tbuckley/cabot-search huggingface dataset:
Abstract 16305: Cardiac and Circulatory Adaptation to Volume Overload: The Impact of Reduction of High-flow Arterio-venous Fistula
Authors: Peter Wohlfahrt, Slavomir Rokosny, Peter Balaz, Daniel Palous, Vojtech Melenovsky
Journal: Circulation (2015)

Introduction: Heart failure is present in one out of three patients on hemodialysis and is the leading cause of death. Because increased blood flow through the arteriovenous fistula (AVF) leads to volume overload potentially causing high-output heart failure, reduction (e.g. aneurysmorrhaphy) or occlusion of a hyperfunctional AVF (hAVF) is commonly performed. However, there are no clear indications for these procedures. The aim of this study was to evaluate the impact of aneurysmorrhaphy on hemodynamics and cardiac structure in patients with hAVF. Methods: Thirty patients (age 52 ± 12 years, 73% male) with hAVF (flow ≥ 1.5 L/min) were examined before, at 6 and 12 months after aneurysmorrhaphy. Results: Relationship between AVF flow and cardiac index (CI) was weak and nonlinear. In total, 16 patients had normal CI (2.5 - 3.8 L/min/m2) and 14 high CI (4.0 - 6.0 L/min/m2). While the AVF flow did not differ between groups (3.1±1.4 vs. 3.5±0.8 L/min, p=0.34), there was a difference in CI (3.3±0.7 vs. 4.7±0.5, p&lt;0.001). After operation AVF flow significantly and similarly decreased in both groups, while CI decreased only in the high CI group (Table 1). Similarly, there was a significant decrease in left ventricular end-diastolic diameter and mass, left atrial and right ventricular diameter and pulmonary systolic pressure in the high CI, but not in the normal CI group (Table 1). Conclusions: Aneurysmorrhaphy of a hAVF leads to positive heart remodeling only in patients with elevated CI. Increased CI, but not increased AVF flow, should be used as an indication for aneurysmorrhaphy.
The Incidence of HBV Reactivation in Patients Receiving First-Line R-CHOP Chemotherapy: Three-Year Follow-up Results from a Prospective, Observational Study
Authors: Jianqiu Wu, Yongping Song, Liping Su, Mingzhi Zhang, Wei Li, Yu Hu, Xiaohong Zhang, Yuhuan Gao, Zuoxing Niu, Ru Feng, Wei Wang, Jiewen Peng, Xuenong Ouyang, Xiaolin Li, Changping Wu, Weijing Zhang, Yun Zeng, Zhen Xiao, Yingmin Liang, Yongzhi Zhuang, Jishi Wang, Zimin Sun, Hai Bai, Tongjian Cui, Jifeng Feng
Journal: Blood (2017)
Abstract 54: Genome-wide CRISPR screen identifies potential therapeutic combination of EGFR and FGFR inhibitors in oral cancer
Authors: Megan Ludwig, Andrew Birkeland, Sai Nimmagadda, Sue Foltin, Aditi Kulkarni, Hui Jiang, Thomas Carey, J. Chad Brenner
Journal: Clinical Cancer Research (2017)

Abstract Oral squamous cell carcinoma (OSCC) is a disease with poor survival with few novel treatment options in development. While EGFR is commonly over-expressed, targeting EGFR has had limited success possibly because of compensatory pathways rescuing cell survival. Inhibiting compensatory pathways in combination with EGFR signaling may result in greater efficacy. To identify compensatory pathways, we used a Genome-wide CRISPR-Cas9 Knock-Out (GeCKO) library to identify genetic knockouts that sensitized OSCC cell lines to EGFR inhibition. This CRISPR library established a pool of knockouts targeting over 18,000 genes, and upon selection of the GeCKO pool we identified gene knockouts in the FGFR pathway increased sensitivity to the EGFR inhibitor gefitinib. We further profiled this combination with viability assays and found that 6/14 (43%) cell lines responded to the combination of EGFR and FGFR inhibition, suggesting that the FGFR pathway could be a common compensatory mechanism to loss of EGFR signaling. In complement, we again used CRISPR-Cas9 to generate a syngeneic EGFR knockout (KO) OSCC cell line. The parent OSCC cell line is responsive to the EGFR and FGFR dual inhibition, and the EGFR KO derivative retains sensitivity to FGFR-targeted monotherapies. We expect that this EGFR KO cell line will be a useful tool in further evaluating the compensatory mechanism of the FGFR pathway. In total, we describe the use of genome-wide CRISPR-Cas9 library to discover the synergistic combination of EGFR and FGFR inhibition, with follow-up indicating that the FGFR pathway could be a common compensatory mechanism to EGFR inhibition. Targeting compensatory mechanisms in combination with EGFR-targeted therapy could be clinically beneficial, including the combination of EGFR and FGFR inhibition. Citation Format: Megan Ludwig, Andrew Birkeland, Sai Nimmagadda, Sue Foltin, Aditi Kulkarni, Hui Jiang, Thomas Carey, J. Chad Brenner. Genome-wide CRISPR screen identifies potential therapeutic combination of EGFR and FGFR inhibitors in oral cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 54.
The prognostic implications of redox protein expression in stage I-III triple-negative breast cancer.
Authors: Soohyeon Lee, Da Rae Kim, Min Whan Kim
Journal: Journal of Clinical Oncology (2013)

1035 Background: It is well known that increased reactive oxidative stress (ROS) in cancer cells correlates with poor prognosis and aggressiveness of tumor cells. The aim of this study is to investigate the expression of redox proteins in triple-negative, early breast cancer (TNBC) which shows aggressive phenotype among breast cancer and to demonstrate relationships between expression of ROS markers and clinical outcomes. Methods: Tissues from 135 cases of TNBC from curative surgery at Severance Hospital, Seoul, Korea, from December 2005 to January 2008 were analyzed. Immnunochemical (IHC) staining for redox proteins including thioredoxin reductase, glutathione S-transferase (GST) α, catalase, vitamin D-up-regulated protein 1 (VUDP), and manganese superoxide dismutase (MnSOD) was performed to evaluate the difference between clinicopathological parameters. The mono-carboxylate transporter 4 (MCT4) in stroma was done by IHC staining, too. Results: The median age of 135 TNBC patients was 48 (range 27-76). TNM staging were as follows; T1 (n=52, 38.5%), T2 (n=81, 60%), T3 (n=2, 1.5%), N0 (n=88, 65.2%), N1 (n=35, 25.9%), N2 (n=8, 5.9%), N3(n=4, 3.0%). Median follow up was 59 months (range 12-99). Samples were divided into high or low ROS expression level semi-quantitatively. The catalase high expressed group was tend to have lower N stage (p=0.016), lower tumor recurrence (p=0.02) as well as longer overall survival rates (p=0.05). Higher expression of MTC4 in stroma was strongly associated with higher MnSOD expression group analysis (p=0.015) and had significantly longer overall survival (p=0.032). Conclusions: This study shows the expression of ROS proteins could contribute defining aggressiveness of TNBC as well as the prognosis. Considering the lack of targeted molecules as well as molecular heterogeneity of TNBC, ROS markers may provide clues to clinical outcomes in TNBC.
Incidence of suicide, hospital-presenting non-fatal self-harm, and community-occurring non-fatal self-harm in adolescents in England (the iceberg model of self-harm): a retrospective study
Authors: Galit Geulayov, Deborah Casey, Keltie C McDonald, Pauline Foster, Kirsty Pritchard, Claudia Wells, Caroline Clements, Navneet Kapur, Jennifer Ness, Keith Waters, Keith Hawton
Journal: The Lancet Psychiatry (2017)
Regulation of chromosome segregation in oocytes and the cellular basis for female meiotic errors
Authors: Jessica Greaney, Zhe Wei, Hayden Homer
Journal: Human Reproduction Update (2017)

Meiotic chromosome segregation in human oocytes is notoriously error-prone, especially with ageing. Such errors markedly reduce the reproductive chances of increasing numbers of women embarking on pregnancy later in life. However, understanding the basis for these errors is hampered by limited access to human oocytes. Important new discoveries have arisen from molecular analyses of human female recombination and aneuploidy along with high-resolution analyses of human oocyte maturation and mouse models. Here, we review these findings to provide a contemporary picture of the key players choreographing chromosome segregation in mammalian oocytes and the cellular basis for errors. A search of PubMed was conducted using keywords including meiosis, oocytes, recombination, cohesion, cohesin complex, chromosome segregation, kinetochores, spindle, aneuploidy, meiotic cell cycle, spindle assembly checkpoint, anaphase-promoting complex, DNA damage, telomeres, mitochondria, female ageing and female fertility. We extracted papers focusing on mouse and human oocytes that best aligned with the themes of this review and that reported transformative and novel discoveries. Meiosis incorporates two sequential rounds of chromosome segregation executed by a spindle whose component microtubules bind chromosomes via kinetochores. Cohesion mediated by the cohesin complex holds chromosomes together and should be resolved at the appropriate time, in a specific step-wise manner and in conjunction with meiotically programmed kinetochore behaviour. In women, the stage is set for meiotic error even before birth when female-specific crossover maturation inefficiency leads to the formation of at-risk recombination patterns. In adult life, multiple co-conspiring factors interact with at-risk crossovers to increase the likelihood of mis-segregation. Available evidence support that these factors include, but are not limited to, cohesion deterioration, uncoordinated sister kinetochore behaviour, erroneous microtubule attachments, spindle instability and structural chromosomal defects that impact centromeres and telomeres. Data from mice indicate that cohesin and centromere-specific histones are long-lived proteins in oocytes. Since these proteins are pivotal for chromosome segregation, but lack any obvious renewal pathway, their deterioration with age provides an appealing explanation for at least some of the problems in older oocytes. Research in the mouse model has identified a number of candidate genes and pathways that are important for chromosome segregation in this species. However, many of these have not yet been investigated in human oocytes so it is uncertain at this stage to what extent they apply to women. The challenge for the future involves applying emerging knowledge of female meiotic molecular regulation towards improving clinical fertility management.
Tratamiento endoscópico del divertículo de Zenker mediante pinza “SB-knife”. Serie descriptiva multicéntrica
Authors: A Repiso, M Muñoz-Navas, A Del Pozo, JM Riesco, JM Martín, P Rosón, OG Bernardo, G Cacho, M Domínguez, L Sánchez, F Sánchez, E De La Morena
Journal: Endoscopy (2017)

La pinza “SB-knife” (Sumitomo Bakeliteco., Ltd., Tokyo, Japan) es un dispositivo monopolar de corte y coagulación, de uso a través del canal del endoscopio que podría ser una alternativa para el tratamiento endoscópico del divertículo de Zenker. El objetivo de esta serie es valorar su utilidad y seguridad.
Finding Evolutionary Processes Hidden in Cryptic Species
Authors: Torsten H. Struck, Jeffrey L. Feder, Mika Bendiksby, Siri Birkeland, José Cerca, Vladimir I. Gusarov, Sonja Kistenich, Karl-Henrik Larsson, Lee Hsiang Liow, Michael D. Nowak, Brita Stedje, Lutz Bachmann, Dimitar Dimitrov
Journal: Trends in Ecology & Evolution (2017)
Forces of nature
Authors: Sophie Cook, Navjoyt Ladher
Journal: BMJ (2017)

We have another bumper crop of Christmas articles in The BMJ this year, so read on as you raise a glass to the festive season—but not too big a glass (doi:10.1136/bmj.j5623).

The natural world features in several papers, exploring links between environmental conditions and health: from weather and joint pain (doi:10.1136/bmj.j5326) to thunderstorm asthma …
Abstract 04: Caspase-8 is a novel candidate driver gene in head and neck squamous cell carcinoma
Authors: Burak Uzunparmak, Antje Lindemann, Mitchell J. Frederick, Jeffrey N. Myers, Curtis R. Pickering
Journal: Clinical Cancer Research (2017)

Abstract Integrated genomic analysis of head and neck squamous cell carcinoma (HNSCC) has identified a heterogeneous spectrum of alterations dominated by tumor suppressor genes. An interesting new candidate driver gene is Caspase-8 (CASP8), which is mutated in 18% of oral cavity HPV-negative tumors. CASP8 is not obviously a part of any well-characterized driver pathway in HNSCC, and its role in this tumor type is unknown. In TCGA genomic data CAPS8 mutant tumors have a unique spectrum of alterations and expression changes, including a dramatic increase in markers of inflammation, which suggest they are a genomic subtype of HNSCC. CAPS8 is a key component of the extrinsic apoptotic pathway, but it also has a role in necrotic death, inflammation, and other pathways. We have characterized human and mouse CASP8 knock-out cell lines in vitro and in vivo in order to begin to understand the function of this gene in HNSCC. Loss of CASP8 function prevents extrinsic apoptosis and alters proliferation and tumorigenicity. It may also regulate the antitumor immune response. CASP8 is an exciting new candidate driver gene in HNSCC that may offer new opportunities for therapeutic intervention. Citation Format: Burak Uzunparmak, Antje Lindemann, Mitchell J. Frederick, Jeffrey N. Myers, Curtis R. Pickering. Caspase-8 is a novel candidate driver gene in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 04.
Abstract 254: A Novel Mechanism for Aberrant Aldosterone Production in Heart Failure
Authors: Jin Endo, Kaoru Yamashita, Naohiro Yoshida, Kentaro Ito, Atsuhiro Ichihara, Keiichi Fukuda, Motoaki Sano
Journal: Circulation Research (2016)

Objective: Aldosterone production by the adrenal gland is mainly regulated by the renin-angiotensin system (RAS), which is normally suppressed by a high-salt diet. However, plasma aldosterone levels are elevated in proportion to the severity of heart failure even if caused by high-salt intake. The inappropriate increase in plasma aldosterone level could not be diminished by pharmacological blockade of the RAS. We investigated the cellular mechanism underlying the aberrant aldosterone production in heart failure beyond the activation of RAS. Methods and Results: Dahl-salt sensitive rats fed high salt diet developed malignant hypertension, resulting in heart failure with increased plasma aldosterone level. The gene expression pattern of the adrenal gland from heart failure rats showed strikingly upregulated β3-adrenergic receptor (β3-AR) expression. Immunohistochemical staining confirmed that heart failure increased β3-AR expression in zona glomerulosa cells in adrenal gland of Dahl-salt sensitive rats. And the staining of pimonidazole, a hypoxia probe, revealed that the outer layer of adrenal cortex in the heart failure rat was under hypoxic condition. Hypoxia and DMOG, a chemical stabilizer of hypoxia-inducible factor, strongly induced β3-AR mRNA expression in H295R human adrenocortical carcinoma cells. Hypoxia-reoxygenation stimuli induced aldosterone production from H295R cells, which was blocked by SR59230A, a selective β3-AR antagonist, but not by losartan, an angiotensin II receptor blocker (ARB). Hypoxia endowed catecholamine responsiveness in H295R cells by increased β3-AR expression, wherein β3-AR agonist increased the phosphorylation levels of hormone-sensitive lipase (HSL) through activation of ERK pathway. Conclusions: In the present study, we demonstrated that the β3-AR induction in adrenal gland by hypoxia played an important role in aberrant aldosterone production in heart failure. The catecholamine stimuli through β3-AR in adrenocortical cells caused the ERK-mediated phosphorylation of HSL, suggesting that the HSL promotes lipolysis to supply substrates for the aldosterone biosynthesis.
Reduction in undiagnosed HIV infection in the European Union/European Economic Area, 2012 to 2016
Authors: Ard van Sighem, Anastasia Pharris, Chantal Quinten, Teymur Noori, Andrew J Amato-Gauci
Journal: Eurosurveillance (2017)

It is well-documented that early HIV diagnosis and linkage to care reduces morbidity and mortality as well as HIV transmission. We estimated the median time from HIV infection to diagnosis in the European Union/European Economic Area (EU/EEA) at 2.9 years in 2016, with regional variation. Despite evidence of a decline in the number of people living with undiagnosed HIV in the EU/EEA, many remain undiagnosed, including 33% with more advanced HIV infection (CD4 < 350 cells/mm3).
Blocking the Feedback Loop between Neuroendocrine Differentiation and Macrophages Improves the Therapeutic Effects of Enzalutamide (MDV3100) on Prostate Cancer
Authors: Chao Wang, Guang Peng, Hai Huang, Fei Liu, De-Pei Kong, Ke-Qin Dong, Li-He Dai, Zhe Zhou, Kai-Jian Wang, Jun Yang, Yan-Qiong Cheng, Xu Gao, Min Qu, Hong-Ru Wang, Feng Zhu, Qin-Qin Tian, Dan Liu, Li Cao, Xin-Gang Cui, Chuan-Liang Xu, Dan-Feng Xu, Ying-Hao Sun
Journal: Clinical Cancer Research (2017)

Purpose: Androgen deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer; ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated macrophages (TAM). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism.Experimental Design: The association between enzalutamide-induced NED and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide-resistant mouse xenografts, and a coculture system. The underlying mechanisms were assessed using in vitro cytokine antibody arrays, ELISAs, chromatin immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model was established to evaluate the in vivo effects of combined IL6 receptor (IL6R) and high mobility group box 1 (HMGB1) inhibition on enzalutamide resistance.Results: High CD163 expression was observed in ADT-treated prostate cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide-resistant xenografts, indicating the crucial roles of NED and TAMs in enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression facilitated TAM recruitment and polarization and drove NED via β-catenin stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited enzalutamide-induced resistance in an orthotopic prostate cancer mouse model.Conclusions: Enzalutamide elevates HMGB1 levels, which recruits and activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the enzalutamide-induced NED of prostate cancer, forming a positive feedback loop between NED in prostate cancer and TAMs. The combined inhibition of IL6R and HMGB1 may serve as a new treatment for enzalutamide resistance in patients with advanced or metastatic prostate cancer. Clin Cancer Res; 24(3); 708-23. ©2017 AACR.
Multisensory control of ingestive movements and the myth of food addiction in obesity
Authors: David A. Booth
Journal: Behavioral and Brain Sciences (2017)

Some individuals have a neurogenetic vulnerability to developing strong facilitation of ingestive movements by learned configurations of biosocial stimuli. Condemning food as addictive is mere polemic, ignoring the contextualised sensory control of the mastication of each mouthful. To beat obesity, the least fattening of widely recognised eating patterns needs to be measured and supported.
Familial Cancer Clustering in Urothelial Cancer: A Population-Based Case–Control Study
Authors: Christopher Martin, Claire L Leiser, Brock O’Neil, Sumati Gupta, William T Lowrance, Wendy Kohlmann, Samantha Greenberg, Piyush Pathak, Ken R Smith, Heidi A Hanson
Journal: JNCI Journal of the National Cancer Institute (2017)

Family history of bladder cancer confers an increased risk for concordant and discordant cancers in relatives. However, previous studies investigating this relationship lack any correction for smoking status of family members. We conducted a population-based study of cancer risks in relatives of bladder cancer patients and matched controls with exclusion of variant subtypes to improve the understanding of familial cancer clustering.Case subjects with urothelial carcinoma were identified using the Utah Cancer Registry and matched 1:5 to cancer-free controls from the Utah Population Database. Cox regression was used to determine the risk of cancer in first-degree relatives, second-degree relatives, first cousins, and spouses. A total of 229 251 relatives of case subjects and 1 197 552 relatives of matched control subjects were analyzed. To correct for smoking status, we performed a secondary analysis excluding families with elevated rates of smoking-related cancers. All statistical tests were two-sided.First- and second-degree relatives of case subjects had an increased risk for any cancer diagnosis (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 1.03 to 1.09, P < .001; HR = 1.04, 95% CI = 1.02 to 1.07, P = .001) and urothelial cancer (HR = 1.73, 95% CI = 1.50 to 1.99, P < .001; HR = 1.35, 95% CI = 1.21 to 1.51, P < .001). Site-specific analysis found increased risk for bladder (HR = 1.69, 95% CI = 1.47 to 1.95, P < .001), kidney (HR = 1.30, 95% CI = 1.08 to 1.57, P = .006), cervical (HR = 1.25, 95% CI = 1.06 to 1.49, P = .01), and lung cancer (HR = 1.34, 95% CI = 1.19 to 1.51, P < .001) in first-degree relatives. Second-degree relatives had increased risk for bladder (HR = 1.35, 95% CI = 1.2 to 1.5, P < .001) and thyroid cancer (HR = 1.18, 95% CI = 1.03 to 1.35, P = .02). Spouses showed an increased risk for laryngeal (HR = 2.68, 95% CI = 1.02 to 7.05, P = .04) and cervical cancer (HR = 1.57, 95% CI = 1.13 to 2.17, P = .007). These results did not substantively change after correction for suspected smoking behaviors.Our results suggest familial urothelial cancer clustering independent of smoking, with increased risk in relatives for both concordant and discordant cancers, suggesting shared genetic or environmental roots. Identifying families with statistically significant risks for non-smoking-related urothelial cancer would be extremely informative for genetic linkage studies.