tbuckley/cabot-search huggingface dataset:
African Ancestry–Specific Alleles and Kidney Disease Risk in Hispanics/Latinos
Authors: Holly J. Kramer, Adrienne M. Stilp, Cathy C. Laurie, Alex P. Reiner, James Lash, Martha L. Daviglus, Sylvia E. Rosas, Ana C. Ricardo, Bamidele O. Tayo, Michael F. Flessner, Kathleen F. Kerr, Carmen Peralta, Ramon Durazo-Arvizu, Matt Conomos, Timothy Thornton, Jerome Rotter, Kent D. Taylor, Jainwen Cai, John Eckfeldt, Han Chen, George Papanicolau, Nora Franceschini
Journal: Journal of the American Society of Nephrology (2016)

African ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry-specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit β gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios. Overall, 41.4% of participants were male, 44.6% of participants had a Caribbean background, and the mean age of all participants was 46.1 years. The Caribbean background group, compared with the Mainland background group, had a higher frequency of two APOL1 alleles (1.0% versus 0.1%) and the HBB variant (2.0% versus 0.7%). In the Caribbean background group, presence of APOL1 alleles (2 versus 0/1 copies) or the HBB variant (1 versus 0 copies) were significantly associated with albuminuria (odds ratio [OR], 3.2; 95% confidence interval [95% CI], 1.7 to 6.1; and OR, 2.6; 95% CI, 1.8 to 3.8, respectively) and albuminuria and/or eGFR<60 ml/min per 1.73 m2 (OR, 2.9; 95% CI, 1.5 to 5.4; and OR, 2.4; 95% CI, 1.7 to 3.5, respectively). The urine albumin-to-creatinine ratio genome-wide association scan identified associations with the HBB variant among all participants, with the strongest association in the Caribbean background group (P=3.1×10-10 versus P=9.3×10-3 for the Mainland background group). In conclusion, African-specific alleles associate with CKD in Hispanics/Latinos, but allele frequency varies by Hispanic/Latino background/ancestry.
Response to: ‘Could abatacept directly target expanded plasmablasts in IgG4-related disease?’ by Alegria <i>et al</i>
Authors: Motohisa Yamamoto, Hiroki Takahashi, Kenichi Takano, Tetsuo Himi, Hiroshi Nakase
Journal: Annals of the Rheumatic Diseases (2016)

Response to: 'Could abatacept directly target expanded plasmablasts in IgG4-related disease?' by Alegria et alWe thank Alegria et al 1 for their response to our letter. 2IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory disorder that can involve various organs, but its origin remains unknown. 3Although elevated levels of circulating plasmablasts are observed in the active phase of IgG4-RD 4 5 the pathogenesis cannot be fully explained by plasmablasts alone.In our report, 2 we described a patient treated with abatacept who presented with complete depletion of circulating CD19 + cells at the secondary failure of rituximab.Because the serum levels of IgG4 decreased suddenly, the circulating plasmablasts and tissue resident plasma cells might also have decreased (figure 1).Despite this condition, the patient relapsed.It is important to identify the mechanism of the secondary failure of rituximab in this patient, and we consider that T cells play an important role in the pathogenesis of IgG4-RD.As previously described, we did not know the specific reason why abatacept was effective in this patient because there was no expression of CD28 in the biopsy specimens.It is possible that follicular helper T cells are decreased by abatacept. 2Alternatively, abatacept may make dendritic cells and macrophages secrete indoleamine 2,3-deoxygenase, which can inhibit the proliferation of T cells. 6As Alegria et al noted, there is of course the possibility that abatacept affects both CD19 + B cells and CD19 + CD38 high plasmablasts.It was recently reported that abatacept is effective for systemic lupus erythematosus (SLE). 7Elevated levels of plasmablasts, which have a population, that is, different from IgG4-RD, are observed in SLE. 8 Understanding how abatacept works in SLE may be a reference for understanding why it was effective in this patient.This patient has now successfully completed a 17th administration of abatacept without any adverse effects, and her condition is very good.Although her serum levels of IgG4 initially continued to decline, they have recently remained around 200 mg/dL.We consider that maintenance treatment is needed even when administering abatacept.It is important to both identify the reasons for the efficacy of abatacept in IgG4-RD and verify the clinical efficacy of abatacept in IgG4-RD.
Long-term survival after reduced-intensity allogeneic transplantation for advanced lymphoproliferative disorders
Authors: D Bron, Pierre Zachee, K Theunissen, A Ferrant, P Lewalle, C Doyen, L Noens, Walter Schroyens, D Selleslag, H Demuynck, R Schots, S Michiels, A De Meuter, Johan Maertens
Journal: Annals of Oncology (2011)
XPD and ERCC1 polymorphisms of the nucleotide excision repair pathway in outcome of larynx squamous cell carcinoma patients.
Authors: Carla Tyene Nakata, Ericka Francislaine Dias Costa, Bruno De Araujo Lima Franca, Leisa Lopes Aguiar, Fernanda Proa Ferreira, Ligia Traldi Macedo, Carlos Takahiro Chone, Jose A. Rinck, Gustavo Jacob Lourenco, Carmen Silvia Passos Lima
Journal: Journal of Clinical Oncology (2016)

e17523 Background: DNA repair plays an important role in head and neck squamous cell carcinoma (HNSCC) development. Inherited genetic alterations, such as single nucleotide polymorphisms (SNPs), may influence the individual ability of repairing DNA damage, having proliferation of tumor cells as consequence. The roles of XPD c.2251A > C and ERCC1 c.354C > T SNPs in outcome of larynx squamous cell carcinoma (LSCC) patients are unclear, and therefore this was the aim of the present study. Methods: DNA of 144 patients (132 males, 12 females; 114 well or moderately differentiated tumors, 13 poor differentiated tumors; 36 tumors of stages I or II, 108 tumors of stages III or IV) was analyzed by PCR-RFLP. Patients were treated by surgery, radio and/or chemotherapy with cisplatin. The statistical analyses were realized using the Kaplan-Meier method and univariate and multivariate Cox analyses. Results: The median follow-up time of 144 LSCC patients was 43.4 months (range: 1.0-140.5 months). The estimated probabilities of 60-month progression-free survival (PFS) and overall survival (OS) were 50.7% and 51.6%, respectively. At the date of analysis, January 2016, 70 patients were alive, 7 of them with LSCC and 63 without LSCC, 74 patients died, 56 of them by disease and 18 by others causes. At 60 months of follow-up, PFS and OS were shorter in males and in patients with poorly differentiated tumors and stage III or IV tumors (Kaplan-Meier estimates, univariate and multivariate Cox analyses), as previously reported. A tendency for worse PFS was seen in patients with XPD AA or AC genotype when compared to others (47.8% vs. 76.9%, P= 0.06). Patients with XPD AA or AC genotype had 3.50 more chances for relapsing in multivariate analysis. Patients with the AC haplotype (wild alleles of XPD c.2251A > C and ERCC1 c.354C > T SNPs) (44.1% vs. 60.7%, P= 0.04) presented worse PFS compared to others (Kaplan-Meier estimates). Carriers of the AC haplotype had 1.77 more chances of tumor relapse on multivariate analysis. Conclusions: Our data present preliminary evidence that XPDc.2251A > C and ERCC1c.354C > T SNPs acts as independent prognostic factors in patients with LSCC, possibly due to their effects on chemoradiation.
Serpinb3 Up-Regulates Hypoxia Inducible Factors-1alpha and -2alpha in Liver Cancer Cells through Different Mechanisms
Authors: S. Cannito, G. Villano, C. Turato, E. Morello, B. Foglia, E. Novo, S. Quarta, S. Colombatto, F. Lopitz-Otsoa, T. Cardoso, M.L. Martinez-Chantar, P. Pontisso, M. Parola
Journal: Journal of Hepatology (2016)
Liver serine palmitoyltransferase activity deficiency in early life impairs adherens junctions and promotes tumorigenesis
Authors: Zhiqiang Li, Inamul Kabir, Hui Jiang, Hongwen Zhou, Jenny Libien, Jianying Zeng, Albert Stanek, Peiqi Ou, Kailyn R. Li, Shane Zhang, Hai H. Bui, Ming‐Shang Kuo, Tae‐Sik Park, Benjamin Kim, Tilla S. Worgall, Chongmin Huan, Xian‐Cheng Jiang
Journal: Hepatology (2016)

Serine palmitoyltransferase is the key enzyme in sphingolipid biosynthesis. Mice lacking serine palmitoyltransferase are embryonic lethal. We prepared liver-specific mice deficient in the serine palmitoyltransferase long chain base subunit 2 gene using an albumin-cyclization recombination approach and found that the deficient mice have severe jaundice. Moreover, the deficiency impairs hepatocyte polarity, attenuates liver regeneration after hepatectomy, and promotes tumorigenesis. Importantly, we show that the deficiency significantly reduces sphingomyelin but not other sphingolipids in hepatocyte plasma membrane; greatly reduces cadherin, the major protein in adherens junctions, on the membrane; and greatly induces cadherin phosphorylation, an indication of its degradation. The deficiency affects cellular distribution of β-catenin, the central component of the canonical Wnt pathway. Furthermore, such a defect can be partially corrected by sphingomyelin supplementation in vivo and in vitro.The plasma membrane sphingomyelin level is one of the key factors in regulating hepatocyte polarity and tumorigenesis. (Hepatology 2016;64:2089-2102).
An exploration of relapse data by hazard rate as a means of developing biological insights into the natural history and treatment of breast cancer: Data from the ’Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial and the Milan Institute database
Authors: M. Baum, J. Cuzick, A. Howell, A. Buzdar, R. Demicheli, M. Greco, M. Retsky, B. Hrushesky
Journal: Journal of Clinical Oncology (2005)

612 Background The hazard rate (HR) for relapse following primary surgery for breast cancer demonstrates two peaks. The first, and steepest, peak occurs at approximately 18–24 months after surgery and may result from the activation of dormant/latent metastases by the initiation of angiogenesis, the expression of the genetic mechanisms responsible for wound healing, and the induction of proliferative activity in single quiescent tumor cells through growth factors. The second, flatter, peak occurs approximately 5–6 years after surgery and is thought to result from the stochastic transition of occult metastases from a latent to an active state, representing an “echo” of the natural history of the original disease. Method The ATAC trial compared 5 years of adjuvant tamoxifen (T) versus 5 years of adjuvant anastrozole (A), a third-generation aromatase inhibitor (AI), in women with early breast cancer, and 68-month follow-up data were reported in December 2004. Here, we compare this data with a matched series from the Milan Institute database of patients, who were treated before the introduction of systemic adjuvant therapy to produce a semi-quantitative comparison. Results The shape and timing of the signal for HR were identical for each of the three data sets (T, A and Milan), with the first peak at 18–24 months and the second peak beginning to appear at 4–5 years following primary therapy. However, in the T and A groups, the peaks were substantially flattened. The most striking aspect of our comparison was the near-obliteration of the first peak in the A group. Conclusion A possible explanation for the reduction in the first peak with anastrozole relates to the fact that COX2 expression, a natural response to wounding, leads indirectly to the activation of the aromatase enzyme. Therefore, an AI might in part suppress the activation of dormant metastases by the act of surgery. If this is the case, AIs should be initiated at (or even before) surgery in order to optimize this effect. Furthermore, this benefit might be enhanced by the concomitant use of a COX2 inhibitor. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Novartis, Pfizer AstraZeneca AstraZeneca, Novartis, Pfizer
Lenalidomide Administered for the Initial Treatment of Chronic Lymphocytic Leukemia (CLL) Patients- In Vivo Modulation of the Leukemia Cell Surface Phenotype and Association with Tumor Flare Reaction (TFR).
Authors: Danelle James, Esther D Avery, Ling Zhang, Jamie Gould, Andrew Greaves, Januario E. Castro, Laura Z. Rassenti, Thomas J. Kipps
Journal: Blood (2009)
Statins Are Associated With Reduced Mortality in Multiple Myeloma
Authors: Kristen Marie Sanfilippo, Jesse Keller, Brian F. Gage, Suhong Luo, Tzu-Fei Wang, Gerald Moskowitz, Jason Gumbel, Brandon Blue, Katiuscia O’Brian, Kenneth R. Carson
Journal: Journal of Clinical Oncology (2016)

Purpose The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and Methods From the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. Results We identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P < .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P < .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. Conclusion In this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies.
Quality of basic maternal care functions in health facilities of five African countries: an analysis of national health system surveys
Authors: Margaret E Kruk, Hannah H Leslie, Stéphane Verguet, Godfrey M Mbaruku, Richard M K Adanu, Ana Langer
Journal: The Lancet Global Health (2016)

Global efforts to increase births at health-care facilities might not reduce maternal or newborn mortality if quality of care is insufficient. However, little systematic evidence exists for the quality at health facilities caring for women and newborn babies in low-income countries. We analysed the quality of basic maternal care functions and its association with volume of deliveries and surgical capacity in health-care facilities in five sub-Saharan African countries.In this analysis, we combined nationally representative health system surveys (Service Provision Assessments by the Demographic and Health Survery Programme) with data for volume of deliveries and quality of delivery care from Kenya, Namibia, Rwanda, Tanzania, and Uganda. We measured the quality of basic maternal care functions in delivery facilities using an index of 12 indicators of structure and processes of care, including infrastructure and use of evidence-based routine and emergency care interventions. We regressed the quality index on volume of births and confounders (public or privately managed, availability of antiretroviral therapy services, availability of skilled staffing, and country) stratified by facility type: primary (no caesarean capacity) or secondary (has caesarean capacity) care facilities. The Harvard University Human Research Protection Program approved this analysis as exempt from human subjects review.The national surveys were completed between April, 2006, and May, 2010. Our sample consisted of 1715 (93%) of 1842 health-care facilities that provided normal delivery service, after exclusion of facilities with missing (n=126) or invalid (n=1) data. 1511 (88%) study facilities (site of 276 965 [44%] of 622 864 facility births) did not have caesarean section capacity (primary care facilities). Quality of basic maternal care functions was substantially lower in primary (index score 0·38) than secondary care facilities (0·77). Low delivery volume was consistently associated with poor quality, with differences in quality between the lowest versus highest volume facilities of -0·22 (95% CI -0·26 to -0·19) in primary care facilities and -0·17 (-0·21 to -0·11) in secondary care facilities.More than 40% of facility deliveries in these five African countries occurred in primary care facilities, which scored poorly on basic measures of maternal care quality. Facilities with caesarean section capacity, particularly those with birth volumes higher than 500 per year, had higher scores for maternal care quality. Low-income and middle-income countries should systematically assess and improve the quality of delivery care in health facilities to accelerate reduction of maternal and newborn deaths.None.
Five-Year on-Treatment Systematically Monitoring of Dynamic Changes of Liver Stiffness Measurement with Transient Elastography Compared with Paired Liver Biopsies in a Randomized Controlled Trial in Chronic Hepatitis B Patients
Authors: J. Sun, Q. Xie, D. Tan, Q. Ning, J. Niu, X. Bai, R. Fan, X. Liang, S. Chen, J. Cheng, Y. Yu, H. Wang, M. Xu, G. Shi, M. Wan, X. Chen, H. Tang, J. Sheng, X. Dou, J. Shi, H. Ren, M. Wang, H. Zhang, Z. Gao, C. Chen, H. Ma, Y. Chen, J. Jia, J. Hou
Journal: Journal of Hepatology (2016)
Insured Patients with Hepatocellular Carcinoma in the United States are More Likely to have Hepatocellular Carcinoma within Milan Criteria, are More Likely to Receive Treatment, and have Higher Survival Compared to Uninsured and Medicaid Patients
Authors: J. Wang, J. Ha, M. Tana, T. Bhuket, B. Liu, Z. Younossi, R. Wong
Journal: Journal of Hepatology (2016)
The Accuracy of Transient Elastography and Comparison of Non-Invasive Markers for Assessing Fibrosis in Korean Patients with Non-Alcoholic Fatty Liver Disease
Authors: L.H. Won, C.K. Sik, K.B. Kyung, K.S. Up, K. Do Young, A.S. Hoon, P.Y. Nyun, H. Kwang-Hyub, P.J. Yong
Journal: Journal of Hepatology (2016)
Les taux des marqueurs viraux chez les donneurs de sang non-rémunérés en Europe ont diminué de 1990 à 1996
Authors: K Müller-Breitkreutz, T Evers, R Perry
Journal: Eurosurveillance (1998)

Malgre l’application universelle des technologies d’inactivation et d’elimination virales pendant la preparation des produits derives du plasma (1,2), l’exclusion des dons infectieux avant toute autre procedure reste la premiere etape essentielle pour la securite des produits derives du plasma et le determinant majeur pour la securite des produits sanguins labiles non traites.
AVDLIB 2: News Direct-Acting Antiviral (DDA) in HCV Patients with Advanced Liver Disease. Final Results of a the Second Multicenter Prospective Observational Study in Real Life Practice in France
Authors: D. Ouzan, G. Penaranda, P. Delasalle, C. Renou, M. Antoni, P. Toulemonde, P. Halfon, S. Bresson-Hadni, J. Liautard, M. Bourlière
Journal: Journal of Hepatology (2016)
Six Cycles of BEACOPP Tailored Based on Interim Scintigraphy Provide Favorable Outcome for Patients with Standard and Advanced Risk Hodgkin Lymphoma and Female Fertility Is Preserved: Results of a 10-Year Follow-up
Authors: Eldad J Dann, Zeev Blumenfeld, Rachel Bar-Shalom, Irit Avivi, Menachem Ben-Shachar, Odelia Goor, Diana Libster, Diana Gaitini, Jacob M. Rowe, Ron Epelbaum
Journal: Blood (2011)
Patients with Relapsed or Progressive Multiple Myeloma Treated with Lenalidomide in the Compassionate Use Program. Spanish Registry, Preliminary Analysis.
Authors: Adrian Alegre, B. Aguado, A. Alonso, V. Anso, C. Cabrera, M. Fuertes, A. Garcia, I. Garcia, J. Hernandez, A. Ibañez, J. Martinez, G. Ramirez, J.N. Rodriguez, J. Vercher, R. Rodríguez-Notario, J. de la Serna
Journal: Blood (2007)
Multicenter observational study of reactivation of hepatitis B virus (HBV) caused by chemotherapy for solid tumors (ST).
Authors: Shunsuke Kondo, Masafumi Ikeda, Masatoshi Kudo, Seijin Nadano, Junji Furuse, Yukio Osaki, Takashi Kumada, Kazuyoshi Ohkawa, Masashi Mizokami
Journal: Journal of Clinical Oncology (2014)

1590 Background: Reactivation of HBV has often been reported in patients (pts) with malignant lymphoma administered combination chemotherapy regimens containing rituximab. Recently, HBV reactivation has been reported even in pts with STs. However, the incidence of HBV reactivation in pts with STs and the treatment outcomes in pts with HBV reactivation have not yet been fully elucidated. Therefore, we prospectively investigated the incidence of HBV reactivation in pts with STs receiving first-line chemotherapy and the clinical outcomes of these patients. Methods: ST pts with seropositivity for HBsAg [sAg(+)], or seronegativity for HBsAg and seropositivity for HBcAb and/or HBsAb [c/sAb(+)], receiving first-line chemotherapy including neoadjuvant or adjuvant chemotherapy, were enrolled. HBV DNA was at least measured at the termination of the first-line chemotherapy, and at 3, 6, and 12 months after the termination of first-line chemotherapy. It was also measured in cases where HBV reactivation was suspected, such as based on increase in the serum levels of transaminases. HBV reactivation was defined as a 10-fold or greater increase in the titer of HBV DNA. Results: A total of 379 pts [sAg(+), 35 pts; c/sAb(+), 344 pts] were enrolled in this study. Any cancer types and regimens were included, and the median period of measurements of HBV DNA was 74 days (range, 13-248 days). Among the pts with sAg(+), HBV reactivation occurred in 9 pts, and the incidence rates at 6, 12 and 18 months were 6.8%, 30.0%, and 35.8%, respectively. Among pts with c/sAb(+), HBV reactivation occurred in 7 pts, and the incidence rates at 6, 12 and 18 months were 0.6%, 2.0% and 3.1%, respectively. Four of the seven pts with c/sAb(+) showing HBV reactivation improved without antiviral therapy, and there were no pts with increased serum transaminase levels or fulminant hepatitis in this series. Conclusions: HBV reactivation in ST pts with c/sAb(+) was rare, and no case with clinically significant HBV reactivation was detected by periodic measurement of HBV DNA and proper management at the first sign of reactivation. Clinical trial information: UMIN000005369.
Cultural group selection is plausible, but the<i>predictions</i>of its hypotheses should be tested with real-world data
Authors: Peter Turchin, Thomas E. Currie
Journal: Behavioral and Brain Sciences (2016)

Abstract The evidence compiled in the target article demonstrates that the assumptions of cultural group selection (CGS) theory are often met, and it is therefore a useful framework for generating plausible hypotheses. However, more can be said about how we can test the predictions of CGS hypotheses against competing explanations using historical, archaeological, and anthropological data.
P0381 : Clinical impact of achieving sustained virological response in hepatitis C virus-infected patients with early stage hepatocellular carcinoma
Authors: K. Tsuchiya, Y. Asano, N. Tamaki, Y. Yasui, S. Suzuki, T. Hosokawa, H. Nakanishi, J. Itakura, M. Kurosaki, N. Izumi
Journal: Journal of Hepatology (2015)
PUB130 Thymic Malignancies. A Single Institution Series from 2006-2016
Authors: Flávio Cabral, Maria Tsukazan, Jayme Rios, Jayme Heck, Renata Rosental, Gabriel Schwarcke, Maicon Cimarosti, Joao Schmit, Antonio Pinto
Journal: Journal of Thoracic Oncology (2017)