 loss were not a result of effects on acute infarct size but were associated with unrestrained fibroblast proliferation, impaired scar remodeling, reduced fibroblast-derived collagen synthesis, and perturbed alignment of myofibroblast arrays in the infarct. Polarized light microscopy in Sirius red-stained sections demonstrated that the changes in fibroblast morphology were associated with perturbed organization of the collagenous matrix in the infarcted area. In contrast, α-smooth muscle actin expression by infarct myofibroblasts was not affected by Smad3 loss. Smad3 critically regulated fibroblast function, activating integrin-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2) expression. Smad3 loss in cardiomyocytes attenuated remodeling and dysfunction after infarction. Cardiomyocyte-specific Smad3 loss did not affect acute infarct size but was associated with attenuated cardiomyocyte apoptosis in the remodeling myocardium, accompanied by decreased myocardial NOX-2 levels, reduced nitrosative stress, and lower matrix metalloproteinase-2 expression.In healing myocardial infarction, myofibroblast- and cardiomyocyte-specific activation of Smad3 has contrasting functional outcomes that may involve activation of an integrin/reactive oxygen axis.
Lumen-apposing metal stent for pediatric use: report of a challenging case
Authors: Massimiliano Mutignani, Edoardo Forti, Alberto Tringali, Marcello Cintolo, Diego Falchetti, Vincenzo Argento, Lorenzo Dioscoridi
Journal: Endoscopy (2017)

Endoscopic ultrasound (EUS)-guided interventions are as feasible in pediatric populations as they are in adult patients [1]. However, some special features must be considered: the ducts are smaller and thinner, and require special care by the endoscopists [1] [2] [3]. Adult endoscopes and devices can be used safely in children > 3 years of age or > 15 kg in weight, according to the literature [1] [4]. However, lumen-apposing metal stents (LAMS) have rarely been used in pediatric patients without adverse events [5].
Resveratrol mediates cell fate in human uterine cancer cells through prostaglandin inhibition
Authors: Émilie Sexton, Kim Leblanc, Pascal Lemoine, Eric Asselin
Journal: Cancer Research (2005)

751  In the Western world, endometrial cancer is the most common gynecologic cancer and is the fourth importance among all feminine cancers. Cyclooxygenase-1 and -2 (COX-1 and -2) are the limiting enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. The PGs have been shown to be implicated in evolution and tumor transformation, particularly, PGE2. Four prostaglandin E2 receptors have been found: EP1, EP2, EP3 and EP4. The aim of this study was to determine if resveratrol, a natural anti-oxidant found in red wine, could influence the production of PGs and apoptotic cell death or cellular proliferation. Six different human uterine cancer cell lines were used for this study. Real-time RT-PCR and Western analyses were carried out to measure COX-1, COX-2, EP1, EP2, EP3 and EP4 expression. The results indicated that all cell lines expressed both COX isoforms and the four EP receptors at different levels. In experiment two, cells were treated with various concentrations of resveratrol for different length of time. MTT proliferation assay revealed that resveratrol induced maximal cell proliferation of RL-95-2 cells in a dose dependent manner after 24 hours, which was reduced after 48 and 72 hours. Resveratrol had no effect on KLE cells in term of proliferation but inhibited cell proliferation in HeLa and HEC-1-A in a dose and time dependant manner. In Ishikawa and TOV-1078D cells, a novel human endometrial cancer cell line, the effect of resveratrol was biphasic: cell proliferation was increased at low concentration whereas higher concentrations resulted in a decreased of cell proliferation in a time dependent manner. Hoechst nuclear staining indicated that resveratrol induced apoptosis in HeLa, HEC-1-A, Ishikawa and TOV-1078D but not in KLE and RL-95-2 cells. Since we have showed that Akt activity can directly up-regulate COX-2 gene expression and PGE2 secretion, in experiment two Western blot analyses were carried out to determine the possible involvement of the PI3-K/PTEN/Akt pathway in this process. Results indicate that, depending on the cell line, resveratrol can act positively and negatively on Akt phosphorylation in those wild types (HeLa, HEC-1-A and KLE) and mutated PTEN (RL-95-2, Ishikawa and TOV-1078D) human uterine cancer cells and that COX-1 and COX-2 expressions are influenced by resveratrol. In response to resveratrol PGE2 secretion was decreased in HeLa, HEC-1-A and Ishikawa cells. The results suggest that resveratrol, through its action on prostaglandin biosynthesis, could be an important regulator of cell survival in uterine cancer. Supported by CIHR (MOP-66987).
NEUROGENIC DIFFERENTIATION 1 (NEUROD1) IS REQUIRED FOR THE DE NOVO EXPRESSION OF SECRETIN AND THE NEUROENDOCRINE DIFFERENTIATION OF SMALL CHOLANGIOCYTES DURING THE DAMAGE OF LARGE CHOLANGIOCYTES
Authors: Romina Mancinelli, Paolo Onori, Eugenio Gaudio, Antonio Franchitto, S Kopriva, G Alpini, M White, Y Ueno, FY Meng, SS Glaser, J Venter, S DeMorrow
Journal: Hepatology (2010)
Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial
Authors: Philip McGuire, Philip Robson, Wieslaw Jerzy Cubala, Daniel Vasile, Paul Dugald Morrison, Rachel Barron, Adam Taylor, Stephen Wright
Journal: American Journal of Psychiatry (2017)

Objective: Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia. Method: In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S). Results: After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=−1.4, 95% CI=−2.5, −0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=−0.5, 95% CI=−0.8, −0.1) and as not severely unwell (CGI-S: treatment difference=−0.3, 95% CI=−0.5, 0.0) by the treating clinician. Patients who received CBD also showed greater improvements that fell short of statistical significance in cognitive performance (BACS: treatment difference=1.31, 95% CI=−0.10, 2.72) and in overall functioning (GAF: treatment difference=3.0, 95% CI=−0.4, 6.4). CBD was well tolerated, and rates of adverse events were similar between the CBD and placebo groups. Conclusions: These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.
OA 02.01 Randomized Phase II Study of Anetumab Ravtansine or Vinorelbine in Patients with Metastatic Pleural Mesothelioma
Authors: H.L. Kindler, S. Novello, D. Fennell, G. Blumenschein, A. Bearz, G. Ceresoli, J. Aerts, J. Spicer, P. Taylor, A. Greystoke, K. Nackaerts, L. Calabro, S. Burgers, R. Jennens, A. Sporchia, A. Walter, J. Siegel, B. Childs, C. Elbi, R. Hassan
Journal: Journal of Thoracic Oncology (2017)
GP based weight loss programme can reverse type 2 diabetes
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Nearly half the people with type 2 diabetes who lost weight as part of a trial in primary care did not have the disease a year later, prompting calls for widespread use of weight management programmes as a routine part of care.

Previous research by the current study team from Glasgow and Newcastle confirmed the “twin cycle hypothesis”—that type 2 diabetes is caused by excess fat within the liver and pancreas—and established that the disease can go into remission by consuming a very low calorie diet. But it has not been known whether this type of intensive weight management works in routine primary care.

The Diabetes Remission Clinical Trial (DiRECT), …
Abstract A01: Mechanisms of breast cancer risk in shift workers: Epigenetic changes in the circadian pathway
Authors: Shan Zienolddiny
Journal: Cancer Research (2017)

Abstract Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm can increase breast cancer risk. Circadian disruption may also affect epigenetic factors such as 5-methyl cytosine methylation in DNA. DNA hypermethylation generally is associated with increased cancer risk, if it occurs in tumor suppressor genes. Some of the circadian genes are known to function as tumor suppressor genes. DNA methylation in cirdavdian genes and its association with breast cancer risk in shiftworkers is little investigated and the limited available data are inconclusive. We here investigated DNA methyalation at 5-meC sites in the promoter regions of core circadian and melatonin receptor genes as a potential mechanism for night work-related breast cancer risk. A nested breast cancer case-control study of nurses working night shifts comprising of seven-hundred breast cancer cases and matched controls was conducted. Methylation at 5-meC sites in a number of core circadian and melatonin receptor genes was in DNA from sputum samples obtained from cases and controls. Changes in methylation status of the 5-meC in DNA (methylation index) and the odds of breast cancer associated with DNA methylation was calculated in relation to the duration and intensity of night shiftwork. We demonstrate that generally the methylation of 5-meC is low for all the genes that were analyzed. However, we will present analyses of the effects of work schedules and duration, as number of consecutive night shifts, on epigenetic changes. The hypothesis is that increased breast cancer risk in workers with long periods of consecutive night shifts may be associated with changes in methylation status of the genes regulation the circadian rhythm. Citation Format: Shan Zienolddiny. Mechanisms of breast cancer risk in shift workers: Epigenetic changes in the circadian pathway [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A01.
Laurence Gregory Wells
Authors: Catherine Lake, Jonathan Lake
Journal: BMJ (2017)

After qualifying Laurence Gregory Wells (“Greg”) took a characteristically principled stance. With his wife, Mary, he moved from Cape Town to rural Zululand to work at the Charles Johnson Memorial Hospital in Nqutu, inspired by the work of Anthony and Maggie Barker. Working with the Zulu community was highly unusual for South Africans, and not without significant personal and professional risk …
Sustained T follicular helper cell response is essential for control of chronic viral infection
Authors: Ute Greczmiel, Nike Julia Kräutler, Alessandro Pedrioli, Ilka Bartsch, Paola Agnellini, Gregor Bedenikovic, James Harker, Kirsten Richter, Annette Oxenius
Journal: Science Immunology (2017)

During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5+ T follicular helper cell (TFH) lineage. Whether these TFH cells contribute to the immune response to chronic viral infection has remained unclear. Using chronic lymphocytic choriomeningitis virus (LCMV) infection in conjunction with an in vivo system where TFH cells can be conditionally ablated, we have established that these TFH cells do in fact play an important protective function. Specifically, we demonstrate that these TFH cells are essential for the late emergence of neutralizing LCMV-specific antibodies that keep viral titers in check and ultimately allow mice to clear the virus. By supporting the generation of neutralizing antibodies, we show that sustained activity of TFH cells promotes control of the chronic infection in face of exhausted CD8 T cell responses.
Madeiran Arabidopsis thaliana Reveals Ancient Long-Range Colonization and Clarifies Demography in Eurasia
Authors: Andrea Fulgione, Maarten Koornneef, Fabrice Roux, Joachim Hermisson, Angela M Hancock
Journal: Molecular Biology and Evolution (2017)

The study of model organisms on islands may shed light on rare long-range dispersal events, uncover signatures of local evolutionary processes, and inform demographic inference on the mainland. Here, we sequenced the genomes of Arabidopsis thaliana samples from the oceanic island of Madeira. These samples include the most diverged worldwide, likely a result of long isolation on the island. We infer that colonization of Madeira happened between 70 and 85 ka, consistent with a propagule dispersal model (of size ≥10), or with an ecological window of opportunity. This represents a clear example of a natural long-range dispersal event in A. thaliana. Long-term effective population size on the island, rather than the founder effect, had the greatest impact on levels of diversity, and rates of coalescence. Our results uncover a selective sweep signature on the ancestral haplotype of a known translocation in Eurasia, as well as the possible importance of the low phosphorous availability in volcanic soils, and altitude, in shaping early adaptations to the island conditions. Madeiran genomes, sheltered from the complexities of continental demography, help illuminate ancient demographic events in Eurasia. Our data support a model in which two separate lineages of A. thaliana, one originating in Africa and the other from the Caucasus expanded and met in Iberia, resulting in a secondary contact zone there. Although previous studies inferred that the westward expansion of A. thaliana coincided with the spread of human agriculture, our results suggest that it happened much earlier (20-40 ka).
Living near physical activity facilities is associated with lower BMI, UK study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Living near facilities for physical activity, such as gyms or swimming pools, is strongly associated with having a lower body mass index (BMI), a lower percentage of body fat, and a smaller waist circumference in middle age, a UK study has shown.1

The analysis of observational data from UK Biobank also showed adiposity was associated, although less strongly, with living near fast food outlets.

“The results of our study suggest that increasing access to local physical activity facilities and, possibly, reducing access to fast food …
State of Victoria will allow voluntary euthanasia from mid 2019
Authors: Paul Smith
Journal: BMJ (2017)

Victoria has become the first state in Australia to legalise voluntary euthanasia. After a marathon debate the state parliament passed the legislation on 29 November.

The landmark legal change, to take effect in mid 2019, will allow terminally ill adult patients who face intolerable suffering to apply for an assisted death.

The news has divided doctors across Australia. Australian Medical Association Victoria said that it would “cause anguish for some members of our profession, as well as the public.” Lorraine Baker, the group’s president, said, “This is a significant change in medical practice and patient care and requires the strongest safeguards and protections.”

The legislative model was based on recommendations made by an expert advisory group led by Brian …
PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non–Small Cell Lung Cancer Patients with Malignant Pleural Effusion
Authors: Yen-Han Tseng, Hsiang-Ling Ho, Chiung-Ru Lai, Yung-Hung Luo, Yen-Chiang Tseng, Jacqueline Whang-Peng, Yi-hsuan Lin, Teh-Ying Chou, Yuh-Min Chen
Journal: Journal of Thoracic Oncology (2017)
Pure erythroid leukemia
Authors: Barbara J. Bain
Journal: American Journal of Hematology (2017)

Mea culpa. Wang et al.1 are quite right to point out that in the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues pure erythroid leukemia that evolves from a myelodysplastic syndrome (MDS) is not recognized as acute myeloid leukemia (AML) with myelodysplasia-related changes, because it does not meet the criterion of having at least 20% peripheral blood or bone marrow blasts. Since this condition is recognized as AML and evolves from MDS, this is somewhat puzzling. Perhaps how it is best categorized should be reconsidered in the next revision of the WHO classification. The valuable data of Wang et al.1, 2 will help to better define the nature of this rare condition. Meanwhile, it does seem that cases that are therapy related are indeed classified as therapy-related myeloid neoplasm rather than as pure erythroid leukemia.
Progress on catastrophic health spending in 133 countries: a retrospective observational study
Authors: Adam Wagstaff, Gabriela Flores, Justine Hsu, Marc-François Smitz, Kateryna Chepynoga, Leander R Buisman, Kim van Wilgenburg, Patrick Eozenou
Journal: The Lancet Global Health (2017)

The goal of universal health coverage (UHC) requires inter alia that families who get needed health care do not suffer undue financial hardship as a result. This can be measured by the percentage of people in households whose out-of-pocket health expenditures are large relative to their income or consumption. We aimed to estimate the global incidence of catastrophic health spending, trends between 2000 and 2010, and associations between catastrophic health spending and macroeconomic and health system variables at the country level.We did a retrospective observational study of health spending using data obtained from household surveys. Of 1566 potentially suitable household surveys, 553 passed quality checks, covering 133 countries between 1984 and 2015. We defined health spending as catastrophic when it exceeded 10% or 25% of household consumption. We estimated global incidence by aggregating up from every country, using a survey for the year in question when available, and interpolation and model-based estimates otherwise. We used multiple regression to explore the relation between a country's incidence of catastrophic spending and gross domestic product (GDP) per person, the Gini coefficient for income inequality, and the share of total health expenditure spent by social security funds, other government agencies, private insurance schemes, and non-profit institutions.The global incidence of catastrophic spending at the 10% threshold was estimated as 9·7% in 2000, 11·4% in 2005, and 11·7% in 2010. Globally, 808 million people in 2010 incurred catastrophic health spending. Across 94 countries with two or more survey datapoints, the population-weighted median annual rate of change of catastrophic payment incidence was positive whatever catastrophic payment incidence measure was used. Incidence of catastrophic payments was correlated positively with GDP per person and the share of GDP spent on health, and incidence correlated negatively with the share of total health spending channelled through social security funds and other government agencies.The proportion of the population that is supposed to be covered by health insurance schemes or by national or subnational health services is a poor indicator of financial protection. Increasing the share of GDP spent on health is not sufficient to reduce catastrophic payment incidence; rather, what is required is increasing the share of total health expenditure that is prepaid, particularly through taxes and mandatory contributions.Rockefeller Foundation, Ministry of Health of Japan, UK Department for International Development (DFID).
A Policy That Encourages Wastage of Expensive Medications—The JW Modifier
Authors: Daniel A. Goldstein, Abigail Hirsch
Journal: JAMA Oncology (2017)

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