tbuckley/cabot-search huggingface dataset:
Epidemiology and socioeconomic impact of the rheumatic diseases on indigenous people: an invisible syndemic public health problem
Authors: Ingris Peláez-Ballestas, Ysabel Granados, Rosana Quintana, Adalberto Loyola-Sánchez, Flor Julián-Santiago, Celenia Rosillo, Alfonso Gastelum-Strozzi, Jose Alvarez-Nemegyei, Natalia Santana, Adriana Silvestre, Cesar Pacheco-Tena, Mario Goñi, Conrado García-García, Ligia Cedeño, Bernardo A Pons-Éstel
Journal: Annals of the Rheumatic Diseases (2018)

Epidemiological studies in Latin America suggest indigenous people lack proper healthcare for musculoskeletal (MSK) and rheumatic diseases. Objectives This study aimed to estimate the prevalence of MSK disorders and rheumatic diseases in eight Latin American indigenous communities, and to identify which factors influence such prevalence using network analysis and syndemic approach. Methods This is a cross-sectional, community-based census study according to Community-Oriented Program for the Control of Rheumatic Diseases methodology. Individuals with MSK pain, stiffness or swelling in the past and/or during the last 7 days were evaluated by participating physicians. A descriptive, univariable and multivariable analysis was performed, followed by a network analysis. Results We surveyed 6155 indigenous individuals with a mean age of 41.2 years (SD 17.6; range 18–105); 3757 (61.0%) were women. Point prevalence in rank order was: low back pain in 821 (13.3%); osteoarthritis in 598 (9.7%); rheumatic regional pain syndromes in 368 (5.9%); rheumatoid arthritis in 85 (1.3%); undifferentiated arthritis in 13 (0.2%); and spondyloarthritis in 12 (0.1%). There were marked variations in the prevalence of each rheumatic disease among the communities. Multivariate models and network analysis revealed a complex relationship between rheumatic diseases, comorbidities and socioeconomic conditions. Conclusions The overall prevalence of MSK disorders in Latin American indigenous communities was 34.5%. Although low back pain and osteoarthritis were the most prevalent rheumatic diseases, wide variations according to population groups occurred. The relationship between rheumatic diseases, comorbidities and socioeconomic conditions allows taking a syndemic approach to the study.
Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma
Authors: Regina Alemany, David S. Moura, Andres Redondo, Javier Martinez-Trufero, Silvia Calabuig, Carlos Saus, Antonia Obrador-Hevia, Rafael Ramos, Victor H. Villar, Claudia Valverde, Maria Angeles Vaz, Javier Medina, Irene Felipe-Abrio, Nadia Hindi, Miguel Taron, Javier Martin-Broto
Journal: Clinical Cancer Research (2018)

Purpose: Nilotinib plus doxorubicin showed to be synergistic regarding apoptosis in several sarcoma cell lines. A phase I/II trial was thus designed to explore the feasibility of nilotinib as coadjuvant of doxorubicin by inhibiting MRP-1/P-gp efflux activity. The phase I part of the study is presented here.Patients and Methods: Nilotinib 400 mg/12 hours was administered in fixed dose from day 1 to 6, and doxorubicin on day 5 of each cycle. Three dose escalation levels for doxorubicin at 60, 65, and 75 mg/m2 were planned. Cycles were repeated every 3 weeks for a total of 4 cycles. Eligible subtypes were retroperitoneal liposarcoma, leiomyosarcoma, and unresectable/metastatic high-grade chondrosarcoma.Results: Thirteen patients were enrolled: 7 chondrosarcoma, 4 liposarcoma, and 2 leiomyosarcoma. In 46 cycles administered, the most relevant grade 3/4 adverse effects per patient were neutropenia 54%, febrile neutropenia 15%, and asthenia 8%. No cardiac toxicity was observed. Only one dose-limiting toxicity (febrile neutropenia) was reported in the third dose level. With regard to efficacy, 1 partial response (1 liposarcoma), 9 stable diseases (5 chondrosarcoma, 2 liposarcoma, 1 leiomyosarcoma), and 3 progressive diseases (2 chondrosarcoma and 1 leiomyosarcoma) were present. ABCB1 and ABCC1 RNA expression levels decreased by 58.47-fold and 1.47-fold, respectively, on day 5 of the cycle.Conclusions: Combination of MRP-1/P-gp inhibitor, nilotinib, as coadjuvant with doxorubicin is feasible; it appears not to add substantial toxicity compared with doxorubicin alone. Pharmacodynamic study supports this concept. The recommended dose for the phase II part for doxorubicin was 75 mg/m2Clin Cancer Res; 24(21); 5239-49. ©2018 AACR.
The importance of exact conceptual replications
Authors: Richard E. Petty
Journal: Behavioral and Brain Sciences (2018)

Abstract Although Zwaan et al. argue that original researchers should provide a replication recipe that provides great specificity about the operational details of one's study, I argue that it may be as important to provide a recipe that allows replicators to conduct a study that matches the original in as many conceptual details as possible (i.e., an exact conceptual replication).
Incorporating Coexisting Chronic Illness into Decisions about Patient Selection for Lung Cancer Screening. An Official American Thoracic Society Research Statement
Authors: M. Patricia Rivera, Nichole T. Tanner, Gerard A. Silvestri, Frank C. Detterbeck, Martin C. Tammemägi, Robert P. Young, Christopher G. Slatore, Tanner J. Caverly, Cynthia M. Boyd, Dejana Braithwaite, Joelle T. Fathi, Michael K. Gould, Jonathan M. Iaccarino, Stephen P. Malkoski, Peter J. Mazzone, Lynn T. Tanoue, Nancy L. Schoenborn, Javier J. Zulueta, Renda Soylemez Wiener
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsResultsDiscussionReferencesCITING ARTICLES
Identification of the Oxidized Low-Density Lipoprotein Scavenger Receptor CD36 in Plasma
Authors: AaseHandberg, KlausLevin, KurtHøjlund, HenningBeck-Nielsen
Journal: Circulation (2006)

Background— Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature atherosclerosis is the major cause of morbidity and mortality in type 2 diabetes. Here, we report the identification of a soluble form of CD36 (sCD36) in plasma and hypothesize that sCD36 would be elevated in patients with type 2 diabetes and insulin resistance. Methods and Results— sCD36 in plasma was demonstrated by immunopurification and Western blotting. We established ELISA assays to determine sCD36 in plasma and measured sCD36 in obese type 2 diabetic patients, obese nondiabetic relatives, and obese and lean control subjects. sCD36 was markedly elevated in type 2 diabetic patients compared with both lean (5-fold) and obese (2- to 3-fold) control subjects. There was a strong, inverse correlation between sCD3...
Activation of CD4+ T Lymphocytes Improves Wound Healing and Survival After Experimental Myocardial Infarction in Mice
Authors: UlrichHofmann, NiklasBeyersdorf, JohannesWeirather, AnnaPodolskaya, JohannBauersachs, GeorgeErtl, ThomasKerkau, StefanFrantz
Journal: Circulation (2012)

Background—The role of adaptive immunity, especially CD4+ T-helper cells, has not yet been systematically investigated in wound healing and remodeling after myocardial infarction (MI). Therefore, we studied whether CD4+ T cells become activated and influence wound healing after experimental MI in mice. Methods and Results—When we compared sham versus MI in wild-type (WT) mice, T-cell receptor–dependent activation of both conventional Foxp3− and regulatory Foxp3+ CD4+ T cells could be demonstrated in heart-draining lymph nodes within the first week after MI. Concomitantly, we found infiltration of CD4+ T cells in infarcted myocardium. To study the role of CD4+ T cells in wound healing and remodeling, CD4+ T-cell–deficient mice (CD4 knockout [KO], MHCIIΔ/Δ) and T-cell receptor–transgenic OT-II mice recognizing an irrelevant ovalbumin-derived peptide were studied. Serial echocardiography up to day 56 after MI revealed increased left ventricular dilation in CD4 KO compared with WT mice. Within the infarcted m...
Prognostic Significance of Tumor-Infiltrating B Cells and Plasma Cells in Human Cancer
Authors: Maartje C.A. Wouters, Brad H. Nelson
Journal: Clinical Cancer Research (2018)

Abstract There is abundant evidence that tumor-infiltrating CD8+ T cells contribute positively to antitumor immunity; however, the role of tumor-infiltrating B cells (TIL-B) and plasma cells (PC) remains controversial, leading to differing opinions about whether immunotherapies should be designed to enhance or inhibit these cells. Through a comprehensive PubMed search, we reviewed publications with cohorts of 50 or more cases in which the prognostic value of TIL-B/PC was assessed by immunohistochemistry and/or gene-expression analysis. Sixty-nine studies representing 19 cancers met our review criteria. The large majority of studies assessed TIL-B by immunohistochemical detection of CD20. Of these, 50.0% reported a positive prognostic effect for CD20+ TIL-B, whereas the remainder found a neutral (40.7%) or negative (9.3%) effect. These differences in prognostic effect were not attributable to cancer type, other clinicopathologic factors, or differing technical approaches. The prognostic significance of TIL-B/PC was generally concordant with that of CD3+ and/or CD8+ T cells, and the prognostic effect of T cells was generally stronger when TIL-B and/or PC were also present. Additionally, 21 studies inferred the presence of TIL-B/PC from gene-expression data, and a large majority reported a positive prognostic effect. Although more studies are required involving additional cancer types and independent patient cohorts, the weight of evidence supports a positive role for TIL-B and PC in antitumor immunity, suggesting that enhancement of these responses should be considered in the design of cancer immunotherapies.
Retinoic Acid Receptor‐β Is Downregulated in Hepatocellular Carcinoma and Cirrhosis and Its Expression Inhibits Myosin‐Driven Activation and Durotaxis in Hepatic Stellate Cells
Authors: Ernesto Cortes, Dariusz Lachowski, Alistair Rice, Antonios Chronopoulos, Benjamin Robinson, Stephen Thorpe, David A Lee, Lucia A Possamai, Haiyun Wang, David J Pinato, Armando E. del Río Hernández
Journal: Hepatology (2018)

Hepatic stellate cells (HSCs) are essential perisinusoidal cells in both healthy and diseased liver. HSCs modulate extracellular matrix (ECM) homeostasis when quiescent, but in liver fibrosis, HSCs become activated and promote excess deposition of ECM molecules and tissue stiffening via force generation and mechanosensing. In hepatocellular carcinoma (HCC), activated HSCs infiltrate the stroma and migrate to the tumor core to facilitate paracrine signaling with cancer cells. Because the function of HSCs is known to be modulated by retinoids, we investigated the expression profile of retinoic acid receptor beta (RAR-β) in patients with cirrhosis and HCC, as well as the effects of RAR-β activation in HSCs. We found that RAR-β expression is significantly reduced in cirrhotic and HCC tissues. Using a comprehensive set of biophysical methods combined with cellular and molecular biology, we have elucidated the biomechanical mechanism by which all trans-retinoic acid promotes HSC deactivation via RAR-β-dependent transcriptional downregulation of myosin light chain 2 expression. Furthermore, this also abrogated mechanically driven migration toward stiffer substrates. Conclusion: Targeting mechanotransduction in HSCs at the transcriptional level may offer therapeutic options for a range of liver diseases.
Outcomes Following Neoadjuvant Chemotherapy for Breast Cancer in Women Aged 40 Years and Younger: Impact of Pathologic Nodal Response
Authors: Margaret M. Kozak, Clare E. Jacobson, Rie von Eyben, Erqi L. Pollom, Melinda Telli, Kathleen C. Horst
Journal: Journal of the National Comprehensive Cancer Network (2018)

Purpose: We sought to evaluate whether pathologic nodal response was predictive of outcomes in women aged ≤40 years with breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: A total of 220 patients treated with NAC between 1991 and 2015 were retrospectively reviewed. Pathologic complete response (pCR) was defined as no evidence of residual invasive tumor in the breast and lymph nodes (LNs) (ypT0/Tis ypN0); partial response if there was no tumor in the LNs but residual tumor in the breast (ypT+ ypN0) or residual tumor in the LNs (ypT0/Tis ypN+); and limited response if there was residual tumor in both the breast and the LNs (ypT+ ypN+). Kaplan-Meier and Cox proportional hazards analyses were performed to identify factors predictive for overall survival (OS). Results: A total of 155 patients were included. Following NAC, 39 patients (25.2%) achieved pCR, 57 (36.8%) achieved a partial response (either ypT+ ypN0 or ypT0/Tis ypN+), and 59 (38.1%) had a limited response. A total of 22 patients (14.2%) experienced local failure, 20 (12.9%) experienced regional failure, and 59 (38.1%) experienced distant failure. Median OS for patients who achieved pCR was not reached, and was significantly worse for patients who had residual disease in the breast and/or LNs (P<.001). No difference in OS was seen among patients who had residual disease in the breast alone versus those who remained LN-positive (97 vs 83 months, respectively; P=.25). Subset analysis did not reveal differences in OS based on year of treatment or cN1 disease at the time of initial diagnosis. Conclusions: Women aged ≤40 years who achieved pCR had excellent outcomes; however, those who achieved a pathologic response in the LNs but had residual disease in the breast continued to have outcomes similar to those who remained LN-positive.
Combined local immunostimulatory radioisotope therapy and systemic immune checkpoint blockade imparts potent antitumour responses
Authors: Yu Chao, Ligeng Xu, Chao Liang, Liangzhu Feng, Jun Xu, Ziliang Dong, Longlong Tian, Xuan Yi, Kai Yang, Zhuang Liu
Journal: Nature Biomedical Engineering (2018)
Incidence of Gastroschisis in California
Authors: Jamie E. Anderson, Yvonne Cheng, Jacob T. Stephenson, Payam Saadai, Rebecca A. Stark, Shinjiro Hirose
Journal: JAMA Surgery (2018)

Albert Stuart Reece, MBBS (Hons), FRCS (Ed), FRCS (Glas), FRACGP, MD; Gary Kenneth Hulse, PhD, BBSc (Hons), MBSc
Sustained oligoclonal T cell expansion correlates with durable response to anti-PD1 therapy.
Authors: Sope Omowale Olugbile, Kazuma Kiyotani, Jae Hyun Park, Philip C. Hoffman, Livia Szeto, Jyoti D. Patel, Everett E. Vokes, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2017)

3061 Background: Immune checkpoint blockers have demonstrated durable response in many tumor types including lung cancer. This clinical benefit is however restricted to a subset of patients in whom longitudinal assessments of their tumor microenvironment have revealed increase CD8+ T cell infiltration. However detailed characterization of this T cell dynamics at clonal levels in a large population of patients is yet to be reported. Such analyses will provide vital insight into the mechanism of tumor eradication in responders. Methods: We performed next-generation sequencing of T cell receptor β chain in longitudinal tumor and peripheral blood samples obtained from lung cancer patients treated with immunotherapies. We first extracted RNA from these samples and synthesized cDNA with 5’RACE adapter using SMART library construction kit (Clontech). We then amplified TCR β gene products to prepare sequence libraries which were analyzed with MiSeq system (Illumina). Results: Here we report on TCR receptor β chain sequencing data for 29 patients in whom we had 3 or more serial samples. Thirteen (45%) of the selected patients in this cohort had durable response and seven (24%) had radiological complete response. We confirmed that there is concordance between the expanded T cell clone at tumor site and the peripheral blood. In one responder, we found expansion of a dominant T cell clone (20%) at a metastatic site where he had pathological complete response on day 17 of treatment and the same clone remained persistent in his peripheral blood (24%) at week 48 of therapy. Similarly in other responders, there were T cell clonal expansions detected as early as week 2 after only one cycle of treatment and such clones remained at high frequencies several months afterwards. Such pattern of early and sustained clonal expansions were absent among non-responders even while they remained on therapy. Conclusions: We found durable response to immune checkpoint blockade to correlate with early and sustained expansion of one to two dominant T cell clones in this selected patient cohort.
Abstract 13691: Long-Term Outcomes of Elderly Patients Who Underwent Surgery, Angioplasty or Medical Treatment - 10 Year Follow-Up. Mass II Trial
Authors: Paulo C Rezende, Eduardo G Lima, Ricardo D Vieira, Cibele L Garzillo, Desidério Favarato, Alexandre C Pereira, Alexandre C Hueb, Paulo R Soares, Jose A Ramires, Whady Hueb
Journal: Circulation (2011)

Purpose:  As population becomes proportionally older, Coronary Artery Disease (CAD) is diagnosed in more advanced ages. There are few studies comparing the treatment options for CAD in elderly patients. This current investigation compares the treatment options for CAD in patients ≥ 65 years.   Methods:  This study is a post-hoc analysis of the Medical, Angioplasty or Surgery Study (MASS II), a randomized trial comparing medical treatment (MT), percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) in 611 multivessel CAD patients with preserved left ventricular function. Patients were separated according to age: ≥ 65 years (n=200) and    Results:  Patients ≥ 65 years (n=200) were randomized for MT (n=68), PCI (n=68) or CABG (n=64) treatment. The overall survival rates in each strategy were 63% MT, 69% PCI and 66% CABG, p=0.93. The survival rates free of combined events were 43% MT, 38% PCI and 66% CABG, p =0.007. The survival rates free of MI were 82% MT, 77% PCI and 90% CABG, p = 0.17 and the survival rates free of reinterventions were 59% MT, 58% PCI and 91% CABG, p=0.0003. When we compare the groups (age ≥ 65 years versus age   Conclusion  There was no prognostic difference between the three options for the treatment of CAD in elderly patients in terms of overall mortality. However, CABG was associated with fewer incidences of combined events and reinterventions. When compared to younger patients, the older group who underwent PCI had a higher incidence of MI.
Subtype-specific signaling pathways and genomic aberrations associated with prognosis of glioblastoma
Authors: Ae Kyung Park, Pora Kim, Leomar Y Ballester, Yoshua Esquenazi, Zhongming Zhao
Journal: Neuro-Oncology (2018)

A high heterogeneity and activation of multiple oncogenic pathways have been implicated in failure of targeted therapies in glioblastoma (GBM).Using The Cancer Genome Atlas data, we identified subtype-specific prognostic core genes by a combined approach of genome-wide Cox regression and Gene Set Enrichment Analysis. The results were validated with 8 combined public datasets containing 608 GBMs. We further examined prognostic chromosome aberrations and mutations.In classical and mesenchymal subtypes, 2 receptor tyrosine kinases (RTKs) (MET and IGF1R), and the genes in RTK downstream pathways such as phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and nuclear factor-kappaB (NF-kB), were commonly detected as prognostic core genes. Classical subtype-specific prognostic core genes included those in cell cycle, DNA repair, and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Immune-related genes were enriched in the prognostic genes showing negative promoter cytosine-phosphate-guanine (CpG) methylation/expression correlations. Mesenchymal subtype-specific prognostic genes were those related to mesenchymal cell movement, PI3K/Akt, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), Wnt/β-catenin, and Wnt/Ca2+ pathways. In copy number alterations and mutations, 6p loss and TP53 mutation were associated with poor and good survival, respectively, in the classical subtype. In the mesenchymal subtype, patients with PIK3R1 or PCLO mutations showed poor prognosis. In the glioma CpG island methylator phenotype (G-CIMP) subtype, patients harboring 10q loss, 12p gain, or 14q loss exhibited poor survival. Furthermore, 10q loss was significantly associated with the recently recognized G-CIMP subclass showing relatively low CpG methylation and poor prognosis.These subtype-specific alterations have promising potentials as new prognostic biomarkers and therapeutic targets combined with surrogate markers of GBM subtypes. However, considering the small number of events, the results of copy number alterations and mutations require further validations.
Association of atopic dermatitis with cardiovascular risk factors and diseases
Authors: M. Standl, F. Tesch, H. Baurecht, E. Rodriguez, M. Müller-Nurasyid, C. Gieger, A. Peters, R. Wang-Sattler, C. Prehn, J. Adamski, F. Kronenberg, H. Schulz, S. Koletzko, T. Schikowski, A. von Berg, I Lehmann, D. Berdel, J. Heinrich, J. Schmitt, S. Weidinger
Journal: Allergy (2017)