bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal Residual Disease after Conventional Treatment Significantly Impacts on Progression-Free Survival of Patients with Follicular Lymphoma: The FIL FOLL05 Trial
Authors: Galimberti Sara , Luminari Stefano , Ciabatti Elena , Grassi Susanna , Guerrini Francesca , Dondi Alessandra , Marcheselli Luigi , Ladetto Marco , Piccaluga Pier Paolo , Gazzola Anna , Mannu Claudia , Monitillo Luigia , Mantoan Barbara , Del Giudice Ilaria , Della Starza Irene , Cavalli Marzia , Arcaini Luca , Tucci Alessandra , Palumbo Giuseppe Alberto , Rigacci Luigi , Pulsoni Alessandro , Vitolo Umberto , Boccomini Carola , Vallisa Daniele , Bertoldero Giovanni , Gaidano Gianluca , Musto Pellegrino , Petrini Mario , Federico Massimo
Published: October 2014

Purpose: The role of the minimal residual disease (MRD) in follicular lymphoma is still debated. In this study, we assessed whether the BCL2/IGH rearrangement could have a prognostic role in patients receiving R-CHOP, R-FM, or R-CVP.

Experimental Design: DNAs from 415 patients among the 504 cases enrolled in the FOLL05 trial (NCT00774826) were centralized and assessed for the BCL2/IGH at diagnosis, at the end of treatment, and after 12 and 24 months.

Results: At diagnosis, the molecular marker was detected in 53% of cases. Patients without molecular marker or with a low molecular tumor burden (<1 × 10−4 copies) showed higher complete remission (CR) rate and longer progression-free survival (PFS; 3-year PFS 80% vs. 59%; P = 0.015). PFS was significantly conditioned by the PCR status at 12 and 24 months, with 3-year PFS of 66% for MRD− cases versus 41% for those MRD+ at 12 months (P = 0.015), and 84% versus 50% at 24 months (P = 0.014). The MRD negativity at 12 and 24 months resulted in an improved PFS both in CR and in partial remission (PR) patients (3-year PFS = 72% for cases CR/PCR− vs. 32% for those CR/PCR+ vs. 62% for those PR/PCR− and 25% for patients in PR/PCR+; P = 0.001). The prognostic value of MRD at 12 and 24 months of follow-up was confirmed also in multivariate analysis.

Conclusions: In this study, standardized molecular techniques have been adopted and applied on bone marrow samples from a large cohort. Data reported show that the MRD detection is a powerful independent predictor of PFS in patients with follicular lymphoma receiving conventional chemoimmunotherapy. Clin Cancer Res; 20(24); 6398–405. ©2014 AACR.
The Human Agonistic CD40 Antibody ADC-1013 Eradicates Bladder Tumors and Generates T-cell–Dependent Tumor Immunity
Authors: Mangsbo Sara M. , Broos Sissela , Fletcher Erika , Veitonmäki Niina , Furebring Christina , Dahlén Eva , Norlén Per , Lindstedt Malin , Tötterman Thomas H. , Ellmark Peter
Published: October 2014

Purpose: Local administration of immune-activating antibodies may increase the efficacy and reduce the immune-related adverse events associated with systemic immunotherapy of cancer. Here, we report the development and affinity maturation of a fully human agonistic CD40 antibody (IgG1), ADC-1013.

Experimental Design: We have used molecular engineering to generate an agonistic antibody with high affinity for CD40. The functional activity of ADC-1013 was investigated in human and murine in vitro models. The in vivo effect was investigated in two separate bladder cancer models, both using human xenograft tumors in immune deficient NSG mice and using a syngeneic bladder cancer model in a novel human CD40 transgenic mouse.

Results: Activation of dendritic cells (DC) by ADC-1013 results in upregulation of the costimulatory molecules CD80 and CD86, and secretion of IL12. ADC-1013 also activates DCs from human CD40 transgenic mice, and peptide-pulsed and ADC-1013–stimulated DCs induce antigen-specific T-cell proliferation in vitro. In vivo, treatment with ADC-1013 in a syngeneic bladder cancer model, negative for hCD40, induces significant antitumor effects and long-term tumor-specific immunity. Furthermore, ADC-1013 demonstrates significant antitumor effects in a human bladder cancer transplanted into immunodeficient NSG mice.

Conclusions: Our data demonstrate that ADC-1013 induces long-lasting antitumor responses and immunologic memory mediated by CD40 stimulation. To the best of our knowledge, ADC-1013 represents the first immunomodulatory antibody developed for local immunotherapy of cancer. Clin Cancer Res; 21(5); 1115–26. ©2014 AACR.

See related commentary by Dronca and Dong, p. 944
The Novel Organic Arsenical Darinaparsin Induces MAPK-Mediated and SHP1-Dependent Cell Death in T-cell Lymphoma and Hodgkin Lymphoma Cells and Human Xenograft Models
Authors: Ravi Dashnamoorthy , Bhalla Savita , Gartenhaus Ronald B. , Crombie Jennifer , Kandela Irawati , Sharma Jaya , Mazar Andrew , Evens Andrew M.
Published: October 2014

Purpose: Darinaparsin (Zio-101) is a novel organic arsenical compound with encouraging clinical activity in relapsed/refractory T-cell lymphoma (TCL) and Hodgkin lymphoma (HL); however, little is known about its mechanism of action.

Experimental Design: TCL cell lines (Jurkat, Hut78, and HH) and HL cell lines (L428, L540, and L1236) were examined for in vitro cell death by MTT assay and Annexin V–based flow cytometry. Jurkat and L540-derived xenografts in SCID mice were examined for in vivo tumor inhibition and survival. Biologic effects of darinaparsin on the MAPK pathway were investigated using pharmacologic inhibitors, RNAi and transient transfection for overexpression for SHP1 and MEK.

Results: Darinaparsin treatment resulted in time- and dose-dependent cytotoxicity and apoptosis in all TCL and HL cell lines. In addition, darinaparsin had more rapid, higher, and sustained intracellular arsenic levels compared with arsenic trioxide via mass spectrometry. In vivo experiments with Jurkat (TCL) and L540 (HL)-derived lymphoma xenografts showed significant inhibition of tumor growth and improved survival in darinaparsin-treated SCID mice. Biologically, darinaparsin caused phosphorylation of ERK (and relevant downstream substrates) primarily by decreasing the inhibitory SHP1 phosphatase and coimmunoprecipitation showed significant ERK/SHP1 interaction. Furthermore, ERK shRNA knockdown or constitutive overexpression of SHP1 resulted in increased apoptosis, whereas cotreatment with pharmacologic MEK inhibitors resulted in synergistic cell death. Conversely, SHP1 blockade (via pharmacologic inhibition or RNAi) and MEK constitutive activation decreased darinaparsin-related cell death.

Conclusions: Altogether, these data show that darinaparsin is highly active in HL and TCL and its activity is dependent primarily on MAPK mechanisms. Clin Cancer Res; 20(23); 6023–33. ©2014 AACR.
Synergy Between VEGF/VEGFR Inhibitors and Chemotherapy Agents in the Phase I Clinic
Authors: Tang Chad , Hess Kenneth , Jardim Denis Leonardo F. , Gagliato Debora De Melo , Tsimberidou Apostolia M. , Falchook Gerald , Fu Siqing , Janku Filip , Naing Aung , Piha-Paul Sarina , Subbiah Vivek , Wheler Jennifer , Zinner Ralph G. , Kurzrock Razelle , Ellis Lee M. , Meric-Berstam Funda , Hong David S.
Published: October 2014

Purpose: We hypothesized that chemotherapy synergizes with VEGF/VEGFR (VEGF/R) inhibitors in patients with advanced solid malignancies.

Experimental Design: Patients treated on phase I protocols between December 2004 and July 2013 (n = 1,498) were included in this analysis. The primary outcome was clinical benefit, defined as stable disease ≥6 months, complete response, or partial response. Two odds ratios (OR) for achieving clinical benefit were calculated: one for patients treated with VEGF/R inhibitors (OR with VEGF/R) and another for patients treated without (OR without VEGF/R). To compare these two ORs, an interaction term was included in the multivariate model: (chemotherapy/factor of interest)×(VEGF/R). We took significant interaction terms (Pinteraction < 0.05) to suggest effect modification (either synergy or antagonism) with VEGF/R inhibitors.

Results: All patients treated with VEGF/R inhibitors exhibited higher OR for clinical benefit than those who were not [OR = 1.9; 95% confidence interval (CI), 1.5–2.4; P < 0.0001]. Use of chemotherapy agents concomitant with VEGF/R inhibitors was associated with significantly higher OR for clinical benefit compared with chemotherapy use without VEGF/R inhibitors [OR with VEGF/R = 1.6 (95% CI, 1.1–2.5) vs. OR without VEGF/R = 0.4 (95% CI, 0.3–0.6), Pinteraction = 0.02]. Specifically, the antimetabolite class was associated with the greatest increase in OR for clinical benefit [OR with VEGF/R = 2.7 (95% CI, 1.5–4.7) vs. OR without VEGF/R = 0.2 (95% CI 0.1–0.3), Pinteraction = 0.004].

Conclusions: VEGF/R inhibitor was found to synergize with chemotherapeutics. This effect was most pronounced with the antimetabolite class. Clin Cancer Res; 20(23); 5956–63. ©2014 AACR.
Alterations Associated with Androgen Receptor Gene Activation in Salivary Duct Carcinoma of Both Sexes: Potential Therapeutic Ramifications
Authors: Mitani Yoshitsugu , Rao Pulivarthi H. , Maity Sankar N. , Lee Yu-Chen , Ferrarotto Renata , Post Julian C. , Licitra Lisa , Lippman Scott M. , Kies Merrill S. , Weber Randal S. , Caulin Carlos , Lin Sue-Hwa , El-Naggar Adel K.
Published: October 2014

Purpose: To investigate the molecular events associated with the activation of androgen receptor (AR) as a potential therapeutic target in patients with salivary duct carcinoma (SDC).

Experimental Design: Comprehensive molecular and expression analysis of the AR gene in 35 tumor specimens (20 males and 15 females) and cell lines derived from SDC using Western blotting and RT-PCR, FISH analysis, and DNA sequencing was conducted. In vitro and in vivo animal studies were also performed.

Results: AR expression was detected in 70% of the tumors and was mainly nuclear and homogenous in both male and female SDCs, although variable cytoplasmic and/or nuclear localization was also found. We report the identification of ligand-independent AR splice variants, mutations, and extra AR gene copy in primary untreated SDC tumors. In contrast to prostate cancer, no AR gene amplification was observed. In vitro knockdown of AR in a female derived SDC cell line revealed marked growth inhibition in culture and in vivo androgen-independent tumor growth.

Conclusions: Our study provides new detailed information on the molecular and structural alterations associated with AR gene activation in SDC and sheds more light on the putative functional role of AR in SDC cells. On the basis of these data, we propose that patients with SDC (male and female) can be stratified for hormone-based therapy in future clinical trials. Clin Cancer Res; 20(24); 6570–81. ©2014 AACR.
Changing the Paradigms of Treatment in Peripheral T-cell Lymphoma: From Biology to Clinical Practice
Authors: O'Connor Owen A. , Bhagat Govind , Ganapathi Karthik , Pedersen Martin Bjerregaard , D'Amore Francesco , Radeski Dejan , Bates Susan E.
Published: October 2014

Despite enormous advances in our understanding of aggressive lymphomas, it is clear that progress in the peripheral T-cell lymphomas (PTCL) has lagged well behind other B-cell malignancies. Although there are many reasons for this, the one commonly cited notes that the paradigms for diffuse large B-cell lymphoma (DLBCL) were merely applied to all patients with PTCL, the classic “one-size-fits-all” approach. Despite these challenges, progress is being made. Recently, the FDA has approved four drugs for patients with relapsed/refractory PTCL over the past 5 years, and if one counts the recent Japanese approval of the anti-CCR4 monoclonal antibody for patients with adult T-cell leukemia/lymphoma, five drugs have been approved worldwide. These efforts have led to the initiation of no fewer than four randomized clinical studies exploring the integration of these new agents into standard CHOP (cyclophosphamide–Adriamycin–vincristine–prednisone)–based chemotherapy regimens for patients with newly diagnosed PTCL. In addition, a new wave of studies are exploring the merits of novel drug combinations in the disease, an effort to build on the obvious single-agent successes. What has emerged most recently is the recognition that the PTCL may be a disease-characterized by epigenetic dysregulation, which may help explain its sensitivity to histone deacetylase (HDAC) inhibitors, and open the door for even more creative combination approaches. Nonetheless, advances made over a relatively short period of time are changing how we now view these diseases and, hopefully, have poised us to finally improve its prognosis.

See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”

Clin Cancer Res; 20(20); 5240–54. ©2014 AACR.
DNA Methylation Levels at Chromosome 8q24 in Peripheral Blood Are Associated with 8q24 Cancer Susceptibility Loci
Authors: Barry Kathryn Hughes , Moore Lee E. , Sampson Joshua , Yan Liying , Meyer Ann , Oler Andrew J. , Chung Charles C. , Wang Zhaoming , Yeager Meredith , Amundadottir Laufey , Berndt Sonja I.
Published: October 2014

Chromosome 8q24 has emerged as an important region for genetic susceptibility to various cancers, but little is known about the contribution of DNA methylation at 8q24. To evaluate variability in DNA methylation levels at 8q24 and the relationship with cancer susceptibility single nucleotide polymorphisms (SNPs) in this region, we quantified DNA methylation levels in peripheral blood at 145 CpG sites nearby 8q24 cancer susceptibility SNPs or MYC using pyrosequencing among 80 Caucasian men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. For the 60 CpG sites meeting quality control, which also demonstrated temporal stability over a 5-year period, we calculated pairwise Spearman correlations for DNA methylation levels at each CpG site with 42 8q24 cancer susceptibility SNPs. To account for multiple testing, we adjusted P values into q values reflecting the false discovery rate (FDR). In contrast to the MYC CpG sites, most sites nearby the SNPs demonstrated good reproducibility, high methylation levels, and moderate-high between-individual variation. We observed 10 statistically significant (FDR < 0.05) CpG site–SNP correlations. These included correlations between an intergenic CpG site at Chr8:128393157 and the prostate cancer SNP rs16902094 (ρ = −0.54; P = 9.7 × 10−7; q = 0.002), a PRNCR1 CpG site at Chr8:128167809 and the prostate cancer SNP rs1456315 (ρ = 0.52; P = 1.4 × 10−6; q = 0.002), and two POU5F1B CpG sites and several prostate/colorectal cancer SNPs (for Chr8:128498051 and rs6983267, ρ = 0.46; P = 2.0 × 10−5; q = 0.01). This is the first report of correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk. Cancer Prev Res; 7(12); 1282–92. ©2014 AACR.
Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
Authors: Wan Lei , Tan Hsueh-Li , Thomas-Ahner Jennifer M. , Pearl Dennis K. , Erdman John W. , Moran Nancy E. , Clinton Steven K.
Published: October 2014

Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer–related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation–related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. Cancer Prev Res; 7(12); 1228–39. ©2014 AACR.
The Human Cathelicidin LL-37 Host Defense Peptide Upregulates Tight Junction-Related Proteins and Increases Human Epidermal Keratinocyte Barrier Function
Authors: Akiyama Toshihiro , Niyonsaba François , Kiatsurayanon Chanisa , Nguyen Toan The , Ushio Hiroko , Fujimura Tsutomu , Ueno Takashi , Okumura Ko , Ogawa Hideoki , Ikeda Shigaku
Published: October 2014

Both psoriasis and atopic dermatitis (AD) are not only associated with an impaired stratum corneum barrier, but also with abnormal expression of the tight junction (TJ) proteins. Because host defense peptides, including LL-37, are overexpressed in lesional psoriatic skin but are downregulated in lesional AD skin, we hypothesized that LL-37 might regulate the TJ function in keratinocytes. We demonstrated that LL-37 selectively increased the expression of several claudins and occludin, and enhanced their membrane distribution. Furthermore, LL-37 elevated the transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers, and this activity was weakened by the claudin inhibitor ochratoxin A. A characterization of the molecular mechanism underlying the regulation of the TJ barrier by LL-37 revealed that LL-37 induced the activation of the Rac1, atypical PKC, glycogen synthase kinase-3 and PI3K pathways, and the specific inhibition of these pathways reversed the LL-37-mediated regulation of TJ function. In addition, LL-37 enhanced the expression of differentiation markers under the control of ochratoxin A, suggesting an association between LL-37-induced TJ function and keratinocyte differentiation. These data provide novel evidence that, in addition to its antimicrobial and other immunoregulatory functions, LL-37 contributes to cutaneous immunity by strengthening the skin's barrier function.
Cystic Fibrosis Sputum DNA Has NETosis Characteristics and Neutrophil Extracellular Trap Release Is Regulated by Macrophage Migration-Inhibitory Factor
Authors: Dwyer Markryan , Shan Qiang , D'Ortona Samantha , Maurer Rie , Mitchell Robert , Olesen Hanne , Thiel Steffen , Huebner Johannes , Gadjeva Mihaela
Published: October 2014

Neutrophils are the main proinflammatory cell type in chronically infected lungs of cystic fibrosis (CF) patients; however, they fail to effectively clear the colonizing pathogens. Here, we investigated the molecular composition of non-mucoid and mucoid Pseudomonas aeruginosa-induced neutrophil extracellular traps (NETs) in vitro and compared them to the DNA-protein complexes present in the CF sputum. The protein composition of P. aeruginosa-induced NET fragments revealed that irrespective of the inducing stimuli, NET fragments were decorated with a conserved set of proteins. The DNA-protein complexes derived from CF sputum were consistent with NETosis and shared a similar protein signature, suggesting that the majority of the extracellular DNA was NET derived. The ability of polymorphonuclear leukocytes to produce NETs in response to P. aeruginosa was driven by macrophage migration-inhibitory factor (MIF) by promoting mitogen-activated protein kinase. Analysis of 132 CF patient samples revealed that elevated MIF protein levels correlated with poorer lung function. We suggest that targeting MIF by small molecular inhibitors might reduce the presence of extracellular DNA and serve as an adjunct to the use of antimicrobial drugs that could ultimately reduce bacterial fitness in the lungs during the later stages of CF disease.
Complement Protein C1q and Adiponectin Stimulate Mer Tyrosine Kinase-Dependent Engulfment of Apoptotic Cells through a Shared Pathway
Authors: Galvan Manuel D. , Hulsebus Holly , Heitker Thomas , Zeng Erliang , Bohlson Suzanne S.
Published: October 2014

The failure to clear apoptotic cells is linked to defects in development and autoimmunity. Complement component C1q is required for efficient engulfment of apoptotic cells (efferocytosis), and C1q deficiency leads to the development of lupus. We recently identified a novel molecular mechanism for C1q-dependent efferocytosis in murine macrophages. C1q elicited the expression of Mer tyrosine kinase (Mer), a receptor that regulates efficient efferocytosis and prevention of autoimmunity. To characterize the C1q-dependent signal transduction mechanism, pathway analysis of the transcriptome from C1q-activated macrophages was performed, and it identified the adiponectin signaling pathway as significantly upregulated with C1q. Adiponectin is structurally homologous to C1q and regulates cellular metabolism via downstream activation of 5′adenosine monophosphate-activated protein kinase (AMPK). Macrophage stimulation with C1q resulted in the activation of AMPK, and silencing of AMPK expression using siRNA-inhibited C1q-dependent efferocytosis. Adiponectin signaling also stimulates activation of nuclear receptors, and inhibition of the nuclear receptor retinoid X receptor abrogated C1q-dependent Mer expression and efferocytosis. Furthermore, adiponectin elicited Mer expression and Mer-dependent efferocytosis in macrophages similar to cells stimulated with C1q. Collectively, our results suggest that C1q and adiponectin share a common signal transduction cascade to promote clearance of apoptotic cells, and identify a novel molecular pathway required for efficient efferocytosis.
No Evidence of Mammary Tumor Virus env Gene-Like Sequences among Iranian Women with Breast Cancer
Authors: Ahangar Oskouee Mahin , Shahmahmoodi Shohreh , Jalilvand Somayeh , Mahmoodi Mahmood , Ziaee Abed-Ali , Esmaeili Heidar Ali , Mokhtari-Azad Talat , Yousefi Maryam , Mollaei-Kandelous Yaghoob , Nategh Rakhshandeh
Published: October 2014

Objective: The mouse mammary tumor virus (MMTV) is the well-established etiological agent of mammary tumors in mice. A series of studies have implicated that a human murine mammary tumor virus-like virus occurs in human breast cancer, but it is unclear whether it has any causal role. Methods: The aim of the present study was to investigate the presence of MMTV env gene-like sequences in a group of Iranian women with or without breast cancer. A total of 65 breast cancer and 65 noncancerous breast specimens from the Department of Pathology of Tabriz University in East Azerbaijan, Iran, were analyzed by nested PCR. Results: All breast cancer and benign breast samples were negative for MMTV env gene-like DNA. Conclusion: These results indicate that the MMTV env gene-like virus may not play a significant role in the etiology of breast cancer among Iranian women.
Outcomes of Infected Cardiovascular Implantable Devices in Dialysis Patients
Authors: Opelami Oluwaseun , Sakhuja Ankit , Liu Xiaobo , Tang W.H. Wilson , Schold Jesse D. , Navaneethan Sankar D.
Published: October 2014

Background/Aims: Dialysis patients are at a higher risk for cardiovascular implantable electronic device (CIED) infection-related hospitalizations. We compared the outcomes and cost for dialysis and non-dialysis patients hospitalized with CIED infections. Methods: We conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) discharge records from 2005 to 2010. Patients with CIED infections were identified using ICD-9 codes for device-related infections or device procedure along with bacteremia, endocarditis or systemic infection. Dialysis patients were identified using ICD-9 codes. Multivariable logistic and linear regressions were performed to examine in-hospital mortality, length of stay and cost. Results: Of the 87,798 estimated hospitalizations with CIED infections, 6,665 (7.6%) were dialysis patients. CIED-infection-related hospitalization has increased over time among dialysis patients. In-hospital mortality was higher among dialysis patients (13.6% vs. 5.9%, p < 0.001). In the multivariable model, dialysis patients had higher odds of in-hospital mortality (odds ratio 1.98; 95% CI: 1.6, 2.4) compared to the non-dialysis group. Dialysis patients had a longer median length of stay (12 days vs. 7 days, p < 0.001) and majority required extended care facility upon discharge (51.2% vs. 35.0%, p < 0.001) compared to the non-dialysis group. Dialysis status was associated with 50.3% increased cost of hospitalization (p < 0.001). Conclusion: CIED-infection related hospitalization is increasing among patients undergoing dialysis and is associated with higher in-hospital mortality, longer hospital stay and higher costs of hospitalization. Future studies should examine the reasons for such a high risk and find means to improve outcomes in dialysis population.
Increased Dialysate MCP-1 is Associated with Cardiovascular Mortality in Peritoneal Dialysis Patients: A Prospective Observational Study
Authors: Ko Kwang Il , Park Kyoung Sook , Lee Mi Jung , Doh Fa Mee , Kim Chan Ho , Koo Hyang Mo , Oh Hyung Jung , Park Jung Tak , Han Seung Hyeok , Kang Shin-Wook , Yoo Tae-Hyun
Published: October 2014

Background: The aim of this study was to investigate the association between the dialysate MCP-1 (dMCP-1) and systemic inflammatory and nutritional markers in peritoneal dialysis (PD) patients. In addition, we examined the prognostic value of dMCP-1 on all-cause or cardiovascular mortality in these patients. Methods: We prospectively followed 169 prevalent PD patients from April 1st 2008 to December 31st 2012. At baseline, dMCP-1 and serum biochemical parameters including high sensitivity CRP (hs-CRP) and albumin were checked. All-cause mortality and cause of death were evaluated during the follow-up period. Based on the median level of dMCP-1, patients were classified as either low or high dMCP-1 groups. Results: Mean age, hs-CRP, and D/Pcr ratio at 4 h were significantly higher, while serum albumin levels and %lean body mass (LBM) were significantly lower in the high dMCP-1 group. During the mean follow-up period of 47.7 months, all-cause mortality and cardiovascular mortality rate were significantly higher in the high dMCP-1 group (9.6 and 6.3 per 100 person-years, respectively) compared to the low dMCP-1 group (5.1 and 3.1 per 100 person-years, respectively; p = 0.021, 0.038). In multivariate Cox analysis, high dMCP-1 was a significant independent predictor of all-cause mortality (hazard ratio: 1.83, 95% confidence interval: 1.03-3.24, p = 0.039). Conclusions: dMCP-1 levels are closely correlated with nutritional and systemic inflammatory markers in PD patients. In addition, increased dMCP-1 is significantly associated with higher all-cause and cardiovascular mortality. These findings suggest that local peritoneal inflammation could contribute to poor clinical outcomes in PD patients.
Verrucous Oesophageal Carcinoma: Single Case Report and Case Series Including 15 Patients - Issues for Consideration of Therapeutic Strategies
Authors: Behrens Angelika , Stolte Manfred , Pech Oliver , May Andrea , Ell Christian
Published: October 2014

Background: Verrucous carcinomas (VC) of the oesophagus are a rarity. Due to their histological resemblance to squamous cell carcinoma, the diagnostic and treatment standards applicable to the latter have so far also been applied to VC as a disease entity. Quite limited data are available including two case series of 5 or 11 patients. The present study reports on a single case treated by local endoscopic therapy and a series of 15 patients, 9 of whom received local endoscopic therapy. Methods: The data for patients diagnosed with VC of the oesophagus who had been treated from January 1999 to May 2011 were analysed retrospectively. Results: 15 patients with the diagnosis of oesophageal VC were included. The male-female ratio was 3:1. 9 of 11 pT1-VC patients presented with the cardinal symptom dysphagia or odynophagia. For the majority of the patients, the growth pattern is one of extensive superficial expansion showing a median length of 9 cm (range: 2-22 cm). Surprisingly, none of the VC patients showed lymph node or distant metastasis. 9 of 15 VC patients received local endoscopic therapy; 4 were treated with curative intent and 5 were treated palliatively. 3 patients underwent oesophageal resection, and definitive chemoradiotherapy was administered in a further 3 patients. One severe complication, consisting of a postoperative anastomotic insufficiency with a fatal outcome, occurred in this group of patients. Conclusion: This is the largest published study describing patients diagnosed with VC of the oesophagus so far. The option of local endoscopic therapy and its results in 9 patients are reported for the first time. The superficial growth pattern of the tumour and the frequent absence of lymph node or distant metastasis suggest that endoscopic resection can be carried out as a diagnostic and/or therapeutic approach. Due to the rarity of this entity, the case numbers are unfortunately so limited that evidence-based recommendations are unlikely to become available even in the future.
Validity of Acute Stroke Lesion Volume Estimation by Diffusion-Weighted Imaging–Alberta Stroke Program Early Computed Tomographic Score Depends on Lesion Location in 496 Patients With Middle Cerebral Artery Stroke
Authors: Schröder Julian , Cheng Bastian , Ebinger Martin , Köhrmann Martin , Wu Ona , Kang Dong-Wha , Liebeskind David S. , Tourdias Thomas , Singer Oliver C. , Christensen Soren , Campbell Bruce , Luby Marie , Warach Steven , Fiehler Jens , Fiebach Jochen B. , Gerloff Christian , Thomalla Götz , Albers Gregory , Davis Stephen , Donnan Geoffrey , Fisher Marc , Furlan Anthony , Grotta James , Hacke Werner , Kidwell Chelsea , Koroshetz Walter , Lees Kennedy R. , Lev Michael , Sorensen A. Gregory , Thijs Vincent , Wardlaw Joanna , Wintermark Max , Hao Qing , Kim Jong S. , Breuer Lorenz , Treszl Andras , Forkert Nils D. , Galinovic Ivana , Rosenkranz Michael , Engelhorn Tobias , Endres Matthias , Dousset Vincent
Published: October 2014

Background and Purpose—

Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL.

Methods—

We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume.

Results—

A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (
r
=–0.78;
P
<0.0001). With regards to lesion localization, correlation was weaker in deep MCA region (
r
=–0.19;
P
=0.038) when compared with superficial (
r
=–0.72;
P
<0.001) or combined superficial and deep MCA lesions (
r
=–0.72;
P
<0.001). Receiver-operating characteristics analysis revealed ASPECTS≤6 as best cutoff to identify ≥100-mL DWI lesion volume; however, positive predictive value was low (0.35).

Conclusions—

ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.
Sexual selection by female choice prevents speciation reversal in a hybridizing trio of mormyrid fish in southern Africa: evidence from playback experiments of electric organ discharges
Authors: Schmid Daniela , Kramer Leo Bernd
Published: October 2014

We studied the question of whether or not female choice among variant forms of species-specific male advertising signals, electric organ discharges (EODs), is a factor in preventing panmixy in a parapatric sibling complex of three species of mormyrid fish, inhabiting three parallel rivers in southern Africa. The three species’ EODs are characteristically differentiated in waveform. The Upper Zambezi River is inhabited by Pollimyrus marianne Kramer, van der Bank, Flint, Sauer-Gürth & Wink, 2003, the Okavango River by P. castelnaui (Boulenger, 1911), and the smaller Kwando River in their middle by P. cuandoensis Kramer, van der Bank & Wink, 2013, which is their hybrid species of unidirectional origin. P. castelnaui females ( out of 5) and P. marianne females ( of 5) responded stronger to playback of the EODs of male conspecifics compared to those of male P. cuandoensis. Pollimyrus castelnaui and P. marianne females neither preferred nor discriminated against the male EODs of each other’s species, respectively (one exception). The single P. cuandoensis female available preferred a P. marianne male EOD over one of its own species, and was neutral in all other tests. This suggests that female resistance in the two main system species to P. cuandoensis male EODs is an evolved one, effectively limiting hybridization to the Kwando. The females of the two main system species, P. castelnaui and P. marianne, thus prevent panmixy in the Okavango and the Zambezi, respectively, thereby keeping up the three-sibling species complex by discriminating female choice against P. cuandoensis males in the Okavango-Kwando-Zambezi system.
Anti-snake behaviour in a facultative cooperative breeder, the Cape ground squirrel
Authors: Phillips M.A. , Waterman J.M.
Published: October 2014

Predator harassment is an anti-predator behaviour that may increase an individual’s risk of predation, as individuals approach, threaten and harass a potential predator, yet this behaviour is still not well understood. The Cape ground squirrel (Xerus inauris) is a highly social facultative cooperative breeder from southern Africa that harasses several species of venomous snakes. We examined whether harassment was part of alloparental care by comparing harassment behaviours among different age and sex classes in Cape ground squirrel social groups. We also assessed how individuals adjusted their behaviour dependent on levels of risk by examining the Cape ground squirrel’s harassment behaviour among non-venomous, and two species of venomous snakes. We found adult females with emerged juvenile offspring took the most risk, harassing for longer durations and at higher intensities than other group members, suggesting that snake harassment was a maternal behaviour. Females with juvenile offspring only harassed the highest risk elapid snake but increased vigilance and inspection with increasing snake risk suggesting that the Cape ground squirrel can discriminate between different types of snake predators.
Body mass and attractivity of female offspring are negatively affected by food restriction of meadow vole (Microtus pennsylvanicus) dams during lactation
Authors: Sabau Ramona M. , Pierson Lyndsey , Ferkin Michael H.
Published: October 2014

The environment experienced by pups during lactation (nutrition and maternal behaviour) can contribute not only to sexual development, but also to individual differences in offspring sexual behaviour. We tested the hypothesis that female offspring of meadow vole dams (Microtus pennsylvanicus) that were 30% food restricted (FR) during days 1–7 of lactation (FR 1–7), days 8–14 of lactation (FR 8–14), or days 15–21 of lactation (FR 15–21) show negative effects on their food intake, growth, and the three components of sexual behaviour (attractivity, proceptivity and receptivity) as compared with female offspring of control dams. With the exception of age 29 days or age 34 days, the body weights of female offspring of FR 1–7 dams and FR 8–14 dams between days 21 and 48 were lower than the body weights of female offspring of FR 15–21 dams and those of control dams. Female offspring of FR 1–7 dams maintained a lower body weight than the other female offspring throughout the study. Female offspring of FR 8–14 and FR 15–21 dams produced odours that were less attractive to males than odours produced by those of FR 1–7 and control dams. Female offspring of FR dams and control dams did not differ in their measures of proceptivity and receptivity. However, the total amount of time allocated for copulation by males was shorter for those males that were paired with female offspring of FR 1–7 dams than it was for those that were paired with the female offspring of FR 8–14, FR15–21, and control dams. The results of this study, coupled with those found in a study conducted on the male offspring of FR dams, indicate that for female offspring days 1–7 and for male offspring days 8–14 of lactation are the time periods during which food restriction of dams had the greatest impact on deficits in sexual behaviour and body mass in meadow voles.
Animated images as a tool to study visual communication: a case study in a cooperatively breeding cichlid
Authors: Fischer Stefan , Taborsky Barbara , Burlaud Rebecca , Fernandez Ahana Aurora , Hess Sybille , Oberhummer Evelyne , Frommen Joachim G.
Published: October 2014

Investigating the role of visual information in animal communication often involves the experimental presentation of live stimuli, mirrors, dummies, still images, video recordings or computer animations. In recent years computer animations have received increased attention, as this technology allows the presentation of moving stimuli that exhibit a fully standardized behaviour. However, whether simple animated 2D-still images of conspecific and heterospecific stimulus animals can elicit detailed behavioural responses in test animals is unclear thus far. In this study we validate a simple method to generate animated still images using PowerPoint presentations as an experimental tool. We studied context-specific behaviour directed towards conspecifics and heterospecifics, using the cooperatively breeding cichlid Neolamprologus pulcher as model species. N. pulcher did not only differentiate between images of conspecifics, predators and herbivorous fish, but they also showed adequate behavioural responses towards the respective stimulus images as well as towards stimulus individuals of different sizes. Our results indicate that even simple animated still images, which can be produced with minimal technical effort at very low costs, can be used to study detailed behavioural responses towards social and predatory challenges. Thus, this technique opens up intriguing possibilities to manipulate single or multiple visual features of the presented animals by simple digital image-editing and to study their relative importance to the observing fish. We hope to encourage further studies to use animated images as a powerful research tool in behavioural and evolutionary studies.
Wealth Accumulation in an Urban Context
Authors: Kotzageorgis Phokion , Papastamatiou Demetrios
Published: October 2014

By examining the fortunes of the 57 richest Muslims in Thessaloniki in the eighteenth century, this paper aims to contribute to the discussion on wealth accumulation in Ottoman lands. Basing our research on the probate inventories of the city, we attempt to delineate the profile of the rich in Thessaloniki. Our conclusions underline the role of credit and çiftlik exploitation in capital formation in the city. Furthermore, we suggest a distinct pattern regarding the existence or non-existence of magnate families in the Balkans which was distinct from the position in the Arab lands of the empire.
Editing the Fihrist of Ibn al-Nadīm
Authors: Stewart Devin J.
Published: October 2014

Arabic and Islamic studies, whether of the Abbasid or later periods, suffer from the lack of reliable editions of fundamental resources such as al-Ṭabarī’sTārīkh al-rusul wa-l-mulūk, al-Masʿūdī’sMurūj al-dhahab wa-maʿādin al-jawhar, Abū l-Faraj al-Iṣbahānī’sKitāb al-Aghānī, and others, despite a long history of scholarly interest in, and intensive use of these particular texts. The appearance in 2009 of the new edition of theFihristof Ibn al-Nadīm (d. 380/990) by Ayman Fuʾād Sayyid (hereafterafs) provides an opportunity to reflect on this general problem by considering the historical progress made in the editing and contextualization of this text that is central to the understanding of Abbasid history and letters and to nearly all the intellectual traditions that had arisen in the Islamic world by the fourth/tenth century. As will become clear, the complex history of scholarship on theFihristis an object lesson on the problem of failing adequately to take into account the work of earlier editors and scholars, made particularly difficult in this case by linguistic barriers and limited access to widely scattered publications. The following remarks attempt to reviewafs’s edition of theFihrist, to compare the views ofafs, the Russian scholar Valeriy V. Polosin, and others regarding the context and background of theFihrist, and to give an overview of the current state of knowledge about Ibn al-Nadīm and theFihrist. It will be argued that, beyond reliably publishing the contents of the earliest extant manuscript of theFihrist, substantial emendations to the text are required to produce a reliable edition of the work. An evaluation ofafs’s emendations to the text is followed by a number of additional proposed emendations.
Re-establishment of the name Pombalia, and new combinations from the polyphyletic Hybanthus (Violaceae)
Authors: De Paula-Souza Juliana , Ballard, Jr. Harvey Eugene
Published: October 2014

This paper introduces the re-establishment of Pombalia Vand., the earliest generic designation for the predominantly South American lineage of the polyphyletic Hybanthus Jacq. (Violaceae). Recent molecular-based phylogenies and ongoing morphological studies have resulted in the recognition of 41 species and one variety in this group, requiring their transfer to the currently monotypic Pombalia, as proposed here. The study also revealed the necessity to lectotypify 20 of the basionyms.
Abies jaliscana (Pinaceae): A new combination in section Grandis and a key to the species of Abies in western Mexico
Authors: Vazquez-García J. Antonio , Shalisko Viacheslav , Cuevas-Guzmán Ramon , Muñiz-Castro Miguel A. , Manilla-Blandón Mauricio R.
Published: October 2014

Recent morphological and phenological data support recognition of Abies jaliscana (Martínez) Mantilla, A. Vázquez & Shalisko at the species level. A key to distinguish A. jaliscana from other species of Abies in western Mexico is provided.
Erythroxylum sobraleanum (Erythroxylaceae): A new species from Southeastern Brazil
Authors: Loiola Maria Iracema Bezerra , Cordeiro Luciana Silva
Published: October 2014

Erythroxylum sobraleanum (Erythroxylaceae) is described and illustrated as a new species from Minas Gerais, Southeastern Brazil, and positioned in Erythroxylum sect. Archerythroxylum. This species grows in the Seasonal semi-deciduous montane forest, on the Serra da Mantiqueira. It is recognized by the long-triangular stipules, non-striate, membranaceous, 3-setulose, with fimbriolate to entire margin, leaves membranaceous, flowers at the apex of short shoots, and styles connate 2/3 its length in dolichostylous flowers. Affinity relationships with other species of Erythroxylum are presented and discussed.
Cheirimedon foscae sp. nov. (Amphipoda: Lysianassidae: Tryphosinae) from the deep sea Campos Basin, Southwestern Atlantic Ocean
Authors: SIQUEIRA SILVANA GOMES L. , SEREJO CRISTIANA S.
Published: October 2014

A new species of lysianassid amphipod belonging to the genus Cheirimedon was collected on the continental slope of the Campos Basin, the largest oil reserve in Brazilian waters. This is the first record of the genus Cheirimedon from the Atlantic Ocean, which was previously restricted to the Antarctic and Tasmanian sea. The new species is fully illustrated and compared with related species. Additionally, a world key to the Cheirimedon species is provided.
A new species of Canace Haliday from Portugal, with a revised key to species (Diptera: Canacidae: Canacinae)
Authors: MUNARI LORENZO , ALMEIDA JORGE MOTA
Published: October 2014

A new species of Canace Haliday, in Curtis, 1837 from Portugal is described. This species, related to C. actites Mathis, 1982, is known so far from a single maritime locality near Lisbon. A key to species of the genus is also provided.
Feedbacks of Sea Surface Temperature to Wintertime Storm Tracks in the North Atlantic
Authors: Gan Bolan , Wu Lixin
Published: October 2014

In this study, the lagged maximum covariance analysis is performed on winter storm-track anomalies, represented by the meridional heat flux by synoptic-scale (2–8 days) transient eddies and sea surface temperature (SST) anomalies in the North Atlantic, which are both derived from reanalysis datasets spanning the twentieth century. The analysis shows significant seasonal and interannual coupling between storm-track and SST variations. On seasonal time scales, it is found that SST anomalies in the preceding early winter (November–December), which are expected to change the lower-tropospheric baroclinicity, can significantly influence storm tracks in early spring (March); that is, an intensification and slight northward shift of storm tracks in response to a midlatitude SST dipole, with a cold pole centered to the southeast of Newfoundland and a warm pole in the western subtropical Atlantic. This storm-track response pattern is similar to the storm-track forcing pattern in early spring, which resembles the dominant mode of storm tracks. At interannual time scales, it is found that the wintertime (January–March) storm-track and SST anomalies are mutually reinforced, manifesting as a zonal-dipole-like pattern in storm-track anomalies (with dominant negative anomalies in the downstream) coupled with a midlatitude SST monopole (with warm anomalies centered to the south and east of Newfoundland).
Satellite and Argo Observed Surface Salinity Variations in the Tropical Indian Ocean and Their Association with the Indian Ocean Dipole Mode
Authors: Du Yan , Zhang Yuhong
Published: October 2014

This study investigates sea surface salinity (SSS) variations in the tropical Indian Ocean (IO) using the Aquarius/Satelite de Aplicaciones Cientificas-D (SAC-D) and the Soil Moisture and Ocean Salinity (SMOS) satellite data and the Argo observations during July 2010–July 2014. Compared to the Argo observations, the satellite datasets generally provide SSS maps with higher space–time resolution, particularly in the regions where Argo floats are sparse. Both Aquarius and SMOS well captured the SSS variations associated with the Indian Ocean dipole (IOD) mode. Significant SSS changes occurred in the central equatorial IO, along the Java–Sumatra coast, and south of the equatorial IO, due to ocean circulation variations. During the negative IOD events in 2010, 2013, and 2014, westerly wind anomalies strengthened along the equator, weakening coastal upwelling off Java and Sumatra and decreasing SSS. South of the equatorial IO, an anomalous cyclonic gyre changed the tropical circulation, which favored the eastward high-salinity tongue along the equator and the westward low-saline tongue in the south. An upwelling Rossby wave favored the increase of SSS farther to the south. During the positive IOD events in 2011 and 2012, the above-mentioned processes reversed, although the decrease of SSS was weaker in magnitude.