tbuckley/cabot-search huggingface dataset:
Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study
Authors: Oana P Zaharia, Klaus Strassburger, Alexander Strom, Gidon J Bönhof, Yanislava Karusheva, Sofia Antoniou, Kálmán Bódis, Daniel F Markgraf, Volker Burkart, Karsten Müssig, Jong-Hee Hwang, Olof Asplund, Leif Groop, Emma Ahlqvist, Jochen Seissler, Peter Nawroth, Stefan Kopf, Sebastian M Schmid, Michael Stumvoll, Andreas F H Pfeiffer, Stefan Kabisch, Sergey Tselmin, Hans U Häring, Dan Ziegler, Oliver Kuss, Julia Szendroedi, Michael Roden, Bengt-Frederik Belgardt, Anette Buyken, Jürgen Eckel, Gerd Geerling, Hadi Al-Hasani, Christian Herder, Jong-Hee Hwang, Andrea Icks, Jörg Kotzka, Oliver Kuss, Eckart Lammert, Daniel Markgraf, Karsten Müssig, Wolfgang Rathmann, Michael Roden, Julia Szendroedi, Dan Ziegler
Journal: The Lancet Diabetes & Endocrinology (2019)
Potential of Genome Editing to Improve Aquaculture Breeding and Production
Authors: Remi L. Gratacap, Anna Wargelius, Rolf Brudvik Edvardsen, Ross D. Houston
Journal: Trends in Genetics (2019)

Aquaculture is the fastest growing food production sector and is rapidly becoming the primary source of seafood for human diets. Selective breeding programs are enabling genetic improvement of production traits, such as disease resistance, but progress is limited by the heritability of the trait and generation interval of the species. New breeding technologies, such as genome editing using CRISPR/Cas9 have the potential to expedite sustainable genetic improvement in aquaculture. Genome editing can rapidly introduce favorable changes to the genome, such as fixing alleles at existing trait loci, creating de novo alleles, or introducing alleles from other strains or species. The high fecundity and external fertilization of most aquaculture species can facilitate genome editing for research and application at a scale that is not possible in farmed terrestrial animals.
A phase Ib trial of FOLFIRINOX plus saridegib, an oral hedgehog (Hh) inhibitor, in pts with advanced pancreatic cancer (PDAC).
Authors: Andrew H. Ko, Noelle K. LoConte, Emily Kantoff, Robert W. Ross, Elizabeth G. Trehu, Margaret A. Tempero, Robin Katie Kelley, Alan Paul Venook, Timothy Wu, Hedy Lee Kindler
Journal: Journal of Clinical Oncology (2012)

3105 Background: FOLFIRINOX has emerged as the optimal 1 st -line treatment option for pts with advanced PDAC and good performance status; whether it can serve as the backbone upon which to add targeted agents in clinical trial design remains uncertain. The goal of this multicenter phase Ib study is to evaluate FOLFIRINOX in combination with saridegib, a novel oral agent that inhibits the Hh signaling pathway. In preclinical models of PDAC, saridegib increases chemotherapy delivery by depleting peritumoral stroma and increasing vascularity. Methods: Pts with previously untreated metastatic or locally advanced PDAC and ECOG PS 0-1 were eligible. Treatment consists of once-daily saridegib with concurrent administration of biweekly FOLFIRINOX (omitting the 5-FU bolus). A 3+3 dose escalation design was used (see dose levels below). Prophylactic WBC growth factor support is mandated. DLT definitions include ALT/AST ≥10x ULN, grade 4 plts or ANC ≥5 d, or grade 3-4 nonheme toxicity. CT scans are obtained every 4 cycles. Limited PK analyses are performed. Results: Seven pts have been enrolled at the first 2 dose levels. Grade 1-2 AEs include GI (N/V/D), dehydration, fatigue, and LFT abnormalities. There was one DLT (grade 3 ALT elevation) at DL2. Other serious toxicities seen include grade 3 nausea (DL1) and grade 3 diarrhea (DL2). Tumor shrinkage has been observed in all 4 pts at DL1, ranging from 17-54%, with 2 unconfirmed PRs. Final MTD determination and updated safety and efficacy data will be presented at the meeting. Conclusions: A modified FOLFIRINOX regimen can be safely administered in combination with novel agents in clinical trials of PDAC. While saridegib was not beneficial when added to gemcitabine in a separate randomized phase II study, early evidence of significant responses on the current trial suggests that a more intensive chemotherapy platform may represent a preferable strategy in PDAC trial design. [Table: see text]
Temporal trends in incidence and patient characteristics in cardiogenic shock following acute myocardial infarction from 2010 to 2017: a Danish cohort study
Authors: Ole K.L. Helgestad, Jakob Josiassen, Christian Hassager, Lisette O. Jensen, Lene Holmvang, Anne Sørensen, Martin Frydland, Annmarie T. Lassen, Nanna L.J. Udesen, Henrik Schmidt, Hanne B. Ravn, Jacob E. Møller
Journal: European Journal of Heart Failure (2019)
Retrospective review of patients with adenocarcinoma of the pancreas and ovarian metastasis: Clinical characteristics, treatment strategies, and survival data
Authors: G. S. Falchook, G. R. Varadhachary, R. A. Wolff
Journal: Journal of Clinical Oncology (2006)

14068 Background: Ovarian metastasis from pancreatic adenocarcinoma is rare, and data on clinical features, treatment, and survival are limited. Methods: Charts of 19 patients with pancreatic adenocarcinoma and ovarian metastasis identified by the UTMDACC tumor registry from 1984–2005 were reviewed. Results: Clinical characteristics and survival data are in the Table. Data were limited in patients seen for single-visit second-opinion consultation or for whom only pathology was available. Other synchronous metastatic sites included peritoneum (11), liver (9), lung (5), fallopian tubes (4), uterus (2), colon (2), appendix (1), and brain (1). Ovarian metastasis size varied from “studding” to 20 cm. Among the 12 patients known to have received chemotherapy, 10 underwent resection of the ovarian metastasis. Among these, 5 patients achieved a partial response (PR) in liver metastases, peritoneal metastases, or the pancreatic primary. 3 patients received chemotherapy before resection of the ovarian metastasis, but none demonstrated a response in the ovarian metastasis. Chemotherapy regimens achieving a PR included cisplatin/paclitaxel, gemcitabine/oxaliplatin, gemcitabine/cisplatin, gemcitabine/C225, and gemcitabine/docetaxel/capecitabine. Conclusions: Pancreatic adenocarcinoma with ovarian metastasis is rare, and patients often present with an ovarian mass prior to the pancreatic adenocarcinoma diagnosis. Surgical resection of ovarian metastasis may play a palliative role in symptomatic patients since the survival of these patients appears favorable and response of ovarian metastasis to chemotherapy has not been observed. [Table: see text] No significant financial relationships to disclose.
Authors’ response: Measles outbreak in Gothenburg urban area, Sweden, 2017/18: lower viral load in breakthrough infections
Authors: Nicklas Sundell, Leif Dotevall, Magnus Lindh, Johan Westin, Jan-Åke Liljeqvist, Tomas Bergström, Marie Studahl, Lars-Magnus Andersson
Journal: Eurosurveillance (2019)

Preview this article: Authors’ response: Measles outbreak in Gothenburg urban area, Sweden, 2017/18: lower viral load in breakthrough infections, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/30/eurosurv-24-30-6-1.gif
Abstract 1086: Immune checkpoint inhibitors <i>CD300A</i> and <i>LAIR1</i> are associated with poor prognosis in clear cell renal cell carcinoma
Authors: Jonas Sjolund, David Lindgren, Helén Nilsson, Martin E. Johansson, Hakan Axelson, Kristian Pietras
Journal: Cancer Research (2019)

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 receptor (PD-1) have been shown to improve the survival of patients with clear cell renal cell carcinoma (CCRCC). However, a benefit for CCCRC patients was observed with the FDA-approved PD-1 inhibitor Nivolumab irrespective of PD-1 ligand (PD-L1) expression status indicating there are potentially additional CCRCC checkpoint molecules worth exploring for targeted therapy. We therefore analyzed RNAseq data (n=534, CCRCCs; n=72, normal kidney specimens) from the TCGA project, and found that PD-L1 was not upregulated in CCRCC when compared to normal tissue whereas other checkpoint members i.e. CD300A and LAIR1 were among the most significantly upregulated genes in CCRCCs. In terms of overall survival, high expression of PD-L1 was associated with better outcome in CCRCCs while high expression of CD300A and LAIR1 were significantly associated with worse outcomes. We confirmed these findings in two independent cohorts of CCRCC patients. Furthermore, we performed cell type enrichment analysis, which showed that CD300A and LAIR1 are most likely expressed by tumor-associated macrophages in the CCRCC tumor microenvironment. Our results suggest that PD1/PDL1 might be suboptimal targets in CCRCC and that there are additional unexplored immune checkpoint molecules that warrant our attention. Note: This abstract was not presented at the meeting. Citation Format: Jonas Sjolund, David Lindgren, Helén Nilsson, Martin E. Johansson, Hakan Axelson, Kristian Pietras. Immune checkpoint inhibitors CD300A and LAIR1 are associated with poor prognosis in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1086.
Detection of Aedes flavopictus (Yamada, 1921), Netherlands, June 2019
Authors: Adolfo Ibáñez-Justicia, Bart van de Vossenberg, Rens van den Biggelaar, Joris Voogd, Eveline Metz, Frans Jacobs, Marian Dik, Arjan Stroo
Journal: Eurosurveillance (2019)

In June 2019, a single specimen collected at a used tyre company was identified as Aedes flavopictus (Yamada, 1921), a sibling species of Ae. albopictus . Ae. flavopictus has not been recorded outside Japan and South Korea. Although it has only shown dengue virus vector competence under laboratory conditions, its detection demonstrates the value of active surveillance at risk locations and molecular tools for timely intervention against exotic mosquitoes with potential future public health impact.
A Surrogate Function for One-Dimensional Phylogenetic Likelihoods
Authors: Brian C Claywell, Vu Dinh, Mathieu Fourment, Connor O McCoy, Frederick A Matsen IV
Journal: Molecular Biology and Evolution (2017)

Phylogenetics has seen a steady increase in data set size and substitution model complexity, which require increasing amounts of computational power to compute likelihoods. This motivates strategies to approximate the likelihood functions for branch length optimization and Bayesian sampling. In this article, we develop an approximation to the 1D likelihood function as parametrized by a single branch length. Our method uses a four-parameter surrogate function abstracted from the simplest phylogenetic likelihood function, the binary symmetric model. We show that it offers a surrogate that can be fit over a variety of branch lengths, that it is applicable to a wide variety of models and trees, and that it can be used effectively as a proposal mechanism for Bayesian sampling. The method is implemented as a stand-alone open-source C library for calling from phylogenetics algorithms; it has proven essential for good performance of our online phylogenetic algorithm sts.
Differences on breast cancer management and surgical approach in six European breast cancer units
Authors: A. Celebic, M. Halaska, O. Kosovac, D. Stojiljkovic, Z. Milovanovic, N. Miletic, R. Dzodic
Journal: Journal of Clinical Oncology (2006)

10737 Background: Paper was aimed to compare differences in pre-operative management, decision on surgery and surgical approach for breast cancer in six European Breast Cancer Units in Italy, France, Czech Republic and Serbia and Montenegro, and to discuss impact of detected differences on outcome of the disease. Methods: The authors of this paper, who have been invited as young visiting/observing/training guests by four prestigious European Breast Cancer Units in Italy and France (National Cancer Institute - Milan, European Institute of Oncology - Milan, Institute Gustave Roussy - Villejuif, Institute Curie - Paris) as fellows of different European and international institutions (EUSOMA, EACR, ESSO, UICC, ESO, FECS, French Government) in the period 2003–2005, tried to detect and compare differences regarding pre-surgical evaluation, decision making and surgical approach for breast cancer as well as to discuss the impact of identified changes on outcome of the disease. The special attention has been directed to inspection of such small details as waiting list for consultation and hospitalisation, way of decision for surgical intervention (individual or oncology meeting/staff), horizontal or oblique incision for mastectomy, duration of hospital stay, sentinel node procedure (blue dye, radioactive tracer or both, one or two-days protocol, imunochistochemistry examinations during frozen section or not), preferred way of breast reconstruction, number of assistants during operation, drainage, preservation of intercostobrachial nerve during axillary surgery, suture, etc. The data were collected according to personal presence in different institutes, observation and asking the questions. Descriptive statistics were used to show the differences among the parameters under comparison. Results: This study which clearly showed a great range of differences, sometimes very significant, in parameters regarding pre-surgical evaluation and surgical treatment of breast cancer. Conclusions: Although being found, and sometimes significant, the observed differences in several parameters regarding pre-operative evaluation and surgical treatment of breast cancer in six European breast cancer units do not have influence to the outcome of the breast cancer. No significant financial relationships to disclose.
A comparative analysis of distant recurrence risk assessments by Oncotype DX recurrence score alone and integrated with clinicopathologic factors in early-stage breast cancer.
Authors: Ciara Marie Kelly, Rose Beamish, John McCaffrey, Martina SMITH, John Crown, Miriam O'Connor, Sharon F. McGee, Seamus O'Reilly, Eugene J. Moylan, Ana M. Gonzalez-Angulo, Jennifer Keating Litton, Lajos Pusztai, Catherine Margaret Kelly
Journal: Journal of Clinical Oncology (2013)

598 Background: Treatment planning for patients with node negative, ER-positive, HER-2 negative breast cancer often incorporates the use of prognostic and predictive tools like Oncotype DX. Prior to the availabilty of Oncotype DX, clinicopathologic factors such as age, nodal status, tumour size and grade were used to determine risk of recurrence (ROR). RSPC represents a validated formal integration of oncotype DX recurrence score (RS) and clinicopathologic factors that further refines prognostic accuracy. RSPC does not improve the prediction of likelihood of chemotherapy benefit. The objective of this study was to compare distant recurrence risk assessment by RS and RSPC. Methods: We included patients with node negative, ER-positive, HER2-negative breast cancer who had Oncotype DX testing routinely or on clinical trial. We retrospectively reviewed patient charts and extracted clinicopathological and RS data. We calculated the RSPC using the RSPC educational tool. A comparative analysis was performed looking at the statification of patients into low (LR), intermediate (IR) and high (HR) ROR groups by RS and RSPC. The cut offs for low, intermediate and high risk by the RSPC were set to less than 12%, 12-20% and more than 20% risk of distant recurrence at 10yrs, corresponding to the risks of recurrence associated with the RS categories. Results: We identified 658 patients from 5 academic hospitals in Ireland and the US. Oncotype DX RS classified the following proportions of patients into three risk groups for distant recurrence: LR, n=334 (50.5%), IR, n=259 (39.4%), HR, n=67 (10.1%). RSPC classified the following proportion of patients into the three risk groups for recurrence: LR, n= 455 (69.1%), IR, n=110 (16.7%), HR, n=93 (14.1%). RSPC reclassified 72.6% (n=188) of the IR group (59.1% (n=153) from IR to LR and 13.5% (n=35) from IR to HR). RPSC reclassified 10.5% (n=35) of the LR group (8.1% (n=27) from LR to IR, and 2.4% (n=8) from LR to HR). RSPC reclassified 25.3% (n=17) of the HR group (17.9% (n=12) from HR to IR, and 7.4% (n=5) from HR to LR). Conclusions: RSPC reclassified 240 patients (36.5%) and was most helpful reassigning the IR group.
A potential role of microvesicle-containing miR-223/142 in lung inflammation
Authors: Duo Zhang, Heedoo Lee, Xiaoyun Wang, Michael Groot, Lokesh Sharma, Charles S Dela Cruz, Yang Jin
Journal: Thorax (2019)

Background Uncontrolled lung inflammation is one of the prominent features in the pathogenesis of lung infection- associated acute lung injury (ALI). Microvesicles (MVs) are extracellular nanovesicles that are generated via direct membrane budding. Methods Bronchoalveolar lavage fluid (BALF) samples were collected from mice with or without intratracheal lipopolysaccharide (LPS) instillation. BALF MVs were characterised and MV-containing microRNA (miRNA) profiles were assessed and confirmed. Secretion and function of MV-containing miR-223/142 (MV-miR-223/142) were analysed in vivo. Results In BALF, MVs are mainly derived from macrophages in response to LPS. After intratracheal instillation (i.t.) of LPS or Klebsiella pneumoniae , MV-containing miR-223/142 are dramatically induced in both BALF and serum. Mechanistically, miRNA 3′ end uridylation mediates the packing of miR-223/142 into MVs. To investigate the functional role of MV-miR-223/142, we loaded miR-223/142 mimics into unstimulated MVs and delivered them into the murine lungs via i.t. The miR-223/142 mimics-enriched MVs selectively targeted lung macrophages and suppressed the inflammatory lung responses that were triggered by LPS or K. pneumoniae . Mechanistically, miR-223 and miR-142 synergistically suppress Nlrp3 inflammasome activation in macrophages via inhibition of Nlrp3 and Asc, respectively. Conclusions In the pathogenesis of lung macrophage-mediated inflammatory responses, MV-miR-223/142 secretion is robustly enhanced and detectable in BALF and serum. Furthermore, restoration of intracellular miR-223/142 via vesicle-mediated delivery suppresses macrophage activation and lung inflammation via inhibition of Nlrp3 inflammasome activation.
Predictors of autologous stem cell transplant related mortality in older adults
Authors: H. D. Klepin, V. Harish, J. Lovato, Y. Keung, J. Owen, D. Hurd
Journal: Journal of Clinical Oncology (2006)

16509 Background: Autologous stem cell transplantation (ASCT) is increasingly performed in older adults. Predictors of transplant related mortality (TRM) are not well established in this population. Our objective was to identify characteristics associated with TRM in older adults treated with ASCT. Methods: A retrospective chart review was conducted to identify all patients ≥ 60 years of age treated with ASCT at our institution between July 1990 and July 2005. We used logistic regression to investigate the effect of baseline characteristics and of transplant complications on TRM. Results: 143 patients met eligibility criteria of whom 139 were evaluable for the 100 day mortality outcome. The median age was 64.5 (range 60–76.6) years, 34% were female. Primary diagnoses included non-Hodgkin’s lymphoma (55%), multiple myeloma (29%), acute myelogenous leukemia (8%), breast cancer (5%), and Hodgkin’s lymphoma (3%). 100 day TRM was 7.9%. The mean time to engraftment (absolute neutrophil count &gt;1000) was 12.2 ± 5.5 days. Complications included bacteremia (26.3%), cardiac events (myocardial infarction, congestive heart failure or arrhythmia) (11.5%), renal failure (7.4%), and respiratory failure (6.7%). Multivariate analysis including age, sex, diagnosis, number of comorbidities, number of medications, congestive heart failure, coronary artery disease, diabetes mellitus, hemoglobin, and creatinine at the time of transplant did not identify any baseline predictors of 100 day TRM (p &gt; .05 for all). Development of renal failure or respiratory failure during transplantation was associated with increased TRM with an odds ratio of 11.2 (CI 2.5, 49.2) and 13.6 (CI 3.0, 62.2) respectively. Peritransplant cardiac events or bacteremia were not associated with increased TRM. Conclusions: Development of renal failure or respiratory failure is associated with increased TRM in this study. However, age and baseline comorbidities are not predictive of TRM. Future prospective studies should incorporate specific measures of functional and cognitive status which may be more reflective of decreased physiologic reserve in older adults being considered for ASCT. No significant financial relationships to disclose.
Poor NKG2C+ Adaptive NK Cell Recovery at Early Stage after Allo-HSCT Increased the Occurrence of Refractory Cytomegalovirus Infection
Authors: Xingxing Yu, Xiangyu Zhao, Xunhong Cao, Xuefei Liu, Xuying Pei, Xiaosu Zhao, Ying-Jun Chang, Yu Wang, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Xiao Jun Huang
Journal: Blood (2018)
Pragmatics and social motivation in autism
Authors: Mikhail Kissine
Journal: Behavioral and Brain Sciences (2019)

Abstract Pragmatic deficits constitute a central feature of autism, which is highly relevant to Jaswal &amp; Akhtar's criticisms of the social motivation theory of autism. Recent research reveals that while certain context-based interpretations are accessible, more complex pragmatic phenomena remain challenging for people on the spectrum. Such a selective pragmatic impairment is difficult to account for in motivational terms.
SMAD5 expression and inhibition of the mitotic kinase aurora-A on sensitivity of breast cancer cells to chemotherapy.
Authors: Mateusz Opyrchal, Ianko Iankov, James N. Ingle, Jeffrey L. Salisbury, Evanthia Galanis, Antonino D'Assoro
Journal: Journal of Clinical Oncology (2013)

e13516 Background: Breast cancer affects thousands of women each year. Epithelial to Mesenchymal transition (EMT) has been associated with increased metastatic potential of cancer cells as well as resistance to chemotherapy. Predicatively, presence of EMT leads to worse prognosis. We have recently showed that Aurora-A plays a key role in development of EMT and increased ability of breast cancer cells for self renewal. Therefore we hypothesized that inhibition of Aurora-A will lead to increased sensitivity to chemotherapy. Methods: The hypothesis was tested in vitro. Cellular proliferation was tested using MTT assay and protein levels were determined on Western blots. Results: In ER+ cell line, MCF7, constitutive activation of Raf-1/MAPK signaling pathway leads to aberrant activation of Aurora-A kinase activity. These cells have decreased sensitivity to treatment with paclitaxel when compared to parental MCF7 cells. This effect is even more pronounced with over-expression of Aurora-A. The sensitivity to paclitaxel was restored with inhibition of Aurora-A by novel inhibitor, Alisertib. This was further explored in triple negative cells (MDA-MB-231) and cells expressing Her-2/neu (BT474) which express higher levels of Aurora-A. Combination of Alisertib and paclitaxel was superior when compared to either therapy alone. Similar effect was seen with use of anthracyclines. Inhibition of Aurora-A resulted in decreased SMAD5 expression as well as decreased Akt phosphorylation. Current studies are investigating a role of Aurora-A in developing chemoresistance through activating SMAD5. In vivo experiments evaluating combination therapies in breast cancer animal model are ongoing. Conclusions: Inhibition of Aurora-A by Alisertib resulted in decreased SMAD5 nuclear phosphorylation and increased effectiveness of chemotherapeutic agents in breast cancer cells. These results contribute to better understanding of signaling pathways involved in resistance of breast cancer cells to chemotherapy. This knowledge could be extremely useful in developing more effective treatments for breast cancer patients both in neo-adjuvant, adjuvant and metastatic settings.