tbuckley/cabot-search huggingface dataset:
Prostaglandins—tour d'horizon
Authors: Samuel Vaisrub
Journal: JAMA (1974)

More than two centuries ago, Theophile de Bordeau (1722-1766) expressed the belief that every organ and tissue produces substances that are discharged into the blood to affect other parts of the body. This notion, which must have seemed far-fetched to his contemporaries, appears to us now as an intuitive perception. Apart from hormones secreted by well-demarcated, specialized organs, we recognize that substances with more diffuse sources in numerous tissues and organs affect many parts. One such group of substances are the<i>prostaglandins</i>. Slow to get started—their name dates back to 1935—the prostaglandins are now in the foreground of medical research. Though in many areas our understanding of these biologically active cyclic fatty acids still hovers between hypothesis and confirmed theory, prostaglandins have already found a place in certain clinical situations. The known stimulating action of prostaglandins on the uterus permits their intra-amniotic instillation for terminating pregnancy in midterm. They can
Resource requirements for essential universal health coverage: a modelling study based on findings from Disease Control Priorities, 3rd edition
Authors: David A Watkins, Jinyuan Qi, Yoshito Kawakatsu, Sarah J Pickersgill, Susan E Horton, Dean T Jamison
Journal: The Lancet Global Health (2020)

BackgroundDisease Control Priorities, 3rd edition (DCP3), published two model health benefits packages (HBPs). This study estimates the overall costs and individual component costs of these packages in low-income countries (LICs) and lower-middle-income countries (lower-MICs).MethodsThis study reports on our Disease Control Priorities Cost Model (DCP-CM), developed as part of the DCP3 project to determine the overall costs of the 218 health sector interventions recommended in the model HBP termed essential universal health coverage (EUHC). Model inputs included data on intervention unit costs, demographic and epidemiological data to quantify the populations in need of specific interventions, baseline coverage indicators, and estimates of required health system costs to support direct service delivery. The DCP-CM was informed primarily by published estimates of economic costs of interventions measured from the health system perspective. We estimated counterfactual annual costs for the year 2015. We disaggregated costs according to intervention characteristics (delivery platform, delivery timing, and health system objective) and did one-way and probabilistic sensitivity analyses with determination of 95% credible intervals (Crls).FindingsAt 80% population coverage, the annual cost of EUHC would be US$79 (95% Crl 60–110) per capita (in 2016 US dollars) in LICs and US$130 (100–180) per capita in lower-MICs. As a share of 2015 gross national income (GNI), additional investments would require 8·0% (95% Crl 5·7–11·3) in LICs and 4·2% (2·9–5·9) in lower-MICs. A highest priority subpackage comprising 115 of the EUHC interventions would cost approximately half of these amounts (3·7% [2·6–5·3] of 2015 GNI in LICs and 2·0% [1·4–2·8] in lower-MICs). Mortality-reducing interventions would require around two-thirds of the overall package costs, with interventions to reduce mortality at age 5–69 years from non-communicable disease and injury comprising the highest share of total EUHC costs in both income groups (37·6% [37·2–37·9] in LICs and 43·0% [42·6–43·4] in lower-MICs). Interventions addressing chronic health conditions (requiring 45·5% [44·8–46·4] 2015 GNI for LICs and lower-MICs combined) and interventions delivered in health centres (requiring 49·8% [49·5–50·2] 2015 GNI for LICs and lower-MICs combined) would each comprise the plurality of costs.InterpretationImplementation of EUHC would require costly investment, especially in LICs. DCP-CM is available as an online tool that can inform local HBP deliberation and support efficient investment in UHC, especially as countries pivot towards non-communicable disease and injury care.FundingBill & Melinda Gates Foundation, Trond Mohn Foundation, and Norwegian Agency for Development Cooperation.
Abstract 17373: Prevalence and Predictors of Atrial Fibrillation Type Among Individuals With Recent Onset of Atrial Fibrillation
Authors: Francisco Javier Ruperti-Repilado, Laura Doerig, Steffen Blum, Stefanie Aeschbacher, Philipp Krisai, Peter Ammann, Paul Erne, Giorgio Moschovitis, Marcello di Valentino, Dipen Shah, Jürg Schläpfer, Samuel Stempfel, Michael Kühne, Christian Sticherling, Stefan Osswald, David Conen
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) is considered to be a progressive disease starting with short intermittent episodes, which over time progress to more sustained arrhythmia events. However, li...
Full-field optical coherence tomography: novel imaging technique for extemporaneous high-resolution analysis of mucosal architecture in human gut biopsies
Authors: Lucille Quénéhervé, Raphael Olivier, Michalina J Gora, Céline Bossard, Jean-François Mosnier, Emilie Benoit a la Guillaume, Claude Boccara, Charlène Brochard, Michel Neunlist, Emmanuel Coron
Journal: Gut (2020)

Full-field optical coherence tomography (FFOCT) is an imaging technique of biological tissue based on tissue light reflectance analysis. We evaluated the feasibility of imaging fresh digestive mucosal biopsies after a quick mounting procedure (5 min) using two distinct modalities of FFOCT. In static FFOCT mode, we gained high-resolution images of general gut tissue-specific architecture, such as oesophageal papillae, gastric pits, duodenal villi and colonic crypts. In dynamic FFOCT mode, we imaged individual epithelial cells of the mucosal lining with a cellular or subcellular resolution and identified cellular components of the lamina propria. FFOCT represents a promising dye-free imaging tool for on-site analysis of gut tissue remodelling.
Abstract 14143: Steady State Exercise at Ventilatory Anaerobic Threshold in Elderly Subjects; The Pattern of Blood Lactate Change
Authors: Kazuyuki Kominami, Toko Katsuragawa, Keiko Imahashi, Mitsuyo Murakami, Masatoshi Akino, Hirotaka Nishijima
Journal: Circulation (2017)

Incremental exercise testing (IncEx) is commonly employed to determine the optimal training work rate. VAT is often suggested as a good indicator; however, how it actually manifests during steady s...
IMPACT OF THE CLINICAL SYNTAX SCORE ON 5-YEAR CLINICAL OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION FROM SHINANO REGISTRY
Authors: Daisuke Kashiwagi, Takashi Miura, Hisanori Yui, Shusaku Mruyama, Chie Nakamura, Ayumu Nagae, Takahiro Sakai, Keisuke Senda, Tamon Kato, Tatsuya Saigusa, Soichiro Ebisawa, Ayako Okada, Hirohiko Motoki, Koichiro Kuwahara
Journal: Journal of the American College of Cardiology (2019)
Harnessing stemness and PD-L1 expression by AT-rich interaction domain-containing protein 3B in colorectal cancer
Authors: Tsai-Tsen Liao, Chun-Chi Lin, Jeng-Kae Jiang, Shung-Haur Yang, Hao-Wei Teng, Muh-Hwa Yang
Journal: Theranostics (2020)

Background and Aims: Cancer stem cells (CSCs) have been shown to be responsible for the tumor initiation, metastasis, and therapeutic resistance of colorectal cancer (CRC). Recent studies have also indicated the importance of CSCs in escaping immune surveillance. However, the coordinated epigenetic control of the stem cell signature and the key molecule(s) involved in immunosurveillance of colorectal CSCs (CRCSCs) are unclear. Here, we investigated the role of a histone modifier, AT-rich interaction domain-containing protein 3B (ARID3B), in CRC. Methods: CRC patient-derived xenografts (PDXs) with knockout of ARID3B induced by CRISPR/Cas9 in vivo were used. Molecular/cellular biology assays were performed. Clinical data obtained from The Cancer Genome Atlas, as well as from our cohort (Taipei Veterans General Hospital), were analyzed. Results: ARID3B was crucial for the growth of CRC, and ARID3B promoted the stem-like features of CRC. Mechanistically, ARID3B activated Notch target genes, intestinal stem cell (ISC) genes, and programmed death-ligand 1 (PD-L1) through the recruitment of lysine-specific demethylase 4C (KDM4C) to modulate the chromatin configuration for transcriptional activation. Clinical sample analyses showed that the coexpression of ARID3B and the Notch target HES1 correlated with a worse outcome and that ARID3B and PD-L1 were highly expressed in the consensus molecular subtype 4 of CRC. Pharmacological inhibition of KDM4 activity reversed the ARID3B-induced signature. Conclusion: We reveal a noncanonical Notch pathway for activating Notch target genes, ISC genes, and PD-L1 in CRC. This finding explains the immune escape of CRCSCs and indicates a potential group that may benefit from immune checkpoint inhibitors. Epigenetic drugs for reversing stem-like features of CRC should also be investigated.
Risk factors for tuberculosis in HIV-infected persons. A prospective cohort study. The Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA)
Authors: G Antonucci, E Girardi, M C Raviglione, G Ippolito
Journal: JAMA (1995)

<h3>Objective.</h3> —To analyze how demographic, clinical, and laboratory characteristics influence the risk of tuberculosis in human immunodeficiency virus (HIV)— infected individuals; to examine the incidence of tuberculosis associated with change in skin test responsiveness in HIV-infected, tuberculin-negative, nonanergic individuals. <h3>Design.</h3> —Multicenter cohort study. <h3>Setting.</h3> —Twenty-three infectious disease units in public hospitals in Italy. <h3>Subjects.</h3> —A consecutive sample of 3397 HIV-infected subjects were considered for entry in the study. Of these, 2695 who were followed up for at least 4 weeks were enrolled in the study; 739 subjects (27.4%) were unavailable for follow-up. The median duration of follow-up was 91 weeks. <h3>Main Outcome Measure.</h3> —Culture-proven tuberculosis. <h3>Results.</h3> —Eighty-three episodes of tuberculosis were observed. Incidence rates of tuberculosis were 5.42 per 100 person-years among tuberculin-positive subjects, 3.00 per 100 person-years among anergic subjects, and 0.45 per 100 person-years among tuberculin-negative nonanergic subjects. In multivariate analysis, being tuberculin-positive (hazard ratio [HR], 9.94; 95% confidence interval [CI], 3.84 to 25.72) or anergic (HR, 3.35; 95% CI, 1.40 to 8.00), or having a CD4<sup>+</sup>lymphocyte count less than 0.20× 10<sup>9</sup>/L (HR, 4.87; 95% CI, 2.35 to 10.11) or between 0.20 and 0.35×10<sup>9</sup>/L (HR, 2.35; 95% CI, 1.09 to 5.05) were statistically significantly associated with the risk of tuberculosis. Incidence of tuberculosis increased with decreasing levels of CD4<sup>+</sup>lymphocytes in the three groups of subjects with different skin test responsiveness. Skin tests were repeated 1 year after enrollment in 604 tuberculin-negative nonanergic subjects; three cases of tuberculosis were observed among the 13 subjects who converted to tuberculin reactivity. <h3>Conclusions.</h3> —Risk of tuberculosis in HIV-infected persons can be more precisely quantified by jointly considering skin test reactivity and CD4<sup>+</sup>lymphocyte count. Periodic skin tests in tuberculin-negative nonanergic individuals can be useful in identifying individuals at high risk of active tuberculosis. (<i>JAMA</i>. 1995;274:143-148)
Covid-19: Important potential side effects of wearing face masks that we should bear in mind
Authors: Antonio Ivan Lazzarino, Andrew Steptoe, Mark Hamer, Susan Michie
Journal: BMJ (2020)

In their editorial Greenhalgh et al advise that surgical masks should be worn in public to prevent some transmission of covid-19,1 adding that we should sometimes act without definitive evidence, just in case. Two side effects of wearing face masks in public have already been highlighted:
50P Cardiosafe nano-formulation of doxorubicin allows coadministration with trastuzumab in neoadjuvant setting improving antitumor efficacy and preventing trastuzumab-mediated cardiotoxicity in HER2 + murine model of breast cancer
Authors: S. Mazzucchelli, F. Andreata, A. Bonizzi, M. Sevieri, M. Truffi, L. Sitia, R. Ottria, F. Silva, P.F. Zerbi, D. Prosperi, F. Corsi
Journal: Annals of Oncology (2020)
Editorial: Fulminant hepatic failure
Authors: H. H. Hussey
Journal: JAMA (1973)

Fulminant hepatic failure, especially when characterized by deep coma, forebodes severe morbidity and high mortality. The Fulminant Hepatic Failure Surveillance Study reports an overall mortality of 22% in 318 patients, and of those having deep coma only 17.6% survived.<sup>1</sup>Fulminant hepatitis following halothane anesthesia had the worst prognosis, only 4% of 53 patients surviving. Age above 45 years and the presence of complications also worsened the prognosis. Exchange transfusions offered the best hope for survival, 24% of 166 patients living compared to 10% of 101 patients who received no special treatment. Companion reports by Burnell and by Buckner and their colleagues<sup>2,3</sup>afford means for comparison of treatment of fulminant hepatic failure by cross circulation or by plasma exchange. Burnell et al applied cross circulation in three patients, one having acute hepatic necrosis of viral origin (presumably serum hepatitis), the second having hepatitis following a second use of halothane
成人急性骨髄性白血病(AML)における末梢血液のWTI遺伝子mRNA検出の予後影響
Authors: Miyawaki S, Hatsumi N, Tamaki T, Naoe T, Ozawa K, Kitamura K, Karasuno T, Mitani K, Kodera Y, Yamagami T, Koga D
Journal: Blood (2005)
Is CBT the dominant non-drug IBS treatment? The rise of dietary therapies
Authors: Anupam Rej, Rachel Louise Buckle, Christian Charles Shaw, Nick Trott, Imran Aziz, David S Sanders
Journal: Gut (2020)

We read with interest the editorial by Lackner and Jaccard, which discusses the largest cognitive–behavioural therapy (CBT) trial for irritable bowel syndrome (IBS) to date.1 2 The study by Everitt et al highlights the superiority of both web-based and telephone delivered CBT in comparison to usual treatment for individuals with IBS.2 In light of these results, Lackner nd Jaccard suggest that CBT is the dominant non-drug IBS treatment.1 We would disagree with this statement, and wish to highlight the benefit of dietary therapies to manage patients with IBS.

Traditional dietary advice is the first-line dietary intervention for individuals with IBS, as recommended by national guidelines, but is based …
Abstract 17944: DAPIT Knockdown Induces Dilated Cardiomyopathy Phenotypes in Zebrafish
Authors: Yoji Nagata, Tetsuo Konno, Yoshihiro Asano, Kenshi Hayashi, Masa-aki Kawashiri, Masakazu Yamagishi
Journal: Circulation (2017)

Background: The pathogenesis of dilated cardiomyopathy (DCM) could be partially a result of adenosine triphosphate (ATP) dysregulation in the myocardium. Diabetes-associated protein in insulin-sens...
The diagnostic value of prostate cancer between holmium laser enucleation of the prostate and transurethral resection of the prostate for benign prostatic hyperplasia: A retrospective comparative study
Authors: Gaofei He, Chengfang Sun, Yuanyuan Shu, Bohan Wang, Chuanjun Du, Jimin Chen, Jiaming Wen
Journal: International Journal of Surgery (2020)
Immunomodulatory effects of renin–angiotensin system inhibitors on T lymphocytes in mice with colorectal liver metastases
Authors: Dora Lucia Vallejo Ardila, Katrina A Walsh, Theodora Fifis, Rita Paolini, Georgios Kastrappis, Christopher Christophi, Marcos Vinicius Perini
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background It is now recognized that many anticancer treatments positively modulate the antitumor immune response. Clinical and experimental studies have shown that inhibitors of the classical renin–angiotensin system (RAS) reduce tumor progression and are associated with better outcomes in patients with colorectal cancer. RAS components are expressed by most immune cells and adult hematopoietic cells, thus are potential targets for modulating tumor-infiltrating immune cells and can provide a mechanism of tumor control by the renin–angiotensin system inhibitors (RASi). Aim To investigate the effects of the RASi captopril on tumor T lymphocyte distribution in a mouse model of colorectal liver metastases. Methods Liver metastases were established in a mouse model using an autologous colorectal cancer cell line. RASi (captopril 750 mg/kg) or carrier (saline) was administered to the mice daily via intraperitoneal injection, from day 1 post-tumor induction to endpoint (day 15 or 21 post-tumor induction). At the endpoint, tumor growth was determined, and lymphocyte infiltration and composition in the tumor and liver tissues were analyzed by flow cytometry and immunohistochemistry (IHC). Results Captopril significantly decreased tumor viability and impaired metastatic growth. Analysis of infiltrating T cells into liver parenchyma and tumor tissues by IHC and flow cytometry showed that captopril significantly increased the infiltration of CD3 + T cells into both tissues at day 15 following tumor induction. Phenotypical analysis of CD45 + CD3 + T cells indicated that the major contributing phenotype to this influx is a CD4 and CD8 double-negative T cell (DNT) subtype, while CD4 + T cells decreased and CD8 + T cells remained unchanged. Captopril treatment also increased the expression of checkpoint receptor PD-1 on CD8 + and DNT subsets . Conclusion Captopril treatment modulates the immune response by increasing the infiltration and altering the phenotypical composition of T lymphocytes and may be a contributing mechanism for tumor control.
Exposure to Drinking Water Chlorination by-Products and Fetal Growth and Prematurity: A Nationwide Register-Based Prospective Study
Authors: Melle Säve-Söderbergh, Jonas Toljander, Carolina Donat-Vargas, Marika Berglund, Agneta Åkesson
Journal: Environmental Health Perspectives (2020)

Background: Chlorination is globally used to produce of safe drinking water. Chlorination by-products are easily formed, and there are indications that these are associated with adverse reproductive outcomes. Objectives: We conducted a nationwide register-based prospective study to assess whether gestational exposure to the four most common chlorination by-products [total trihalomethanes (TTHMs)] via tap water was associated with risk of small for gestational age (SGA), preterm delivery, and very preterm delivery. To date, this is one of the largest studies assessing drinking water TTHM-associated adverse reproductive outcomes. Methods: We included all singleton births 2005–2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, ≤2 operating waterworks, adequate information on chlorination treatment, and a sufficient number of routine TTHM measurements in tap water. Individual maternal second and third trimester exposure was obtained by linking TTHM measurements to residential history, categorized into no chlorination, <5, 5–15, and >15μg TTHM/L. Outcomes and covariates were obtained via the linkage to Swedish health and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression using inverse probability weighting. We stratified the analyses by chlorination treatment (chloramine, hypochlorite). Results: Based on approximately 500,000 births, we observed a TTHM dose-dependent association with increased risk of SGA, confined to treatment with hypochlorite, corresponding to a multivariable-adjusted OR=1.20 (95% CI: 1.08, 1.33) comparing drinking water TTHM >15μg to the unexposed. Similar results were obtained when, instead of unexposed, the lowest exposure category (<5μg/L TTHM) was used as reference. No clear associations were observed for preterm delivery and very preterm delivery. Discussion: Chlorination by-products exposure via drinking water was associated with increased risk of SGA in areas with hypochlorite treatment. https://doi.org/10.1289/EHP6012
Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression
Authors: Juan Liu, Cen Zhang, Hao Wu, Xiao-Xin Sun, Yanchen Li, Shan Huang, Xuetian Yue, Shou-En Lu, Zhiyuan Shen, Xiaoyang Su, Eileen White, Bruce G. Haffty, Wenwei Hu, Zhaohui Feng
Journal: Journal of Clinical Investigation (2020)

Phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme of serine synthesis, is frequently overexpressed in human cancer. PHGDH overexpression activates serine synthesis to promote cancer progression. Currently, PHGDH regulation in normal cells and cancer is not well understood. Parkin, an E3 ubiquitin ligase involved in Parkinson's disease, is a tumor suppressor. Parkin expression is frequently downregulated in many types of cancer, and its tumor-suppressive mechanism is poorly defined. Here, we show that PHGDH is a substrate for Parkin-mediated ubiquitination and degradation. Parkin interacted with PHGDH and ubiquitinated PHGDH at lysine 330, leading to PHGDH degradation to suppress serine synthesis. Parkin deficiency in cancer cells stabilized PHGDH and activated serine synthesis to promote cell proliferation and tumorigenesis, which was largely abolished by targeting PHGDH with RNA interference, CRISPR/Cas9 KO, or small-molecule PHGDH inhibitors. Furthermore, Parkin expression was inversely correlated with PHGDH expression in human breast cancer and lung cancer. Our results revealed PHGDH ubiquitination by Parkin as a crucial mechanism for PHGDH regulation that contributes to the tumor-suppressive function of Parkin and identified Parkin downregulation as a critical mechanism underlying PHGDH overexpression in cancer.
Abstract 10200: Relationship Between Coronary Arterial 18F-sodium Fluoride Uptake and Epicardial Adipose Tissue Analyzed on Computed Tomography
Authors: Toshiro Kitagawa, Yumiko Nakamoto, Ko Sasaki, Yutaka Hirokawa, Yasuki Kihara
Journal: Circulation (2019)

Background: 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has the potential to detect high-risk coronary plaques. Epicardial adipose tissue (EAT) reportedly correlates with coron...
Bridging the treatment gap in infant medulloblastoma: molecularly informed outcomes of a globally feasible regimen
Authors: Lorena V Baroni, Claudia Sampor, Adriana Gonzalez, Fabiana Lubieniecki, Gabriela Lamas, Carlos Rugilo, Ute Bartels, Ayala Heled, Kyle S Smith, Paul A Northcott, Eric Bouffet, Daniel Alderete, Vijay Ramaswamy
Journal: Neuro-Oncology (2020)

Abstract Background Infant medulloblastoma represents an enormous challenge in neuro-oncology, due to their simultaneous high-risk of recurrence and high risk of severe neurodevelopmental sequelae with craniospinal irradiation. Currently infant medulloblastoma are treated with intensified protocols, either comprising intraventricular methotrexate or autologous transplant, both of which carry significant morbidity and are not feasible in the majority of the world. We sought to evaluate the molecular predictors of outcome in a cohort of infants homogeneously treated with induction chemotherapy, focal radiation and maintenance chemotherapy. Methods In a retrospective analysis, 29 young children treated with a craniospinal irradiation sparing strategy from Hospital Garrahan in Buenos Aires were profiled using Illumina HumanMethylationEPIC arrays, and correlated with survival. Results Twenty-nine children (range, 0.3–4.6 y) were identified, comprising 17 sonic hedgehog (SHH), 10 Group 3/4, and 2 non-medulloblastomas. Progression-free survival (PFS) across the entire cohort was 0.704 (95% CI: 0.551–0.899). Analysis by t-distributed stochastic neighbor embedding revealed 3 predominant groups, SHHβ, SHHγ, and Group 3. Survival by subtype was highly prognostic with SHHγ having an excellent 5-year PFS of 100% (95% CI: 0.633–1) and SHHβ having a PFS of 0.56 (95% CI: 0.42–1). Group 3 had a PFS of 0.50 (95% CI: 0.25–1). Assessment of neurocognitive outcome was performed in 11 patients; the majority of survivors fell within the low average to mild intellectual disability, with a median IQ of 73.5. Conclusions We report a globally feasible and effective strategy avoiding craniospinal radiation in the treatment of infant medulloblastoma, including a robust molecular correlation along with neurocognitive outcomes.