bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-236: Imprime PGG conjugated directly to protein enables cross-presentation of antigen that generates multifunctional cytotoxic T cells
Authors: Fulton Ross B. , Leonardo Steven , Michel Kyle , Wurst Lindsay , Phelon Trinda , Danielson Mike , Gorden Keith
Published: August 2015

Imprime PGG is a soluble yeast-derived β-1,3/1,6 glucan innate immune cell modulator that is in phase 3 and multiple phase 2 clinical trials in combination with complement activating monoclonal antibodies (e.g. bevacizumab, cetuximab). We have previously shown that Imprime binds to complement receptors and modulates the function of a variety of immune cells, including monocytes, neutrophils, and B cells. We have also demonstrated that Imprime PGG binds to various subsets of dendritic cells (DCs) and can cause intermediate upregulation of MHC class II and the co-stimulatory molecules CD80/86 critical for antigen presentation and T cell activation. Based on these findings, we hypothesized that Imprime PGG conjugated to a protein would efficiently deliver antigen to DCs and prime a cytotoxic CD8+ T cell response.

To test this hypothesis, we employed the model antigen chicken ovalbumin (OVA) in a C57BL/6 mouse model to examine the generation of OVA-specific CD8+ T cell responses. We covalently linked OVA to Imprime PGG to generate a β-glucan/protein conjugate (Imprime-OVA). Using T cell receptor transgenic OT-I CD8+ T cells to track responses to OVA, we treated mice with Imprime-OVA intravenously and examined the expansion and functional quality of the T cell response 7 days later at the peak of expansion. Following Imprime-OVA treatment, OVA-specific CD8 T cells underwent vigorous expansion, upregulated the transcription factor Tbet, which is central to developing effector functions, and gained the ability to produce the cytokines IFN-γ, TNF-α and IL-2. By comparison, OVA alone did not generate a functional CD8+ T cell response and instead induced anergy. To determine if cross-presenting DCs are required for CD8+ T cell activation, we used mice deficient in the transcription factor Batf3, which selectively eliminates CD8α+ cross-presenting DCs. Following treatment with the Imprime-OVA conjugate in these Batf3-/- mice, the expansion of OVA-specific CD8+ T cells was more than 10-fold reduced compared to that in wild-type mice. Further, these cells failed to develop effector functions, indicating that CD8α+ cross-presenting DCs are crucial for this response. Together, these data show that an Imprime PGG-protein conjugate can effectively elicit the expansion and functional activation of cytotoxic T cells and may have utility as a potential cancer vaccine platform.

Citation Format: Ross B. Fulton, Steven Leonardo, Kyle Michel, Lindsay Wurst, Trinda Phelon, Mike Danielson, Keith Gorden. Imprime PGG conjugated directly to protein enables cross-presentation of antigen that generates multifunctional cytotoxic T cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-236. doi:10.1158/1538-7445.AM2015-LB-236
Abstract LB-240: SMARCE1 suppresses EGFR expression and controls responses to MET and ALK inhibitors in lung cancer
Authors: Papadakis* Andreas , Sun* Chong , Knijnenburg Theo , Xue Yibo , Grernrum Wipawadee , Hölzel Michael , Nijkamp Wouter , Wessels Lodewyk , Beijersbergen Roderick , Bernards# Rene , Huang# Sidong
Published: August 2015

Recurrent inactivating mutations in components of SWI/SNF chromatin-remodelling complexes have been identified across cancer types, supporting their roles as tumour suppressors in modulating oncogenic signalling pathways. We report here that SMARCE1 loss induces EGFR expression and confers resistance to MET and ALK inhibitors in non-small cell lung cancers (NSCLCs). We found that SMARCE1 binds to regulatory regions of the EGFR locus and suppresses EGFR transcription in part through regulating expression of Polycomb Repressive Complex component CBX2. Addition of the EGFR inhibitor gefitinib restores the sensitivity of SMARCE1 knockdown cells to MET and ALK inhibitors in NSCLCs. Our findings link SMARCE1 to EGFR oncogenic signalling and suggest targeted treatment options for SMARCE1 deficient tumours.

ACKNOWLEDGEMENTS: *Equal contribution. #Corresponding authors. This work was supported by grants from Canadian Institutes of Health Research (CIHR) grant MOP-130540 (S.H.), Canada Research Chair (CRC), the European Research Council (ERC), the Dutch Cancer Society (KWF), the EU COLTHERES project and grants by the Netherlands Organization for Scientific Research (NWO) to the Cancer Genomics Center Netherlands (CGC.NL).

Citation Format: Andreas Papadakis*, Chong Sun*, Theo Knijnenburg, Yibo Xue, Wipawadee Grernrum, Michael Hölzel, Wouter Nijkamp, Lodewyk Wessels, Roderick Beijersbergen, Rene Bernards#, Sidong Huang#. SMARCE1 suppresses EGFR expression and controls responses to MET and ALK inhibitors in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-240. doi:10.1158/1538-7445.AM2015-LB-240
Abstract LB-270: Screening of novel phytochemical/s that can protect breast epithelial cells from PhIP induced cytotoxicity
Authors: Jain Ashok K.
Published: August 2015

Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is a known food carcinogen abundantly found in cooked meat. Several studies have shown that PhIP can induce tumors in breast, prostate and colon cells and rodent models. Metabolism of PhIP results in the formation of free radicals (ROS) and PhIP metabolites are known to produce DNA adduct and DNA strand breaks. The metabolism and mutational effects of PhIP are well defined. Phytochemicals are known to inhibit cytotoxic and genotoxic effects. Therefore, we hypothesized that the right combination of antioxidants and or phytochemical (naturally present in fruits, vegetables and spices) along with grilled meat should be capable of suppressing the PhIP induced cytotoxicity and development of breast cancer. Therefore, a model system using human breast epithelial cells (MCF 10A) was developed to mimic the cellular changes and test various antioxidants in presence or absence of PhIP. We have tested four vitamins (C, K3, D3, and E), Gingerol (6 and 10), N-acetyl cysteine, glutathione and curcumin at varying concentrations. The protective effect of these compounds was evaluated using cell viability assay, DCF assay to quantify ROS production, Comet assay to quantify the DNA damage and DNA adduct formation by immunofluorescence method. Results indicate that presence of these compounds improves cell viability as compared to PhIP treated group. However, curcumin showed significant differences and PhIP induced cell cytotoxicity was consistently reverted to normal in presence of Curcumin. Gene expression analysis using RT PCR technique indicates that curcumin interact via multi molecular targets. Hence, the present study suggests that Curcumin is a promising natural compound to regress the effect of PhIP induced cell cytotoxicity in breast cells.

Citation Format: Ashok K. Jain. Screening of novel phytochemical/s that can protect breast epithelial cells from PhIP induced cytotoxicity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-270. doi:10.1158/1538-7445.AM2015-LB-270
Abstract LB-276: Effect of lay health worker intervention on complinace of hepatitis B vaccinations in Asian Americans: Randomizd control trial
Authors: Juon Hee-Soon , Kim Frederic , Strong Carol , Park Eunmi
Published: August 2015

Background/Context: Asian Americans are at high risk with contracting the Hepatitis B virus (HBV). There are preventive measures with vaccinations that could be administered. However, there are several barriers that preclude Asian Americans from receiving the proper care.

Purpose: To implement lay health worker (LHW) telephone intervention using randomized control trial.

Setting: Asian American community-based organizations in the Baltimore-Washington Metropolitan area from April 2013 to March 2014.

Participants: 232 Asian American adults who were unprotected and 18 years of age or older.

Intervention: Calling those in the intervention group to remind to receive a 3-shot series for HBV vaccinations at month 1, 2, and 5.

Data collection/analysis: In a parent study, 600 Asian Americans participated in study by completing pretest, reading photo novel, and doing free Hepatitis B screening. A week later, participants received the results (i.e., protected, unprotected, and infected). In this study, those unprotected was assigned to either intervention or control group. The intervention group received the LHW intervention. Seven months after the pretest, those unprotected (n = 187) were followed by phone. The outcome measure was whether they had received a series of vaccines over 6 months with 3 groups (none, 1 or 2 vaccines, and completed). Multinomial logistic regressions were used.

Results: We found that those in the intervention group were more likely to have 1 or more vaccines than the control group, compared to no vaccination group (OR = 3.04, 95% CI, 1.16, 8.00). Also, those in the intervention group were more likely to complete a series of vaccinations than the control group, compared to no vaccination group (OR = 7.29, 95% CI 3.39, 5.67). We also found that time is the most important barriers preventing them from seeking hepatitis B vaccinations.

Conclusion: The LHW intervention was successful in increasing the chances to protect them from HBV infection in high risk group of Asian Americans. This study suggests that it is very critical to implement this culturally integrated LHW intervention program to reduce liver cancer health disparities among Asian Americans.

Mulitivariate mulitinomial logistic regression model for having hepatitis B vaccinations (n = 187)None vs. 1or 2 vaccinesNone vs completedOR (95% CI)OR (95% CI)Control1.001.00Intervention3.04 (1.16, 8.00)7.29 (3.39, 5.67)

Citation Format: Hee-Soon Juon, Frederic Kim, Carol Strong, Eunmi Park. Effect of lay health worker intervention on complinace of hepatitis B vaccinations in Asian Americans: Randomizd control trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-276. doi:10.1158/1538-7445.AM2015-LB-276
Abstract LB-279: Quantitative flux measurements of serum protein catabolism in PDAC and other KRAS-mutant cancers
Authors: Nofal Michel , Zhang Kevin , Rabinowitz Josh
Published: August 2015

Activating KRAS mutations are prevalent in human cancer and are associated with poor prognosis. Among these malignancies is pancreatic ductal adenocarcinoma (PDAC), which is universally KRAS-driven and almost universally lethal. PDAC tumors are extremely fibrotic and hypovascularized, limiting perfusion of nutrients into the tumor, and tumor cells exhibit an altered metabolic program to support survival and proliferation in this environment. One metabolic activity upregulated in these tumor cells is the uptake and catabolism of serum protein. This process yields a substantial alternative source of amino acids and can support the proliferation of cultured cells lacking free essential amino acids. However, existing methods for assaying the uptake and degradation of intact protein provide qualitative outputs, and as such, do not yield accurate estimates of flux from serum protein to amino acid monomers. Here, we present a method for quantitative measurement of the catabolic production of amino acids from serum protein in cultured cells. By culturing cells in medium containing fully 13C-labeled glucose and amino acids supplemented with unlabeled albumin, we distinguish amino acids taken up as monomers from the medium from serum protein-derived amino acids. Using a variant of classical metabolic flux analysis, we derive flux estimates for serum protein catabolism from measurements of amino acid abundance and isotopic labeling over time. Our method is highly sensitive (i.e. can estimate “baseline” serum protein catabolism in KRAS wild-type cell lines) and yields precise estimates of amino acid influx from serum protein for all proteinogenic amino acids. We have measured serum protein catabolism in a variety of cultured cell lines and find that protein catabolism yields amino acids in comparable amounts to conventional uptake in various pancreatic and non-pancreatic lines. This approach enables estimation of protein catabolic flux in any cell line and can be used to assay the effects of various genetic and pharmacological perturbations on serum protein catabolism with high sensitivity and while accounting for growth rate differences.

Citation Format: Michel Nofal, Kevin Zhang, Josh Rabinowitz. Quantitative flux measurements of serum protein catabolism in PDAC and other KRAS-mutant cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2015-LB-279
Abstract LB-287: iKnife in neurosurgery: intraoperative real-time, in vivo biochemical characterization of brain tumors with high spatial resolution
Authors: Vaqas Babar , Balog Julia , Roncaroli Federico , Takats Zoltan , O'Neill Kevin
Published: August 2015

The purpose of this study was to prove that rapid intraoperative tissue identification of brain tumours using Rapid Evaporative Ionization Mass Spectrometry (REIMS, used surgically as the iKnife) with high spatial resolution is possible in order to help establish a tissue diagnosis and to maximise the extent of tumour resection.

A single centre prospective observational study was designed involving a consecutive series of patients undergoing craniotomy and resection of WHO grade II, III and IV tumours. A neuronavigation system was used to register iKnife readings for the first time during surgery for brain tumour resection. Precise intraoperative readings from different tumour zones were taken and compared to matched core biopsy samples verified by routine histopathology.

This protocol worked well, allowing in-vivo mass spectrometry readings to be taken with accurate histology. Analysis of data from the first 6 cases shows distinct phospholipid spectral patterns for Grade II and IV tumours. An increased intensity of sulfatides were observed in the white matter of the grade II tumours.

Our neuronavigational platform for the iKnife has revealed unique in-vivo spectra for different intrinsic brain tumours. As more cases are added to our spectral database we hope to describe in-vivo intra-tumoural variations which may shed important light into intrinsic brain tumour biology.

Citation Format: Babar Vaqas, Julia Balog, Federico Roncaroli, Zoltan Takats, Kevin O'Neill. iKnife in neurosurgery: intraoperative real-time, in vivo biochemical characterization of brain tumors with high spatial resolution. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-287. doi:10.1158/1538-7445.AM2015-LB-287
Abstract LB-296: Small RNA profiling of human testicular germ cell tumor tissue samples shows abundant tRNA fragments and global loss of piRNA
Authors: Rounge Trine B. , Furu Kari , Skotheim Rolf , Haugen Trine B. , Enerly Espen , Grotmol Tom
Published: August 2015

Small non-coding RNAs play essential roles in tumorigenesis. However, their role in testicular germ cell tumor (TGCT), the most common malignancy in young males in most western countries, is largely unknown. In particular, a comprehensive analysis of the small RNA composition, including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), and tRNA-derived small RNAs and their interactions, are lacking. tRNA-derived small RNAs have been shown to bind to the piRNA-associated protein HIWI2, indicating crosstalk between small RNA pathways.

We have employed small RNA sequencing on 22 human TGCT samples from 5 histological subtypes, 3 carcinoma in situ, and 12 normal testis samples. The sequences from each sample group were analyzed according to sequence length, base composition, and their association with repeats, exons, tRNAs, piRNAs, and miRNAs. Most sequences 24-32 nucleotides in length, displayed piRNA characteristics. Expression analyses of the small RNA contigs demonstrated global loss of small RNAs in TGCT compared to normal testis.

A large proportion of the 33-36 nt RNA sequences derives from mature tRNAs, predominantly from the 5′ end. We did not identify differences in the expression of 5′ tRNA halves between normal and cancer tissue samples; however, 3 shorter 5′ tRNA fragments showed differential expression. Although components of the same pathways might be involved in piRNA and tRNA-derived small RNAs biogenesis, expression differences in TGCT samples suggest independent regulation of key components in response to the carcinogenic process.

Our results show subtype-specific microRNA expression, as well as a global loss of piRNAs in all TGCT histological subtypes when compared to normal testicular tissue. In addition, we document the presence of large amounts of tRNA-derived sequences in both TGCT and normal samples, which may provide new insight into the association between the tRNA fragments and piRNA biogenesis. These results may be valuable in the identification of new biomarkers for TGCT.

Citation Format: Trine B. Rounge, Kari Furu, Rolf Skotheim, Trine B. Haugen, Espen Enerly, Tom Grotmol. Small RNA profiling of human testicular germ cell tumor tissue samples shows abundant tRNA fragments and global loss of piRNA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-296. doi:10.1158/1538-7445.AM2015-LB-296
Abstract SY02-02: Shared risk factors for diabetes, cardiovascular disease, and cancer in a low-income population
Authors: Blot William J. , Hargreaves Margaret , Zheng Wei
Published: August 2015

Diabetes, cardiovascular disease (CVD) and cancer are the three most common chronic disease afflicting Americans today, but few investigations have compared and contrasted disease-specific risk factors, especially among low-income populations where incidence of the conditions is elevated. Herein we examine major lifestyle and social determinants of the illnesses, including cigarette smoking, obesity, physical activity, and socioeconomic status, and how they predict subsequent disease-specific mortality within the Southern Community Cohort Study (SCCS). The SCCS is tracking a population of approximately 85,000 adults age 40-79, two-thirds African American, recruited during 2002-2009 predominantly from community health centers (CHCs) across 12 southeastern states. Since CHCs provide basic health care and preventative services in underserved areas, the cohort comprises many individuals, both black and white, with low income and educational levels. Participants enrolling at CHCs were interviewed using a structured comprehensive questionnaire and then followed for mortality via linkage with the National Death Index. CVD and cancer were the leading causes among the nearly 7,500 deaths observed, and diabetes was reported by nearly 20% of participants at cohort entry. In Cox modeling, mortality hazard ratios (HRs) rose markedly and steadily with increasing cigarette smoking amounts for both CVD and cancer, but more so for cancer. HRs were elevated among the obese, but only mildly and only for CVD and not cancer. Diabetes prevalence, however, was very strongly and linearly related to body mass index (BMI), with 6- and 12-fold higher odds of diabetes among blacks and whites, respectively, with BMI ≥ 40 vs <25 kg/m2. HRs were modestly elevated among the most sedentary (and modestly decreased among the most physically active), more so for CVD than cancer. Low socioeconomic status, especially low income, was a strong (for CVD), modest (for diabetes) and weak (for cancer) risk factor. The findings indicate that these common diseases tend to share many of the same determinants, raising the possibility that mechanisms by which these exposures affect cardiovascular disease and diabetes may also relate to cancer risk and that public health measures aimed at other chronic diseases may have benefits for cancer prevention.

Citation Format: William J. Blot, Margaret Hargreaves, Wei Zheng. Shared risk factors for diabetes, cardiovascular disease, and cancer in a low-income population. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY02-02. doi:10.1158/1538-7445.AM2015-SY02-02
Abstract SY30-04: Can protein discovery with complete molecular specificity increase return on investment for cancer biomarkers
Authors: Kelleher Neil
Published: August 2015

Bottom-up proteomics relies on the use of proteases and is the method of choice for identifying thousands of protein groups in complex samples. Top-down proteomics has been shown to be robust for direct analysis of small proteins and offers a solution to the “peptide-to-protein” inference problem inherent with bottom-up. This talk will focus on the results in our recently accepted manuscript which describes the first large-scale integration of genomic, bottom-up and top-down proteomic data for comparative analysis of patient-derived mouse xenograft models of basal and luminal B human breast cancer, WHIM2 and WHIM16, respectively. Using these well-characterized xenograft models established by the National Cancer Institute Clinical Proteomic Tumor Analysis Consortium, we compared and contrasted the performance of bottom-up and top-down proteomics to detect cancer-specific aberrations at the peptide and proteoform levels, and to measure differential expression of proteins and proteoforms. For proteins in the range of 0-30 kDa, bottom-up proteomics quantified 3,519 protein groups from 49,185 peptides, while top-down proteomics quantified 982 proteoforms mapping to 358 proteins. Examples of both concordant and discordant quantitation were found in an approximately 60:40 ratio, providing a unique opportunity for top-down to fill in missing information. The two techniques showed complementary performance, with bottom-up yielding 8 times more identifications of 0-30 kDa proteins in xenograft proteomes, but failing to detect differences in post-translational modifications, such as phosphorylation pattern changes of alpha-endosulfine. This initial study illustrates the potency of a combined bottom-up and top-down proteomics approach to deepen our knowledge of cancer biology, especially when genomic data are available.

Citation Format: Neil Kelleher. Can protein discovery with complete molecular specificity increase return on investment for cancer biomarkers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY30-04. doi:10.1158/1538-7445.AM2015-SY30-04
Abstract SY45-01: Defining the origin of tumor heterogeneity in epithelial cancers
Authors: Blanpain Cedric
Published: August 2015

Different theories have been proposed to explain tumor heterogeneity including the cancer cell of origin. Here, we developed genetically engineered mouse models allowing lineage tracing together with oncogenic activation in different cell lineages, and assessed whether the cancer cell of origin controls tumor heterogeneity. Mouse skin squamous cell carcinoma (SCC) arising from the interfollicular epidermis (IFE) are all well-differentiated SCCs. In contrast, tumors that arise from the same oncogenic hits in the hair follicle (HF) lineages displayed considerable heterogeneity ranging from well-differentiated SCCs to fibroblastic-like cancers exhibiting epithelial to mesenchymal transition (EMT) features. I will discuss further evidence that the cancer cell of origin controls EMT-related tumor heterogeneity and the underlying molecular mechanisms that promote multilineage differentiation, tumor propagation, EMT and metastasis in primary skin SCCs. Breast cancer is the most frequent cancer in women and consists of heterogeneous types of tumors that are classified into different histological and molecular subtypes. PIK3CA and p53 are the two most frequently mutated genes and are associated with different types of human breast cancers. I will present new results uncovering the cellular origin of mammary tumors. These results have important implications for our understanding of the mechanisms controlling tumor heterogeneity and the development of new strategies to block tumor initiation.

This work is supported by the WELBIO, the FNRS, the Fondation Bettencourt-Schuler and the Fondation Baillet-Latour.

Citation Format: Cedric Blanpain. Defining the origin of tumor heterogeneity in epithelial cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY45-01. doi:10.1158/1538-7445.AM2015-SY45-01
Behavioral Evidence for an Impairment of Affective Theory of Mind Capabilities in Chronic Depression
Authors: Mattern Margarete , Walter Henrik , Hentze Charlotte , Schramm Elisabeth , Drost Sarah , Schoepf Dieter , Fangmeier Thomas , Normann Claus , Zobel Ingo , Schnell Knut
Published: August 2015

Background: The only treatment specifically developed for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), is based amongst others on the hypothesis that chronically depressed patients (CD) show considerable deficits of affective theory of mind (ToM) capabilities. Data are scarce, however, and it remains unclear if ToM deficits are specific or if they arise from global cognitive deficits associated with depression. This study investigates the specific deficits of affective ToM abilities in CD. Sampling and Methods: ToM abilities were assessed in 26 medication-free CD and 26 matched healthy controls (HC) by means of a previously established false-belief ToM cartoon task. Since the task allowed an intern control for cognitive factors - operationalized in a visuospatial ToM task - it was possible to investigate specific affective ToM deficits. Results: As hypothesized, the CD showed a significant specific slowdown of affective ToM compared to cognitive ToM (3rd person perspective) when compared to HC. Simultaneously, we observed a general deterioration of all ToM functions in CD. Conclusions: This study provides evidence that CD have a mentalization deficit, specifically for affective ToM functions. This deficit is combined with a general deterioration of ToM functions, most likely attributable to frequently described cognitive deficits in depression.
The Clinical Utility of the Diagnostic Criteria for Psychosomatic Research: A Review of Studies
Authors: Porcelli Piero , Guidi Jenny
Published: August 2015

Background: The Diagnostic Criteria for Psychosomatic Research (DCPR) are a set of 12 psychosomatic syndromes and are provided with a reliable diagnostic structured interview. The DCPR have been proposed 20 years ago as an integrative assessment strategy that supplements the traditional psychiatric nosography for identifying patients within a given illness population whose psychosocial factors have clinical significance. This paper reviews their clinical utility, conceived as the degree and the amount of influence that the instrument has on multiple decisions and outcomes in clinical practice. Methods: Published reports which involved the use of the DCPR were identified by searching electronic databases. Studies which best displayed the clinical utility of the DCPR system were then selected and reviewed. Results: The DCPR system showed its clinical utility regarding the following clinical issues: (1) subtyping medical patients, (2) identifying subthreshold or undetected syndromes, (3) evaluating the burden of somatic syndromes, and (4) predicting treatment outcomes and identifying risk factors. Conclusions: The DCPR may help clinicians during the assessment process to recognize clinical conditions underlying symptom presentation, with important therapeutic and prognostic implications.
The Impact of the in utero and Early Postnatal Environments on Grey and White Matter Volume: A Study with Adolescent Monozygotic Twins
Authors: Levesque Melissa L. , Fahim Cherine , Ismaylova Elmira , Verner Marie-Pier , Casey Kevin F. , Vitaro Frank , Brendgen Mara , Dionne Ginette , Boivin Michel , Tremblay Richard E. , Booij Linda
Published: August 2015

Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development.
Whole-Saliva Fluoride Levels and Saturation Indices in 65+ Elderly during Use of Four Different Toothpaste Regimens
Authors: Ekstrand Kim Rud , Ekstrand Mia Linding , Lykkeaa Joan , Bardow Allan , Twetman Svante
Published: August 2015

Background: Elderly individuals suffering from subnormal saliva secretion combined with inadequate oral hygiene may develop rampant caries and caries in parts of the dentition not normally affected by caries if preventive measures are not undertaken. Such measures include elevating fluoride levels at the saliva/biofilm/tooth interface. Aim: To analyse whole-saliva fluoride levels and mineral saturation indices during different fluoride toothpaste regimens in home-living elderly. Materials and Methods: Whole saliva was collected from 27 subjects (7 males and 20 females, mean age 73.5 ± 6.1 years) at ten time points covering the whole day during five 2-week periods. During the first period, participants used their normal toothpaste without instructions (baseline). This was followed by TP1: 1,450-ppm NaF toothpaste; TP2: 1,450-ppm monofluorophosphate (MFP) toothpaste with addition of calcium; TP3: 5,000-ppm NaF toothpaste, and TP4: the same toothpaste with additional ‘smearing' of toothpaste on the teeth, twice daily. During TP1-TP4, the participants were instructed to brush 3 times per day using 1.5 g of toothpaste without rinsing. Results: Salivary fluoride levels increased with toothpaste fluoride content (p < 0.001), although major interindividual and intraindividual variations were observed. The highest fluoride values appeared in the morning and at night (p < 0.001). Saturation indices for calcium fluoride were affected by the fluoride content in pastes (p < 0.05). Concerning hydroxyapatite and fluorapatite, indices were highest with the MFP toothpaste and extra calcium (NS to p < 0.05). Conclusions: Use of a high-fluoride toothpaste resulted in significantly increased fluoride levels in whole saliva and mineral saturation indices were indeed influenced by choice of toothpaste.
Aralia elata Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy
Authors: Kim Seong-Jae , Yoo Woong-Sun , Kim Hwajin , Kwon Jeong Eun , Hong Eun-Kyung , Choi Meeyoung , Han Yongseop , Chung Inyoung , Seo Seongwook , Park Jongmoon , Yoo Ji-Myong , Choi Wan-Sung
Published: August 2015

Background/Aims: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. Methods: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF-κB) were examined. Results: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP-immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-κB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. Conclusions: These results indicate that A. elata prevents diabetes-induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy.
Dialysis Facility Transplant Philosophy and Access to Kidney Transplantation in the Southeast
Authors: Gander Jennifer , Browne Teri , Plantinga Laura , Pastan Stephen O. , Sauls Leighann , Krisher Jenna , Patzer Rachel E.
Published: August 2015

Background: Little is known about the impact of dialysis facility treatment philosophy on access to transplant. The aim of our study was to determine the relationship between the dialysis facility transplant philosophy and facility-level access to kidney transplant waitlisting. Methods: A 25-item questionnaire administered to Southeastern dialysis facilities (n = 509) in 2012 captured the facility transplant philosophy (categorized as ‘transplant is our first choice', ‘transplant is a great option for some', and ‘transplant is a good option, if the patient is interested'). Facility-level waitlisting and facility characteristics were obtained from the 2008-2011 Dialysis Facility Report. Multivariable logistic regression was used to examine the association between the dialysis facility transplant philosophy and facility waitlisting performance (dichotomized using the national median), where low performance was defined as fewer than 21.7% of dialysis patients waitlisted within a facility. Results: Fewer than 25% (n = 124) of dialysis facilities reported ‘transplant is our first option'. A total of 131 (31.4%) dialysis facilities in the Southeast were high-performing facilities with respect to waitlisting. Adjusted analysis showed that facilities who reported ‘transplant is our first option' were twice (OR 2.0; 95% CI 1.0-3.9) as likely to have high waitlisting performance compared to facilities who reported that ‘transplant is a good option, if the patient is interested'. Conclusions: Facilities with staff who had a more positive transplant philosophy were more likely to have better facility waitlisting performance. Future prospective studies are needed to further investigate if improving the kidney transplant philosophy in dialysis facilities improves access to transplantation.
Genetic Architecture of Lacunar Stroke
Authors: Traylor Matthew , Bevan Steve , Baron Jean-Claude , Hassan Ahamad , Lewis Cathryn M. , Markus Hugh S.
Published: August 2015

Background and Purpose—

Lacunar strokes comprise ≈20% of all strokes. Despite this frequency, their pathogenesis is poorly understood. Previous genome-wide association studies in lacunar stroke have been disappointing, which may be because of phenotypic heterogeneity. Pathological and radiological studies suggest that there may be different pathologies underlying lacunar strokes. This has led to the suggestion of 2 subtypes: isolated lacunar infarcts and multiple lacunar infarcts and leukoaraiosis.

Methods—

We performed genome-wide analyses in a magnetic resonance imaging–verified cohort of 1012 younger onset lacunar stroke cases and 964 controls. Using these data, we first estimated the heritability of lacunar stroke and its 2 hypothesized subtypes, and secondly, we determined whether this is enriched for regulatory regions in the genome, as defined by data from Encyclopedia of DNA Elements (ENCODE) and other sources. Finally, we determine the evidence for a polygenic contribution from rare variation to lacunar stroke and its subtypes.

Results—

Our results indicate a substantial heritable component to magnetic resonance imaging–verified lacunar stroke (20%–25%) and its 2 subtypes (isolated lacunar infarct, 15%–18%; multiple lacunar infarcts/leukoaraiosis, 23%–28%). This heritable component is significantly enriched for sites affecting expression of genes. In addition, we show that the risk of the 2 subtypes of lacunar stroke in isolation, but not in combination, is associated with rare variation in the genome.

Conclusions—

Lacunar stroke, when defined on magnetic resonance imaging, is a highly heritable complex disease. Much of this heritability arises from regions of the genome affecting gene regulation. Rare variation affects 2 subtypes of lacunar in isolation, suggesting that they may have distinct genetic susceptibility factors.
High-Resolution Intracranial Pressure Burden and Outcome in Subarachnoid Hemorrhage
Authors: Magni Federico , Pozzi Matteo , Rota Matteo , Vargiolu Alessia , Citerio Giuseppe
Published: August 2015

Background and Purpose—

Intracranial pressure (ICP) control is a therapeutic target in patients with aneurysmal subarachnoid hemorrhage, although only a limited number of studies assessed its course and effect on outcome. Pressure–time dose (PTD
ICP
) is a method to quantify the burden and the time spent above a defined threshold of ICP. PTD
ICP
or its relationship with outcome has never been evaluated in aneurysmal subarachnoid hemorrhage.

Methods—

Analysis of data prospectively collected from aneurysmal subarachnoid hemorrhage patients admitted to Neurointensive Care Unit. Monitored data, including intraparenchymal ICP, were digitally recorded minute-by-minute in the first 7 days. PTD
ICP
(mm Hg h) was computed using 4 predefined thresholds (15, 20, 25, and 30 mm Hg). Outcome was assessed through Extended Glasgow Outcome Scale at hospital discharge and at 6 months.

Results—

Fifty-five patients were enrolled. Forty-two patients (76%) presented with a poor clinical grade. Overall, mortality was 17% at hospital discharge and 34% at 6 months. Half of patients required extensive therapy to control high ICP during day 1. Median ICP was 10 mm Hg (4–75), whereas median PTD
ICP15
, PTD
ICP20
, PTD
ICP25
, PTD
ICP30
were, respectively, 13, 4, 2, and 1 mm Hg h. We observed an association between mortality at hospital discharge and higher level of PTD
ICP
using 20, 25, and 30 mm Hg as thresholds and between exposure to a moderate-level PTD
ICP30
and unfavorable long-term outcome.

Conclusions—

PTD
ICP
may better define one of the insults that the brain suffers after aneurysmal rupture, and exposure to moderate PTD
ICP30
was significant prognostic factor of 6-month unfavorable outcome.
The Truth Before and After: Brain Potentials Reveal Automatic Activation of Event Knowledge during Sentence Comprehension
Authors: Nieuwland Mante S.
Published: August 2015

How does knowledge of real-world events shape our understanding of incoming language? Do temporal terms like “before” and “after” impact the online recruitment of real-world event knowledge? These questions were addressed in two ERP experiments, wherein participants read sentences that started with “before” or “after” and contained a critical word that rendered each sentence true or false (e.g., “Before/After the global economic crisis, securing a mortgage was easy/harder”). The critical words were matched on predictability, rated truth value, and semantic relatedness to the words in the sentence. Regardless of whether participants explicitly verified the sentences or not, false-after-sentences elicited larger N400s than true-after-sentences, consistent with the well-established finding that semantic retrieval of concepts is facilitated when they are consistent with real-world knowledge. However, although the truth judgments did not differ between before- and after-sentences, no such sentence N400 truth value effect occurred in before-sentences, whereas false-before-sentences elicited an enhanced subsequent positive ERPs. The temporal term “before” itself elicited more negative ERPs at central electrode channels than “after.” These patterns of results show that, irrespective of ultimate sentence truth value judgments, semantic retrieval of concepts is momentarily facilitated when they are consistent with the known event outcome compared to when they are not. However, this inappropriate facilitation incurs later processing costs as reflected in the subsequent positive ERP deflections. The results suggest that automatic activation of event knowledge can impede the incremental semantic processes required to establish sentence truth value.
Task-positive Functional Connectivity of the Default Mode Network Transcends Task Domain
Authors: Elton Amanda , Gao Wei
Published: August 2015

The default mode network (DMN) was first recognized as a set of brain regions demonstrating consistently greater activity during rest than during a multitude of tasks. Originally, this network was believed to interfere with goal-directed behavior based on its decreased activity during many such tasks. More recently, however, the role of the DMN during goal-directed behavior was established for internally oriented tasks, in which the DMN demonstrated increased activity. However, the well-documented hub position and information-bridging potential of midline DMN regions indicate that there is more to uncover regarding its functional contributions to goal-directed tasks, which may be based on its functional interactions rather than its level of activation. An investigation of task-related changes in DMN functional connectivity during a series of both internal and external tasks would provide the requisite investigation for examining the role of the DMN during goal-directed task performance. In this study, 20 participants underwent fMRI while performing six tasks spanning diverse internal and external domains in addition to a resting-state scan. We hypothesized that the DMN would demonstrate “task-positive” (i.e., positively contributing to task performance) changes in functional connectivity relative to rest regardless of the direction of task-related changes in activity. Indeed, our results demonstrate significant increases in DMN connectivity with task-promoting regions (e.g., anterior insula, inferior frontal gyrus, middle frontal gyrus) across all six tasks. Furthermore, canonical correlation analyses indicated that the observed task-related connectivity changes were significantly associated with individual differences in task performance. Our results indicate that the DMN may not only support a “default” mode but may play a greater role in both internal and external tasks through flexible coupling with task-relevant brain regions.
The Neural Bases of the Semantic Interference of Spatial Frequency-based Information in Scenes
Authors: Kauffmann Louise , Bourgin Jessica , Guyader Nathalie , Peyrin Carole
Published: August 2015

Current models of visual perception suggest that during scene categorization, low spatial frequencies (LSF) are processed rapidly and activate plausible interpretations of visual input. This coarse analysis would then be used to guide subsequent processing of high spatial frequencies (HSF). The present fMRI study examined how processing of LSF may influence that of HSF by investigating the neural bases of the semantic interference effect. We used hybrid scenes as stimuli by combining LSF and HSF from two different scenes, and participants had to categorize the HSF scene. Categorization was impaired when LSF and HSF scenes were semantically dissimilar, suggesting that the LSF scene was processed automatically and interfered with categorization of the HSF scene. fMRI results revealed that this semantic interference effect was associated with increased activation in the inferior frontal gyrus, the superior parietal lobules, and the fusiform and parahippocampal gyri. Furthermore, a connectivity analysis (psychophysiological interaction) revealed that the semantic interference effect resulted in increasing connectivity between the right fusiform and the right inferior frontal gyri. Results support influential models suggesting that, during scene categorization, LSF information is processed rapidly in the pFC and activates plausible interpretations of the scene category. These coarse predictions would then initiate top–down influences on recognition-related areas of the inferotemporal cortex, and these could interfere with the categorization of HSF information in case of semantic dissimilarity to LSF.
An updated checklist of the mosses of Paraguay
Authors: O’Shea Brian J. , Price Michelle J.
Published: August 2015

The original checkelist of mosses for Paraguay listed 137 species for the country, based on literature reports. An updated checklist has been compiled here, with corrections and additional names added from recent literature records, and in some cases from herbarium records. A total of 240 moss species, including 8 infraspecific taxa, from 94 genera and 38 families are now recorded for Paraguay. This total includes 8 published nomina nuda and 9 taxa that are listed as present in the country but which lack any specific locality reference. Forty-three taxa are apparent endemics to Paraguay and warrant further taxonomic evaluation. The 240 taxa now recorded for Paraguay are listed here along with relevant bibliographical or locality references. A supplementary list of synonyms is also included.
Rediagnosis of Callianideidae and its genera (Crustacea: Decapoda: Axiidea), and description of a new species of Heardaxius Sakai, 2011
Authors: POORE GARY C. B.
Published: August 2015

Callianideidae and Thomassiniidae, two families of Axiidea, are synonymised and Callianideidae diagnosed. The six genera, Callianidea H. Milne Edwards, 1837, Crosniera Kensley & Heard, 1991, Mictaxius Kensley & Heard, 1991, Heardaxius Sakai, 2011, Paracallianidea Sakai, 1992 and Thomassinia de Saint Laurent, 1979 are diagnosed and all species listed. Garyia Sakai, 2011 is synonymised with Thomassinia. A key to genera is provided. A new species Heardaxius rogerbamberi is described from Papua New Guinea. Thomassinia aimsae Poore, 1997 is newly recorded from Papua New Guinea.