tbuckley/cabot-search huggingface dataset:
Year in review 2014: basic science and epidemiology
Authors: Clare Lloyd, Paul Cullinan
Journal: Thorax (2015)

### Another good year for biomarkers

Identification of a systemic molecular signature facilitating early diagnosis and enabling targeted therapy is the Holy Grail for the investigators of many pulmonary diseases, particularly those with heterogeneous presentation such as chronic obstruction pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). Genome-wide gene expression profiling of large groups of patients has revealed a clear gene signature for elastogenesis during COPD and identified fibulin-5 as a potential molecular target.1 Genetic regulation of gene expression patterns was investigated by integrative genomics which identified cystatin C (CST3) and CD22 as causal genes for airflow obstruction.2 The fact that these gene expression patterns in COPD are dynamic during treatment, reflecting disease severity, highlights the potential of this approach for the development of molecular phenotype-driven therapy for COPD.3 Similarly, a coordinated approach was used to assess the relationship between gene expression patterns, pathological features and systemic biomarkers to identify indicators of disease severity in patients with IPF. MMP3 and CXCL13 emerged as systemic biomarkers that reflect brochiolisation and lymphoid aggregates and are predicted to be of clinical value as prognostic or surrogate markers of disease severity in these patients.4 An alternative method of predicting cancer risk in patients presenting with endobronchial squamous metaplasia is the identification of DNA copy number aberration. This technique has proved a highly accurate biomarker for assessment of disease progression and could assist in deciding which patients with endobronchial lesions may benefit from more aggressive treatment or closer surveillance.5

### Smoking and steroids

Further evidence that smoking is bad for you—and your immune system—stems from a series of papers examining the effect of cigarette smoke on innate immune function. Tobacco smoke blunted secretion of key innate cytokines such as interferon γ and tumour necrosis factor α and impaired the ability of macrophages derived from peripheral blood or the airways to …
Abstract 3903: Differential transcript expression in nasopharyngeal carcinoma by cDNA microarray analysis
Authors: Timothy T.C. Yip, Dora L.W. Kwong, Roger K.C. Ngan, Cadmon K.P. Lim, Wai-Wai Cheng, Victor W.S. Ma, Stephen C.K. Law, Loretta Tse
Journal: Cancer Research (2015)

Abstract By cDNA microarray, gene expression profiling was carried out in 360 paired tumor &amp; normal biopsies from 60 nasopharyngeal cancer (NPC) patients at 3 time points, namely, at diagnosis of NPC, on treatment with an anti-inflammatory drug, Celecoxib (Celec) and on radiotherapy (RT). We found 1 cluster of 82 transcripts with statistically significant difference in expression between tumor &amp; normal tissues at diagnosis, a second cluster of 214 tumor versus normal transcripts on Celec treatment and finally a third cluster of 202 tumor versus normal transcripts on RT. Differential expression of selected tumor associated transcripts was confirmed by RT-PCR. These include 8 tumor up-regulated transcripts with 3 encoding for immunological/inflammatory molecules, IL8, CXCL9 &amp; CXCL10, 1 matrix metallopeptidase, MMP12, which breaks down extracellular matrix and thus is associated with cancer metastasis, 1 osteonectin protein which is involved in cell shape changes and thus related to cancer invasion, SPARC, 1 bone morphogenic protein with a role in tissue differentiation, GREM1, 1 GTPase-activating protein for phorbol ester receptor, CHN1 and a sorting nexin family member with a role in intracellular trafficking, SNX10. Genes which were prominently down-regulated in tumor were a variety of polymorphic xenobiotic detoxification enzyme genes or genes with antioxidant function (e.g. GSTA1, GSTA2, GSTA3, CYP4B1, ALDH1A1, ADHFE1, MAOB, NQO1 &amp; OAT). Many genes were also down-regulated by RT in tumor tissues and one notable example was TOP2A which encodes topoisomerase 2A involving in chromosome condensation &amp; chromatid separation during DNA replication, CLDN1 which has tight junction adhesion function, ANLN which is required for cytokinesis, and STMN1 which can regulate microtubule filament. These genes had good potential in applying for clinical applications in diagnosis or treatment of NPC in the future. Further exploration of the clinical applications of these genes is underway. Citation Format: Timothy T.C. Yip, Dora L.W. Kwong, Roger K.C. Ngan, Cadmon K.P. Lim, Wai-Wai Cheng, Victor W.S. Ma, Stephen C.K. Law, Loretta Tse. Differential transcript expression in nasopharyngeal carcinoma by cDNA microarray analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3903. doi:10.1158/1538-7445.AM2015-3903
TNF-α enhances Th9 cell differentiation and antitumor immunity via TNFR2-dependent pathways
Authors: Yuxue Jiang, Jintong Chen, Enguang Bi, Yinghua Zhao, Tianxue Qin, Yiming Wang, Alison Wang, Sujun Gao, Qing Yi, Siqing Wang
Journal: Journal for ImmunoTherapy of Cancer (2019)

Tumor specific Th9 cells are potential effector cells for adoptive therapy of human cancers. TNF family members OX40L, TL1A and GITRL have been shown to promote the induction of Th9 cells and antitumor immunity. However, the role of TNF-α, the prototype of the TNF superfamily cytokines, in Th9 cell differentiation and their antitumor efficacy is not defined. Here, we showed that TNF-α potently promoted naïve CD4+ T cells to differentiate into Th9 cells in vitro. Furthermore, the addition of TNF-α during Th9 cell differentiation increased T cell survival and proliferation. More importantly, the adoptive transfer of TNF-α-treated Th9 cells induced more potent antitumor effects than regular Th9 cells in mouse tumor model. TNF-α signals via two cell surface receptors, TNFR1 and TNFR2. Mechanistic studies revealed that TNF-α drove Th9 cell differentiation through TNFR2 but not TNFR1. In addition, under Th9 polarizing condition, TNF-α activated STAT5 and NF-κB pathways in T cells in a TNFR2-dependent manner. Inhibition of STAT5 and NF-κB pathways by their specific inhibitors impaired TNF-α-induced Th9 cell differentiation. Our results identified TNF-α as a new powerful inducer of Th9 cells and clarified the molecular mechanisms underlying TNF-α-induced Th9 cell differentiation.
Abstract 11636: Critical Roles of Mast Cells in Streptozotocin-Induced Diabetic Cardiomyopathy
Authors: Wenqian Fang, Aina He, Kun Zhao, Peter Libby, Guoping Shi
Journal: Circulation (2018)

Introduction: Mast cells (MCs) have recently been implicated in the pathogenesis of diet-induced type-2 diabetes, obesity, atherosclerosis, and abdominal aortic aneurysms by releasing pro-inflammat...
Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis
Authors: Jackie L Nam, Kaoru Takase-Minegishi, Sofia Ramiro, Katerina Chatzidionysiou, Josef S Smolen, Désirée van der Heijde, Johannes W Bijlsma, Gerd R Burmester, Maxime Dougados, Marieke Scholte-Voshaar, Ronald van Vollenhoven, Robert Landewé
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations. Methods MEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained. Results The RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or ‘spacing’ was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B). Conclusions This systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.
17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia
Authors: Cristina Bagacean, Adrian Tempescul, David Ternant, Anne Banet, Nathalie Douet-Guilbert, Anne Bordron, Boutahar Bendaoud, Hussam Saad, Mihnea Zdrenghea, Christian Berthou, Gilles Paintaud, Yves Renaudineau
Journal: Journal for ImmunoTherapy of Cancer (2019)

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy.However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)).This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study.Accordingly, 44 CLL patients were included in the study, and among them 9 presented a del(17p).Next, a total of 233 rituximab sera were selected for a pharmacokinetic study and analyzed in a two-compartment model showing important differences when del(17p) CLL patients were compared with non-del(17p) patients treated with rituximab and chemotherapy: (1) clearance of rituximab was faster; (2) central volume of rituximab distribution V1 (peripheral blood) was reduced while peripheral volume V2 (lymphoid organs and tissues) was increased; and (3) the rate of rituximab elimination (Kout) was faster.In contrast, the group with a better prognosis harboring isolated del(13q) presented a slower rate of elimination (Kout).Pharmacokinetic parameters were independent from the other factors tested such as age, sex, chemotherapy regimen (fludarabine/cyclophosphamide versus bendamustine), IGHV mutational status, and FCGR3A 158VF status.In conclusion, this study provides an additional argument to consider that del(17p) is effective not only to control chemoresistance but also monoclonal antibody activity, based on higher rituximab turnover.
P165 Molecular and cellular biomarkers that discriminate juvenile idiopathic arthritis from septic arthritis
Authors: N Nziza, M Cren, A Carbasse, P Mahe, M Delpont, D Sabah, H Chevassus, M Khalil, T Mura, C Jorgensen, P Plence, E Jeziorski, I Duroux-Richard, F Apparailly
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Juvenile idiopathic arthritis (JIA) and septic arthritis (SA) are the most frequent cause of arthritis among children under the age of 16 years. JIA is an inflammatory disorder with articular inflammation that persists for more than 6 weeks, while SA is caused by bacterial infection in children joints. Although these diseases have different physiopathological basis and involve different treatments and prognoses, they share clinical similarities. <h3>Objectives</h3> To date, there are no markers sufficiently reliable to discriminate between these two forms of arthritis at the onset of the disease. Our goal is to identify diagnostic biomarkers capable of discriminating between JIA and SA. To that end, we focused on microRNAs (miRNAs) and myeloid cell subsets, both playing a major role in the immune system. <h3>Methods</h3> We analyzed serum and synovial fluid (SF) samples from JIA or SA patients using a miRNAs Whole Transcriptome Assay associated with a next-generation sequencing detection technology to measure the expression level of 2083 miRNAs in a pilot study (oligoarticular JIA (oJIA): n=5; SA: n=3) and validated using RT-qPCR in a replicative study (oJIA: n=9; SA: n=9). In parallel, we performed a phenotypic characterization of peripheral blood (PB) and SF myeloid subpopulations using a flow cytometer (oJIA: n=9; SA: n=8). <h3>Results</h3> Principal component analysis and hierarchical clustering characterizations did not show significant differences between serum miRNAs of oJIA and SA patients. However, we observed a distinct miRNA profile signature in SF between the two diseases with 16 upregulated miRNAs and 5 down-regulated that perfectly discriminates oJIA and SA (p&lt;0.01). In addition, phenotypic characterization revealed the existence of 5 myeloid cell subsets with distinct accumulation profile between the SF of oJIA and SA (p&lt;0.05). <h3>Conclusions</h3> In this study, we propose for the first time a SF-based miRNA signature as well as 5 myeloid cell subsets that discriminate between oJIA and SA and might be used as potential diagnosis markers in juvenile arthritis. Moreover, these markers give an insight into the mecanisms that are differentially altered between inflammatory and infectious arthritis. <h3>Disclosure of Interest</h3> None declared.
Acoustic Pattern Recognition and Courtship Songs: Insights from Insects
Authors: Christa A. Baker, Jan Clemens, Mala Murthy
Journal: Annual Review of Neuroscience (2019)

Across the animal kingdom, social interactions rely on sound production and perception. From simple cricket chirps to more elaborate bird songs, animals go to great lengths to communicate information critical for reproduction and survival via acoustic signals. Insects produce a wide array of songs to attract a mate, and the intended receivers must differentiate these calls from competing sounds, analyze the quality of the sender from spectrotemporal signal properties, and then determine how to react. Insects use numerically simple nervous systems to analyze and respond to courtship songs, making them ideal model systems for uncovering the neural mechanisms underlying acoustic pattern recognition. We highlight here how the combination of behavioral studies and neural recordings in three groups of insects-crickets, grasshoppers, and fruit flies-reveals common strategies for extracting ethologically relevant information from acoustic patterns and how these findings might translate to other systems.
Self Assessment Colour Review of Hepatobiliary Medicine
Authors: W Rosenberg
Journal: Gut (2004)

R Chapman, H C Bodenheimer jr. London: Manson Publishing, 2003, £16.95, pp 192. ISBN ISBN 1-874545-48-0

Roger Chapman and Henry Bodenheimer have produced a useful addition to the libraries of gastroenterologists with an interest in liver disease. Hepatobiliary Medicine provides 180 questions and answers in 190 pages covering a wide range of hepatobiliary problems. The book will fit in a white coat pocket and is printed on high quality glossy paper. The questions comprise case histories illustrated with laboratory test results and photographs of histology and imaging investigations. Unfortunately, the reproduction does not allow readers to recognise some of the histological and imaging abnormalities referred to in the text, but most …
Improving Pleasure and Motivation in Schizophrenia: A Randomized Controlled Clinical Trial
Authors: Jérôme Favrod, Alexandra Nguyen, Joséphine Chaix, Joanie Pellet, Laurent Frobert, Caroline Fankhauser, Alban Ismailaj, Armando Brana, Gwennaïg Tamic, Caroline Suter, Shyhrete Rexhaj, Philippe Golay, Charles Bonsack
Journal: Psychotherapy and Psychosomatics (2019)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia. The main hypothesis of this study is that patients who attend 8 one-hour sessions of PEPS and treatment as usual (TAU) will have lower total apathy-avolition and anhedonia-asociality composite scores on the Scale for the Assessment of Negative Symptoms (SANS) than patients who attend only TAU. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Eighty participants diagnosed with schizophrenia or schizoaffective disorder were randomized to receive either TAU or PEPS + TAU. The participants were assessed by independent evaluators before randomization (T0), in a post-test after 8 weeks of treatment (T1) and at a 6-month follow-up (T2). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The post-test results and 6-month follow-up assessments according to an intention-to-treat analysis showed that the apathy and anhedonia composite scores on the SANS indicated statistically greater clinical improvements in PEPS participants than in non-PEPS participants. In the post-test, anhedonia but not apathy was significantly improved, thus favouring the PEPS condition. These results were sustained at the 6-month follow-up. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; PEPS is an effective intervention to reduce anhedonia in schizophrenia. PEPS is a short, easy-to-use, group-based, freely available intervention that is easy to implement in a variety of environments (ClinicalTrials.gov ID: NCT02593058).
The importance of the post-disaster context in fostering human resilience
Authors: Carl F Weems
Journal: The Lancet Planetary Health (2019)

Severe stress during or following natural disasters is suggested to be associated with a variety of health and mental health issues, such as post-traumatic stress disorder, anxiety, depression, and somatic complaints. This situation is also associated with multiple outcome trajectories and the importance of fostering resilience.1,2 Resilience is defined by exposure to risk, such as facing disaster-related personal distress or resource loss, as well as the positive functioning of some individuals compared with others, such as quicker adaptation or smaller heath effects, despite having experienced a similar level of risk.
IPI-504: A Novel hsp90 Inhibitor with In Vitro and In Vivo Anti-Tumor Activity.
Authors: Constantine S. Mitsiades, Nicholas Mitsiades, Melissa Rooney, Joseph Negri, Corey C. Geer, Melissa Pink, Christine Pien, Teru Hideshima, Dharminder Chauhan, Nikhil C. Munshi, Paul G. Richardson, John Barrett, Jeffrey K. Tong, David Grayzel, Vito Palombella, Julian Adams, Kenneth C. Anderson
Journal: Blood (2004)
Treatment of Relapse of Clinical Stage I Nonseminomatous Germ Cell Tumors on Surveillance
Authors: Robert J. Hamilton, Madhur Nayan, Lynn Anson-Cartwright, Eshetu G. Atenafu, Philippe L. Bedard, Aaron Hansen, Peter Chung, Padraig Warde, Joan Sweet, Martin O’Malley, Jeremy Sturgeon, Michael A.S. Jewett
Journal: Journal of Clinical Oncology (2019)

Active surveillance (AS) for testicular nonseminomatous germ cell tumors (NSGCT) is widely used. Although there is no consensus for optimal treatment at relapse on surveillance, globally patients typically receive chemotherapy. We describe treatment of relapses in our non-risk-adapted NSGCT AS cohort and highlight selective use of primary retroperitoneal lymph node dissection (RPLND).From December 1980 to December 2015, 580 patients with clinical stage I NSGCT were treated with AS, and 162 subsequently relapsed. First-line treatment was based on relapse site and extent. Logistic regression was used to explore factors associated with need for multimodal therapy on AS relapse.Median time to relapse was 7.4 months. The majority of relapses were confined to the retroperitoneum (66%). After relapse, first-line treatment was chemotherapy for 95 (58.6%) and RPLND for 62 (38.3%), and five patients (3.1%) underwent other therapy. In 103 (65.6%), only one modality of treatment was required: chemotherapy only in 58 of 95 (61%) and RPLND only in 45 of 62 (73%). Factors associated with multimodal relapse therapy were larger node size (odds ratio, 2.68; P = .045) in patients undergoing chemotherapy and elevated tumor markers (odds ratio, 6.05; P = .008) in patients undergoing RPLND. When RPLND was performed with normal markers, 82% required no further treatment. Second relapse occurred in 30 of 162 patients (18.5%). With median follow-up of 7.6 years, there were five deaths (3.1% of AS relapses, but 0.8% of whole AS cohort) from NSGCT or treatment complications.The retroperitoneum is the most common site of relapse in clinical stage I NSGCT on AS. Most are cured by single-modality treatment. RPLND should be considered for relapsed patients, especially those with disease limited to the retroperitoneum and normal markers, as an option to avoid chemotherapy.
Estrogen, Stress, and Depression: Cognitive and Biological Interactions
Authors: Kimberly M. Albert, Paul A. Newhouse
Journal: Annual Review of Clinical Psychology (2019)

This article reviews the interactions of estrogen changes and psychosocial stress in contributing to vulnerability to major depressive disorder (MDD) in women. Estrogen modulates brain networks and processes related to changes in stress response, cognition, and emotional dysregulation that are core characteristics of MDD. Synergistic effects of estrogen on cognitive and emotional function, particularly during psychosocial stress, may underlie the association of ovarian hormone fluctuation and depression in women. We propose a model of estrogen effects on multiple brain systems that interface with stress-related emotional and cognitive processes implicated in MDD and discuss possible mechanisms through which reproductive events and changes in estrogen may contribute to MDD risk in women with other concurrent risk factors.
Chromothripsis in High-Risk Myelodysplastic Syndromes: Incidence, Genetic Features, Clinical Implications, and Impact on Survival of Patients Treated with Azacytidine (Data from Czech MDS Group)
Authors: Zuzana Zemanova, Kyra Michalova, Karla Svobodova, Jana Brezinova, Halka Lhotska, Libuse Lizcova, Iveta Sarova, Silvia Izakova, Lucie Hodanova, Denisa Vesela, Sarka Ransdorfova, Monika Belickova, Jitka Vesela, Helena Polackova, Magda Siskova, Radana Neuwirtova, Jaroslav Cermak, Tomas Stopka, Anna Jonasova
Journal: Blood (2018)