tbuckley/cabot-search huggingface dataset:
Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors—Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)
Authors: C.T. Rieger, B. Liss, S. Mellinghoff, D. Buchheidt, O.A. Cornely, G. Egerer, W.J. Heinz, M. Hentrich, G. Maschmeyer, K. Mayer, M. Sandherr, G. Silling, A. Ullmann, M.J.G.T. Vehreschild, M. von Lilienfeld-Toal, H.H. Wolf, N. Lehners
Journal: Annals of Oncology (2018)

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.
Letter by Jin-shan and Xue-bin Regarding Article, “Pericarditis as a Marker of Occult Cancer and a Prognostic Factor for Cancer Mortality”
Authors: He Jin-shan, Li Xue-bin
Journal: Circulation (2018)

We read with great interest the article by Søgaard and colleagues 1 about pericarditis as a marker of occult cancer.The article indicates that pericarditis may be a marker of occult lung and breast cancer, as well as hematologic and unspecified metastatic cancers, and it is associated with worse survival among patients with certain cancers.We have several questions about this article.First, pericarditis is the most common disease of the pericardium, with an annual incidence rate of ≈30 per 100 000 people; the causes include infection, trauma, autoimmune disease, and cancer.Considering economic and patient-related costs, performing extended screening such as whole-body scans for high-risk patients with cancer is reasonable.Other than old age and pericardial effusion, are there any other characteristics used as risk factors for pericarditis with cancer?Second, extended screening such as whole-body scans may increase patients' exposure to radiation and anxiety associated with the diagnostic workup.Are there special signs of computed tomography or magnetic resonance imaging examinations of patients of pericarditis with cancer to make the diagnosis simpler?What about positron emission tomography-computed tomography?Is it useful for increasing the diagnostic rate and lowering radiation exposure?Last, cancer-related pericarditis is most commonly caused by metastasis.However, in this research, among the patients with pericarditis, 40% have localized cancer, 36% have metastatic cancer, and 24% have an unknown or missing cancer stage.The corresponding proportions for patients without pericarditis are 42%, 37%, and 22%, respectively.Why is there no difference in the proportions of metastatic patients between them?
Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4–insufficient subjects
Authors: Charlotte Schwab, Annemarie Gabrysch, Peter Olbrich, Virginia Patiño, Klaus Warnatz, Daniel Wolff, Akihiro Hoshino, Masao Kobayashi, Kohsuke Imai, Masatoshi Takagi, Ingunn Dybedal, Jamanda A. Haddock, David M. Sansom, Jose M. Lucena, Maximilian Seidl, Annette Schmitt-Graeff, Veronika Reiser, Florian Emmerich, Natalie Frede, Alla Bulashevska, Ulrich Salzer, Desirée Schubert, Seiichi Hayakawa, Satoshi Okada, Maria Kanariou, Zeynep Yesim Kucuk, Hugo Chapdelaine, Lenka Petruzelkova, Zdenek Sumnik, Anna Sediva, Mary Slatter, Peter D. Arkwright, Andrew Cant, Hanns-Martin Lorenz, Thomas Giese, Vassilios Lougaris, Alessandro Plebani, Christina Price, Kathleen E. Sullivan, Michel Moutschen, Jiri Litzman, Tomas Freiberger, Frank L. van de Veerdonk, Mike Recher, Michael H. Albert, Fabian Hauck, Suranjith Seneviratne, Jana Pachlopnik Schmid, Antonios Kolios, Gary Unglik, Christian Klemann, Carsten Speckmann, Stephan Ehl, Alan Leichtner, Richard Blumberg, Andre Franke, Scott Snapper, Sebastian Zeissig, Charlotte Cunningham-Rundles, Lisa Giulino-Roth, Olivier Elemento, Gregor Dückers, Tim Niehues, Eva Fronkova, Veronika Kanderová, Craig D. Platt, Janet Chou, Talal A. Chatila, Raif Geha, Elizabeth McDermott, Su Bunn, Monika Kurzai, Ansgar Schulz, Laia Alsina, Ferran Casals, Angela Deyà-Martinez, Sophie Hambleton, Hirokazu Kanegane, Kjetil Taskén, Olaf Neth, Bodo Grimbacher
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 13968: AMPK Regulates Cardiac Looping by Phosphorylating CLIP-170 that Determines the Directional Cell Migration and Polarity
Authors: Atsushi Nakano, Naoki Mochizuki, Masafumi Kitakaze, Seiji Takashima
Journal: Circulation (2010)

Introduction:  AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism not only in metabolic organs but also in the heart as evidenced by AMPK gene-modified mice. However, the downstream targets of AMPK that regulates physiological function in the heart have not been fully identified.   Methods and Results:  To identify a novel AMPK substrate, we performed unique two-step column chromatography. We identified a novel AMPK substrate; cytoplasmic linker protein of 170 KDa (CLIP-170). CLIP-170 is one of the microtubule plus-end proteins regulating microtubule dynamics. AMPK phosphorylates Ser 311 of CLIP-170 both  in vitro  and  in vivo . Inhibition of AMPK or expression of a non-phosphorylatable CLIP-170 mutant in cultured cells resulted in prolonged and increased accumulation of CLIP-170 at microtubule plus ends and slower tubulin polymerization/depolymerization. The failure of microtubule dynamics caused by the defect of CLIP-170 phosphorylation by AMPK led to stabilization of microtubules and perturbed cell migration. All of these phenotypes were rescued by expression of a phosphomimetic CLIP-170 mutant, supporting the importance of CLIP-170 phosphorylation by AMPK. Consistently,  in vivo , zebrafish specifically expressing non-phosphorylatable CLIP-170 in heart showed abnormal heart looping without the commitment of cardiac precursor cell to cardiomyocytes, indicating the essential role of AMPK for cardiomyocyte migration.   Conclusions:  AMPK controls basic cellular functions by regulating microtubule dynamics through CLIP-170 phosphorylation. This newly identified signalling pathway determines the cellular and tissue polarity in the heart.
P99The diagnostic significance of toll-like receptors-4 and heat-shock protein 70 assay in acute myocardial infarction and ischemic stroke
Authors: E V Konstantinova, N S Chipigina, V H Shurdumova, A A Bogdanova, A G Kochetov, O V Lyang, A M Sapozhnikov
Journal: Cardiovascular Research (2018)

Background: Data on the use of warm or cold cardioplegia solutions to achieve protection during cardiac surgery are controversial.There is substantial evidence that numbers of microRNAs (miRNAs) have either deleterious or protective effect in setting of myocardial ischemia/reperfusion (IR).The present study was aimed to clarify 1) the impact of warm blood or cold blood cardioplegia solutions on the expression of microRNAs in left ventricle tissue sample in a relevant model of human cardiopulmonary bypass (CPB) in pigs.Methods: Adult pigs were anesthetized (mean body weight 5262 kg) and monitored for baseline hemodynamic function.Hearts were arrested by antegrade administration of St. Thomas' blood cardioplegia (cold: 4 C, n¼6 vs. warm: 37 C, n¼6) for 60 min of ischemia followed by 60 min of on-pump reperfusion.Hemodynamic functions were monitored for further 90 min of reperfusion.Left ventricular (LV) tissue samples were taken for the assessment of microRNA expression profiling using next-generation sequencing technology and pathways enrichment analysis was performed using DIANA-miRPath.Results: The warm group showed improved systolic left ventricular pressure (p<0.05) and reduced wedge pressure during reperfusion (p<0.01).CK-MB levels were lower in the warm group (p<0.01).Overall 238 miRNAs were detected in all samples with a minimum read count of 1 Tags per million (TPM, expression level).Principal component analysis suggested that miRNAs expression was primarily influenced by the temperature of cardioplegia solution.The following microRNAs showed significant difference between groups; miR-451, miR-144, miR-146b, miR-9-1, miR-455 and miR-503.Interestingly, microRNAs having cardioprotective effects such as miR-144, miR-451 showed higher expression in the warm cardioplegia group in comparison to cold (miR-144: 5706153 vs 3106213 TPM, and miR-451: 13956493 vs 4536199 TPM; P<0.05, respectively).According to the hallmark of IR, the most relevant KEGG-pathways revealed by enrichment analysis were Hippo -and TGF-b signalling pathways, which were previously found to be differentially regulated in setting of myocardial IR-injury.Conclusion: Regulation of miRNA expression in myocardial tissue samples is primarily influenced by the temperature of cardioplegia solutions following IR.Of importance, improved hemodynamic function and reduction of IR-injury are associated with the elevation of cardioprotective miRNAs expression after warm cardioplegic arrest.
Evidence of Intertissue Differences in the DNA Damage Response and the Pro-oncogenic Role of NF-κB in Mice with Disengaged BRCA1–PALB2 Interaction
Authors: Amar Hekmat Mahdi, Yanying Huo, Yongmei Tan, Srilatha Simhadri, Gabriele Vincelli, Jie Gao, Shridar Ganesan, Bing Xia
Journal: Cancer Research (2018)

The BRCA1-PALB2-BRCA2 axis plays an essential role in DNA homologous recombination repair, defect in which drives genome instability and cancer development. How cells with defects in this pathway respond to DNA damage in vivo and how tumors develop from these cells remain poorly defined. Here, we analyzed several aspects of the DNA damage response in multiple tissues of Palb2-mutant mice in which the interaction between PALB2 and BRCA1 is disengaged. Without any challenge, the mutant mice showed increased endogenous DNA damage. Following ionizing radiation, the mutant mice displayed higher levels of DNA breaks and stronger induction of p53 and p21, but continued DNA synthesis, reduced apoptosis, and accelerated tumor development. The differences in p21 induction, DNA synthesis, and apoptosis between wild-type and mutant mice were substantially more pronounced in the mammary gland than in the intestine, suggesting a potential contributing factor to the increased risk and the tissue specificity of BRCA/PALB2-associated tumor development. Moreover, the mutant mice showed higher levels of reactive oxygen species and constitutive activation of NF-κB, an antiapoptotic transcription factor inducible by both DNA damage and oxidative stress. Treatment of the mutant mice with an inhibitor of NF-κB reactivated apoptosis and delayed tumor development following radiation. Thus, our results also suggest a prosurvival and pro-oncogenic role of NF-κB in PALB2-mutant cells.Significance: This study explores novel tumor suppression mechanisms of the BRCA1-PALB2 DNA damage response pathway and implicates NF-κB activation as a protumorogenic event and possible therapeutic target. Cancer Res; 78(14); 3969-81. ©2018 AACR.
Hepatitis B Virus Seropositivity in Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitors: Preliminary Results of a Single-Center Cross-Sectional Study
Authors: Nurgul Ozgur Yurttas, Burak Sarilar, Ahmet Emre Eskazan, Deniz Ozmen, Dilek Keskin, Sevil Sadri, Selin Berk, Ayse Salihoglu, M. Cem Ar, Seniz Ongoren, Zafer Baslar, Yildiz Aydin, Teoman Soysal
Journal: Blood (2017)
Rearrangement of the Protein Phosphatase 1 Interactome During Heart Failure Progression
Authors: David Y. Chiang, Katherina M. Alsina, Eleonora Corradini, Martin Fitzpatrick, Li Ni, Satadru K. Lahiri, Julia O. Reynolds, Xiaolu Pan, Larry Scott, Albert J.R. Heck, Xander H.T. Wehrens
Journal: Circulation (2018)

Heart failure (HF) is a complex disease with a rising prevalence despite advances in treatment. Protein phosphatase 1 (PP1) has long been implicated in HF pathogenesis, but its exact role is both unclear and controversial. Most previous studies measured only the PP1 catalytic subunit (PP1c) without investigating its diverse set of interactors, which confer localization and substrate specificity to the holoenzyme. In this study, we define the PP1 interactome in cardiac tissue and test the hypothesis that this interactome becomes rearranged during HF progression at the level of specific PP1c interactors.Mice were subjected to transverse aortic constriction and grouped on the basis of ejection fraction into sham, hypertrophy, moderate HF (ejection fraction, 30%-40%), and severe HF (ejection fraction <30%). Cardiac lysates were subjected to affinity purification with anti-PP1c antibodies followed by high-resolution mass spectrometry. PP1 regulatory subunit 7 (Ppp1r7) was knocked down in mouse cardiomyocytes and HeLa cells with adeno-associated virus serotype 9 and siRNA, respectively. Calcium imaging was performed on isolated ventricular myocytes.Seventy-one and 98 PP1c interactors were quantified from mouse cardiac and HeLa lysates, respectively, including many novel interactors and protein complexes. This represents the largest reproducible PP1 interactome data set ever captured from any tissue, including both primary and secondary/tertiary interactors. Nine PP1c interactors with changes in their binding to PP1c were strongly associated with HF progression, including 2 known (Ppp1r7 and Ppp1r18) and 7 novel interactors. Within the entire cardiac PP1 interactome, Ppp1r7 had the highest binding to PP1c. Cardiac-specific knockdown in mice led to cardiac dysfunction and disruption of calcium release from the sarcoplasmic reticulum.PP1 is best studied at the level of its interactome, which undergoes significant rearrangement during HF progression. The 9 key interactors that are associated with HF progression may represent potential targets in HF therapy. In particular, Ppp1r7 may play a central role in regulating the PP1 interactome by acting as a competitive molecular "sponge" of PP1c.
Comparison of ElastPQ Shear-wave Elastography (ElastPQ-SWE) and FibroScan Transient Elastography (F-TE) for liver fibrosis staging in patients with NAFLD
Authors: D. Roccarina, L.I. Prat, M. Guerrero, E. Buzzetti, M. Rosselli, M. Pinzani, E. Tsochatzis
Journal: Journal of Hepatology (2018)
Abstract #2589: Identification of direct Smad3 target genes mediating the TGF-beta-dependent \#8220;metastatic switch\#8221;
Authors: Misako Sato, Mitsutaka Kadota, Clifford Robert, Hongen Zhang, Maxwell Lee, Lalage Wakefield
Journal: Cancer Research (2009)

Transforming Growth Factor-beta (TGF-beta) has a complex dual role in carcinogenesis, acting as a tumor suppressor in early cancer development and as a prometastatic factor later in tumor progression. Perturbations in the TGF-beta system are seen in most human tumors. A key question is to understand what causes the tumor cells response to TGF-beta to switch from tumor suppression to metastasis promotion. We have shown that this \#8220;metastatic switch\#8221; occurs in a well-defined xenograft model of breast cancer. TGF-beta suppresses tumorigenesis in the MCF10Ca1h (M3) line, but promotes metastasis in the genetically highly-related MCF10Ca1a (M4) cell line. This pair of cell lines represents an ideal model to identify the critical molecular changes in the TGF-beta pathway that underlie the \#8220;metastatic switch\#8221;. I hypothesize that genetic and/or epigenetic alteration of direct target genes of Smad3, a key transcription factor of the TGF-beta pathway, occur during cancer progression and cause the cellular response to TGF-beta to switch from tumor suppression to tumor promotion. To address this, I used chromatin immuno-precipitation combined with Affymetrix promoter tiling array (ChIP-on-chip) to identify regions that are directly bound with Smad3 in different stages of breast cancer. Sixty Smad3 binding regions were identified at high stringency, most of which (95%) were novel. Expression status of these genes was analyzed in breast cancer datasets and I observed significant correlation with patient survival in clinical cohorts, suggesting that the identified Smad3 binding regions are enriched for genes that are relevant to breast cancer progression.  Among the 60 Smad3 binding regions identified, many overlapped between M3 and M4 cell lines. However, by integrating the Chip-on-chip data with gene expression data, I have found that 25% of those Smad3 target genes are differentially regulated between M3 and M4 cell lines either by physical association to Smad3 and/or at subsequent transcriptional level. My finding suggests that this subset of Smad3 target genes could function as key mediators of the TGF-beta driven \#8220;metastatic switch\#8221; in breast cancer progression. I further validate those set of genes and establish a Smad3-based gene expression signature that distinguishes tumor suppressor from pro-metastatic activity of TGF-beta. My approach may provide novel strategies to normalize cancer cell responses to TGF-beta, eliminating the pro-progression responses and restoring the tumor suppressor responses.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2589.
Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus
Authors: Jinfeng Wang, Jiayong Zheng, Wenyu Shi, Nan Du, Xiaomin Xu, Yanming Zhang, Peifeng Ji, Fengyi Zhang, Zhen Jia, Yeping Wang, Zhi Zheng, Hongping Zhang, Fangqing Zhao
Journal: Gut (2018)

Objective The initial colonisation of the human microbiota and the impact of maternal health on neonatal microbiota at birth remain largely unknown. The aim of our study is to investigate the possible dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus (GDM) and to estimate the potential risks of the microbial shift to neonates. Design Pregnant women and neonates suffering from GDM were enrolled and 581 maternal (oral, intestinal and vaginal) and 248 neonatal (oral, pharyngeal, meconium and amniotic fluid) samples were collected. To avoid vaginal bacteria contaminations, the included neonates were predominantly delivered by C-section, with their samples collected within seconds of delivery. Results Numerous and diverse bacterial taxa were identified from the neonatal samples, and the samples from different neonatal body sites were grouped into distinct clusters. The microbiota of pregnant women and neonates was remarkably altered in GDM, with a strong correlation between certain discriminatory bacteria and the oral glucose tolerance test. Microbes varying by the same trend across the maternal and neonatal microbiota were observed, revealing the intergenerational concordance of microbial variation associated with GDM. Furthermore, lower evenness but more depletion of KEGG orthologues and higher abundance of some viruses (eg, herpesvirus and mastadenovirus) were observed in the meconium microbiota of neonates associated with GDM. Conclusion GDM can alter the microbiota of both pregnant women and neonates at birth, which sheds light on another form of inheritance and highlights the importance of understanding the formation of early-life microbiome.
Analyzing the Duration Between Acute Insult and ACLF in a Chinese 14 centers, prospective study for natural course of ACLF
Authors: G. Wenyi, B.-Y. Xu, X. Zheng, J. Chen, X.-B. Wang, Y. Huang, Y. Gao, Z.-J. Meng, Z.-P. Qian, F. Liu, X.-B. Lu, J. Shang, H. Li, S. Wang, H. Li
Journal: Journal of Hepatology (2018)
Cancer antigen 125 (CA125) and the law of unintended consequences.
Authors: Scheryll Paula Alken, Linda E. Coate, Bernie Woulfe, NIamh O'Leary, Ivana M Capin, Ophelia Blake, Rajnish K. Gupta
Journal: Journal of Clinical Oncology (2017)

e18327 Background: CA125 is a serum tumour marker used to monitor patients with ovarian cancer (OvCa). Its usefulness as a screening tool remains unproven. There is no restriction in its use at our institution, a university teaching hospital. We sought to establish patterns of testing during one calendar year (2013), focussing on the economic costs of such unrestricted testing. Methods: A lookback of the CA125 reports issued by the Biochemistry Laboratory was undertaken. The CA125 requests were from physicians within the hospital &amp; from the community. Individual requests for CA125 &amp; those part of tumour marker panel were included &amp; correlated with radiology &amp; histopathology records to identify subsequent investigations (invxs) &amp; diagnoses (dxs). Economic costings were provided by hospital finance department. For the purpose of this study we only included the costs of invxs triggered by out of range CA 125 test results. Results: In 2013, 7,132 CA125 measurements were performed. 871 repeat tests, 40 tests performed on men &amp; 16 tests with inadequate patient identifiers were excluded. Of the remaining 6,205 patient tests; median age was 53yrs (range 13 – 96yrs); median CA125 was 5.5 IU/L (range 0.1 – 22452 IU/L). Out of range tests (&gt;35 IU/L) led to 619 ultrasound scans, 339 CT scans. In total, 20 new cases of OvCa were dx. The crude cost per new dx was €11,459.80. Median time to diagnosis was 4 days (range -2 – 251), median CA125 at dx was 271 (range 8.1 - 9444). Median age at dx was 62 (range 40 – 87). 65% of dx were made during inpatient stays;10% by family physicians;25% by gynaecologists. There was a statistically significant difference in median CA125 in patients diagnosed with OvCa, compared to those who were not dx with a malignant condition (p&lt;0.0001); this was not true of age at dx (p=0.27). Conclusions: This study underlines the lack of efficacy in unrestricted serum CA125 testing &amp; that such testing creates a significant economic burden on hospitals, far in excess of the cost of the CA125 test alone. We plan to implement guidelines in our institution &amp; will reassess this issue following an education programme with local clinicians. [Table: see text]
Antitrust, Market Exclusivity, and Transparency in the Pharmaceutical Industry
Authors: Michael S. Sinha, Gregory D. Curfman, Michael A. Carrier
Journal: JAMA (2018)

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Fast-track HCV check-up enhances possibility of sustained virologicalresponse in HCV infected patients
Authors: T. Antonini, M.G. Tateo, P. Attali, E. De Martin, A. Coilly, B. Roche, R. Sobesky, D. Samuel, A.M. Roque-Afonso, J.-C. Duclos-Vallée
Journal: Journal of Hepatology (2018)