tbuckley/cabot-search huggingface dataset:
High Glucose Induces Mesangial Cell Apoptosis through miR-15b-5p and Promotes Diabetic Nephropathy by Extracellular Vesicle Delivery
Authors: Yi-Chun Tsai, Mei-Chuan Kuo, Wei-Wen Hung, Ling-Yu Wu, Ping-Hsun Wu, Wei-An Chang, Po-Lin Kuo, Ya-Ling Hsu
Journal: Molecular Therapy (2020)

Diabetic nephropathy (DN) is an increasing threat to human health and is regarded as an important public issue. The pathophysiologic mechanisms of DN are complicated. The initiating molecular events triggering the loss function in mesangial cells (MCs) in DN are not well known. In this cross-disciplinary study, transcriptome analysis of high glucose (HG)-treated mouse MCs (MMCs) using next-generation sequencing and systematic bioinformatics analyses indicated that miR-15b-5p and its downstream target B cell lymphoma 2 (BCL-2) contribute to HG-induced apoptosis in MMCs. HG elevated miR-15b-5p expression, which in turn decreased the translation of BCL-2, leading to MMC apoptosis under HG. Apoptosis of MCs was enhanced in the presence of extracellular vesicles isolated from the urine of type 2 diabetic patients with high levels of miR-15b-5p. Furthermore, increased levels of urinary miR-15b-5p were found in db/db mice and type 2 diabetic patients, and such levels correlated with low baseline kidney function and rapid decline in kidney function during a mean of follow-up period of 2.4 ± 0.1 years. Therefore, miR-15b-5p induced mesangial cells apoptosis by targeting BCL-2 under HG. miR-15b-5p has the potential to predict kidney injury in DN. Blocking the miR-15b-5p epigenetic regulatory network could be a potential therapeutic strategy to prevent mesangial apoptosis in DN. Diabetic nephropathy (DN) is an increasing threat to human health and is regarded as an important public issue. The pathophysiologic mechanisms of DN are complicated. The initiating molecular events triggering the loss function in mesangial cells (MCs) in DN are not well known. In this cross-disciplinary study, transcriptome analysis of high glucose (HG)-treated mouse MCs (MMCs) using next-generation sequencing and systematic bioinformatics analyses indicated that miR-15b-5p and its downstream target B cell lymphoma 2 (BCL-2) contribute to HG-induced apoptosis in MMCs. HG elevated miR-15b-5p expression, which in turn decreased the translation of BCL-2, leading to MMC apoptosis under HG. Apoptosis of MCs was enhanced in the presence of extracellular vesicles isolated from the urine of type 2 diabetic patients with high levels of miR-15b-5p. Furthermore, increased levels of urinary miR-15b-5p were found in db/db mice and type 2 diabetic patients, and such levels correlated with low baseline kidney function and rapid decline in kidney function during a mean of follow-up period of 2.4 ± 0.1 years. Therefore, miR-15b-5p induced mesangial cells apoptosis by targeting BCL-2 under HG. miR-15b-5p has the potential to predict kidney injury in DN. Blocking the miR-15b-5p epigenetic regulatory network could be a potential therapeutic strategy to prevent mesangial apoptosis in DN.
A Plasma Proteomic Signature Predicts Outcomes in a Phase 3 Study of Gemcitabine (G) + Cisplatin (C) ± Sorafenib in First Line Stage IIIB or IV NSCLC
Authors: J.F. Vansteenkiste, L. Paz-Ares, T.Q.G. Eisen, D. Heigener, W. Eberhardt, M. Thomas, C. Zhou, A. Santoro, C. Lathia, H. Roder
Journal: Annals of Oncology (2012)
Dupilumab as a <i>potential</i> steroid-sparing treatment for IgG4-related disease
Authors: Emanuel Della-Torre, Marco Lanzillotta, Mona-Rita Yacoub
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the article from Simpson et al on the efficacy of dupilumab—an anti-IL-4 receptor alfa monoclonal antibody—in a patient with multi-organ IgG4-related disease (IgG4-RD) involving the retroperitoneum and, apparently, the prostate and the parotid glands.1 According to the case presentation, the patient refused immunosuppressive agents due to the risk of adverse events, and treating physicians decided to start him on 40 mg oral prednisone. Subcutaneous dupilumab was added based on multiple concomitant poorly controlled atopic manifestations including asthma, dermatitis and periorbital angioedema. Prednisone was tapered over 2 months and then withdrawn. Dupilumab was administered subcutaneously at initial dose of 600 mg, followed by 300 mg injections every other week for 12 months. Three months later, amelioration of all manifestations was observed, and after 12 months on dupilumab, retroperitoneal fibrosis was dramatically improved. Sensible decrease in …
Androgen Receptor Activation in Prostatic Tumor Cell Lines by Insulin-Like Growth Factor-1, Keratinocyte Growth Factor and Epidermal Growth Factor
Authors: Zoran Culig, Alfred Hobisch, Marcus V. Cronauer, Christian Radmayr, Jan Trapman, Anton Hittmair, Georg Bartsch, Helmut Klocker
Journal: European Urology (1995)
Abstract 100: Neuroprotection Provided by Transnasal Airflow-Induced Brain Cooling in a Model of Pediatric Cardiac Arrest
Authors: Zeng-Jin Yang, C. Danielle Hopkins, Shawn Adams, Ewa Kulikowicz, Harikrishna S Tandri, Raymond C Koehler
Journal: Circulation (2019)

Introduction: High transnasal airflow at ambient temperature increases evaporative cooling of the nasal passages and drives a countercurrent heat exchange between cooled venous blood draining the nasal turbinates with cephalic arterial blood. Hypothesis: High transnasal airflow is not inferior to standard surface cooling in protecting the brain in an infant swine model of asphyxic cardiac arrest. Methods: Arterial O2 saturation was decreased to ~35% for 45 min followed by 7 min airway occlusion to produce asphyxic cardiac arrest in 2-week-old anesthetized piglets (4 kg). Viable neuronal counts were assessed at 6 days of recovery in 6 groups (n=5-9): 1) sham surgery, 2) normothermic recovery, 3) surface cooling to decrease rectal temperature from 38.5 to 34C between 10-120 min 4) transnasal cooling with airflow of 32 L/min from 10-120 min, 5) surface cooling onset delayed until 120 min ROSC, and 6) transnasal cooling delayed by 120 min ROSC. In all 4 cooling groups, hypothermia was sustained at 34C with surface cooling until 20 h ROSC followed by 6-8 h of rewarming. Results: Nasal airflow of 32 L/min decreased brain temperature from 38.3±0.3°C to 33.8±0.6 within 60 min without spatial temperature gradients in these 45-g brains. Surface cooling and transnasal airflow rescued the number of viable neurons in putamen from 38±23% (% of sham viable neurons; ±SD) in the normothermic group to 67±33% and 76±36%, respectively, when initiated at 10 min ROSC, and to 72±30% and 61±25%, respectively, when initiated at 120 min. In sensorimotor cortex, surface cooling and transnasal airflow rescued neurons from 56±36% in the normothermic group to 89±37% and 89±29%, respectively, when initiated at 10 min ROSC, and to 84±19% and 81±28%, respectively, when initiated at 120 min. Conclusions: The use of a high transnasal airflow is as effective as standard surface cooling when initiated at 10 or 120 min after ROSC in protecting vulnerable putamen and sensorimotor cortex from asphyxic cardiac arrest in infant piglets. Because of its simplicity, portability, and low cost, we postulate that transnasal cooling potentially could be deployed in the field by first responders for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.
Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness
Authors: Sandra Muñoz-Galván, Blanca Felipe-Abrio, Eva M. Verdugo-Sivianes, Marco Perez, Manuel P. Jiménez-García, Elisa Suarez-Martinez, Purificacion Estevez-Garcia, Amancio Carnero
Journal: Molecular Cancer (2020)

Ovarian cancer is one of the most common and malignant cancers, partly due to its late diagnosis and high recurrence. Chemotherapy resistance has been linked to poor prognosis and is believed to be linked to the cancer stem cell (CSC) pool. Therefore, elucidating the molecular mechanisms mediating therapy resistance is essential to finding new targets for therapy-resistant tumors.shRNA depletion of MYPT1 in ovarian cancer cell lines, miRNA overexpression, RT-qPCR analysis, patient tumor samples, cell line- and tumorsphere-derived xenografts, in vitro and in vivo treatments, analysis of data from ovarian tumors in public transcriptomic patient databases and in-house patient cohorts.We show that MYPT1 (PPP1R12A), encoding myosin phosphatase target subunit 1, is downregulated in ovarian tumors, leading to reduced survival and increased tumorigenesis, as well as resistance to platinum-based therapy. Similarly, overexpression of miR-30b targeting MYPT1 results in enhanced CSC-like properties in ovarian tumor cells and is connected to the activation of the Hippo pathway. Inhibition of the Hippo pathway transcriptional co-activator YAP suppresses the resistance to platinum-based therapy induced by either low MYPT1 expression or miR-30b overexpression, both in vitro and in vivo.Our work provides a functional link between the resistance to chemotherapy in ovarian tumors and the increase in the CSC pool that results from the activation of the Hippo pathway target genes upon MYPT1 downregulation. Combination therapy with cisplatin and YAP inhibitors suppresses MYPT1-induced resistance, demonstrating the possibility of using this treatment in patients with low MYPT1 expression, who are likely to be resistant to platinum-based therapy.
P1.24 Loss of Succinate Dehydrogenase in Midgut Carcinoids as Prognostic Factor: A New Marker of Personalized Cancer Medicine in Neuroendocrine Tumours?
Authors: M. Milione, F. de Braud, R. Buzzoni, S. Pusceddu, V. Mazzaferro, A. Damato, G. Pelosi
Journal: Annals of Oncology (2012)
Placental Growth Factor (PIGF) as a Biomarker in Patients (PTS) With Solid Tumors Treated With Linifanib (ABT-869)
Authors: E.M. Mc Keegan, B.C. Goh, H.C. Toh, N. Tannir, A. Chakravartty, P.J. Ansell, S. Datwyler, M.D. McKee, J.L. Ricker, D.M. Carlson
Journal: Annals of Oncology (2012)
Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)
Authors: Pui Y. Lee, Erinn S. Kellner, Yuelong Huang, Elissa Furutani, Zhengping Huang, Wayne Bainter, Mohammed F. Alosaimi, Kelsey Stafstrom, Craig D. Platt, Tali Stauber, Somech Raz, Irit Tirosh, Aaron Weiss, Michael B. Jordan, Christa Krupski, Despina Eleftheriou, Paul Brogan, Ali Sobh, Zeina Baz, Gerard Lefranc, Carla Irani, Sara S. Kilic, Rasha El-Owaidy, M.R. Lokeshwar, Pallavi Pimpale, Raju Khubchandani, Eugene P. Chambers, Janet Chou, Raif S. Geha, Peter A. Nigrovic, Qing Zhou
Journal: Journal of Allergy and Clinical Immunology (2020)
Second Interim Analysis of the Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib (GIDEON) Study According to Disease Stage
Authors: B. Daniele, J. Turnes, G. Bodoky, C. Papandreou, A. Hubert, P. Stål, V.A. Gorbunova, F. Serejo, A. Croitoru, P. Mathurin
Journal: Annals of Oncology (2012)
Cancer Stem Cell Markers in Clinical Pancreatic Cancer: Impact of CD44 + /CD24 + /EPCAM+ Expression on Histology and Prognosis
Authors: Y. Ohara, T. Oda, Y. Akashi, R. Miyamoto, K. Yamada, S. Hashimoto, N. Ohkohchi
Journal: Annals of Oncology (2012)
Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration
Authors: Alexander Drilon, Jeffrey W. Clark, Jared Weiss, Sai-Hong Ignatius Ou, D. Ross Camidge, Benjamin J. Solomon, Gregory A. Otterson, Liza C. Villaruz, Gregory J. Riely, Rebecca S. Heist, Mark M. Awad, Geoffrey I. Shapiro, Miyako Satouchi, Toyoaki Hida, Hidetoshi Hayashi, Danielle A. Murphy, Sherry C. Wang, Sherry Li, Tiziana Usari, Keith D. Wilner, Paul K. Paik
Journal: Nature Medicine (2020)
Role of HDACs in normal and malignant hematopoiesis
Authors: Pan Wang, Zi Wang, Jing Liu
Journal: Molecular Cancer (2020)

Abstract Normal hematopoiesis requires the accurate orchestration of lineage-specific patterns of gene expression at each stage of development, and epigenetic regulators play a vital role. Disordered epigenetic regulation has emerged as a key mechanism contributing to hematological malignancies. Histone deacetylases (HDACs) are a series of key transcriptional cofactors that regulate gene expression by deacetylation of lysine residues on histone and nonhistone proteins. In normal hematopoiesis, HDACs are widely involved in the development of various lineages. Their functions involve stemness maintenance, lineage commitment determination, cell differentiation and proliferation, etc. Deregulation of HDACs by abnormal expression or activity and oncogenic HDAC-containing transcriptional complexes are involved in hematological malignancies. Currently, HDAC family members are attractive targets for drug design, and a variety of HDAC-based combination strategies have been developed for the treatment of hematological malignancies. Drug resistance and limited therapeutic efficacy are key issues that hinder the clinical applications of HDAC inhibitors (HDACis). In this review, we summarize the current knowledge of how HDACs and HDAC-containing complexes function in normal hematopoiesis and highlight the etiology of HDACs in hematological malignancies. Moreover, the implication and drug resistance of HDACis are also discussed. This review presents an overview of the physiology and pathology of HDACs in the blood system.
Dendritic Cell Therapy for Patients with Refractory Solid Tumours
Authors: P.P. Bapsy, B. Sharan, C. Kumar, A. Mahmood, B. Rangarajan, S. Atilli, M. Jain, S. Subramanian, S. Rajappa, M. Srivastava
Journal: Annals of Oncology (2012)
European Inter-Institutional Impact Study of Mammaprint
Authors: P. Cusumano, D.G. Generali, E. Ciruelos, L. Manso, I. Ghanem, E. Lifrange, G. Jerusalem, J. Klaase, L. Stork-Sloots, M. Lutke Holzik
Journal: Annals of Oncology (2012)
S-1 Plus Cisplatin Versus Docetaxel Plus Cisplatin in Chemotherapy-Naive Patients with Advanced Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase III Study (TCOG0701)
Authors: S. Niho, A. Gemma, H. Sakai, K. Kubota, M. Nishio, A. Inoue, H. Okamoto, H. Isobe, H. Kunitoh, Y. Takiguchi, K. Kobayashi, Y. Nakamura, N. Katakami, M. Takeuchi, S. Kudoh
Journal: Annals of Oncology (2012)
On the identification of the blood vessel confounding effect in intravoxel incoherent motion (IVIM) Diffusion-Weighted (DW)-MRI in liver: An efficient sparsity based algorithm
Authors: Jie Liu, Giulio Gambarota, Huazhong Shu, Longyu Jiang, Benjamin Leporq, Olivier Beuf, Ahmad Karfoul
Journal: Medical Image Analysis (2020)
Gold–silver nanoshells promote wound healing from drug-resistant bacteria infection and enable monitoring via surface-enhanced Raman scattering imaging
Authors: Jian He, Yue Qiao, Hongbo Zhang, Jun Zhao, Wanli Li, Tingting Xie, Danni Zhong, Qiaolin Wei, Shiyuan Hua, Yinhui Yu, Ke Yao, Hélder A. Santos, Min Zhou
Journal: Biomaterials (2020)
Stress-Only Adenosine CMR Improves Diagnostic Yield in Stable Symptomatic Patients With Coronary Artery Calcium
Authors: Dorine Rijlaarsdam-Hermsen, Mallory Lo-Kioeng-Shioe, Ron T. van Domburg, Jaap W. Deckers, Dirkjan Kuijpers, Paul R.M. van Dijkman
Journal: JACC. Cardiovascular imaging (2020)
Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy
Authors: Genaro Hernandez, Ting Luo, Tanveer A. Javed, Li Wen, Michael A. Kalwat, Kevin Vale, Farah Ammouri, Sohail Z. Husain, Steven A. Kliewer, David J. Mangelsdorf
Journal: Science Translational Medicine (2020)

The exocrine pancreas expresses the highest concentrations of fibroblast growth factor 21 (FGF21) in the body, where it maintains acinar cell proteostasis. Here, we showed in both mice and humans that acute and chronic pancreatitis is associated with a loss of FGF21 expression due to activation of the integrated stress response (ISR) pathway. Mechanistically, we found that activation of the ISR in cultured acinar cells and mouse pancreata induced the expression of ATF3, a transcriptional repressor that directly bound to specific sites on the Fgf21 promoter and resulted in loss of FGF21 expression. These ATF3 binding sites are conserved in the human FGF21 promoter. Consistent with the mouse studies, we also observed the reciprocal expression of ATF3 and FGF21 in the pancreata of human patients with pancreatitis. Using three different mouse models of pancreatitis, we showed that pharmacologic replacement of FGF21 mitigated the ISR and resolved pancreatitis. Likewise, inhibition of the ISR with an inhibitor of the PKR-like endoplasmic reticulum kinase (PERK) also restored FGF21 expression and alleviated pancreatitis. These findings highlight the importance of FGF21 in preserving exocrine pancreas function and suggest its therapeutic use for prevention and treatment of pancreatitis.
On the human uniqueness of the temporal reasoning system
Authors: Carlos Montemayor
Journal: Behavioral and Brain Sciences (2019)

Abstract A central claim by Hoerl &amp; McCormack is that the temporal reasoning system is uniquely human. But why exactly? This commentary evaluates two possible options to justify the thesis that temporal reasoning is uniquely human, one based on considerations regarding agency and the other based on language. The commentary raises problems for both of these options.
Prophylaxis of Neutropenia During Adjuvant Dac (Docetaxel, Doxorubicin, Cyclophosphamide) Chemotherapy with Dicarbamin in Patients with Early Breast Cancer
Authors: M.V. Kopp, I.A. Koroleva, L.V. Shaplygin, A.S. Machalova
Journal: Annals of Oncology (2012)
Abstract 15588: Coronary Blood Flow in Hypertrophic Obstructive Cardiomyopathy: The Critical Role of the Aortic Root
Authors: Nadine Francis, Heba Aguib, Mazen Abou Gamrah, Peter Philip, Hesham Bahaa, Ryo Torii, Christopher Broyd, Ahmed El Guindy, Magdi Yacoub
Journal: Circulation (2018)

Background: The pattern of coronary flow and wave intensity has been shown to be perturbed in Hypertrophic obstructive cardiomyopathy (HOCM). The contribution of Aortic root flow dynamics on the co...
scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation
Authors: E. Madissoon, A. Wilbrey-Clark, R. J. Miragaia, K. Saeb-Parsy, K. T. Mahbubani, N. Georgakopoulos, P. Harding, K. Polanski, N. Huang, K. Nowicki-Osuch, R. C. Fitzgerald, K. W. Loudon, J. R. Ferdinand, M. R. Clatworthy, A. Tsingene, S. van Dongen, M. Dabrowska, M. Patel, M. J. T. Stubbington, S. A. Teichmann, O. Stegle, K. B. Meyer
Journal: Genome biology (2019)

The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific.In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.
Problems With Clinical Application of Low-Dose Vasopressin for Traumatic Hemorrhagic Shock
Authors: Tobias Gauss, Pierre Bouzat, Francois-Xavier Ageron
Journal: JAMA Surgery (2020)

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Sixty seconds on . . . the NHS funding bill
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Ministers would like you to think so. The newly re-elected Conservative government has published a bill to enshrine in law its manifesto pledge of a “historic” £33.9bn (€39.7bn; $44bn) extra a year for the NHS by the end of the parliamentary term.

The government says it’s the biggest cash boost the NHS has ever had. This is technically correct, but only because this …
Serum Levels of VEGF Pre- and Post-Treatment With Bevacizumab (BEV) for Early Stage Breast Cancer (ESBC): ICORG 08-10
Authors: A.M. Canonici, I. Parker, T. O'Shea, B. Moulton, G. Gullo, M.J. Kennedy, D. Tryfonopoulos, N. Walsh, N. O'Donovan, J.P. Crown
Journal: Annals of Oncology (2012)
Abstract 411: Location of Collapse is Independently Associated With Initial Rhythm and Survival in Out-Of-Hospital Cardiac Arrest
Authors: Iris Oving, Michiel Hulleman, Paulien C Homma, Stefanie G Beesems, Hanno L Tan, Rudolph W Koster, Marieke T Blom
Journal: Circulation (2019)

Introduction: Out-of-hospital cardiac arrest (OHCA) at a home location is associated with lower rates of shockable initial rhythm (SIR) and survival than OHCA at a public location. While this is generally attributed to unfavourable resuscitation characteristics, it might also be explained by differences in pre-existing disease or medication use between patients with OHCA at home and those in public. We compared medical history and medication use between home and public OHCA patients, and determined whether these factors explain the association between OHCA location and SIR or survival. Methods: Data from ARREST, an OHCA registry in the Netherlands, were used (Jan 2009 - Dec 2012). We assessed the association between OHCA location and a) presence of SIR and b) survival to hospital discharge in a multivariable regression analysis taking medical history, medication use, resuscitation characteristics and demographics into account. Next, the relative contribution of the abovementioned variables to variance in both outcome measures was estimated using the Nagelkerke test. Results: In total, 1724 patients were included (1278 [74.1%] home OHCA, 446 [25.9%] public OHCA). OHCA location was significantly associated with rates of SIR (home 39.1%, public 75.1%; P &lt;0.01) and survival to hospital discharge (home 17.2%, public 47.3%; P &lt;0.01). Adding resuscitation characteristics to models of SIR rate and survival rate resulted in the largest increase in explained variance (Figure 1A and 1B), whereas adding pre-existing disease or medication use to the models resulted in only a limited increase in explained variance (Figure 1A and 1B). Conclusions: Location of OHCA remains significantly associated with lower rates of SIR and survival, even when adjusted for medical history, medication use, resuscitation characteristics and demographics; an unexplained gap remains. Both medical history and medication use only explain a modest proportion of the variance of SIR and survival.