tbuckley/cabot-search huggingface dataset:
Several Faces of Glutaminase Regulation in Cells
Authors: Ana C.P. Mafra, Sandra M.G. Dias
Journal: Cancer Research (2019)

Abstract The cancer target glutaminase (GLS) has proven to be a fascinating protein. Since it was first described to be regulated by the oncogene Myc 10 years ago, several other transcriptional, posttranscriptional, and posttranslational regulatory mechanisms have emerged, and the list is growing. A recent study by Deng and colleagues revealed that an antisense (AS) long noncoding RNA named GLS-AS, which is negatively regulated by Myc, downregulates GLS in pancreatic cancer. The Myc/GLS-AS/GLS regulatory axis is activated by nutrient stress, which is important for the often hypovascular pancreatic cancer, displaying the significance of GLS for the progression of this highly lethal type of cancer. See related article by Deng et al., p. 1398
Pneumonitis Related to Melanoma Immunotherapy
Authors: Francisco Javier García-Gómez, María Carmen Álamo-de la Gala, Pablo Antonio de la Riva-Pérez, Luis de la Cruz-Merino, María de la Cinta Calvo-Morón
Journal: Clinical Nuclear Medicine (2019)

Several regimens of immunotherapy have recently proven successful for multiple cancers, due to increased survival and quality of life. Rarely, immunotherapy with anti-programmed cell death protein 1 and programmed death-ligand 1 antibodies across cancer may cause immune-related pulmonary toxicity, with a low overall incidence, being particularly low among patients with melanoma and highest among individuals with lung cancer. In this vein, pulmonary toxicity is staged at 4 degrees according to the severity of the clinic and radiological findings, and its management is based on suppression of immunotherapy and administration of glucocorticoids. We report a case of pulmonary toxicity related to melanoma immunotherapy observed by F-FDG PET/CT.
FGFR3 mutations in upper urinary tract tumors are independent from microsatellite instability and associated with favorable outcome and a lower rate of bladder cancer recurrence
Authors: A Hartmann, J W Catto, J Van Oers, M Burger, R Stoehr, P J Wild, O Cussenot, Azzouzi A-R., M Meuth, F C Hamdy, E Zwarthoff
Journal: Cancer Research (2006)
Optimized Bioactive Glass: the Quest for the Bony Graft
Authors: Henri Granel, Cédric Bossard, Lisa Nucke, Fabien Wauquier, Gael Y. Rochefort, Jérôme Guicheux, Edouard Jallot, Jonathan Lao, Yohann Wittrant
Journal: Advanced Healthcare Materials (2019)

Abstract Technological advances have provided surgeons with a wide range of biomaterials. Yet improvements are still to be made, especially for large bone defect treatment. Biomaterial scaffolds represent a promising alternative to autologous bone grafts but in spite of the numerous studies carried out on this subject, no biomaterial scaffold is yet completely satisfying. Bioactive glass (BAG) presents many qualifying characteristics but they are brittle and their combination with a plastic polymer appears essential to overcome this drawback. Recent advances have allowed the synthesis of organic–inorganic hybrid scaffolds combining the osteogenic properties of BAG and the plastic characteristics of polymers. Such biomaterials can now be obtained at room temperature allowing organic doping of the glass/polymer network for a homogeneous delivery of the doping agent. Despite these new avenues, further studies are required to highlight the biological properties of these materials and particularly their behavior once implanted in vivo. This review focuses on BAG with a particular interest in their combination with polymers to form organic–inorganic hybrids for the design of innovative graft strategies.
The effect of sunscreen on vitamin D: a review
Authors: R.E. Neale, S.R. Khan, R.M. Lucas, M. Waterhouse, D.C. Whiteman, C.M. Olsen
Journal: British Journal of Dermatology (2019)

Sunscreen use can prevent skin cancer, but there are concerns that it may increase the risk of vitamin D deficiency. We aimed to review the literature to investigate associations between sunscreen use and vitamin D3 or 25 hydroxyvitamin D [25(OH)D] concentration. We systematically reviewed the literature following the Meta‐analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We identified manuscripts published in English between 1970 and 21 November 2017. Eligible studies were experimental [using an artificial ultraviolet radiation (UVR) source], field trials or observational studies. The results of each of the experimental studies and field trials are described in detail. Two authors extracted information from observational studies, and applied quality scoring criteria that were developed specifically for this question. These have been synthesized qualitatively. We included four experimental studies, three field trials (two were randomized controlled trials) and 69 observational studies. In the experimental studies sunscreen use considerably abrogated the vitamin D3 or 25(OH)D production induced by exposure to artificially generated UVR. The randomized controlled field trials found no effect of daily sunscreen application, but the sunscreens used had moderate protection [sun protection factor SPF) ~16]. The observational studies mostly found no association or that self‐reported sunscreen use was associated with higher 25(OH)D concentration. There is little evidence that sunscreen decreases 25(OH)D concentration when used in real‐life settings, suggesting that concerns about vitamin D should not negate skin cancer prevention advice. However, there have been no trials of the high‐SPF sunscreens that are now widely recommended. What's already known about this topic? Previous experimental studies suggest that sunscreen can block vitamin D production in the skin but use artificially generated ultraviolet radiation with a spectral output unlike that seen in terrestrial sunlight. Nonsystematic reviews of observational studies suggest that use in real life does not cause vitamin D deficiency. What does this study add? This study systematically reviewed all experimental studies, field trials and observational studies for the first time. While the experimental studies support the theoretical risk that sunscreen use may affect vitamin D, the weight of evidence from field trials and observational studies suggests that the risk is low. We highlight the lack of adequate evidence regarding use of the very high sun protection factor sunscreens that are now recommended and widely used.
Identification of a leukemia-initiating stem cell in human mast cell leukemia
Authors: Gregor Eisenwort, Irina Sadovnik, Juliana Schwaab, Mohamad Jawhar, Alexandra Keller, Gabriele Stefanzl, Daniela Berger, Katharina Blatt, Gregor Hoermann, Martin Bilban, Michael Willmann, Christiana Winding, Wolfgang R. Sperr, Michel Arock, Thomas Rülicke, Andreas Reiter, Peter Valent
Journal: Leukemia (2019)
Clinicopathological and prognostic significance of preoperative plasma fibrinogen level in patients with upper urinary tract urothelial carcinoma: A retrospective tumor marker prognostic study
Authors: Rongzong Liu, Xuejian Zhou, Lujia Zou, Qi Chen, Yun Hu, Jimeng Hu, Xiaobo Wu, Haowen Jiang
Journal: International Journal of Surgery (2019)
Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis
Authors: Kotaro Shide, Takuro Kameda, Ayako Kamiunten, Asami Oji, Yoshinori Ozono, Masaaki Sekine, Arata Honda, Akira Kitanaka, Keiichi Akizuki, Yuki Tahira, Kenichi Nakamura, Tomonori Hidaka, Yoko Kubuki, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Satoru Hasuike, Shojiro Yamamoto, Kenji Nagata, Masahito Ikawa, Kazuya Shimoda
Journal: Blood Cancer Journal (2019)

Abstract Calreticulin ( CALR ) exon 9 frameshift mutations, commonly detected in essential thrombocythemia (ET) and primary myelofibrosis patients, activate signal transducer and activator of transcription (STAT) proteins in the presence of Myeloproliferative Leukemia Virus (MPL) and induce ET in vivo. Loss of the KDEL motif, an endoplasmic reticulum retention signal, and generation of many positively charged amino acids (AAs) in the mutated C-terminus are thought to be important for disease induction. To test this hypothesis, we generated mice harboring a Calr frameshift mutation using the CRISPR/Cas9 system. Deletion of 19-base pairs in exon 9 (c.1099-1117del), designated the del19 mutation, induced loss of the KDEL motif and generated many positively charged AAs, similar to human mutants. Calr del19 mice exhibited mild thrombocytosis, slightly increased megakaryocytes, and mild splenomegaly. In vitro experiments revealed that the murine CALR del19 mutant had a weaker ability to combine with murine MPL than the human CALR del52 mutant. Consequently, STAT5 activation was also very weak downstream of the murine mutant and murine MPL, and may be the reason for the mild disease severity. In summary, loss of the KDEL motif and positively charged AAs in the C-terminus of CALR is insufficient for MPL binding and ET development.
Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis
Authors: Ting Wen, Bruce J. Aronow, Yrina Rochman, Mark Rochman, Kiran KC, Phil J. Dexheimer, Philip Putnam, Vincent Mukkada, Heather Foote, Kira Rehn, Sam Darko, Daniel Douek, Marc E. Rothenberg
Journal: Journal of Clinical Investigation (2019)

T cell heterogeneity is highly relevant to allergic disorders. We resolved the heterogeneity of human tissue CD3+ T cells during allergic inflammation, focusing on a tissue-specific allergic disease, eosinophilic esophagitis (EoE). We investigated 1088 single T cells derived from patients with a spectrum of disease activity. Eight disparate tissue T cell subtypes (designated T1–T8) were identified, with T7 and T8 enriched in the diseased tissue. The phenotypes of T7 and T8 resemble putative Treg (FOXP3+) and effector Th2-like (GATA3+) cells, respectively. Prodigious levels of IL-5 and IL-13 were confined to HPGDS+ CRTH2+IL-17RB+FFAR3+CD4+ T8 effector Th2 cells. EoE severity closely paralleled a lipid/fatty acid–induced activation node highlighted by the expression of the short-chain fatty acid receptor FFAR3. Ligands for FFAR3 induced Th2 cytokine production from human and murine T cells, including in an in vivo allergy model. Therefore, we elucidated the defining characteristics of tissue-residing CD3+ T cells in EoE, a specific enrichment of CD4+ Treg and effector Th2 cells, confinement of type 2 cytokine production to the CD4+ effector population, a highly likely role for FFAR3 in amplifying local Th2 responses in EoE, and a resource to further dissect tissue lymphocytes and allergic responses.
Abstract 16559: Routine Cardiac Implantable Electronic Device Interrogation at the Point of Care - Implications for Stroke Prevention and Management
Authors: Matthew D Pugh, Peter H Belott, Kristina L Greenwood, Patricia L McNamee, Besa Smith, Terri L Craig, Jack Mardekian, Jeffrey Trocio, Divina Fanning, Eric Carda
Journal: Circulation (2017)

Introduction: Atrial fibrillation (AF) confers a five-fold increased risk of stroke. Clinical guidelines emphasize identifying AF as a strategy to reduce stroke risk. Cardiac implantable electronic device (CIED) interrogation at the point of care may facilitate AF detection, increasing opportunities to identify patients at high risk for stroke. This study sought to quantify AF prevalence and assess stroke risk in patients with a CIED who presented to the emergency department (ED). Methods: This non-interventional, retrospective observational study included consecutive adult patients with a CIED who presented at a single facility ED and received device interrogation regardless of reason for the ED visit, by utilizing point of care technology that interprets data from device manufacturers and produces actionable reports regarding device function and detected arrhythmias. Five-hundred and twenty-five device interrogations were conducted across 494 unique patients over an eight month period in 2015. Relevant ...
The utility of prognostic indices, early events, and histological subtypes on predicting outcomes in non‐follicular indolent B‐cell lymphomas
Authors: Sean I. Tracy, Melissa C. Larson, Andrew L. Feldman, Matthew J. Maurer, Anne J. Novak, Susan L. Slager, Jose C. Villasboas, Cristine Allmer, Thomas M. Habermann, Umar Farooq, Sergei Syrbu, James R. Cerhan, Brian K. Link
Journal: American Journal of Hematology (2019)

Indolent B-cell lymphomas other than follicular lymphoma account for up to 10% of all B-cell neoplasms. While they typically follow a slowly progressive course, some patients experience rapid progression and early mortality. Prognostic scoring systems have not been adopted, hindering the ability of clinicians or researchers to predict outcomes, or risk-stratify patients during clinical trials. To address this, we evaluated the utility of existing prognostic indices and novel, early disease-related outcomes, to predict subsequent long term survival. Baseline characteristics and outcomes data were generated from a longitudinal cohort study that prospectively enrolled 632 patients newly diagnosed with marginal zone lymphoma, lymphoplasmacytic lymphomas, or B-cell lymphomas not otherwise specified, beginning in 2002. The International Prognostic Index (IPI), Follicular Lymphoma International Prognostic Index (FLIPI), and MALT International prognostic index (MALT-IPI) demonstrated c-statistics that ranged from 0.593-0.612 for event-free survival (EFS), and 0.683-0.714 for overall survival (OS). Patients who attained event-free survival at 12 months (EFS12) experienced similar mortality to the US general population (standardized mortality ratio [SMR] 1.19; 95% CI 0.95-1.46). Patients who did not attain EFS12 had subsequent worse morality (SMR 3.14 (95% CI 2.05-4.59). The MALT-IPI demonstrated utility in predicting subsequent long-term outcomes among patients with non-follicular indolent B-cell lymphomas. This index should be used by clinicians giving guidance to patients at the time of initial diagnosis, and risk stratification during clinical studies. The divergent long-term outcomes experienced by patients who do or do not attain EFS12 suggest there exists a subset of patients who harbor high-risk disease. Future research efforts should focus on methods to identify these patients at the time of diagnosis, in order to enable risk-tailored therapy.
Reply to Leijte <i>et al.</i>: Fever in Sepsis: Still a Hot Topic
Authors: Sivasubramanium V. Bhavani, Philip A. Verhoef, Matthew M. Churpek
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

an immunological basis for the hypothesis of Bhavani and colleagues, who state that hyperthermia may be the result of a more proinflammatory phenotype, whereas a less pronounced immune response might relate to a lower (or absent) temperature increase.In view of the more favorable prognosis of hyperthermic patients in whom temperature swiftly increases and quickly resolves, a more pronounced but adequately balanced proinflammatory response is of apparent benefit to the host.This further elucidates why dozens of trials using immunosuppressive agents failed to improve sepsis outcome and stresses the need for therapies aimed at maintaining or restoring a well-functioning immune system.
The Prognostic Value of Baseline 18F-FDG PET/CT in Human Papillomavirus–Positive Versus Human Papillomavirus–Negative Patients With Oropharyngeal Cancer
Authors: Zeno A. R. Gouw, Matthew D. La Fontaine, Simon van Kranen, Jeroen B. van de Kamer, Wouter V. Vogel, Erik van Werkhoven, Jan-Jakob Sonke, Abrahim Al-Mamgani
Journal: Clinical Nuclear Medicine (2019)

Oropharynx cancer (OPC) is heterogeneous; human papillomavirus (HPV)-positive and HPV tumors represent 2 disease entities with a different prognosis. Earlier studies investigating the prognostic value of pretreatment F-FDG PET in OPC are small or included patients with unknown HPV status. This study assessed the prognostic value of PET variables, in a large cohort with balanced HPV status.Retrospectively, primary tumor SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from baseline FDG PET/CT of patients with OPC treated with (chemo)radiation. The Pearson correlation between the PET variables was calculated. With linear regression, the correlation between the PET variables and HPV status, age, smoking status, T stage, N stage, and American Joint Committee on Cancer stage was calculated. Univariable and multivariable Cox models analyzed local control, overall survival, and disease-free survival (DFS).Of 201 patients, 109 were HPV. Metabolic tumor volume and TLG correlated (r = 0.96), as did SUVpeak and SUVmax (r = 0.97). The PET variables correlated strongest with HPV status and T stage. These two accounted for 40% of the variance of MTV and 33% of TLG. Human papillomavirus-negative tumors had a significantly higher SUVmax, SUVpeak, MTV, and TLG. In univariable analysis, all PET variables were significantly associated with local control, overall survival, and DFS. In multivariable analysis, TLG was significantly associated to DFS in patients with HPV OPC (hazard ratio, 1.005; 95% confidence interval, 1.001-1.010; P = 0.03). However, we did not observe this in HPV patients.Increased baseline TLG is associated with worse DFS in HPV OPC and might be used as biomarker for risk stratification in these patients. Interestingly, we could not identify this association in HPV patients.
Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial
Authors: Juan F Masa, Babak Mokhlesi, Iván Benítez, Francisco Javier Gomez de Terreros, Maria Ángeles Sánchez-Quiroga, Auxiliadora Romero, Candela Caballero-Eraso, Joaquin Terán-Santos, Maria Luz Alonso-Álvarez, Maria F Troncoso, Mónica González, Soledad López-Martín, José M Marin, Sergi Martí, Trinidad Díaz-Cambriles, Eusebi Chiner, Carlos Egea, Javier Barca, Francisco-José Vázquez-Polo, Miguel A Negrín, María Martel-Escobar, Ferran Barbe, Jaime Corral, Galo Fernández, Estrella Ordax-Carbajo, Nicolás González-Mangado, Teresa Gómez-García, María-Ángeles Martínez-Martínez, Elena Ojeda-Castillejo, Daniel López Padilla, Santiago J Carrizo, Begoña Gallego, Mercedes Pallero, Odile Romero, María Antonia Ramón, Eva Arias, Jesús Muñoz-Méndez, Cristina Senent, José N. Sancho-Chust, Nieves Belén Navarro Soriano, Emilia Barrot, José M. Benítez, Jesús Sánchez-Gómez, Rafael Golpe, Ana Santiago-Recuerda, Silvia Gómez, Mónica Bengoa
Journal: The Lancet (2019)
Abstract 16572: Association of Atrial Fibrosis With Major Adverse Cardiac Events in Patients With Non-valvular Atrial Fibrillation
Authors: Jordan B King, Mukul Singhal, Gagan Kaur, Kara Johnson, Christina Pacchia, Joseph Biskupiak, Nassir Marrouche
Journal: Circulation (2015)

Background: Extensive of atrial fibrosis has been demonstrated to significantly predict success of catheter ablation. However, impact of extensive fibrosis on other aspects of patient care and long-term prognosis is unknown. Methods: We conducted a historical cohort study to assess the hypothesis that increased degree of atrial fibrosis is independently associated with major adverse cardiac events (MACE). We reviewed 853 patients with non-valvular atrial fibrillation (NVAF) and quantified fibrosis. Logistic regression models were used to evaluate the association of percent fibrosis on experiencing a MACE. Linear splines were utilized to allow the functional form of the exposure to vary at high (&gt;15%) and low (&lt;15%) fibrosis scores. The outcome of interest was a composite of MACE: myocardial infarction (MI), ischemic stroke (IS), or venous thromboembolism (VTE). Results: The mean age of the cohort was 66.2±12.4 with 66% male and 79% white. During a median follow-up of 2.9 years, 69 (8.1%), 46 (5.4%), 52 (6.1%), and 156 (18.3%) of patients experienced an MI, IS, VTE, or MACE, respectively. High fibrosis patients were more likely to be older, male, and have a higher CHA2DS2-VASc score. In the unadjusted analysis, increased fibrosis was associated with increased odds of a MI (OR [95% CI] P-Value: 1.30 [1.00, 1.68] 0.05) or any MACE (1.28 [1.06, 1.56] 0.01), but not with IS or VTE. After adjusting for potential confounders, increasing fibrosis levels had significantly increased odds of MI (1.53 [1.02, 2.28] 0.04) and VTE (1.52 [1.17, 2.86] &lt;0.01) when fibrosis levels were above 15%. There was no significant association below 15%. The odds of a MACE was significant above 15% (1.64 [1.18, 2.27] &lt;0.01) and across all fibrosis scores (1.23 [1.01, 1.49] 0.04), but was insignificant when only fibrosis levels below 15% were examined. Conclusions: Advanced degree of atrial fibrosis in patients with NVAF is independently associated with increased risk of MI, VTE and a composite of MACE.
REST-DRD2 mechanism impacts glioblastoma stem cell–mediated tumorigenesis
Authors: Anantha L Marisetty, Li Lu, Bethany L Veo, Bin Liu, Cristian Coarfa, Mohamed Mostafa Kamal, Dina Hamada Kassem, Khushboo Irshad, Yungang Lu, Joy Gumin, Verlene Henry, Adriana Paulucci-Holthauzen, Ganesh Rao, Veerabhadran Baladandayuthapani, Frederick F Lang, Gregory N Fuller, Sadhan Majumder
Journal: Neuro-Oncology (2019)

Glioblastoma (GBM) is a lethal, heterogeneous human brain tumor, with regulatory mechanisms that have yet to be fully characterized. Previous studies have indicated that the transcriptional repressor REST (repressor element-1 silencing transcription factor) regulates the oncogenic potential of GBM stem cells (GSCs) based on level of expression. However, how REST performs its regulatory role is not well understood.We examined 2 independent high REST (HR) GSC lines using genome-wide assays, biochemical validations, gene knockdown analysis, and mouse tumor models. We analyzed in-house patient tumors and patient data present in The Cancer Genome Atlas (TCGA).Genome-wide transcriptome and DNA-binding analyses suggested the dopamine receptor D2 (DRD2) gene, a dominant regulator of neurotransmitter signaling, as a direct target of REST. Biochemical analyses and mouse intracranial tumor models using knockdown of REST and double knockdown of REST and DRD2 validated this target and suggested that DRD2 is a downstream target of REST regulating tumorigenesis, at least in part, through controlling invasion and apoptosis. Further, TCGA GBM data support the presence of the REST-DRD2 axis and reveal that high REST/low DRD2 (HRLD) and low REST/high DRD2 (LRHD) tumors are specific subtypes, are molecularly different from the known GBM subtypes, and represent functional groups with distinctive patterns of enrichment of gene sets and biological pathways. The inverse HRLD/LRHD expression pattern is also seen in in-house GBM tumors.These findings suggest that REST regulates neurotransmitter signaling pathways through DRD2 in HR-GSCs to impact tumorigenesis. They further suggest that the REST-DRD2 mechanism forms distinct subtypes of GBM.