tbuckley/cabot-search huggingface dataset:
Final results of a phase II study of modified FOLFOX6 (mFOLFOX6) and erlotinib (E) in patients with metastatic adenocarcinoma of the esophagus (Eso) and gastroesophageal junction (GEJ).
Authors: Z. A. Wainberg, L. Lin, B. DiCarlo, K. M. Dao, R. Patel, D. J. Park, R. Elashoff, N. Ryba, J. R. Hecht
Journal: Journal of Clinical Oncology (2010)

4050 Background: There is increased recognition that cancers of the upper GI tract are comprised of distinct epidemiological and molecular entities. Erlotinib (E) has shown activity in patients with adenocarcinoma of the Eso/GEJ, but not in patients with distal gastric cancer. mFOLFOX6 is one of several active cytotoxic regimens commonly used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of combined mFOLFOX6 and E in patients with untreated metastatic Eso/GEJ cancers. Methods: Patients with previously untreated metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg/m2, 5-FU 400 mg/m2, LV 400 mg/m2 on day 1, 5-FU 2,400 mg/m2 over 48 hours, and E 150 mg PO daily. Treatment was repeated every 14 days. The primary objective is to improve objective response rate of oxaliplatin based therapy from 34.8% (Al-Batran, SE, JCO 2008) to 44.8%. Secondary objectives include toxicity, and overall survival (OS). Target accrual is 38 patients based on a type I error of 10% and a power of 90%. Results: 34 patients have been treated and are evaluable to date: median age of 59 (range 36-79), all patients had an ECOG of 0 or 1. We observed 16 partial responses, 1 CR (ORR of 50%, 95% CI 32.1-67.9%), with 13/34 (38%) having stable disease. With 8.5 month median follow-up, median overall survival was 11.0 months (95% CI: 7.8-12.6 months). 86.5% of all adverse events were grade 1-2, and 13.5% were grade 3-4. Grade 3-4 related adverse events include: diarrhea/dehydration (24%), peripheral neuropathy (6%), neutropenia (9%), rash (9%) fatigue (9%). Relationship between mutation status (KRas, BRaf and EGFR), and HER2 amplification and clinical response to FOLFOX+ E is currently ongoing and final results will be presented. Conclusions: We surpassed our threshold for efficacy with an objective RR of 50%. In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and E is active, has an acceptable toxicity profile and FOLFOX ± E could be considered for further development. To our knowledge this is the first trial to selectively examine the addition of a targeted agent to chemotherapy in a clinically defined subset of upper GI cancers. No significant financial relationships to disclose.
Scientific Issues Relevant to Setting Regulatory Criteria to Identify Endocrine-Disrupting Substances in the European Union
Authors: Rémy Slama, Jean-Pierre Bourguignon, Barbara Demeneix, Richard Ivell, Giancarlo Panzica, Andreas Kortenkamp, R. Thomas Zoeller
Journal: Environmental Health Perspectives (2016)

Endocrine disruptors (EDs) are defined by the World Health Organization (WHO) as exogenous compounds or mixtures that alter function(s) of the endocrine system and consequently cause adverse effects in an intact organism, or its progeny, or (sub)populations. European regulations on pesticides, biocides, cosmetics, and industrial chemicals require the European Commission to establish scientific criteria to define EDs.
PTH-127 Nottingham-cambridge liver transplant (OLT) combined service evaluation
Authors: M Kasi, B Griffiths, A Butler, E Mowlem, S Smith, A Mierkalns, G Aithal, E Wilkes, M James
Journal: Gut (2015)

<h3>Introduction</h3> UK liver transplant centres frequently link with other tertiary liver centres to improve access for patient and secure a broader referral base, and is consistent with a “hub-and-spoke model” for liver services. Our aim is to evaluate outcomes from the Nottingham-Cambridge transplantation service. <h3>Method</h3> Nottingham-Cambridge outreach liver transplant service was established in 2010. We recorded demographics, disease aetiology, indication, time of referral and listing, UKELD, complications and 3-year survival following transplantation. Outcomes were compared to historical controls of published data from Addenbrooke’s transplant service. <h3>Results</h3> 106 patients were reviewed between 2010–2014. 18 patients (16.9%) received transplant at Addenbrooke’s prior to 2010, 88 (83%) were considered for transplant after 2010. There were 50 males (mean age 52 +/- 12.4 SD years) and 38 females (mean age 52.3 +/- 12.3 SD years). Aetiologies were alcoholic liver disease n = 30 (34%), hepatitis C n = 18 (20.5%), hepatitis B n = 4 (4.5%), autoimmune including PBC and PSC n = 15 (17%), metabolic n = 11 (12.5%), cryptogenic cirrhosis n = 4 (4.5%), paracetamol overdose n = 2 (2.2%) and biliary atresia, familial intrahepatic cholestasis, erythrohepatic porphyria and polycystic liver kidney disease each of n = 1 (1.1%). Chronic liver disease remains the main indication for transplant n = 73 (83%), acute liver failure and hepatocellular carcinoma each contributed to n = 6 (6.8%), graft failure of n = 3 (3.4%). Average time from referral to listing for transplant was 90 days and mean UKELD is 55. 42/88 (47.7%) received transplant, 9/88 (10.2%) patients are currently listed, 21/88 (23.8%) patients were deferred, 4 (4.5%) suspended once listed, 6 (6.8%) failed assessment for transplant, 1 undergoing assessment, 3 died while on waiting list and 2 died before assessment. Average time after listing to receive transplant was 136 days, compared to historical control of 135 days (95% CI 100–170; p=ns). 90-day graft and patient survivals were 97.6% and 95.2% compared to 93.5% (95% CI 84–96.6%; p=ns) and 95.1% (95% CI 86.1–98.7%; p=ns). Complications occurred in 16/42 transplanted; 2 deaths (4.8%), 4 (9.5%) anastomotic biliary strictures, 2 (13.3%) cholestatic hepatitis C, 2 (4.8%) depression and one each (2.4%) of hepatic artery thrombosis, splenic artery aneurysm, PRES-associated seizures, atypical cellular injury, recidivism and ongoing hepato-pulmonary syndrome. <h3>Conclusion</h3> The Nottingham-Cambridge satellite service has waiting times, survival outcomes comparable to Addenbrooke’s transplant unit outcomes and this support the extension of such collaboration throughout the UK. This requires close collaboration between clinical teams. <h3>Disclosure of interest</h3> None Declared.
Near‐Infrared‐Light‐Assisted Photothermal Polymerization for Transdermal Hydrogelation and Cell Delivery
Authors: Hwangjae Lee, Solchan Chung, Min‐Gon Kim, Luke P. Lee, Jae Young Lee
Journal: Advanced Healthcare Materials (2016)

Photopolymerization of hydrogels has been widely used to encapsulate cells and support their growth in 3D environments. However, common light sources (i.e., ultraviolet and visible light) strongly interact with biological systems and are therefore inappropriate for in vivo applications, such as transdermal polymerization. Using near infrared (NIR) light that minimally interacts with living tissues, this study investigates NIR light-assisted photothermal polymerization (NAPP) of diacrylated polyethylene glycol (PEGDA), in which interactions between NIR light and gold nanorods activate a thermal initiator (i.e., AIPH), resulting in generation of radicals for polymerization of PEGDA. Gelation parameters, including precursor concentrations and NIR power, are investigated to minimize the use of initiator and temperature increases (<43 °C) during NAPP. Cell viability is as high as 80% after NAPP-based encapsulation. Incorporation of polyethylene glycol (PEG) modified with a cell-adhesive peptide moiety (Arg-Gly-Asp) into the gel system further enables prolongation of cell viability during incubation up to 7 d. NAPP results in successful transdermal gelation and good viability of the transplanted cells. Thus, this new cell encapsulation approach, demonstrated for the first time in this study, will benefit various applications, including cell delivery and remote control over cellular environments.
Older people need an individualised approach to treating hypertension
Authors: Sean G Ninan
Journal: BMJ (2016)

It is disappointing that an article on treating hypertension in patients with comorbidities does not mention frailty.1 While the authors point out that optimum blood pressure targets for older people are unclear, they quote National Institute for Health and Care Excellence guidance recommending a target blood pressure below 150/90 mm Hg as if a “one size fits all” approach is appropriate. Older people need an individualised approach. Although many …
Pressure sores
Authors: J. Kulkarni
Journal: BMJ (1994)

Pressure soresNot considered a priority by medical staff EDrrOR,-R K Vohra and C N McCollum's review of pressure sores is a timely reminder of the continuing silent epidemic of pressure sores both in hospital and in the community.'Pressure sores impose two main penalties, financial and human.The financial costs are high and result from additional treatment, a prolonged stay in hospital, and a further demand on clinic (nursing) time.Prevention of pressure sores is based on constant vigilance and early action, with awareness being the keynote of success.A colleague and I conducted a detailed survey with a semistructured questionnaire in a university teaching hospital; medical staff responded poorly to the questionnaire because pressure sores were not considered to be a priority.2Only about a quarter of medical staff routinely assessed patients with regard to their risk of pressure sores, though most nursing and therapy staff performed routine assessments.Hospital staff other than nursing staff were unaware of any protocols for assessing pres- sure sores.Most of the respondents thought that the cost of treating an inpatient with a pressure sore was less than £;1000; this indicates their unaware- ness of the true cost.It is prudent to apply low technology early rather than high technology at a later stage.If equipment is required it should be compatible with existing equipment, and unless costs are realistic the strategy is doomed to failure.
Quantitative Laughter Detection, Measurement, and Classification—A Critical Survey
Authors: Sarah Cosentino, Salvatore Sessa, Atsuo Takanishi
Journal: IEEE Reviews in Biomedical Engineering (2016)

The study of human nonverbal social behaviors has taken a more quantitative and computational approach in recent years due to the development of smart interfaces and virtual agents or robots able to interact socially. One of the most interesting nonverbal social behaviors, producing a characteristic vocal signal, is laughing. Laughter is produced in several different situations: in response to external physical, cognitive, or emotional stimuli; to negotiate social interactions; and also, pathologically, as a consequence of neural damage. For this reason, laughter has attracted researchers from many disciplines. A consequence of this multidisciplinarity is the absence of a holistic vision of this complex behavior: the methods of analysis and classification of laughter, as well as the terminology used, are heterogeneous; the findings sometimes contradictory and poorly documented. This survey aims at collecting and presenting objective measurement methods and results from a variety of different studies in different fields, to contribute to build a unified model and taxonomy of laughter. This could be successfully used for advances in several fields, from artificial intelligence and human-robot interaction to medicine and psychiatry.
Involvement of Transcription Factor Encoded by the Mouse mi Locus (MITF ) in Expression of p75 Receptor of Nerve Growth Factor in Cultured Mast Cells of Mice
Authors: Tomoko Jippo, Eiichi Morii, Kumiko Tsujino, Tohru Tsujimura, Young-Mi Lee, Dae-Ki Kim, Hiroshi Matsuda, Hyung-Min Kim, Yukihiko Kitamura
Journal: Blood (1997)
Massive Periaortic and Periarterial Fibrosis
Authors: W. Glenn Reed, Regis W. Stinely
Journal: New England Journal of Medicine (1959)

FIBROUS tissue has a very wide distribution throughout the body, forming supporting structures such as fascia, tendons and ligaments. It makes up the stroma of organs as well as that of benign and malignant tumors. It has a vital role in inflammation and repair.1 Because of the ubiquity of fibrous tissue, the differentiation of its neoplasms from inflammatory or degenerative changes is sometimes difficult. In the case presented below a fibrous mass lying retroperitoneally and around coronary arteries defied exact classification.Case ReportA 56-year-old man, about 7 months before admission to the hospital, on March 16, 1954, had begun . . .
TCTAP A-003 Two Years Results Following Bioresorbable Vascular Scaffold Implantation in ST-Segment Elevation Myocardial Infarction Patients
Authors: Alfonso Ielasi, Bernardo Cortese Cortese, Attilio Varricchio, Maurizio Tespili, Giuseppe Steffenino
Journal: Journal of the American College of Cardiology (2016)
Antibody against Serum-Hepatitis Antigen
Authors: Alfred M. Prince, Wolf Szmuness, Kenneth R. Woods, George F. Grady
Journal: New England Journal of Medicine (1971)

Abstract The passive hemagglutination method was used to evaluate serum-hepatitis (SH, Australia/ HAA) antibody content of conventional, convalescent and hyperimmune gamma-globulin preparations.  antibody was detected at low titer in most batches of conventional gamma  (less than 1:2 to 1:64), in contrast to a titer of 1:512,000 in gamma  prepared from hemophilic plasma containing known precipitating antibody (SH immune globulin). Injection of SH immune globulin resulted in the appearance of  antibody that remained detectable for at least two months in the blood of half of the recipients. A study of the distribution of antibody titers in volunteer and paid blood donors showed that  antibody was 10 times more frequent among paid donors. Antibody levels in these populations were generally quite low in comparison to those present in patients with hemophilia. Cautious clinical investigation is required before SH immune globulin can be accepted for use in prevention, modification ...
TCTAP A-143 Calcification Predominantly Progressed in In-Stent Segment Compared with Non-Stented Segment in Target Vessel over a Decade After Bare-Metal Stent Implantation
Authors: Takahiro Watanabe, Kazuhiko Yumoto, Shota Ikeda, Yuichi Hanaki, Tomoyuki Fukuzawa, Shingo Tanaka, Hajime Aoki
Journal: Journal of the American College of Cardiology (2016)
Hysteroscopy before in-vitro fertilisation (inSIGHT): a multicentre, randomised controlled trial
Authors: Janine G Smit, Jenneke C Kasius, Marinus J C Eijkemans, Carolien A M Koks, Ronald van Golde, Annemiek W Nap, Gabrielle J Scheffer, Petra A P Manger, Annemieke Hoek, Benedictus C Schoot, Arne M van Heusden, Walter K H Kuchenbecker, Denise A M Perquin, Kathrin Fleischer, Eugenie M Kaaijk, Alexander Sluijmer, Jaap Friederich, Ramon H M Dykgraaf, Marcel van Hooff, Leonie A Louwe, Janet Kwee, Corry H de Koning, Ineke C A H Janssen, Femke Mol, Ben W J Mol, Frank J M Broekmans, Helen L Torrance
Journal: The Lancet (2016)
Retracted: Multifunctional Polymeric Nanosystems for Dual‐Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors
Authors: Fatima Zohra Dahmani, Yan Xiao, Juan Zhang, Yao Yu, Jianping Zhou, Jing Yao
Journal: Advanced Healthcare Materials (2016)

Combination of antiangiogenesis and chemotherapy holds vast promise for effective inhibition of tumor proliferation and invasion. Herein, a multifunctional self-assembled nanosystem consisting of amphiphilic c(RGDyK)-functionalized low-molecular-weight heparin-gambogic acid conjugate (cRHG) is developed, using c(RGDyK) peptide as αv β3 integrin targeting moiety to realize a double-targeted delivery to both tumor cells and angiogenic vasculature. cRHG with a markedly decreased anticoagulant activity can self-assemble into nanosized particles (around 150 nm). cRHG nanoparticles effectively inhibit vascular endothelial growth factor (VEGF)-triggered tube-like formation of HUVEC and neovascularization of subcutaneous Matrigel plugs. More importantly, the targeting ability of cRHG nanoparticles is revealed by their efficient internalization by αv β3 integrin-positive cells (U87MG and HUVEC) in vitro and obvious accumulation of Cy7/cRHG in the tumor site with strong fluorescence signals in both cancer cells and neovasculature. Besides, cRHG maintains the in vitro cytotoxic activity of gambogic acid, while achieving the highest in vivo antitumor activity in U87MG mouse xenograft model and displaying better safety profile than free drugs solutions. Mechanistic investigations reveal the substantial inhibition of hypoxia-inducible factor-1 alpha, VEGF, and CD31 expression by cRHG nanoparticles with remarkable down-regulation of VEGFR2 phosphorylation. These results suggest that cRHG nanoparticles provide a versatile nanoplatform for efficacious combinatorial tumor therapy.
Abstract 2974: Midterm Results Of Resynchronization Therapy In Pediatrics: Do We Need New Guidelines?
Authors: Anne M Dubin, Kathryn K Collins, George F Van Hare, V. M Reddy, Debra Hanisch, Nancy Chiesa, David N Rosenthal
Journal: Circulation (2007)

Cardiac resynchronization therapy (CRT) is an accepted therapy for adults with dilated cardiomyopathy (DCM) and has been shown to improve ejection fraction and functional capacity. CRT has been used in children for over 4 years with a variety of indications which differ substantially from those commonly used for adult patients. We reviewed the results of CRT in the combined Stanford-UCSF pediatric electrophysiology program over the past 4 years, in order to evaluate efficacy of CRT in different clinical scenarios. We have provided CRT to 31 patients (15 female) between 2003 and 2007. The mean age at implantation was 7.3 ± 6.6 years. 21 patients had congenital heart disease (CHD) of whom 4 had single ventricle physiology. 5 patients had DCM and 5 had congenital complete heart block with reduced LV systolic function (CCHB). All patients with DCM met criteria for CRT in adults (QRS duration &lt; 120 msec and EF &gt; 35%). Implantation in the other patient groups was performed at the discretion of the physician. Mean follow-up was 26 ± 15 months. Ejection Fraction (EF), by echo, was 30 ± 11% at baseline which improved to 41 ± 19% at last follow-up (p &lt; 0.05). EF as well as LV end diastolic volume and LV end systolic volume showed immediate improvement followed by additional continued improvement over the study period. CHD and CCHB patients reported improved symptoms and had improved cardiac indices by echo. DCM patients, however, showed no improvement and instead had a gradual decrease in ejection fraction over the study period (30 ± 11% to 18 ± 11%, p&lt; 0.01). Two of the 5 DCM patients were transplanted, and one died of pump failure. Conclusions: CRT is efficacious in selected patients with congenital heart disease, or those with congenital complete heart block. The role of CRT in pediatric patients with dilated cardiomyopathy is less clear, but adult selection criteria may not be applicable to children. Comparison of EF preCRT and at last follow-up
Effects of Noise Exposure on Systemic and Tissue-Level Markers of Glucose Homeostasis and Insulin Resistance in Male Mice
Authors: Lijie Liu, Fanfan Wang, Haiying Lu, Shuangfeng Cao, Ziwei Du, Yongfang Wang, Xian Feng, Ye Gao, Mingming Zha, Min Guo, Zilin Sun, Jian Wang
Journal: Environmental Health Perspectives (2016)

Epidemiological studies have indicated that noise exposure is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the nature of the connection between noise exposure and T2DM remains to be explored.We explored whether and how noise exposure affects glucose homeostasis in mice as the initial step toward T2DM development.Male ICR mice were randomly assigned to one of four groups: the control group and three noise groups (N20D, N10D, and N1D), in which the animals were exposed to white noise at 95 decibel sound pressure level (dB SPL) for 4 hr per day for 20 successive days, 10 successive days, or 1 day, respectively. Glucose tolerance and insulin sensitivity were evaluated 1 day, 1 week, and 1 month after the final noise exposure (1DPN, 1WPN, and 1MPN). Standard immunoblots, immunohistochemical methods, and enzyme-linked immunosorbent assays (ELISA) were performed to assess insulin signaling in skeletal muscle, the morphology of β cells, and plasma corticosterone levels.Noise exposure for 1 day caused transient glucose intolerance and insulin resistance, whereas noise exposure for 10 and 20 days had no effect on glucose tolerance but did cause prolonged insulin resistance and an increased insulin response to glucose challenge. Akt phosphorylation and GLUT4 translocation in response to exogenous insulin were decreased in the skeletal muscle of noise-exposed animals.Noise exposure at 95 dB SPL caused insulin resistance in male ICR mice, which was prolonged with longer noise exposure and was likely related to the observed blunted insulin signaling in skeletal muscle.Liu L, Wang F, Lu H, Cao S, Du Z, Wang Y, Feng X, Gao Y, Zha M, Guo M, Sun Z, Wang J. 2016. Effects of noise exposure on systemic and tissue-level markers of glucose homeostasis and insulin resistance in male mice. Environ Health Perspect 124:1390-1398; http://dx.doi.org/10.1289/EHP162.
Case 8-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, C. Trey, A.K. Bhan
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 47-year-old man was admitted to the hospital for liver transplantation because of severe hepatic failure.The patient was in a good general state of health until approximately six weeks earlier, when painless jaundice developed. Laboratory studies showed that the bilirubin was 150 μmol per liter (8.9 mg per 100 ml) and the serum aspartate aminotransferase (ASAT) 1147 U per liter. An abdominal ultrasonographic examination was reported to show no dilatation of the bile ducts and no evidence of an intra-hepatic mass; marked splenomegaly was present, without ascites.Three weeks later the patient was admitted to another . . .
E-cigarettes are a “gateway from smoking,” RCP concludes
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Smokers should be actively encouraged to swap their tobacco cigarettes for electronic cigarettes because “vaping” is much safer than smoking and is likely to benefit UK public health, a report from the Royal College of Physicians (RCP) says.1

Since e-cigarettes became available in the United Kingdom in 2007 their use has been surrounded in controversy. The 206 page report, Nicotine without Smoke: Tobacco Harm Reduction , examined evidence on the science, public policy, regulation, and ethics surrounding e-cigarettes.

The report concluded that the use of e-cigarettes is likely to lead to attempts to quit that would not otherwise have …
Development of bioactive materials for glioblastoma therapy
Authors: Jun Yang, Yan Li, Tianlu Zhang, Xin Zhang
Journal: Bioactive Materials (2016)

Glioblastoma is the most common and deadly human brain cancers. Unique barriers hinder the drug delivering pathway due to the individual position of glioblastoma, including blood-brain barrier and blood-brain tumor barrier. Numerous bioactive materials have been exploited and applied as the transvascular delivery carriers of therapeutic drugs. They promote site-specific accumulation and long term release of the encapsulated drugs at the tumor sites and reduce side effects with systemic delivery. And the delivery systems exhibit a certain extent of anti-glioblastoma effect and extend the median survival time. However, few of them step into the clinical trials. In this review, we will investigate the recent studies of bioactive materials for glioblastoma chemotherapy, including the inorganic materials, lipids and polymers. These bioactive materials construct diverse delivery vehicles to trigger tumor sites in brain intravenously. Herein, we exploit their functionality in drug delivery and discuss the deficiency for the featured tumors, to provide guidance for establishing optimized therapeutic drug formulation for anti-glioblastoma therapy and pave the way for clinical application.