tbuckley/cabot-search huggingface dataset:
miR-590-3p Promotes Ovarian Cancer Growth and Metastasis via a Novel FOXA2–Versican Pathway
Authors: Mohamed Salem, Jacob A. O'Brien, Stefanie Bernaudo, Heba Shawer, Gang Ye, Jelena Brkić, Asma Amleh, Barbara C. Vanderhyden, Basel Refky, Burton B. Yang, Sergey N. Krylov, Chun Peng
Journal: Cancer Research (2018)

Abstract miRNAs play important roles in gene regulation, and their dysregulation is associated with many diseases, including epithelial ovarian cancer (EOC). In this study, we determined the expression and function of miR-590-3p in EOC. miR-590-3p levels were higher in high-grade carcinoma when compared with low-grade or tumors with low malignant potential. Interestingly, plasma levels of miR-590-3p were significantly higher in patients with EOC than in subjects with benign gynecologic disorders. Transient transfection of miR-590-3p mimics or stable transfection of mir-590 increased cell proliferation, migration, and invasion. In vivo studies revealed that mir-590 accelerated tumor growth and metastasis. Using a cDNA microarray, we identified forkhead box A2 (FOXA2) and versican (VCAN) as top downregulated and upregulated genes by mir-590, respectively. miR-590-3p targeted FOXA2 3′ UTR to suppress its expression. In addition, knockdown or knockout of FOXA2 enhanced cell proliferation, migration, and invasion. Overexpression of FOXA2 decreased, whereas knockout of FOXA2 increased VCAN mRNA and protein levels, which was due to direct binding and regulation of the VCAN gene by FOXA2. Interrogation of the TCGA ovarian cancer database revealed a negative relationship between FOXA2 and VCAN mRNA levels in EOC tumors, and high FOXA2/low VCAN mRNA levels in tumors positively correlated with patient survival. Finally, overexpression of FOXA2 or silencing of VCAN reversed the effects of mir-590. These findings demonstrate that miR-590-3p promotes EOC development via a novel FOXA2–VCAN pathway. Significance: Low FOXA2/high VCAN levels mediate the tumor-promoting effects of miR-590-3p and negatively correlate with ovarian cancer survival. Cancer Res; 78(15); 4175–90. ©2018 AACR.
Prognosis of ALF of unknown cause: results of the French multicentre prospective HASIPRO study
Authors: A. Coilly, S. Dharancy, C. Duvoux, V.D. Martino, Jérôme Dumortier, S. Radenne, L. Alric, C. Besch, C. Francoz, J. Perarnaud, M. Rudler, N. Carbonell, C. Silvain, V. Leroy, A.V. Pichard, G. Lassailly, F. Artru, T. Antonini, H. Agostini, C. Piedvache, J.-C. Duclos-Vallée, P. Ichai, D. Samuel
Journal: Journal of Hepatology (2018)
Immunogenomic Analyses of Advanced Serous Ovarian Cancer Reveal Immune Score is a Strong Prognostic Factor and an Indicator of Chemosensitivity
Authors: Dapeng Hao, Jie Liu, Meng Chen, JingJing Li, Li Wang, Xiaobo Li, Qi Zhao, Li-jun Di
Journal: Clinical Cancer Research (2018)

Purpose: Ovarian cancer is one of the first human cancers for which in situ immune response was reported to be important for the clinical outcome. To elucidate the mechanistic relationship between immune repertoire and cancer genotype in ovarian cancer, the development of a well-defined immune score for ovarian cancer is required.Experimental Design: From a collection of 2,203 patient samples of advanced ovarian cancer from public available resources, we evaluated the prognostic values for a compendium of immune marker genes and proposed an immune score. The relationships between immune score, tumor-infiltrating immune cells, cancer genotypes, and their impact on patient outcome were characterized.Results: Loss of chemokine and IFNγ pathway genes is frequent in ovarian cancer and is significantly associated with low immune score and poor outcome. Chemotherapy can increase the immune score of tumors by inducing the expression of IFNγ inducible chemokines. High immune score is significantly associated with BRCA1/2 mutation status and the response to chemotherapy. Multivariate analysis revealed that immune score is a strong predictor of patient survival and the response to immunotherapy.Conclusions: Our results reveal the drivers of the immune repertoire of advanced ovarian cancer and demonstrate the importance of immune score as an independent prognostic signature and a potent indicator of intratumoral immune status. Clin Cancer Res; 24(15); 3560-71. ©2018 AACR.
Eluid Content of the Nucleus Pulposus as a Factor in the Disk Syndrome
Authors: H. D. Bush, W. G. Horton, D. L. Smare, A. Naylor
Journal: BMJ (1956)

MEDICAL JOURNALfor cases of lung and heart disease.It is also a useful technique in the management of the second stage of labour in primigravidae.The risk of aspiration pneumonia is obviated, and for this reason the technique can help to reduce mortality and morbidity.There were no foetal deaths that could be attributed to the anaesthetic used.It is suggested that this is a simpler form of analgesia than caudal and spinal analgesia, and one which allows for full oxygenation of the mother and the foetus.The maternal complications were comparatively slight and the length of stay in hospital was not increased, though 9 out of the 57 patients had oedema, bruising, or haematoma formation.In three cases another form of anaesthesia was given in order to accomplish a technically more difficult delivery.My thanks are due to Miss Janet Bottomley and Mr. Oswald Lloyd for their permission to perform the pudendal nerve blocks and to report the results.
Prostate-Specific Membrane Antigen–Negative Metastases—A Potential Pitfall in Prostate-Specific Membrane Antigen PET
Authors: Benjamin Noto, Katharina Auf der Springe, Sebastian Huss, Thomas Allkemper, Lars Stegger
Journal: Clinical Nuclear Medicine (2018)

Abstract 68 Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression. This case demonstrates the possibility of PSMA-negative metastases of prostate cancer an important pitfall that should be known to physicians interpreting PSMA PET.
The underlying pathophysiology and therapeutic approaches for osteoporosis
Authors: Harshika Awasthi, Dayanandan Mani, Divya Singh, Atul Gupta
Journal: Medicinal Research Reviews (2018)

Abstract With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect. The proper understanding of pathophysiology of the disease is essential for designing or investigating an effective and safe anti‐osteoporotic agent. This review represents a discussion around the molecular targets with their implications in disease progression, available therapeutic options, the emerging targets, and the importance of designing an effective anti‐osteoporotic agent.
CD4+ RORgt+ T cells, CD4+ T-bet+ T cells, CD4+ CD25+ Foxp3+ T cells and CD8+ T cells are differentially altered in liver and adipose tissue of mice fed a high-fat high-fructose diet in a time-dependent manner
Authors: M. Van Herck, L. Vonghia, P. Michielsen, C. Bridts, D. Ebo, J. De Man, B. De Winter, S. Francque
Journal: Journal of Hepatology (2018)
Tumour-homing chimeric polypeptide-conjugated polypyrrole nanoparticles for imaging-guided synergistic photothermal and chemical therapy of cancer
Authors: Mengmeng Sun, Jianwen Guo, Hanjun Hao, Tong Tong, Kun Wang, Weiping Gao
Journal: Theranostics (2018)

Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency.To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer.Methods: A tumour-homing chimeric polypeptide C-ELP-F3 was genetically engineered, and chemoselectively conjugated to polypyrrole (PPy) nanoparticles via a facile thiol-maleimide coupling reaction to form ELP-F3 conjugated PPy (PPy-ELP-F3) nanoparticles.Doxorubicin (DOX) was physically adsorbed onto PPy-ELP-F3 nanoparticles to yield DOX-loaded PPy-ELP-F3 (DOX/PPy-ELP-F3) nanoparticles.The physicochemical properties of DOX/PPy-ELP-F3 were characterized.The pharmacokinetics of DOX/PPy-ELP-F3 was studied in a mouse model.The photoacoustic imaging and photothermal imaging of tumours were tested in a melanoma-bearing mouse model.The photothermal-chemical combination therapy of tumours was investigated by using melanoma cells in vitro and in a melanoma-bearing mouse model.Results: DOX/PPy-ELP-F3 nanoparticles showed enhanced cytotoxicity to melanoma cells in vitro and improved tumour-targeting efficiency in vivo, as compared with both DOX/PPy-ELP nanoparticles without the tumour-homing function and free DOX.The photothermal effect of DOX/PPy-ELP-F3 nanoparticles could accelerate the release of DOX from PPy-ELP-F3.Under the guidance of photoacoustic and photothermal imaging, the synergy of photothermal and chemical therapy could completely abolish tumours without detectable systemic toxicity.Conclusion: Tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugatedpolymer nanoparticles are promising as a new multifunctional drug delivery platform for highly-efficient imaging guided combination therapy.
Estrogen receptor R1 and CAD are host factors for HDV replication and antiviral targets
Authors: E. Verrier, A. Weiss, C. Bach, L. Heydmann, L. Mailly, T. Garcia, P. Pale, C. Schuster, C. Sureau, M. Zeisel, L. Brino, T. Baumert
Journal: Journal of Hepatology (2018)
Opal, but not MARS improves patients albumin binding function measured by Electron Spin Resonance (ESR) in a prospective multicenter trial
Authors: A. Kortgen, J. Stange, C. Sponholz, H. Schmidt, C. Wilms, H.U. Gerth, S. Mitzner, M. Dollinger, T. Hassanein
Journal: Journal of Hepatology (2018)
Caveolae-mediated mesenchymal stem cell labelling by PSS-coated PLGA PFOB nano-contrast agent for MRI
Authors: Hieu Vu Quang, Chi-Chih Chang, Ping Song, Ellen-Margrethe Hauge, Jørgen Kjems
Journal: Theranostics (2018)

Rationale: Non-invasive tracking of transplanted cells is critical in evaluating delivery, migration and prognosis of cell therapies.Methods: We formulated a nano-contrast agent consisting of a perfluorooctylbromide (PFOB) core within a shell of poly (lactic-co-glycolic acid) (PLGA) followed by a coat of polystyrene sulfonate (PSS) for 19 F MRI.The nano-contrast agent (PSS-NP) was characterised by DLS and the uptake efficiency of the nano-contrast agent (PSS-NP) was tested using flow cytometry, in vitro MRI and confocal microscopy.In vitro and in vivo assays of labelled cells were tested for their ability to provide an MRI signal while retaining their osteoblastic differentiation capabilities.Results: PSS-NPs were internalised via caveolae-mediated endocytosis in mesenchymal stromal/stem cells without affecting cell proliferation and differentiation in osteoblasts, both in vitro and in vivo.Furthermore, labelled cells were monitored by 19 F MRI for up to 2 months after transplantation in mice.In particular, PSS-NP-labelled cells can be used to monitor the enhanced immune rejection of grafted human cells in normal BALB/c mice compared to immune-compromised NOD/SCID mice.One week after transplantation, 40% of the 19 F MRI signal was lost in normal mice, whereas only 10% was lost in immune-compromised mice.Conclusion: Overall, these results show that PSS-NPs can label MSCs effectively, and be employed in vivo as a novel nano-contrast agent for non-invasive cell tracking using clinically relevant 19 F MRI techniques.
Abstract 11335: Therapeutic Hypothermia Improves Cardiac Function After Successful Resuscitation From Cardiac Arrest in a Rat Model of Myocardial Infarction
Authors: Hao Li, Jeonghyun Park, Yinlun Wen, Fengqing Song, Xiaobo Wu, Wei Wang, Tianfeng Hua, Mary A Peberdy, Joseph Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: We previously demonstrated that hypothermia improves post-resuscitation myocardial function in cardiac arrest animal models without coronary artery disease. In the present study, we investigated the effects of therapeutic hypothermia on post resuscitation myocardial function in a more clinically relevant rat model of myocardial infarction. Hypothesis: The therapeutic hypothermia improves post-resuscitation myocardial function after cardiac arrest and cardiopulmonary resuscitation in a rat model of myocardial infarction. Methods: Myocardial infarction was produced by left coronary artery (LCA) ligation 90 min prior to induction of ventricular fibrillation (VF). CPR with mechanical ventilation and precordial compression was initiated after 6 min of untreated VF. Defibrillation was attempted after 8 min of CPR. Animals were randomized into 2 groups: (1) Myocardial infarction-Normothermia group (MI-NT group, n=6), the core temperature was maintained at 37.0±0.2°C during resuscitation and next 4 hours after resuscitation; (2) Myocardial infarction-Hypothermia group (MI-HT group, n=6), the core temperature was maintained at 32.0±0.5°C during resuscitation and next 4 hours after resuscitation. Results: All animals were resuscitated successfully. Post-resuscitation ejection fraction (EF) and cardiac output (CO) were significantly greater in animals treated with hypothermia. ( p &lt;0.01, Figure 1 and 2). Conclusions: Therapeutic hypothermia significantly reduces the severity of post-resuscitation myocardial systolic dysfunction in a rat model of myocardial infarction.
Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis
Authors: Derek K Chu, Lisa H-Y Kim, Paul J Young, Nima Zamiri, Saleh A Almenawer, Roman Jaeschke, Wojciech Szczeklik, Holger J Schünemann, John D Neary, Waleed Alhazzani
Journal: The Lancet (2018)
Lateral Recumbent or Prone Positioning for PET of the Urinary Bladder
Authors: Marc R.J. ten Broek, Peter J. Ausems, Erik T. te Beek
Journal: Clinical Nuclear Medicine (2018)

Evaluation of the urinary bladder on PET with F-FDG is hampered by accumulation of activity in the urinary bladder due to physiological excretion of F-FDG in urine. We present 2 examples that demonstrate the utility of delayed scanning in lateral recumbent or prone position to improve evaluation of the bladder by differentiating between active bladder wall lesions and intraluminal activity. Changing the body position from a supine to a lateral recumbent or prone position can result in migration of intraluminal activity due to gravitational force, whereas F-FDG uptake in bladder wall lesions will show no migration.
42Pericardial adipose tissue regulates granulopoiesis, fibrosis and cardiac function after myocardial infarction
Authors: M Horckmans, M Bianchini, D Santovito, RTA Megens, M Vacca, M Di Eusanio, A Moschetta, C Weber, J Duchene, S Steffens
Journal: Cardiovascular Research (2018)
Post-treatment liver stiffness measurement is not useful to predict hepatocellular carcinoma in HCV patients who achieve SVR
Authors: S. Shili, S. Giovanna, J. Foucher, V. Anne, H. Jean-Baptiste, M. Francois, F. Chermak, P.-H. Bernard, V. De Ledinghen, C. Hezode
Journal: Journal of Hepatology (2018)
P75Shortening and calcium transport in epicardial and endocardial ventricular myocytes from the streptozotocin-induced diabetic rat
Authors: F C Howarth, L Al Kury, V Sydorenko, MMA Smail, M A Qureshi, A Shmygol, M Oz, J Singh
Journal: Cardiovascular Research (2018)

Background/Introduction: Diabetes mellitus (DM) is a serious global health problem. According to the International Diabetes Federation Atlas 2015 the estimated number of people with DM worldwide is expected to increase from 415 million in 2015 to 642 million in 2040. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Electromechanical function is frequently compromised in the diabetic heart.

Purpose: To investigate the regional effects of DM on shortening and calcium (Ca2+) transport in epicardial (EPI) and endocardial (ENDO) myocytes from the left ventricle of streptozotocin (STZ) - induced...
Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients with Melanoma Treated with Pembrolizumab
Authors: Richard W. Joseph, Jeroen Elassaiss-Schaap, Richard Kefford, Wen-Jen Hwu, Jedd D. Wolchok, Anthony M. Joshua, Antoni Ribas, F. Stephen Hodi, Omid Hamid, Caroline Robert, Adil Daud, Roxana Dronca, Peter Hersey, Jeffrey S. Weber, Amita Patnaik, Dinesh P. de Alwis, Andrea Perrone, Jin Zhang, S. Peter Kang, Scot Ebbinghaus, Keaven M. Anderson, Tara C. Gangadhar
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The purpose of this study was to assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1–89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites; all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs. 23%; P &amp;lt; 0.001) and improved OS (HR, 0.38; P &amp;lt; 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P &amp;lt; 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1–positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma. Clin Cancer Res; 24(20); 4960–7. ©2018 AACR. See related commentary by Warner and Postow, p. 4915
Simplifying Treatment and Reducing Recurrence for Patients With Early-Stage Bladder Cancer
Authors: Samuel D. Kaffenberger, David C. Miller, Matthew E. Nielsen
Journal: JAMA (2018)

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CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes
Authors: Zhongming Ma, Akiyuki Taruno, Makoto Ohmoto, Masafumi Jyotaki, Jason C. Lim, Hiroaki Miyazaki, Naomi Niisato, Yoshinori Marunaka, Robert J. Lee, Henry Hoff, Riley Payne, Angelo Demuro, Ian Parker, Claire H. Mitchell, Jorge Henao-Mejia, Jessica E. Tanis, Ichiro Matsumoto, Michael G. Tordoff, J. Kevin Foskett
Journal: Neuron (2018)
Emergence of carbapenem-resistant Acinetobacter nosocomialis strain ST410 harbouring plasmid-borne blaOXA-72 gene in Taiwan
Authors: H.-Y. Chen, Y.-S. Yang, W.-J. Hsu, Y.-C. Chou, L.-S. Huang, Y.-C. Wang, T.-S. Chiueh, J.-R. Sun
Journal: Clinical Microbiology and Infection (2018)
402Circulating histones are major mediators of cardiac complications in sepsis
Authors: G Wang, Y Alhamdi, S T Abrams, C H Toh
Journal: Cardiovascular Research (2018)

Introduction:The most common pathological change in critical illness is multiple organ failure, including cardiac complications, which often leads to early death.However, the underlying molecular mechanisms are not fully understood.Recently, the secondary hit by circulating histones causes great attention.Method: Both septic animal models and patients with sepsis were investigated.Circulating histones were detected and their association with organ injury markers was analyzed.Intervention with anti-histone antibodies was carried out to confirm the cause-effect relationship.Results: Circulating histones were dramatically elevated in both animal models and septic patients.Their levels were strongly associated with the severity of organ injury, particularly cardiac injury marker, cardiac troponins.Using anti-histone scFv in mouse models could significantly reduce the release of cardiac troponins as well as the incidence of the cardiac arrhythmia, and cardiac failure induced by histone infusion or sepsis.In addition, histones binding prothrombin initialized coagulation and significantly contribute to dysregulated coagulation leading to disseminated intravascular coagulation (DIC) and microcirculation impairment.Conclusion: Circulating histones play critical roles in sepsis, including inflammation, coagulation activation, and multiple organ injury, particularly cardiac complications.This lays a foundation for future anti-histone intervention to reduce the unacceptably high mortality rates of sepsis.