bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive characterization of cis-acting splicing-associated variants in human cancer
Authors: Shiraishi Yuichi , Kataoka Keisuke , Chiba Kenichi , Okada Ai , Kogure Yasunori , Tanaka Hiroko , Ogawa Seishi , Miyano Satoru
Published: July 2017

Although many driver mutations are thought to promote carcinogenesis via abnormal splicing, the landscape of these splicing-associated variants (SAVs) remains unknown due to the complexity of splicing abnormalities. Here we developed a statistical framework to identify SAVs disrupting or newly creating splice site motifs and applied it to sequencing data from 8,976 samples across 31 cancer types. We constructed a catalog of 14,438 SAVs, approximately 50% of which consist of SAVs disrupting non-canonical splice sites (including the 3rd and 5th intronic bases of donor sites) or newly creating splice sites. Smoking-related signature substantially contributes to SAV generation. As many as 14.7% of samples harbor at least one SAVs in cancer-related genes, particularly in tumor suppressors. Importantly, in addition to previously reported intron retention, exon skipping or alternative splice site usage more frequently affected these genes. Our findings delineate a comprehensive portrait of SAVs, providing a basis for cancer precision medicine.
HECIL: A Hybrid Error Correction Algorithm for Long Reads with Iterative Learning
Authors: Choudhury Olivia , Chakrabarty Ankush , Emrich Scott J.
Published: July 2017

Second-generation sequencing techniques generate short reads that can result in fragmented genome assemblies. Third-generation sequencing platforms mitigate this limitation by producing longer reads that span across complex and repetitive regions. Currently, the usefulness of such long reads is limited, however, because of high sequencing error rates. To exploit the full potential of these longer reads, it is imperative to correct the underlying errors. We propose HECIL—Hybrid Error Correction with Iterative Learning—a hybrid error correction framework that determines a correction policy for erroneous long reads, based on optimal combinations of decision weights obtained from short read alignments. We demonstrate that HECIL outperforms state-of-the-art error correction algorithms for an overwhelming majority of evaluation metrics on diverse real data sets includingE. coli,S. cerevisiae, and the malaria vector mosquitoA. funestus. We further improve the performance of HECIL by introducing an iterative learning paradigm that improves the correction policy at each iteration by incorporating knowledge gathered from previous iterations via confidence metrics assigned to prior corrections.

Availability and Implementation

https://github.com/NDBL/HECIL

Contact

semrich@nd.edu
Self-organization mechanism of distinct microtubule orientations in axons and dendrites
Authors: Naoki Honda , Uegaki Katsuhiro , Ishii Shin
Published: July 2017

The identities of axons and dendrites are acquired through the self-organization of distinct microtubule (MT) orientations during neuronal polarization. The axon is generally characterized by a uniform MT orientation with all plus-ends pointing outward to the neurite terminal (‘plus-end-out’ pattern). On the other hand, the MT orientation pattern in the dendrites depends on species: vertebrate dendrites have a mixed alignment with both plus and minus ends facing either the terminal or the cell body (‘mixed’ pattern), whereas invertebrate dendrites have a ‘minus-end-out’ pattern. However, how MT organizations are developed in the axon and the dendrites is largely unknown. To investigate the mechanism of MT organization, we developed a biophysical model of MT kinetics, consisting of polymerization/depolymerization and MT catastrophe coupled with neurite outgrowth. The model simulation showed that the MT orientation can be controlled mainly by the speed of neurite growth and the hydrolysis rate. With a low hydrolysis rate, vertebrate plus-end-out and mixed microtubule patterns emerged in fast- and slow-growing neurites, respectively. In contrast, with a high hydrolysis rate, invertebrate plus-end-out and minus-end-out microtubule patterns emerged in fast- and slow-growing neurites, respectively. Thus, our model can provide a unified understanding of distinct microtubule organizations by simply changing the parameters.
Membrane bending begins at any stage of clathrin-coat assembly and defines endocytic dynamics
Authors: Scott Brandon L. , Sochacki Kem A. , Low-Nam Shalini T. , Bailey Elizabeth M. , Luu QuocAhn , Hor Amy , Dickey Andrea M. , Smith Steve , Kerkvliet Jason G. , Taraska Justin W. , Hoppe Adam D.
Published: July 2017

Summary Paragraph

Clathrin-mediated endocytosis internalizes membrane from the cell surface by reshaping flat regions of membrane into spherical vesicles(1, 2). The relationship between membrane bending and clathrin coatomer assembly has been inferred from electron microscopy and structural biology, without directly visualization of membrane bending dynamics (3–6). This has resulted in two distinct and opposing models for how clathrin bends membrane (7–10). Here, polarized Total Internal Reflection Fluorescence microscopy was improved and combined with electron microscopy, atomic force microscopy, and super-resolution imaging to measure membrane bending during endogenous clathrin and dynamin assembly in living cells. Surprisingly, and not predicted by either model, the timing of membrane bending was variable relative to clathrin assembly. Approximately half of the time, membrane bending occurs at the start of clathrin assembly, in the other half, the onset of membrane bending lags clathrin arrival, and occasionally completely assembled flat clathrin transitions into a pit. Importantly, once the membrane bends, the process proceeds to scission with similar timing. We conclude that the pathway of coatomer formation is versatile and can bend the membrane during or after the assembly of the clathrin lattice. These results highlight the heterogeneity in this fundamental biological process, and provide a more complete nanoscale view of membrane bending dynamics during endocytosis.
The use of gamification mechanics to increase employee and user engagement in participative healthcare services
Authors: Hammedi Wafa , Leclerq Thomas , Van Riel Allard C.R.
Published: July 2017

Purpose

Gamification introduces game-like properties into routine service processes to make them more engaging for service employees and users alike. The purpose of this paper is to investigate the effects of gamification mechanics, or game design principles, on user engagement in gamified healthcare services.

Design/methodology/approach

Through observations, interviews and the study of desk materials, two cases of gamified healthcare services, each using different game mechanics, are analyzed.

Findings

Gamification mechanics produce four distinct experiential outcomes in patients: challenge, entertainment, social dynamics, and escapism. Patient engagement can be stimulated through these outcomes. However, to fully enjoy the benefits of gamified services, users are often expected to acquire and use new skills. The relative absence of these skills (or difficulties in acquiring them), depending on users’ medical predispositions and age, may defer or negatively moderate the positive effects of gamification on engagement. In the case of progressively decreasing capabilities (e.g. in the case of aging users or users with degenerative diseases, whose physical or mental disabilities may be emphasized by the mechanics), it is recommended that health professionals adapt the mechanics accordingly or search for alternative options to increase patient well-being.

Research limitations/implications

The study was conducted in healthcare, and caution must be exercised in generalizing the findings to other domains. However, the finding that gamified service users’ disabilities - or the lack of required abilities – may negatively impact the encouraging or engaging effects of the use of gamification appears to be relatively universal.

Originality/value

This study contributes to service research, specifically in the healthcare domain, by providing insight into employees’ and users’ motivations for using gamified service processes, the experiential impact of gamification mechanics, the individual factors that influence users’ gamified experience and multiple forms of cognitive, emotional and behavioral engagement outcomes. A research agenda is developed.
Oral health strategy for the older people in social protection centers in Villavicencio, Colombia
Authors: Rodas Avellaneda Claudia Patricia , Angarita Díaz María del Pilar , Nemocon Ramírez Luis Francisco , Pinzón Castro Luis Alexys , Robayo Herrera Yenny Tatiana , Rodriguez Baquero Ines Leonilde , González Sanchez Rocio del Pilar
Published: July 2017

Purpose

The purpose of this paper is to design and to implement an oral health educational strategy that targeted an older population residing in three social protection centers (SPC) in Villavicencio, Colombia.

Design/methodology/approach

The first phase consisted in determining the oral health of older citizens in the SPC. To do this, the research group gathered patients’ personal information and indices. The second phase consisted in the development of an educational strategy based on the population’s requirements. The educational strategy, focusing on oral hygiene and denture care, was implemented for the older people and their caregivers. The third and final phase consisted in the research group measuring the effect of the designed strategy by repeating oral diagnoses for the older people six months after strategy implementation.

Findings

The results of the assessment indicated that implementing a strategy to strengthen oral hygiene care was positive, given that statistically significant reductions were observed in the soft plaque index and the Gingival Index (p<0.05).

Research limitations/implications

As a result of the complexity of the population, the data obtained after the strategy was implemented were significantly reduced. However, these results indicate that an educational strategy can have an effect on this type of population.

Originality/value

Implementing a strategy that promotes oral hygiene education and brushing skills, fosters good oral behavior and helps the older people in SPC to remember the information taught, thus contributing to their oral hygiene.
Measuring young consumers’ sustainable consumption behavior: development and validation of the YCSCB scale
Authors: Fischer Daniel , Böhme Tina , Geiger Sonja Maria
Published: July 2017

Purpose

Promoting sustainable consumption among young consumers has become a key priority on the research agenda in such different fields as education for sustainable development, environmental psychology and consumer policy. Progress in this field has been hampered by a lack of sophisticated research instruments capable of measuring consumption behaviors that are relevant both in terms of their sustainability impacts and their suitability for teenagers. This study aims to address this research gap and presents a scale for young consumers’ sustainable consumption behaviors (YCSCB) in the areas of food and clothing.

Design/methodology/approach

The scale was developed in a two-step, mixed-methods approach. In an initial qualitative interview study, the actual behaviors of theoretically selected young consumers (n= 8) were identified with regard to acquiring, using and disposing of consumer goods in the areas of food and clothing. The YCSCB scale was constructed using the findings of this qualitative study and then validated in a subsequent quantitative study (n= 155).

Findings

The YCSCB scale is a valid and reliable scale to measure young consumers’ sustainable consumption behavior in the areas of food (n= 14 items) and clothing (n= 13 items).

Originality/value

The findings of this research provide a twofold contribution to advancing research on YCSCB. Firstly, it presents a consolidated scale that is explicitly constructed for teenagers and their consumption contexts. Secondly, it proposes a heuristic for developing more sophisticated measurements of SCB among young consumers that would allow a comparison between studies, is focused on behaviors (instead of confounding behaviors with intentions, attitudes or values) and is impact-oriented in terms of sustainability relevance.
Angiotensin II‐preconditioning is associated with increased PKCε/PKCδ ratio and prosurvival kinases in mitochondria
Authors: Nuñez Rebeca E , Javadov Sabzali , Escobales Nelson
Published: July 2017

Angiotensin II‐preconditioning (APC) has been shown to reproduce the cardioprotective effects of ischaemic preconditioning (IPC), however, the molecular mechanisms mediating the effects of APC remain unknown. In this study, Langendorff‐perfused rat hearts were subjected to IPC, APC or both (IPC/APC) followed by ischaemia‐reperfusion (IR), to determine translocation of PKCε, PKCδ, Akt, Erk1/2, JNK, p38 MAPK and GSK‐3β to mitochondria as an indicator of activation of the protein kinases. In agreement with previous observations, IPC, APC and IPC/APC increased the recovery of left ventricular developed pressure (LVDP), reduced infarct size (IS) and lactate dehydrogenase (LDH) release, compared to controls. These effects were associated with increased mitochondrial PKCε/PKCδ ratio, Akt, Erk1/2, JNK, and inhibition of permeability transition pore (mPTP) opening. Chelerythrine, a pan‐PKC inhibitor, abolished the enhancements of PKCε but increased PKCδ expression, and inhibited Akt, Erk1/2, and JNK protein levels. The drug had no effect on the APC‐ and IPC/APC‐induced cardioprotection as previously reported, but enhanced the post‐ischaemic LVDP in controls. Losartan, an angiotensin II type 1 receptor (AT1‐R) blocker, abolished the APC‐stimulated increase of LVDP and reduced PKCε, Akt, Erk1/2, JNK, and p38. Both drugs reduced ischaemic contracture and LDH release, and abolished the inhibition of mPTP by the preconditioning. Chelerythrine also prevented the reduction of IS by APC and IPC/APC. These results suggest that the cardioprotection induced by APC and IPC/APC involves an AT1‐R‐dependent translocation of PKCε and survival kinases to the mitochondria leading to mPTP inhibition. In chelerythrine‐treated hearts, however, alternate mechanisms appear to maintain cardiac function.
Detection of viable Helicobacter pylori inside free‐living amoebae in wastewater and drinking water samples from Eastern Spain
Authors: Moreno‐Mesonero Laura , Moreno Yolanda , Alonso José Luis , Ferrús M. Antonia
Published: July 2017

Helicobacter pylori is one of the most concerning emerging waterborne pathogens. It has been suggested that it could survive in water inside free‐living amoebae (FLA), but nobody has studied this relationship in the environment yet. Thus, we aimed to detect viable H. pylori cells from inside FLA in water samples. Sixty‐nine wastewater and 31 drinking water samples were collected. FLA were purified and identified by PCR and sequencing. For exclusively detecting H. pylori inside FLA, samples were exposed to sodium hypochlorite and assayed by specific PMA‐qPCR, DVC‐FISH and culture. FLA were detected in 38.7% of drinking water and 79.7% of wastewater samples, even after disinfection. In wastewater, Acanthamoeba spp. and members of the family Vahlkampfiidae were identified. In drinking water, Acanthamoeba spp. and Echinamoeba and/or Vermamoeba were present. In 39 (58.2%) FLA‐positive samples, H. pylori was detected by PMA‐qPCR. After DVC‐FISH, 21 (31.3%) samples harboured viable H. pylori internalized cells. H. pylori was cultured from 10 wastewater samples. To our knowledge, this is the first report that demonstrates that H. pylori can survive inside FLA in drinking water and wastewater, strongly supporting the hypothesis that FLA could play an important role in the transmission of H. pylori to humans.
Insurance for Technology Adoption: An Experimental Evaluation of Schemes and Subsidies with Maize Farmers in Mexico
Authors: Freudenreich Hanna , Mußhoff Oliver
Published: July 2017

For farmers in developing countries, the combination of both risk aversion and the lack of insurance is often a major impediment to adoption of productivity‐enhancing technologies, such as higher yielding hybrid seed. In a framed field experiment with Mexican maize farmers, we investigate whether bundling hybrid seed with an insurance scheme can increase its adoption, while also controlling for risk aversion. We test insurance schemes with different levels of risk coverage and premium subsidies and find that (1) all schemes significantly increase the degree of adoption of the higher yielding seed, (2) partial insurance schemes perform worse than full insurance, (3) weather index insurance with geographical basis risk performs no worse than indemnity insurance, and (4) premium subsidies significantly increase the adoption effect of indemnity insurance, but not that of index insurance.
Annual Estimates of Recharge, Quick‐Flow Runoff, and Evapotranspiration for the Contiguous U.S. Using Empirical Regression Equations
Authors: Reitz M. , Sanford W.E. , Senay G.B. , Cazenas J.
Published: July 2017

This study presents new data‐driven, annual estimates of the division of precipitation into the recharge, quick‐flow runoff, and evapotranspiration (ET) water budget components for 2000‐2013 for the contiguous United States (CONUS). The algorithms used to produce these maps ensure water budget consistency over this broad spatial scale, with contributions from precipitation influx attributed to each component at 800 m resolution. The quick‐flow runoff estimates for the contribution to the rapidly varying portion of the hydrograph are produced using data from 1,434 gaged watersheds, and depend on precipitation, soil saturated hydraulic conductivity, and surficial geology type. Evapotranspiration estimates are produced from a regression using water balance data from 679 gaged watersheds and depend on land cover, temperature, and precipitation. The quick‐flow and ET estimates are combined to calculate recharge as the remainder of precipitation. The ET and recharge estimates are checked against independent field data, and the results show good agreement. Comparisons of recharge estimates with groundwater extraction data show that in 15% of the country, groundwater is being extracted at rates higher than the local recharge. These maps of the internally consistent water budget components of recharge, quick‐flow runoff, and ET, being derived from and tested against data, are expected to provide reliable first‐order estimates of these quantities across the CONUS, even where field measurements are sparse.
The Contribution of Foreign Real Estate Investment to Housing Price Growth in Australian Capital Cities
Authors: Guest Ross , Rohde Nicholas
Published: July 2017

This paper models the effects of foreign investment in real estate on housing prices in Australia. We use a variety of panel data models that account for cross‐sectional heterogeneity across Australian cities and find that increases in investment are significant predictors of rises in the Australian Bureau of Statistics’ Residential Property Price Index. Our results are generally robust and suggest that increases in foreign investment account for between 20% and 30% of the rise in housing prices between 2004 and 2014 in Sydney and Melbourne. In other capital cities the effects appear to be negligible. Some policy implications of our findings are discussed.
Implementing comprehensive land claims agreements in Canada: Towards an analytical framework
Authors: Alcantara Christopher
Published: July 2017

Although there is a rich literature on the negotiation and contents of comprehensive land claims agreements, very little has been written on the dynamics of their implementation. This article contributes by sketching out a framework for analyzing the interactions between Indigenous, federal, and provincial/territorial governments in the implementation of modern treaties in Canada. It finds that a useful way for conceptualizing these situations is to focus on two characteristics relating to the treaty provisions and the signatories while remaining sensitive to the effects of time and other contextual factors.
Screening protocols to monitor respiratory status in primary immunodeficiency disease: findings from a European survey and subclinical infection working group
Authors: Jolles S , Sánchez-Ramón S , Quinti I , Soler-Palacín P , Agostini C , Florkin B , Couderc L-J , Brodszki N , Jones A , Longhurst H , Warnatz K , Haerynck F , Matucci A , de Vries E
Published: July 2017

Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%). The frequency of clinic visits varied both within and between centres: every 1–12 months for adult patients and every 3–6 months for paediatric patients. Patients diagnosed with lung diseases were more likely to receive pharmaceutical therapies and received a wider range of therapies than patients without lung disease. Variation existed between centres in the frequency with which some clinical and laboratory monitoring tests are performed, including exercise tests, laboratory testing for IgG subclass levels and specific antibodies, and lung function tests such as spirometry. Some tests were carried out more frequently in adults than in children, probably due to difficulties conducting these tests in younger children. The percentage of patients seen regularly by a chest physician, or who had microbiology tests performed following chest and sinus exacerbations, also varied widely between centres. Our survey revealed a great deal of variation across Europe in how frequently patients with PID visit the clinic and how frequently some monitoring tests are carried out. These results highlight the urgent need for consensus guidelines on how to monitor lung complications in PID patients.
Current insights into the role of human β-defensins in atopic dermatitis
Authors: Chieosilapatham P , Ogawa H , Niyonsaba F
Published: July 2017

Anti-microbial peptides or host defence peptides are small molecules that display both anti-microbial activities and complex immunomodulatory functions to protect against various diseases. Among these peptides, the human β-defensins (hBDs) are localized primarily in epithelial surfaces, including those of the skin, where they contribute to protective barriers. In atopic dermatitis skin lesions, altered skin barrier and immune dysregulation are believed to be responsible for reduced hBD synthesis. Impaired hBD expression in the skin is reportedly the leading cause of increased susceptibility to bacterial and viral infection in patients with atopic dermatitis. Although hBDs have considerable beneficial effects as anti-microbial agents and immunomodulators and may ameliorate atopic dermatitis clinically, recent evidence has also suggested the negative effects of hBDs in atopic dermatitis development. In the current review, we provide an overview of the regulation of hBDs and their role in the pathogenesis of atopic dermatitis. The efforts to utilize these molecules in clinical applications are also described.
A novel variant of DHH in a familial case of 46,XY disorder of sex development: Insights from molecular dynamics simulations
Authors: Paris Francoise , Flatters Delphine , Caburet Sandrine , Legois Bérangère , Servant Nadège , Lefebvre Hervé , Sultan Charles , Veitia Reiner A.
Published: July 2017

Objective

Disorders of sex development (DSD) are a heterogeneous group of conditions affecting the differentiation and development of the internal and external genitalia. Here, we aimed at identifying the genetic cause of DSD in two 46,XY sisters from a consanguineous family.

Design

We performed a whole‐exome sequencing of two 46,XY female individuals. Sanger sequencing was used to validate the most likely candidate variant, affecting the desert hedgehog (DHH) gene. Molecular dynamics simulations were performed to get insights into the impact of the variant on protein structure and on its interaction with the protein partner BOC (brother of CDO/cell adhesion molecule, downregulated by oncogenes).

Patients

The index patient presented with a female phenotype, primary amenorrhoea (low oestradiol and testosterone and high FSH and LH). She also had an apparent absence of intra‐abdominal gonads and uterus, facial dysmorphy, psychomotor retardation and neuropathy. Her sister displayed a similar gonadal and endocrinological picture, without dysmorphy or psychomotor retardation.

Results

Whole‐exome sequencing revealed a homozygous variant in DHH leading to the p.Trp173Cys substitution. The relevant Trp residue is conserved, and its alteration was predicted to be deleterious. Molecular dynamics simulations showed that the mutation increases the conformational flexibility of the protein and potentially alters its interaction with BOC, a positive regulator of Hedgehog signalling. We do not exclude an interference of the mutation with DHH‐intein‐mediated auto‐processing.

Conclusions

This report increases the number of described homozygous DHH variants and highlights the importance of advanced bioinformatic tools to better understand the pathogenicity of human variants.
Novel non‐neutral mitochondrial DNA mutations found in childhood acute lymphoblastic leukemia
Authors: Järviaho T. , Hurme‐Niiranen A. , Soini H.K. , Niinimäki R. , Möttönen M. , Savolainen E.‐R. , Hinttala R. , Harila‐Saari A. , Uusimaa J.
Published: July 2017

Mitochondria produce adenosine triphosphate (ATP) for energy requirements via the mitochondrial oxidative phosphorylation (OXPHOS) system. One of the hallmarks of cancer is the energy shift toward glycolysis. Low OXPHOS activity and increased glycolysis are associated with aggressive types of cancer. Mitochondria have their own genome (mitochondrial DNA [mtDNA]) encoding for 13 essential subunits of the OXPHOS enzyme complexes. We studied mtDNA in childhood acute lymphoblastic leukemia (ALL) to detect potential pathogenic mutations in OXPHOS complexes. The whole mtDNA from blood and bone marrow samples at diagnosis and follow‐up from 36 ALL patients were analyzed. Novel or previously described pathogenic mtDNA mutations were identified in 8 out of 36 patients. Six out of these 8 patients had died from ALL. Five out of 36 patients had an identified poor prognosis genetic marker, and 4 of these patients had mtDNA mutations. Missense or nonsense mtDNA mutations were detected in the genes encoding subunits of OXPHOS complexes, as follows: MT‐ND1, MT‐ND2, MT‐ND4L and MT‐ND6 of complex I; MT‐CO3 of complex IV; and MT‐ATP6 and MT‐ATP8 of complex V. We discovered mtDNA mutations in childhood ALL supporting the hypothesis that non‐neutral variants in mtDNA affecting the OXPHOS function may be related to leukemic clones.
Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients
Authors: Chérot E. , Keren B. , Dubourg C. , Carré W. , Fradin M. , Lavillaureix A. , Afenjar A. , Burglen L. , Whalen S. , Charles P. , Marey I. , Heide S. , Jacquette A. , Heron D. , Doummar D. , Rodriguez D. , Billette de Villemeur T. , Moutard M.‐L. , Guët A. , Xavier J. , Périsse D. , Cohen D. , Demurger F. , Quélin C. , Depienne C. , Odent S. , Nava C. , David V. , Pasquier L. , Mignot C.
Published: July 2017

Although whole‐exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM‐referenced genes called “medical exome” (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non‐syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.
Conversion from calcineurin inhibitors to mTOR inhibitors as primary immunosuppressive drugs in pediatric heart transplantation
Authors: Asante‐Korang Alfred , Carapellucci Jennifer , Krasnopero Diane , Doyle Abigail , Brown Brian , Amankwah Ernest
Published: July 2017

There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections, and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995 to 2015. Nineteen patients were switched from tacrolimus (n=15) or cyclosporin (n=4) to everolimus (n=4) or sirolimus (n=15) due to nephrotoxicity (n=5), malignancy (n=8), EBV viremia/reactive plasmacytic changes (n=5), and immune hemolytic anemia (n=1). We monitored for rejection, infection, BUN, creatinine, hyperlipidemia, EBV and CMV copies, CBC, cardiac allograft vasculopathy (CAV), and death. Target trough levels of sirolimus and everolimus were 4‐10. Four treatment failures included debilitating rash, bone marrow suppression, recurrent rejection, and renal transplantation. There were no deaths. One patient had recurrent rejection episodes, and tacrolimus was reinitiated. One patient with preexisting CAV underwent heart retransplantation. One patient, who was treated for PTLD, transformed to CD30+ Hodgkins disease, and was treated with brentuximab. There were three acute rejection episodes. Median creatinine preswitch was higher 0.82 than postswitch 0.78 (P=.016). Median eGFR was lower preswitch, 75.6, than postswitch, 91.2 (P=.0004). These results indicate that conversion to mTORI as primary immunosuppression may be safely accomplished in some pediatric heart transplant patients.
CD13 is a marker for onychofibroblasts within nail matrix onychodermis: Comparison of its expression patterns in the nail unit and in the hair follicle
Authors: Park Ji‐Hye , Lee Dong‐Youn , Jang Kee‐Taek , Ha Sang‐Yun , Kwon Ghee Young , Lee Kyung‐Hoon , Shim Jong Sup , Kwon Eun Ji
Published: July 2017

Background

We previously demonstrated the presence of onychodermis, a specialized mesenchymal cell population beneath the nail matrix and proximal nail bed demonstrating CD10 expression. We hypothesize that the onychodermis could be the nail analog of the follicular dermal papilla, which is known to express CD13. We compare CD13 expression patterns between specialized mesenchymes of nail and hair, and compare these findings with CD10 expression patterns.

Methods

CD10 and CD13 immunohistochemistry was performed on polydactyly and adult cadaveric nail units, and on hair follicles in scalp nevus sebaceus excision specimens.

Results

CD10 and CD13 were expressed in the mesenchyme below the nail matrix and nail bed. Stronger CD13 expression was observed in the mesenchyme containing onychofibroblasts below the nail matrix compared with that below the nail bed. CD10 was expressed in the dermal sheath of terminal hair follicles, but it was expressed in the dermal sheath and follicular dermal papilla of primitive hair follicles within nevus sebaceus lesions. CD13 was expressed in the dermal sheath and dermal papilla of terminal and primitive hair follicles.

Conclusion

CD13 may be a marker for onychofibroblasts within nail matrix onychodermis. We demonstrate CD13 expression in the specialized mesenchymes of both nail and hair.
Effect of optogenetic manipulation of accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine‐induced behavioral sensitization
Authors: Kang Byeong Jun , Song Shelly Sooyun , Wen Lei , Hong Ki‐Pyo , Augustine George J. , Baik Ja‐Hyun
Published: July 2017

Repetitive exposure to addictive drugs causes synaptic modification in the mesocorticolimbic dopamine (DA) system. Dopamine D1 receptors (D1R) or D2 receptors (D2R) expressed in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) play critical roles in the control of addictive behaviors. Optogenetic activation of D2R‐expressing MSNs (D2R‐MSNs) in the NAc previously demonstrated that these neurons play a key role in withdrawal‐induced plasticity. Here, we examined the effect of optogenetic inhibition of D2R‐MSNs in the NAc on cocaine‐induced behavioral sensitization. Adeno‐associated viral vectors encoding archaerhodopsin (ArchT) were delivered into the NAc of D2‐Cre transgenic mice. Activation of ArchT produced photoinhibition of D2R‐MSNs and caused disinhibition of neighboring MSNs in the NAc. However, such optogenetic silencing of D2R‐MSNs in the NAc in vivo affected neither the initiation nor the expression of cocaine‐induced behavioral sensitization. Similarly, photoinhibition of NAc D2R‐MSNs in the NAc during the drug withdrawal period did not affect the expression of cocaine‐induced behavioral sensitization. More detailed analysis of the effects of optogenetic activation of D2R‐MSNs suggests that D2R‐MSNs in the NAc exert important modulatory effects on neighboring MSN neurons, which may control the balanced output of NAc MSNs to control addictive behaviors.
Utility of digital subtraction angiography‐based collateral evaluation in medically treated acute symptomatic basilar artery stenosis
Authors: Lee W.‐J. , Jung K.‐H. , Ryu Y. J. , Kim J.‐M. , Lee S.‐T. , Chu K. , Kim M. , Lee S. K. , Roh J.‐K.
Published: July 2017

Background and purpose

Although a stroke from atherosclerosis in the basilar artery (BA) often presents with mild initial stroke severity, it has heterogeneous clinical courses. We investigated the efficacy of digital subtraction angiography (DSA)‐based collateral perfusion evaluation in association with long‐term outcomes of medically treated symptomatic basilar artery stenosis.

Methods

From a registry database of all consecutive patients with stroke, we included 98 medically treated patients (due to mild initial stroke severity) [National Institute of Health Stroke Scale (NIHSS) scores ≤ 4; symptomatic basilar artery stenosis, 70–99%] with available initial diagnostic DSA. Basilar collateral scoring was performed via the DSA, using a modified version of the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system in both the superior cerebellar artery and anterior/posterior‐inferior cerebellar artery territories (score 0–8). The outcomes were designated as the 90‐day modified Rankin Scale (mRS90) score (poor, 3–6). Student's t‐test, chi‐square test and logistic regression analyses were used to identify factors associated with a poor outcome.

Results

The median initial NIHSS score was 2 [interquartile range (IQR), 0–3], median posterior circulation Alberta Stroke Program Early CT Score was 8 (IQR, 7–10), median collateral score was 7 (IQR, 7–8) and 20 (20.4%) had poor mRS90 scores. In multivariate analysis, poorer collateral scores (P = 0.003), higher NIHSS scores (P = 0.005) and lower posterior circulation Alberta Stroke Program Early CT Score (P = 0.017) were independently associated with a poor mRS90 score.

Conclusions

The DSA‐based collateral scoring of the BA large branches might predict long‐term outcome in medically treated symptomatic basilar artery stenosis with mild initial severity. Evaluation of BA collateral perfusion status might be useful to determine appropriate treatment strategies.
The ecology of fish in the surf zones of ocean beaches: A global review
Authors: Olds Andrew D. , Vargas‐Fonseca Elena , Connolly Rod M. , Gilby Ben L. , Huijbers Chantal M. , Hyndes Glenn A. , Layman Craig A. , Whitfield Alan K. , Schlacher Thomas A.
Published: July 2017

The surf zones of ocean beaches provide habitat for a diversity of fishes and are prime sites for recreational angling and commercial net fisheries. Here, we review the global literature (152 studies) on surf fish ecology to better inform fisheries management and coastal conservation planning. These studies suggest that surf zones support diverse fish assemblages, which are characterized by high numerical dominance (10 species typically comprise 95% of catches), but also show that few families are especially common. The composition of assemblages is highly variable, changing with fluctuations in water temperature, wave climate and the biomass of drifting algae or seagrass. Fish use surf zones as feeding habitats and transit routes, but these areas might not be widely used as spawning sites or juvenile nurseries. These systems are under escalating human pressures, most notably from coastal urbanization and recreational angling. Despite the recognized ecological and economic importance of surf‐zone fishes, few studies have tested for impacts of urbanization or fishing. The benefits of marine reserves for fish in surf zones are also rarely measured. We suggest that progress will be made by moving from largely descriptive studies to hypothesis‐driven research, which is guided by contemporary ecological theory and adapts modern techniques from research in other ecosystems. A key challenge is to obtain empirical data that are needed to improve the effectiveness of fisheries management and underpin conservation planning for coastal waters.
Survive the droughts, I wish you well: Principles and cases of liquidity risk management
Authors: Tuckman Bruce
Published: July 2017

Short‐term, liquid assets are highly valued by lenders, but pose liquidity risk management challenges to borrowers. Basic principles to meet those challenges are to conduct liquidity stress scenario analysis; to form business plans for each stress scenario; to hold enough capital to sustain the planned, post‐shock balance sheet; and to hold a large enough liquidity reserve to survive the transition from the pre‐ to the post‐shock balance sheet. Historical failures, like Northern Rock, Bear Stearns, and MF Global have a lot to teach about implementing these principles. While regulatory frameworks constrain liquidity positions, they are no substitute for firm‐specific liquidity risk management.
“Do you dive?”: Methodological considerations for engaging with “volume”
Authors: Squire Rachael
Published: July 2017

The idea that we inhabit three dimensions is clearly not new, yet the explicit articulation of “volume” in recent literature has proved to be an extremely useful means through which to produce novel insights into the conduct and practice of geopolitics. Although the value of engaging with “volume” has been well established and taken discussions in new directions, yet the practicalities of doing this research are yet to be considered in great detail. How methodologically do we approach the three‐dimensional within political geography? Although this paper does not seek to outline a methodological framework, it draws on my own research to prompt discussion about the role of “immersive” methodologies in generating different perspectives within political geography. The paper ends by suggesting that a stronger interface between political geography and methodologies utilised in other geographical subdisciplines might be useful in producing novel insights into the earth's geopolitical volumes.
Prediction of geriatric rehabilitation outcomes: Comparison between three cognitive screening tools
Authors: Heyman Noemi , Tsirulnicov Tatyana , Ben Natan Merav
Published: July 2017

Aim

Comparison between the predictions of functional rehabilitation outcomes at a department of geriatric rehabilitation using three cognitive screening tools – Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).

Methods

This study is a prospective study. The study participants were 212 patients aged 65 and older admitted to rehabilitation departments at a geriatric facility in central Israel, from April 2016 to October 2016. The cognitive functioning of each patient was assessed using the MMSE, MoCA, and IQCODE. Upon discharge, rehabilitation outcomes were examined using the Functional Independence Measure (FIM), cognitive FIM, delta FIM (Δ FIM), and ADL.

Results

Cognitive impairment was found to interfere with the rehabilitation process. The MMSE was the best predictor of functional rehabilitation outcomes at discharge, compared to the IQCODE, while the MoCA did not predict these measures. In addition, when distinguishing between patients by ethnicity (Jewish versus Arab), the MMSE and the IQCODE predicted FIM upon discharge among Jewish patients, while only the IQCODE predicted FIM upon discharge among Arab patients.

Conclusions

The research findings show that cognitive assessment upon admission for rehabilitation – MMSE among Jewish patients and IQCODE among Arab patients – can help predict functional rehabilitation outcomes and make the appropriate adaptations in the rehabilitation program. Geriatr Gerontol Int 2017; 17: 2507–2513.
New insights into sinusoidal obstruction syndrome
Authors: Piccin Andrea , Sartori Maria T. , Bisogno Gianni , Van Schilfgaarde Muriel , Saggiorato Graziella , Pierro Angela M. D. , Corvetta Daisy , Marcheselli Luigi , Mega Andrea , Gastl Günther , Cesaro Simone
Published: July 2017

Background

Entry criteria included patients who developed sinusoidal obstruction syndrome (SOS) at a single centre from January 2000 to December 2011. Patients who underwent haemopoietic stem cell transplantation or actinomicyn‐based chemotherapy for nephroblastoma were selected. The study group comprised five patients with SOS who were compared with a control group of seven patients without SOS.

Aim

To study the relationships between endothelial extracellular vesicles (EV) and plasminogen‐activator inhibitor type 1(PAI‐1) to assess their modification in the early phase of SOS.

Methods

Consecutive blood samples were tested for cell‐derived EV, PAI‐1 and coagulation parameters. Any statistically significant correlation between all datasets was searched.

Results

Antithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI‐1:Ag and PAI‐1:act showed an inverse relationship with platelet counts (coef. −0.034, SE = 0.016; P = 0.041 and −0.052, SE = 0.019; P = 0.011 respectively). During follow up, PAI‐1:Ag was inversely related to EV CD144+ (coef. −0.261, SE = 0.094; P = 0.007) and antithrombin (coef −0.509, SE = 0.175; P = 0.005). PAI‐1:act showed an inverse association with EV CD144+ (coef.−0.251, SE = 0.121; P = 0.043), EV CD31+/CD41+ (coef. −0.004, SE = 0.002; P = 0.026) and antithrombin (coef. −0.470, SE = 0.220; P = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and also showed a change over time.

Conclusion

This study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI‐1, as a new biomarker for SOS.
Predict disease progression from T‐cell phenotypes in northern pig‐tailed macaques (Macaca leonina) during SIVmac239 infection
Authors: Zhang Ming‐Xu , Zheng Hong‐Yi , Jiang Jin , Song Jia‐Hao , Chen Min , Xiao Yu , Lian Xiao‐Dong , Song Tian‐Zhang , Tian Ren‐Rong , Pang Wei , Zheng Yong‐Tang
Published: July 2017

Macaca leonina (northern pig‐tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analysed, for the first time, the correlations between T‐cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T‐cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T‐cell count and CD4 : CD8 ratio, and lower plasma viral load than NPs. CD4+ T‐cell count and CD4 : CD8 ratio decreased more sharply in NPs than in SPs. Furthermore, T cells in NPs were more highly differentiated, at least in acute infection, than in SPs. These results indicated that T‐cell phenotypes were correlated with disease progression in SIVmac239‐infected NPMs and these correlations may provide valuable guidance for the improvement of therapeutic strategies tested in NPMs.
Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome
Authors: Guo Qing‐Hua , Wang Cheng‐Zhi , Wu Zhi‐Qiang , Qin Yan , Han Bai‐Yu , Wang An‐Ping , Wang Bao‐An , Dou Jing‐Tao , Wu Xiao‐Sheng , Mu Yi‐Ming
Published: July 2017

Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole‐exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.