tbuckley/cabot-search huggingface dataset:
Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe
Authors: Selidji T. Agnandji, Angela Huttner, Madeleine E. Zinser, Patricia Njuguna, Christine Dahlke, José F. Fernandes, Sabine Yerly, Julie-Anne Dayer, Verena Kraehling, Rahel Kasonta, Akim A. Adegnika, Marcus Altfeld, Floriane Auderset, Emmanuel B. Bache, Nadine Biedenkopf, Saskia Borregaard, Jessica S. Brosnahan, Rebekah Burrow, Christophe Combescure, Jules Desmeules, Markus Eickmann, Sarah K. Fehling, Axel Finckh, Ana Rita Goncalves, Martin P. Grobusch, Jay Hooper, Alen Jambrecina, Anita L. Kabwende, Gürkan Kaya, Domtila Kimani, Bertrand Lell, Barbara Lemaître, Ansgar W. Lohse, Marguerite Massinga-Loembe, Alain Matthey, Benjamin Mordmüller, Anne Nolting, Caroline Ogwang, Michael Ramharter, Jonas Schmidt-Chanasit, Stefan Schmiedel, Peter Silvera, Felix R. Stahl, Henry M. Staines, Thomas Strecker, Hans C. Stubbe, Benjamin Tsofa, Sherif Zaki, Patricia Fast, Vasee Moorthy, Laurent Kaiser, Sanjeev Krishna, Stephan Becker, Marie-Paule Kieny, Philip Bejon, Peter G. Kremsner, Marylyn M. Addo, Claire-Anne Siegrist
Journal: New England Journal of Medicine (2015)

The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa.We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo.No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants.In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).
THE TECHNIC OF CHENOPODIUM ADMINISTRATION IN HOOKWORM DISEASE
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Case 52-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, F.M. Hasan, E.J. Mark
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 71-year-old man was admitted to the hospital because of a suspected exacerbation of chronic obstructive pulmonary disease.The patient had smoked three packs of cigarettes daily for 20 years and stopped 28 years before entry. Nineteen years before admission he had a myocardial infarct, with subsequent angina pectoris. Two years later a triple coronary-artery-bypass graft procedure was performed, and the patient was free of chest pain thereafter.Four years before admission a diagnosis of chronic obstructive pulmonary disease was made, and the patient's symptoms gradually worsened despite treatment. The results of pulmonary-function tests and blood gas . . .
<i>WRN</i> Promoter CpG Island Hypermethylation Does Not Predict More Favorable Outcomes for Patients with Metastatic Colorectal Cancer Treated with Irinotecan-Based Therapy
Authors: Linda J.W. Bosch, Yanxin Luo, Victoria V. Lao, Petur Snaebjornsson, Geert Trooskens, Ilse Vlassenbroeck, Sandra Mongera, Weiliang Tang, Piri Welcsh, James G. Herman, Miriam Koopman, Iris D. Nagtegaal, Cornelis J.A. Punt, Wim van Criekinge, Gerrit A. Meijer, Raymond J. Monnat, Beatriz Carvalho, William M. Grady
Journal: Clinical Cancer Research (2016)

WRN promoter CpG island hypermethylation in colorectal cancer has been reported to increase sensitivity to irinotecan-based therapies. We aimed to characterize methylation of the WRN promoter, determine the effect of WRN promoter hypermethylation upon expression, and validate a previous report that WRN promoter hypermethylation predicts improved outcomes for patients with metastatic colorectal cancer (mCRC) treated with irinotecan-based therapy.WRN methylation status was assessed using methylation-specific PCR and bisulfite sequencing assays. WRN expression was determined using qRT-PCR and Western blotting. WRN methylation status was correlated with overall survival (OS) and progression-free survival (PFS) in 183 patients with mCRC. Among these patients, 90 received capecitabine monotherapy as first-line therapy, and 93 received capecitabine plus irinotecan (CAPIRI) therapy as part of the CAIRO phase III clinical trial.WRN mRNA and WRN protein expression levels were low in colorectal cancer cell lines and in primary colorectal cancer and were largely independent of WRN methylation status. Patients with methylated WRN colorectal cancer had a shorter OS compared with patients who had unmethylated WRN colorectal cancer (HR = 1.6; 95% confidence interval [CI], 1.2-2.2; P = 0.003). Patients with unmethylated WRN showed a significantly longer PFS when treated with CAPIRI compared with capecitabine alone (HR = 0.48; 95% CI, 0.32-0.70; P = 0.0001). In contrast, patients did not benefit from adding irinotecan to capecitabine when WRN was methylated (HR = 1.1; 95% CI, 0.69-1.77; P = 0.7).WRN expression is largely independent of WRN promoter hypermethylation in colorectal cancer. Moreover, we could not validate the previous finding that WRN promoter hypermethylation predicts improved clinical outcomes of mCRC treated with irinotecan-based therapy and found instead the opposite result. Clin Cancer Res; 22(18); 4612-22. ©2016 AACR.
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Authors: Caroline Wigerup, Sven Påhlman, Daniel Bexell
Journal: Pharmacology & Therapeutics (2016)

Insufficient tissue oxygenation, or hypoxia, contributes to tumor aggressiveness and has a profound impact on clinical outcomes in cancer patients. At decreased oxygen tensions, hypoxia-inducible factors (HIFs) 1 and 2 are stabilized and mediate a hypoxic response, primarily by acting as transcription factors. HIFs exert differential effects on tumor growth and affect important cancer hallmarks including cell proliferation, apoptosis, differentiation, vascularization/angiogenesis, genetic instability, tumor metabolism, tumor immune responses, and invasion and metastasis. As a consequence, HIFs mediate resistance to chemo- and radiotherapy and are associated with poor prognosis in cancer patients. Intriguingly, perivascular tumor cells can also express HIF-2α, thereby forming a "pseudohypoxic" phenotype that further contributes to tumor aggressiveness. Therefore, therapeutic targeting of HIFs in cancer has the potential to improve treatment efficacy. Different strategies to target hypoxic cancer cells and/or HIFs include hypoxia-activated prodrugs and inhibition of HIF dimerization, mRNA or protein expression, DNA binding capacity, and transcriptional activity. Here we review the functions of HIFs in the progression and treatment of malignant solid tumors. We also highlight how HIFs may be targeted to improve the management of patients with therapy-resistant and metastatic cancer.
Analysis of European Patients Enrolled in a Global Early Access Protocol with Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer Progressing After Chemotherapy
Authors: D. Castellano, S. Bracarda, M. Tucci, O. Capoun, V. Matveev, G. Bodoky, G. Fountzilas, G. Kacso, M. Borre, I. Skoneczna, A. Londhe, P. De Porre, D. Atlan, B. Goon, E. Lee, T. McGowan, V. Naini, A. Molina, C.N. Sternberg
Journal: Annals of Oncology (2014)
SURG-06CALCITRIOL SELECTIVELY ENHANCE QUALITY OF 5-AMINOLEVULINIC ACID METABOLIC IMAGING IN GLIOMAS
Authors: Shiguang Zhao
Journal: Neuro-Oncology (2015)

INTRODUCTION: Gliomas are characterized by their local invasiveness and poor prognosis. It has been demonstrated that the survival benefit is associated with the extent of surgical resection. But it is difficult to distinguish tumor margins due to the infiltrative nature, and gliomas often recur within 2-3 cm from the borders of the resection cavity. Recently, Fluorescence-guided surgery with 5-aminolevulinic acid (ALA) for resection of gliomas has been used as an effective therapeutic approach to discriminate malignant tissue from brain tissue and to facilitate patient prognosis. However, insufficient protoporphyrin IX accumulation may limit the benefits of it in low-grade glioma and the marginal area. METHODS: To be able to understand how to overcome these issues, human glioma cells and normal astrocytes were used as the model system. Glioma cells and astrocytes were preconditioned with calcitriol for 48 hours and then incubated with ALA. Changes in ALA-induced PpIX fluorescence were assessed. Furthermore, expression of porphyrin synthetic enzymes in pretreated glioma cells was analyzed. RESULTS: Calcitriol can be administered prior to ALA as a non-toxic preconditioning regimen to significantly enhance ALA- induced PpIX levels and fluorescence. This increase in PpIX level was detected preferentially in glioma versus normal cells. Furthermore, mechanistic studies documented that expression of the porphyrin synthesis enzymes coproporphyrinogen oxidase was increased by calcitriol at the mRNA level. CONCLUSION: We demonstrated for the first time a simple, non-toxic and highly effective preconditioning regimen to selectively enhance PpIX fluorescence in glioma cells. This finding suggests that the combined treatment of glioma cells with calcitriol plus ALA may provide an effective and selective therapeutic modality to enhance ALA-induced PpIX fluorescent quality for improving discrimination of tumor tissue.
Far‐Red Fluorescent Lipid‐Polymer Probes for an Efficient Labeling of Enveloped Viruses
Authors: William Lacour, Salim Adjili, Julie Blaising, Arnaud Favier, Karine Monier, Sarra Mezhoud, Catherine Ladavière, Christophe Place, Eve‐Isabelle Pécheur, Marie‐Thérèse Charreyre
Journal: Advanced Healthcare Materials (2016)

Far-red emitting fluorescent lipid probes are desirable to label enveloped viruses, for their efficient tracking by optical microscopy inside autofluorescent cells. Most used probes are rapidly released from membranes, leading to fluorescence signal decay and loss of contrast. Here, water-soluble lipid-polymer probes are synthesized harboring hydrophilic or hydrophobic far-red emitting dyes, and exhibiting enhanced brightness. They efficiently label Hepatitis C Virus pseudotyped particles (HCVpp), more stably and reproducibly than commercial probes, and a strong fluorescence signal is observed with a high contrast. Labeling with such probes do not alter virion morphology, integrity, nor infectivity. Finally, it is shown by fluorescence microscopy that these probes enable efficient tracking of labeled HCVpp inside hepatocarcinoma cells used as model hepatocytes, in spite of their autofluorescence up to 700 nm. These novel fluorescent lipid-polymer probes should therefore enable a better characterization of early stages of infection of autofluorescent cells by enveloped viruses.
The chemotherapy-induced peripheral neuropathy (CIPN) outcome measure standardization (CI-PeriNomS) study: From consensus to validity and reliability in CIPN assessment.
Authors: Guido Cavaletti
Journal: Journal of Clinical Oncology (2012)

9089 Background: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a debilitating and dose limiting complication of cancer treatment. However, the impact of CIPN has never been studied in a clinimetric manner, in its impact on quality of life. This study was performed to select appropriate outcome measures and to establish, for the first time with a clinimetric approach, their validity and reproducibility. Methods: After literature review and a consensus meeting, face/content validity were obtained for the following scales: the National Cancer Institute Common-Toxicity-Criteria (NCI-CTC), the Total Neuropathy Score (TNSc), the modified INCAT sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CIPN20 quality of life measures. 281 patients with stable CIPN were examined through an EU/US collaboration involving 20 oncology/neurology centers. For each scale the inter- and intra-rater agreement was evaluated by means of weighted K-Cohen coefficients and 95% confidence intervals, when analyzing qualitative ordinal scales and by means of Spearman's rank correlation coefficient and t-test when analyzing quantitative ordinal scales. The adopted weights for the estimate of K-Cohen coefficients were the Fleiss-Cohen weights. For validity purposes, the Kruskal-Wallis equality-of-populations rank test was performed relating the mISS and TNSc to the NCI-CTC grades. Results: Proper, although slightly different, inter-/intra-observer scores (i.e. r &gt; 0.7) were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also high for the EORTC QLQ-C30 and for the recently developed and never formally tested CIPN20. Acceptable validity scores were obtained through correlation between the the mISS and TNSc to the NCI-CTC scores (p values ranging from 0.04 to &lt; 0.001). Conclusions: Proper validity and reliability scores were demonstrated for the set of selected outcome measures in CIPN. These results will allow to base new trials on a solid methodological background, although future studies are warranted to investigate the responsiveness issues.
Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer
Authors: Guangcun Cheng, Xuemei Fan, Mingang Hao, Jinglong Wang, Xiaoming Zhou, Xueqing Sun
Journal: Molecular Cancer (2016)

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein that can directly regulate apoptosis and metastasis. In this study, we investigated the functional and molecular mechanisms by which TIMP-1 influences triple-negative breast cancer (TNBC). The expression level of TIMP-1 in breast cancer tissues was analyzed using the ONCOMINE microarray database. The overall survival of patients with distinct molecular subtypes of breast cancer stratified by TIMP-1 expression levels was evaluated using Kaplan–Meier analysis. Bisulfate sequencing PCR (BSP) was used to analyze the methylation status of the TIMP-1 promoter. Real-time-PCR (RT-PCR), Western blot and ELISA assays were used to evaluate gene and protein expression in cell lines and human tissue specimens. In addition, TIMP-1 function was analyzed using a series of in vitro and in vivo assays with cells in which TIMP-1 was inhibited using RNAi or neutralizing antibodies. We found that serum TIMP-1 levels were strongly enhanced in patients with TNBC and that elevated TIMP-1 levels were associated with a poor prognosis in TNBC. However, TIMP-1 levels were not significantly associated with overall survival in other subtypes of breast cancer or in the overall population of breast cancer patients. We also report the first evidence that the TIMP-1 promoter is hypomethylated in TNBC cell lines compared with non-TNBC cell lines, suggesting that aberrant TIMP-1 expression in TNBC results from reduced DNA methylation. RNAi-mediated silencing of TIMP-1 in TNBC cells induced cell cycle arrest at the G1 phase and reduced cyclin D1 expression. In addition, mechanistic analyses revealed that the p-Akt and p-NF-κB signaling pathways, but not the GSK-3β and MAPK1/2 pathways, are associated with TIMP-1 overexpression in TNBC cells. Moreover, neutralizing antibodies against TIMP-1 significantly decreased the rate of tumor growth in vivo. Our findings suggest that TIMP-1 is a biomarker indicative of a poor prognosis in TNBC patients and that targeting TIMP-1 may provide an attractive therapeutic intervention specifically for triple-negative breast cancer patients.
Language and utilization of women's cancer screening: The association of Spanish language with receipt of mammography and Pap smear testing
Authors: G. Suneja, J. Diaz, M. Roberts, W. Rakowski
Journal: Journal of Clinical Oncology (2008)

1543 Background: Latina women are more likely to be diagnosed with advanced breast cancer and have higher mortality rates than non-Latina White women. Latinas’ cervical cancer rates are nearly twice that of non-Latina Whites and mortality rates are 50% higher. Some data suggest that low English proficiency is a barrier to cancer screening. The goal of this study was to examine the relationship between language and receipt of women's cancer screening tests among Latinas and non-Latinas using a geographically diverse, population-based sample of women. Methods: Cross-sectional analysis of the CDC's Behavioral Risk Factor Surveillance System (BRFSS) 2006 survey was conducted. Women completing the survey in a state recording data from English and Spanish-speaking participants were included. Women aged 21–64 and without hysterectomy were included in the study sample for Pap smear testing. The mammography sample was limited to women aged 40–64 years. We estimated crude and adjusted odds ratios of respondents’ reported test receipt by self-reported Latina/non-Latina ethnicity and language. Results: Of 53,598 respondents, 70% of Latinas responding in Spanish (LRS) reported having had mammography within the last 2 years, compared to 66% of Latinas responding in English (LRE) and 74% of English-speaking non-Latinas (NL). In multivariable analyses, LRS had 2.25 times the odds (AOR=2.25, 95% CI, 1.65–3.07), and LRE had 1.05 times the odds of having received mammography (AOR=1.05, 95% CI, 0.86–1.28) compared to NL. Of 60,363 respondents, 79% of LRS reported having had Pap smear testing within the last 3 years, compared to 77% of LRE and 84% of English-speaking NL. In multivariable analysis, compared to NL, LRS had 1.91 times the odds (AOR=1.91, 95% CI, 1.42–2.59) of having received Pap smear testing. LRE had the same odds of receiving Pap smear testing as NL (AOR=1.00, 95% CI, 0.82–1.81). Conclusions: Spanish-speaking Latinas had higher adjusted odds of receiving women's cancer screening tests as compared to English-speaking Latinas and English-speaking non-Latinas. Further investigation is needed to determine if these results are an accurate reflection of increased utilization of cancer screening services among Spanish-speaking Latina women. No significant financial relationships to disclose.
Brief Report: Influence of HLA–DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans
Authors: So‐Young Bang, Ji‐Young Choi, Songree Park, Jeongim Choi, Seung‐Jae Hong, Hye‐Soon Lee, Chan‐Bum Choi, Sang‐Cheol Bae
Journal: Arthritis & Rheumatology (2015)

To investigate the association between HLA-DRB1 alleles and systemic lupus erythematosus (SLE) susceptibility and features of SLE, such as clinical manifestations and autoantibody profiles, in a Korean population.We tested the genetic associations between HLA-DRB1 alleles and SLE susceptibility and clinical subphenotypes in 1,089 patients with SLE and 2,161 control subjects, including a discovery set (475 patients and 1,119 controls) and a replication set (614 patients and 1,042 controls). We used a relative predispositional effects (RPEs) method to examine the independent effect of each allele associated with SLE or its subphenotypes.We identified 4 HLA-DRB1 alleles that were associated with increased susceptibility to SLE, 2 of which had been detected previously (*15:01; P for RPE = 1.11 × 10(-13) , odds ratio [OR] 1.88) and *09:01 (P for RPE = 1.59 × 10(-5) , OR 1.46), and 2 of which were novel alleles (*08:03 [P for RPE = 8.80 × 10(-8) , OR 1.62]) and *07:01 (P for RPE = 1.14 × 10(-6) , OR 1.57)]. In addition, protective effects on the development of SLE were observed for 2 novel alleles (HLA-DRB1*12:02 [P for RPE = 6.35 × 10(-4) , OR 0.49]) and *11:01 [P for RPE = 1.24 × 10(-3) , OR 0.59]). The SLE risk alleles had an additive genetic effect, as demonstrated by the finding that double copies of these alleles (OR 3.38) had larger risk effects size compared with single copies (OR 1.95) and no copy (OR 1 [reference]). In a subphenotype analysis, various HLA-DRB1 alleles (including SLE risk alleles) were observed to have significant predispositional effects on diverse clinical manifestations. In particular, HLA-DRB1*15:01 (OR 2.30), *09:01 (OR 2.46), *07:01 (OR 2.61), and *08:03 (OR 2.97) were strongly associated with the risk of anti-Sm antibody production.We detected 6 HLA-DRB1 alleles that were associated with SLE in Koreans. The SLE risk alleles promoted the production of autoantibodies, including anti-Sm, and diverse clinical manifestations.
Three new lignan glucosides from the roots of Scutellaria baicalensis
Authors: Hailin Long, Haijing Zhang, Anjun Deng, Lin Ma, Lianqiu Wu, Zhihong Li, Zhihui Zhang, Wenjie Wang, Jiandong Jiang, Hailin Qin
Journal: Acta Pharmaceutica Sinica B (2016)

Three new lignan glucosides, baicalensinosides A-C (1-3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofuran-type lignan glycoside with a mono-hydroxyl substitution at the 7'-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin (OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 μmol/L, compounds 1-3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively.