tbuckley/cabot-search huggingface dataset:
Influence of polymorphisms of the DNA repair genes ERCC2 and ERCC5 on anticancer drugs response.
Authors: Francois Moisan, Nicolas Ricard, Philippe Pourquier, Jacques Robert, Valerie Le Morvan
Journal: Cancer Research (2008)

4788  ERCC2 (XPD) and ERCC5 (XPG) belong to the nucleotide excision repair (NER) pathway. ERCC2 is part of the TFIIH transcription complex, which is stabilized by ERCC5. Both ERCC2 and ERCC5 are required for the association of the CAK subcomplex (CDK7-Cycline H-MAT1) with the core TFIIH. They bear several common polymorphisms that have been studied for their involvement in cancer risk. Some studies have suggested in addition a potential role of these polymorphisms in the efficiency of cisplatin. We have used the NCI-60 panel of human tumor cell lines as a model for establishing relationships between the presence of the polymorphism in the genome of the cell lines and their responsiveness to a large number of anticancer drugs. Two single-nucleotide polymorphisms (SNP) in ERCC2 (asp312asn and lys751gln) and one SNP in ERCC5 (asp1104his) were determined in DNA extracts of the NCI-60 panel, using PCR-RFLP techniques. These data were compared to the cytotoxicity of 135 core drugs against the panel as well as to ERCC2 and ERCC5 gene expression. Both cytotoxicity and expression data were extracted from the NCI database (http://dtp.nci.nih.gov). The variant homozygous ERCC2 cell lines expressed the ERCC2 gene to a significantly lower level than the common homozygous and heterozygous cell lines, while there was no significant difference in ERCC5 gene expression as a function of the genotype. We have shown that the lys751gln of ERCC2 and the asp1104his of ERCC5 SNPs were significantly associated to the cytotoxicity of taxanes, the variant ERCC2 genotype being associated to higher taxane activity and the variant ERCC5 genotype to lower taxane activity. This prompted us to generate isogenic cell lines differing only by one of these SNPs. We first cloned wild-type and variant cDNAs in a pTracer eukaryotic expression vector; then, transformed Xeroderma pigmentosum patient cell lines with either ERCC2 (XP6BE) or ERCC5 (XPCS1LV) deficiency were transfected to establish stable cell lines. Comparative cytotoxicity evaluation of paclitaxel and cisplatin were undertaken in the isogenic pairs, as well as drug- and UV-induced DNA damage. Since TFIIH is involved not only in DNA repair but also in mRNA transcription and cell cycle progression, we hypothesize that impaired ERCC2 or ERCC5 proteins may cause the liberation of CAK, allowing it to exert its activity on the G2/M transition. Enhancing mitosis entry would then lead to hypersensitivity to spindle poisons, explaining thus the effect of ERCC2 and ERCC5 polymorphisms on taxane sensitivity. The impairment of ERCC2 activity would be due to its lower expression level, the lys751gln polymorphism leading to an important rearrangement of mRNA secondary structure that we have evidenced in silico. The impairment of ERCC5 activity would be due to the fact that the common 1104his allele in Caucasians encodes an unusual aminoacid at this position. These hypotheses are under exploration.
Quality Oncology Practice Initiative (QOPI): Preliminary results from a Brazilian academic public oncology service.
Authors: Daniel Iracema Cubero, Felipe Melo Cruz, Suelen Patricia dos Santos Martins, Joao Glasberg, Thomas Giollo Rivelli, Arinilda Silva Campos, Leandro Luongo Matos, Auro Del Giglio
Journal: Journal of Clinical Oncology (2012)

e16568 Background: The Quality Oncology Practice Initiative (QOPI) is a voluntary program developed by ASCO to aid oncology practices in quality self-assessment and continuous improvement of patient records. It consists of a cyclical, semiannual measurement of the adequacy of several care processes pertaining to some important aspects of patient care. Few academic cancer centers have been QOPI participants in the United States and there aren’t reports to our knowledge of any Latin American Cancer Center adopting this strategy. Methods: This study shows the pilot initiative to implement the QOPI at the ABC School of Medicine, Discipline of Oncology, a large public academic cancer center of Santo André, São Paulo, Brazil. Results: From January 2008 to December 2010, we consecutive selected 37 patients with gastric cancer, 40 with breast cancer, 33 with lung cancer and 40 colorectal cancer. The table below shows the first round of the core QOPI. Conclusions: There are several opportunities for improvement such as assessing and recording of pain and analgesic use, documentation patient consent and of the intent of chemotherapy and providing patients with their chemotherapy summaries. Our current electronic record will be modified to reflect the aforementioned needs in order to improve our results in the following rounds of QOPI program. [Table: see text]
The multiple facets of psychopathy in attack and defense conflicts
Authors: Tiago O. Paiva, Rui C. Coelho, Rita Pasion, Beatriz Ribeiro, Pedro R. Almeida, Fernando Ferreira-Santos, João Marques-Teixeira, Fernando Barbosa
Journal: Behavioral and Brain Sciences (2019)

Abstract With respect to De Dreu and Gross's article, we comment on the psychological functions for attack and defense, focusing on associations between individual differences in psychopathic personality traits and the behavioral patterns observed in attack-defense conflicts. We highlight the dimensional nature of psychopathy and formulate hypothetical associations between distinct traits, their different behavioral outcomes, and associated brain mechanisms.
Variable performance of different commercial systems for testing carbapenem susceptibility of KPC carbapenemase-producing Escherichia coli
Authors: A. Antonelli, M. Coppi, G. Camarlinghi, E.M. Parisio, M. Nardone, E. Riccobono, T. Giani, R. Mattei, G.M. Rossolini
Journal: Clinical Microbiology and Infection (2019)

ObjectivesThe aim was to evaluate different methods for testing carbapenem susceptibility of Escherichia coli producing KPC-type carbapenemase.MethodsSusceptibility to imipenem, meropenem and ertapenem was assayed using the reference broth microdilution method and several commercial methods (Vitek2, MicroScan, Etest, MIC Test Strip) starting from the same bacterial suspension. Susceptibility to imipenem and meropenem was also tested by Sensititre and disc diffusion (Bio-Rad). Results were interpreted according to EUCAST clinical breakpoints. Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization (ISO) guidelines and also considering the new EUCAST definitions. Genotypic diversity of isolates was evaluated with a RAPD profiling protocol.ResultsOf 54 KPC-positive E. coli isolates, 5.6%, 7.4% and 0% were susceptible standard dosing regimen (S), 55.6%, 72.2% and 0% susceptible increased exposure (I), and 38.9%, 20.4% and 100.0% resistant (R) to imipenem, meropenem and ertapenem, respectively, using the reference broth microdilution method. CA lower than 90% were observed with all systems for imipenem and meropenem using both the ISO and the modified EUCAST criteria. With ertapenem, CA >90% was observed with all methods except Vitek2. RAPD profiling revealed a remarkable genotypic diversity of the isolates, supporting that results were not biased by an oligoclonal nature of the collection.ConclusionsCommercial methods can be unreliable for testing susceptibility to carbapenems of KPC-producing E. coli. Susceptibility should be confirmed by reference broth microdilution.
Comprehensive serial analysis of gene expression of the cervical epithelium transcriptome
Authors: Ashleen Shadeo, Raj Chari, Calum MacAulay, Wan L Lam
Journal: Cancer Research (2007)

3715  Background: Approximately 500,000 women are diagnosed with cervical cancer worldwide each year and more than half of them will die from this disease. Investigation of genes expressed in preinvasive lesions compared to those expressed by normal cervical epithelium will yield insight to the early stages of disease. As such, establishing a baseline which to compare to, is important in elucidating the abnormal biology of disease. In this study we consider the normal cervical tissue transcriptome and investigate the similarities and differences in relation to CIN III by Long-SAGE (L-SAGE).  Objectives: (1) to characterize global gene expression patterns in normal cervical tissue and CIN III by functional group (2) to establish a gene signature unique to normal cervical tissue (3) to identify genes highly expressed in normal cervical tissue showing altered expression in CIN III.  Materials and Methods: Two normal and two CIN III cervical biopsies collected just prior to LEEP were collected at the BCCA in Vancouver and the LEEP specimen was used to establish the biopsy grade by a pathologist. Biopsy specimens were stored in RNAlater and were used for L-SAGE library construction. Libraries were sequenced and individual sequence tags mapped using NCBI SAGE Genie. High expressers in normal libraries (> 500 tags per million) were characterized and investigated for changes in expression level in CIN III using a modified Z-Test.  Results: Four SAGE libraries were sequenced to an average of 172,848 tags deep. 118 unique tags were highly expressed in normal cervical tissue while 107 of these mapped to unique genes. The most highly expressed gene families were, ribosomal, calcium-binding and keratinizing in normal cervical epithelia. The same genes were assessed for expression in CIN III. Five genes showed altered expression in CIN III when compared to normal and three were confirmed in a new tissue panel by QRT PCR. In addition, we have identified twelve unique Human Papillomavirus 16 (HPV 16) tags in the CIN III libraries.  Conclusion: Gene expression changes that parallel the progression stages will help to furthering our understanding of cervical cancer development and identify novel treatment targets. Establishing a baseline which to compare such aberrations is essential for this effort to proceed. We have focused our investigation on those tags most abundantly expressed in normal cervical tissue and have evaluated these genes in terms of tissue specificity, conserved expression and altered expression in CIN III lesions.   This work is supported by Genome Canada and NIH P01 CA82710-06.
Chronic hyperglycemia as a risk factor in implant therapy
Authors: Fawad Javed, Georgios E. Romanos
Journal: Periodontology 2000 (2019)

Abstract It has been estimated that by 2030, the number of patients with diabetes aged &gt; 64 years will be &gt; 82 million in underdeveloped countries, and &gt; 48 million in developed countries. Chronic hyperglycemia delays wound healing by reducing the expression of growth factors in the wound fluid and re‐epithelialization. Impaired wound healing in patients with diabetes has also been associated with inhibition of the production of stromal cell‐derived factor‐1alpha by several tissues including bone marrow, brain, heart, spleen, and gingivae. Chronic hyperglycemia interferes with the osseointegration of implants by deferring the expression of fibronectin and integrins. Results from experimental studies have shown a significantly higher bone‐to‐implant contact around implants placed in healthy animals compared with animals with streptozotocin‐induced diabetes. Moreover, persistent hyperglycemia plays a role in abnormal differentiation of osteoclasts, thereby making bone tissue more susceptible to resorption. Furthermore, persistent hyperglycemia has also been associated with increased peri‐implant soft tissue inflammation (increased peri‐implant bleeding on probing and probing depth) and crestal bone loss. Clinical studies have shown that under optimal glycemic control dental implants can show success and survival rates of up to 100% in patients diagnosed with diabetes. Although patients with diabetes can undergo dental implant therapy and can exhibit implant survival similar to those in systemically healthy individuals, the contribution of glycemic control and regular oral hygiene maintenance cannot be disregarded.
Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial
Authors: David B. Antcliffe, Shalini Santhakumaran, Robert M. L. Orme, Josie K. Ward, Farah Al-Beidh, Kieran O’Dea, Gavin D. Perkins, Mervyn Singer, Daniel F. McAuley, Alexina J. Mason, Mary Cross, Deborah Ashby, Anthony C. Gordon
Journal: Intensive Care Medicine (2019)
2019 EULAR recommendations for the generic core competences of health professionals in rheumatology
Authors: Lisa Edelaar, Elena Nikiphorou, George E Fragoulis, Annamaria Iagnocco, Catherine Haines, Margot Bakkers, Lurdes Barbosa, Nada Cikes, Mwidimi Ndosi, Jette Primdahl, Yeliz Prior, Polina Pchelnikova, Valentin Ritschl, Valentin Sebastian Schäfer, Hana Smucrova, Inger Storrønning, Marco Testa, Dieter Wiek, Theodora P M Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2019)

To maintain and optimise the quality of care provided by health professionals in rheumatology (HPRs), adequate educational offerings are needed. This task force (TF) aimed to develop evidence-based recommendations for the generic core competences of HPRs, with specific reference to nurses, physical therapists (PTs) and occupational therapists (OTs) to serve as a basis for their postgraduate education.The EULAR standardised operating procedures for the development of recommendations were followed. A TF including rheumatologists, nurses, PTs, OTs, patient-representatives, an educationalist, methodologists and researchers from 12 countries met twice. In the first TF meeting, 13 research questions were defined to support a systematic literature review (SLR). In the second meeting, the SLR evidence was discussed and recommendations formulated. Subsequently, level of evidence and strength of recommendation were assigned and level of agreement (LoA) determined (0-10 rating scale).Three overarching principles were identified and 10 recommendations were developed for the generic core competences of HPRs. The SLR included 79 full-text papers, 20 of which addressed the competences, knowledge, skills, attitudes and/or educational needs of HPRs from multiple professions. The average LoA for each recommendation ranged from 9.42 to 9.79. Consensus was reached both on a research and educational agenda.Evidence and expert opinion informed a set of recommendations providing guidance on the generic core competences of HPRs. Implementation of these recommendations in the postgraduate education of HPRs at the international and national level is advised, considering variation in healthcare systems and professional roles.
SP0016 The spondyloarthropathies as a paradigm for the induction of an autoimmune response by bacteria
Authors: J Sieper
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> The spondyloarthropathies (SpA) comprise ankylosing spondylitis (AS), reactive arthritis (ReA) or Reiter’s syndrome, arthritis/spondylitis with inflammatory bowel disease (IBD) and arthritis/spondylitis with psoriasis. The main link between each other is the association with HLA-B27, the same pattern of peripheral joint involvement with an asymmetrical arthritis predominantly of the lower limbs, and the possible occurrence of sacroiliitis, spondylitis, enthesitis and uveitis. Bacteria play a central role in the pathogenesis of the SpA. This is most obvious in ReA which is triggered by preceding bacterial infections of the urogenital or gastroenteral tract. In arthritis/spondylitis associated with IBD a causative role of gut bacteria is also assumed which can stimulate the cellular immune sytem because the breakage of the gut barrier. Because between 20–50% of HLA-B27-positive patients with ReA or IBD move on to AS a causative or triggering role of bacteria can also be assumed in AS. Due to more recent studies using new imaging techniques such as MRI and immunohistological investigations it can now be assumed that the immunopathology of SpA occurs typically at the interphase of bone and cartilage and that synovitis is only a secondary event. Although at the moment it cannot be excluded that bacteria or pieces of bacteria persist in these structures this seems to be unlikely. Thus, an autoimmune response triggered by a bacterial infection seems to be more likely. Cartilage derived proteins such as aggrecan could be, according to studies in animal models of SpA and to studies in SpA patients, a primary target of this autoimmune response. Such a response could be due to cross-reactivity with a bacterial antigen. This possible course of events leading to a chronic immune response in SpA has to be proven in the near future. The identification of target antigens would offer the possibility to switch off the antigen-specific immune response as a new exciting treatment option.
Pulmonary Artery Hypertension-Specific Therapy Improves Exercise Tolerance and Outcomes in Exercise-Induced Pulmonary Hypertension
Authors: Kenya Kusunose, Hirotsugu Yamada, Susumu Nishio, Yukina Hirata, Yoshihito Saijo, Yuta Torii, Nao Yamada, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata
Journal: JACC. Cardiovascular imaging (2019)
Comparison of Outcome after Allogeneic Stem Cell Transplantation in AML Patients in First or Second Complete Remission Following Either Fludarabin/Busulfan, Flamsa-TBI or Flamsa-Bu Conditioning
Authors: Thomas Heinicke, Myriam Labopin, Christoph Schmid, Didier Blaise, Arne Brecht, Jean Yves Cahn, Yosr Hicheri, Anne Huynh, Bruno Lioure, Noel Milpied, Ghulam Mufti, Christof Scheid, Gérard Socié, Bipin N. Savani, Arnon Nagler
Journal: Blood (2017)
Association Between Pancreatic Fistula and Long-term Survival in the Era of Neoadjuvant Chemotherapy
Authors: Thomas Hank, Marta Sandini, Cristina R. Ferrone, Clifton Rodrigues, Maximilian Weniger, Motaz Qadan, Andrew L. Warshaw, Keith D. Lillemoe, Carlos Fernández-del Castillo
Journal: JAMA Surgery (2019)

In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited.To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS.This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017.Pancreatic cancer surgery with or without NAT.Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model.Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002).Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
Advantaged- and disadvantaged-group members have motivations similar to those of defenders and attackers, but their psychological characteristics are fundamentally different
Authors: Nurit Shnabel, Julia Becker
Journal: Behavioral and Brain Sciences (2019)

Abstract Modern societies are characterized by group-based hierarchies. Similar to attackers, disadvantaged-group members wish to change the status quo; like defenders, advantaged-group members wish to protect it. However, the psychological arrays that are typical of disadvantaged- and advantaged-group members are opposite to those of attackers and defenders – suggesting that the Attacker-Defender Game does not capture the dynamics between advantaged and disadvantaged groups.
Intestinal resection rates in Crohn’s disease decline across two different epidemiological areas: a consistent observation not merely due to introduction of anti-TNFα
Authors: Evelien M J Beelen, C Janneke van der Woude, Annemarie C de Vries
Journal: Gut (2019)

With great interest we have read the manuscript written by Murthy et al , published in Gut in June 2019, on the influence of anti-tumour necrosis factor alpha (TNFα) therapy introduction on the rate of hospitalisation and intestinal resection rates in IBD.1 Despite the difference in the source of data between both studies (Canada: health administrative data and the Netherlands: nationwide pathology database), a declining rate of intestinal resections in Crohn’s disease has been confirmed in Canada, at equal rates as the decline that has been observed in the Netherlands.2 

The authors used an advanced statistical method to …
Are Lifestyle Therapies Effective for NAFLD Treatment?
Authors: Nermeen N. El-Agroudy, Anica Kurzbach, Roman N. Rodionov, John O’Sullivan, Michael Roden, Andreas L. Birkenfeld, Dominik H. Pesta
Journal: Trends in Endocrinology and Metabolism (2019)

HighlightsDue to its high prevalence, nonalcoholic fatty liver disease (NAFLD) is becoming an increasingly important health issue. In the absence of an established pharmacological therapy, lifestyle therapies, including dietary modifications and physical activity, are of increasing clinical significance.Although weight loss can improve IHL, distribution of macro- and micronutrients, the role of total calories, type of diet, and physical activity is less clear. Some evidence suggests consumption of a Mediterranean diet, high fiber and protein intake, as well as physical activity, regardless of modality or intensity, have beneficial effects on intrahepatic lipids.Recent advances also indicate that meal timing, such as shifting a higher number of daily calorie intake to the morning, can benefit NAFLD.AbstractNonalcoholic fatty liver disease (NAFLD) is becoming the most common liver disorder worldwide. Specifically, nonalcoholic steatohepatitis (NASH) and fibrosis pose an enormous burden for patients and health-care systems. In the absence of approved pharmacological therapies, effective lifestyle interventions for NAFLD, such as dietary strategies and exercise training, are currently the therapeutic strategies of choice. This review covers the influence of macronutrient quality and quantity (i.e., low-carbohydrate and high-protein diets), for successful reduction of intrahepatocellular lipids (IHL). Moreover, we discuss the effectiveness of different modalities of physical exercising with and without weight loss. These lifestyle modifications not only provide strategies to reduce IHL but may also hold a still underestimated potential to induce improvement and/or even remission of NAFLD.