tbuckley/cabot-search huggingface dataset:
Clinical Assessment and Management of Delirium in the Palliative Care Setting
Authors: Shirley Harvey Bush, Sallyanne Tierney, Peter Gerard Lawlor
Journal: Drugs (2017)

Delirium is a neurocognitive syndrome arising from acute global brain dysfunction, and is prevalent in up to 42% of patients admitted to palliative care inpatient units. The symptoms of delirium and its associated communicative impediment invariably generate high levels of patient and family distress. Furthermore, delirium is associated with significant patient morbidity and increased mortality in many patient populations, especially palliative care where refractory delirium is common in the dying phase. As the clinical diagnosis of delirium is frequently missed by the healthcare team, the case for regular screening is arguably very compelling. Depending on its precipitating factors, a delirium episode is often reversible, especially in the earlier stages of a life-threatening illness. Until recently, antipsychotics have played a pivotal role in delirium management, but this role now requires critical re-evaluation in light of recent research that failed to demonstrate their efficacy in mild- to moderate-severity delirium occurring in palliative care patients. Non-pharmacological strategies for the management of delirium play a fundamental role and should be optimized through the collective efforts of the whole interprofessional team. Refractory agitated delirium in the last days or weeks of life may require the use of pharmacological sedation to ameliorate the distress of patients, which is invariably juxtaposed with increasing distress of family members. Further evaluation of multicomponent strategies for delirium prevention and treatment in the palliative care patient population is urgently required.
分岐度を制御する単純による広い近赤外範囲内でのin vivoでの癌治療のための金ナノ樹枝状結晶の調整光熱特性【Powered by NICT】
Authors: Qiu Penghe, Yang Mingying, Qu Xuewei, Huai Yanyan, Zhu Ye, Mao Chuanbin
Journal: Biomaterials (2016)
Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway
Authors: Meng Li, Chengfu Xu, Junping Shi, Jiexia Ding, Xingyong Wan, Dahua Chen, Jianguo Gao, Chunxiao Li, Jie Zhang, Yiming Lin, Zhenhua Tu, Xiaoni Kong, Youming Li, Chaohui Yu
Journal: Gut (2017)

Objective Accumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H 2 S) biosynthesis. Design Hepatic MPST expression was evaluated in mice and patients with NAFLD. A variety of molecular approaches were used to study the effects of MPST regulation on hepatic steatosis in vivo and in vitro. Results In vitro treatment of hepatocytes with FFAs upregulated MPST expression, which was partially dependent on NF-κB/p65. Hepatic MPST expression was markedly increased in high fat diet (HFD)-fed mice and patients with NAFLD. Partial knockdown of MPST via adenovirus delivery of MPST short hairpin RNA or heterozygous deletion of the Mpst gene significantly ameliorated hepatic steatosis in HFD-fed mice. Consistently, inhibition of MPST also reduced FFA-induced fat accumulation in L02 cells. Intriguingly, inhibition of MPST significantly enhanced rather than decreased H 2 S production, whereas MPST overexpression markedly inhibited H 2 S production. Co-immunoprecipitation experiments showed that MPST directly interacted with and negatively regulated cystathionine γ-lyase (CSE), a major source of H 2 S production in the liver. Mechanistically, MPST promoted steatosis via inhibition of CSE/H 2 S and subsequent upregulation of the sterol regulatory element-binding protein 1c pathway, C-Jun N-terminal kinase phosphorylation and hepatic oxidative stress. Conclusions FFAs upregulate hepatic expression of MPST and subsequently inhibit the CSE/H 2 S pathway, leading to NAFLD. MPST may be a potential therapeutic target for NAFLD.
Margaret McCartney: Innovation without sufficient evidence is a disservice to all
Authors: Margaret McCartney
Journal: BMJ (2017)

Breeding with the vigour of rabbits, a variety of private GP services are springing up and jostling for your attention. Why spend hours phoning your own GP when you can choose a private GP by looks and price, having immediate access online or by app without needing to leave your home? Recruitment for GPs in such companies is increasingly competitive, with advertisements promising hourly rates and perks unfamiliar to NHS employees.

Some of these companies have bigger ambitions. “Why couldn’t Babylon be a patient’s NHS GP?” asks Ali Parsa, CEO of Babylon—an IT company whose app, he says, is faster and more accurate than doctors in risk assessing cases.1 The NHS in north London has gone further, commissioning his company to offer “symptom advice” through a smartphone app service—“NHS 111 powered by Babylon”2—although …
An Inexpensive, Point‐of‐Care Urine Test for Bladder Cancer in Patients Undergoing Hematuria Evaluation
Authors: Abhinav P. Acharya, Kathryn M. Theisen, Andres Correa, Thiagarajan Meyyappan, Abraham Apfel, Tao Sun, Tatum V. Tarin, Steven R. Little
Journal: Advanced Healthcare Materials (2017)

Abstract Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70–98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office‐based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases (“Ammps”) is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin‐conjugated alginate (Fe(II)) nanoparticles by collagenases generates free‐floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation.
Frequent promoter hypermethylation of deleted in liver cancer-1 (DLC-1) gene in human leukemias
Authors: Kin Fai Cheung, Kin Mang Lau, Natalie P. H. Chan, Wai Shan Wong, Ki Wai Chik, Matthew M. K. Shing, Raymond S. M. Wong, Gregory Cheng, Chi Kong Li, Ho Keung Ng, Margaret H. L. Ng
Journal: Cancer Research (2005)

1832  Aberrant promoter methylation, leading to inactivation of cancer-related gene, plays an important role in human carcinogenesis. DLC-1 at 8p21.3-22 is frequently deleted and transcriptionally silenced by promoter hypermethylation in hepatocellular carcinoma. Previous studies indicated that it had anti-proliferative effects on various cancer cells. We investigated promoter methylation of DLC-1 in human leukemias at diagnosis. A total of 84 primary bone marrow samples of acute lymphoblastic leukemia (ALL) (childhood, n=35; adult, n=11), chronic lymphocytic leukemia (CLL, n=7), acute myeloid leukemia (AML, n=12), chronic myelogenous leukemia (CML, n=13), acute biphenotypic leukemia (ABL, n=6) and 6 leukemic cell lines were analyzed by using combined bisulfite restriction analysis (COBRA). The methylation CpG sites were further examined by bisulfite sequencing. Results indicated that 71% (25/35) of childhood and 45% (5/11) of adult ALL samples, and 86% (5/6) of CLL samples had DLC-1 promoter hypermethylation. In contrast, DLC-1 hypermethylation was found in 1 of 12 AML (8%) and 3 of 13 CML (23%) samples. There were 67% (4/6) ABL samples with this aberrant methylation. Of 14 samples of peripheral blood lymphocytes tested as normal controls from healthy blood donors, none showed DLC-1 promoter hypermethylation. For the cell lines, complete hypermethylation was found in RS4;11 and HL-60 whereas REH, 697 and CCRF-CEM showed partial hypermethylation. The DLC-1 promoter was unmethylated in MOLT-3 cells. The methylation status was verified by bisulfite sequencing and the sequencing results indicated that over 90% of CpG sites (n=35 in the promoter region at nucleotide +20 to +310) were methylated in both RS4;11 and HL-60 cells. Concordantly, semi-quantitative RT-PCR analysis demonstrated no expression of DLC-1 transcripts in RS4;11 and HL60 cells while the transcripts were detected in all other cell lines. For the controls, all 10 normal peripheral blood lymphocyte samples tested expressed DLC-1 mRNA. To further demonstrate the inverse correlation, RS4;11 cells were treated with DNA demethylating agent (5-aza-2’-deoxycytidine) for 4 days. Reactivation of DLC-1 mRNA expression was achieved in a dose-dependent manner. In conclusion, we demonstrated high frequencies of DLC-1 promoter hypermethylation in both acute and chronic lymphoid leukemias but relatively low frequencies in myeloid leukemias. Our finding suggested that DLC-1 aberrant methylation may play an important role in lymphoid leukemiogenesis.
Combination Immunotherapy with NY-ESO-1-Specific CAR+ T Cells with T-Cell Vaccine Improves Anti-Myeloma Effect
Authors: Krina Patel, Simon Olivares, Harjeet Singh, Lenka V. Hurton, Mary Helen Huls, Muzaffar H. Qazilbash, Partow Kebriaei, Richard E. Champlin, Laurence J.N. Cooper
Journal: Blood (2016)
Junior doctor is suspended for dishonesty over annual leave
Authors: Clare Dyer
Journal: BMJ (2017)

A junior doctor who claimed to be ill when he was really in Spain, leaving a hospital ward without cover, has been suspended for two months by a medical practitioners tribunal.

Robert Coddington was a foundation year 1 doctor working at Nottingham University Hospitals NHS Foundation Trust in 2015 when he left for four days in Spain. He had initially asked for four days’ leave ending on 31 July, but, after failing to find cover for the last …
The Role of Circulating Neutrophils in Increased Procoagulant Activity after Acute Ischemic Stroke
Authors: Zhipeng Yao, Tao Li, Muhua Cao, Ruishuang Ma, Xiaoming Wu, Lixiu Wang, Lu Zhao, Yan Zhang, Yayan Bi, Junjie Kou, Jin Zhou, Jialan Shi
Journal: Blood (2016)
EVALUATION OF THE EFFECTIVENESS OF IN-HOSPITAL TREATMENT OF CHRONIC HEART FAILURE PATIENTS DURING EXACERBATION BY NON-INVASIVE NET LUNG IMPEDANCE MONITORING DURING ADMISSION
Authors: Michael Shochat, Avraham Shotan, Iris Dahan, Mark Kazatsker, Lubov Vasilenko, Yaniv Levy, Ilia Shochat, Aaron Frimerman, Aya Asif, David Blondheim, Simcha Meisel
Journal: Journal of the American College of Cardiology (2013)
SP0082 Immunogenicity of biologics in inflammatory bowel diseases
Authors: A Gils
Journal: Annals of the Rheumatic Diseases (2017)

Anti-tumor necrosis factor-alpha and anti-integrin monoclonal antibodies show great benefits for inducing and maintaining remission, healing the mucosa and restoring the quality of life of patients with inflammatory bowel diseases. The therapeutic potential of these intrinsically powerful biologicals is tempered by a high variability in clinical response. Whereas primary non-response is defined as the lack of clinical response to treatment, assessed 8–12 weeks after initiation, secondary loss of response is defined as loss of clinical benefit after initially responding which can be attributed to disease-related or drug-related factors. Assays have been developed to determine the concentration of the therapeutic antibody in serum of the treated patient. The trough concentration is the concentration just before the next administration and for practical reasons therapeutic drug monitoring is mainly based on measurement of these trough concentrations. Several studies have reported correlations between through concentration of infliximab, adalimumab, golimumab, vedolizumab and clinical outcome. Optimal therapeutic windows have been defined for both infliximab and adalimumab. A panel of prospective studies in which dosage regimens are adapted in order to achieve target trough infliximab concentrations that correlate with beneficial therapeutic outcomes have been initiated. Immunogenicity is the capability of biologicals to elicit an unwanted immune response that results in the formation of anti-drug antibodies. Anti-drug antibodies can be non-neutralizing or neutralizing. Non-neutralizing antibodies do not impair the drug-target interaction but may increase clearance of the drug resulting in lower serum concentrations. Neutralizing anti-drug antibodies compete with the target for the antigen-binding site and modulate directly the activity of the drug in addition to the enhanced clearance of the drug. A number of anti-drug antibody assays to quantify the immunogenicity of biologicals have been developed. Most of the assays quantify the total amount of anti-drug antibodies but comparing anti-drug antibody concentrations between different assays is hampered by the use of different calibrators and by the fact that drug tolerance differs among assays ranging from extreme drug sensitive over various forms of drug tolerant to drug resistant anti-drug antibody asssays. The clinical relevance of the different type of anti-drug antibody assays remains to be proven. Combining therapeutic drug concentrations and anti-drug antibody concentrations with relevant patient, disease and drug information will lead to optimal dosing of patients aiming at optimal clinical, biochemical and endoscopic outcomes. <h3>Disclosure of Interest</h3> A. Gils Grant/research support from: IIR grants from pfizer, Speakers bureau: speakers fee by Pfizer, MSD, Abbvie, Takeda, JnJ
Abstract 14489: Identification of Resident Cardiac Cell-type Enriched Proteomes Reveals Novel Cardiac Fibroblast Markers in Myocardial Infarct Zones
Authors: Jake Cosme, Kathryn Lipsett, Melissa Noronha, Parveen Sharma, Joshua Backx, Jason Huber, Alex Ignatchenko, Ruth Isserlin, Peter P Liu, Jeremy Simpson, Thomas Kislinger, Anthony O Gramolini
Journal: Circulation (2016)

Introduction:  The heart is composed of multiple constituent cell types with the most abundant cells being cardiomyocytes (CM), fibroblasts (FB), endothelial (EC) and smooth muscle (SMC) cells. Cardiac large scale studies often compare healthy and diseased tissues, losing some of the cellular origin of these (mal)adaptive changes. Thus, studies are limited by lack of knowledge of the complete protein complement of individual cell types.   Methods:  We employed sub-fractionation methods to attain cellular fractions from 2-3 week cultured human cardiac FB, cardiac muscle-derived CM, coronary artery EC, and coronary artery SMC. Peptides were analyzed via 9-cycle MuDPIT analysis. Protein abundance was calculated with spectral counting. Protein expression was assessed using human cardiac tissue staining in the Human Protein Atlas (HPA). FB-enriched proteins were further evaluated in a mouse model of myocardial infarction (MI) through immunofluorescence (IF) imaging.   Results:  Shotgun proteomics identified a total of 2320 FB, 2310 CM, 2247 EC, and 2209 SMC proteins and 2853 proteins overall. Statistical analysis identified 367 FB-enriched, 97 CM-enriched, 340 EC-enriched, and 52 SMC-enriched proteins. We investigated the functional annotations of our enriched datasets via Gene Set Enrichment Analysis. We rank ordered cell-specific enrichment of proteins via magnitude and significance of enrichment. For several of the highly ranked cell type-enriched proteins, we assessed HPA to identify supportive of our protein candidates. We then mapped candidates to an independent proteome dataset of hypertrophic cardiomyopathy (HCM) to elucidate each resident cell’s contributions to the proteome changes of HCM. With FB enrichment data being the most pronounced, we then validated expression of multiple highly-ranked candidates (GRB2, AKR1B1, and PRDX1) in MI tissue sections. Staining showed higher expression in the highly fibrotic infarct scar of 4-week post-MI relative to border and non-infarct regions, confirming the cellular phenotype of our candidates.   Conclusion:  Our study has provided the most complete proteomic analysis of specific human cardiac cell types. Potential cell-type markers have been validated by HPA as well as our own IF imaging of MI.
Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants
Authors: Edgar Delgado-Eckert, Oliver Fuchs, Nitin Kumar, Juha Pekkanen, Jean-Charles Dalphin, Josef Riedler, Roger Lauener, Michael Kabesch, Maciej Kupczyk, Sven-Erik Dahlen, Erika von Mutius, Urs Frey
Journal: Thorax (2017)

Rationale Asthma is characterised by inflammation and reversible airway obstruction. However, these features are not always closely related. Fluctuations of daily lung function contain information on asthma phenotypes, exacerbation risk and response to long-acting β-agonists. Objectives In search of subgroups of asthmatic participants with specific lung functional features, we developed and validated a novel clustering approach to asthma phenotyping, which exploits the information contained within the fluctuating behaviour of twice-daily lung function measurements. Methods Forced expiratory volume during the first second (FEV 1 ) and peak expiratory flow (PEF) were prospectively measured over 4 weeks in 696 healthy and asthmatic school children (Protection Against Allergy – Study in Rural Environments (PASTURE)/EFRAIM cohort), and over 1 year in 138 asthmatic adults with mild-to-moderate or severe asthma (Pan-European Longitudinal Assessment of Clinical Course and BIOmarkers in Severe Chronic AIRway Disease (BIOAIR) cohort). Using enrichment analysis, we explored whether the method identifies clinically meaningful, distinct clusters of participants with different lung functional fluctuation patterns. Measurements and main results In the PASTURE/EFRAIM dataset, we found four distinct clusters. Two clusters were enriched in children with well-known clinical characteristics of asthma. In cluster 3, children from a farming environment predominated, whereas cluster 4 mainly consisted of healthy controls. About 79% of cluster 3 carried the asthma-risk allele rs7216389 of the 17q21 locus. In the BIOAIR dataset, we found two distinct clusters clearly discriminating between individuals with mild-to-moderate and severe asthma. Conclusions Our method identified dynamic functional asthma and healthy phenotypes, partly independent of atopy and inflammation but related to genetic markers on the 17q21 locus. The method can be used for disease phenotyping and possibly endotyping. It may identify participants with specific functional abnormalities, potentially needing a different therapeutic approach.
Erratum. Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived? Diabetes Care 2017;40:813–820
Authors: Muhammad Abdul-Ghani, Ralph A. DeFronzo, Stefano Del Prato, Robert Chilton, Rajvir Singh, Robert E.J. Ryder
Journal: Diabetes Care (2017)

In the article listed above, the sentence on page 814 that reads “There also were more serious hypoglycemic events …
Production of Malignancy in Vitro. VI. Pathology of Tumors Produced
Authors: Anderson Nettleship, Wilton R. Earle, Mary P. Clapp, Emma Shelton
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Production of Malignancy in Vitro. VI. Pathology of Tumors Produced Get access Anderson Nettleship, Anderson Nettleship passed assistant surgeon (R) National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle, Wilton R. Earle senior cytologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary P. Clapp, Mary P. Clapp technical assistance National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Emma Shelton Emma Shelton National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 2, October 1943, Pages 229–248, https://doi.org/10.1093/jnci/4.2.229 Published: 01 October 1943
Deconstructing Superorganisms and Societies to Address Big Questions in Biology
Authors: Patrick Kennedy, Gemma Baron, Bitao Qiu, Dalial Freitak, Heikki Helanterä, Edmund R. Hunt, Fabio Manfredini, Thomas O’Shea-Wheller, Solenn Patalano, Christopher D. Pull, Takao Sasaki, Daisy Taylor, Christopher D.R. Wyatt, Seirian Sumner
Journal: Trends in Ecology & Evolution (2017)
The Early Stages of Carcinogenesis by 20-Methylcholanthrene in the Skin of the Mouse. I. Experimental Technique and Macroscopic Changes&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: W. Cramer, R. E. Stowell
Journal: JNCI Journal of the National Cancer Institute (1942)

The Early Stages of Carcinogenesis by 20-Methylcholanthrene in the Skin of the Mouse. I. Experimental Technique and Macroscopic Changes Get access W. Cramer, W. Cramer research associate, research associate in cytology Barnard Free Skin and Cancer Hospital, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar R. E. Stowell R. E. Stowell research fellow Barnard Free Skin and Cancer Hospital, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 4, February 1942, Pages 369–378, https://doi.org/10.1093/jnci/2.4.369 Published: 01 February 1942
Are indexed values better for defining exercise pulmonary hypertension?
Authors: Jason Weatherald, Athénaïs Boucly, Edmund Lau, Laurent Godinas, Laurent Savale, Xavier Jaïs, David Montani, Olivier Sitbon, Gérald Simonneau, Marc Humbert, Denis Chemla, Philippe Hervé
Journal: European Respiratory Journal (2017)

Pulmonary hypertension (PH) is defined by resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg [1]. Patients with pulmonary vascular disease (PVD) or left heart disease (LHD) may demonstrate abnormal haemodynamic responses to exercise even when resting mPAP is normal [2]. After the 4th World Symposium on PH in 2008, exercise PH, defined as mPAP >30 mmHg during exercise, was abandoned due to a lack of supportive evidence and the observation that mPAP frequently exceeds 30 mmHg in healthy individuals who attain high cardiac output (CO) [3, 4]. A disproportionate increase in mPAP relative to CO during exercise, however, reflects either an increase in pulmonary vascular resistance (PVR), as in PVD, or elevated left ventricular filling pressure in LHD. Therefore, attention to the mPAP/CO relationship, such as the mPAP/CO slope or the total pulmonary resistance (TPRmax) >3 Wood units (WU) at maximal exercise, could refine the definition of an abnormal haemodynamic response to exercise in order to reduce false positive diagnoses [5–7]. Indeed, combining mPAP (mPAPmax) >30 mmHg and the TPRmax >3 WU at maximal exercise has been demonstrated to have high accuracy in discriminating patients with PVD or LHD and resting mPAP ≤20 mmHg from controls or healthy volunteers [7]. Furthermore, these criteria have superior diagnostic performance compared to either the mPAP/CO slope or change in mPAP/CO during exercise [8]. No advantage to using indexed total pulmonary resistance in the definition of exercise pulmonary hypertension <http://ow.ly/tmgi30dMN5T> We would like to acknowledge Marie Line Goubet and Antoine Goineau from the Cardiac Catheterization Laboratory, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital de Bicêtre (Le Kremlin-Bicêtre, France) for their assistance in performing exercise haemodynamic testing.