tbuckley/cabot-search huggingface dataset:
Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial
Authors: Sanjeevan Muruganandan, Maree Azzopardi, Deirdre B Fitzgerald, Ranjan Shrestha, Benjamin C H Kwan, David C L Lam, Christian C De Chaneet, Muhammad Redzwan S Rashid Ali, Elaine Yap, Claire L Tobin, Luke A Garske, Phan T Nguyen, Christopher Stanley, Natalia D Popowicz, Christopher Kosky, Rajesh Thomas, Catherine A Read, Charley A Budgeon, David Feller-Kopman, Nick A Maskell, Kevin Murray, Y C Gary Lee
Journal: The Lancet Respiratory Medicine (2018)
Evolution and landscape of clinical trials for breast cancer patients.
Authors: Semih Dogan, Aicha Goubar, Monica Arnedos, Suzette Delaloge, Fabrice Andre
Journal: Journal of Clinical Oncology (2012)

1601 Background: Recent advances in cancer research are expected to have dramatically changed the way clinical trials are being done. In an effort to outline new trends of clinical research in the breast cancer area, we have evaluated the evolution of clinical trials started between 2006 and 2011. Methods: 622 clinical trials, started during the first semester 2006, the second semester 2008 and the first semester 2011, were analyzed. The data source was Clinicaltrials.gov. 30 items were included in the database. Results: The overall number of patients included in prospective clinical trials increased over these periods (n=67,820, n=91,429, n=98,417). However, when large epidemiological cohorts are excluded, a significant fall in the number of patients is seen (n=67,820, n=44,554, n=37,417). The absolute number of therapeutic trials also decreased during this time (n=93, n=99, n=78), mainly related to the dramatic fall in the number of trials testing conventional treatments (n=40, n=24, n=20). In the meantime, the number of trials testing targeted agents remained similar (n=46, n=67, n=50). Interestingly, in the same time, the number of trials testing a targeted agent in a population defined by a biomarker increased (n=1, n=6, n=14). At the opposite, prospective studies aimed at validating biomarkers did not increase, and remained only driven by large consortiums. As illustration, when we exclude RxPONDER trial, the biomarker-validation studies opened in 2011 planned to include only 2 493 patients, representing 2% of the breast cancer research field. Prospective trials testing social sciences and supportive care (n= 70, n=72, n=70) tend to become as important as therapeutic trials. Finally, large epidemiological cohorts opened in 2011 will represent more than 60% of the patients included in clinical trials. Conclusions: The part of cohorts and social sciences in breast cancer research is increasing and represents now the majority of the clinical research activity. When the analysis focuses on therapeutic trials, the breast cancer field recently shifted to targeted agents and early data suggest that therapeutic research is increasingly incorporating companion biomarker. Analysis on all 2,762 clinical trials done between 2006 and 2011 will be presented.
Abstract 14663: Mechanisms of Ventricular Tachycardia Recurrence and Outcomes of Repeat Catheter Ablation After Cardiac Sympathetic Denervation in Nonischemic Cardiomyopathy Patients
Authors: Ricky Yu, Marmar Vaseghi, Olujimi A Ajijola, Roderick Tung, Noel G Boyle, Kalyanam Shivkumar
Journal: Circulation (2016)

Background: Cardiac sympathetic denervation (CSD) is a useful adjunct for treatment of ventricular tachycardia (VT). The mechanisms of VT recurrence after CSD and outcomes of repeat catheter ablati...
The effects of sphingosine 1-phosphate (S1P) on proliferation of gastric cancer cells with different receptor expression profiles
Authors: Hiroharu Yamashita, Joji Kitayama, Dai Shida, Hironori Yamaguchi, Ken Mori, Hirokazu Nagawa
Journal: Cancer Research (2004)

2748   Previous data from our laboratory has indicated that there is a functional link between the beta-adrenergic receptor pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in breast cancer cell lines and these pathways were involved in growth regulation of these cells. The ER (+) cell lines MCF-7, MDA MB-361 and ZR-75.1 and the ER (-) cell line MDA MB-453 expressed mRNA for the GIRK1 channel while the ER (-) cell lines MDA MB-468 and MDA MB-435 did not express GIRK1 (Proc. Am. Assoc. Can. Res., 43:350). We wanted to determine if GIRK channels were expressed in other human cancers. GIRK1 mRNA was expressed in four of seven small cell lung cancer (SCLC) cell lines. It was expressed in WBA, H-69, H-82, and H-146, but not expressed in H-209, H-187, or H-526. Using real-time PCR, we determined GIRK2 & 4 mRNA expression in the 7 SCLC cell lines. Threshold (C T ) values for GIRK 2 were WBA-19.82, H-69-23.54, H-82-27.16, H-146-no expression, H-187-no expression, H-209, 24.53, H-526-27.55. C T  values for GIRK4 were WBA-30.56, H-69-32.18, H-82-27.71, H-146-40.54, H-187-31.60, H-209-24.64, H-526-23.21. GIRK2 & 4 mRNA expression was determined using the same cDNA sample, indicating that the lack of GIRK2 expression in H-146 and H-187 was real. Treatment of H-69 and H-82 cells with beta 2  adrenergic antagonist ICI118,551 (1 μM) daily for 7 days led to slight decreases of GIRK1 mRNA expression levels. Current studies are underway to determine the growth regulatory pathways stimulated by these pathways. We feel these may be important regulatory pathways since no expression of mRNA of the three GIRK channels (1,2,4) was found in hamster pulmonary neuroendocrine cells, a suggested cell of origin for SCLC. In addition, GIRK1 was not found in the normal breast epithelial cell line MCF10A. We have also determined using RT-PCR, that GIRK1 mRNA was not expressed in normal pancreatic cells, nor in four pancreatic cancer cell lines (PANC-1, ASPC, BXPC-3, CAPAN-1). We feel that this data may indicate that stimulation of GIRK channels and/or stimulation of beta-adrenergic signaling can activate similar signaling pathways in both small cell lung cancer and breast cancer.
Safety and outcomes of an oncologic robotic whipple program.
Authors: Benjamin D Powers, Jose Mario Pimiento, Sabrina D Saeed, Danielle Deperalta, Pamela Joy Hodul, Jason B. Fleming, Mokenge Peter Malafa
Journal: Journal of Clinical Oncology (2018)

393 Background: Robotic-assisted surgery is a new technology being used more commonly in surgical oncology. We evaluated the outcomes of robotic pancreaticoduodenectomy over time from a single U.S. cancer center. Methods: The Moffitt Cancer Center Tumor Registry was queried for robotic pancreaticoduodenectomy cases performed by two surgeons from 2012-2017 after IRB approval. Descriptive statistics and analyses with t-test and chi-square test were performed. Results: 61 case were analyzed; the first cohort comprised 31 cases and the second cohort comprised the next 30 cases. The most common pre-operative diagnosis was adenocarcinoma. For the entire cohort, the estimated blood loss was 498mL, ASA class was 2.5, and OR duration 546 minutes. The first cohort had 14 conversions to open Whipple and the second cohort had 11. There were no anesthesia or surgical complications. There was one 30-day mortality and one R1 resection. There was no significant difference in EBL, OR transfusions, or post-op transfusions. There was a significant decrease in the operative time between the two cohorts. Additionally, there was a significant increase in total number of nodes examined in the second cohort, though no difference in the number of positive nodes. Conclusions: In selected patients, robotic pancreaticoduodenectomy is a safe alternative to open pancreaticoduodenectomy. Published data suggest a learning curve of approximately 60-80 cases. In our cohort we observed a significant decrease in OR time and an increase in lymph node retrieval after 31 cases, suggesting an earlier inflection point. Further studies are needed to examine additional follow-up and outcome variables. [Table: see text]
Transformation of follicular lymphoma
Authors: Wenchee Siow, Kieran Burton, Helen Eagleton, Carolyn Campbell, Barbara J. Bain
Journal: American Journal of Hematology (2018)

A 73-year-old woman presented with a 3-week history of fevers and sudden weight loss. Her past medical history included stage IV follicular lymphoma diagnosed 9 years earlier, which had been treated with rituximab-based immunochemotherapy. Clinical examination showed bilateral cervical and axillary lymphadenopathy, and splenomegaly. She was found to be bicytopenic with a hemoglobin concentration of 99 g/L, white cell count of 7.4 × 109/L, and platelet count of 8 × 109/L. Lymphocyte count was 5.2 × 109/L and neutrophil count 1.5 × 109/L. A blood film showed a minor population of small lymphocytes with cleft nuclei, consistent with the previous diagnosis of follicular lymphoma. However, in addition, there were large lymphoid cells with prominent nucleoli, some with a high nucleocytoplasmic ratio. Some had cleft nuclei and were consistent with large centrocytes (top left and right). Others had round or oval nuclei, and were consistent with centroblasts (bottom left and right). Bone marrow fluorescence in situ hybridization showed 36 out of 40 cells to have an IGH/BCL2 rearrangement, as expected in follicular lymphoma. In addition, 24 of 40 cells showed a MYC rearrangement. These findings were indicative of a high-grade transformation of follicular lymphoma, with MYC rearrangement and BCL2 juxtaposed to the IGH locus. The peripheral blood film can thus reveal not only a diagnosis of follicular lymphoma1 but also of high grade transformation of this lymphoma. The authors declare that they have no conflicts of interest with the contents of this article.
Macrophage Sphingomyelin Synthase 2 Deficiency Decreases Atherosclerosis in Mice
Authors: JingLiu, ChongminHuan, MahuaChakraborty, HongqiZhang, DaLu, Ming-ShangKuo, GuoqingCao, Xian-ChengJiang
Journal: Circulation Research (2009)

Rationale: Sphingomyelin synthase (SMS)2 contributes to de novo sphingomyelin (SM) biosynthesis and plasma membrane SM levels. SMS2 deficiency in macrophages diminishes nuclear factor κB and mitogen-activated protein kinase activation induced by inflammatory stimuli. Objective: The effects of SMS2 deficiency on the development of atherosclerosis are investigated. Methods and Results: We measured cholesterol efflux from macrophages of wild-type (WT) and SMS2 knockout (KO) mice. We transplanted SMS2 KO mouse bone marrow into low-density lipoprotein (LDL) receptor (LDLr) knockout mice (SMS2−/−→LDLr−/−), creating a mouse model of SMS2 deficiency in the macrophages. We found that SMS2 deficiency caused significant induction of cholesterol efflux in vitro and in vivo. Moreover, we found that SMS2 KO mice had less interleukin-6 and tumor necrosis factor α in the circulation before and after endotoxin stimulation, compared with controls. More importantly, after 3 months on a western-type diet, SMS2−/−→LDLr−/− mic...
Human resources required for antimicrobial stewardship teams: a Dutch consensus report
Authors: J. ten Oever, M. Harmsen, J. Schouten, M. Ouwens, P.D. van der Linden, C.M. Verduin, B.J. Kullberg, J.M. Prins, M.E.J.L. Hulscher
Journal: Clinical Microbiology and Infection (2018)
Osteoporosis Treatment After Hip Fracture
Authors: Douglas C. Bauer
Journal: JAMA Network Open (2018)

Rishi J. Desai, MS, PhD; Mufaddal Mahesri, MD, MPH; Younathan Abdia, MS, PhD; Julie Barberio, BS; Angela Tong, MS; Dongmu Zhang, PhD; Panagiotis Mavros, PhD; Seoyoung C. Kim, MD, ScD; Jessica M. Franklin, PhD
CUX1-ALK, a Novel ALK Rearrangement That Responds to Crizotinib in Non–Small Cell Lung Cancer
Authors: Meiling Zhang, Qian Wang, Yan Ding, Guoqun Wang, Yunqian Chu, Xiang He, Xue Wu, Yang W. Shao, Kaihua Lu
Journal: Journal of Thoracic Oncology (2018)
Amplified Transmural Dispersion of Repolarization as the Basis for Arrhythmogenesis in a Canine Ventricular-Wedge Model of Short-QT Syndrome
Authors: FabriceExtramiana, CharlesAntzelevitch
Journal: Circulation (2004)

Background— The short-QT syndrome is a new clinical entity characterized by corrected QT intervals <300 ms and a high incidence of ventricular tachycardia (VT) and fibrillation (VF). Gain-of-function mutations in the gene for outward potassium currents have been shown to underlie the congenital syndrome. The present study examined the cellular basis of VT/VF in an experimental model associated with short QT intervals created with a potassium channel activator. Methods and Results— Transmembrane action potentials from epicardial and M regions, 4 transmural unipolar electrograms, and a pseudo-ECG were simultaneously recorded in canine arterially perfused left ventricular wedge preparations. At a basic cycle length of 2000 ms, pinacidil (2 to 3 μmol/L) abbreviated the QT interval from 303.7±5.4 to 247.3±6.9 ms (mean±SEM, P<0.0001). The maximal transmural dispersion of repolarization (TDRmax) increased from 27.0±3.8 to 64.9±9.2 ms (P<0.01), and an S2 applied to the endocardium induced a polymorphic VT (pVT) i...
Interleukin 6 trans-signalling and risk of future cardiovascular events
Authors: Louise Ziegler, Ashwini Gajulapuri, Paolo Frumento, Alice Bonomi, Håkan Wallén, Ulf de Faire, Stefan Rose-John, Bruna Gigante
Journal: Cardiovascular Research (2018)

The pro-inflammatory response to interleukin 6 (IL6) trans-signalling in atherosclerosis is driven by the IL6 and soluble IL6 receptor (sIL6R) binary complex. The binary IL6:sIL6R complex is inactivated by sgp130 through the formation of the ternary IL6:sIL6R:sgp130 complex. The aim of this study was to investigate if IL6 trans-signalling, estimated by a ratio between the binary and ternary complexes, associates with the risk of future cardiovascular events (CVE) in a Swedish cohort of 60-year-old men and women (n = 4232).Binary and ternary complex levels expressed in nanomol/Litre were derived from serum concentrations of IL6, sIL6R, and sgp130. Cox regression models were used to assess the risk of CVE (myocardial infarction, angina pectoris, and ischaemic stroke, n = 525), expressed as hazard ratio (HR) with 95% confidence interval (CI), associated with increasing circulating levels of the three molecules and with the binary/ternary complex ratio. Estimates were adjusted for the common cardiovascular (CV) risk factors. To assess the level of IL6-trans-signalling, we estimated the binary/ternary complex ratio and then analysed the association with CVE risk. A ratio higher than the median, representing a relative excess of the active binary complex was associated with increased CVE risk (adjusted HR 1.44, 95% CI 1.21-1.72).The ratio between the functional moieties of IL6 trans-signalling, IL6:sIL6R, and IL6:sIL6R:sgp130, was associated with CVE risk indicating that it could be a promising marker of CV risk and possibly be used in selecting patients for anti-inflammatory therapy.
CCG blocks GP at Hand’s request to expand to Birmingham over safety concerns
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Clinical commissioners have rejected a request from the service GP at Hand to subcontract its digital service from its London base to a site in Birmingham because of concerns over patient safety.

Board papers published by Hammersmith and Fulham Clinical Commissioning Group show that GP at Hand submitted a request on 22 June 2018 to “vary their subcontracting arrangements” with the CCG by adding a site in Birmingham.1 The digital service, run by an NHS general practice in Hammersmith in partnership with the technology company Babylon and which operates from five physical clinics in London,23 is keen to expand. The proposed Birmingham clinic would operate in the same way as the London satellite clinics, with patients able to see a GP at the location if they chose to.

But Hammersmith and Fulham CCG rejected the proposal after Birmingham and Solihull CCG …
Postoperative Changes in the Electrocardiogram in Congenital Heart Disease
Authors: Bernhardlandtman
Journal: Circulation (1954)

Electrocardiograms of 41 cases of coarctation and of 73 cases of patent ductus arteriosus were analyzed before and after surgical correction of the defect. The changes in the electrocardiogram which occurred after surgical repair of the coarctation were considered to be due to the diminished load on the left ventricle. In 65 of the cases of patent ductus arteriosus, electrocardiographic signs of left ventricular hypertrophy were recorded. Eight patients, seven of whom presented atypical murmurs, showed evidence of right ventricular or combined ventricular hypertrophy. Following ligation of the ductus, the electrocardiogram became normal in the majority of the cases.
Abstract P187: Increasing CVD and CVD Risk Among PLWHA in Louisiana 2002-2012
Authors: Tekeda F Ferguson, Xinnan Wang, Lauren Dyer, Susanne Straif-Bourgeois, Dayana Rojas, Patrick Maloney, Zhide Fang, Lynn Besch
Journal: Circulation (2018)

Introduction: While effective HIV treatments have decreased the likelihood of AIDS-defining illnesses among people aging with HIV, HIV-associated non-AIDS conditions are more common in individuals with long-standing HIV infection, including cardiovascular disease (CVD), hypertension, diabetes mellitus, and renal failure among others. It has been estimated that 30% of deaths among those with well-controlled viral load has been attributed to CVD, compared to 23.5% in the general US population. The purpose of this study was to determine the prevalence trends of CVD in people living with HIV/AIDS (PLWHA) in South Louisiana. Methods: A ten-year retrospective cohort study was conducted using data abstracted from the Louisiana State University (LSU) Health Care Services Division, Disease Management Evaluation Database (DMED) that included patients who received care within the LSU Medical System 7 state facilities. Inclusion criteria included 18 years of age or above, a positive HIV lab test, and a HIV diagnose code. Total sample size for the analysis was 9,374. The presence of CVD was established using ICD9 Diagnosis codes, patient vitals, and lab results. CVD outcomes evaluated included myocardial infarction, coronary artery disease, hypertension, heart failure, and stroke. All analyses were conducted in SAS 9.4. Results: The racial distribution was 24% white, 67% black, 2% other, and 7% unknown; distribution by sex remained stabled over the ten-year period approximately 58% male and 42% female. The mean age of the clinic population increased from 39.24±10.17 to 45.09±10.46 over the ten year period. There has been a positive trend in CVD among the HIV Clinic population, from 23.0% to 50.7% prevalence. There was an increase in hypertension, heart failure, stroke, and coronary artery disease among PLWHA. Hypertension showed the largest increase in prevalence from 19.4% to 44.8%. A positive trend and in increased Framingham Risk score was also observed (p&lt; 0.05). Conclusion: As PLWHA continue to increase in age, mortality and hospital admissions attributed to CVD has the potential to continue to increase. Data from this project has the potential to guide additional screening recommendations and practices, ultimately resulting in more timely detection of disease, which improves outcomes for patients.
Pulmonary Vascular Disease across the Life Span: A Call for Bridging Pediatric and Adult Cardiopulmonary Research and Care
Authors: Steven H. Abman, Andrew T. Lovering, Bradley A. Maron
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

a need to understand more about what drives this change and when.The patient-centered goals are to prevent low lung function de novo and to develop interventions that can "improve" low lung function in childhood.Repeated measurements of spirometry must have been made in hundreds of thousands of children as part of clinical practice, clinical trials, and epidemiologic studies.We live in an increasingly data-rich world, and the use of already acquired data offers an attractive method to complement results from birth cohorts such as the ALSPAC cohort, and to obtain results much more quickly and less expensively.It is quite possible that all the data we need have already been collected.
Tanglegrams Are Misleading for Visual Evaluation of Tree Congruence
Authors: Damien M de Vienne
Journal: Molecular Biology and Evolution (2019)

Evolutionary Biologists are often faced with the need to compare phylogenetic trees. One popular method consists in visualizing the trees face to face with links connecting matching taxa. These tanglegrams are optimized beforehand so that the number of lines crossing (the entanglement) is minimal. This representation is implicitly justified by the expectation that the level of entanglement is correlated with the level of similarity (or congruence) between the trees compared. Using simulations, I show that this correlation is actually very weak, which should preclude the use of such technique for getting insight into the level of congruence between trees.
Olive Phenol Hydroxytyrosol Prevents Passive Smoking–Induced Oxidative Stress
Authors: FrancescoVisioli, ClaudioGalli, ElenaPlasmati, SerenaViappiani, AliciaHernandez, ClaudioColombo, AngeloSala
Journal: Circulation (2000)

Background—Oxidative stress is involved in the onset of several degenerative disorders, and epidemiological studies indicate that a high intake of dietary antioxidants, as in the case of the Mediterranean basin, is protective. Olive mill waste waters (OMWWs) are a byproduct of olive oil production rich in phenolic antioxidants, such as hydroxytyrosol. We tested the effects of a low dose of an OMWW extract in a model of sidestream smoke–induced oxidative stress in rats by evaluating the urinary excretion of 8-iso-prostaglandin (PG) F2α (iPF2α-III). Methods and Results—An OMWW extract (5 mg/kg, providing 414 μg/kg of hydroxytyrosol) was administered to rats daily for 4 days, during which time the animals were exposed to sidestream smoke for 20 minutes once a day. Daily urines were collected, and the urinary excretion of 8-iso-PGF2α was evaluated as an index of oxidative stress–induced in vivo lipid peroxidation. The exposure of rats to passive smoking increased the urinary excretion of 8-iso-PGF2α by 44±4.2...
Recurrence of a Familial Giant Multilocular Cardiac Myxoma in a Patient With Carney's Complex
Authors: FelixGuenther, MatthiasSiepe, ChristianSchlensak, KonradAumann, AlexandraAnton, Wolf-DirkNiesen, FilizMarkfeld-Erol, ChristophBode, AnnetteGeibel
Journal: Circulation (2011)
Replications can cause distorted belief in scientific progress
Authors: Michał Białek
Journal: Behavioral and Brain Sciences (2018)

If we want psychological science to have a meaningful real-world impact, it has to be trusted by the public. Scientific progress is noisy; accordingly, replications sometimes fail even for true findings. We need to communicate the acceptability of uncertainty to the public and our peers, to prevent psychology from being perceived as having nothing to say about reality.
FACE-Q皮肤癌模块:外观满意度和QoL
Authors: E.H. Lee, A.F. Klassen, S.J. Cano, K.S. Nehal, A.L. Pusic
Journal: British Journal of Dermatology (2018)

通过手术治疗面部皮肤癌的患者通常会留下疤痕。术后,患者对其外观的满意度是一项重要但往往被忽视的疗效(即目标),而患者对其手术美学效果的看法(即对其外观的影响程度)可能因外科医生而异。研究表明,患者如何看待皮肤癌手术后的面部疤痕,可能会影响他们对所接受护理的看法以及其生活质量。本研究测试了“Face‐Q皮肤癌模块”,旨在衡量面部和疤痕外观、与外观相关的心理痛苦(疤痕对患者心理健康的影响程度)、癌症担忧和患者体验。研究利用209名经历面部皮肤癌手术的患者提供的反馈,测试了Face‐Q皮肤癌模块内的每项评分,发现FACE‐Q皮肤癌模块为医生提供了一整套有意义且在科学上合理的面部皮肤癌人群评分标准。此模块不仅在患者临床领域非常实用,也有助于研究。
Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis
Authors: Norma Maugeri, Annalisa Capobianco, Patrizia Rovere-Querini, Giuseppe A. Ramirez, Enrico Tombetti, Patrizia Della Valle, Antonella Monno, Valentina D’Alberti, Anna Maria Gasparri, Stefano Franchini, Armando D’Angelo, Marco E. Bianchi, Angelo A. Manfredi
Journal: Science Translational Medicine (2018)

Platelet microparticles from patients with systemic sclerosis prompt endothelial cell activation, neutrophil recruitment, and lung fibrosis.