tbuckley/cabot-search huggingface dataset:
HER2-Specific T-Cell Immune Responses in Patients Vaccinated with Truncated HER2 Protein Complexed with Nanogels of Cholesteryl Pullulan
Authors: Shigehisa Kitano, Shinichi Kageyama, Yasuhiro Nagata, Yoshihiro Miyahara, Atsunori Hiasa, Hiroaki Naota, Satoshi Okumura, Hiroshi Imai, Taizo Shiraishi, Masahiro Masuya, Masakatsu Nishikawa, Junzo Sunamoto, Kazunari Akiyoshi, Takashi Kanematsu, Andrew M. Scott, Roger Murphy, Eric W. Hoffman, Lloyd J. Old, Hiroshi Shiku
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We developed a complex of tumor antigen protein with a novel nanoparticle antigen delivery system of cholesteryl pullulan (CHP). To target HER2 antigen, we prepared truncated HER2 protein 1-146 (146HER2) complexed with CHP, the CHP-HER2 vaccine. We designed a clinical study to assess the safety of the vaccine and HER2-specific T-cell immune responses measured by the newly developed enzyme-linked immunospot assay with mRNA-transduced phytohemagglutinin-stimulated CD4+ T cells in HLA-A2402-positive patients with therapy-refractory HER2-expressing cancers. Experimental Design: Nine patients with various types of solid tumors were enrolled. Each patient was s.c. vaccinated biweekly with 300 μg of CHP-HER2 vaccine for three times followed by booster doses. HER2-specific T-cell responses were evaluated by enzyme-linked immunospot assay by targeting autologous phytohemagglutinin-stimulated CD4+ T cells transduced with 146HER2-encoding mRNA to cover both identified peptides and unknown epitopes for MHC class I and class II that might exist in the sequence of the vaccine protein. Results: CHP-HER2 vaccine was well tolerated; the only adverse effect was grade 1 transient skin reaction at the sites of vaccination. HER2-specific CD8+ and/or CD4+ T-cell immune responses were detected in five patients who received four to eight vaccinations, among whom both T-cell responses were detected in these patients. In four patients with CD8+ T-cell responses, two patients reacted to previously identified HER263-71 peptide and the other two reacted only to 146HER2 mRNA-transduced cells. Conclusions: CHP-HER2 vaccine was safe and induced HER2-specific CD8+ and/or CD4+ T-cell immune responses.
Deaths among humanitarian workers
Authors: M. Sheik
Journal: BMJ (2000)

The nature of humanitarian relief has changed dramatically in the past decade as conflicts have ceased being wars between states and are now largely internal conflict taking place amid the anarchy of weakened or collapsed states.1 Increasingly, civilians and those who try to protect and assist them are seen as legitimate targets for extortion, harassment, rape, and brutality.2 Providing assistance while protecting the providers is the dilemma facing all international aid organisations. 3 4 To gain a better understanding of deaths in this group, we analysed 382 deaths in humanitarian workers between 1985 and 1998.

Most humanitarian organisations believe that the number of deaths among relief workers has been increasing.5 Although data exist for deaths among development workers, Peace Corps volunteers, and other expatriates, there have been no data on deaths among humanitarian workers.6–9

#### Summary points

Wars between states have been largely replaced by internal conflict and anarchy, which have put the lives of civilians and humanitarian workers at ever increasing risk

Between 1985 and 1998 nearly a half of deaths traced were in workers from UN programmes, and a quarter were in UN peacekeepers

Most deaths were due to intentional violence (guns or other weapons), many associated with banditry

One third of deaths occurred in the first 90 days of service, with 17% dying within the first 30 days; the timing of death was unrelated to previous field experience

The number of deaths peaked with the Rwanda crisis in 1994 and has been decreasing for all groups except for non-governmental organisations, where it continues to increase

We collected information from the records of aid agencies and organisations. We included any death between 1985 and 1998 occurring in workers in the field or as a result of them having worked in the field during emergency or …
Abnormal autonomic stress responses in obstructive sleep apnoea are reversed by nasal continuous positive airway pressure
Authors: D Veale, JL Pepin, B Wuyam, PA Levy
Journal: European Respiratory Journal (1996)

Obstructive sleep apnoea (OSA) is associated with abnormalities in autonomic stress tests, which are tests of cardiovascular response in the autonomic nervous system (ANS). The level of abnormality has been related to the level of overnight arterial oxygen saturation (Sa,O2). We have studied ANS function pre- and post-treatment with nasal continuous positive airway pressure (nCPAP) in six males with moderately severe or severe OSA (apnoea/hypopnoea index (AHI) median 51 (range 14-74 events.h-1 of sleep). Tests consisted of heart rate responses to Valsalva manoeuvre, deep breathing, and change of posture from lying to standing. In addition, systolic blood pressure (SBP) response to standing and diastolic blood pressure (DBP) response to handgrip were studied. Each abnormal test (compared to published normal values) scored +1.0 and each marginal test result (90-95% confidence interval for normals) scored +0.5. A total score was calculated for the five tests performed in the evening and morning (maximum score 10 per patient). Patients had been receiving treatment for more than 1 year (median 471 (389-624) days) and objective compliance was monitored by a clock counter in the nCPAP machines. Five of six patients had regularly used nCPAP (mean 7.8 h.night-1) and all showed a normalization in ANS test score: pre-nCPAP 2 (1-4.5), post-nCPAP 0.2 (0-0.5) (p &lt; 0.05, Wilcoxon signed rank test). One poorly compliant subject (No. 6; nCPAP 3 h.night-1) had a deterioration in ANS test score: 1 pre-nCPAP to 1.5 post-nCPAP. The improvement in ANS test score in the five compliant patients was positively correlated with an improvement in mean Sa,O2 during sleep posttreatment. We conclude that successful treatment of obstructive sleep apnoea leads to normalization of impaired autonomic stress responses.
Antagonism of Platelet-Derived Growth Factor Receptor in Non–Small Cell Lung Cancer: Rationale and Investigations
Authors: Julie E. Bauman, Keith D. Eaton, Renato G. Martins
Journal: Clinical Cancer Research (2007)

Abstract Molecules that target growth and survival pathways in cancer cells have revolutionized the treatment of cancer. Imatinib mesylate is one such agent inhibiting the tyrosine kinase that results from the Bcr-Abl translocation. Imatinib is also a potent inhibitor of the platelet-derived growth factor receptor. The platelet-derived growth factor receptor is crucial in the regulation of interstitial fluid pressure, as well as in the function of pericytes. Increased interstitial fluid pressure is a common feature of solid tumors and is thought to impede transcapillary transport of chemotherapy. Preclinical data show that platelet-derived growth factor receptor antagonism decreases interstitial fluid pressure, augments intratumoral concentration of chemotherapy, and impairs tumor growth. Pericytes are important cells in the vascular support structure of tumors regulating endothelial cell survival and directing capillary growth. Preclinical data suggest that dual targeting of pericytes and endothelial cells is a more effective antiangiogenic strategy than antiendothelial monotherapy. Two phase II studies in advanced non–small cell lung cancer are currently under way with imatinib. The first trial evaluates the use of intermittent imatinib and weekly paclitaxel in elderly patients. The second trial evaluates a novel maintenance strategy of imatinib and the antivascular endothelial growth factor antibody bevacizumab after first-line chemotherapy with bevacizumab. These trials should indicate whether encouraging preclinical data can be translated into clinical benefit in non–small cell lung cancer.
What Have We Learned About Interventions to Reduce Medical Errors?
Authors: Helen I. Woodward, Oliver T. Mytton, Claire Lemer, Iain E. Yardley, Benjamin M. Ellis, Paul D. Rutter, Felix E.C. Greaves, Douglas J. Noble, Edward Kelley, Albert W. Wu
Journal: Annual Review of Public Health (2010)

Medical errors and adverse events are now recognized as major threats to both individual and public health worldwide. This review provides a broad perspective on major effective, established, or promising strategies to reduce medical errors and harm. Initiatives to improve safety can be conceptualized as a “safety onion” with layers of protection, depending on their degree of remove from the patient. Interventions discussed include those applied at the levels of the patient (patient engagement and disclosure), the caregiver (education, teamwork, and checklists), the local workplace (culture and workplace changes), and the system (information technology and incident reporting systems). Promising interventions include forcing functions, computerized prescriber order entry with decision support, checklists, standardized handoffs and simulation training. Many of the interventions described still lack strong evidence of benefit, but this should not hold back implementation. Rather, it should spur innovation accompanied by evaluation and publication to share the results.
Paediatrics in Berlin
Authors: A. Barbato, F. Bertuola, C. Kuehni, M. Korppi, S. Kotecha, M. W. Pijnenburg, F. Ratjen, P. Seddon, A. Bush
Journal: European Respiratory Journal (2009)

The aim of this report is to describe the highlights of the European Respiratory Society annual congress in Berlin, Germany. The best abstracts in asthma and allergy, cystic fibrosis, respiratory infection, paediatric and neonatal intensive care, paediatric investigative techniques (in particular respiratory physiology and bronchoscopy) and respiratory epidemiology are presented and set in the context of the current literature.
Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor–based orthotopic xenograft mouse models of pediatric glioma
Authors: Zhigang Liu, Xiumei Zhao, Hua Mao, Patricia A. Baxter, Yulun Huang, Litian Yu, Lalita Wadhwa, Jack M. Su, Adekunle Adesina, Lazlo Perlaky, Mary Hurwitz, Neeraja Idamakanti, Seshidhar Reddy Police, Paul L. Hallenbeck, Richard L. Hurwitz, Ching C. Lau, Murali Chintagumpala, Susan M. Blaney, Xiao-Nan Li
Journal: Neuro-Oncology (2013)

Seneca Valley virus (SVV-001) is a nonpathogenic oncolytic virus that can be systemically administered and can pass through the blood-brain barrier. We examined its therapeutic efficacy and the mechanism of tumor cell infection in pediatric malignant gliomas.In vitro antitumor activities were examined in primary cultures, preformed neurospheres, and self-renewing glioma cells derived from 6 patient tumor orthotopic xenograft mouse models (1 anaplastic astrocytoma and 5 GBM). In vivo therapeutic efficacy was examined by systemic treatment of preformed xenografts in 3 permissive and 2 resistant models. The functional role of sialic acid in mediating SVV-001 infection was investigated using neuraminidase and lectins that cleave or competitively bind to linkage-specific sialic acids.SVV-001 at a multiplicity of infection of 0.5 to 25 replicated in and effectively killed primary cultures, preformed neurospheres, and self-renewing stemlike single glioma cells derived from 4 of the 6 glioma models in vitro. A single i.v. injection of SVV-001 (5 × 10(12) viral particles/kg) led to the infection of orthotopic xenografts without harming normal mouse brain cells, resulting in significantly prolonged survival in all 3 permissive and 1 resistant mouse models (P < .05). Treatment with neuraminidase and competitive binding using lectins specific for α2,3-linked and/or α2,6-linked sialic acid significantly suppressed SVV-001 infectivity (P < .01).SVV-001 possesses strong antitumor activity against pediatric malignant gliomas and utilizes α2,3-linked and α2,6-linked sialic acids as mediators of tumor cell infection. Our findings support the consideration of SVV-001 for clinical trials in children with malignant glioma.
Update on the Methods of the U.S. Preventive Services Task Force: Estimating Certainty and Magnitude of Net Benefit
Authors: George F. Sawaya, Janelle Guirguis-Blake, Michael LeFevre, Russell Harris, Diana Petitti
Journal: Annals of Internal Medicine (2007)

The major goal of the U.S. Preventive Services Task Force (USPSTF) is to provide a reliable and accurate source of evidence-based recommendations on a wide range of preventive services. In this article, the USPSTF updates and reviews the process by which it evaluates evidence, determines the certainty and magnitude of net benefit, and gives a final letter grade to recommendations. Because direct evidence about prevention is often unavailable, the Task Force usually considers indirect evidence. To guide its selection of indirect evidence, a “chain of evidence” is constructed within an analytic framework. The Task Force examines evidence of various research designs that addresses the key questions within the framework. New terms have been added to describe the USPSTF's judgment about the evidence for each key question: “convincing,” “adequate,” or “inadequate.” For increased clarity, the USPSTF has changed its description of overall evidence of net benefit for the preventive service from “good,” “fair,” or “poor” quality to “high,” “moderate,” or “low” certainty. This rating considers the extent to which an uninterrupted chain of evidence exists across the analytic framework. Individual studies will continue to be judged as being of “good,” “fair,” or “poor” quality. Using outcomes tables, the USPSTF estimates the magnitude of benefits and the magnitude of harms, and synthesizes them into an estimate of the magnitude of net benefit. Although some judgment is required at all steps, the USPSTF strives to make the process as explicit and transparent as possible. The USPSTF anticipates that its methods for making evidence-based recommendations will continue to evolve.
Hypoglycemia and Clinical Outcomes in Patients With Diabetes Hospitalized in the General Ward
Authors: Alexander Turchin, Michael E. Matheny, Maria Shubina, James V. Scanlon, Bonnie Greenwood, Merri L. Pendergrass
Journal: Diabetes Care (2009)

Hypoglycemia is associated with adverse outcomes in mixed populations of patients in intensive care units. It is not known whether the same risks exist for diabetic patients who are less severely ill. In this study, we aimed to determine whether hypoglycemic episodes are associated with higher mortality in diabetic patients hospitalized in the general ward.This retrospective cohort study analyzed 4,368 admissions of 2,582 patients with diabetes hospitalized in the general ward of a teaching hospital between January 2003 and August 2004. The associations between the number and severity of hypoglycemic (<or=50 mg/dl) episodes and inpatient mortality, length of stay (LOS), and mortality within 1 year after discharge were evaluated.Hypoglycemia was observed in 7.7% of admissions. In multivariable analysis, each additional day with hypoglycemia was associated with an increase of 85.3% in the odds of inpatient death (P = 0.009) and 65.8% (P = 0.0003) in the odds of death within 1 year from discharge. The odds of inpatient death also rose threefold for every 10 mg/dl decrease in the lowest blood glucose during hospitalization (P = 0.0058). LOS increased by 2.5 days for each day with hypoglycemia (P < 0.0001).Hypoglycemia is common in diabetic patients hospitalized in the general ward. Patients with hypoglycemia have increased LOS and higher mortality both during and after admission. Measures should be undertaken to decrease the frequency of hypoglycemia in this high-risk patient population.
Inherited Diseases Involving G Proteins and G Protein–Coupled Receptors
Authors: Allen M. Spiegel, Lee S. Weinstein
Journal: Annual Review of Medicine (2004)

Heterotrimeric G proteins couple seven-transmembrane receptors for diverse extracellular signals to effectors that generate intracellular signals altering cell function. Mutations in the gene encoding the alpha subunit of the G protein-coupling receptors to stimulation of adenylyl cyclase cause developmental abnormalities of bone, as well as hormone resistance (pseudohypoparathyroidism caused by loss-of-function mutations) and hormone hypersecretion (McCune-Albright syndrome caused by gain-of-function mutations). Loss- and gain-of-function mutations in genes encoding G protein-coupled receptors (GPCRs) have been identified as the cause of an increasing number of retinal, endocrine, metabolic, and developmental disorders. GPCRs comprise an evolutionarily conserved gene superfamily ( 1 ). By coupling to heterotrimeric G proteins, GPCRs transduce a wide variety of extracellular signals including monoamine, amino acid, and nucleoside neurotransmitters, as well as photons, chemical odorants, divalent cations, hormones, lipids, peptides and proteins. Following a brief overview of G protein-coupled signal transduction, we review the growing body of evidence that mutations in genes encoding GPCRs and G proteins are an important cause of human disease.
Endothelial Replacement and Angiogenesis in Arteriosclerotic Lesions of Allografts Are Contributed by Circulating Progenitor Cells
Authors: Yanhua Hu, Fergus Davison, Zhongyi Zhang, Qingbo Xu
Journal: Circulation (2003)

Endothelial regeneration and angiogenesis in the intima of the arterial wall are key events in the pathogenesis of transplantation arteriosclerosis. The traditional hypothesis that damaged endothelial cells are replaced by remaining cells of the donor vessel has been challenged by recent observations, but the cell origins of large arteries and microvessels are still not well established.Aortic segments were allografted between Balb/c and TIE2-LacZ (C57BL/6) mice expressing beta-galactosidase (gal) in endothelial cells. beta-gal+ cells in TIE2-LacZ vessels grafted to Balb/c mice completely disappeared, whereas the positive cells found in Balb/c aorta allografted into TIE2-LacZ mice 4 weeks after surgery indicated a host origin. En face analysis of allograft vessels displayed a unique distribution of beta-gal+ cells on the surface at 3 days, 1 week, and 4 weeks. Interestingly, 35+/-19% beta-gal+ cells were found in arterial segments allografted into chimeric mice with TIE2-LacZ bone marrows. Furthermore, endothelial cells of microvessels within allografts had a beta-gal+ staining in the media at 1 week and in the neointimal lesions and adventitia at 4 weeks. Allograft studies in chimeric mice demonstrated that beta-gal+ cells of microvessels in transplant arteriosclerosis were derived from bone marrow progenitors.We provide strong evidence that endothelial cells of neointimal lesions in allografts are derived from circulating progenitor cells and that bone marrow-derived progenitors are responsible for angiogenesis of the allograft, that is, the formation of microvessels in transplant arteriosclerosis.
Randomized, Single-Blind, Controlled Trial of a Specialist Behavior Therapy Team for Challenging Behavior in Adults With Intellectual Disabilities
Authors: Angela Hassiotis, Dan Robotham, Anton Canagasabey, Renee Romeo, Diane Langridge, Robert Blizard, Shahed Murad, Michael King
Journal: American Journal of Psychiatry (2009)

Community-based specialist behavior therapy teams may be helpful in managing challenging behavior, but evidence of their effectiveness is limited. This study was designed to examine the effectiveness and costs associated with treatment by a specialist behavior therapy team.This was a parallel-group, randomized, single-blind controlled trial carried out in an intellectual disabilities service in England. Participants were 63 male and female service users with mild to severe intellectual disability who presented with challenging behavior. The interventions were standard treatment plus applied behavioral analysis (N=32) and standard treatment only (N=31). The primary outcome measure was challenging behavior, as measured by total and subscale scores on the Aberrant Behavior Checklist 3 and 6 months after randomization. Secondary outcome measures were psychiatric comorbidity assessed at 3 and 6 months using the Psychiatric Assessment Schedule for Adults With a Developmental Disability Checklist (PAS-ADD) and total costs recorded at 6 months. Multilevel modeling was used to compare square root transformations of Aberrant Behavior Checklist scores.Significant differences were found in the transformed total scores on the Aberrant Behavior Checklist (difference=-0.89, 95% CI=-1.74 to -0.04) and transformed lethargy and hyperactivity subscale scores (common intervention effect=-0.56, 95% CI=-0.97 to -0.15). Standard care participants fared worse on the PAS-ADD comorbid organic disorder subscale. There was a clear trend for lower overall costs of the intervention.Use of a specialist behavior therapy team in addition to standard treatment appears to be more effective in improving challenging behavior and may have financial advantages over standard treatment.
Effects of hyperlipoproteinemias and their treatment on the peripheral circulation
Authors: Robert Zelis, Dean T. Mason, Eugene Braunwald, Robert I. Levy
Journal: Journal of Clinical Investigation (1970)

The purpose of this study was to determine the effect of familial hyperlipoproteinemia (HLP) on peripheral vascular disease (PVD) and the extent to which the vascular disease (PVD) and the extent to which the vascular disease is modified by treatment of the lipoprotein disorder. PVD was detected plethysmographically by observing a diminished peak reactive hyperemia blood (PRHBF) following ischemia. The value for PRHBF in the extremity demonstrating the lowest response in 32 normal subjects (age 19-50 yr) was 39.6+/-1.5 SEM, ml/min per 100 g. Patients with untreated HLP. who had PRHBF below the lower limit of normal, were 2 of 11 type II, 9 of 12 type III, 1 of 10 type IV. As a group, patients with type III HLP showed diminished PRHBF (26.6 +/-3.0 ml/min per 100 g, P <0.01). In view of the high incidence of PVD and the striking reduction in serum lipids and complete resorption of xanthomas observed in type III HLP with therapy, six patients were studied before and after 3-6 months of treatment with a therapeutic diet and clofibrate. PRHBF in the most severely affected extremity increased markedly, from 20.4 +/-1.6 to 31.9 +/-1.8 ml/min per 100 g (P<0.01), indicating a dramatic increase in maximum blood flow to this extremity. In two type III patients with PVD not treated, no change in PRHBF occurred over 5 months. In two other type III patients the PRHBF increased 17% during the first 25 days of therapy concomitant with a 30% reduction in whole blood viscosity. Over the next 120 days, blood viscosity decreased only an additional 4.6% whereas the PRHBF increased 57%, indicating that the observed changes seen in the PRHBF with therapy of type III patients can be only minimally accounted for by changes in the viscosity of the blood. Thus, patients with type III HLP are particularly susceptible to the development of PVD and objective improvement of PVD can occur with medical treatment of this lipid transport disorder.
Surgical Innovations Arising from the Iraq and Afghanistan Wars
Authors: Geoffrey S.F. Ling, Peter Rhee, James M. Ecklund
Journal: Annual Review of Medicine (2010)

The delivery of combat casualty care poses numerous challenges including austere conditions, limited supplies and medical personnel, and multiple simultaneous patients. However, the exigent circumstances of the battlefield compel the development of research and the advancement of adaptive, practical medical technologies to support and sustain military health. In Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), modern changes in medical management, coupled with improved protective gear and evacuation capabilities, have facilitated the highest survival rate in combat history.