tbuckley/cabot-search huggingface dataset:
Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial
Authors: Jacobien Veenemans, Paul Milligan, Andrew M. Prentice, Laura R. A. Schouten, Nienke Inja, Aafke C. van der Heijden, Linsey C. C. de Boer, Esther J. S. Jansen, Anna E. Koopmans, Wendy T. M. Enthoven, Rob J. Kraaijenhagen, Ayse Y. Demir, Donald R. A. Uges, Erasto V. Mbugi, Huub F. J. Savelkoul, Hans Verhoef
Journal: PLoS Medicine (2011)

It is uncertain to what extent oral supplementation with zinc can reduce episodes of malaria in endemic areas. Protection may depend on other nutrients. We measured the effect of supplementation with zinc and other nutrients on malaria rates.In a 2×2 factorial trial, 612 rural Tanzanian children aged 6-60 months in an area with intense malaria transmission and with height-for-age z-score≤-1.5 SD were randomized to receive daily oral supplementation with either zinc alone (10 mg), multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Intervention group was indicated by colour code, but neither participants, researchers, nor field staff knew who received what intervention. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. The primary outcome, an episode of malaria, was assessed among children reported sick at a primary care clinic, and pre-defined as current Plasmodium infection with an inflammatory response, shown by axillary temperature ≥37.5°C or whole blood C-reactive protein concentration ≥ 8 mg/L. Nutritional indicators were assessed at baseline and at 251 days (median; 95% reference range: 191-296 days). In the primary intention-to-treat analysis, we adjusted for pre-specified baseline factors, using Cox regression models that accounted for multiple episodes per child. 592 children completed the study. The primary analysis included 1,572 malaria episodes during 526 child-years of observation (median follow-up: 331 days). Malaria incidence in groups receiving zinc, multi-nutrients without zinc, multi-nutrients with zinc and placebo was 2.89/child-year, 2.95/child-year, 3.26/child-year, and 2.87/child-year, respectively. There was no evidence that multi-nutrients influenced the effect of zinc (or vice versa). Neither zinc nor multi-nutrients influenced malaria rates (marginal analysis; adjusted HR, 95% CI: 1.04, 0.93-1.18 and 1.10, 0.97-1.24 respectively). The prevalence of zinc deficiency (plasma zinc concentration <9.9 µmol/L) was high at baseline (67% overall; 60% in those without inflammation) and strongly reduced by zinc supplementation.We found no evidence from this trial that zinc supplementation protected against malaria.ClinicalTrials.gov NCT00623857
Adoptive T-cell Transfer Therapy and Oncogene-Targeted Therapy for Melanoma: The Search for Synergy
Authors: Mei Li M. Kwong, Bart Neyns, James C. Yang
Journal: Clinical Cancer Research (2013)

Abstract The clinical strengths of immunotherapy and small-molecule inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway appear to be largely complementary for the treatment of advanced melanoma. In current practice, most patients with BRAF V600 mutant melanomas will see both modalities. Several in vitro and in vivo studies suggest that combining immunotherapy with MAPK inhibition may have synergistic effects. First, mouse models show that adoptive cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by vemurafenib could provide a vaccine-like stimulus to adoptively transferred T cells. Second, both in mice and in early clinical trials, melanoma metastases treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third, MAPK inhibition upregulates the expression of some melanoma antigens and, therefore, may enhance T-cell recognition of vemurafenib-treated melanomas. Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally, some investigators have found that an optimal antitumor effect from MAPK inhibition is dependent on an intact host immune response. Currently, the Surgery Branch of the National Cancer Institute has initiated a phase II trial combining the BRAF inhibitor vemurafenib with ACT using tumor-infiltrating lymphocytes in patients with BRAF-mutant tumors to investigate the safety and efficacy of this combination. The proposed mechanisms for synergy between these two modalities can be complex, and their optimal combination may require testing a variety of sequences and schedules. Clin Cancer Res; 19(19); 5292–9. ©2013 AACR.
Is lung function worsening during adolescence in cystic fibrosis? A retrospective study
Authors: Sonia Volpi, Annachiara Marostica, Ciro D'Orazio, Giovanna Amenta, Emily Pintani, Baroukh Assael
Journal: European Respiratory Journal (2012)

Adolescence is a vulnerable period for patients with cystic fibrosis (CF). It is generally recognized that during adolescence morbidity is higher, lung function declines at higher rates and adherence to treatments decreases. However, specific data on spirometry in this age have only seldom been reported.

The aim of our study was to analyze lung function throughout infancy and adolescence in cohorts of CF patients diagnosed after neonatal screening.

We rectrospectively evaluated the spirometry of patients 59 born in the years 1992 - 1994 who had been visited at least three times yearly and compared the decline in FEV1 and FEF 25-75 (both % predicted) in pre- adolescence (pre ado; age range 8-12 years.) and during adolescence (age range 13-17 years).

The mean decrease in FEV1% was -0.35 (SD ± 11.9) in the pre ado period and -1.41 (SD ± 11,7) during adolescence with no significant difference in decline between the two periods, (p= 0.45, paired t test). However, the mean variation in FEF 25-75 was 7.9% (SD ± 32) in pre ado and -6.7 (SD ± 26) during adolescence (p= 0.009)

Our data show that lung function decreases during adolescence in CF patients as reflected by a loss in FEF 25-75 which is consistent with an anatomical damage initially located in smaller peripheral airways. Although FEV1 is universally adopted as a surrogate outcome it seems to be poorly sensitive in evaluating lung disease progression in CF during adolescence.
Active Care Management Supported by Home Telemonitoring in Veterans With Type 2 Diabetes
Authors: Roslyn A. Stone, R. Harsha Rao, Mary Ann Sevick, Chunrong Cheng, Linda J. Hough, David S. Macpherson, Carol M. Franko, Rebecca A. Anglin, D. Scott Obrosky, Frederick R. DeRubertis
Journal: Diabetes Care (2009)

OBJECTIVE We compared the short-term efficacy of home telemonitoring coupled with active medication management by a nurse practitioner with a monthly care coordination telephone call on glycemic control in veterans with type 2 diabetes and entry A1C ≥7.5%. RESEARCH DESIGN AND METHODS Veterans who received primary care at the VA Pittsburgh Healthcare System from June 2004 to December 2005, who were taking oral hypoglycemic agents and/or insulin for ≥1 year, and who had A1C ≥7.5% at enrollment were randomly assigned to either active care management with home telemonitoring (ACM+HT group, n = 73) or a monthly care coordination telephone call (CC group, n = 77). Both groups received monthly calls for diabetes education and self-management review. ACM+HT group participants transmitted blood glucose, blood pressure, and weight to a nurse practitioner using the Viterion 100 TeleHealth Monitor; the nurse practitioner adjusted medications for glucose, blood pressure, and lipid control based on established American Diabetes Association targets. Measures were obtained at baseline, 3-month, and 6-month visits. RESULTS Baseline characteristics were similar in both groups, with mean A1C of 9.4% (CC group) and 9.6% (ACM+HT group). Compared with the CC group, the ACM+HT group demonstrated significantly larger decreases in A1C at 3 months (1.7 vs. 0.7%) and 6 months (1.7 vs. 0.8%; P &amp;lt; 0.001 for each), with most improvement occurring by 3 months. CONCLUSIONS Compared with the CC group, the ACM+HT group demonstrated significantly greater reductions in A1C by 3 and 6 months. However, both interventions improved glycemic control in primary care patients with previously inadequate control.
Independent Review of E2100: A Phase III Trial of Bevacizumab Plus Paclitaxel Versus Paclitaxel in Women With Metastatic Breast Cancer
Authors: Robert Gray, Suman Bhattacharya, Christopher Bowden, Kathy Miller, Robert L. Comis
Journal: Journal of Clinical Oncology (2009)

E2100, an open-label, randomized, phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG), demonstrated a significant improvement in progression-free survival (PFS) and overall response rate (ORR) with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer.An independent, blinded review of radiologic and clinical data was performed, assessing progression and response according to Response Evaluation Criteria in Solid Tumors. In addition, ECOG's investigator assessments were reanalyzed using the same methods applied to the independent review. The primary end point was PFS as assessed by an independent review facility (IRF).The addition of bevacizumab to paclitaxel resulted in a statistically significant improvement in PFS using both the IRF and investigator assessments. Hazard ratios for PFS (0.48, 95% CI, 0.385 to 0.607; P < .0001 for the IRF v 0.42, 95% CI, 0.34 to 0.52; P < .0001 for ECOG investigators) and the improvement in median PFS (11.3 v 5.8 months for the IRF v 11.4 v 5.8 months for ECOG investigators) were similar. Among patients with measurable disease at baseline, the IRF-assessed ORR was significantly higher in patients treated with paclitaxel and bevacizumab (48.9% v 22.2%; P < .0001).The risk of progression was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming a substantial and robust bevacizumab treatment effect. The consistency between the IRF and ECOG analyses validates the original data previously reported by ECOG in this open-label trial.
Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement
Authors: Duvuru Geetha, Ulrich Specks, John H. Stone, Peter A. Merkel, Philip Seo, Robert Spiera, Carol A. Langford, Gary S. Hoffman, Cees G.M. Kallenberg, E. William St. Clair, Barri J. Fessler, Linna Ding, Nadia K. Tchao, David Ikle, Brett Jepson, Paul Brunetta, Fernando C. Fervenza
Journal: Journal of the American Society of Nephrology (2014)

Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m2 × 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3–6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegener's Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m2; P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids.
The Influence of Comorbidities on Overall Survival Among Older Women Diagnosed With Breast Cancer
Authors: J. L. Patnaik, T. Byers, C. DiGuiseppi, T. D. Denberg, D. Dabelea
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundPrevious studies have shown that summary measures of comorbid conditions are associated with decreased overall survival in breast cancer patients. However, less is known about associations between specific comorbid conditions on the survival of breast cancer patients.
Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer
Authors: Ruud H. Wijdeven, Baoxu Pang, Sabina Y. van der Zanden, Xiaohang Qiao, Vincent Blomen, Marlous Hoogstraat, Esther H. Lips, Lennert Janssen, Lodewyk Wessels, Thijn R. Brummelkamp, Jacques Neefjes
Journal: Cancer Research (2015)

Abstract The topoisomerase II poisons doxorubicin and etoposide constitute longstanding cornerstones of chemotherapy. Despite their extensive clinical use, many patients do not respond to these drugs. Using a genome-wide gene knockout approach, we identified Keap1, the SWI/SNF complex, and C9orf82 (CAAP1) as independent factors capable of driving drug resistance through diverse molecular mechanisms, all converging on the DNA double-strand break (DSB) and repair pathway. Loss of Keap1 or the SWI/SNF complex inhibits generation of DSB by attenuating expression and activity of topoisomerase IIα, respectively, whereas deletion of C9orf82 augments subsequent DSB repair. Their corresponding genes, frequently mutated or deleted in human tumors, may impact drug sensitivity, as exemplified by triple-negative breast cancer patients with diminished SWI/SNF core member expression who exhibit reduced responsiveness to chemotherapy regimens containing doxorubicin. Collectively, our work identifies genes that may predict the response of cancer patients to the broadly used topoisomerase II poisons and defines alternative pathways that could be therapeutically exploited in treatment-resistant patients. Cancer Res; 75(19); 4176–87. ©2015 AACR.
Activation of the p62‐Keap1‐NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells
Authors: Xiaofang Sun, Zhanhui Ou, Ruochan Chen, Xiaohua Niu, De Chen, Rui Kang, Daolin Tang
Journal: Hepatology (2015)

Ferroptosis is a recently recognized form of regulated cell death caused by an iron‐dependent accumulation of lipid reactive oxygen species. However, the molecular mechanisms regulating ferroptosis remain obscure. Here, we report that nuclear factor erythroid 2‐related factor 2 (NRF2) plays a central role in protecting hepatocellular carcinoma (HCC) cells against ferroptosis. Upon exposure to ferroptosis‐inducing compounds (e.g., erastin, sorafenib, and buthionine sulfoximine), p62 expression prevented NRF2 degradation and enhanced subsequent NRF2 nuclear accumulation through inactivation of Kelch‐like ECH‐associated protein 1. Additionally, nuclear NRF2 interacted with transcriptional coactivator small v‐maf avian musculoaponeurotic fibrosarcoma oncogene homolog proteins such as MafG and then activated transcription of quinone oxidoreductase‐1, heme oxygenase‐1, and ferritin heavy chain‐1. Knockdown of p62, quinone oxidoreductase‐1, heme oxygenase‐1, and ferritin heavy chain‐1 by RNA interference in HCC cells promoted ferroptosis in response to erastin and sorafenib. Furthermore, genetic or pharmacologic inhibition of NRF2 expression/activity in HCC cells increased the anticancer activity of erastin and sorafenib in vitro and in tumor xenograft models. Conclusion: These findings demonstrate novel molecular mechanisms and signaling pathways of ferroptosis; the status of NRF2 is a key factor that determines the therapeutic response to ferroptosis‐targeted therapies in HCC cells. (H epatology 2016;63:173–184)
Fatigue and underperformance in athletes: the overtraining syndrome.
Authors: R Budgett
Journal: British Journal of Sports Medicine (1998)

The overtraining syndrome affects mainly endurance athletes. It is a condition of chronic fatigue, underperformance, and an increased vulnerability to infection leading to recurrent infections. It is not yet known exactly how the stress of hard training and competition leads to the observed spectrum of symptoms. Psychological, endocrinogical, physiological, and immunological factors all play a role in the failure to recover from exercise. Careful monitoring of athletes and their response to training may help to prevent the overtraining syndrome. With a very careful exercise regimen and regeneration strategies, symptoms normally resolve in 6-12 weeks but may continue much longer or recur if athletes return to hard training too soon.
Aggressive forms of periodontitis secondary to systemic disorders
Authors: Ahmed Khocht, Jasim M. Albandar
Journal: Periodontology 2000 (2014)

Abstract A number of systemic disorders increase a patient’s susceptibility to destructive periodontitis and have impacts on periodontal disease progression and severity. The underlying factors are usually genetic and are mainly related to alterations in the immune response and in certain endocrine functions, leading to various syndromes in which periodontitis and/or early tooth loss are secondary manifestations. Neutrophils are important immune defense cells that play a significant role in controlling the spread of microbial plaque infections in the dentogingival region. This review focuses on a selected group of systemic disorders that are associated with alterations in either neutrophil counts (quantitative disorders) or function (qualitative disorders), and defects in the mineralization of bone and dental tissues. In most of these diseases controlling the periodontal disease progression is very challenging. Proper diagnosis is a prerequisite for proper management of the periodontal problem. Future advances in research, including gene targeting and the resolution of enzyme deficiencies, may bring about remedies of the underlying systemic disorders and may significantly improve the outcome of periodontal treatment in these patients.
First In Vivo Application of Microwave Radiometry in Human Carotids
Authors: Konstantinos Toutouzas, Charalampos Grassos, Maria Drakopoulou, Andreas Synetos, Eleftherios Tsiamis, Constantina Aggeli, Konstantinos Stathogiannis, Dimitrios Klettas, Nikolaos Kavantzas, Georgios Agrogiannis, Efstratios Patsouris, Christos Klonaris, Nikolaos Liasis, Dimitrios Tousoulis, Elias Siores, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2012)
Cave-Associated Histoplasmosis: Trinidad
Authors: Dewitt Brown
Journal: JAMA (1988)

<h3>To the Editor. —</h3> I was particularly interested in the report on "Cave-Associated Histoplasmosis—Costa Rica"<sup>1</sup>because of a personal experience with this condition during World War II, prior to the recognition of histoplasmosis. In 1943, with a group of eight airmen, I was sent into the mountains of Trinidad to rescue a member of our squadron who had fallen into a 30-ft shaft about a half mile into a cave while exploring with a fellow. It was during the rainy season and we had a narrow "window" of time to get in and out, as the passages reportedly would flood. We found an 8-ft entrance that soon opened into a large cavern where the air was filled with disturbed bats and the screeching of sea hawks and the floor was deep in bat guano. We found our man deep in the cave with a fractured spine and other injuries
Are Racial Differences in Squamous Cell Esophageal Cancer Explained by Alcohol and Tobacco Use?
Authors: L. M. Brown, R. N. Hoover, R. S. Greenberg, J. B. Schoenberg, A. G. Schwartz, G. M. Swanson, J. M. Liff, D. T. Silverman, R. B. Hayes, L. M. Pottern
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Are Racial Differences in Squamous Cell Esophageal Cancer Explained by Alcohol and Tobacco Use? Get access Linda Morris Brown, Linda Morris Brown * Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md *Correspondence to: Linda Morris Brown, M.P.H., National Institutes of Health, Executive Plaza North, Rm. 415. Bethesda. MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert N. Hoover, Robert N. Hoover Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Raymond S. Greenberg, Raymond S. Greenberg Division of Epidemiology, Emory University School of Public HealthAtlanta. Ga Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet B. Schoenberg, Janet B. Schoenberg Special Epidemiology Program, New Jersey State Department of HealthTrenton Search for other works by this author on: Oxford Academic PubMed Google Scholar Ann G. Schwartz, Ann G. Schwartz Department of Clinical Epidemiology and Family Medicine, University of Pittsburgh School of MedicinePittsburgh, Pa Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Marie Swanson, G. Marie Swanson College of Human Medicine, Michigan State UniversityEast Lansing Search for other works by this author on: Oxford Academic PubMed Google Scholar Jonathan M. Liff, Jonathan M. Liff Division of Epidemiology, Emory University School of Public HealthAtlanta. Ga Search for other works by this author on: Oxford Academic PubMed Google Scholar Debra T. Silverman, Debra T. Silverman Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard B. Hayes, Richard B. Hayes Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda M. Pottern Linda M. Pottern Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 17, 7 September 1994, Pages 1340–1345, https://doi.org/10.1093/jnci/86.17.1340 Published: 07 September 1994 Article history Received: 04 April 1994 Accepted: 20 June 1994 Published: 07 September 1994