tbuckley/cabot-search huggingface dataset:
Abstract C63: The analysis of microbiota composition between tumor and normal tissues in pancreatic cancer and the comparison with the public data of NCBI
Authors: Hwi Wan Choi, Jinju Kim, Eo Jin Kim, Eunsung Jun
Journal: Cancer Research (2019)

Abstract Purpose: The translocation of gut bacteria and its derivatives may be an essential factor contributing to the various diseases of the pancreas. However, microbial function on the development and progression of pancreatic cancer is not clear and the research is still lacking. The aim of this study is to analyze the composition of microbiota in pancreatic cancer tissue and to compare the result with the existing public data. Methods: We obtained the cancer and normal tissues from patients who underwent pancreatic cancer surgery in Korea (IRB: 2018-0710), and total bacterial genomic DNA was purified from tissue. Through the gene sequencing of 16S rRNA (V3-V4 lesion), we analyzed the quantitative and qualitative composition of microbiome. Then we compared the microbiome composition with public data of NCBI (SRP132007). Results: We successfully performed the gene sequencing of 16s rRNA from 12 tumor tissues and 6 normal tissues. Based on the results obtained from the tumor and normal tissues, we compared the composition from the phylum to the species levels. We confirmed that there were significant differences in the microbiome composition of the tumor and normal tissues and identified various strains of 20 or more species with a high specificity in tumor or normal tissues. In addition, through the comparison with SRP132007 data, we confirmed a distinct difference between the two groups. Conclusions: We have analyzed the patterns and characteristics of tumor or normal specific microbiomes through pancreatic cancer tissues. There is a clear difference between the two groups with environmental differences, even in the microbiomes of patients with the same disease. We expect to further clarify the importance of microbiomes in pancreatic cancer and point to the development of new therapies through further studies. Citation Format: Hwi Wan Choi, Jinju Kim, Eo Jin Kim, Eunsung Jun. The analysis of microbiota composition between tumor and normal tissues in pancreatic cancer and the comparison with the public data of NCBI [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C63.
Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study
Authors: Elisé G. Kaboré, Charles Guenancia, Ines Vaz-Luis, Antonio Di Meglio, Barbara Pistilli, Charles Coutant, Paul Cottu, Anne Lesur, Thierry Petit, Florence Dalenc, Philippe Rouanet, Antoine Arnaud, Olivier Arsene, Mahmoud Ibrahim, Johanna Wassermann, Geneviève Boileau-Jolimoy, Anne-Laure Martin, Jérôme Lemonnier, Fabrice André, Patrick Arveux
Journal: PLoS Medicine (2019)

Background In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity. Methods and findings Using prospective data collected from 2012–2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I–III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10–8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6–40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort. Conclusions In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498). Trial registration ClinicalTrials.gov NCT01993498.
Antibody and T cell responses against avian and microbial antigens associate with hypersensitivity pneumonitis disease parameters in pigeon breeders
Authors: Sajidah F. Hasan, Agnieszka Jozwik, Adrian Heaps, Nirupma Kakkar, Iona Donnelly, Sharon Cookson, Stephen J. Bourke, Charles McSharry, Stephen M. Todryk
Journal: Allergy (2019)
Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics
Authors: Janine A.M. Kamphuis, Marijke Linschoten, Maarten J. Cramer, Eelke H. Gort, Anna van Rhenen, Folkert W. Asselbergs, Pieter A. Doevendans, Arco J. Teske
Journal: JACC CardioOncology (2019)

Cancer therapy–related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m2/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted.
Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells
Authors: Peng-Fei Zhang, Xu Pei, Ke-Sang Li, Li-Na Jin, Fei Wang, Jing Wu, Xue-Mei Zhang
Journal: Molecular Cancer (2019)

Abstract Background Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. Methods The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. Results Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. Conclusion Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.
Methotrexate and Cytarabine for Adult Patients with Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study
Authors: Xinxin Cao, Jian Li, Ai-lin Zhao, Xue-min Gao, Hua-cong Cai, Lu Zhang, Yan Zhang, Jun Feng, Miao Chen, Tie-nan Zhu, Na Niu, Jian Sun, Zhi-yong Liang, Dao-Bin Zhou, Ming-hui Duan
Journal: Blood (2019)
Macrolide combination therapy for hospitalised CAP patients? An individualised approach supported by machine learning
Authors: Carolina Garcia-Vidal, Catia Cillóniz, Antoni Torres
Journal: European Respiratory Journal (2019)

<b>The article by König and co-workers paves the way for the selection of a subset of patients with CAP in whom combination initial therapy including macrolides could improve outcomes using a new and interesting mathematical approach</b>http://bit.ly/2p8RdCD
Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study (vol 66, pg 589, 2007)
Authors: W. de Jager, P. A. H. Hoppenreijs, N. M. Wulffraat, L. R. Wedderburn, W. Kuis, B. J. Prakken
Journal: Annals of the Rheumatic Diseases (2008)
Public-access defibrillation and neurological outcomes in patients with out-of-hospital cardiac arrest in Japan: a population-based cohort study
Authors: Takahiro Nakashima, Teruo Noguchi, Yoshio Tahara, Kunihiro Nishimura, Satoshi Yasuda, Daisuke Onozuka, Taku Iwami, Naohiro Yonemoto, Ken Nagao, Hiroshi Nonogi, Takanori Ikeda, Naoki Sato, Hiroyuki Tsutsui
Journal: The Lancet (2019)
Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases
Authors: Elias L. Salfati, Emily G. Spencer, Sarah E. Topol, Evan D. Muse, Manuel Rueda, Jonathan R. Lucas, Glenn N. Wagner, Steven Campman, Eric J. Topol, Ali Torkamani
Journal: Genome Medicine (2019)

Abstract Background Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis. Methods Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem “molecular autopsy” cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest. Results Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively. Conclusions The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.
The projected impact of geographic targeting of oral cholera vaccination in sub-Saharan Africa: A modeling study
Authors: Elizabeth C. Lee, Andrew S. Azman, Joshua Kaminsky, Sean M. Moore, Heather S. McKay, Justin Lessler
Journal: PLoS Medicine (2019)

Background Cholera causes an estimated 100,000 deaths annually worldwide, with the majority of burden reported in sub-Saharan Africa. In May 2018, the World Health Assembly committed to reducing worldwide cholera deaths by 90% by 2030. Oral cholera vaccine (OCV) plays a key role in reducing the near-term risk of cholera, although global supplies are limited. Characterizing the potential impact and cost-effectiveness of mass OCV deployment strategies is critical for setting expectations and developing cholera control plans that maximize the chances of success. Methods and findings We compared the projected impacts of vaccination campaigns across sub-Saharan Africa from 2018 through 2030 when targeting geographically according to historical cholera burden and risk factors. We assessed the number of averted cases, deaths, and disability-adjusted life years and the cost-effectiveness of these campaigns with models that accounted for direct and indirect vaccine effects and population projections over time. Under current vaccine supply projections, an approach optimized to targeting by historical burden is projected to avert 828,971 (95% CI 803,370–859,980) cases (equivalent to 34.0% of projected cases; 95% CI 33.2%–34.8%). An approach that balances logistical feasibility with targeting historical burden is projected to avert 617,424 (95% CI 599,150–643,891) cases. In contrast, approaches optimized for targeting locations with limited access to water and sanitation are projected to avert 273,939 (95% CI 270,319–277,002) and 109,817 (95% CI 103,735–114,110) cases, respectively. We find that the most logistically feasible targeting strategy costs US$1,843 (95% CI 1,328–14,312) per DALY averted during this period and that effective geographic targeting of OCV campaigns can have a greater impact on cost-effectiveness than improvements to vaccine efficacy and moderate increases in coverage. Although our modeling approach does not project annual changes in baseline cholera risk or directly incorporate immunity from natural cholera infection, our estimates of the relative performance of different vaccination strategies should be robust to these factors. Conclusions Our study suggests that geographic targeting substantially improves the cost-effectiveness and impact of oral cholera vaccination campaigns. Districts with the poorest access to improved water and sanitation are not the same as districts with the greatest historical cholera incidence. While OCV campaigns can improve cholera control in the near term, without rapid progress in developing water and sanitation services or dramatic increases in OCV supply, our results suggest that vaccine use alone is unlikely to allow us to achieve the 2030 goal.
Targeting cancers through TCR-peptide/MHC interactions
Authors: Qinghua He, Xianhan Jiang, Xinke Zhou, Jinsheng Weng
Journal: Journal of Hematology & Oncology (2019)

Adoptive T cell therapy has achieved dramatic success in a clinic, and the Food and Drug Administration approved two chimeric antigen receptor-engineered T cell (CAR-T) therapies that target hematological cancers in 2018. A significant issue faced by CAR-T therapies is the lack of tumor-specific biomarkers on the surfaces of solid tumor cells, which hampers the application of CAR-T therapies to solid tumors. Intracellular tumor-related antigens can be presented as peptides in the major histocompatibility complex (MHC) on the cell surface, which interact with the T cell receptors (TCR) on antigen-specific T cells to stimulate an anti-tumor response. Multiple immunotherapy strategies have been developed to eradicate tumor cells through targeting the TCR-peptide/MHC interactions. Here, we summarize the current status of TCR-based immunotherapy strategies, with particular focus on the TCR structure, activated signaling pathways, the effects and toxicity associated with TCR-based therapies in clinical trials, preclinical studies examining immune-mobilizing monoclonal TCRs against cancer (ImmTACs), and TCR-fusion molecules. We propose several TCR-based therapeutic strategies to achieve optimal clinical responses without the induction of autoimmune diseases.
Tribunal rejects call to strike off doctor who received “inadequate induction” from hospital
Authors: Clare Dyer
Journal: BMJ (2019)

A medical practitioners tribunal has refused the General Medical Council’s (GMC) request to strike off a doctor who admitted a catalogue of clinical errors, took breaks without telling colleagues, and forged a certificate of employment, after the tribunal determined that he had received inadequate induction and support from the hospital that employed him.

The tribunal instead suspended Tarek Seda for 12 months, the maximum period available. Its chair, Christina Moller, said, “In view of the trust’s undoubted failings, acknowledged in their own internal report, the tribunal took the view that it would not be proportionate to erase Dr Seda on the basis of his failings, serious though they were.”

Moller also accused the GMC of initially failing to pass on information to its expert witness about deficiencies in Seda’s workplace that were potentially mitigating factors in his conduct.

In June 2017 Seda, who qualified in Egypt in 2002, had recently started working as a specialty doctor in emergency medicine at King’s Mill Hospital, part of Sherwood Forest Hospitals NHS Foundation Trust. During two consecutive night shifts he made basic errors in treating three patients. …
Abstract 423: Kinase Independent Signaling of PI3Kγ Mediates Cardiac Fibrosis
Authors: Maradumane L Mohan, Lisa M Grove, Mitchell A Olman, Sathyamangla V Naga Prasad
Journal: Circulation Research (2016)

Phosphoinositide 3 Kinase γ (PI3Kγ) belongs to a family of lipid kinases genetic deletion of which leads to pressure overload induced cardiac fibrosis in mice. However, the mechanism by which PI3Kγ mediates cardiac fibrosis is unknown. Cardiac fibrosis is a key underlying cause of fatal heart failure. A well-known fibrogenic mechanism is the generation of myofibroblasts, which are characterized by overexpression of smooth muscle α-actin (αSMA). Myofibroblast is a fibrosis-effector cell that produces pro-fibrotic cytokines and exuberant extracellular matrix that leads to cardiac fibrosis. To evaluate the role of PI3Kγ in fibrotic phenotype, cardiac tissue lysates from 3 months old WT and PI3Kγ null (PI3Kγ -/- ) mice were assessed for the expression of αSMA. Interestingly, there is significant up-regulation of αSMA in PI3Kγ -/- in comparison to littermate controls (WT) even at baseline suggesting that loss of PI3Kγ predisposes the hearts towards fibrosis. To directly confirm that PI3Kγ -/- cardiac fibroblasts (CF) exhibit a myofibroblast phenotype even at baseline, CF were isolated from hearts of WT and PI3Kγ -/- mice and assessed for myofibroblast phenotype by immunostaining for αSMA in stress fibers. Fluorescence microscopy on the CF from PI3Kγ -/- mice showed intense immunostaining for αSMA with greater number of cells exhibiting αSMA in stress fibers when compared to CF from WT mice. Consistently, immunoblotting showed significantly higher αSMA protein levels in PI3Kγ -/- CF compared to WT CF suggesting that PI3Kγ -/- fibroblasts are “primed” to undergo myofibroblast differentiation. To determine the role of kinase-independent function of PI3Kγ in vivo, we generated unique mice lines with cardiomyocyte-specific expression of either kinase-dead PI3Kγ (PI3Kγ inact ) or constitutively active PI3Kγ ( Myr PI3Kγ) in the global PI3Kγ -/- (PI3Kγ inact /PI3Kγ -/- or Myr PI3Kγ/PI3Kγ -/- ) and measured αSMA. Surprisingly, abundance of αSMA protein is significantly reduced in PI3Kγ inact /PI3Kγ -/- when compared to WT and PI3Kγ -/- mice. These data reveal that kinase-independent function of PI3Kγ is a key component in the myocyte-initiated pathway that ultimately drives CF to become myofibroblasts uncovering a novel mechanism of regulating pro-fibrotic signals.
Impaired cardiac contractile reserve on dobutamine stress echocardiography predicts development of hepatorenal syndrome
Authors: Anoop Koshy, Benjamin Cailes, Omar Farouque, Adam Testro, Jithin Sajeev, Jay Ramchand, Paul Calafiore, Hamid Salehi, Piyush Srivastava, Matthew Peverelle, Han Lim, Hui-Chen Han, Andrew Teh, Paul Gow
Journal: Journal of Hepatology (2019)
Abstract I05: Heterocellular interactions in the tumor microenvironment
Authors: Claus Jorgensen
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDA) is characterized by a heterocellular microenvironment, exhibiting tumor-promoting as well as tumor-restrictive effects. Tumor cells coerce host cells, such as fibroblasts and myeloid cells, to remodel the stroma, which results in altered stiffness, cell-cell signaling, and modified tumor cell function. The rules governing tumor-stromal interactions are currently not clearly defined. To demark and characterize the cellular components of the tumor microenvironment we devised protein-based marker panels for single-cell analysis by cytometry by time of flight (CyTOF), specifically aimed at defining populations of cancer-associated fibroblast (CAFs). Importantly, we employed cell surface markers, enabling isolation and functional characterization of identified stromal populations. Using these panels, we interrogated tumors from the pdx1-cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC) genetic engineered model of pancreatic cancer. We observe previously defined CAF populations expressing markers for myofibroblastic CAFs (myCAF); inflammatory CAFs (iCAF) and antigen presenting CAFs (apCAF). In addition to these CAF populations, we observe that differential expression of the auxiliary receptor for the TGFβ receptor complex, endoglin (CD105), demarks two distinct fibroblast populations that are present in murine and human PDA. In addition, we observe CD105-positive (CD105+) and -negative (CD105-) fibroblasts in normal healthy pancreas, liver, and lung, indicating that the presence of these CAFs in tumors is likely due to local expansion. Isolated fibroblasts preserve differential expression of CD105+ and CD105- throughout extended in vitro culture, co-culture, and treatment with regulators of fibroblast function, indicating that CD105 may act as a bona fide lineage marker. We find that while both CD105+/- lineages are able to adapt a general myCAF or iCAF polarization, they show distinct regulation of specific genes. Using a syngeneic subcutaneous co-transplant model, we demonstrate that CD105+ fibroblasts are tumor-promoting, while CD105- fibroblasts are highly tumor-restrictive. Interestingly, both mechanisms are mediated by differential regulation of CD8 T cell-dependent adaptive immunity. Together these data define two novel, functionally distinct fibroblast populations in PDA with pro- or antitumorigenic effects. Citation Format: Claus Jorgensen. Heterocellular interactions in the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I05.
Reply to Eva Compérat, Mahul Amin, Victor Reuter’s Editorial Reply re: Murali Varma, Brett Delahunt, Theodorus van der Kwast. Grading Noninvasive Bladder Cancer: World Health Organisation 1973 or 2004 May Be the Wrong Question. Eur Urol 2019;76:413–5
Authors: Murali Varma, Brett Delahunt, Theodorus van der Kwast
Journal: European Urology (2019)