tbuckley/cabot-search huggingface dataset:
Microrna-198: A novel tumor suppressor in prostate cancer.
Authors: Jessica Ray, Christianne Hoey, Xiaoyong Huang, Paul Christopher Boutros, Stanley K. Liu
Journal: Journal of Clinical Oncology (2018)

92 Background: microRNAs (miRNAs) are small non-coding RNA molecules which act as repressors of gene function, and have been identified as playing substantial roles in cancer as both tumor suppressors and oncogenes. miR-198 has been reported to be down-regulated in several cancers, with low expression associated with worse overall survival. In addition, miR-198 has demonstrated tumor suppressor effects by altering several hallmarks of cancer. Despite compelling evidence in other cancers, miR-198's role in prostate cancer aggression has not yet been evaluated. Methods: Experiments were conducted by overexpressing miR-198 in three prostate cancer cell lines: DU145, LNCaP and 22RV1. To examine miR-198's effect on hallmarks of cancer in vitro, we used standard protocols to assay proliferation, colony formation, cell cycle profile, migration, and invasive potential. Gene array, qPCR, western blotting, and siRNA knockdown experiments were used to establish miR-198 downstream targets. Results: Overexpression of the candidate tumor suppressor miR-198 diminished proliferation in all prostate cancer cell lines and significantly impaired colony formation in soft agar. Subsequently, miR-198 expression was also demonstrated to reduce growth and tumor formation in vivo using LNCaP xenografts. Gene arrays and in silico target prediction identified several candidate targets, none of which have been previously linked to miR-198. MIB1, an E3 ubiquitin ligase, was the only target we have since identified to be reduced with miR-198 overexpression at both the RNA and protein levels. Knockdown of MIB1 recapitulated miR-198's effects on proliferation and colony formation, and further experiments are underway to demonstrate a direct binding relationship. An additional gene array with MIB1 siRNA will be performed to highlight pathways through which MIB1/miR-198 suppress tumorigenesis. Conclusions: Our evidence supports miR-198 as an important tumor suppressor in prostate cancer, with elevated expression impairing proliferation, colony formation, and in vivo tumor formation. This investigation into miR-198 highlights a potential role as a prostate cancer biomarker, or as a potential target of therapeutics to restore miRNA activity.
Progress in the diagnosis and therapy of melanoma
Authors: T. Wiesner, A. Zbyszewski
Journal: British Journal of Dermatology (2018)

In the past decade, strategies to treat metastatic melanoma have undergone a fundamental paradigm shift. Targeted therapies and more recently immunomodulatory agents have largely replaced unspecific cytotoxic chemotherapies. These new mechanism‐based therapies have demonstrated an improved overall survival in patients with metastatic melanoma and, in a small proportion of patients, even induce long‐lasting treatment responses. Yet immunomodulatory therapies are frequently associated with severe side‐effects, and the overall long‐term survival rate for most patients remains low. In contrast, if melanoma has not yet spread to other organs, surgical removal is usually curative. Consequently, early recognition of melanoma, before metastasis, is central to reducing morbidity and mortality. In this editorial, we summarize some important epidemiological and clinical studies on melanoma published in the BJD in the recent years. Firstly, we will focus on studies that aim to detect melanoma early – before spreading to other organs – and later we discuss studies investigating the treatment strategies for metastasized melanoma.
Amino Acid PET Tracer Accumulation in Cortical Ischemia
Authors: Christof Rottenburger, Soroush Doostkam, Marco Prinz, Stephan Meckel, Guido Nikkhah, Philipp T. Meyer, Thomas Reithmeier
Journal: Clinical Nuclear Medicine (2010)

The use of amino acid PET tracers like F-18 fluorethyltyrosine (FET) in the diagnostic workup of brain tumors has gained widespread acceptance. We report a case of a man who initially presented with focal neurologic symptoms. CT scan revealed a lesion suspicious of an ischemia or a low-grade glioma. The lesion showed high amino acid uptake in the FET PET examination, but without evidence of tumor tissue in the following stereotactic biopsy. A second FET PET examination 7 weeks later showed normal tracer uptake. Follow-up contrast enhanced CT finally confirmed a vascular embolic event as cause for the false-positive PET result.
ASSOCIATION BETWEEN COFFEE CONSUMPTION AND RISK OF HEART FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chayakrit Krittanawong, Hafeez Ul Hassan Virk, Ann Farrell, Mario Roberto Rodriguez Rivera, Bing Yue, Xin Wei, Eelin Wilson, Mariam Khandaker, Ritu Raj Singh, Zhen Wang, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
APPLICATION OF THE HYBRID APPROACH FOR PERCUTANEOUS CORONARY INTERVENTIONS FOR CHRONIC TOTAL OCCLUSIONS: UPDATE FROM AN INTERNATIONAL MULTICENTER REGISTRY
Authors: Peter Tajti, Dimitrios I. Karmpaliotis, Khaldoon Alaswad, Farouc Jaffer, Robert Yeh, Mitul Patel, Ehtisham Mahmud, James Choi, M. Nicholas Burke, Anthony Doing, Catalin Toma, Barry Uretsky, Elizabeth Holper, David Kandzari, Nicholas Lembo, Santiago Garcia, Oleg Krestyaninov, Dmitrii Khelimskii, Michalis Koutouzis, Jeffrey Moses, Ajay Kirtane, Ziad Ali, Bavana Rangan, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)
CLINICAL IMPACT OF CREATING A PREDETERMINED ATRIAL COMMUNICATION IN THE MANAGEMENT OF SEVERE PULMONARY HYPERTENSION USING THE ATRIAL FLOW REGULATOR DEVICE
Authors: Joseph Vettukattil, Ramasamy Rajeshkumar, Nagib Dahdah, Dietmar Schranz, Ata Firouzi, Sven Dittrich, Daniel Springmüller, Vishal Kaley, Bennett Samuel, Kothandam Sivakumar
Journal: Journal of the American College of Cardiology (2018)
MHC-II expression to drive a unique pattern of adaptive resistance to antitumor immunity through receptor checkpoint engagement.
Authors: Justin M. Balko, Douglas Buckner Johnson, Daniel Ying Wang, Paula Ericsson-Gonzalez, Mellissa Nixon, Roberto Salgado, Violeta Sanchez, Daniel Schreeder, Ju Young Kim, Jennifer Bordeaux, Melinda Sanders, Randall S. Davis
Journal: Journal of Clinical Oncology (2018)

180 Background: Anti-PD-1 therapy is effective in many cancers, but tumor-intrinsic factors governing response and resistance are largely unknown. MHC-II (HLA-DR) expression on tumor cells can predict response to anti-PD-1. Thus, we sought to determine the molecular features of MHC-II+ tumors in the evolution of anti-PD-1 response. Methods: We performed RNA-seq on 58 anti-PD-1 treated melanoma and lung tumors, including a subset of matched specimens prior to treatment and at acquired resistance. We performed immunohistochemistry (IHC) for immunologic markers, including HLA-DR on tumor cells. In triple-negative breast cancers (TNBC; n = 103), we performed IHC and/or quantitative immunofluorescence (QIF) for LAG3, PD-L1, CD4, CD8, Fc-receptor-like 6 (FCRL6), and granzyme B (GZMB). QIF images were assessed by Automated Quantitative Analysis (AQUA). To determine the functional effect of MHC-II on tumor cells, we generated isogenic MHC-II+ mouse tumors and assessed immune responsiveness and efficacy of checkpoint inhibition. Results: We identified unique inflammatory signatures in HLA-DR+ tumors, correlating with enhanced pre-treatment CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and response to anti-PD-1. LAG3+ and FCRL6+ TILs were enriched in HLA-DR+ tumors. LAG3 and FCRL6, known inhibitory receptors which bind MHC-II, were elevated at anti-PD-1 resistance. Similarly, in &gt; 100 TNBCs, HLA-DR+ tumor cells associated with increased CD4+ and CD8+ TILs and enhanced LAG3+ and FCRL6+ TILs. Further, presence of MHC-II-suppressing (LAG3+/FCRL6+) TILs associated with decreased GZMB+ CD8+ T cells, suggesting suppressed cytotoxicity. In mice, enforced expression of MHC-II on tumor cells enhanced CD4-enhanced anti-tumor immunity but was thwarted by LAG3+ TIL recruitment. Combined anti-LAG3 and anti-PD-1 therapy was selectively effective in MHC-II+ tumors. Conclusions: MHC-II+ tumors are immunologically active and may circumvent anti-tumor immunity by targeting MHC-II antigen presentation via recruitment of MHC-II-suppressing TILs. MHC-II expression may be useful to stratify patients to anti-PD-1/anti-LAG3 and eventually, anti-PD-1/anti-FCRL6 combinations.
OUTCOMES OF CORONARY ATHERECTOMY WITH AND WITHOUT PERCUTANEOUS VENTRICULAR ASSIST DEVICE: A PROPENSITY MATCHED ANALYSIS
Authors: Rupak Desai, Bhrugesh Shah, Rushik Bhuva, Upenkumar Patel, Malav Patel, Rajesh Sachdeva, Gautam Kumar
Journal: Journal of the American College of Cardiology (2018)
ATYPICAL FAST-SLOW ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA UTILIZING A SLOW PATHWAY CONNECTED TO THE RIGHT ATRIAL FREE WALL ALONG THE TRICUSPID ANNULUS
Authors: Yoshiaki Kaneko, Tadashi Nakajima, Akihiko Nogami, Yasuya Inden, Tetsuya Asakawa, Itsuro Morishima, Akira Mizukami, Tadanobu Irie, Takashi Iizuka, Shuntaro Tamura, Chihiro Ota, Yasunori Kanzaki, Kazuya Nakagawa, Makoto Suzuki, Masahiko Kurabayashi
Journal: Journal of the American College of Cardiology (2018)
Effects of neuroimmune axis modulation by aprepitant on antipruritic and global disease severity in patients with cutaneous T-cell lymphoma
Authors: S.G. Kwatra, E. Boozalis, M.M. Kwatra
Journal: British Journal of Dermatology (2018)

Linked Article: Maroñas‐Jiménez L et al. Br J Dermatol 2018; 178:e273–e274.
Immune dysregulation in peripheral blood mononuclear cells from patients with liver cancer.
Authors: Juhua Zhou
Journal: Journal of Clinical Oncology (2018)

55 Background: Immune regulation may play an important role in cancer development. The immune dysregulation and underlying mechanisms in patients with liver cancer have not fully understood. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from patients with liver cancer. Deep-sequencing, FACS analysis, ELISA and real-time PCR were used to analyze the immune dysregulation and underlying mechanisms in patients with liver cancer. Results: Our analysis discovered that the percentages of immune cell populations in PBMC from patients with liver cancer were significantly different from those in normal controls. Specifically, the percents of B cells and regulatory T cells were high in PBMC from patients with liver cancer. Expression of 161 genes such as EGF, IRF3, CD177, MAP2K2 and MMP9 was found to be significantly inhibited, but 66 genes including CD19, CD70, FOXP1 and IL-32 were significantly up-regulated in PBMC from patients with liver cancer. Further analysis showed that 190 long non-coding RNAs (lncRNAs) were significantly down-regulated; whereas150 lncRNAs were significantly up-regulated in PBMC from patients with liver cancer. Dysregulated lncRNAs were involved in the control of immune cell signaling, cell division and differentiation. Conclusions: The results suggest that the immune dysregulation may play a critical role in the pathogenesis of liver cancer. It also has a great implication in the development of immune therapeutic methods for patients with liver cancer.
Asb2α–Filamin A Axis Is Essential for Actin Cytoskeleton Remodeling During Heart Development
Authors: Arnaud Métais, Isabelle Lamsoul, Armelle Melet, Sandrine Uttenweiler-Joseph, Renaud Poincloux, Sonia Stefanovic, Amélie Valière, Anne Gonzalez de Peredo, Alexandre Stella, Odile Burlet-Schiltz, Stéphane Zaffran, Pierre G. Lutz, Christel Moog-Lutz
Journal: Circulation Research (2018)

Rationale: Heart development involves differentiation of cardiac progenitors and assembly of the contractile sarcomere apparatus of cardiomyocytes. However, little is known about the mechanisms that regulate actin cytoskeleton remodeling during cardiac cell differentiation. Objective: The Asb2α (Ankyrin repeat-containing protein with a suppressor of cytokine signaling box 2) CRL5 (cullin 5 RING E3 ubiquitin ligase) triggers polyubiquitylation and subsequent degradation by the proteasome of FLNs (filamins). Here, we investigate the role of Asb2α in heart development and its mechanisms of action. Methods and Results: Using Asb2 knockout embryos, we show that Asb2 is an essential gene, critical to heart morphogenesis and function, although its loss does not interfere with the overall patterning of the embryonic heart tube. We show that the Asb2α E3 ubiquitin ligase controls Flna stability in immature cardiomyocytes. Importantly, Asb2α-mediated degradation of the actin-binding protein Flna marks a previously unrecognized intermediate step in cardiac cell differentiation characterized by cell shape changes and actin cytoskeleton remodeling. We further establish that in the absence of Asb2α, myofibrils are disorganized and that heartbeats are inefficient, leading to embryonic lethality in mice. Conclusions: These findings identify Asb2α as an unsuspected key regulator of cardiac cell differentiation and shed light on the molecular and cellular mechanisms determining the onset of myocardial cell architecture and its link with early cardiac function. Although Flna is known to play roles in cytoskeleton organization and to be required for heart function, this study now reveals that its degradation mediated by Asb2α ensures essential functions in differentiating cardiac progenitors.
EDITOR'S CHOICE: Living with MTAS
Authors: Peter Cross
Journal: BMJ (2007)

As far as I am aware there has never been a time when morale in the NHS has not been at an all time low. And yet, for junior doctors at least, things have happened in the past year to justify that overworked phrase. Firstly, there was the news that international medical graduates who were not on the highly skilled migrant programme had been told that they were not wanted and advised to return home. Then we started to hear of musical chairs on some senior house officer rotations where, for instance, six juniors were told they would have to …
PREDICTORS AND IMPACT OF DE NOVO AORTIC REGURGITATION IN PATIENTS WITH CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICES
Authors: Jeong Rang Park, Peter A. Brady, Alfredo Clavell, Joseph Maleszewski, Vuyisile Nkomo, Sorin Pislaru, John Stulak, Grace Lin
Journal: Journal of the American College of Cardiology (2018)
Adaptation of adherent-invasive <i>E. coli</i> to gut environment: Impact on flagellum expression and bacterial colonization ability
Authors: Gwladys Sevrin, Sébastien Massier, Benoit Chassaing, Allison Agus, Julien Delmas, Jérémy Denizot, Elisabeth Billard, Nicolas Barnich
Journal: Gut Microbes (2018)

The pathogenesis of Crohn's disease (CD) is multifactorial and involves genetic susceptibility, environmental triggers and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are flagellated bacteria more prevalent in CD patients than in healthy subjects and promote chronic intestinal inflammation. We aim at deciphering the role of flagella and flagellin modulation by intestinal conditions. AIEC flagellum expression is required for optimal adhesion to and invasion of intestinal epithelial cells. Interestingly, differential flagellin regulation was observed between commensal E. coli (HS) and AIEC (LF82) strains: flagellum expression by AIEC bacteria, in contrast to that of commensal E. coli, is enhanced under intestinal conditions (the presence of bile acids and mucins). Flagella are involved in the ability of the AIEC LF82 strain to cross a mucus layer in vitro and in vivo, conferring a selective advantage in penetrating the mucus layer and reaching the epithelial surface. In a CEABAC10 mouse model, a non-motile mutant (LF82-ΔfliC) exhibits reduced colonization that is restored by a dextran sodium sulfate treatment that alters mucus layer integrity. Moreover, a mutant that continuously secretes flagellin (LF82-ΔflgM) triggers a stronger inflammatory response than the wild-type strain, and the mutant's ability to colonize the CEABAC10 mouse model is decreased. Overexpression of flagellin in bacteria in contact with epithelial cells can be detrimental to their virulence by inducing acute inflammation that enhances AIEC clearance. AIEC pathobionts must finely modulate flagellum expression during the infection process, taking advantage of their specific virulence gene regulation to improve their adaptability and flexibility within the gut environment.
Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD
Authors: Tengfei Ma, Yifeng Cheng, Emily Roltsch Hellard, Xuehua Wang, Jiayi Lu, Xinsheng Gao, Cathy C. Y. Huang, Xiao-Yan Wei, Jun-Yuan Ji, Jun Wang
Journal: Nature Neuroscience (2018)
Local authorities must pay public health doctors same as NHS, says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

Public health doctors employed by local authorities should receive the same pay and terms and conditions as NHS consultants, the BMA has said.

Delegates at the BMA’s annual conference of public health medicine in London on 27 April voted in favour of a motion calling for local authorities to provide pay and terms and conditions that are “at least commensurate” with those in the NHS.

The motion said that …
Clinical significance of lymphatic flows around pylorus identified by sentinel node mapping in patients with gastric cancer.
Authors: Junya Aoyama, Hirofumi Kawakubo, Shuhei Mayanagi, Kazumasa Fukuda, Koichi Suda, Rieko Nakamura, Norihito Wada, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2018)

12 Background: The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries. The suprapyloric lymph nodes (No. 5) and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) are classified in the right gastric artery (r-GA) basin, and the subpyloric lymph nodes (No. 6) are classified in the right gastroepiploic artery (r-GEA) basin. The aim of this study is to analyze the lymphatic flows between these lymph nodes and basins. Methods: Five hundred and fourty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. Results: We detected SN No. 5 in 36 (6.6 %) patients. In these patients, we detected SN No. 5 with SNs that belonged to the left gastric artery (l-GA) basin (69 %), r-GA basin (14 %), and r-GEA basin (44 %). No. 6 was detected as SN significantly more frequently with SN No. 5. We detected SN No. 6 in 100 (18.2 %) patients. In these patients, we detected SN No. 6 with SNs that belonged to the l-GA basin (42 %), left gastroepiploic artery (l-GEA) basin (4 %), r-GA basin (28 %), and r-GEA basin (41 %). No. 4d, No. 5 and No. 8a were detected as SNs significantly more frequently with SN No. 6. We detected SN No. 8a in 43 (7.8 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the l-GA basin (65 %), l-GEA basin (7 %), r-GA basin (21 %), r-GEA basin (58 %), and posterior gastric artery (p-GA) basin (7 %). No. 6 and No. 9 were detected as SNs significantly more frequently with SN No. 8a. SN No. 5 and No. 8a were tend to be detected with not SNs that belonged to the r-GA basin but No. 6, and SN No. 6 was detected significantly more frequently with No. 4d, No. 5 and No. 8a. Conclusions: Our findings show that lymphatic flows exist not only between lymph nodes which are belonged to the same basin, but also between No. 5 and No.6, and No.6 and No. 8a. On the other hand, the lymphatic flows between No. 5 and No. 8a seem to be limited. Our results suggest that the lymph node dissection of No. 6 given lymphatic flows from lesser curvature side and retroperitoneal side is important for surgery of gastric cancer.
Ultrasonography and Power Doppler Studies in Chikungunya Disease: Comment on the Article by Chang et al
Authors: Roberto Mogami, Flavio Sztajnbock, Ana C. B. Koifman, André de A. Vieira, Rodrigo S. Torezan, Mirhelen M. De Abreu, Yêdda de F. B. Chagas, João L. P. Vaz
Journal: Arthritis & Rheumatology (2018)

To the Editor: We read with interest the recent article by Chang et al regarding the frequency of chronic joint pain following chikungunya infection 1. We would like to congratulate the authors for their excellent study, a pioneer in the American continents, in such a large cohort (500 patients) and over a lengthy period of time. Our group recently performed studies in 50 patients with a confirmed diagnosis of chikungunya fever 2, 3. The study was performed between 2016 and 2017 in Rio de Janeiro, Brazil. In our study, ultrasonography was used to examine lesions on the wrists, hands, and ankles. As in the study by Chang et al, there was a predominance of female patients. However, parameters such as educational level and absenteeism from work were not positively correlated with disease severity 4. Based on our observations about the data that were collected and partially analyzed, the use of power Doppler studies could have relevance for predicting cases with a worse prognosis or cases that do not respond adequately to steroids or immunosuppressive drugs or cases that may progress to other forms of arthritis such as rheumatoid arthritis (RA) or psoriatic arthritis (PsA). In the Chang article, the definition of the initial period of infection is unclear. Classically, there are 3 phases of disease: acute (first 10 days), subacute (between 10 and 90 days), and chronic (after 90 days). In our studies 2, 3, 5, ultrasonography was performed, on average, during the subacute stage of the disease. We believe that this period is the most appropriate for identifying, with ultrasonography and power Doppler studies, cases with the potential to evolve poorly. In their study in a cohort of 500 patients, the authors did not cite any case that has evolved into other forms of arthritis. In our smaller series, 2 cases of arthritis (RA and PsA, respectively) were identified after chikungunya infection. Was the exclusion of patients with RA or PsA deliberate? Patients with the chronic form of chikungunya fever may have mild, moderate, or severe presentations, and it can be estimated by the number of compromised joints and the presence of neurologic symptoms (for example, carpal tunnel syndrome). Thus, some patients may have only mild pain in 1 joint and others may present with a severe polyarticular form that prevents them from working or may progress to RA. It would have been interesting if the authors discriminated the degree of impairment in patients in whom chronic pain developed.
Summary of rapid responses Used and exploited
Authors: Birte Twisselmann
Journal: BMJ (2006)

A recent article by John Bonner ( BMJ Career Focus 2006;332:123-4) and the news item ( BMJ Career Focus 2006;332:112) detailed the proposed visa changes for international medical graduates training and working in the United Kingdom. To say that the reaction was an uproar understates it.

The overwhelming majority of correspondents expressed their understandable chagrin and frustration, rather drowning out the one or two who were actually in favour of the new regulations or actually managed to see some advantage. Conspiracy theories were mooted and Orwellian double-speak thrown into the discussion; greed and hypocrisy were all too frequently …
Safety of Mixed Tree Nut Oral Food Challenges in the Management of Multi-Tree Nut Allergic Children and Adolescents
Authors: Annette Carlisle, Andrea Bell, Emily Shelton, Peggy L. Chandler, Sheva K. Chervinskiy, Anne M. Hiegel, Joshua L. Kennedy, Tamara T. Perry, Stacie M. Jones, Amy M. Scurlock, Robbie D. Pesek
Journal: Journal of Allergy and Clinical Immunology (2018)