tbuckley/cabot-search huggingface dataset:
Immuno-oncology from the perspective of somatic evolution
Authors: Santiago González, Nadezda Volkova, Philip Beer, Moritz Gerstung
Journal: Seminars in Cancer Biology (2017)

The past years have witnessed significant success for cancer immunotherapies that activate a patient’s immune system against their cancer cells. At the same time our understanding of the genetic changes driving tumor evolution have progressed dramatically. The study of cancer genomes has shown that tumors are best understood as cell populations governed by the rules of evolution, leading to the emergence and spread of cell lineages with pathogenic mutations. Moreover, somatic evolution can explain the acquisition of mutations conferring drug resistance in the ever-lasting battle for reaching even fitter cell states. Here, we review the current state of the art of somatic cancer evolution and mechanisms of immune control and escape. We also revisit the principles of immunotherapy from the perspective of somatic evolution and discuss the basic rules of resistance to immunotherapies as dictated by evolution.
Global microRNA expression profiling in the liver biopsies of hepatitis B virus–infected patients suggests specific microRNA signatures for viral persistence and hepatocellular injury
Authors: Avishek Kumar Singh, Sheetalnath Babasaheb Rooge, Aditi Varshney, Madavan Vasudevan, Ankit Bhardwaj, Senthil Kumar Venugopal, Nirupama Trehanpati, Manoj Kumar, Robert Geffers, Vijay Kumar, Shiv Kumar Sarin
Journal: Hepatology (2017)

Hepatitis B virus (HBV) can manipulate the microRNA (miRNA) regulatory networks in infected cells to create a permissive environment for viral replication, cellular injury, disease onset, and its progression. The aim of the present study was to understand the miRNA networks and their target genes in the liver of hepatitis B patients involved in HBV replication, liver injury, and liver fibrosis. We investigated differentially expressed miRNAs by microarray in liver biopsy samples from different stages of HBV infection and liver disease (immune‐tolerant [n = 8], acute viral hepatitis [n = 8], no fibrosis [n = 16], early [F1+F2, n = 19] or late [F3+F4, n = 14] fibrosis, and healthy controls [n = 7]). miRNA expression levels were analyzed by unsupervised principal component analysis and hierarchical clustering. Analysis of miRNA–mRNA regulatory networks identified 17 miRNAs and 18 target gene interactions with four distinct nodes, each representing a stage‐specific gene regulation during disease progression. The immune‐tolerant group showed elevated miR‐199a‐5p, miR‐221‐3p, and Let‐7a‐3p levels, which could target genes involved in innate immune response and viral replication. In the acute viral hepatitis group, miR‐125b‐5p and miR‐3613‐3p were up, whereas miR‐940 was down, which might affect cell proliferation through the signal transducer and activator of transcription 3 pathway. In early fibrosis, miR‐34b‐3p, miR‐1224‐3p, and miR‐1227‐3p were up, while miR‐499a‐5p was down, which together possibly mediate chronic inflammation. In advanced fibrosis, miR‐1, miR‐10b‐5p, miR‐96‐5p, miR‐133b, and miR‐671‐5p were up, while miR‐20b‐5p and miR‐455‐3p were down, possibly allowing chronic disease progression. Interestingly, only 8 of 17 liver‐specific miRNAs exhibited a similar expression pattern in patient sera. Conclusion : miRNA signatures identified in this study corroborate previous findings and provide fresh insight into the understanding of HBV‐associated liver diseases which may be helpful in developing early‐stage disease diagnostics and targeted therapeutics. (H epatology 2018;67:1695‐1709)
The Oddie Children
Authors: M. Therese Southgate
Journal: JAMA (1980)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Solitude and Sunshine in Daniel Defoe’s <i>Robinson Crusoe</i>
Authors: Natalia M. Fontecilla, Scott A Norton
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Losers of Primary Cilia Gain the Benefit of Survival
Authors: Gladiola Goranci-Buzhala, Elke Gabriel, Aruljothi Mariappan, Jay Gopalakrishnan
Journal: Cancer Discovery (2017)

Abstract Summary: In this issue, Zhao and colleagues demonstrate that loss of primary cilia in medulloblastoma cells confers resistance to the Smoothened (SMO) inhibitor sonidegib. When treated with sonidegib, medulloblastoma cells lost their cilia and gained resistance. Surprisingly, loss of cilia is associated with recurrent mutations in ciliogenesis genes that are eventually able to drive drug resistance. These findings uncover a previously unknown mechanism of cancer cells in gaining a “persister-like” state against anticancer agents at the expense of losing primary cilia. Cancer Discov; 7(12); 1374–5. ©2017 AACR. See related article by Zhao et al., p. 1436.
Progress in the Treatment of Hodgkin’s Lymphoma
Authors: Dan L. Longo, Vincent T. DeVita
Journal: New England Journal of Medicine (2017)

Although there has been considerable research activity in the treatment of Hodgkin's lymphoma since advanced stages of the disease became curable with combination chemotherapy in the 1960s, the most significant advances have involved the maintenance of a particular level of antitumor efficacy while acute and late toxic side effects and their attendant mortality are reduced. These advances include the preservation of high response rates at reduced levels of toxicity with the current standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); the demonstration that various forms of radiation therapy were associated with unacceptably high levels of long-term toxicity; the application . . .
Bisphosphonates: a therapeutic option for knee osteoarthritis?
Authors: Willem F Lems
Journal: Annals of the Rheumatic Diseases (2017)

Osteoarthritis (OA) is one of the rheumatic diseases with the highest incidence and prevalence, which are expected to rise in current ageing populations.1 Unfortunately, in contrast to inflammatory rheumatic diseases such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, there are hardly any treatment options that modify the course of OA,2 except for some data on glucosamine and chondrotoine on radiological progression.3 4 In fact, the only instruments we have are symptomatics: analgesics, exercise therapy, weight loss for those with a high body mass index (BMI), intra-articular injections2 and orthopaedic surgery for those with severe or end-stage OA.

Nowadays, the disease is regarded as a whole joint disease that affects different structures in and around the joint capsule: the cartilage and also the synovial tissue, subchondral bone, muscles, ligaments and entheses are involved.5 6 In the absence of effective therapeutic options that modify the course of the disease, it is attractive to split up the options for interventions in different targets: cartilage, subchondral bone, synovitis and central pain regulation.5–7 Against that background, the study by Neogi et al 8 is very welcome: they showed that the risk of knee replacement (KR) therapy in patients with knee-OA was 25% lower in bisphosphonate (BP) users than in non-BP users, a remarkable difference, with large potential consequences, at least for elderly individuals with osteoporosis and OA.

Recent experimental and clinical studies have demonstrated that changes in subchondral bone and a crosstalk between subchondral bone and cartilage play an important role in the development of OA,9 although the pathophysiology and changes in subchondral bone have not …
Abstract 19714: Growth Parameters, Bone Mineral Density and Secondary Hyperparathyroidism After Fontan Operation: Results From the Multidisciplinary Clinic at the CHOP Single Ventricle Survivorship Program
Authors: Edna E Mancilla, Benjamin Zielonka, Jill Brodsky, Jeffrey Roizen, Babette Zemel, David J Goldberg, Kathryn M Dodds, Jack Rychik
Journal: Circulation (2016)

Background/Objectives: Height and lean mass deficits are reported in patients with single ventricle physiology after Fontan operation (FO). Our objective is to determine growth, areal bone mineral ...
Submucosal tunneling endoscopic resection for seven esophageal leiomyomas
Authors: Xiaoyu Tang, Yuyong Tan, Liang Lv, Deliang Liu
Journal: Endoscopy (2017)

A 47-year-old man came to our hospital with half a year's history of chest discomfort. An upper gastrointestinal endoscopy detected seven protruding lesions distributed in a dispersed fashion on different areas of the esophageal walls ([Fig. 1]), about 23 – 32 cm from the incisors. Endoscopic ultrasound (EUS) revealed the tumors to be originating from the muscularis propria layer, without any malignant features ([Fig. 2]). Although he was told that a "wait and see" approach could be taken at first, the patient requested active treatment.
ASXL1 c.1934dup;p.Gly646Trpfs*12—a true somatic alteration requiring a new approach
Authors: Costas K. Yannakou, Kate Jones, Michelle McBean, Ella R. Thompson, Georgina L. Ryland, Ken Doig, John Markham, David Westerman, Piers Blombery
Journal: Blood Cancer Journal (2017)
Flexible timing by temporal scaling of cortical responses
Authors: Jing Wang, Devika Narain, Eghbal A. Hosseini, Mehrdad Jazayeri
Journal: Nature Neuroscience (2017)

Musicians can perform at different tempos, speakers can control the cadence of their speech, and children can flexibly vary their temporal expectations of events. To understand the neural basis of such flexibility, we recorded from the medial frontal cortex of nonhuman primates trained to produce different time intervals with different effectors. Neural responses were heterogeneous, nonlinear, and complex, and they exhibited a remarkable form of temporal invariance: firing rate profiles were temporally scaled to match the produced intervals. Recording from downstream neurons in the caudate and from thalamic neurons projecting to the medial frontal cortex indicated that this phenomenon originates within cortical networks. Recurrent neural network models trained to perform the task revealed that temporal scaling emerges from nonlinearities in the network and that the degree of scaling is controlled by the strength of external input. These findings demonstrate a simple and general mechanism for conferring temporal flexibility upon sensorimotor and cognitive functions.
Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer
Authors: Luz Garcia-Alonso, Francesco Iorio, Angela Matchan, Nuno Fonseca, Patricia Jaaks, Gareth Peat, Miguel Pignatelli, Fiammetta Falcone, Cyril H. Benes, Ian Dunham, Graham Bignell, Simon S. McDade, Mathew J. Garnett, Julio Saez-Rodriguez
Journal: Cancer Research (2017)

Transcriptional dysregulation induced by aberrant transcription factors (TF) is a key feature of cancer, but its global influence on drug sensitivity has not been examined. Here, we infer the transcriptional activity of 127 TFs through analysis of RNA-seq gene expression data newly generated for 448 cancer cell lines, combined with publicly available datasets to survey a total of 1,056 cancer cell lines and 9,250 primary tumors. Predicted TF activities are supported by their agreement with independent shRNA essentiality profiles and homozygous gene deletions, and recapitulate mutant-specific mechanisms of transcriptional dysregulation in cancer. By analyzing cell line responses to 265 compounds, we uncovered numerous TFs whose activity interacts with anticancer drugs. Importantly, combining existing pharmacogenomic markers with TF activities often improves the stratification of cell lines in response to drug treatment. Our results, which can be queried freely at dorothea.opentargets.io, offer a broad foundation for discovering opportunities to refine personalized cancer therapies.Significance: Systematic analysis of transcriptional dysregulation in cancer cell lines and patient tumor specimens offers a publicly searchable foundation to discover new opportunities to refine personalized cancer therapies. Cancer Res; 78(3); 769-80. ©2017 AACR.
Zwitterionic starch-based hydrogel for the expansion and “stemness” maintenance of brown adipose derived stem cells
Authors: Dianyu Dong, Tong Hao, Changyong Wang, Ying Zhang, Zhihui Qin, Boguang Yang, Wancai Fang, Lei Ye, Fanglian Yao, Junjie Li
Journal: Biomaterials (2017)
Reply to Georgios Papadopoulos, Charalampos Fragkoulis, and Konstantinos Ntoumas’ Letter to the Editor re: Bimal Bhindi, Igor Frank, Ross J. Mason, et al. Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy: A Pathologic Stage-matched Analysis. Eur Urol 2017;72:660–4
Authors: Bimal Bhindi, Stephen A. Boorjian
Journal: European Urology (2017)
Importance of Hypotension and Its Definition After Cardiac Arrest
Authors: Ari R. Joffe
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
CHIP Regulates Aquaporin-2 Quality Control and Body Water Homeostasis
Authors: Qi Wu, Hanne B. Moeller, Donté A. Stevens, Rebekah Sanchez-Hodge, Gabrielle Childers, Marleen L.A. Kortenoeven, Lei Cheng, Lena L. Rosenbaek, Carrie Rubel, Cam Patterson, Trairak Pisitkun, Jonathan C. Schisler, Robert A. Fenton
Journal: Journal of the American Society of Nephrology (2017)

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches, we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro . shRNA knockdown of CHIP in CCD cells increased AQP2 protein t 1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2. CHIP knockdown increased the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIP E3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We did not observe significant changes in other water- or sodium-transporting proteins in the gene-modified mice. In summary, these results suggest that CHIP regulates AQP2 and subsequently, renal water handling.
Using data from a behavioural survey of men who have sex with men (MSM) to estimate the number likely to present for HIV pre-exposure prophylaxis (PrEP) in Ireland, 2017
Authors: Laura Nic Lochlainn, Kate O’Donnell, Caroline Hurley, Fiona Lyons, Derval Igoe
Journal: Eurosurveillance (2017)

In Ireland, men who have sex with men (MSM) have increased HIV risk. Pre-exposure prophylaxis (PrEP), combined with safe sex practices, can reduce HIV acquisition. We estimated MSM numbers likely to present for PrEP by applying French PrEP criteria to Irish MSM behavioural survey data. We adjusted for survey bias, calculated proportions accessing testing services and those likely to take PrEP. We estimated 1-3% of MSM in Ireland were likely to present for PrEP.
PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis (vol 6, pg 333, 2004)
Authors: R H Cao, M A Bjorndahl, P Religa, S Clasper, S Garvin, D Gaiter, B Meister, F Ikomi, K Tritsoris, S Dissing, T Ohhashi, D G Jackson, Y H Cao
Journal: Cancer Cell (2006)
Correlación entre los hallazgos sugerentes de enfermedad celíaca en la endoscopia digestiva alta y la biopsia duodenal
Authors: R Ríos León, I Garcia De La Filia Molina, E Sanchez Rodriguez, L Crespo Pérez, Á Flores De Miguel, A Guerrero García, C González Olivares, A Albillos Martínez
Journal: Endoscopy (2017)

En numerosos estudios se señala la importancia del aspecto duodenal en la endoscopia digestiva alta (EDA) de pacientes con enfermedad celíaca (EC). Sin embargo, la sensibilidad y especificidad es muy variable, por lo que su utilidad continúa en discusión.
The Inhibitory NKR-P1B:Clr-b Recognition Axis Facilitates Detection of Oncogenic Transformation and Cancer Immunosurveillance
Authors: Miho Tanaka, Jason H. Fine, Christina L. Kirkham, Oscar A. Aguilar, Antoaneta Belcheva, Alberto Martin, Troy Ketela, Jason Moffat, David S.J. Allan, James R. Carlyle
Journal: Cancer Research (2018)

Natural killer (NK) cells express receptors specific for MHC class I (MHC-I) molecules involved in "missing-self" recognition of cancer and virus-infected cells. Here we elucidate the role of MHC-I-independent NKR-P1B:Clr-b interactions in the detection of oncogenic transformation by NK cells. Ras oncogene overexpression was found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells, mediated in part via the Raf/MEK/ERK and PI3K pathways. Ras-driven Clr-b downregulation occurred at the level of the Clrb (Clec2d) promoter, nascent Clr-b transcripts, and cell surface Clr-b protein, in turn promoting missing-self recognition via the NKR-P1B inhibitory receptor. Both Ras- and c-Myc-mediated Clr-b loss selectively augmented cytotoxicity of oncogene-transformed leukemia cells by NKR-P1B+ NK cells in vitro and enhanced rejection by WT mice in vivo Interestingly, genetic ablation of either one (Clr-b+/-) or two Clr-b alleles (Clr-b-/-) enhanced survival of Eμ-cMyc transgenic mice in a primary lymphoma model despite preferential rejection of Clr-b-/- hematopoietic cells previously observed following adoptive transfer into naïve wild-type mice in vivo Collectively, these findings suggest that the inhibitory NKR-P1B:Clr-b axis plays a beneficial role in innate detection of oncogenic transformation via NK-cell-mediated cancer immune surveillance, in addition to a pathologic role in the immune escape of primary lymphoma cells in Eμ-cMyc mice in vivo These results provide a model for the human NKR-P1A:LLT1 system in cancer immunosurveillance in patients with lymphoma and suggest it may represent a target for immune checkpoint therapy.Significance: A mouse model shows that an MHC-independent NK-cell recognition axis enables the detection of leukemia cells, with implications for a novel immune checkpoint therapy target in human lymphoma. Cancer Res; 78(13); 3589-603. ©2018 AACR.
Preservative-Free Prostaglandin Analogs and Prostaglandin/Timolol Fixed Combinations in the Treatment of Glaucoma: Efficacy, Safety and Potential Advantages
Authors: Gábor Holló, Andreas Katsanos, Kostas G. Boboridis, Murat Irkec, Anastasios G. P. Konstas
Journal: Drugs (2017)