bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying breast cancer risk loci by global differential allele-specific expression (DASE) analysis in mammary epithelial transcriptome
Authors: Gao Chuan , Devarajan Karthik , Zhou Yan , Slater Carolyn M , Daly Mary B , Chen Xiaowei 
Published: October 2012

AbstractBackgroundThe significant mortality associated with breast cancer (BCa) suggests a need to improve current research strategies to identify new genes that predispose women to breast cancer. Differential allele-specific expression (DASE) has been shown to contribute to phenotypic variables in humans and recently to the pathogenesis of cancer. We previously reported that nonsense-mediated mRNA decay (NMD) could lead to DASE ofBRCA1/2,which is associated with elevated susceptibility to breast cancer. In addition to truncation mutations, multiple genetic and epigenetic factors can contribute to DASE, and we propose that DASE is a functional index forcis-acting regulatory variants and pathogenic mutations, and that global analysis of DASE in breast cancer precursor tissues can be used to identify novel causative alleles for breast cancer susceptibility.ResultsTo test our hypothesis, we employed the Illumina® Omni1-Quad BeadChip in paired genomic DNA (gDNA) and double-stranded cDNA (ds-cDNA) samples prepared from eight BCa patient-derived normal mammary epithelial lines (HMEC). We filtered original array data according to heterozygous genotype calls and calculated DASE values using the Log ratio of cDNA allele intensity, which was normalized to the corresponding gDNA. We developed two statistical methods, SNP- and gene-based approaches, which allowed us to identify a list of 60 candidate DASE loci (DASE ≥ 2.00,P≤ 0.01, FDR ≤ 0.05) by both methods. Ingenuity Pathway Analysis of DASE loci revealed one major breast cancer-relevant interaction network, which includes two known cancer causative genes,ZNF331(DASE = 2.31,P= 0.0018, FDR = 0.040) andUSP6(DASE = 4.80,P= 0.0013, FDR = 0.013), and a breast cancer causative gene,DMBT1(DASE=2.03,P= 0.0017, FDR = 0.014). Sequence analysis of a 5′ RACE product ofDMBT1demonstrated thatrs2981745,a putative breast cancer risk locus, appears to be one of the causal variants leading to DASE inDMBT1.ConclusionsOur study demonstrated for the first time that global DASE analysis is a powerful new approach to identify breast cancer risk allele(s).
Effects of manganese on routine semen quality parameters: results from a population-based study in China
Authors: Li Yuyan , Wu Junqing , Zhou Weijin , Gao Ersheng 
Published: October 2012

Abstract

Background
Manganese (Mn) is an essential element in humans but its effect on semen quality is unclear. This study therefore aimed to assess the effects of Mn on semen quality in healthy men with no occupational exposure to Mn.

Methods
Semen samples were obtained from healthy Chinese men 20–59 years old who were recruited from six provinces in China. Individuals with urogenital tract diseases, tuberculosis, or occupational exposure to heavy metals were excluded. A questionnaire survey was conducted, and the external genitalia, semen quality, and serum Mn levels were examined.

Results
A total of 1,179 volunteers were enrolled in this study. The median serum Mn concentration was 8.2 μg/L (25th percentile (P25)=3.7 μg/L, P75=16.2μg/L). After adjusted area (six provinces), abstinence interval, season, registered residence, age of subjects, education level, income, smoking, and drinking, the risk of teratospermia was increased at serum Mn concentrations >19.40 μg/L (P80) group, with an adjusted odds ratio of 2.27 (95% confidence interval: 1.18–4.37).

Conclusion
High serum Mn levels appeared to have harmful effects on sperm morphology and motility among healthy men with no occupational exposure to Mn.
Student tutors for hands-on training in focused emergency echocardiography – a randomized controlled trial
Authors: Kühl Matthias , Wagner Robert , Bauder Markus , Fenik Yelena , Riessen Reimer , Lammerding-Köppel Maria , Gawaz Meinrad , Fateh-Moghadam Suzanne , Weyrich Peter , Celebi Nora 
Published: October 2012

Abstract

Background
Focused emergency echocardiography performed by non-cardiologists has been shown to be feasible and effective in emergency situations. During resuscitation a short focused emergency echocardiography has been shown to narrow down potential differential diagnoses and to improve patient survival. Quite a large proportion of physicians are eligible to learn focused emergency echocardiography. Training in focused emergency echocardiography usually comprises a lecture, hands-on trainings in very small groups, and a practice phase. There is a shortage of experienced echocardiographers who can supervise the second step, the hands-on training. We thus investigated whether student tutors can perform the hands-on training for focused emergency echocardiography.

Methods
A total of 30 volunteer 4th and 5th year students were randomly assigned to a twelve-hour basic echocardiography course comprising a lecture followed by a hands-on training in small groups taught either by an expert cardiographer (EC) or by a student tutor (ST). Using a pre-post-design, the students were evaluated by an OSCE. The students had to generate two still frames with the apical five-chamber view and the parasternal long axis in five minutes and to correctly mark twelve anatomical cardiac structures. Two blinded expert cardiographers rated the students’ performance using a standardized checklist. Students could achieve a maximum of 25 points.

Results
Both groups showed significant improvement after the training (p < .0001). In the group taught by EC the average increased from 2.3±3.4 to 17.1±3.0 points, and in the group taught by ST from 2.7±3.0 to 13.9±2.7 points. The difference in improvement between the groups was also significant (p = .03).

Conclusions
Hands-on training by student tutors led to a significant gain in echocardiography skills, although inferior to teaching by an expert cardiographer.
Educational application for visualization and analysis of electric field strength in multiple electrode electroporation
Authors: Mahnič-Kalamiza Samo , Kotnik Tadej , Miklavčič Damijan 
Published: October 2012

Abstract

Background
Electrochemotherapy is a local treatment that utilizes electric pulses in order to achieve local increase in cytotoxicity of some anticancer drugs. The success of this treatment is highly dependent on parameters such as tissue electrical properties, applied voltages and spatial relations in placement of electrodes that are used to establish a cell-permeabilizing electric field in target tissue. Non-thermal irreversible electroporation techniques for ablation of tissue depend similarly on these parameters. In the treatment planning stage, if oversimplified approximations for evaluation of electric field are used, such as U/d (voltage-to-distance ratio), sufficient field strength may not be reached within the entire target (tumor) area, potentially resulting in treatment failure.

Results
In order to provide an aid in education of medical personnel performing electrochemotherapy and non-thermal irreversible electroporation for tissue ablation, assist in visualizing the electric field in needle electrode electroporation and the effects of changes in electrode placement, an application has been developed both as a desktop- and a web-based solution. It enables users to position up to twelve electrodes in a plane of adjustable dimensions representing a two-dimensional slice of tissue. By means of manipulation of electrode placement, i.e. repositioning, and the changes in electrical parameters, the users interact with the system and observe the resulting electrical field strength established by the inserted electrodes in real time. The field strength is calculated and visualized online and instantaneously reflects the desired changes, dramatically improving the user friendliness and educational value, especially compared to approaches utilizing general-purpose numerical modeling software, such as finite element modeling packages.

Conclusion
In this paper we outline the need and offer a solution in medical education in the field of electroporation-based treatments, e.g. primarily electrochemotherapy and non-thermal irreversible tissue ablation. We present the background, the means of implementation and the fully functional application, which is the first of its kind. While the initial feedback from students that have evaluated this application as part of an e-learning course is positive, a formal study is planned to thoroughly evaluate the current version and identify possible future improvements and modifications.
Effects of corticosteroid on the expressions of neuropeptide and cytokine mRNA and on tenocyte viability in lateral epicondylitis
Authors: Han Soo Hong , An Hee Jung , Song Ji Ye , Shin Dong Eun , Kwon Young Do , Shim Jong Sup , Lee Soon Chul 
Published: October 2012

Abstract

Background
The purpose of this study was to determine the reaction mechanism of corticosteroid by analyzing the expression patterns of neuropeptides (substance P (SP), calcitonin gene related peptide (CGRP)) and of cytokines (interleukin (IL)-1α, tumor growth factor (TGF)-β) after corticosteroid treatment in lateral epicondylitis. In addition, we also investigated whether corticosteroid influenced tenocyte viability.

Methods
The corticosteroid triamcinolone acetonide (TAA) was applied to cultured tenocytes of lateral epicondylitis, and the changes in the mRNA expressions of neuropeptides and cytokines and tenocyte viabilities were analyzed at seven time points. Quantitative real-time polymerase chain reaction and an MTT assay were used.

Results
The expression of SP mRNA was maximally inhibited by TAA at 24 hours but recovered at 72 hours, and the expressions of CGRP mRNA and IL-1α mRNA were inhibited at 24 and 3 hours, respectively. The expression of TGF-β mRNA was not significant. Tenocyte viability was significantly reduced by TAA at 24 hours.

Conclusions
We postulate that the reaction mechanism predominantly responsible for symptomatic relief after a corticosteroid injection involves the inhibitions of neuropeptides and cytokines, such as, CGRP and IL-1α. However the tenocyte viability was compromised by a corticosteroid.
TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors
Authors: Arts Rob J W , Joosten Leo A B , van der Meer Jos W M , Netea Mihai G 
Published: October 2012

Abstract
Review of the intracellular pathway of TREM-1 signaling, its interactions with PRR pathways, focusing on TLRs and NLRs.
TREM-1 is an important signaling receptor expressed on neutrophils and monocytes that plays an important role in systemic infections. Here, we review the intracellular signaling pathways that mediate the immunological effects of TREM-1. Because of the absence of signaling motifs, TREM-1 constitutively associates with DAP12 for induction of intracellular signals. After phosphorylation of DAP12, production of chemokines and cytokines is induced. Moreover, TREM-1 also modulates signaling pathways induced by known classes of PRRs, such as TLRs and NLRs. The exact mechanisms through which TREM-1 influences TLR and NLR pathways are still largely elusive.
Thrombin-induced CCN2 expression in human lung fibroblasts requires the c-Src/JAK2/STAT3 pathway
Authors: Bai Kua-Jen , Chen Bing-Chang , Pai Hui-Chen , Weng Chih-Ming , Yu Chung-Chi , Hsu Ming-Jen , Yu Ming-Chih , Ma Hon-Ping , Wu Chih-Hsiung , Hong Chuang-Ye , Kuo Min-Liang , Lin Chien-Huang 
Published: October 2012

Abstract
Thrombin might activate c-Src to induce JAK2 activation, which causes STAT3 activation, inducing CCN2 expression in human lung fibroblasts.
Thrombin is a multifunctional serine protease and an important fibrotic mediator that induces CCN2 expression. We previously showed that thrombin induces CCN2 expression via an ASK1-dependent JNK/AP-1 pathway in human lung fibroblasts. In this study, we further investigated the roles of c-Src, JAK2, and STAT3 in thrombin-induced CCN2 expression. Thrombin-induced CCN2 expression and CCN2-Luc activity were attenuated by a JAK inhibitor (AG490) and JAK2DN, STAT3DN, and the STAT decoy ODN. Moreover, transfection of cells with a CCN2-mtSTAT-Luc construct inhibited thrombin-induced CCN2-Luc activity. Treatment of cells with thrombin caused JAK2 phosphorylation at Tyr1007/1008 and STAT3 phosphorylation at Tyr705 in time-dependent manners. Thrombin-induced STAT3 phosphorylation was inhibited by AG490 and JAK2DN. Thrombin-induced STAT3 binding to the CCN2 promoter was analyzed by a DNA-binding affinity pull-down assay. In addition, thrombin-induced CCN2 expression and CCN2-Luc activity were inhibited by c-SrcDN and PP2 (an Src inhibitor). Transfection of cells with c-SrcDN also inhibited thrombin-induced JAK2 and STAT3 phosphorylation. Taken together, these results indicate that thrombin might activate c-Src to induce JAK2 activation, which in turn, causes STAT3 activation, and finally induces CCN2 expression in human lung fibroblasts.
Symptomatic Treatment With Lanreotide Microparticles in Inoperable Bowel Obstruction Resulting From Peritoneal Carcinomatosis: A Randomized, Double-Blind, Placebo-Controlled Phase III Study
Authors: Mariani Pascale , Blumberg Joëlle , Landau Alain , Lebrun-Jezekova Daniela , Botton Estelle , Beatrix Olivier , Mayeur Didier , Herve Robert , Maisonobe Pascal , Chauvenet Laure 
Published: October 2012

Purpose To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. Patients and Methods In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. Results More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P < .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P < .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. Conclusion These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.
CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer–Specific Death, and Increased Risk of a Second Breast Cancer
Authors: Weischer Maren , Nordestgaard Børge G. , Pharoah Paul , Bolla Manjeet K. , Nevanlinna Heli , van't Veer Laura J. , Garcia-Closas Montserrat , Hopper John L. , Hall Per , Andrulis Irene L. , Devilee Peter , Fasching Peter A. , Anton-Culver Hoda , Lambrechts Diether , Hooning Maartje , Cox Angela , Giles Graham G. , Burwinkel Barbara , Lindblom Annika , Couch Fergus J. , Mannermaa Arto , Grenaker Alnæs Grethe , John Esther M. , Dörk Thilo , Flyger Henrik , Dunning Alison M. , Wang Qin , Muranen Taru A. , van Hien Richard , Figueroa Jonine , Southey Melissa C. , Czene Kamila , Knight Julia A. , Tollenaar Rob A.E.M. , Beckmann Matthias W. , Ziogas Argyrios , Christiaens Marie-Rose , Collée Johanna Margriet , Reed Malcolm W.R. , Severi Gianluca , Marme Frederik , Margolin Sara , Olson Janet E. , Kosma Veli-Matti , Kristensen Vessela N. , Miron Alexander , Bogdanova Natalia , Shah Mitul , Blomqvist Carl , Broeks Annegien , Sherman Mark , Phillips Kelly-Anne , Li Jingmei , Liu Jianjun , Glendon Gord , Seynaeve Caroline , Ekici Arif B. , Leunen Karin , Kriege Mieke , Cross Simon S. , Baglietto Laura , Sohn Christof , Wang Xianshu , Kataja Vesa , Børresen-Dale Anne-Lise , Meyer Andreas , Easton Douglas F. , Schmidt Marjanka K. , Bojesen Stig E. 
Published: October 2012

Purpose We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer–specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer–specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor–positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer–specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor–positive first breast cancer only. Conclusion Among women with estrogen receptor–positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer–specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.
Clinical Outcome of the ACCORD 12/0405 PRODIGE 2 Randomized Trial in Rectal Cancer
Authors: Gérard Jean-Pierre , Azria David , Gourgou-Bourgade Sophie , Martel-Lafay Isabelle , Hennequin Christophe , Etienne Pierre-Luc , Vendrely Véronique , François Eric , de La Roche Guy , Bouché Olivier , Mirabel Xavier , Denis Bernard , Mineur Laurent , Berdah Jean-François , Mahé Marc-André , Bécouarn Yves , Dupuis Olivier , Lledo Gérard , Seitz Jean-François , Bedenne Laurent , Juzyna Béata , Conroy Thierry 
Published: October 2012

Purpose The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. Patients and Methods Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. Results At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). Conclusion At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.
Referral Practices of Oncologists to Specialized Palliative Care
Authors: Wentlandt Kirsten , Krzyzanowska Monika K. , Swami Nadia , Rodin Gary M. , Le Lisa W. , Zimmermann Camilla 
Published: October 2012

Purpose To describe current referral practices of oncologists to specialized palliative care (SPC) and define demographic characteristics, practice situations, and opinions associated with referral. Methods Physician members of the Canadian Association of Medical Oncologists, Canadian Association of Radiation Oncologists, and Canadian Society of Surgical Oncology were invited to participate in an anonymous survey assessing SPC referral practices. Participants received two e-mailed and two mailed invitations. Results The response rate was 72% (603 of 839 physicians); 37% were medical oncologists/hematologists, 50% were radiation oncologists, and 12% were surgical oncologists. Ninety-four percent reported that SPC was available to them, but only 37% reported that these services accepted patients on chemotherapy. Eighty-four percent referred terminally ill patients usually/always, but generally for uncontrolled symptoms or discharge planning late in the disease course. One third would refer to SPC earlier if it was renamed supportive care. Predictors of higher referral frequency included comprehensiveness of available SPC services (P = .004), satisfaction with SPC availability (P < .001), SPC acceptance of patients receiving chemotherapy (P < .001), and oncologist ease with referring patients to a palliative care service before they were close to death (P < .001). Controlling for specialty, predictors of referral at diagnosis or during chemotherapy, rather than later, included satisfaction with SPC service availability (P < .001) and SPC service acceptance of patients on chemotherapy (P < .001). Conclusion Oncologists referred patients frequently to SPC, but generally late in the disease course for patients with uncontrolled symptoms. Availability of comprehensive SPC, especially for patients receiving chemotherapy, and persisting definitional issues seem to be the main barriers preventing timely referral.
The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy
Authors: Rodrigue Amélie , Coulombe Yan , Jacquet Karine , Gagné Jean-Phillipe , Roques Céline , Gobeil Stéphane , Poirier Guy , Masson Jean-Yves 
Published: October 2012

Summary
The interplay between homologous DNA recombination and mitotic progression is poorly understood. The five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3) are key enzymes for DNA double-strand break repair. In our search for specific functions of the various RAD51 paralogs, we found that inhibition of XRCC3 elicits checkpoint defects, while inhibition of RAD51B or RAD51C induces G2/M cell cycle arrest in HeLa cells. Using live-cell microscopy we show that in XRCC3-knockdown cells the spindle assembly checkpoint persists and there is a higher frequency of chromosome misalignments, anaphase bridges, and aneuploidy. We observed centrosome defects in the absence of XRCC3. While RAD51B and RAD51C act early in homologous recombination, XRCC3 functions jointly with GEN1 later in the pathway at the stage of Holliday junction resolution. Our data demonstrate that Holliday junction resolution has critical functions for preventing aberrant mitosis and aneuploidy in mitotic cells.