tbuckley/cabot-search huggingface dataset:
Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial
Authors: Feng-Cai Zhu, Zheng-Lun Liang, Xiu-Ling Li, Heng-Ming Ge, Fan-Yue Meng, Qun-Ying Mao, Yun-Tao Zhang, Yue-Mei Hu, Zhen-Yu Zhang, Jing-Xin Li, Fan Gao, Qing-Hua Chen, Qi-Yan Zhu, Kai Chu, Xing Wu, Xin Yao, Hui-Jie Guo, Xiao-Qin Chen, Pei Liu, Yu-Ying Dong, Feng-Xiang Li, Xin-Liang Shen, Jun-Zhi Wang
Journal: The Lancet (2013)
Glucose induces intracisternal type A retroviral gene transcription and translation in pancreatic beta cells.
Authors: E H Leiter, J W Fewell, E L Kuff
Journal: The Journal of Experimental Medicine (1986)

C57BL/KsJ (BKs) and CBA/J, but not C57BL/6J (B6) mice are susceptible to the diabetogenic action of the obesity gene, "diabetes" (db). BKs and CBA/J, but not B6 mice, constitutively express intracisternal type A particles (IAP), an endogenous class of retrovirus, in beta cells and in cortical thymocytes. IAP genetic expression in these cell types included production of the group-specific antigen, p73, as well as higher-molecular mass p73-related antigens (p114-120). We used islet culture techniques to show that both transcription and translation of IAP genomes in beta cells in enhanced by glucose. Maintenance of CBA/J islets for 48 h in 16.5 mM glucose-containing medium effected a fivefold induction of IAP protein synthesis in comparison to islets cultured in low- (5.5 mM) glucose medium. Analysis of RNA from 16.5 mM glucose-cultured islets revealed induction of 7.2 and 5.4 kbp transcripts known to code for p73 and the p114-120 polypeptides, respectively. This induction in CBA/J islets was 10-15-fold on a tissue basis, and 5-7-fold on an RNA basis. Glucose induction of preproinsulin mRNA levels was also analyzed in the same samples. Islets cultured in 16.5 mM glucose showed an eightfold higher level on a tissue basis, and a fourfold increase in terms of total recovered RNA. Comparison of these glucose-inducible parameters in islets isolated from the diabetes-susceptible BKs strain vs. the resistant B6 strain revealed that expression of the group-specific retroviral p73 antigen was limited to BKs beta cells. This inbred strain control of p73 expression was also found in cortical thymocytes, with B6 thymocytes producing a 117 kD component to the exclusion of p73, while both components were expressed in thymocytes from normal BKs mice. In comparison to normal BKs males, thymocytes from four week-old genetically diabetic (db/db) BKs males showed no change in labeling of p117, but showed a sharply diminished incorporation into p73. This suggested that accelerated thymic involution characteristic of db/db mice may entail selective elimination of p73-producing cells. The possibility that glucose-stressed BKs pancreatic beta cells are marked for autoimmune elimination by the elaboration of p73 or other IAP-related proteins is discussed.
The effect of Sendai virus infection on bactericidal and transport mechanisms of the murine lung
Authors: George J. Jakab, Gareth M. Green
Journal: Journal of Clinical Investigation (1972)

Pulmonary virus infections predispose to bacterial infections in the lung. The mechanism of this effect was studied by quantitative comparison of the effects of airborne acute viral infection on pulmonary transport vs. in situ bactericidal mechanisms in mice. Animals infected by aerosol with 104 TCID50 of Sendai virus developed pathologic pulmonary changes of interstitial pneumonitis, bronchial epithelial desquamation, and peribronchial mononuclear cell infiltration 7 days later. At that time, the mice were challenged with an aerosol of viable 32P-labeled Staphylococcus aureus. Pulmonary bactericidal activity and physical transport by the lung were determined by the determination of viable staphylococcal and 32P radiotracer counts respectively at 4, 24, 48, and 72 hr after bacterial challenge. Infected mice showed a significant decrease from normal in the rate of reduction of viable bacterial counts in the first 4 hr after challenge followed by a proliferation of the staphylococci. By contrast, radiotracer removal rates at 4 and 24 hr were similar in infected and noninfected mice. There was a small but significant retention of 32P in the lungs of the infected animals at the later periods. These data demonstrate that bacterial multiplication associated with virus infection of lungs is related to defects in in situ bactericidal (phagocytic) mechanisms rather than transport mechanisms of the lung, despite histologic evidence of extensive destruction of bronchial-ciliated epithelium.
General Cardiovascular Risk Profile for Use in Primary Care
Authors: Ralph B. D’Agostino, Ramachandran S. Vasan, Michael J. Pencina, Philip A. Wolf, Mark Cobain, Joseph M. Massaro, William B. Kannel
Journal: Circulation (2008)

Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents.We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors.A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.
Importance of Maintaining the Rdi of Bendamustine Combined with Rituximab with Relapsed or Refractory Indolent Nhl
Authors: Kenji Miyazawa, Ayumi Nakamura, Yuki Kojima, Yasuhiko Miyata, Hirokazu Nagai, Hiroatsu Iida, Shuichi Matsumoto
Journal: Annals of Oncology (2014)
Examination of 41 cases of laryngeal tuberculosis observed between 1975-1985
Authors: F Galietti, GE Giorgis, G Gandolfi, A Astesiano, C Miravalle, A Ardizzi, G Favata, D Miscioscia
Journal: European Respiratory Journal (1989)

Forty one cases of laryngeal tuberculosis, accounting for 0.8% of all cases of tuberculosis observed in 1975-1985, are evaluated. The mean age was 53 yrs, the male/female ratio 9:1. In all cases current or earlier pulmonary tuberculosis was noted. The laryngeal sites affected were, in order of frequency: true vocal cords, epiglottis, false cords and laryngeal ventricles, arytenoid and interarytenoid area, subglottic area. The patients were usually treated with isoniazid, rifampicin, ethambutol for 6-12 months. Two cases required excision of laryngeal lesions. The results of chemotherapy were good.
Cisplatin in Combination With Either Gemcitabine or Irinotecan in Carcinomas of Unknown Primary Site: Results of a Randomized Phase II Study—Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01)
Authors: Stéphane Culine, Alain Lortholary, Jean-Jacques Voigt, Roland Bugat, Christine Théodore, Frank Priou, Marie-Christine Kaminsky, Thierry Lesimple, Xavier Pivot, Bruno Coudert, Jean-Yves Douillard, Yacine Merrouche, Jelila Allouache, Alain Goupil, Sylvie Négrier, Juliette Viala, Peter Petrow, Jeannine Bouzy, Agnès Laplanche, Karim Fizazi
Journal: Journal of Clinical Oncology (2003)

To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site.Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done.A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively.This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.
Can Social Interventions Prevent Tuberculosis?
Authors: Anurag Bhargava, Madhukar Pai, Madhavi Bhargava, Ben J. Marais, Dick Menzies
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: There is consensus on the need to address social determinants of tuberculosis (TB) to achieve TB control, but evidence based on interventions is lacking.Objectives: We reanalyzed data from the sociomedical experiment performed at the Papworth Village Settlement in England, where the impact of stable employment and adequate housing and nutrition on the incidence of TB infection and disease in children living with parents with active TB was documented during 1918–1943.Methods: Information on 315 children of patients, who lived at Papworth, was abstracted from a published monograph. Overall and age-specific occurrence of TB infection, disease, and deaths among children born in the settlement (village-born cohort) were compared with those of children born outside and admitted later (admitted cohort) to Papworth.Measurements and Main Results: The annual risks of infection in the village-born and admitted cohorts were 20 and 24%, respectively. Of 24 children who developed TB disease, only one was village-born. Among children 5 years of age or less, there was zero incidence of TB in the village-born, compared with five cases (1,217/100,000 person-years) among children born outside Papworth. In the admitted cohort, among children 13 years of age and older, the incidence of TB before admission to Papworth was 5,263/100,000 person-years, whereas it was 341/100,000 person-years while living in Papworth.Conclusions: At Papworth social interventions including adequate nutrition did not reduce TB transmission but did reduce the incidence of TB disease in children living with parents with active TB. These results are relevant today for prevention of TB in children of patients with active TB, particularly with multidrug-resistant TB in high-burden settings.
Unravelling the complexity of COPD by microRNAs: it's a small world after all
Authors: Emmanuel T. Osei, Laura Florez-Sampedro, Wim Timens, Dirkje S. Postma, Irene H. Heijink, Corry-Anke Brandsma
Journal: European Respiratory Journal (2015)

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the fourth leading cause of death worldwide. Chronic inflammation and repair processes in the small airways are characteristic of COPD. Despite extensive efforts from researchers and industry, there is still no cure for COPD, hence an urgent need for new therapeutic alternatives. MicroRNAs are such an option; they are small noncoding RNAs involved in gene regulation. Their importance has been shown with respect to maintaining the balance between health and disease. Although previous reviews have discussed the expression of microRNAs related to lung disease, a detailed discussion regarding the function of differential miRNA expression in the pathogenesis of COPD is lacking. In this review we link the expression of microRNAs to different features of COPD and explain their importance in the pathogenesis of this disease. We further discuss their potential to contribute to the development of future therapeutic strategies.
C-peptide Response to Meal Challenge in Nondiabetic and Diabetic Adults Living in Wadena, Minnesota
Authors: Sally A Bushhouse, Frederick C Goetz, David R Jacobs, Alan P Bender, L Ronald French, Patricia G Oestreich, Mindy S Geisser
Journal: Diabetes Care (1992)

OBJECTIVE The goal of the study was to provide cross-sectional descriptive data on the response of C-peptide to a vigorous meal stimulus in a population-based sample of nondiabetic adults compared with a population-based sample of adults with NIDDM. Available information is scanty, especially in subjects &amp;gt; 50 yr old. RESEARCH DESIGN AND METHODS The group under study included 377 adults without previously known diabetes randomly chosen from the population of the city of Wadena, Minnesota, almost all of northern European background, and 88 adults with known diabetes. PCP was measured 90 min after ingestion of 480 ml liquid meal Ensure-Plus, which includes 95 g dextrose, 26 g protein, and 25 g fat. C-peptide also was measured in a 260-min urine collection after the meal challenge. Novo antibody M1221 was used for C-peptide assay throughout the study. Participants whose medical record indicated insulin-dependent diabetes with a history of acetone production were excluded from analyses. RESULTS The distribution of UCP and PCP in this group of subjects appears very broad. Both the highest and lowest values for C-peptide were observed in individuals with diabetic glucose tolerance. The mean and median values in the nondiabetic group are higher than in previously published reports. After statistical adjustment for age, sex, BMI, and concomitant plasma glucose, participants with IGT produced significantly more C-peptide than the group with NGT (3.48 vs. 2.96 nM PCP, P &amp;lt; 0.05). Participants with diabetic glucose tolerance and who were not taking insulin produced as much or more C-peptide than either the NGT or IGT groups, depending on the statistical model used for adjusting for plasma glucose. Diabetic participants who were taking insulin produced significantly lower amounts of C-peptide than any of the non-insulin-taking groups (∼ 30% of the C-peptide produced by the non-insulin-taking diabetic participants). A decline in PCP production with increasing years since diagnosis (5.7%/yr) was observed exclusively in the insulin-taking NIDDM participants. Effect modification by glucose tolerance classification was observed on the relationship between plasma glucose and PCP: PCP increased with increasing plasma glucose in NGT and IGT groups, but a nonsignificant negative relationship was exhibited in diabetic participants. CONCLUSIONS The data suggest that two forms of NIDDM may exist, crudely distinguished by the clinical decision to use insulin to control blood glucose levels. The insulin-taking diabetic individuals may experience a greater likelihood of pancreatic failure, whereas non-insulin-taking diabetic individuals probably experience stable pancreatic function over the course of their disease. Longitudinal observation of the Wadena cohort will provide more insight into this possibility.
How Effective Is Dose-Intensive/Myeloablative Therapy Against Ewing’s Sarcoma/Primitive Neuroectodermal Tumor Metastatic to Bone or Bone Marrow? The Memorial Sloan-Kettering Experience and a Literature Review
Authors: Brian H. Kushner, Paul A. Meyers
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Attempts to improve outcomes of patients with Ewing’s sarcoma/primitive neuroectodermal tumor (ES/PNET) metastatic to bone/bone marrow (BM) have focused on chemotherapy dose intensification strategies. We now present results achieved with that approach, as carried out at Memorial Sloan-Kettering Cancer Center (MSKCC) and as reported in the literature. PATIENTS AND METHODS: Twenty-one unselected MSKCC patients with newly diagnosed ES/PNET metastatic to bone/BM received the “P6” protocol which includes cycles of cyclophosphamide (4.2 g/m 2 )/doxorubicin (75 mg/m 2 )/vincristine and cycles of ifosfamide (9 g/m 2 )/etoposide (500 mg/m 2 ). Patients in complete/very good partial remission (CR/VGPR) after P6 received myeloablative therapy with either total-body irradiation (TBI) (hyperfractionated 15 Gy)/melphalan (180 mg/m 2 ) or thiotepa (900 mg/m 2 )/carboplatin (1,500 mg/m 2 ). We reviewed the literature. RESULTS: Only one MSKCC patient became a long-term event-free survivor; all but one relapse was in a distant site. Initial responses to P6 were CR/VGPR in 19 patients, but eight of them plus two others developed PD while receiving or shortly after completing P6. Eight patients were treated with TBI/melphalan: four relapsed 2 to 7 months after transplantation; two died early of toxicity; one died of pulmonary failure 17 months after transplantation (no evidence of ES/PNET); and one remains in CR at more than 7 years. The three patients treated with thiotepa/carboplatin relapsed 3 to 4 months after transplantation. All reports on large series of unselected patients with ES/PNET metastatic to bone/BM showed similarly unsatisfactory results. Poor outcome was seen with use of active agents for ES/PNET–cyclophosphamide, ifosfamide, doxorubicin, dactinomycin, vincristine, etoposide - at standard dosages for prolonged periods of time and at higher dosages in intensive regimens for short or prolonged periods of time. No improvements in event-free survival rates occurred with successive cooperative group or large single-institutional studies that used increasingly aggressive chemotherapeutic approaches. Inclusion of ifosfamide with or without etoposide made no difference nor did consolidation of remission with myeloablative chemoradiotherapy. Secondary leukemia emerged as a major risk with dose-intensive regimens. CONCLUSION: The MSKCC experience and findings reported in the literature suggest that dose-intensive use of the chemotherapy agents with established activity against ES/PNET is reaching its efficacy and toxicity limits. A major impact on prognosis awaits the development of entirely novel therapies.
The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode
Authors: Andrew D. Rule, John C. Lieske, Xujian Li, L. Joseph Melton, Amy E. Krambeck, Eric J. Bergstralh
Journal: Journal of the American Society of Nephrology (2014)

Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials.
Healing after myocardial infarction
Authors: G ERTL, S FRANTZ
Journal: Cardiovascular Research (2005)

Wounding and healing are archaic principles, prerequisite for survival of any biologic material. However, strategies to cope with wounding may be quite different among organisms, species, or among various organs of one species. Today, myocardial infarction and the consequent loss of fully functional myocardium is the major aetiology for heart failure. Despite aggressive primary therapy, prognosis remains serious in patients with large infarction and severe left ventricular dysfunction. Thus, it would be highly desirable to influence healing of the cardiac wound to maintain structure and function of the heart. Herein, we review different, important factors of cardiac healing including reperfusion, mechanical stress, gender, and neurohormonal factors as well as specific factors essential for healing which may be genetic or acquired, emphasizing similarities and discrepancies between different organs and species.
Embryonic Stem Cell–Derived Cardiac Myocytes Are Not Ready for Human Trials
Authors: Mark E. Anderson, Joshua Goldhaber, Steven R. Houser, Michel Puceat, Mark A. Sussman
Journal: Circulation Research (2014)

Recently a preclinical report assessed the efficacy, safety, and feasibility of using human embryonic stem cells to regenerate infarcted myocardium in a non-human primate model.This commentary evaluates that study by pointing out key weaknesses, offering an alternative perspective, and summarizing major unresolved issues.Our conclusion is that significant challenges remain before human embryonic stem cells are ready for use in clinical trials.Ischemic heart disease (IHD) affects millions of patients.The cardiac dysfunction that results from IHD is secondary to the death of cardiac muscle cells.Current IHD treatments are inadequate and there is a need to develop novel therapies to improve the lives of affected patients.New cellular therapies are being developed for repairing damaged hearts via induction of cardiac myocyte regeneration.In our view, approaches that can regenerate new, functional, myocardium need to be tested first in small animal models and then in appropriate large animal models.Those approaches that are shown to be safe and to improve cardiac function in preclinical studies should then be considered for clinical application.In a recent report in Nature, Chong and collaborators describe experiments designed to test the potential of human embryonic stem cell-derived cardiac myocytes (hESC-CMs) to regenerate infarcted myocardium in a non-human primate model. 1 This study was proposed by the authors as proof of concept for trials of these cells in patients.Our commentary looks at this report with an eye toward safety and efficacy of hESC-CMs.