tbuckley/cabot-search huggingface dataset:
P01.114 Expression and prognostic value of the immune checkpoint molecule galectin-9 in glioblastomas
Authors: S Andersen, A M Knudsen, R H Dahlrot, M D Sørensen, B W Kristensen
Journal: Neuro-Oncology (2018)

Glioblastomas are highly malignant with a median survival time below15 months. Immunotherapy has shown promising results in different types of cancer, and novel therapies targeting PD-1/PD-L1 signalling have been approved for treatment of patients with melanoma and lung cancer. Galectin-9, a checkpoint molecule, may be a potential therapeutic target. Galectin-9 and its receptor, TIM-3, are involved in cancer cell aggregation, induced T-cell apoptosis, and tumor progression. Previous studies indicate that galectin-9 may be expressed in high-grade gliomas. The aim of this study was to investigate the expression and prognostic value of galectin-9 in glioblastomas. Tissue from 166 glioblastoma patients from the Region of Southern Denmark glioma cohort was included. The tissue sections were immunohistochemically stained with anti-galectin 9 antibody. Image analysis and area fraction quantification of the stainings were performed using the image analysis software, Visiopharm. Galectin-9 was highly expressed in most glioblastomas, especially in cells with microglial and macrophage morphology, but some glioblastomas had a very limited expression. The mean positive area fraction was 0.06 (range 0.01–0.32). When dichotomized at the median no difference in the median overall survival was observed. Galectin-9 was not associated with overall survival (HR= 0.97, p=0.8) in multivariate analysis including age, performance status, post-surgical treatment and MGMT status. The galectin-9 protein was expressed in most glioblastomas. Targeting of galectin-9 may therefore be of potential value in most glioblastoma patients in order to obtain immune-mediated anticancer effects.Galectin-9 expression was not associated with patient survival. Potential co-localization of alectin-9 and its receptor TIM-3 will be investigated in our future work, as will the correlation with PD-L1 expression, to discover potential strategies for combination treatment.
<i>JAMA Oncology</i>—The Year in Review, 2017
Authors: Mary L. (Nora) Disis
Journal: JAMA Oncology (2018)

This has been a terrific year for JAMA Oncology.Our debut impact factor of 16.56 placed us as one of the highest-ranking oncology journals.JAMA Oncology published 30 of the top 50 papers among oncology journals as measured by Altmetric.We would like to thank our authors, reviewers, and readers for the significant contributions made to the journal this past year.The editorial board and I are honored to have the opportunity to serve the oncology community by offering original, innovative, and timely scientific content that has a direct impact on researchers, clinicians, and the patients we serve.I would like to thank our authors.In 2017, we published 373 total articles including 112 Original Investigations, 31 Viewpoints, and 4 Special Communications.The quality of our published articles is reflected in the 1.7 million downloads of articles from our site and the more than 7500 media mentions of JAMA Oncology articles in print, online, and news services this past year.Choosing papers for the journal was challenging.We received a total of 2083 manuscript submissions in 2017-an impressive 21% increase in submissions from the year prior.These
TGF-β-dependent epithelial-to-mesenchymal transition through Snail1 transcription factor
Authors: Jon Lecanda, Orlando Gil, Allison Chatalbash, Philip Smith, David Fishman, Leslie Gold
Journal: Cancer Research (2007)

5358  Epithelial-to-mesenchymal transition (EMT), important for cell movement during morphogenesis, is reactivated during malignant progression to enable invasion and metastasis. Transforming growth factor-β (TGF-β) induces EMT and stimulates cell migration in a variety of cancer cell types, including mammary carcinomas. Whereas the Snail zinc-finger transcription factors directly repress genes, such as E-cadherin, down-regulated during EMT, the interaction between Snail1/2 and TGF-β is unclear. We show that TGF-β (200 pM) induces Snail1 transcription within 30 minutes by 9-fold and 5.5-fold in the mouse mammary epithelial cell lines, NMuMG and Ras-transformed EpH4 (EpRas), respectively. Snail1 induction is sustained above basal levels for up to 48 hours concomitant with phenotypic conversion of the epithelial cells to a notable mesenchymal/fibroblastic phenotype including a time-dependent consistent decrease in E-cadherin and the tight junction protein, ZO-1, and an increase in N-cadherin and vimentin, as observed by immunofluorescence. By contrast, TGF-β decreases transcription of the homologue member Snail2 by 0.75-fold by one hour with incremental increases over time that remained slightly below basal levels by 48 hours. TGF-β signal transduction directly activates Smad transcription factors. Smad binding elements (SBE) were detected in the Snail1 promoter region suggesting a direct role for TGF-β signaling via Smads in Snail1 induction. Accordingly, TGF-β did not affect Snail1 or Snail2 expression in the Smad4-defective human breast carcinoma cells MDA-MB-468, and inhibitors of the p38 MAPK, PI3K and MEK1/2 pathways partially blocked TGF-β-regulated transcription of both genes. Therefore, TGF-β induces EMT via Smad4 signaling and cross-talk with additional intracellular pathways. Finally, stable over-expression of Snail1 and Snail2 in NMuMG cells mimicked the TGF-β-induced effects consistent with EMT including cell invasion through matrigel coated transwell chambers, down-regulation of ZO-1 and E-cadherin and, up-regulation of vimentin, fibronectin and N-cadherin. However, knock-down of gene transcription with Snail1 siRNA, but not Snail2 siRNA, blocked these TGF-β-induced effects. Therefore, whereas both Snail1 and Snail2 induce EMT and related alterations in markers of EMT, only Snail1 appears to mediate TGF-β induction of the mesenchymal phenotype consistent with its role in metastasis. Further, since TGF-β is present in high concentrations in many cancers and, as blocking Snail1 expression is sufficient to protect NMuMG cells from undergoing EMT induced by TGF-β/Smad signaling, Snail1 may be a rational target to prevent [TGF-β-induced] metastatic disease.
Stretching single titin molecules from failing human hearts reveals titin’s role in blunting cardiac kinetic reserve
Authors: Mei-Pian Chen, Salome A Kiduko, Nancy S Saad, Benjamin D Canan, Ahmet Kilic, Peter J Mohler, Paul M L Janssen
Journal: Cardiovascular Research (2019)

Heart failure (HF) patients commonly experience symptoms primarily during elevated heart rates, as a result of physical activities or stress. A main determinant of diastolic passive tension, the elastic sarcomeric protein titin, has been shown to be associated with HF, with unresolved involvement regarding its role at different heart rates. To determine whether titin is playing a role in the heart rate (frequency-) dependent acceleration of relaxation (FDAR). W, we studied the FDAR responses in live human left ventricular cardiomyocytes and the corresponding titin-based passive tension (TPT) from failing and non-failing human hearts.Using atomic force, we developed a novel single-molecule force spectroscopy approach to detect TPT based on the frequency-modulated cardiac cycle. Mean TPT reduced upon an increased heart rate in non-failing human hearts, while this reduction was significantly blunted in failing human hearts. These mechanical changes in the titin distal Ig domain significantly correlated with the frequency-dependent relaxation kinetics of human cardiomyocytes obtained from the corresponding hearts. Furthermore, the data suggested that the higher the TPT, the faster the cardiomyocytes relaxed, but the lower the potential of myocytes to speed up relaxation at a higher heart rate. Such poorer FDAR response was also associated with a lesser reduction or a bigger increase in TPT upon elevated heart rate.Our study established a novel approach in detecting dynamic heart rate relevant tension changes physiologically on native titin domains. Using this approach, the data suggested that the regulation of kinetic reserve in cardiac relaxation and its pathological changes were associated with the intensity and dynamic changes of passive tension by titin.
Nobel Lectures, Including Presentation Speeches and Laureates' Biographies: Physiology or Medicine 1963-1970
Authors: Charles G. Roland
Journal: JAMA (1973)

With the three preceding volumes, this book makes the published Nobel Prize addresses in physiology or medicine available through 1970. Although few individuals will feel a need to own the set, they should be on the shelves of all scientific libraries. The scientific caliber of the papers is, of course, uncompromisingly high; within these pages some of the world's most inspired investigators report on years—often decades—of creative work. The award list includes such names as Eccles, Huxley, Rous, Huggins, Monod, and von Euler. In general, the literary quality in these works closely parallels the scientific quality, making the addresses readable and fascinating documents. As always, the technical aspects of the book production by Elsevier are excellent. The printing and binding are exemplary. Unfortunately, the current inflation, affecting publishing houses along with other industries in the national economy, is reflected in the price of this volume.
Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial
Authors: Catriona Parker, Shekhar Krishnan, Lina Hamadeh, Julie A E Irving, Roland P Kuiper, Tamas Révész, Peter Hoogerbrugge, Jeremy Hancock, Rosemary Sutton, Anthony V Moorman, Vaskar Saha
Journal: The Lancet Haematology (2019)

The ALLR3 trial investigated outcomes of children with B-cell precursor acute lymphoblastic leukaemia who had late bone marrow relapses. We analysed long-term follow-up outcomes of these patients.
Self referral to physiotherapy for back pain reduces pressure on GP appointments
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Allowing patients with back pain, arthritis, and other musculoskeletal conditions to self refer to physiotherapists based in GP practices cut the proportion needing a GP consultation for back pain and those needing hospital care, pilots by NHS England have shown.

The approach was tested in 41 areas of England and reduced the proportion of patients needing a GP appointment for back pain to as few as 2%.

Patients who self referred to a first …
Long-Term Risk of Heart Failure in Breast Cancer Patients After Adjuvant Chemotherapy With or Without Trastuzumab
Authors: Ann Banke, Emil L. Fosbøl, Marianne Ewertz, Lars Videbæk, Jordi S. Dahl, Mikael Kjær Poulsen, Søren Cold, Maj-Britt Jensen, Gunnar H. Gislason, Morten Schou, Jacob E. Møller
Journal: JACC Heart Failure (2019)
The insertion/deletion polymorphism in the angiotensin I-converting enzyme gene predicts the progression of diabetic nephropathy during ACE inhibition in insulin dependent diabetic patients
Authors: P. Jacobsen, L. Tarnow, P. Rossing, F. Cambien, L. Lecerf, O. Poirier, H. H. Parving
Journal: Journal of the American Society of Nephrology (1995)
Hyperfunctioning Papillary Microcarcinoma Diagnosed by 124I PET/Ultrasound Fusion Imaging
Authors: Philipp Seifert, Falk Gühne, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2019)

A 49-year-old woman presented with a multinodular goiter, causing local symptoms and hyperthyroisdism. Besides a hypofunctioning benign nodule (TIRADS 3, benign in FNAC), the conventional diagnostic revealed another small hyperfunctioning nodule with suspicious ultrasound features (TIRADS 4C). To rule out a trapping-only nodule and topographical misalignments, a I PET/ultrasound fusion was performed and confirmed elevated iodine uptake within the suspicious nodule. Further disseminated autonomous areas are suspected to be additionally responsible for the low TSH-level. Because of the local cervical symptoms and the hyperthyroidism, the patient underwent surgery. The small hyperfunctioning nodule turned out to be a classic papillary microcarcinoma.
Molecular Imaging of Immune Cell Dynamics During De- and Remyelination in the Cuprizone Model of Multiple Sclerosis by [<sup>18</sup>F]DPA-714 PET and MRI
Authors: Bastian Zinnhardt, Michaël Belloy, Inga B. Fricke, Jasmien Orije, Caroline Guglielmetti, Sven Hermann, Stefan Wagner, Michael Schäfers, Annemie Van der Linden, Andreas H. Jacobs
Journal: Theranostics (2019)

: Activation and dysregulation of innate, adaptive and resident immune cells in response to damage determine the pathophysiology of demyelinating disorders. Among the plethora of involved cells, microglia/macrophages and astrocytes play an important role in the pathogenesis of demyelinating disorders. The in-depth investigation of the spatio-temporal profile of these cell types
Effectiveness of influenza vaccine in TNF inhibitors treated patients: comment on the article by Burmester <i>et al</i>
Authors: Giovanni Adami, Angelo Fassio, Giovanni Orsolini, Alessandro Giollo, Davide Gatti, Maurizio Rossini
Journal: Annals of the Rheumatic Diseases (2019)

Tumour necrosis factor-α inhibitors (TNFi) are immunosuppressive therapies that are known to increase infectious risk. Indeed, patients affected by TNFi requiring conditions are at higher risk of influenza compared with healthy controls.1 Furthermore, mildly reduced seroconversion rate after influenza vaccination had been reported in TNFi-treated patients.2 Nonetheless, the immune response is considered large enough to recommend influenza vaccination in all patients affected by rheumatoid arthritis, regardless of treatment.3 However, there are data showing that patients are not being vaccinated as recommended.4 In addition, given that subjects with autoimmune conditions treated with TNFi are at higher risk for influenza,1 the …
Risk Factors for Acute Myeloid Leukemia and Myelodysplastic Syndromes in Patients with Multiple Myeloma: An Updated Analysis
Authors: Gudbjorg Jonsdottir, Magnus Björkholm, Ingemar Turesson, Malin Hultcrantz, Anna Porwit, Yogesh Jethava, Ola Landgren, Sigurður Yngvi Kristinsson
Journal: Blood (2018)
Growth in HIV-1-exposed but uninfected infants treated with lopinavir–ritonavir versus lamivudine: a secondary analysis of the ANRS 12174 trial
Authors: Stéphane Blanche, Thorkild Tylleskär, Marianne Peries, Chipepo Kankasa, Ingunn Engebretsen, Nicolas Meda, James K Tumwine, Mandisa Singata-Madliki, Mwiya Mwiya, Philippe Van de Perre, Nicolas Nagot
Journal: The Lancet HIV (2019)
Abstract IA15: Multiple targetable pathways for epigenetic therapy
Authors: Jean-Pierre Issa
Journal: Cancer Research (2017)

Abstract Epigenetic reprogramming erases the malignant potential of some transformed cells and the aim of epigenetic therapy is to achieve some degree of reprogramming in-vivo by targeting epigenetic writers/readers. The resultant gene expression response includes reactivation of tumor-suppressor genes and differentiation pathways as well as activation of an immune response program, all of which contribute to eventual clinical activity. The DNA methyltransferase inhibitors azacitidine, decitabine and guadecitabine induce clinically meaningful remissions or improvements in 30-60% of patients with myeloid leukemias and prolong survival compared to standard approaches including chemotherapy. This therapy is accompanied by (i) global and gene specific demethylation, (ii) reactivation of silenced gene expression, (iii) delayed responses that correlate with early epigenetic reactivation and result in clonal elimination and (iv) eventual relapses and resistance the mechanisms of which appear to involve genetic evolution in some cases. Multiple other classes of epigenetic modifiers have now been targeted therapeutically including histone acetylases and deacetylases, histone methylases and demethylases, and readers of the epigenetic marks such as the BET family of proteins. Clinical trials of these drugs are ongoing and have already shown impressive clinical activity in selected cases. Using a parallel approach, we have shown that gene expression directed unbiased phenotypic screens can also uncover new and repurposed drugs for epigenetic therapy (e.g. cardiac glycosides, arsenic trioxide, natural products), and unbiased genetic screens have suggested novel targets as well (SWI/SNF proteins, CHD4 etc.). An even greater promise of epigenetic therapy lies in sensitization to other treatment modalities such as chemotherapy and immunotherapy. Ultimately, epigenetic therapy will be integrated into comprehensive treatment plans aimed long term disease control in many human malignancies. Citation Format: Jean-Pierre Issa. Multiple targetable pathways for epigenetic therapy [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA15.
lnCAR: A Comprehensive Resource for lncRNAs from Cancer Arrays
Authors: Yueyuan Zheng, Qingxian Xu, Mengni Liu, Huanjing Hu, Yubin Xie, Zhixiang Zuo, Jian Ren
Journal: Cancer Research (2019)

Abstract Long noncoding RNAs (lncRNA) have emerged as promising biomarkers in cancer diagnosis, treatment, and prognosis. Recent studies suggest that a large number of coding gene expression microarray probes could be reannotated as lncRNAs. Microarray, once the most cutting-edge high-throughput gene expression technology, has been used for thousands of cancer studies and has brought invaluable resources for studying the functions of lncRNA in cancer development. However, a comprehensive lncRNA resource based on microarray data is still lacking. Here, we present lnCAR (lncRNAs from cancer arrays), a comprehensive open resource for providing expression profiles and prognostic landscape of lncRNAs derived from reannotation of public microarray data. Currently, lnCAR contains 52,300 samples for differential expression analysis and 12,883 samples for survival analysis from 10 cancer types. lnCAR allows users to interactively explore any annotated or novel lncRNAs. We believe lnCAR will serve as a valuable resource for the community focused on lncRNA research in cancer. Significance: lnCAR, a new interactive tool of reannotated public cancer-related microarray data, provides expression profiles and prognostic landscapes of lncRNAs across thousands of samples and multiple cancer types.
99mTc-LLEC Renal Dynamic Scan in a Patient With Pelvic Neuroblastoma
Authors: Sreenivasa Reddy Konudula, Peethamber L, Madhusudhanan Ponnusamy, Dhanapathi H, Nandini Pandit
Journal: Clinical Nuclear Medicine (2019)

A 5-month-old boy with ultrasonography showing bilateral hydronephrosis, referred for renal scan. On Tc-L,L,ethylenedicysteine (Tc-LLEC) renal scan, tracer blush in flow images in the region of urinary bladder was seen and tumor mass was suspected. Contrast-enhanced CT showed a soft tissue mass in sacrococcygeal region. Histopathological examination of biopsy tissue revealed malignant round cell tumor and immunohistochemistry consistent with neuroblastoma. I-MIBG scan revealed uptake in the pelvic mass with no distant metastasis.
Vulnerability of Children to Lead Exposure and Toxicity
Authors: Jane S. Lin-Fu
Journal: New England Journal of Medicine (1973)

Lead Ingestion and AbsorptionThe exposure of children to many possible sources of lead takes on special importance because of the degree of oral activity among young children. Most infants begin mouthing objects in the middle of their first year and continue until early in the second year of life, when this activity usually subsides. Persistence of mouthing as a major activity beyond 18 months is considered abnormal.75 PicaPica, a perverted appetite for nonfood items, occurs commonly in preschool children, and is most prevalent among those 18 to 24 months old.75 , 76 In a survey of pica among 486 Negro . . .
126TiP SAKK 16/14: Anti-PD-L1 antibody durvalumab (MEDI4736) in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC): A multicenter single-arm phase II trial
Authors: S.I. Rothschild, A. Zippelius, S. Savic Prince, M. Gonzalez, W. Weder, A. Xyrafas, C. Rusterholz, M. Pless
Journal: Journal of Thoracic Oncology (2018)
Review of US Medical School Finances, 1992-1993
Authors: J L Ganem, J K Krakower, R L Beran
Journal: JAMA (1994)

THIS ANNUAL financial review of all 126 fully accredited US medical schools reports revenues and expenditures for fiscal year 1992-1993 and identifies patterns in the financing of medical education during the past 5 years. We chose 1988-1989 as the base year for two reasons: to show recent patterns in medical school financing amid the current economic climate and to report the more accurate and comparable data that have resulted from simplified financial reporting and uniform definitions established in 1988 by the Liaison Committee on Medical Education (LCME). The review also shows changes in student financial aid during a 5-year period and differences in the funding of public and private medical schools for fiscal year 1992-1993. <h3>DATA SOURCES AND CHARACTERISTICS</h3> For the 1992-1993 fiscal year, all 126 fully accredited US medical schools responded to the LCME Part I-A annual financial questionnaire. For the same fiscal year, 125 accredited US medical schools