tbuckley/cabot-search huggingface dataset:
Basic or enhanced clinician training to improve adherence to malaria treatment guidelines: a cluster-randomised trial in two areas of Cameroon
Authors: Wilfred F Mbacham, Lindsay Mangham-Jefferies, Bonnie Cundill, Olivia A Achonduh, Clare I R Chandler, Joel N Ambebila, Armand Nkwescheu, Dorothy Forsah-Achu, Victor Ndiforchu, Odile Tchekountouo, Mbuh Akindeh-Nji, Pierre Ongolo-Zogo, Virginia Wiseman
Journal: The Lancet Global Health (2014)

The scale-up of malaria rapid diagnostic tests (RDTs) is intended to improve case management of fever and targeting of artemisinin-based combination therapy. Habitual presumptive treatment has hampered these intentions, suggesting a need for strategies to support behaviour change. We aimed to assess the introduction of RDTs when packaged with basic or enhanced clinician training interventions in Cameroon.We did a three-arm, stratified, cluster-randomised trial at 46 public and mission health facilities at two study sites in Cameroon to compare three approaches to malaria diagnosis. Facilities were randomly assigned by a computer program in a 9:19:19 ratio to current practice with microscopy (widely available, used as a control group); RDTs with a basic (1 day) clinician training intervention; or RDTs with an enhanced (3 days) clinician training intervention. Patients (or their carers) and fieldworkers who administered surveys to obtain outcome data were masked to study group assignment. The primary outcome was the proportion of patients treated in accordance with WHO malaria treatment guidelines, which is a composite indicator of whether patients were tested for malaria and given appropriate treatment consistent with the test result. All analyses were by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01350752.The study took place between June 7 and Dec 14, 2011. The analysis included 681 patients from nine facilities in the control group, 1632 patients from 18 facilities in the basic-training group, and 1669 from 19 facilities in the enhanced-training group. The proportion of patients treated in accordance with malaria guidelines did not improve with either intervention; the adjusted risk ratio (RR) for basic training compared with control was 1·04 (95% CI 0·53-2·07; p=0·90), and for enhanced training compared with control was 1·17 (0·61-2·25; p=0·62). Inappropriate use of antimalarial drugs after a negative test was reduced from 84% (201/239) in the control group to 52% (413/796) in the basic-training group (unadjusted RR 0·63, 0·28-1·43; p=0·25) and to 31% (232/759) in the enhanced-training group (0·29, 0·11-0·77; p=0·02).Enhanced clinician training, designed to translate knowledge into prescribing practice and improve quality of care, has the potential to halve overtreatment in public and mission health facilities in Cameroon. Basic training is unlikely to be sufficient to support the behaviour change required for the introduction of RDTs.
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1
Authors: Amy Strange, Francesca Capon, Chris C A Spencer, Jo Knight, Michael E Weale, Michael H Allen, Anne Barton, Gavin Band, Céline Bellenguez, Judith G M Bergboer, Jenefer M Blackwell, Elvira Bramon, Suzannah J Bumpstead, Juan P Casas, Michael J Cork, Aiden Corvin, Panos Deloukas, Alexander Dilthey, Audrey Duncanson, Sarah Edkins, Xavier Estivill, Oliver Fitzgerald, Colin Freeman, Emiliano Giardina, Emma Gray, Angelika Hofer, Ulrike Hüffmeier, Sarah E Hunt, Alan D Irvine, Janusz Jankowski, Brian Kirby, Cordelia Langford, Jesús Lascorz, Joyce Leman, Stephen Leslie, Lotus Mallbris, Hugh S Markus, Christopher G Mathew, W H Irwin McLean, Ross McManus, Rotraut Mössner, Loukas Moutsianas, Asa T Naluai, Frank O Nestle, Giuseppe Novelli, Alexandros Onoufriadis, Colin N A Palmer, Carlo Perricone, Matti Pirinen, Robert Plomin, Simon C Potter, Ramon M Pujol, Anna Rautanen, Eva Riveira-Munoz, Anthony W Ryan, Wolfgang Salmhofer, Lena Samuelsson, Stephen J Sawcer, Joost Schalkwijk, Catherine H Smith, Mona Ståhle, Zhan Su, Rachid Tazi-Ahnini, Heiko Traupe, Ananth C Viswanathan, Richard B Warren, Wolfgang Weger, Katarina Wolk, Nicholas Wood, Jane Worthington, Helen S Young, Patrick L J M Zeeuwen, Adrian Hayday, A David Burden, Christopher E M Griffiths, Juha Kere, André Reis, Gilean McVean, David M Evans, Matthew A Brown, Jonathan N Barker, Leena Peltonen, Peter Donnelly, Richard C Trembath
Journal: Nature Genetics (2010)
Immunologic Aspects of Chronic Obstructive Pulmonary Disease
Authors: Manuel G. Cosio, Marina Saetta, Alvar Agusti
Journal: New England Journal of Medicine (2009)

This review is an account of how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in chronic obstructive pulmonary disease (COPD). The authors present evidence that autoimmunity has a role in the development of COPD.
Depression Treatment and Satisfaction in a Multicultural Sample of Type 1 and Type 2 Diabetic Patients
Authors: Mary de Groot, Brenda Pinkerman, Julie Wagner, Erin Hockman
Journal: Diabetes Care (2006)

OBJECTIVE—To assess rates of depressive symptoms, depression treatment, and satisfaction in a multicultural sample of individuals with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS—This study was conducted with a cross-sectional community-based survey design. RESULTS—The sample (n = 221) was predominantly female (60.3%), had type 2 diabetes (75%), and was middle class with a mean (±SD) age of 54 ± 12 years. A total of 53% were white. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD) (mean 16.4 ± 11.3). Using conservative thresholds (CESD score ≥22), 25.3% of participants reported clinically significant depression. Rates of depression did not differ by ethnic group or diabetes type. The majority (76%) of depressed participants reported treatment (52% antidepressants, 63% mental health providers, 19% alternative healers, and 15% herbal remedies). African Americans were less likely to report any depression treatment, to receive antidepressant medications, or receive treatment from a mental health professional compared with whites. Participants with high depressive symptoms reported general satisfaction with depression treatment experiences. CONCLUSIONS—High rates of depressive symptoms were observed across ethnic groups, yet significant differences in use of depression treatment existed across ethnic groups. Those seeking depression treatment reported satisfaction with a variety of depression treatment modalities. Increased depression screening and treatment may be beneficial for ethnically diverse patients with type 1 and type 2 diabetes.
Premature babies have high death and disability rate
Authors: B. Christie
Journal: BMJ (2000)

One of the largest studies to examine disability rates among extremely premature babies has found that just under half grow up with some form of neurological or developmental disability. Severe forms of disability were present in 23% of babies born at 22–25 weeks, and boys were more likely to be disabled than girls.

The findings provide the clearest indicators to date of the chances of these babies having a disability and will help inform both parents and health professionals of the risks …
A Receptor-Specific Function for Notch2 in Mediating Vascular Smooth Muscle Cell Growth Arrest Through Cyclin-dependent Kinase Inhibitor 1B
Authors: Joshua M. Boucher, Anne Harrington, Bahman Rostama, Volkhard Lindner, Lucy Liaw
Journal: Circulation Research (2013)

Rationale: Deregulated vascular smooth muscle cell (VSMC) proliferation contributes to multiple vascular pathologies, and Notch signaling regulates VSMC phenotype. Objective: Previous work focused on Notch1 and Notch3 in VSMC during vascular disease; however, the role of Notch2 is unknown. Because injured murine carotid arteries display increased Notch2 in VSMC as compared with uninjured arteries, we sought to understand the impact of Notch2 signaling in VSMCs. Methods and Results: In human primary VSMCs, Jagged-1 (Jag-1) significantly reduced proliferation through specific activation of Notch2. Increased levels of p27 kip1 were observed downstream of Jag-1/Notch2 signaling and were required for cell cycle exit. Jag-1 activation of Notch resulted in increased phosphorylation on serine 10, decreased ubiquitination, and prolonged half-life of p27 kip1 . Jag-1/Notch2 signaling robustly decreased S-phase kinase–associated protein, an F-box protein that degrades p27 kip1 during G1. Overexpression of S-phase kinase–associated protein before Notch activation by Jag-1 suppressed the induction of p27 kip1 . Additionally, increased Notch2 and p27 kip1 expression was colocalized to the nonproliferative zone of injured arteries as indicated by co-staining with proliferating cell nuclear antigen, whereas Notch3 was expressed throughout normal and injured arteries, suggesting Notch2 may negatively regulate lesion formation. Conclusions: We propose a receptor-specific function for Notch2 in regulating Jag-1–induced p27 kip1 expression and growth arrest in VSMCs. During vascular remodeling, colocalization of Notch2 and p27 kip1 to the nonproliferating region supports a model where Notch2 activation may negatively regulate VSMC proliferation to lessen the severity of the lesion. Thus, Notch2 is a potential target for control of VSMC hyperplasia.
Analysis of the defects responsible for the impaired regulation of Epstein-Barr virus-induced B cell proliferation by rheumatoid arthritis lymphocytes. I. Diminished gamma interferon production in response to autologous stimulation.
Authors: F Hasler, H G Bluestein, N J Zvaifler, L B Epstein
Journal: The Journal of Experimental Medicine (1983)

T cells of patients with rheumatoid arthritis (RA) do not control the rate of B lymphoblast transformation induced by Epstein-Barr virus (EBV) as efficiently as T cells from healthy individuals; thus, lymphoblast cell lines are established more readily in RA lymphocytes in vitro after EBV infection. In the present experiments, we have asked whether this T cell regulation can be reproduced by lymphocytes. We found that normal T cells, activated in allogeneic or autologous mixed leukocyte reactions (MLR), produce lymphokines that inhibit in vitro EBV-induced B cell proliferation. Allogeneic MLR supernatants inhibited EBV-induced DNA synthesis 62 +/- 4% (mean +/- SE) at 10 d post-infection, whereas autologous MLR supernatants suppressed it 50 +/- 3%. RA T cell supernatants produced in an allogeneic MLR suppressed as well as normal T cell supernatants (64 +/- 5% inhibition). In contrast, supernatants from RA autologous MLR had little inhibitory activity. EBV-induced DNA synthesis at 10 d was reduced only 8 +/- 3%, compared with the 50 +/- 3% suppressive activity of normal autologous MLR supernatants. The magnitude of the proliferative responses in the autologous MLR regenerating the lymphokines was similar in the normal and RA populations. After depletion of adherent cells from the RA auto-MLR stimulators, supernatant inhibitory activities increased to normal levels (from 11 +/- 6 [SE] to 52 +/- 6% [SE]). The inhibitory factor involved in the regulation of in vitro EBV infection is a protein with a molecular weight of approximately 50,000. Its activity is eliminated by hearing at 56 degrees C and by exposure to acid at pH 2. The inhibitory activity is blocked by mixing the MLR supernatants with a polyvalent antisera or monoclonal antibodies specific for human gamma interferon. Gamma interferon produced by activating T cells in allo- or auto-MLR can reproduce T cell-mediated regulation of EBV-induced B cell proliferation, and the failure of RA auto-MLR to generate that lymphokine parallels the defective T cell regulation of EBV-induced B cell proliferation characteristic of RA lymphoid cells.
Endoscopic submucosal dissection of cecal lesions in proximity to the appendiceal orifice
Authors: Harold Jacob, Takashi Toyonaga, Yoshiko Ohara, Eiji Tsubouchi, Hiroshi Takihara, Shinichi Baba, Tetsuya Yoshizaki, Fumiaki Kawara, Shinwa Tanaka, Tsukasa Ishida, Namiko Hoshi, Yoshinori Morita, Eiji Umegaki, Takeshi Azuma
Journal: Endoscopy (2016)

Endoscopic submucosal dissection (ESD) is performed for treatment of various gastrointestinal lesions; however, the cecum in proximity to the appendiceal orifice remains a challenging area. We reviewed our experience with cecal ESD near the appendiceal orifice in order to clarify whether this procedure is a safe and effective therapeutic option.We retrospectively reviewed ESD for lesions within approximately 12 mm of the appendiceal orifice at Kobe University Hospital and an affiliated hospital between January 2003 and December 2014. Lesions were classified as: Type 0, proximity to the appendiceal orifice but does not reach it; Type 1, reaches border of the appendix, but does not enter orifice; Type 2, enters orifice, and transition to normal appendiceal mucosa is discernible on inspection of the appendiceal lumen; and Type 3, enters orifice deeply and tumor edge cannot be observed. ESD was not performed for Type 3 lesions unless appendectomy was performed prior to ESD.A total of 76 lesions satisfied the inclusion criteria (47 Type 0 lesions, 20 Type 1, 6 Type 2, and 3 Type 3). En bloc resection was achieved in 72 lesions (94.7 %). Median specimen size was 49 mm (range 15 - 114 mm), and median tumor size was 35.5 mm (10 - 110 mm). One patient experienced postoperative bleeding, which was treated by endoscopic hemostasis. Another patient who experienced intraoperative perforation and was treated by clip closure later developed appendicitis; he underwent emergency ileocecal surgical resection. Another patient experienced postoperative appendicitis and recovered with antibiotic treatment.ESD in close proximity to the appendiceal orifice seems safe and effective.
New Directions in Cardiac Transplantation
Authors: Abdulaziz Al-khaldi, Robert C. Robbins
Journal: Annual Review of Medicine (2006)

More than three decades of clinical experience in cardiac transplantation resulted in the spread of the procedure worldwide with a wealth of knowledge and advancements. Developments included liberalization of recipient and donor selection criteria, improved surgical techniques, novel immunosuppressive drugs and protocols, new rejection surveillance techniques, and better understanding of the pathophysiology of cardiac allograft vasculopathy to direct interventions for prevention and treatment.
Attenuation of inotropic interventions by myocardial ischaemia
Authors: J. R. SERUR, C. W. URSCHEL
Journal: Cardiovascular Research (1973)

Inotropic interventions are frequently utilized to augment the performance of the depressed heart. The effects of myocardial ischaemia on the response to two such interventions (heart rate and paired ventricular pacing) were evaluated in 15 isolated perfused isovolumic canine hearts. With normal perfusion pressure, increases in heart rate caused parallel changes in left ventricular pressure (LVP) and dP/dt, while similar increments in heart rate in the ischaemic heart caused LVP and dP/dt to fall. At normal perfusion pressures paired ventricular pacing resulted in stable increments in LVP and dP/dt, but during ischaemic perfusion initial increments in LVP and dP/dt were not maintained. The presence of ischaemia therefore places definite limits on the response of the myocardium to inotropic interventions. The effectiveness of these agents may therefore be severely limited in these circumstances.
Increased expression of natural‐killer‐associated and activation antigens in multiple myeloma
Authors: M. Gonźlez, J. F. San Miguel, A. Gascon, M‐J. Moro, J. M. Hernandez, F. Ortega, R. Jimenez, L. Guerras, M. Romero, F. Casanova, M. A. Sanz, J. A. Portero, A. Orfao
Journal: American Journal of Hematology (1992)

Abstract The expression of both natural‐killer (NK)‐associated and activation antigens was studied by flow cytometry in the peripheral blood of 47 untreated multiple myeloma (MM) patients. A significant increase in both absolute and relative numbers of CD57 positive cells as well as in the proportion of CD16 and CD11b cells was observed in patients with MM, specially in those in early stages of the disease (clinical stages I and II), suggesting a possible surveillance mechanism in response to an emerging malignant clone. Additional double stainings showed that strong CD16+ NK cells coexpress the CD56, CD11b, and CD2 antigens, while they lacked CD3, CD5, and WT31 antigens. Moreover, the previously reported increase in CD8 cells present in MM would be mainly due to a subset of CD8 cells that coexpress the CD57 Ags. The expression of activation antigens, especially CD38, was increased in peripheral blood lymphocytes of MM patients, the differences reaching statistical significance both in absolute and relative numbers in those cases with high numbers of CD16 NK cells and thus suggesting that these cells are functionally activated. These results reveal the existence of an increase in NK and activated cells in the peripheral blood of myeloma patients that may reflect a host's immunological mechanism in an attempt to modulate tumor cell growth.
Effect of sputum bacteriology on the quality of life of patients with bronchiectasis
Authors: CB Wilson, PW Jones, CJ O'Leary, DM Hansell, PJ Cole, R Wilson
Journal: European Respiratory Journal (1997)

Bronchiectatic patients have impaired health-related quality of life (QoL) and are prone to chronic lower respiratory tract infections. We have investigated whether impaired QoL is related to sputum bacteriology. Eighty seven patients with non-cystic fibrosis (non-CF) bronchiectasis, in a stable phase of their illness, completed three QoL measures, underwent a computed tomography (CT) scan and lung function tests, and provided a fresh sputum sample for microscopy and culture. The QoL of patients colonized by Pseudomonas aeruginosa (Pa group) was significantly worse than all other patients grouped together (non-Pa group), and specifically those infected by Haemophilus influenzae (Hi group) or who had no bacterial growth (NG group) (p<0.05), but not those infected by other bacterial species (O group). The Pa group had worse lung function, but no significant differences were found between the groups for forced expiratory volume in one second (FEV1) and peak expiratory flow rate. The Pa group had significantly worse bronchiectasis scores than the O, NG and non-Pa groups, but not the Hi group. There were no significant differences between the groups with respect to the number of infective exacerbations in the last year, but the Pa group had significantly more hospital admissions. Patients infected by P. aeruginosa for more than 3 yrs had significantly worse FEV1 (p<0.03) and bronchiectasis scores (p<0.05) than those infected with P. aeruginosa for less time, but not significantly worse QoL. We conclude that, overall, patients infected with P. aeruginosa have worse quality of life, and that P. aeruginosa is associated with a greater extent of disease and worse lung function. Although patients infected with H. influenzae had extensive bronchiectasis their quality of life was better than the P. aeruginosa infected group.
Protein Kinase Cι Is Required for Pancreatic Cancer Cell Transformed Growth and Tumorigenesis
Authors: Michele L. Scotti, William R. Bamlet, Thomas C. Smyrk, Alan P. Fields, Nicole R. Murray
Journal: Cancer Research (2010)

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, with an overall 5-year survival rate of <5%. Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is highly resistant to conventional chemotherapies, underscoring the critical need for new molecular targets for pancreatic cancer chemotherapy. The KRAS proto-oncogene is mutated in >90% of PDAC. Protein kinase Ciota (PKCiota) is required for the oncogenic Ras-mediated transformed growth of lung cancer and intestinal epithelial cells. However, little is known about the role of PKCiota in pancreatic cancer. In this study, we evaluated the expression of PKCiota in human pancreatic cancer and the requirement for PKCiota for the transformed growth and tumorigenicity of PDAC cells. We find that PKCiota is significantly overexpressed in human pancreatic cancer, and high PKCiota expression correlates with poor patient survival. Inhibition of PKCiota expression blocks PDAC cell transformed growth in vitro and tumorigenicity in vivo. Inhibition of PKCiota expression in pancreatic tumors also significantly reduces tumor angiogenesis and metastasis. Analysis of downstream PKCiota effectors implicates the Rac1-MEK/ERK1/2 signaling axis in PKCiota-mediated transformed growth and cellular invasion. Taken together, our data show a required role for PKCiota in the transformed growth of pancreatic cancer cells and reveal a novel role for PKCiota in pancreatic cancer cell metastasis and angiogenesis in vivo. Our results strongly indicate that PKCiota will be an effective target for pancreatic cancer therapy.
Environmental Phthalate Exposure and Preterm Birth
Authors: Kelly K. Ferguson, Thomas F. McElrath, John D. Meeker
Journal: JAMA Pediatrics (2013)

<h3>Importance</h3> Preterm birth is a leading cause of neonatal mortality, with a variety of contributing causes and risk factors. Environmental exposures represent a group of understudied, but potentially important, factors. Phthalate diesters are used extensively in a variety of consumer products worldwide. Consequently, exposure in pregnant women is highly prevalent. <h3>Objective</h3> To assess the relationship between phthalate exposure during pregnancy and preterm birth. <h3>Design, Setting, and Participants</h3> This nested case-control study was conducted at Brigham and Women's Hospital, Boston, Massachusetts. Women were recruited for a prospective observational cohort study from 2006-2008. Each provided demographic data, biological samples, and information about birth outcomes. From within this group, we selected 130 cases of preterm birth and 352 randomly assigned control participants, and we analyzed urine samples from up to 3 time points during pregnancy for levels of phthalate metabolites. <h3>Exposure</h3> Phthalate exposure during pregnancy. <h3>Main Outcomes and Measures</h3> We examined associations between average levels of phthalate exposure during pregnancy and preterm birth, defined as fewer than 37 weeks of completed gestation, as well as spontaneous preterm birth, defined as preterm preceded by spontaneous preterm labor or preterm premature rupture of the membranes (n = 57). <h3>Results</h3> Geometric means of the di-2-ethylhexyl phthalate (DEHP) metabolites mono-(2-ethyl)-hexyl phthalate (MEHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), as well as mono-<i>n</i>-butyl phthalate (MBP), were significantly higher in cases compared with control participants. In adjusted models, MEHP, MECPP, and Σ DEHP metabolites were associated with significantly increased odds of preterm birth. When spontaneous preterm births were examined alone, MEHP, mono-(2-ethyl-5-oxohexyl) phthalate, MECPP, Σ DEHP, MBP, and mono-(3-carboxypropyl) phthalate metabolite levels were all associated with significantly elevated odds of prematurity. <h3>Conclusions and Relevance</h3> Women exposed to phthalates during pregnancy have significantly increased odds of delivering preterm. Steps should be taken to decrease maternal exposure to phthalates during pregnancy.