tbuckley/cabot-search huggingface dataset:
Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies
Authors: P Miossec, C L Verweij, L Klareskog, C Pitzalis, A Barton, F Lekkerkerker, S Reiter, A Laslop, F Breedveld, E Abadie, B Flamion, W Dere, S Mpofu, N Goel, D Ethgen, B Mitlak, S Ormarsdóttir, R Rao, Y Tsouderos, J-Y Reginster
Journal: Annals of the Rheumatic Diseases (2011)

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker–drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed.
The First Venomous Crustacean Revealed by Transcriptomics and Functional Morphology: Remipede Venom Glands Express a Unique Toxin Cocktail Dominated by Enzymes and a Neurotoxin
Authors: Björn M. von Reumont, Alexander Blanke, Sandy Richter, Fernando Alvarez, Christoph Bleidorn, Ronald A. Jenner
Journal: Molecular Biology and Evolution (2013)

Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.
Plant genomics: sowing the seeds of success
Authors: Gemma D Bilsborough
Journal: Genome biology (2013)

Th e exquisite beauty of plants and their importance to life on Earth has captivated scientists throughout history.During antiquity, Th eophrastus began the systematic characterization of plants according to Aristotle's principles of taxonomy.Centuries later, Mendel's studies of the inheritance of traits in pea plants founded the fi eld of genetics, and much of Darwin's work on the evolution of forms by natural selection was supported by experiments on plants.By 2000, the seeds of success were sown in the fi eld of plant genomics with the sequencing of the genome of Arabidopsis thaliana [1], a ubiquitous weed that was adopted as the plant model species in the 1990s due to its many desirable traits, such as a short generation time, small diploid genome, and selfcompatibility.Prior to this adoption of Arabidopsis as a model species, studying a panoply of agronomically and economically important species, such as maize, rice, tomato, petunia and snapdragon, had been favored.Th e burgeoning worldwide human population means the pressure to produce sustainable quantities of food and fuel crops, across a relatively constant land area, has never been higher.To improve yields of crops, it will be imperative to understand the genetic mechanisms con trolling traits of interest, and genomics approaches will be vital to achieve this.Th us, with the topic of plant genomics at an unprecedented level of importance, we feel it is pertinent to highlight the best of plant research in a special issue.
One in three people worldwide is at risk of ill health from household air pollution
Authors: S. Bagcchi
Journal: BMJ (2014)

Household air pollution—caused by burning biomass (solid fuel derived from plant material) or coal for cooking, heating, or lighting—puts more than one in three people worldwide at risk of ill health and early death, a commission has found.

Led by Stephen Gordon from the Liverpool School of Tropical Medicine, United Kingdom, the commission reviewed evidence for the link between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. The researchers found that household air pollution puts an estimated 600-800 million families worldwide at increased risk of illnesses such as respiratory …
Multicenter Study of Decitabine Administered Daily for 5 Days Every 4 Weeks to Adults With Myelodysplastic Syndromes: The Alternative Dosing for Outpatient Treatment (ADOPT) Trial
Authors: David P. Steensma, Maria R. Baer, James L. Slack, Rena Buckstein, Lucy A. Godley, Guillermo Garcia-Manero, Maher Albitar, Julie S. Larsen, Sujata Arora, Michael T. Cullen, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2009)

Decitabine, a DNA-targeted hypomethylating agent, is approved by the United States Food and Drug Administration for treatment of patients with myelodysplastic syndromes (MDS) on a schedule of 15 mg/m(2) administered via intravenous (IV) infusion every 8 hours for 3 days. This study assessed the efficacy and safety of an alternative dosing regimen administered on an outpatient basis in academic and community-based practices.
Chronic Effects of Aorta-Coronary Sinus Anastomosis of Beck in Dogs
Authors: RICHARD W. ECKSTEIN, DAVID S. LEIGHNINGER, JACQUE DALEM, WILLIAM B. NEWBERRY, JAMES H. DEMMING, JAMES L. ORBISON
Journal: Circulation Research (1954)

Studies were made on dogs at various times up to one year following the coronary sinus anastomosis of Beck to determine the chronic effects of the operation. The results indicate that the graft perfuses the capillary bed of the occluded circumflex artery for about five weeks after the operation and then loses its functional contact with the capillary bed probably because of obliterative venous changes. However, as a result of an anoxia, there is definite development of intercoronary collateral vessels during the first few weeks, which persist throughout the year even though there is no arterial occlusion. It is concluded that in dogs the Beck operation is protective against the major effects of coronary ligation because of retrograde capillary flow early and intercoronary anastomoses later.
The effects of radiotherapy on psychosocial and cognitive functioning in adults with a primary brain tumor: a prospective evaluation†
Authors: Maria Kangas, Robyn L. Tate, Janet R. Williams, Robert I. Smee
Journal: Neuro-Oncology (2012)

A paucity of studies have evaluated the biopsychosocial factors contributing to quality of life (QoL) in adults with a primary brain tumor (BT). Our objective was to investigate (i) the effects of radiotherapy on the psychosocial (ie, posttraumatic stress symptoms [PTSS]) and cognitive functioning of adults with a primary BT, assessed preradiotherapy [T1] and postradiotherapy [T2], and (ii) predictors of PTSS and QoL postradiotherapy. Seventy adults with a BT were assessed at T1, and 67 patients were reassessed 3.5 months postradiotherapy. At each assessment, participants completed measures of PTSS, mood, QoL, and quality of social support and neurocognitive tests focusing on memory and executive functioning. Minimal differences in functioning were found between patients according to BT type (benign [n = 45] vs malignant [n = 25]) and tumor laterality (left vs right hemisphere), with 2 exceptions. Individuals with a left hemisphere benign BT experienced greater distress at T1, which declined at T2, whereas individuals with a left hemisphere malignant BT reported poorer social support at T2. The full sample performed poorly on tests of executive functioning, and 17% reported clinically elevated PTSS at T1, which reduced to 13% at T2. Younger age (<65 y), reduced QoL, and elevated anger symptoms at T1 predicted PTSS at T2, whilst having a benign BT, low PTSS, and depressive symptoms at T1 were predictive of improved QoL at T2. Findings highlight the importance of screening for psychosocial and cognitive disturbances in BT patients undergoing treatment to identify those at risk for acute and more prolonged problems.
The Prostate Cancer Susceptibility Variant rs2735839 Near <i>KLK3</i> Gene Is Associated with Aggressive Prostate Cancer and Can Stratify Gleason Score 7 Patients
Authors: Yonggang He, Jian Gu, Sara Strom, Christopher J. Logothetis, Jeri Kim, Xifeng Wu
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Gleason score (GS) 7 prostate cancer is a heterogeneous disease with different clinical behavior. We sought to identify genetic biomarkers that may predict the aggressiveness of GS 7 diseases. Experimental Design: We genotyped 72 prostate cancer susceptibility SNPs identified in genome-wide association studies in 1,827 white men with histologically confirmed prostate adenocarcinoma. SNPs associated with disease aggressiveness were identified by comparing high-aggressive (GS ≥8) and low-aggressive (GS ≤6) cases. The significant SNPs were then tested to see whether they could further stratify GS 7 prostate cancer. Results: Three SNPs—rs2735839, rs10486567, and rs103294—were associated with biopsy-proven high-aggressive (GS ≥8) prostate cancer (P &amp;lt; 0.05). Furthermore, the frequency of the variant allele (A) at rs2735839 was significantly higher in patients with biopsy-proven GS 4+3 disease than in those with GS 3 + 4 disease (P = 0.003). In multivariate logistic regression analysis, patients carrying the A allele at rs2735839 exhibited a 1.85-fold (95% confidence interval, 1.31–2.61) increased risk of being GS 4 + 3 compared with those with GS 3 + 4. The rs2735839 is located 600 base pair downstream of the KLK3 gene (encoding PSA) on 19q13.33 and has been shown to modulate PSA level, providing strong biologic plausibility for its association with prostate cancer aggressiveness. Conclusions: We confirmed the association of the rs2735839 with high-aggressive prostate cancer (GS ≥8). Moreover, we reported for the first time that rs2735839 can stratify GS 7 patients, which would be clinically important for more accurately assessing the clinical behavior of the intermediate-grade prostate cancer and for tailoring personalized treatment and posttreatment management. Clin Cancer Res; 20(19); 5133–9. ©2014 AACR.
Illness perceptions and medication beliefs: Key determinants of adherence to maintenance medication in chronic asthma
Authors: Ad Kaptein
Journal: European Respiratory Journal (2012)

Outcome in asthma is determined not only by pulmonary function or other biomedical characteristics. Illness perceptions and medication beliefs are crucial in predicting outcomes of asthma management. Illness perceptions pertain to patients' subjective beliefs and emotional responses to their asthma. Medication beliefs tap idiosyncratic views on (asthma) medication. Both influence coping and thereby outcome.

I'll review recent studies on this topic, with a range of respondents and careproviders, with patients with varying degree of asthma severity and in different settings of medical care. Examples of how to assess illness perceptions and medication beliefs will be presented and discussed.

All studies report substantial effects of illness perceptions and medication beliefs on various categories of outcomes. These findings emphasize the clinical relevance of addressing patients' beliefs about their illness and its medical management, and suggest that this may improve outcome of asthma care. Examples of recent high-quality intervention studies on this topic will be presented, with a view to how to improve quality of care, and thereby quality of life of patients with asthma. In the era of shared decision making and patient empowerment it appears that addressing and incorporating illness perceptions and medication beliefs into regular clinical care is a must.

Prof. Ad Kaptein, a.a.kaptein@lumc.nl LUMC .  1 Medical Psychology, Leiden University Medical Centre, Leiden, Netherlands.
Analysis of thymocyte MHC specificity with thymocyte hybridomas.
Authors: E T Yeh, B Benacerraf, K L Rock
Journal: The Journal of Experimental Medicine (1984)

Medullary, peanut agglutinin-negative (PNA-), thymocytes were activated in vitro with either exogenous interleukin 1 (IL-1) or accessory cells. T cell blasts from these cultures were subsequently fused to BW5147 to generate thymocyte hybridomas. Fusion frequencies similar to those obtained with peripheral T lymphocytes were observed. A high frequency of these hybrids are triggered to produce IL-2 in the presence of syngeneic accessory cells. Exogenous, nominal antigens do not appear to be required for this activation. Using accessory cells from a series of recombinant inbred mice, the specificity of this hybrid-accessory cell interaction could be mapped to either I-Ak or I-Ek or both. This was confirmed by blocking with alpha Ia monoclonal antibodies (mAbs). A high frequency of these self-reactive cells are also alloreactive. Interestingly, several clones were identified that appear to recognize public Ia determinants broadly shared by different alleles and genetic subregions. Such specificities appear to contrast with those of peripheral T lymphocytes whose specificity is dominated by the genetically polymorphic portion of the Ia molecule. These results document the clonal specificity occurring in the cultures of in vitro activated thymocytes and allow an analysis of at least a portion of the intrathymic repertoire for major histocompatibility complex (MHC) determinants. The implications of these findings are discussed.
Rituximab-treated membranous lupus nephritis: clinical outcome and effects on electron dense deposits
Authors: Thórunn Jónsdóttir, Birgitta Sundelin, Elisabet Welin Henriksson, Ronald F van Vollenhoven, Iva Gunnarsson
Journal: Annals of the Rheumatic Diseases (2011)

Membranous lupus nephritis (MLN) is characterised by proteinuria, a risk of the development of nephrotic syndrome and progressive deterioration in renal function. Despite the usage of various immunosuppressive agents, no solid, evidence-based recommendations for the treatment of MLN have been established and new therapeutic strategies are needed in therapy-resistant cases.1

During the past few years, rituximab has evolved as a promising new agent in severe lupus nephritis.2,–,4 The aim of this study was to evaluate the clinical and histopathological response to treatment with rituximab plus cyclophosphamide in patients with severe and therapy-resistant MLN.

Six female patients with MLN confirmed at a recent renal biopsy were included. The patients were selected for having proteinuria of 2 g/24 h or greater and recent/previous failure of conventional immunosuppressive agents. All patients were treated with ACE and/or, angiotensin II receptor blockers. In all cases, at least four of the American College of Rheumatology criteria for …
Endothelial Progenitor Cells
Authors: Aarif Y. Khakoo, Toren Finkel
Journal: Annual Review of Medicine (2004)

Endothelial progenitor cells are a circulating, bone marrow-derived cell population that appears to participate in both vasculogenesis and vascular homeostasis. Questions persist regarding their functional characteristics, as well as the precise panel of cell surface markers that uniquely define this newly described progenitor cell population. We review experimental results obtained from both animal studies and recent clinical trials that suggest this cell type may have tremendous therapeutic potential for a wide range of human diseases.
Spanish government approves draft bill regulating terminal care
Authors: A. Garcia Rada
Journal: BMJ (2011)

The Spanish cabinet passed a new draft bill on 13 May reaffirming the right of doctors to use whatever drugs they deem necessary to provide relief to patients in the last hours or days of their life, even if this hastens their death. 

The Bill for Regulating the Rights of People Facing the End of Life aims to clarify the rights of terminally ill patients and the obligations of the medical personnel attending them.

One of the most important parts of the draft bill is that it clarifies that patients can request the withdrawal of their treatment even if a doctor believes that it should …
B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells
Authors: Yu Yao, Ran Tao, Xiaomei Wang, Yin Wang, Ying Mao, Liang Fu Zhou
Journal: Neuro-Oncology (2009)

Human glioblastoma is well known for its capacity to interfere with effective antitumor immune responses. B7-H1 is the third member of the B7 family that plays important roles in tumor immune evasion. Recent studies have shown that brain tumor stem-like cells (TSCs) contribute to tumorigenesis and radioresistance. However, the relationship between B7-H1 and the clinical behavior of brain TSCs remains unclear. In the present study, we report that B7-H1 is correlated with the malignancy grade of astrocyte tumors. B7-H1 was significantly upregulated at the growing edge of the tumors. Immunostaining and flow cytometric analysis indicate that B7-H1 was expressed primarily by Ki67-negative tumor cells. In vitro, tumors cultured under medium favoring the growth of neural stem cells were able to form spheres, along with expression of neural stem/progenitor cell markers. These cells were able to differentiate into different neural lineages when cultured in differentiation medium, indicating that these cells have TSC characteristics. We also found that B7-H1 was expressed, but not exclusively on CD133-positive stem cells. Interestingly, we found that CD133-negative tumor cells also had the capacity to form brain tumors. Our data establish a correlation between the expression of the negative costimulatory molecule B7-H1 and the malignancy grade of human gliomas, suggesting that B7-H1 may be a novel tumor marker and target for therapy, although it is not expressed exclusively on brain TSCs.
Detection of transforming growth factor alpha in normal, malignant, and hyperproliferative human keratinocytes.
Authors: A B Gottlieb, C K Chang, D N Posnett, B Fanelli, J P Tam
Journal: The Journal of Experimental Medicine (1988)

Transforming growth factor alpha (TGF-alpha) is a 50-amino acid peptide, previously demonstrated only in transformed cell lines and human tumors, which is structurally homologous to epidermal growth factor (EGF). TGF-alpha expression in keratinocytes from normal individuals, patients with psoriasis, and patients with malignant skin diseases was investigated using an mAb raised against synthetic human TGF-alpha. mAb A1.5 reacted with TGF-alpha, but not EGF, in a sensitive ELISA. Keratinocytes in eight nodular basal cell carcinomas, one morpheic basal cell carcinoma, and one squamous cell carcinoma demonstrated intense membranous immunoperoxidase staining with mAb A1.5. Of even greater interest was the observation that the overlying normal epidermis, as well as the epidermis from five normal skin specimens, were stained by the mAb. Keratinocytes in plaques from 18 psoriasis patients were more intensely stained than those from normal skin. Cultured normal keratinocytes demonstrated membranous staining with mAb A1.5. Absorption of mAb A1.5 with synthetic human TGF-alpha completely removed the reactivity of mAb A1.5 with both basal cell tumors and normal epidermis. The demonstration of TGF-alpha in normal keratinocytes suggests that it plays a role in normal keratinocyte growth, wound healing, and in the pathogenesis of acanthosis.
Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial
Authors: Lee M Krug, Hedy L Kindler, Hilary Calvert, Christian Manegold, Anne S Tsao, Dean Fennell, Ronny Öhman, Ruth Plummer, Wilfried E E Eberhardt, Kazuya Fukuoka, Rabab M Gaafar, Jean-Jacques Lafitte, Gunnar Hillerdal, Quincy Chu, Wieneke A Buikhuisen, Gregory M Lubiniecki, Xing Sun, Margaret Smith, Paul Baas
Journal: The Lancet Oncology (2015)
Desensization Of Hen'S Egg Sensitized Mice As A Result Of Dietary (therapeutic) Intervention With A Specific Mixture Of Non-digestible Oligosaccharides
Authors: A. Hogenkamp, S. de Kivit, L.M.J. Knippels, J. Garssen, B.C.A.M. van Esch
Journal: Journal of Allergy and Clinical Immunology (2012)
Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C
Authors: G. Svegliati-Baroni, G. Faraci, L. Fabris, S. Saccomanno, M. Cadamuro, I. Pierantonelli, L. Trozzi, E. Bugianesi, M. Guido, M. Strazzabosco, A. Benedetti, G. Marchesini
Journal: Gut (2010)

<h3>Objective</h3> To study the mechanism(s) linking insulin resistance (IR) to hepatic fibrosis and the role of the epithelial component in tissue repair and fibrosis in chronic hepatitis C (CHC). <h3>Design</h3> Prospective observational study. <h3>Setting</h3> Tertiary care academic centre. <h3>Patients</h3> 78 consecutive patients with CHC. <h3>Main outcome measures</h3> IR, calculated by the oral glucose insulin sensitivity during oral glucose tolerance test; necroinflammatory activity and fibrosis, defined according to Ishak9s score; steatosis, graded as 0 (&lt;5% of hepatocytes), 1 (5–33%), 2 (33–66%) and 3 (&gt;66%). To evaluate the role of the epithelial component in tissue repair and fibrosis, the expansion of the ductular reaction (DR) was calculated by keratin-7 (CK7) morphometry. Nuclear expression of Snail, downregulation of E-cadherin and expression of fibroblast specific protein-1 (FSP1) and vimentin by CK7-positive cells were used as markers of epithelial-mesenchymal transition in DR elements. <h3>Results</h3> IR, the degree of necroinflammation and expansion of the DR (stratified as reactive ductular cells (RDCs), hepatic progenitor cells and intermediate hepatobiliary cells according to morphological criteria) were all associated with the stage of fibrosis. Nuclear Snail expression, E-cadherin downregulation and vimentin upregulation were observed in RDCs. By dual immunofluorescence for CK7 and FSP1, the number of RDCs undergoing epithelial-mesenchymal transition progressively increased together with the necroinflammatory score. By multivariate analysis, total inflammation and insulin resistance were the only factors significantly predicting the presence of advanced fibrosis (Ishak score ≥3) and the expansion of RDCs. <h3>Conclusion</h3> This study indicates that IR is associated with the degree of necroinflammatory injury in CHC and contributes to hepatic fibrosis by stimulating the expansion of RDCs that express epithelial-mesenchymal transition markers.