tbuckley/cabot-search huggingface dataset:
Expression of SPARC and response to <i>nab</i>-paclitaxel (nab-p) in patients (pts) with metastatic breast cancer (MBC).
Authors: Andreas Schneeweiss, Julia Aigner, Katherina Smetanay, Florian Schuetz, Christof Sohn, Mark Kriegsmann, Dirk Jaeger, Markus Zorn, Andreas Bachinger, Hans-Peter Sinn, Frederik Marme
Journal: Journal of Clinical Oncology (2014)

e12009 Background: To evaluate expression of the albumin-binding glycoprotein secreted protein, acidic and rich in cysteine (SPARC) in tumor cells, tumor stroma and serum as a predictive factor for nab-p. Methods: 44 pts with progressive MBC were prospectively enrolled. Expression of SPARC was measured by immunohistochemistry (IHC) in tumor and stroma cells of primary tumors (n=37) and/or metastatic lesions (n=22). Expression in tumor cells was quantified by an immunoreactive score (IRS) from 0-12 integrating staining intensity and percentage of positive tumor cells. Expression in stroma was semiquantified as 0, 1+ and 2+. SPARC serum levels were determined by ELISA before start of nab-p, before cycle 2 and at progression. Several cut-offs for SPARC negativity/positivity were applied. Association between SPARC expression and overall response rate (ORR, complete response [CR] + partial response [PR]) according to RECIST, disease control rate (DCR, CR+PR + stable disease [SD]), and clinical benefit rate (CBR, CR+PR+SD > 6 months) was analyzed by Fisher’s exact test. Relationship between SPARC expression and progression-free survival (PFS) and overall survival (OS) was determined by stratified Kaplan-Meier-analysis. Results: Nab-p was given as first-, second-, and > second-line in 19, 11 and 14 pts, respectively. Nab-p (starting dose of 150 mg/m2 [38 pts], 125 mg/m2 [2 pts], 100mg/m2 [3 pts] and 70 mg/m2 [1 pt] on days 1, 8, 15 of a 28-day cycle), given for a median of 3 cycles (range 1-10), achieved an ORR of 23% (10 PR), DCR of 66% and CBR of 36%. Median PFS was 5.7 months (95% CI 3.0; 7.9), OS data are not mature yet. SPARC expression of IRS > 2 in tumor cells was detected in 5/37 (14%) primary tumors and 1/22 (5%) metastatic specimens, SPARC expression of 2+ in stroma cells in 28/37 (76%) and 16/22 (73%), respectively. No clear association between expression of SPARC in primary or metastatic tumor tissue or SPARC serum levels and any clinical endpoint could be detected regardless of the various cut-offs applied. Conclusions: So far, there is no clear evidence of SPARC expression as a predictive marker for response to nab-p in MBC. Data from large randomized trials are needed.
Developmental differences between neonatal and adult human erythropoiesis
Authors: Hongxia Yan, John Hale, Julie Jaffray, Jie Li, Yaomei Wang, Yumin Huang, Xiuli An, Christopher Hillyer, Nan Wang, Sandrina Kinet, Naomi Taylor, Narla Mohandas, Anupama Narla, Lionel Blanc
Journal: American Journal of Hematology (2017)

Abstract Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)‐ and peripheral blood (PB)‐HSPC induced toward erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC. Upon in vitro erythroid differentiation, CB‐derived cells proliferated 4‐fold more than PB‐derived cells. However, CB‐derived cells exhibited a delayed kinetics of differentiation, resulting in an increased number of progenitors, notably colony‐forming unit (CFU‐E). The phenotypes of early erythroid differentiation stages also differed between the two sources with a significantly higher percentage of IL3R ‐ GPA ‐ CD34 + CD36 + cells generated from PB‐ than CB‐HSPCs. This subset was found to generate both burst‐forming unit (BFU‐E) and CFU‐E colonies in colony‐forming assays. To further understand the differences between CB‐ and PB‐HSPC, cells at eight stages of erythroid differentiation were sorted from each of the two sources and their transcriptional profiles were compared. We document differences at the CD34, BFU‐E, poly‐ and orthochromatic stages. Genes exhibiting the most significant differences in expression between HSPC sources clustered into cell cycle‐ and autophagy‐related pathways. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis, highlighting the impact of the developmental origin of HSPCs on erythroid differentiation.
Tenascin-C Promotes Tumor Cell Migration and Metastasis through Integrin α9β1–Mediated YAP Inhibition
Authors: Zhen Sun, Anja Schwenzer, Tristan Rupp, Devadarssen Murdamoothoo, Rolando Vegliante, Olivier Lefebvre, Annick Klein, Thomas Hussenet, Gertraud Orend
Journal: Cancer Research (2017)

Abstract Tenascin-C is an extracellular matrix molecule that drives progression of many types of human cancer, but the basis for its actions remains obscure. In this study, we describe a cell-autonomous signaling mechanism explaining how tenascin-C promotes cancer cell migration in the tumor microenvironment. In a murine xenograft model of advanced human osteosarcoma, tenascin-C and its receptor integrin α9β1 were determined to be essential for lung metastasis of tumor cells. We determined that activation of this pathway also reduced tumor cell–autonomous expression of target genes for the transcription factor YAP. In clinical specimens, a genetic signature comprising four YAP target genes represents prognostic impact. Taken together, our results illuminate how tumor cell deposition of tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression. Significance: These results illuminate how the extracellular matrix glycoprotein tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression by employing integrin α9β1, abolishing actin stress fiber formation, inhibiting YAP and its target gene expression, with potential implications for cancer prognosis and therapy. Cancer Res; 78(4); 950–61. ©2017 AACR.
SPF 100+ sunscreen is more protective against sunburn than SPF 50+ in actual use: Results of a randomized, double-blind, split-face, natural sunlight exposure clinical trial
Authors: Joshua D. Williams, Prithwiraj Maitra, Evren Atillasoy, Mei-Miau Wu, Aaron S. Farberg, Darrell S. Rigel
Journal: Journal of the American Academy of Dermatology (2017)
Abstract 20478: Mortality outcomes of Cardiac Implantable Device therapy In Patients With AL type Of Amyloidosis
Authors: Anwar Chahal, Deepak Padmanabhan, Nidhhi Tandon, Alan M Sugrue, Virend K Somers, Angela Dispenzieri, Martha Grogan, Grace Lin, Peter Brady
Journal: Circulation (2016)

Amyloid Light (AL) chain, a sub-type of amyloidosis which can affect the heart and may be associated with sudden cardiac death. Cardiac implantable electronic devices (CIED) use in AL is contentiou...
Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease?
Authors: Zhiqiang Deng, Patricia Sheehan, Shi Chen, Zhenyu Yue
Journal: Molecular Neurodegeneration (2017)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that share genetic risk factors and pathological hallmarks. Intriguingly, these shared factors result in a high rate of comorbidity of these diseases in patients. Intracellular protein aggregates are a common pathological hallmark of both diseases. Emerging evidence suggests that impaired RNA processing and disrupted protein homeostasis are two major pathogenic pathways for these diseases. Indeed, recent evidence from genetic and cellular studies of the etiology and pathogenesis of ALS-FTD has suggested that defects in autophagy may underlie various aspects of these diseases. In this review, we discuss the link between genetic mutations, autophagy dysfunction, and the pathogenesis of ALS-FTD. Although dysfunction in a variety of cellular pathways can lead to these diseases, we provide evidence that ALS-FTD is, in many cases, an autophagy disease.
Родина Саксів: батько — лікар, син — художник
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2017)

Подані життєвий шлях і професійна діяльність найколоритніших представників родини Саксів німецького походження. Лікар Едуард Сакс працював інспектором лікувальної управи в Катеринославі та Тобольську. Його син Микола Сакс — живописець-пейзажист, працював помічником секретаря в Товаристві російських художників у Парижі в 1881 році. Доля цих етнічних німців пов’язана з українським краєм, зокрема з Катеринославом (сучасним містом Дніпро).
Sports-Related Eye Injuries
Authors: Dante J. Pieramici
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
A benefit–risk analysis of rotavirus vaccination, France, 2015
Authors: Adnane Lamrani, Pascale Tubert-Bitter, Catherine Hill, Sylvie Escolano
Journal: Eurosurveillance (2017)

IntroductionTwo vaccines available for protection against rotavirus gastroenteritis (RVGE), Rotarix and RotaTeq, have contributed to a large decrease in the incidence of paediatric diarrhoea in countries where they have been used. However, they have also led to a small increase in the risk of intussusception. Methods: We compare the number of prevented hospitalisations for RVGE to the number of vaccine-induced hospitalised intussusceptions in France. Results: With 9.5% coverage (French 2015 estimation), vaccination was estimated to prevent, annually, a median of 1,074 hospitalisations (2.5th and 97.5th percentiles (2.5th-97.5th): 810-1,378) and 1.4 deaths (2.5th-97.5th: 1.2-1.6) from RVGE. It was also estimated to cause, annually, 5.0 hospitalisations (2.5th-97.5th: 3.2-7.7) and 0.005 deaths (2.5th-97.5th: 0.001-0.015) from intussusception. The benefit-risk ratio is therefore 214 (2.5th-97.5th: 128-362) for hospitalisations and 273 (2.5th-97.5th: 89-1,228) for deaths. Under a hypothetical 92% coverage, rotavirus vaccination with Rotarix would avoid 10,459 (2.5th-97.5th: 7,702-13,498) hospitalisations for RVGE and induce 47.0 (2.5th-97.5th: 25.1-81.4) hospitalisations for intussusception annually, thereby preventing 13.7 (2.5th-97.5th: 11.1-15.2) deaths and inducing 0.05 (2.5th-97.5th: 0.01-0.15) deaths. Conclusion: The benefit-risk ratio in France is similar to that of other European countries.
Abstract 12589: Delayed Therapeutic Hypothermia Protects Against the Myocardial No-reflow Phenomenon Independent of Infarct Size in a Rat Ischemia/reperfusion Model
Authors: Wangde Dai, Robert A Kloner
Journal: Circulation (2016)

Background: Adjunctive therapy in addition to reperfusion to reduce myocardial infarct size has been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. No-reflow predicts poor clinical outcome. In this study, we investigate the effects of a single application of delayed (post-reperfusion) therapeutic hypothermia (TH) on no-reflow in rats. Methods: Rats were subjected to 60 min of coronary artery occlusion followed by 3 hours of reperfusion. Rats were divided into normothermic (n=5) and TH (n=5) groups. In the TH, hypothermia was initiated at 1 minute after coronary artery reperfusion by pumping room-temperature (22 °C) saline into and out of the thoracic cavity for 1 hour. This decreased intra-thoracic temperature to around 27 °C within a few minutes. At 3 hours after reperfusion, hearts were excised for infarct size (tetrazolium staining) and no-reflow zone (Thioflavin S technique) measurement. Results: Ischemic risk area (expressed as % of LV area, assessed by blue dye technique) was 52.4 ± 2.9% in normothermic group and 44.8±3.7% in TH group (p=0.15). Infarct size (expressed as % of risk area) was similar between normothermic (73.8 ±3.8% ) and TH (72.0± 4.0%, p = 0.76) groups. No-reflow area (expressed as % of risk area) was significantly reduced in TH group (18.0 ± 4.4%) compared with normothermic group (39.5 ± 2.9%, P = 0.005). When expressed as % of necrotic area, no-reflow area was reduced by more than half in TH group (25.5 ± 6.4%) versus in normothermic group (54.4 ± 5.3%, P = 0.01). Conclusions: A single delayed TH markedly diminishes reperfusion induced microvascular damage and no-reflow even when initiated after reperfusion, and independent of infarct size.
Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor
Authors: Shadi Khalil, Lorrie Delehanty, Stephen Grado, Maja Holy, Zollie White, Katie Freeman, Ryo Kurita, Yukio Nakamura, Grant Bullock, Adam Goldfarb
Journal: The Journal of Experimental Medicine (2017)

Iron-restricted human anemias are associated with the acquisition of marrow resistance to the hematopoietic cytokine erythropoietin (Epo). Regulation of Epo responsiveness by iron availability serves as the basis for intravenous iron therapy in anemias of chronic disease. Epo engagement of its receptor normally promotes survival, proliferation, and differentiation of erythroid progenitors. However, Epo resistance caused by iron restriction selectively impairs proliferation and differentiation while preserving viability. Our results reveal that iron restriction limits surface display of Epo receptor in primary progenitors and that mice with enforced surface retention of the receptor fail to develop anemia with iron deprivation. A mechanistic pathway is identified in which erythroid iron restriction down-regulates a receptor control element, Scribble, through the mediation of the iron-sensing transferrin receptor 2. Scribble deficiency reduces surface expression of Epo receptor but selectively retains survival signaling via Akt. This mechanism integrates nutrient sensing with receptor function to permit modulation of progenitor expansion without compromising survival.
Cervical Pessary to Prevent Preterm Birth
Authors: Robert M. Silver, D. Ware Branch
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
γδ T cells provide the early source of IFN-γ to aggravate lesions in spinal cord injury
Authors: Guodong Sun, Shuxian Yang, Guangchao Cao, Qianghua Wang, Jianlei Hao, Qiong Wen, Zhizhong Li, Kwok-Fai So, Zonghua Liu, Sufang Zhou, Yongxiang Zhao, Hengwen Yang, Libing Zhou, Zhinan Yin
Journal: The Journal of Experimental Medicine (2017)

Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). γδ T cells, a small subset of T cells, regulate the inflammation process in many diseases, yet their function in SCI is still poorly understood. In this paper, we demonstrate that mice deficient in γδ T cells (TCRδ−/−) showed improved functional recovery after SCI. γδ T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the Vγ4 subtype and express the inflammatory cytokine IFN-γ. Inactivating IFN-γ signaling in macrophages results in a significantly reduced production of proinflammatory cytokines in the cerebrospinal fluid (CSF) of mice with SCIs and improves functional recovery. Furthermore, treatment of SCI with anti-Vγ4 antibodies has a beneficial effect, similar to that obtained with anti–TNF-α. In SCI patients, γδ T cells are detected in the CSF, and most of them are IFN-γ positive. In conclusion, manipulation of γδ T cell functions may be a potential approach for future SCI treatment.
Políticas de vacunación frente a las infecciones por neumococos en Europa
Authors: R G Pebody, T Leino, H Nohynek, W Hellenbrand, S Salmaso, P Ruutu
Journal: Eurosurveillance (2005)

La infeccion por Streptococcus pneumoniae (neumococo) es una causa importante de manifestaciones clinicas invasivas como meningitis, septicemia y neumonia, especialmente en ninos y ancianos. Durante muchos anos ha estado disponible una vacuna polisacarida 23-valente (PPV), y desde 2001 se autorizo una vacuna conjugada heptavalente (PCV) en Europa. Con el objetivo de conocer la politica de vacunacion neumococica en Europa, se distribuyo un cuestionario a los 15 Estados miembros de la Union Europea (UE), Suiza, Noruega y a los diez paises candidatos, como parte de un proyecto financiado por la UE sobre enfermedad neumococica (Pnc-EURO). Veintitres de los 27 paises, constituyentes de la actual UE (mas Noruega y Suiza) completaron el cuestionario. La vacuna PPV se comercializaba en 22 de los 23 paises que respondieron y estaba en las recomendaciones oficiales en 21. En 20 de los 21 paises de los que se disponia de informacion, la vacunacion estaba restringida a aquellos grupos de mayor riesgo de infeccion. El numero de grupos de riesgo monitorizados oscilaba entre uno y doce. Al menos 17 paises recomiendan que la PPV sea administrada a todos los mayores de 65 anos (y en tres paises, a aquellos mayores de 60). Trece paises elaboraron recomendaciones nacionales para la vacunacion con PCV en 2003. Ningun pais recomendaba vacunacion infantil masiva en ese momento, pero si a los grupos especificos de riesgo (entre uno y once), particularmente a los ninos con asplenia (n=13) e infeccion por VIH (n=12). El uso de PCV fue restringido a ninos menores de dos anos en siete paises, y a menores de cinco anos en cuatro paises. Las decisiones futuras sobre el uso de las vacunas neumococicas en Europa se tomaran en base a distintos factores incluyendo: carga local de enfermedad; impacto previsto de cualquier programa universal, en especial la importancia de la sustitucion del serotipo y la inmunidad de grupo; la efectividad de calendarios de dosis reducidos, y coste de la vacuna. Hasta ahora, al menos un pais, Luxemburgo, ha implementado una politica de vacunacion infantil universal con PCV.
Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients
Authors: S. Cerquozzi, D. Barraco, T. Lasho, C. Finke, C. A. Hanson, R. P. Ketterling, A. Pardanani, N. Gangat, A. Tefferi
Journal: Blood Cancer Journal (2017)

Abstract In a recent International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) study, prior arterial events and hypertension were predictors of subsequent arterial thrombosis whereas prior venous events and age ≥65 years predicted venous thrombosis in polycythemia vera (PV). In the current study, we sought to validate the above findings and identify additional predictors of arterial versus venous thrombosis. At a median follow up of 109 months, thrombosis after diagnosis occurred in 128 (22%) patients; 82 (14%) arterial and 57 (10%) venous events. On multivariate analysis, prior arterial events (&lt;0.0001), hyperlipidemia ( p = 0.03), and hypertension ( p = 0.02) predicted subsequent arterial events. In comparison, prior venous events ( p = 0.05), leukocytosis ≥11 × 10 9 /L ( p = 0.002), and major hemorrhage ( p = 0.02) were predictors of subsequent venous events. Salient associations with arterial thrombosis included age ≥ 60 years, hypertension, diabetes, hyperlipidemia and normal karyotype whereas age ≤ 60 years, females, palpable splenomegaly and history of major hemorrhage were associated with venous thrombosis. TET2 or ASXL1 mutations did not impact arterial nor venous thrombosis. In conclusion, we identify distinct associations for arterial versus venous thrombosis in PV and confirm that a prior arterial or venous thrombotic event is the most reliable predictor of subsequent events.
Association of Patient Out-of-Pocket Costs With Prescription Abandonment and Delay in Fills of Novel Oral Anticancer Agents
Authors: Jalpa A. Doshi, Pengxiang Li, Hairong Huo, Amy R. Pettit, Katrina A. Armstrong
Journal: Journal of Clinical Oncology (2017)

Purpose The number of novel oral anticancer agents is increasing, but financial barriers may limit access. We examined associations between out-of-pocket (OOP) costs and reduced and/or delayed treatment initiation. Methods This retrospective claims-based study used 2014 to 2015 data from a large, proprietary, integrated database and included Medicare and commercial insurance enrollees with a new, adjudicated prescription for any of 38 oral anticancer agents. We examined rates of claim reversal (failure to purchase approved prescription), delayed initiation (reversal with subsequent fill of same agent within 90 days after adjudication), and abandonment (reversal with no fill of same agent within 90 days after adjudication) for the index oral anticancer agent. We also examined whether patients filled any alternate oral, injectable, or infusible anticancer agent within 90 days. Logistic regressions controlled for sociodemographic, clinical, and treatment characteristics to estimate adjusted rates. Results Among the final sample (N = 38,111), risk-adjusted rates of claim reversal ranged from 13% to 67%, increasing with higher OOP costs. Although the abandonment rate was 18% overall, risk-adjusted rates were higher in greater OOP cost categories (10.0% for ≤ $10 group v 13.5% for $50.01 to $100 group, 31.7% for $100.01 to $500 group, 41.0% for $500.01 to $2,000 group, and 49.4% for &gt; $2,000 group; P &lt; .001 compared with ≤ $10 group). Rates remained similar after accounting for use of alternate oral, injectable, or infusible anticancer agents. Delayed initiation was also more frequent for higher OOP cost categories (3% in ≤ $10 group v 18% in &gt; $2,000 group; P &lt; .001). Sensitivity and subgroup analyses by insurance type, pharmacy type, sex, and indication identified similar associations. Conclusion Higher OOP costs were associated with higher rates of oral prescription abandonment and delayed initiation across cancers. Fiscally sustainable strategies are needed to improve patient access to cancer medications.