bluuebunny/crossref_metadata_2025 huggingface dataset:
God of the hinge: treating LGBTQIA patients
Authors: Boland Annie
Published: October 2017

This paper looks at systems of gender within the context of analysis. It explores the unique challenges of individuation faced by transsexual, transgender, gender queer, gender non‐conforming, cross‐dressing and intersex patients. To receive patients generously we need to learn how a binary culture produces profound and chronic trauma. These patients wrestle with being who they are whilst simultaneously receiving negative projections and feeling invisible. While often presenting with the struggles of gender conforming individuals, understanding the specifically gendered aspect of their identity is imperative. An analyst's unconscious bias may lead to iatrogenic shaming.

The author argues that rigorous, humble inquiry into the analyst's transphobia can be transformative for patient, analyst, and the work itself. Analysis may, then, provide gender‐variant patients with their first remembered and numinous experience of authentic connection to self. Conjuring the image of a hinge, securely placed in the neutral region of a third space, creates a transpositive analytic temenos. Invoking the spirit of the Trickster in the construction of this matrix supports the full inclusion of gender‐variant patients. Nuanced attunement scaffolds mirroring and the possibility of play. Being mindful that gender is sturdy and delicate as well as mercurial and defined enriches the analyst's listening.
Total Ion Spectra versus Segmented Total Ion Spectra as Preprocessing Tools for Gas Chromatography – Mass Spectrometry Data
Authors: Adutwum Lawrence A. , Abel Robin J. , Harynuk James
Published: October 2017

Alignment of fire debris data from GC‐MS for chemometric analysis is challenged by highly variable, uncontrolled sample and matrix composition. The total ion spectrum (TIS) obviates the need for alignment but loses all separation information. We introduce the segmented total ion spectrum (STIS), which retains the advantages of TIS while retaining some retention information. We compare the performance of STIS with TIS for the classification of casework fire debris samples. TIS and STIS achieve good model prediction accuracies of 96% and 98%, respectively. Baseline removal improved model prediction accuracies for both TIS and STIS to 97% and 99%, respectively. The importance of maintaining some chromatographic information to aid in deciphering the underlying chemistry of the results and reasons for false positive/negative results was also examined.
Sirtuins at the crossroads of stemness, aging, and cancer
Authors: O'Callaghan Carol , Vassilopoulos Athanassios
Published: October 2017

Sirtuins are stress‐responsive proteins that direct various post‐translational modifications (PTMs) and as a result, are considered to be master regulators of several cellular processes. They are known to both extend lifespan and regulate spontaneous tumor development. As both aging and cancer are associated with altered stem cell function, the possibility that the involvement of sirtuins in these events is mediated by their roles in stem cells is worthy of investigation. Research to date suggests that the individual sirtuin family members can differentially regulate embryonic, hematopoietic as well as other adult stem cells in a tissue‐ and cell type‐specific context. Sirtuin‐driven regulation of both cell differentiation and signaling pathways previously involved in stem cell maintenance has been described where downstream effectors involved determine the biological outcome. Similarly, diverse roles have been reported in cancer stem cells (CSCs), depending on the tissue of origin. This review highlights the current knowledge which places sirtuins at the intersection of stem cells, aging, and cancer. By outlining the plethora of stem cell‐related roles for individual sirtuins in various contexts, our purpose was to provide an indication of their significance in relation to cancer and aging, as well as to generate a clearer picture of their therapeutic potential. Finally, we propose future directions which will contribute to the better understanding of sirtuins, thereby further unraveling the full repertoire of sirtuin functions in both normal stem cells and CSCs.
Endogeneity of Return Parameters and Portfolio Selection: An Analysis on Implied Covariances
Authors: Park Koohyun , Rhee Thomas
Published: October 2017

The paper presents a method to measure forward‐looking covariance risk for any two assets even when the explicit market for barter trades does not exist. We argue that the terms of trade in any barter exchanges also follow a martingale process with no arbitrage. We then compute various bivariate martingale probabilities for different assets to value all possible pseudo exchange options. This makes it possible for one to compute implied covariances embedded in the value of any exchange options as in Margrabe (1978). The paper also discusses how these “recoverable” implied return distribution parameters can impact portfolio choice.
How can mindfulness enhance moral reasoning? An examination using business school students
Authors: Pandey Ashish , Chandwani Rajesh , Navare Ajinkya
Published: October 2017

Given the comprehensive influence of mindfulness on human thought and behavior, and the importance of moral reasoning in business decisions, we examine the role of mindfulness as an antecedent to moral reasoning through two studies. In Study 1, we propose and test a theoretically derived model that links mindfulness and moral reasoning, mediated by compassion and egocentric bias using a survey design. In Study 2, we examine whether mindfulness training enhances moral reasoning using an experimental design with graduate students of business management. The findings of Study 1 substantiate the positive association of mindfulness with moral reasoning. We found that this relationship is fully mediated by compassion and egocentric bias. The results of Study 2 suggest that mindfulness meditation training has a positive impact on individuals' states of mindfulness, compassion, and moral reasoning, and decreases egocentric bias. We relate the findings of the study with contemporary neurological research and discuss the theoretical, pedagogical, and managerial implications.
White‐tailed deer as the last megafauna dispersing seeds in Neotropical dry forests: the role of fruit and seed traits
Authors: Jara‐Guerrero Andrea , Escribano‐Avila Gema , Espinosa Carlos Iván , De la Cruz Marcelino , Méndez Marcos
Published: October 2017

Endozoochory is a prominent form of seed dispersal in tropical dry forests. Most extant megafauna that perform such seed dispersal are ungulates, which can also be seed predators. White‐tailed deer (Odocoileus virginianus) is one of the last extant megafauna of Neotropical dry forests, but whether it serves as a legitimate seed disperser is poorly understood. We studied seed dispersal patterns and germination after white‐tailed deer gut passage in a tropical dry forest in southwest Ecuador. Over 23 mo, we recorded ca 2000 seeds of 11 species in 385 fecal samples. Most seeds belonged to four species of Fabaceae: Chloroleucon mangense, Senna mollissima, Piptadenia flava, and Caesalpinia glabrata. Seeds from eight of the 11 species dispersed by white‐tailed deer germinated under controlled conditions. Ingestion did not affect germination of C. mangense and S. mollissima, whereas C. glabrata showed reduced germination. Nevertheless, the removal of fruit pulp resulting from ingestion by white‐tailed deer could have a deinhibition effect on germination due to seed release. Thus, white‐tailed deer play an important role as legitimate seed dispersers of woody species formerly considered autochorous. Our results suggest that more research is needed to fully understand the ecological and evolutionary effects of the remaining extant megafauna on plant regeneration dynamics in the dry Neotropics.
Identification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells
Authors: Satow Reiko , Inagaki Shota , Kato Chiaki , Shimozawa Makoto , Fukami Kiyoko
Published: October 2017

Identification of specific drug targets is very important for cancer therapy. We recently identified zinc finger protein of the cerebellum 5 (ZIC5) as a factor that promotes melanoma aggressiveness by platelet‐derived growth factor D (PDGFD) expression. However, its roles in other cancer types remain largely unknown. Here we determined the roles of ZIC5 in prostate cancer (PCa) and colorectal cancer (CRC) cells. Results showed that ZIC5 was highly expressed in CRC and dedifferentiated PCa tissues, whereas little expression was observed in relevant normal tissues. Knockdown of ZIC5 decreased proliferation of several PCa and CRC cell lines with induction of cell death. ZIC5 knockdown significantly suppressed PDGFD expression transcriptionally, and PDGFD suppression also decreased proliferation of PCa and CRC cell lines. In addition, suppression of ZIC5 or PDGFD expression decreased levels of phosphorylated focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) which are associated with PCa and CRC aggressiveness. Furthermore, knockdown of ZIC5 or PDGFD enhanced death of PCa and CRC cells induced by the anti‐cancer drugs docetaxel or oxaliplatin, respectively. These results suggest that ZIC5 and PDGFD promote survival of PCa and CRC cells by enhancing FAK and STAT3 activity, and that the roles of ZIC5 are consistent across several cancer types.
Legumain correlates with neuroblastoma differentiation and can be used in prodrug design
Authors: Zhang Min , Jiang Zhiteng , Chen Sheng , Wu Zhixiang , Chen Kai , Wu Yeming
Published: October 2017

Neuroblastoma (NB) is a highly malignant solid tumor in children. The cysteine endopeptidase legumain is expressed in adult solid tumors, but its expression in NB has not been examined. In this study, we assayed legumain expression in two NB cell lines and in microarrays of tumor tissues collected from 46 children with undifferentiated NB, differentiated NB, and ganglioneuroblastoma. Correlation analyses showed that legumain was expressed in all NB cell lines tested and that expression correlated with the degree of tumor differentiation. The efficacy, specificity, and toxicity of EMC‐AANL‐DOX, a novel doxorubicin‐based legumain‐activated prodrug, were then evaluated in mouse model of NB. Compared with DOX, EMC‐AANL‐DOX showed greater inhibition of tumor growth and a lower toxicity at high doses. Neither leukocyte or platelet counts nor renal function or cardiac anatomy differed significantly between the EMC‐AANL‐DOX and control groups (p > .05), suggesting that the prodrug caused minimal bone marrow depression and did not induce renal or cardiac damage. The good specificity and efficacy of EMC‐AANL‐DOX and low toxicity recommend its use in the treatment of NB. Correlation analyses of NB differentiation and legumain expression may reveal a novel anti‐tumor‐related functions of the drug and a new strategy for the treatment of pediatric solid tumors.
Genetics in pulmonary arterial hypertension in a large homogeneous Japanese population
Authors: Gamou S. , Kataoka M. , Aimi Y. , Chiba T. , Momose Y. , Isobe S. , Hirayama T. , Yoshino H. , Fukuda K. , Satoh T.
Published: October 2017

Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and more than 50 family members, including secondary patients. Importantly, the study population is a racially, ethnically, and socially homogeneous population. In PAH patients, there is a high incidence of unique mutations in BMPR2, and several mutations are frequently observed in the Japanese population, suggesting that these common and recurring mutations may be highly pathogenic or have high penetrance, explaining why they are found frequently throughout the world. We have also mapped each breakpoint of exonic deletions/duplications and found that most break and rejoining points are in the Alu elements. Reviewing the distribution of the reported mutations on each exon of BMPR2 revealed that the number and frequency of mutations are imbalanced among exons. The penetrance of BMPR2 gene mutations was 3‐fold higher in females than males. Full elucidation of BMPR2‐mediated pathogenic mechanisms in PAH requires persistent efforts to achieve precision or individualized medicine as a therapeutic strategy for PAH.
TNFα and IL‐17A are differentially expressed in psoriasis‐like vs eczema‐like drug reactions to TNFα antagonists
Authors: Deubelbeiss Cornelia , Kolios Antonios G. A. , Anzengruber Florian , French Lars E. , Yawalkar Nikhil , Kempf Werner , Kerl Katrin , Meier Barbara , Navarini Alexander A.
Published: October 2017

Background

Tumor necrosis factor α (TNFα) blocking drugs are in use for a wide range of autoimmune disorders. In up to 5% of patients, this class of drugs produces puzzling cutaneous side effects that are the subject of this investigation, namely psoriasiform and eczema‐like skin inflammation. These side effects can occur after any time of treatment and regardless of the underlying disorders. The exact pathophysiology is as yet unknown.

Methods

A total of 33 patients (19 female, average age 52 years) who had a cutaneous reaction to infliximab, adalimumab or etanercept were included. The type of inflammatory reaction was determined, and the corresponding cytokine expression was evaluated by immunohistochemistry for TNFα, IL‐1β, IL‐22, IL‐6, IL‐17A, IL33, IL‐8 and IL‐36α (semi‐quantitative grading system from − to ++++). In addition, RNA expression levels of IL‐17A and TNFα were confirmed by quantitative real‐time PCR.

Results

IL‐17A (P < .039) and TNFα (P < .008) were expressed at significantly higher levels in psoriasis or pustular‐like reactions (PPR) compared to eczematous‐like reactions (ELR). There was no significant difference in the expression of IL‐1β, IL‐22, IL‐6, IL‐33, IL‐8 and IL‐36α between PPR and ELR.

Conclusion

TNFα and IL‐17A are both cytokines known to be involved in psoriasis but less so in non‐psoriasiform dermatitis or eczema. Therefore, their overexpression in PPR is plausible and suggests that the pathogenesis of PPR mirrors at least in part those of psoriasis. Further investigations will define the exact role of these cytokines in rare cutaneous side effects of anti‐TNFα therapy. Our results suggest that IL‐17A inhibition could be a therapeutic option in patients with anti‐TNF induced psoriasis.
Folliculocystic and collagen hamartoma of tuberous sclerosis: A new case in a female patient and review of literature
Authors: Kaplan Laura , Kazlouskaya Viktoryia , Ugorji Rex , Heilman Edward , Siegel Daniel M. , Glick Sharon A.
Published: October 2017

Folliculocystic and collagen hamartoma (FCCH) of tuberous sclerosis is a rare entity described in 2012 by Torrelo et al. with only 8 cases described, predominantly in males. It presents since birth or early infancy and in the majority of cases is associated with tuberous sclerosis. The hamartoma presents as an exophytic plaque and has distinctive histopathological features including hair follicles, intact or ruptured epidermal cysts, and an increased number of collagen fibers extending to the subcutaneous tissue.

Herein we present an additional case of this rare entity in an 18‐year‐old female who met clinical criteria for tuberous sclerosis. The patient had an exophytic mass in the left temporal area for many years and wanted surgical excision due to its cosmetic appearance. Histopathology of the surgical specimen showed a hamartomatous lesion with multiple large intact epidermal cysts, hairs and increased thickened collagen. The patient has followed up for 1 year after the excision, with no recurrence. Additionally, we provide a literature review of known cases of FCCH as well as its clinical and histopathological differential diagnosis.
Validity of automated measurement of left ventricular ejection fraction and volume using the Philips EPIQ system
Authors: Hovnanians Ninel , Win Theresa , Makkiya Mohammed , Zheng Qi , Taub Cynthia
Published: October 2017

Purpose

To assess the efficiency and reproducibility of automated measurements of left ventricular (LV) volumes and LV ejection fraction (LVEF) in comparison to manually traced biplane Simpson's method.

Method

This is a single‐center prospective study. Apical four‐ and two‐chamber views were acquired in patients in sinus rhythm. Two operators independently measured LV volumes and LVEF using biplane Simpson’s method. In addition, the image analysis software a2DQ on the Philips EPIQ system was applied to automatically assess the LV volumes and LVEF. Time spent on each analysis, using both methods, was documented. Concordance of echocardiographic measures was evaluated using intraclass correlation (ICC) and Bland‐Altman analysis.

Results

Manual tracing and automated measurement of LV volumes and LVEF were performed in 184 patients with a mean age of 67.3 ± 17.3 years and BMI 28.0 ± 6.8 kg/m2. ICC and Bland‐Altman analysis showed good agreements between manual and automated methods measuring LVEF, end‐systolic, and end‐diastolic volumes. The average analysis time was significantly less using the automated method than manual tracing (116 vs 217 seconds/patient, P < .0001).

Conclusion

Automated measurement using the novel image analysis software a2DQ on the Philips EPIQ system produced accurate, efficient, and reproducible assessment of LV volumes and LVEF compared with manual measurement.
Concealing a shiny facial skin appearance by an Aerogel‐based formula. In vitro and in vivo studies
Authors: Cassin G. , Diridollou S. , Flament F. , Adam A. S. , Pierre P. , Colomb L. , Morancais J. L. , Qiu H.
Published: October 2017

Objective

To explore, in vitro and in vivo, the potential interest of an Aerogel‐based formula, in concealing a naturally shiny facial skin.

Methods

In vitro, various formulae and ingredients were applied as a thin film onto contrast plates and studied through measuring the shine induced following pump spraying of a mixture of oleic acid and mineral water as a sebum/sweat mix model. In such a test, an Aerogel ingredient led to very positive results. In vivo, two different formulae with various concentrations of Aerogel were randomly tested on half side of the face vs. bare side of Chinese women, under some provocative environmental conditions, known to enhance facial shine. These conditions comprised a normal activity under a hot and highly humid summer time followed – or not – by a hamam session. Both studies included comparative evaluations using a half‐face procedure (treated/untreated or vehicle). In the first case, evaluations were quantitatively carried out, whereas the second one was based on a quantitative self‐evaluations from standardized full‐face photographs

Results

In vitro, the tested Aerogel, incorporated at 1% or 2% concentration in a common O/W cosmetic emulsion, shows an immediate light scattering effect, thereby masking shine. Such effect appears of much higher amplitude than that of two other tested particulate ingredients (Talc and Perlite). A noticeable remanence of anti‐shine effect was confirmed in vivo in extreme conditions. The latter was self‐perceived by all participants in the second study. This result is likely related to the super hydrophobic behaviour of the Aerogel.

Conclusion

As cosmetic ingredient, this new Aerogel appears as a highly promising ingredient for concealing the facial skin shine, a source of complaint from many consumers living in hot and humid regions.
Evaluation of electrodeposited Mn‐Co protective coatings on Crofer 22 APU steel
Authors: Molin Sebastian
Published: October 2017

Interconnects used in Solid Oxide Cells stacks require protective coatings to lower their parabolic rate constant and block chromium evaporation (on the air side). In this work four different protective coatings on steel are evaluated for their high temperature corrosion resistance and electrical conductivity. A commercial electroplating process was used for the preparation of coatings with different Mn/Co ratios on Crofer 22 APU steel. Oxidation of samples was performed in air at 800°C for 1000 hours. Postmortem analysis of the coated samples was performed by scanning electron microscopy and x‐ray diffractomettry. Based on the results, influence of the Co/Mn ratio on the resulting corrosion properties are discussed. Parabolic rate constant of the coated samples is the lowest for the MnCo sample, whereas electrical resistance is the lowest for the Co sample, which has a corrosion rate similar to the not‐coated alloys.
Blackcurrant pomace from juice processing as partial flour substitute in savoury crackers: dough characteristics and product properties
Authors: Schmidt Carolin , Geweke Insa , Struck Susanne , Zahn Susann , Rohm Harald
Published: October 2017

Berry pomace is a by‐product of juice processing that, after drying and milling, may be used as an ingredient in cereal‐based products. This, on the one hand, not only reduces losses of edible raw material components, but also increases the nutritional value of the target food because of its high dietary fibre and bioactive compounds content. By using savoury crackers as model, this study analyses how a partial flour replacement by blackcurrant pomace (levels: 10%, 20% or 30%) affects physical properties of the respective dough (dynamic rheology in simulated baking, extensibility and adhesiveness) and characteristics of the baked product (colour, texture and sensory properties). Pomace addition significantly affected both systems. By considering the high moisture absorption capacity of this material through water level adaptation in formulations and by only substituting gluten‐free flour (which led to a constant gluten content), it is demonstrated that even a flour replacement of up to 30% leads to acceptable products. A restrained protein development was observed in pomace containing dough, leading to a lower extensibility, and to reduced volume increase and lower breaking force after baking. In contrast, dough handling and sensory acceptance were not corrupted by pomace application even though colour of the final product was changed to a great extent.
Recent advances in malignant melanoma
Authors: Atkinson Victoria
Published: October 2017

In Australia, there is a high incidence of melanoma, and until recently, the treatment and median overall survival for advanced metastatic melanoma had not changed in decades. The recognition of BRAF as an important tumour oncogene in melanoma has led to the development of targeted therapies, and in the last few years, we have seen the impact of these therapies, with significant improvement in response rate, duration of disease control and overall survival for patients with BRAF mutation‐positive metastatic melanoma. Concurrently, the science of immunotherapy has evolved beyond the knowledge of the importance of the immune system in cancer, leading to the development of checkpoint inhibitors. The development of checkpoint inhibitors as a tolerable and effective therapy for metastatic melanoma, which has demonstrated improved response rates, duration of control and overall survival for patients, has implications beyond the care of patients with metastatic melanoma as these therapies are being trialled in other malignancies. This article will review the current standard of care and available therapies for metastatic malignant melanoma.
TIPE1 suppresses invasion and migration through down‐regulating Wnt/β‐catenin pathway in gastric cancer
Authors: Liu Wenwen , Chen Ye , Xie Hua , Guo Yongmin , Ren Dandan , Li Yupeng , Jing Xu , Li Dongliang , Wang Xiao , Zhao Miaoqing , Zhu Tianfeng , Wang Ziying , Wei Xinbing , Gao Fei , Wang Xiaojie , Liu Suxia , Zhang Yan , Yi Fan
Published: October 2017

Epithelial–mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well‐differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1‐medicated Wnt/β‐catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer.
Racemization at the Asp 58 residue in αA‐crystallin from the lens of high myopic cataract patients
Authors: Zhu Xiang‐jia , Zhang Ke‐ke , He Wen‐wen , Du Yu , Hooi Michelle , Lu Yi
Published: October 2017

Post‐translational modifications in lens proteins are key causal factors in cataract. As the most abundant post‐translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of αA‐crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l‐Asp 58 to d‐isoAsp58 in αA‐crystallin has been found in age‐related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l‐Asp 58 to d‐Asp 58 in αA‐crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l‐Asp 58 to d‐isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l‐Asp 58 to d‐Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in αA‐crystallin. The different trend in the conversion of αA‐crystallin by racemization, especially the elevated level of d‐Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC.
Specificity of presenilin‐1‐ and presenilin‐2‐dependent γ‐secretases towards substrate processing
Authors: Stanga Serena , Vrancx Céline , Tasiaux Bernadette , Marinangeli Claudia , Karlström Helena , Kienlen‐Campard Pascal
Published: October 2017

The two presenilin‐1 (PS1) and presenilin‐2 (PS2) homologs are the catalytic core of the γ‐secretase complex, which has a major role in cell fate decision and Alzheimer's disease (AD) progression. Understanding the precise contribution of PS1‐ and PS2‐dependent γ‐secretases to the production of β‐amyloid peptide (Aβ) from amyloid precursor protein (APP) remains an important challenge to design molecules efficiently modulating Aβ release without affecting the processing of other γ‐secretase substrates. To that end, we studied PS1‐ and PS2‐dependent substrate processing in murine cells lacking presenilins (PSs) (PS1KO, PS2KO or PS1‐PS2 double‐KO noted PSdKO) or stably re‐expressing human PS1 or PS2 in an endogenous PS‐null (PSdKO) background. We characterized the processing of APP and Notch on both endogenous and exogenous substrates, and we investigated the effect of pharmacological inhibitors targeting the PSs activity (DAPT and L‐685,458). We found that murine PS1 γ‐secretase plays a predominant role in APP and Notch processing when compared to murine PS2 γ‐secretase. The inhibitors blocked more efficiently murine PS2‐ than murine PS1‐dependent processing. Human PSs, especially human PS1, expression in a PS‐null background efficiently restored APP and Notch processing. Strikingly, and contrary to the results obtained on murine PSs, pharmacological inhibitors appear to preferentially target human PS1‐ than human PS2‐dependent γ‐secretase activity.
Site affinity of whitespotted eagle rays Aetobatus narinari assessed using photographic identification
Authors: Flowers K. I. , Henderson A. C. , Lupton J. L. , Chapman D. D.
Published: October 2017

Photographic identification was used to track the movements of the whitespotted eagle ray Aetobatus narinari around South Caicos, Turks and Caicos Islands. A total of 165 individuals were identified, aided by the computer program I3S Spot. The sex ratio across all study sites in 2015 was not significantly different from 1:1 (χ2 = 2·8, P > 0·05). 33·9% of all individual rays were resighted at least once and the maximum number of days between the first and last sighting was 1640 (median 165, interquartile range, IQR = 698). Sightings of individuals occurred at locations differing from the original sighting location 24·6% of the time (0·7–20 km away). The entire population around South Caicos has yet to be sampled and these rays exhibited site affinity during the study period; they are either resident to South Caicos or are using the area for parts of the year before making movements elsewhere and then returning. Given these results, A. narinari is suited to local‐scale management and conservation efforts.
Temporal changes in hamlet communities (Hypoplectrus spp., Serranidae) over 17 years
Authors: Hench K. , Mcmillan W. O. , Betancur‐R R. , Puebla O.
Published: October 2017

Transect surveys of hamlet communities (Hypoplectrus spp., Serranidae) covering 14 000 m2 across 16 reefs off La Parguera, Puerto Rico, are presented and compared with a previous survey conducted in the year 2000. The hamlet community has noticeably changed over 17 years, with a > 30% increase in relative abundance of the yellowtail hamlet Hypoplectrus chlorurus on the inner reefs at the expense of the other hamlet species. The data also suggest that the density of H. chlorurus has declined and that its distribution has shifted towards shallower depths. Considering that H. chlorurus has been previously identified as one of the few fish showing a positive association with seawater turbidity on the inner reefs of La Parguera and that sedimentation of terrestrial origin has increased over recent decades on these reefs, it is proposed that turbidity may constitute an important but so far overlooked ecological driver of hamlet communities.
Reduction effect of the quantity of radiation exposure and contrast media by image support system in transarterial chemoembolization for the treatment of hepatocellular carcinoma
Authors: Tamai Tsutomu , Taniyama Oki , Oda Kohei , Kasai Ai , Ijyuin Syo , Sakae Haruka , Onishi Hiroka , Tabu Kazuaki , Kumagai Kotaro , Mawatari Seiichi , Moriuchi Akihiro , Uto Hirofumi , Ido Akio
Published: October 2017

Background and Aim

We confirmed the clinical utility of a three‐dimensional navigation system during transarterial chemoembolization.

Methods

We evaluated 128 tumors in 91 patients enrolled between May 2015 and August 2016. We evaluated the accuracy of the three‐dimensional navigation imaging system for all tumors. We compared the patients who were able to undergo route detection using three‐dimensional navigation with previously treated patients who underwent transarterial chemoembolization without using three‐dimensional navigation (n = 21). For 38 patients who underwent super‐selective microcatheter insertion after a feeding artery was identified by three‐dimensional navigation, we confirmed the relationship between the tumors and contrasted liver parenchyma and divided the computed tomography hepatic arteriography findings into four grades. Grade 1: an overlap of > 5 mm, grade 2: an overlap between 0 and 5 mm, grade 3: the borders of the tumor within the liver parenchyma but in contact with the edges, and grade 4: a tumor outside the borders of the liver parenchyma.

Results

Using the three‐dimensional navigation system, we identified a tumor‐feeding artery in 125/128 tumors (97.6%). Furthermore, this system allowed us to significantly reduce the volume of contrast media and the radiation exposure dose in patients undergoing an evaluation. We identified 15 grade 1 tumors (39.5%), 3 grade 2 tumors (7.9%), 11 grade 3 tumors (28.9%), and 9 grade 4 tumors (23.7%) according to our definitions.

Conclusion

The three‐dimensional navigation is useful not only for patients but also for surgeons who have relatively little experience.
Potential drug–drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir ± DASABUVIR ± ribavirin in clinical practice
Authors: González‐Colominas Elena , Londoño María‐Carlota , Morillas Rosa M , Torras Xavier , Mojal Sergi , Lens Sabela , López Dulce , Gallego Adolfo , Mariño Zoe , Ardèvol Mercè , Pagès Neus , Solà Ricard , Carrión Jose A
Published: October 2017

Background & Aims

Drug–drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice.

Methods

177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy.

Results

At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients.

Conclusions

Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one‐quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.
Clinical significance of small‐bowel villous edema in patients with liver cirrhosis: A capsule endoscopy study
Authors: Otani Ichiro , Oka Shiro , Tanaka Shinji , Tsuboi Akiyoshi , Kunihara Sayoko , Nagaoki Yuko , Aikata Hiroshi , Chayama Kazuaki
Published: October 2017

Background and Aim

The relationship between the presence of villous edema (VE) in portal hypertensive enteropathy and clinical factors remains unclear. The aim of this study was to reveal the clinical factors related to VE in patients with liver cirrhosis (LC), and investigate the clinical significance of VE.

Methods

Between February 2009 and September 2016, 363 consecutive patients with LC underwent capsule endoscopy for diagnosing portal hypertensive enteropathy at Hiroshima University Hospital. We evaluated the relationship between the presence of VE and patients' clinical characteristics, findings of esophagogastroduodenoscopy and computed tomography, and survival time.

Results

Villous edema was observed in 131 patients (36%), and severe lesions were found in 71 (20%). The presence of VE was significantly greater in patients with Child–Pugh classification B or C, esophageal varices, portal hypertensive gastropathy (PHG), ascites, portal vein thrombosis (PVT), and splenomegaly. In multivariate analysis, Child–Pugh class B or C, esophageal varices, PVT, and splenomegaly were significant predictive factors for the presence of VE. Severe VE was significantly greater in patients with Child–Pugh class B or C, serum albumin level ≤ 3.2 mg/dL, PHG, and PVT. In multivariate analysis, PHG, Child–Pugh class B or C, PVT, were significant predictive factors for severe VE.

Conclusions

Clinical factors related to portal hypertension were significantly correlated with VE. In particular PVT was correlated with the appearance and exacerbation of VE. Periodic capsule endoscopy in LC patients may lead to early detection of portal hypertension and PVT.
Expression of isotocin is male‐specifically up‐regulated by gonadal androgen in the medaka brain
Authors: Yamashita J. , Kawabata Y. , Okubo K.
Published: October 2017

Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioural processes, ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologues in other animals. In the present study, we show that, in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost orthologue of Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male‐specifically up‐regulated by gonadal androgen, whereas it expression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of the it‐expressing neurones appear to co‐express androgen receptors, suggesting that the effect of androgen on it expression is indirect. We found that the expression of a kisspeptin gene, kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen‐dependent expression of it may be mediated by kiss2 neurones. Our data also show that the isotocin peptide synthesised in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels of it expression are higher in females than in males, androgen may serve to compensate for the female‐biased it expression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids in Oxt/it expression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.
Functional interleukin‐6 receptor‐α is located in tanycytes at the base of the third ventricle
Authors: Anesten F. , Santos C. , Gidestrand E. , Schéle E. , Pálsdóttir V. , Swedung‐Wettervik T. , Meister B. , Patrycja Skibicka K. , Jansson J.‐O.
Published: October 2017

Interleukin (IL)‐6−/− mice develop mature onset obesity, whereas i.c.v. injection of IL‐6 decreases obesity in rodents. Moreover, levels of IL‐6 in cerebrospinal fluid (CSF) were reported to be inversely correlated with obesity in humans. Tanycytes lining the base of the third ventricle (3V) in the hypothalamus have recently been reported to be of importance for metabolism. In the present study, we investigated whether tanycytes could respond to IL‐6 in the CSF. With immunohistochemistry using a well characterised antibody directed against the ligand binding receptor for IL‐6, IL‐6 receptor α (IL‐6Rα), it was found that tanycytes, identified by the two markers, vimentin and dopamine‐ and cAMP‐regulated phosphoprotein of 32 kDa, contained IL‐6Rα. There were fewer IL‐6Rα on another type of ventricle‐lining cells, ependymal cells, as identified by the marker glucose transporter‐1. To demonstrate that the immunoreactive IL‐6Rα were responsive to IL‐6, we injected IL‐6 i.c.v. This treatment increased immunoreactive phosphorylated signal transducer and activator of transcription‐3 (pSTAT3) in tanycytes after 5 minutes and in cells in the medial part of the arcuate nucleus after 5 and 15 minutes. Intracerebroventricular injection of leptin exerted similar effects. As expected, i.p. injection of leptin also induced pSTAT3 staining in the hypothalamus, whereas i.p. IL‐6 injection had little effect on this parameter. Intracerebroventricular or i.p. injection of vehicle only had no effect on pSTAT3‐immunoreactivity. In summary, there are functional IL‐6Rα on tanycytes at the bottom of the 3V, in agreement with the possibility that ventricular administration of IL‐6 decreases obesity in mice via an effect on this cell type.
The Share of Systematic Variation in Bilateral Exchange Rates
Authors: VERDELHAN ADRIEN
Published: October 2017

Sorting countries by their dollar currency betas produces a novel cross section of average currency excess returns. A slope factor (long in high beta currencies and short in low beta currencies) accounts for this cross section of currency risk premia. This slope factor is orthogonal to the high‐minus‐low carry trade factor built from portfolios of countries sorted by their interest rates. The two high‐minus‐low risk factors account for 18% to 80% of the monthly exchange rate movements. The two risk factors suggest that stochastic discount factors in complete markets' models should feature at least two global shocks to describe exchange rates.
Optimal Debt and Profitability in the Trade‐Off Theory
Authors: ABEL ANDREW B.
Published: October 2017

I develop a dynamic model of leverage with tax deductible interest and an endogenous cost of default. The interest rate includes a premium to compensate lenders for expected losses in default. A borrowing constraint is generated by lenders' unwillingness to lend an amount that would trigger immediate default. When the borrowing constraint is not binding, the trade‐off theory of debt holds: optimal debt equates the marginal interest tax shield and the marginal expected cost of default. Contrary to conventional interpretation, but consistent with empirical findings, increases in current or future profitability reduce the optimal leverage ratio when the trade‐off theory holds.
Self‐ and informant perceptions of psychopathic traits in relation to the triarchic model
Authors: Kelley Shannon E. , Edens John F. , Donnellan M. Brent , Mowle Elyse N. , Sörman Karolina
Published: October 2017

Objective

The validity of self‐report psychopathy measures may be undermined by characteristics thought to be defining features of the construct, including poor self‐awareness, pathological lying, and impression management. The current study examined agreement between self‐ and informant perceptions of psychopathic traits captured by the triarchic model (Patrick, Fowler, & Krueger, 2009) and the extent to which psychopathic traits are associated with socially desirable responding.

Method

Participants were undergraduate roommate dyads (N = 174; Mage = 18.9 years; 64.4% female; 59.8% Caucasian) who completed self‐ and informant reports of boldness, meanness, and disinhibition.

Results

Self‐reports of psychopathic traits reasonably aligned with the perceptions of informants (rs = .36–.60), and both predicted various types of antisocial behaviors, although some associations were only significant for monomethod correlations. Participants viewed by informants as more globally psychopathic did not engage in greater positive impression management. However, this response style significantly correlated with self‐ and informant‐reported boldness, suppressing associations with antisocial behavior.

Conclusions

These findings suggest that participants are willing and able to disclose psychopathic personality traits in research settings under conditions of confidentiality. Nonetheless, accounting for response style is potentially useful when using self‐report measures to examine the nature and correlates of psychopathic traits.
Melatonin ameliorates Aβ1-42-induced Alzheimer's cognitive deficits in mouse model
Authors: Gong Yu-Hang , Hua Nan , Zang Xuan , Huang Tao , He Ling
Published: October 2017

Objectives

The objective of this study was to evaluate whether melatonin could ameliorate cognitive function in Aβ1-42-induced mouse model and its underlying mechanisms.

Methods

Series behaviour tests were performed to demonstrate the amelioration of cognitive function of the Alzheimer's disease (AD) mice induced by Aβ1-42. Additionally, enzyme-linked immunosorbent assay was applied to detect the expression of Aβ1-42, BACE1 and p-tau protein in the brain of the AD mice. JC-1 was performed to investigate the role in alleviating mitochondrial damage by melatonin in vitro. Western blot was used to detect the expression of melatonin on apoptosis-related factors caspase-3 and Bcl-2, as well as the expressions of GSK-3β and PP2A to further determine the mechanisms of melatonin on the expression of p-tau protein.

Key findings

Melatonin significantly ameliorated the cognitive function and mitochondrial damage in AD mice, reduced the expression levels of GSK-3β, caspase-3, Aβ1-42, BACE1, p-tau protein and increased the expressions of PP2A and Bcl-2.

Conclusion

From the overall results, we concluded that melatonin alleviated the mitochondrial damage effectively and decreased the expressions of the p-tau and some key proteins of apoptosis, leading to the improvement of cognitive function of the mice induced by Aβ1-42.
An integrated community‐based outpatient therapeutic feeding programme for severe acute malnutrition in rural Southern Ethiopia: Recovery, fatality, and nutritional status after discharge
Authors: Tadesse Elazar , Worku Amare , Berhane Yemane , Ekström Eva‐Charlotte
Published: October 2017

A scaled up and integrated outpatient therapeutic feeding programme (OTP) brings the treatment of severely malnourished children closer to the community. This study assessed recovery from severe acute malnutrition (SAM), fatality, and acute malnutrition up to 14 weeks after admission to a programme integrated in the primary health care system. In this cohort study, 1,048 children admitted to 94 OTPs in Southern Ethiopia were followed for 14 weeks. Independent anthropometric measurements and information on treatment outcome were collected at four home visits. Only 32.7% (248/759) of children with SAM on admission fulfilled the programme recovery criteria at the time of discharge (i.e., gained 15% in weight, or oedema, if present at admission, was resolved at discharge). Of all children admitted to the programme for whom nutritional assessment was done 14 weeks later, 34.6% (321/928) were severely malnourished, and 37.5% (348/928) were moderately malnourished; thus, 72.1% were acutely malnourished. Of the children, 27/982 (2.7%) had died by 14 weeks, of whom all but one had SAM on admission. Children with severe oedema on admission had the highest fatality rate (12.0%, 9/75). The median length of admission to the programme was 6.6 weeks (interquartile range: 5.3, 8.4 weeks). Despite children participating for the recommended duration of the programme, many children with SAM were discharged still acutely malnourished and without reaching programme criteria for recovery. For better outcome of OTP, constraints in service provision by the health system as well as challenges of service utilization by the beneficiaries should be identified and addressed.