tbuckley/cabot-search huggingface dataset:
The Yin and Yang of Cholesteryl Ester Transfer Protein in Cardiovascular Disease
Authors: Prediman K. Shah
Journal: Circulation (2009)

C holesteryl ester transfer protein (CETP) is a 79-kDa glycoprotein, present in humans, rabbits, primates, and hamsters but absent in rodents, dogs, horses, cows, and pigs, that facilitates transfer of cholesteryl ester from high-density lipoprotein (HDL) particles to low-density lipoprotein (LDL)-very-low-density lipoprotein (vLDL) particles in exchange for triglycerides, thereby participating in reverse cholesterol transport and regulating circulating HDL cholesterol (HDL-C) levels. 1,2In 1989, Brown et al 3 described 2 Japanese subjects with markedly elevated HDL-C levels who were homozygous for a point mutation in the 5Ј-splice donor site of intron 14 of the CETP gene, a change that was shown to be incompatible with normal splicing of pre-messenger RNA.The following year, Inazu et al 4 reported that 4 of 11 additional families from 3 different regions of Japan with elevated HDL-C were homozygous or heterozygous for the same mutation with gene-dose-dependent increases in HDL-C levels.Because epidemiological studies had generally shown an inverse relationship between circulating HDL-C levels and coronary heart disease (CHD), loss-offunction CETP mutations associated with increased HDL-C levels were thus thought to confer protection against CHD.This view is further supported by studies that have shown that increased CETP activity is associated with increased atherosclerosis progression and/or cardiovascular risk. 5,6A prospective 7-year follow-up study of American men of Japanese descent from the Honolulu Heart Program suggested that CETP mutations associated with reduced CETP activity and markedly elevated HDL-C (Ͼ60 mg/dL) may confer a lower risk of CHD, 7 although an earlier cross-sectional analysis had suggested the opposite. 8Contrary to these observations, other studies have shown that reduced CETP activity is associated with paradoxically increased CHD despite elevated HDL-C levels. 9 -12A deleterious CETP haplotype was shown to be associated with a 6-fold increase in myocardial infarction risk independent of HDL-C levels. 13Similarly, carriers of CETP Taq1B B2 allele were shown to have increased CHD events over a 10-year follow-up period. 14A recent meta-analysis involving subjects genotyped for 3 common CETP variants
Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection
Authors: Hai-Nv Gao, Hong-Zhou Lu, Bin Cao, Bin Du, Hong Shang, Jian-He Gan, Shui-Hua Lu, Yi-Da Yang, Qiang Fang, Yin-Zhong Shen, Xiu-Ming Xi, Qin Gu, Xian-Mei Zhou, Hong-Ping Qu, Zheng Yan, Fang-Ming Li, Wei Zhao, Zhan-Cheng Gao, Guang-Fa Wang, Ling-Xiang Ruan, Wei-Hong Wang, Jun Ye, Hui-Fang Cao, Xing-Wang Li, Wen-Hong Zhang, Xu-Chen Fang, Jian He, Wei-Feng Liang, Juan Xie, Mei Zeng, Xian-Zheng Wu, Jun Li, Qi Xia, Zhao-Chen Jin, Qi Chen, Chao Tang, Zhi-Yong Zhang, Bao-Min Hou, Zhi-Xian Feng, Ji-Fang Sheng, Nan-Shan Zhong, Lan-Juan Li
Journal: New England Journal of Medicine (2013)

During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus.Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013.Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02).During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).
Mature and Immature Extracranial Teratomas in Children: The UK Children's Cancer Study Group Experience
Authors: Jillian R. Mann, Elizabeth S. Gray, Claire Thornton, Faro Raafat, Kathleen Robinson, Gary S. Collins, Peter Gornall, Simon N. Huddart, Juliet P. Hale, Anthony Oakhill
Journal: Journal of Clinical Oncology (2008)

The purpose of this article is to describe the features, treatment, and risk factors for relapse of children with mature teratoma (MT) and immature teratoma (IT) to assist future treatment plans.Patients were younger than 16 years of age and referred to the UK Children's Cancer Study Group centers with biopsy-proven extracranial MT and IT and no prior chemotherapy. Complete excision, with the coccyx in sacrococcygeal patients, and follow-up, including serum alpha-fetoprotein monitoring for early detection of malignant yolk sac tumor (YST) recurrence, were recommended. Carboplatin, etoposide, and bleomycin (JEB) were given for YST relapse, whereas relapsed MT and IT were treated at clinicians' discretion, usually surgically. Pathology was reviewed and treatments, outcome, and prognostic features assessed.There were 351 patients, 227 with MT, 124 with IT. Tumor sites were: testis (n = 53), ovary (n = 130), sacrococcygeal region (n = 98), thorax (n = 23), and other (n = 47). Surgical resection was incomplete in 26% of MT and 40% of IT patients; 5-year event-free survival was 92.2% and 85.9%, respectively, and 5-year overall survival was 99% and 95.1%. Poorer outcome occurred with incomplete resection, tumor rupture, nongonadal site (particularly sacrococcygeal), young age, higher stage and grade, and gliomatosis peritonei, but not with cyst fluid aspiration/spillage, tumor enucleation, nodal gliomatosis, or microfoci of YST in the tumor (Heifetz lesions). JEB was effective for YST recurrence, but not for MT or IT.Treatment remains primarily surgical, with JEB chemotherapy for YST relapse. No definite response followed JEB for pure MT and IT. Adjuvant chemotherapy after surgery for sacrococcygeal patients is not advocated.
Three deadly sins: hierarchy, etiquette and conformity
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2009)

What's your preference? Do you follow best practice? Or do you make clinical judgements based on the decision-making of your colleagues? Do you obey medicine's natural laws of hierarchy, etiquette and conformity? It is a tricky dilemma, especially for junior doctors who may be the most up-to-date but learn that their clinical team has a very different interpretation of the evidence. These competing influences can cause discomfort and may lead to poor outcomes.
In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen.
Authors: G Kaplan, G Gaudernack
Journal: The Journal of Experimental Medicine (1982)

We demonstrated that the in vitro differentiation of human peripheral blood monocytes to macrophages is dependent on the environment and conditions of monocyte culture. Cultivation of monocytes on glass or microexudate-coated glass gave rise to cells resembling foreign body granuloma macrophages. After an initial rise in Fc receptor- and C3 receptor-mediated phagocytosis, a progressive loss of Fc receptor expression and C3-mediated ingestion were observed. The monocyte surface antigens recognized by the anti-human monocyte monoclonal antibodies 1D5 and 63D3 were lost from the surface of the majority of cells cultured on glass and microexudates. A subpopulation of Fc receptor-positive cells that were 1D5 and 63D3 positive was retained in fully differentiated cell populations. In comparison, monocytes cultivated on collagen matrices gave rise to highly phagocytic cells resembling human resident tissue macrophages. Both Fc- and C3-mediated phagocytosis were enhanced and remained so during the entire length of culture. The surface antigens recognized by the 1D5 antibody, expressed on all freshly seeded monocytes, was maintained on the macrophages. The antigen recognized by the 63D3 antibody was not expressed on mature cells. The present evidence would indicate that variations in expression of phagocytic receptors and the surface antigens 1D5 and 63D3 can be ascribed to the stage of development of the macrophage or its stage of activation, rather than to independent subsets of mononuclear phagocytes.
Cigarette smoking has protective effect on blood pressure and obesity
Authors: Aziz Gumus, Servet Kayhan, Halit Cinarka, Unal Sahin
Journal: European Respiratory Journal (2013)

BACKGROUND:  The relationship between smoking and development of hypertension is uncertain.   OBJECTIVES:  In this study we aimed to determine the relationship between smoking and blood pressure levels.   METHODS:  The effects of cigarette smoking on the development of obesity and hypertension were prospectively evaluated in a cohort of 710 participants. Smoking status, systolic and diastolic blood pressures, body mass index of the participants were evaluated.   RESULTS:  Hypertension was found in 17 persons among 253 current smokers, 11 persons among 65 non-smokers and 88 persons among 392 ex-smokers.  Body mass index was also found to be in low levels in heavy smokers (pack/year), (p   CONCLUSION:  We propose that smoking has negative effect on blood pressure and obesity.
Evaluation of the RABBIT Risk Score for serious infections
Authors: A Zink, B Manger, J Kaufmann, C Eisterhues, A Krause, J Listing, A Strangfeld
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To evaluate the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score for serious infections in patients with rheumatoid arthritis (RA). <h3>Methods</h3> The RABBIT Risk Score for serious infections was developed in 2011 on a cohort of RA patients enrolled in the German biologics register RABBIT between 2001 and 2007. To evaluate this score, we used data from patients enrolled in RABBIT after 1 January 2009. Expected numbers of serious infections and expected numbers of patients with at least one serious infection per year were calculated by means of the RABBIT Risk Score and compared with observed numbers in the evaluation sample. <h3>Results</h3> The evaluation of the score in an independent cohort of 1522 RA patients treated with tumour necrosis factor α (TNFα) inhibitors and 1468 patients treated with non-biological disease-modifying antirheumatic drugs (DMARDs) showed excellent agreement between observed and expected rates of serious infections. For patients exposed to TNF inhibitors, expected as well as observed numbers of serious infections were 3.0 per 100 patient-years (PY). For patients on non-biological DMARDs the expected and observed numbers were 1.5/100 PY and 1.8/100 PY, respectively. The score was highly predictive in groups of patients with low as well as with high infection risk. <h3>Conclusions</h3> The RABBIT Risk Score is a reliable instrument which determines the risk of serious infection in individual patients based on clinical and treatment information. It helps the rheumatologist to balance benefits and risks of treatment, to avoid high-risk treatment combinations and thus to make informed clinical decisions.
Zonisamide for Weight Loss in Obese Adults
Authors: Kishore M Gadde, Deborah M Franciscy, H Ryan Wagner, K Ranga R Krishnan
Journal: JAMA (2003)

Context Zonisamide is a marketed antiepileptic drug that has serotonergic and dopaminergic activity in addition to blockade of sodium and calcium channels. Weight loss was an adverse effect associated with zonisamide treatment in epilepsy clinical trials. Objective To evaluate the efficacy of zonisamide for weight loss in obese adults. Design and Setting Sixteen-week randomized, double-blind, placebo-controlled trial with an optional single-blind extension of the same treatment for another 16 weeks, conducted at Duke University Medical Center from March 2001 to March 2002. Participants Fifty-five (92%) women and 5 (8%) men (mean [SE] body mass index, 36.3 [0.5]; mean age, 37.0 (1.0) years). Interventions Patients were randomly assigned to receive zonisamide (n = 30) or placebo (n = 30). All participants were prescribed a balanced hypocaloric diet (500 kcal/d deficit) and compliance was monitored with self-rated food diaries. Zonisamide therapy was started at 100 mg/d orally, with gradual increase to 400 mg/d and further increase to 600 mg/d for patients losing less than 5% of body weight at the end of 12 weeks. Placebo dosing was identical. Main Outcome Measure Change in body weight. Results Of the 60 randomized patients, 51 completed the 16-week acute phase. In an intent-to-treat analysis using the available data for all randomized participants with the last observation carried forward, the zonisamide group lost more body weight than the placebo group (mean [SE], 5.9 [0.8] kg [6.0% loss] vs 0.9 [0.4] kg [1.0% loss]; t = 5.5; P &amp;amp;lt;.001) during the 16-week period. A longitudinal mixed-model regression for weight change controlling for age, race, sex, body mass index, and percent body fat estimated that zonisamide treatment over the 16-week study duration was associated with significantly greater weight loss than was placebo ( t = 6.4; P &amp;amp;lt;.001). Seventeen (57%) of 30 in the zonisamide group and 3 (10%) of 30 in the placebo group lost at least 5% of body weight ( P &amp;amp;lt;.001) by week 16. Of the 37 participants who entered the extension phase, 36 completed week 32. The zonisamide group (n = 19) had a mean weight loss of 9.2 kg (1.7 kg) (9.4% loss) at week 32 compared with 1.5 kg (0.7 kg) (1.8% loss) for the placebo group (n = 17) ( t = 4.0; P &amp;amp;lt;.001). Zonisamide was tolerated well, with few adverse effects. Conclusion In this short-term, preliminary trial, zonisamide and hypocaloric diet resulted in more weight loss than placebo and hypocaloric diet in the treatment of obesity.
Randomized Phase III Trial Comparing Biweekly Infusional Fluorouracil/Leucovorin Alone or With Irinotecan in the Adjuvant Treatment of Stage III Colon Cancer: PETACC-3
Authors: Eric Van Cutsem, Roberto Labianca, György Bodoky, Carlo Barone, Enrique Aranda, Bernard Nordlinger, Claire Topham, Josep Tabernero, Thierry André, Alberto F. Sobrero, Enrico Mini, Richard Greil, Francesco Di Costanzo, Laurence Collette, Laura Cisar, Xiaoxi Zhang, David Khayat, Carsten Bokemeyer, Arnaud D. Roth, David Cunningham
Journal: Journal of Clinical Oncology (2009)

PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2) as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan. Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia. CONCLUSION Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.
What are the effects of medication adherence interventions in rheumatic diseases: a systematic review
Authors: Jessica S Galo, Pavandeep Mehat, Sharan K Rai, Antonio Avina-Zubieta, Mary A De Vera
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Consistent reports of suboptimal treatment adherence among patients with inflammatory arthritis underscore the importance of understanding how adherence can be promoted and supported. Our objectives were to identify and classify adherence interventions; and assess the evidence on the effects of adherence interventions on outcomes of patients with rheumatic diseases. Methods We conducted a mapped search of Medline, Embase and International Pharmaceutical Abstract databases to identify studies meeting inclusion criteria of: (1) patient population with inflammatory arthritis; (2) evaluation of an intervention or programme targeting medication adherence directly or indirectly; (3) reporting of one or more measures of medication adherence and disease outcome; (4) publication in English, French or Spanish. For our first objective, we applied a structured framework to classify interventions according target (patient vs provider), focus (educational vs behavioural vs affective), implementation (generalised vs tailored), complexity (single vs multifaceted) and provider. For the second objective, we appraised the evidence of effects of interventions on adherence and disease outcomes. Results We identified 23 studies reporting adherence interventions that directly or indirectly addressed treatment adherence in rheumatic diseases and further appraised included RCTs. Interventions that were shown to impact adherence outcomes were generally interventions directed at adherence, tailored to patients and delivered by a healthcare provider. For interventions that were not shown to have impacts, reasons may be those related to the intervention itself, patient characteristics or study methodology. Conclusions Our systematic review shows limited research on adherence interventions in rheumatic diseases with inconsistent impacts on adherence or disease outcome.
Toward an evolutionary basis for resilience to drug addiction
Authors: Serge H. Ahmed
Journal: Behavioral and Brain Sciences (2011)

Abstract According to Müller &amp; Schumann (M&amp;S), people would have evolved adaptations for learning to use psychoactive plants and drugs as instruments that reveal particularly advantageous in modern urban environments. Here I “instrumentalize” this framework to propose an evolutionary basis for the existence of a biological resilience to drug addiction in people.
Immunofluorescence serration pattern analysis as a diagnostic criterion in antilaminin‐332 mucous membrane pemphigoid: immunopathological findings and clinical experience in 10 Dutch patients
Authors: J.B. Terra, H.H. Pas, M. Hertl, F.G. Dikkers, N. Kamminga, M.F. Jonkman
Journal: British Journal of Dermatology (2011)

Antilaminin-332 mucous membrane pemphigoid (anti-LN-332 MMP) is a chronic subepidermal blistering disease characterized by IgG anti-epidermal basement membrane zone (BMZ) autoantibodies against laminin-332 (LN-332).with anti-LN-332 MMP have an increased relative risk of malignancy. Laboratory techniques that are difficult to obtain are needed for diagnosis of anti-LN-332 MMP. Objectives To incorporate direct immunofluorescence (DIF) serration pattern analysis of IgG depositions in the diagnostic criteria of anti-LN-332 MMP.Patients who met our revised inclusion criteria for anti-LN-332 MMP were selected from our biobank over the period 1997-2009. Inclusion criteria were clinical symptoms, DIF serration pattern analysis, indirect immunofluorescence (IIF) on salt-split skin, and antigen-specificity analysis of the serum including immunoblotting and/or immunoprecipitation and/or enzyme-linked immunosorbent assay (ELISA) against native LN-332.Ten patients met the inclusion criteria. A malignancy was found in two patients (20%). In all patients in whom it was performed (n = 9), DIF showed linear IgG deposition along the BMZ in an n-serrated pattern. Nine sera reacted by salt-split skin analysis and bound to the dermal side of the split skin. ELISA against native LN-332 was positive in 78% of the tested sera.Anti-LN-332 MMP can clinically resemble other forms of pemphigoid. Although state-of-the-art laboratory diagnostics are necessary for definite diagnosis, the combination of simple DIF serration pattern and IIF salt-split skin analysis will exclude other forms of MMP and epidermolysis bullosa acquisita from the differential diagnosis. Because of the increased risk for malignancy patients should be thoroughly oncologically screened.
The characteristics, biodistribution, magnetic resonance imaging and biodegradability of superparamagnetic core–shell nanoparticles
Authors: Po-Wei Lee, Sheng-Hsiang Hsu, Jiun-Jie Wang, Jin-Sheng Tsai, Kun-Ju Lin, Shiaw-Pyng Wey, Fu-Rong Chen, Chih-Huang Lai, Tzu-Chen Yen, Hsing-Wen Sung
Journal: Biomaterials (2009)
EU's anti-smoking stance needs to be more than frightening
Authors: T. M Marteau, S. Hall
Journal: BMJ (2001)

EDITOR—Under European Union rules agreed in May 2001, national governments will be able to insist that, from September 2002, tobacco manufacturers devote 30% of the front of cigarette packets and 40% of their backs to messages conveying the dangers of smoking.1

This reflects a wider tendency for messages aimed at motivating change in behaviour to focus on …
Glioma growth inhibition by neurostatin and O-But GD1b
Authors: B. Valle-Argos, D. Gomez-Nicola, M. Nieto-Sampedro
Journal: Neuro-Oncology (2010)

In spite of their low incidence, central nervous system tumors have elevated morbidity and mortality, being responsible for 2.3% of total cancer deaths. The ganglioside O-acetylated GD1b (O-Ac GD1b; neurostatin), present in the mammalian brain, and the semi-synthetic O-butyrylated GD1b (O-But GD1b) are potent glioma proliferation inhibitors, appearing as possible candidates for the treatment of nervous system tumors. Tumoral cell division inhibitory activity in culture correlated with growth inhibition of glioma xenotransplants in Foxn1nu nude mice and intracranial glioma allotransplants. Both O-Ac GD1b and O-But GD1b inhibited in vivo cell proliferation, induced cell cycle arrest, and potentiated immune cell response to the tumor. Furthermore, the increased stability of the butyrylated compound (O-But GD1b) enhanced its activity with respect to the acetylated ganglioside (neurostatin). These results are the first report of the antitumoral activity of neurostatin and a neurostatin-like compound in vivo and indicate that semi-synthetic O-acetylated and O-butyrylated gangliosides are potent antitumoral compounds that should be considered in strategies for brain tumor treatment.