tbuckley/cabot-search huggingface dataset:
Abstract 17763: Multiple Reaction Monitoring-Based, Multiplexed, Absolute Quantitation of 82 Putative Biomarkers of Cardiovascular Disease in Human Plasma
Authors: Dominik Domanski, Derek S Smith, Christine A Miller, Gabriela Cohen-Freue, John S Hill, Carol E Parker, Christoph H Borchers
Journal: Circulation (2011)

Multiplexed biomarker expression profiling of clinical samples can be achieved in a rapid and targeted fashion using mass spectrometry-based multiple reaction monitoring (MRM) quantitation. For this project, a mixture of ~230 peptides standards was created to permit absolute quantitation of 82 putative biomarkers of cardiovascular disease, in human plasma trypsin digests. All experiments were performed on simple tryptic digests of human EDTA-plasma without prior affinity depletion or enrichment. Synthetic purified stable isotope-labeled standard peptides (SIS peptides) were added to the samples after tryptic digestion. For maximum specificity, a high-flow system using UPLC and an Agilent 6490 triple quadrupole mass spectrometer, equipped with an ion-funnel sprayer, were used. Instrumental parameters were empirically determined in order to generate the most abundant precursor ions and ion fragments. The narrow UPLC peak shapes and reproducible retention times assisted in the development of the highly-multiplexed system by increasing the chromatographic “space”. In addition, the larger id column, with a larger amount of packing material, also provided increased “robustness” of the overall system, as demonstrated by 110 analyses of the same sample with no loss of sensitivity or retention time accuracy. Linear responses and lowest limits of quantitation were obtained for all proteins. Sensitivities using the new system were in the low attomole range demonstrating that the high-flow system, which allowed loading more protein digest onto the column, more than compensated for any reduction in electrospray ionization efficiency caused by the higher flow rate. Concentrations of individual peptide standards in the mixture were optimized to approximate endogenous concentrations of analytes for the highest quantitation accuracy. The analytical precision was assessed for each protein assay from LC-MRM/MS analyses performed on 3 different days on different batches of plasma tryptic digests, and was found to be within 10%. Concentrations of proteins were compared to reported literature values. This method, with the same mixture of internal standards, is now being used for the plasma protein expression profiling of cardiovascular disease patients.
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
Authors: Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Joseph Chiu, Robert Paris, Nakorn Premsri, Chawetsan Namwat, Mark de Souza, Elizabeth Adams, Michael Benenson, Sanjay Gurunathan, Jim Tartaglia, John G. McNeil, Donald P. Francis, Donald Stablein, Deborah L. Birx, Supamit Chunsuttiwat, Chirasak Khamboonruang, Prasert Thongcharoen, Merlin L. Robb, Nelson L. Michael, Prayura Kunasol, Jerome H. Kim
Journal: New England Journal of Medicine (2009)

The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control.In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years.In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed.This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.)
Transforming Growth Factor-β and the Immune Response: Implications for Anticancer Therapy
Authors: Stephen H. Wrzesinski, Yisong Y. Wan, Richard A. Flavell
Journal: Clinical Cancer Research (2007)

Abstract Immune homeostasis is a delicate balance between the immune defense against foreign pathogens and suppression of the immune system to maintain self-tolerance and prevent autoimmune disease. Maintenance of this balance involves several crucial networks of cytokines and various cell types. Among these regulators, transforming growth factor-β (TGF-β) is a potent cytokine with diverse effects on hematopoietic cells. Its pivotal function within the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-β controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis and activation of leukocytes in the periphery, including lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. Through its pleiotropic effects on these immune cells, TGF-β prevents the development of autoimmune diseases without compromising immune responses to pathogens. However, overactivation of this pathway can lead to several immunopathologies under physiologic conditions including cancer progression, making it an attractive target for antitumor therapies. This review discusses the biological functions of TGF-β and its effects on the immune system and addresses how immunosuppression by this cytokine can promote tumorigenesis, providing the rationale for evaluating the immune-enhancing and antitumor effects of inhibiting TGF-β in cancer patients.
Web-Based Depression Treatment for Type 1 and Type 2 Diabetic Patients
Authors: Kim M.P. van Bastelaar, François Pouwer, Pim Cuijpers, Heleen Riper, Frank J. Snoek
Journal: Diabetes Care (2011)

Comorbid depression is common in patients with type 1 and type 2 diabetes, adversely affecting quality of life, diabetes outcomes, and mortality. Depression can be effectively treated with cognitive behavior therapy (CBT). The Internet is a new and attractive method for delivering CBT intervention on a large scale at relatively low costs. This study evaluated the effectiveness of Web-based CBT for depression treatment in adults with type 1 or type 2 diabetes, with minimal guidance.A randomized controlled trial was conducted in the Netherlands in 255 adult diabetic patients with elevated depressive symptoms. Primary outcomes were depressive symptoms. Secondary outcomes were diabetes-specific emotional distress and glycemic control. Assessments were at baseline, after treatment, and at the 1-month follow-up.The Web-based CBT was effective in reducing depressive symptoms by intention-to-treat analyses (P = 0.04, d = 0.29; clinical improvement 41% vs. 24% P < 0.001) and by per-protocol analyses (P < 0.001, d = 0.70; clinical improvement, 56% vs. 24% P < 0.001). The intervention reduced diabetes-specific emotional distress (P = 0.03) but had no beneficial effect on glycemic control (P > 0.05).Web-based CBT depression treatment is effective in reducing depressive symptoms in adults with type 1 and type 2 diabetes. In addition, the intervention reduces diabetes-specific emotional distress in depressed patients.
The Healer's Hand
Authors: M. Julian Duttera
Journal: JAMA (1979)

CONCERN for one's fellowman has been characteristic of physicians for centuries. Until the last century, one could argue that this characteristic was, in fact, most of what a physician had to offer among his healing skills. Many older physicians today remember well medicine in the pre-antibiotic era, when one had little choice but to sit by the bedside of a patient with pneumonia, hold the patient's hand, and be present with the family until the fever had broken or the patient had died. For the patient with congestive heart failure, one could do little more than administer digitalis leaf and hope that such a crudely prepared drug would be of help to the patient. But those physicians were not faulted because of their limitations. Their concern and willingness to care for their patients were greatly appreciated and even revered by the persons for whom they cared. Physicians today are viewed
ALCOHOL IN THE ELDERLY
Authors: Mary Dufour, M.D., M.P.H, Richard K. Fuller, M.D., M.S
Journal: Annual Review of Medicine (1995)

▪ Abstract Although older individuals drink less and report fewer alcohol-related problems than do younger individuals, alcohol use and abuse are significant health issues for older patients. The signs and symptoms of alcohol problems and dependence in the elderly may not only differ from those of young problem drinkers, but may also be present at lower levels of alcohol consumption. Older alcoholics do well in alcohol treatment. Therefore, discussion of alcohol consumption is a critical part of every history and physical examination for all patients, including older individuals.
What has been learnt from P/V curves in patients with acute lung injury/acute respiratory distress syndrome
Authors: S.M. Maggiore, J‐C. Richard, L. Brochard
Journal: European Respiratory Journal (2003)

Mechanical impairment of the respiratory system was recognised soon after the description of acute respiratory distress syndrome. The analysis of the pressure/volume ( P / V ) curve of the respiratory system contributed a lot to the understanding of the pathophysiology of acute lung injury and formed the basis for lung protection. The lower and upper inflection points were regarded as points of interest to avoid cyclic derecruitment and overdistension and to optimise ventilatory settings. However, because of the heterogeneity of lung injury, reducing the mechanical properties of the whole respiratory system to a single curve is a schematic approach, which makes interpretation difficult. New data suggest that alveolar re-inflation occurs along the whole P / V curve that can, therefore, be considered as a recruitment curve. The lower inflection point has no relationship with alveolar opening and closure and does not indicate the positive end-expiratory pressure needed to prevent alveolar collapse. The shape of the P / V curve gives information about the extension and the homogeneity of lung injury, indicating the possibility of lung recruitment. The upper inflection point, classically seen as the beginning of overdistension, may also indicate the end of recruitment. The pressure/volume curve offers the unique opportunity of evaluating alveolar recruitment/derecruitment at the bedside that can be helpful for the identification of optimal ventilatory settings and makes the curve a valuable tool for the ventilatory management of acute lung injury.
Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics
Authors: P. Baumgarten, M. Michaelis, F. Rothweiler, T. Starzetz, H. F. Rabenau, A. Berger, L. Jennewein, A. K. Braczynski, K. Franz, V. Seifert, J. P. Steinbach, R. Allwinn, M. Mittelbronn, J. Cinatl
Journal: Neuro-Oncology (2014)

Experimental findings have suggested that human cytomegalovirus (HCMV) infection of tumor cells may exert oncomodulatory effects that enhance tumor malignancy. However, controversial findings have been published on the presence of HCMV in malignant tumors. Here, we present the first study that systematically investigates HCMV infection in human nervous system tumors by highly sensitive immunohistochemistry in correlation with the HCMV serostatus of the patients. Immunohistochemical and quantitative PCR-based methods to detect different HCMV antigens and genomic HCMV DNA were optimized prior to the investigation of pathological samples. Moreover, the pathological results were matched with the HCMV serostatus of the patients. HCMV immediate-early, late, and pp65 antigens could be detected in single cells from HCMV strain Hi91-infected UKF-NB-4 neuroblastoma cells after 1:1024 dilution with noninfected UKF-NB-4 cells. Genomic HCMV DNA could be detected in copy numbers as low as 430 copies/mL. However, we did not detect HCMV in tumors from a cohort of 123 glioblastoma, medulloblastoma, or neuroblastoma patients. Notably, we detected nonspecifically positive staining in tumor tissues of HCMV seropositive and seronegative glioblastoma patients. The HCMV serostatus of 67 glioblastoma patients matched the general epidemiological prevalence data for Western countries (72% of female and 57% of male glioblastoma patients were HCMV seropositive). Median survival was not significantly different in HCMV seropositive versus seronegative glioblastoma patients. The prevalence of HCMV-infected tumor cells may be much lower than previously reported based on highly sensitive detection methods.
Risk factors for patellar tendinopathy: a systematic review of the literature
Authors: Henk van der Worp, Mathijs van Ark, Saskia Roerink, Gert-Jan Pepping, Inge van den Akker-Scheek, Johannes Zwerver
Journal: British Journal of Sports Medicine (2011)

Patellar tendinopathy (PT) is an injury with a high prevalence in sports. Knowledge of risk factors is essential for developing preventive measures and rehabilitation programmes. However, risk factors associated with PT have not yet been systematically studied. This review was undertaken to identify risk factors associated with PT. The literature was systematically searched to identify articles that investigated risk factors for PT. There was no strong or moderate evidence that any investigated risk factor was associated with PT. For nine risk factors there was some evidence: weight, body mass index, waist-to-hip ratio, leg-length difference, arch height of the foot, quadriceps flexibility, hamstring flexibility, quadriceps strength and vertical jump performance. Based on the present evidence, reducing body weight, increasing upper-leg flexibility and quadriceps strength and the use of orthotics may be beneficial treatment options. However, it should be stressed that the evidence for the nine identified risk factors was only limited. Therefore, there is a clear need for high-quality studies in order to identify the exact risk factors associated with PT.
Cardioselective beta-blockers are not only safe in patients with COPD, but may also improve the responsibility of FEV1 to beta-agonist: A meta-analysis of randomized controlled double-blinded trials
Authors: Yingmeng Ni, Guochao Shi
Journal: European Respiratory Journal (2012)

Objective : To assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD   Methods : The EMBASE, MEDLINE, and the Cochrane Controlled Trials Register were searched comprehensively to identify all relevant clinical trials in humans published between 1966 and May 2011. Randomized, blinded, controlled trials that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 s (FEV1) and responsibility of FEV1 to beta-agonist in patients with COPD were included in the analysis. Outcomes measured were the FEV1 and the change of FEV1 after the use of beta-agonist.   Results : Sample size for the cardio-selective beta-blockers was 85 cases, non-selective beta-blockers 46. The results showed that FEV1 declined 0.14L with the use of non-selective beta-blockers (z = 6.78, p    Conclusion : Our meta-analysis suggests that cardioselective beta-blockers is not only safe in patients with COPD, but may also improve the responsibility of FEV1 to beta-agonist.
The ETS Transcription Factor Spi-B Is Required for Human Plasmacytoid Dendritic Cell Development
Authors: Remko Schotte, Maho Nagasawa, Kees Weijer, Hergen Spits, Bianca Blom
Journal: The Journal of Experimental Medicine (2004)

A number of transcription factors that act as molecular switches for hematopoietic lineage decisions have been identified. We recently described the ETS transcription factor Spi-B to be exclusively expressed in plasmacytoid dendritic cells (pDCs), but not in myeloid DCs. To assess whether Spi-B is required for pDC development we used an RNA interference knock down approach to specifically silence Spi-B protein synthesis in CD34+ precursor cells. We observed that a knock down of Spi-B mRNA strongly inhibited the ability of CD34+ precursor cells to develop into pDCs in both in vitro assays as well as in vivo upon injection into recombination activating gene 2−/− γ common−/− mice. The observed effects were restricted to the pDC lineage as the differentiation of pro–B cells and CD14+ myeloid cells was not inhibited but slightly elevated by Spi-B knock down. Knock down of the related ETS factor PU.1 also inhibited in vitro development of CD34+ cells into pDCs. However, in contrast to Spi-B, PU.1 knock down inhibited B cell and myeloid cell development as well. These results identify Spi-B as a key regulator of human pDC development.
The DREAM Complex Mediates GIST Cell Quiescence and Is a Novel Therapeutic Target to Enhance Imatinib-Induced Apoptosis
Authors: Sergei Boichuk, Joshua A. Parry, Kathleen R. Makielski, Larisa Litovchick, Julianne L. Baron, James P. Zewe, Agnieszka Wozniak, Keith R. Mehalek, Nina Korzeniewski, Danushka S. Seneviratne, Patrick Schöffski, Maria Debiec-Rychter, James A. DeCaprio, Anette Duensing
Journal: Cancer Research (2013)

Gastrointestinal stromal tumors (GIST) can be successfully treated with imatinib mesylate (Gleevec); however, complete remissions are rare and patients frequently achieve disease stabilization in the presence of residual tumor masses. The clinical observation that discontinuation of treatment can lead to tumor progression suggests that residual tumor cells are, in fact, quiescent and, therefore, able to re-enter the cell-division cycle. In line with this notion, we have previously shown that imatinib induces GIST cell quiescence in vitro through the APC(CDH1)-SKP2-p27(Kip1) signaling axis. Here, we provide evidence that imatinib induces GIST cell quiescence in vivo and that this process also involves the DREAM complex, a multisubunit complex that has recently been identified as an additional key regulator of quiescence. Importantly, inhibition of DREAM complex formation by depletion of the DREAM regulatory kinase DYRK1A or its target LIN52 was found to enhance imatinib-induced cell death. Our results show that imatinib induces apoptosis in a fraction of GIST cells while, at the same time, a subset of cells undergoes quiescence involving the DREAM complex. Inhibition of this process enhances imatinib-induced apoptosis, which opens the opportunity for future therapeutic interventions to target the DREAM complex for more efficient imatinib responses.
Localised fibrous mesothelioma arising in an intralobar pulmonary sequestration.
Authors: N Paksoy, A Demircan, M Altiner, M Artvinli
Journal: Thorax (1992)

A localised fibrous mesothelioma arising from an intralobar lung sequestration occurred in a 64 year old Turkish woman. This appears to be the first report of a mesothelioma occurring within a pulmonary sequestration.
Prophylactic Use of a Probiotic in the Prevention of Colic, Regurgitation, and Functional Constipation
Authors: Flavia Indrio, Antonio Di Mauro, Giuseppe Riezzo, Elisa Civardi, Cristina Intini, Luigi Corvaglia, Elisa Ballardini, Massimo Bisceglia, Mauro Cinquetti, Emanuela Brazzoduro, Antonio Del Vecchio, Silvio Tafuri, Ruggiero Francavilla
Journal: JAMA Pediatrics (2014)

Infantile colic, gastroesophageal reflux, and constipation are the most common functional gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant social consequences.To investigate whether oral supplementation with Lactobacillus reuteri DSM 17938 during the first 3 months of life can reduce the onset of colic, gastroesophageal reflux, and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions.A prospective, multicenter, double-masked, placebo-controlled randomized clinical trial was performed on term newborns (age <1 week) born at 9 different neonatal units in Italy between September 1, 2010, and October 30, 2012.Parents were asked to record in a structured diary the number of episodes of regurgitation, duration of inconsolable crying (minutes per day), number of evacuations per day, number of visits to pediatricians, feeding changes, hospitalizations, visits to a pediatric emergency department for a perceived health emergency, pharmacologic interventions, and loss of parental working days.In total, 589 infants were randomly allocated to receive L reuteri DSM 17938 or placebo daily for 90 days.Prophylactic use of probiotic.Reduction of daily crying time, regurgitation, and constipation during the first 3 months of life. Cost-benefit analysis of the probiotic supplementation.At 3 months of age, the mean duration of crying time (38 vs 71 minutes; P < .01), the mean number of regurgitations per day (2.9 vs 4.6; P < .01), and the mean number of evacuations per day (4.2 vs 3.6; P < .01) for the L reuteri DSM 17938 and placebo groups, respectively, were significantly different. The use of L reuteri DSM 17938 resulted in an estimated mean savings per patient of €88 (US $118.71) for the family and an additional €104 (US $140.30) for the community.Prophylactic use of L reuteri DSM 17938 during the first 3 months of life reduced the onset of functional gastrointestinal disorders and reduced private and public costs for the management of this condition.clinicaltrials.gov Identifier: NCT01235884.