bluuebunny/crossref_metadata_2025_split huggingface dataset:
Botulinum hemagglutinin-mediated selective removal of cells deviating from the undifferentiated state in hiPSC colonies
Authors: Kim Mee-Hae , Sugawara Yo , Fujinaga Yukako , Kino-oka Masahiro 
Published: March 2017

AbstractThe undifferentiated state of human induced pluripotent stem cells (hiPSCs) depends on their cell–cell and cell–substrate adhesions. In this study, we report that exposure to botulinum hemagglutinin (HA), an E-cadherin function-blocking agent, selectively removed cells that deviated from the undifferentiated state in hiPSC colonies. After HA treatment, cell–cell adhesion was disrupted, deviated cells detached from colony centers, and dividing cells filled these spaces. Because E-cadherin-mediated adhesion was disrupted in undifferentiated cells, stress-fiber formation and focal adhesions were diminished; however, these were subsequently restored, and the cells retained expression of undifferentiated stem cell markers and their differentiation potential. In contrast, actin structures and focal adhesions were lost from deviated cells, and they subsequently died. In undifferentiated and deviated cells, the cadherin/integrin-regulator Rap1 was localized at cell–cell adhesions and in the cytoplasm, respectively. Concurrent HA and Rap1-inhibitor treatment accelerated the deviated-cell detachment and delayed the recovery of hiPSC morphology, but this effect was significantly attenuated by co-treatment with Rap1 activator. Thus, Rap1 regulated E-cadherin–integrin interplay in hiPSC colonies exhibiting deviation, while HA-mediated selective removal of these deviated cells helped maintain the undifferentiated state in the remaining hiPSCs.
Air-coupled ultrasound detection using capillary-based optical ring resonators
Authors: Kim Kyu Hyun , Luo Wei , Zhang Cheng , Tian Chao , Guo L. Jay , Wang Xueding , Fan Xudong 
Published: March 2017

AbstractWe experimentally demonstrate and theoretically analyze high Q-factor (~107) capillary-based optical ring resonators for non-contact detection of air-coupled ultrasound. Noise equivalent pressures in air as low as 215 mPa/√Hz and 41 mPa/√Hz at 50 kHz and 800 kHz in air, respectively, are achieved. Furthermore, non-contact detection of air-coupled photoacoustic pulses optically generated from a 200 nm thick Chromium film is demonstrated. The interaction of an acoustic pulse and the mechanical mode of the ring resonator is also studied. Significant improvement in detection bandwidth is demonstrated by encapsulating the ring resonator in a damping medium. Our work will enable compact and sensitive ultrasound detection in many applications, such as air-coupled non-destructive ultrasound testing, photoacoustic imaging, and remote sensing. It will also provide a model system for fundamental study of the mechanical modes in the ring resonator.
In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain
Authors: Hikishima Keigo , Komaki Yuji , Seki Fumiko , Ohnishi Yasuyuki , Okano Hirotaka J. , Okano Hideyuki 
Published: March 2017

AbstractHundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 μm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.
Identifying Novel Transcriptional and Epigenetic Features of Nuclear Lamina-associated Genes
Authors: Wu Feinan , Yao Jie 
Published: March 2017

AbstractBecause a large portion of the mammalian genome is associated with the nuclear lamina (NL), it is interesting to study how native genes resided there are transcribed and regulated. In this study, we report unique transcriptional and epigenetic features of nearly 3,500 NL-associated genes (NL genes). Promoter regions of active NL genes are often excluded from NL-association, suggesting that NL-promoter interactions may repress transcription. Active NL genes with higher RNA polymerase II (Pol II) recruitment levels tend to display Pol II promoter-proximal pausing, while Pol II recruitment and Pol II pausing are not correlated among non-NL genes. At the genome-wide scale, NL-association and H3K27me3 distinguishes two large gene classes with low transcriptional activities. Notably, NL-association is anti-correlated with both transcription and active histone mark levels among genes not significantly enriched with H3K9me3 or H3K27me3, suggesting that NL-association may represent a novel gene repression pathway. Interestingly, an NL gene subgroup is not significantly enriched with H3K9me3 or H3K27me3 and is transcribed at higher levels than the rest of NL genes. Furthermore, we identified distal enhancers associated with active NL genes and reported their epigenetic features.
Dengue virus infection increases microglial cell migration
Authors: Jhan Ming-Kai , Tsai Tsung-Ting , Chen Chia-Ling , Tsai Cheng-Chieh , Cheng Yi-Lin , Lee Yi-Chao , Ko Chiung-Yuan , Lin Yee-Shin , Chang Chih-Peng , Lin Liang-Tzung , Lin Chiou-Feng 
Published: March 2017

AbstractActivated microglial cells are present in dengue virus (DENV)-infected brains; however, the possible effects of DENV on microglia remain unclear. Here, we demonstrated DENV caused infection, including viral entry, RNA replication, viral protein expression, and virus release, in the murine microglial cell line BV2. DENV infection caused an increase in the formation of the multipolar phenotype in vitro and in vivo without affecting cell growth and cytotoxicity. DENV infection considerably increased cell motility and disrupting either actin filaments or clathrin retarded such effect. Increase in cell migration was only occurred by DENV infection following a clathrin-regulated endocytosis of DENV entry. Ultraviolet-inactivated DENV did not affect cell migration, and pharmacologically blocking toll-like receptor (TLR) 3 and TLR3-related signaling pathways reduced the DENV-induced increase in cell migration. These results demonstrate an advanced effect of DENV infection on microglial migration via a mechanism involving viral entry, RNA release, and TLR3 signal activation.
Development of improved vaccine cell lines against rotavirus
Authors: Wu Weilin , Orr-Burks Nichole , Karpilow Jon , Tripp Ralph A. 
Published: March 2017

AbstractRotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine.
MicroRNA screening identifies miR-134 as a regulator of poliovirus and enterovirus 71 infection
Authors: Orr-Burks Nichole Lynn , Shim Byoung-Shik , Wu Weilin , Bakre Abhijeet A. , Karpilow Jon , Tripp Ralph A. 
Published: March 2017

AbstractMicroRNAs (miRNAs) regulate virus replication through multiple mechanisms. Poliovirus causes a highly debilitating disease and though global efforts to eradicate polio have sharply decreased polio incidence, unfortunately three countries (Afghanistan, Nigeria and Pakistan) remain polio-endemic. We hypothesize that understanding the host factors involved in polio replication will identify novel prophylactic and therapeutic targets against polio and related viruses. In this data set, employing genome wide screens of miRNA mimics and inhibitors, we identified miRNAs which significantly suppressed polio replication. Specifically, miR-134 regulates poliovirus replication via modulation of ras-related nuclear protein (RAN), an important component of the nuclear transport system. MiR-134 also inhibited other Picornaviridae viruses including EV71, a growing concern and a high priority for vaccination in Asian countries like China. These findings demonstrate a novel mechanism for miRNA regulation of poliovirus and other Picornaviridae viruses in host cells, and thereby may provide a novel approach in combating infection and a potential approach for the development of anti-Picornaviridae strategies.
Linking Environmental Exposure to Toxicity
Authors: Oki Noffisat , Leonard Jeremy , Nelms Mark , Bell Shannon , Tan Yu-Mei , Burgoon Lyle , Edwards Stephen 
Published: March 2017

As the number of chemicals and environmental toxicants in commerce continue to increase, so does the need to understand the links between exposure to these stressors and any potential toxic reactions. Assessing the impact of these stressors on public health as well as our environment requires an understanding of the underlying mechanistic processes connecting their introduction into the environment to the associated adverse outcomes.Traditional in vivo methods of toxicity testing have become too costly and inefficient. In recent times, in vitro high-throughput toxicity screening methods have been introduced to reduce the burden of in vivo testing and keep pace with the ever increasing number of required tests. The adverse outcome pathway (AOP) concept has been adopted by many in the toxicology community as a framework for linking the biological events that occur from the point of contact with these stressors and the resulting adverse outcome. This provides a mechanistic framework for understanding the potential impacts of perturbations that are measured via in vitro testing strategies. The aggregate exposure pathway (AEP) has been proposed as a companion framework to the AOP. The goal of the AEP is to describe the path the introduction of the stressor into the environment at its source to a target site within an individual that is comparable with the concentrations in the in vitro toxicity tests. Together, these frameworks provide a comprehensive view of the source to adverse outcome continuum.Standardizing our representation of the mechanistic information in this way allows for increased interoperability for computational models describing different parts of the system. It also aids in translating new research in exposure science and toxicology for risk assessors and decision makers when assessing the impact of specific stressors on endpoints of regulatory significance.
The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors
Authors: Jiménez-Castro Mónica B. , Negrete-Sánchez Elsa , Casillas-Ramírez Araní , Gulfo Jose , Álvarez-Mercado Ana I. , Cornide-Petronio María Eugenia , Gracia-Sancho Jordi , Rodés Juan , Peralta Carmen 
Published: March 2017

In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)–protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.
Disaster management curricula: strategy to create doctors with disaster resilience in Aceh, Indonesia
Authors: Wahyuniati N , Maulana R , Ichsan I 
Published: March 2017

Abstract
Faculty of Medicine of Syiah Kuala University has one special block called Disaster Management block (the last block on the curricula) on Competency-Based Curriculum of Medical Sciences with the Problem-Based Learning method. This block has four credits, allocated seven weeks learning period including one week for evaluation. The placement of disaster management block in the 7th semester (last semester) aims to allow students to implement more easily the complete basic and clinical medical knowledge and then have it integrated with the management capabilities during adisaster. This article evaluates two components: 1) Disaster management module, by comparing the content of modules used in three different academic years, the academic year 2013/2014, 2014/2015 and 2015/2016, 2) The final grade, by comparing the final grade of disaster management block in 4 years (comparing students class of 2008, 2009, 2010 and 2011). The results revealed that on every academic year there were additions and strengthening of the material to ensure that students achieve a complete learning experience, and there was a slight increase in student’s grades where the number of students who receive grades A has increased while the number of students who receive grades E decreased.
AQUA-DUCT: a ligands tracking tool
Authors: Magdziarz Tomasz , Mitusińska Karolina , Gołdowska Sandra , Płuciennik Alicja , Stolarczyk Michał , Ługowska Magdalena , Góra Artur 
Published: March 2017

Abstract

Motivation
The identification and tracking of molecules which enter active site cavity requires screening the positions of thousands of single molecules along several thousand molecular dynamic steps. To fill the existing gap between tools searching for tunnels and pathways and advanced tools employed for accelerated water flux investigations, we have developed AQUA-DUCT.

Results
AQUA-DUCT is an easy-to-use tool that facilitates analysis of the behaviour of molecules that penetrate any selected region in a protein. It can be used for any type of molecules, e.g. water, oxygen, carbon dioxide, organic solvents, ions.

Availability and Implementation
Linux, Windows, macOS, OpenBSD, http://www.aquaduct.pl.

Supplementary information
Supplementary data are available at Bioinformatics online.
Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK
Authors: Kerr Marion , Pears Robert , Miedzybrodzka Zofia , Haralambos Kate , Cather Moyra , Watson Melanie , Humphries Steve E. 
Published: March 2017

Aims
Familial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH.

Methods and Results
A Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services. The estimated incremental cost effectiveness ratio (ICER) was £5806 and the net marginal lifetime cost per relative tested was £2781. More than 80% of lifetime costs were diagnosis-related and incurred in the 1st year. In UK services, 23% of 6396 index cases were mutation-positive. For each mutation-positive index case, 1.33 relatives were tested, resulting overall in a rate of 0.31 tested relatives per tested index case. If the number of relatives tested per tested index case rose to 3.2 (projected by National Institute for Health and Care Excellence in 2008) the ICER would reduce to £2280 and lifetime costs to £1092.

Conclusion
Cascade testing of relatives of those with suspected FH is highly cost effective. The current Europe-wide high levels of undiagnosed FH, and associated morbidity and mortality, mean adoption of cascade services should yield substantial quality of life and survival gains.
Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the Fusion Rates. What is the Optimal Graft Material?
Authors: Parajón Avelino , Alimi Marjan , Navarro-Ramirez Rodrigo , Christos Paul , Torres-Campa Jose M , Moriguchi Yu , Lang Gernot , Härtl Roger 
Published: March 2017

AbstractBACKGROUNDMinimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an increasingly popular procedure with several potential advantages over traditional open TLIF.OBJECTIVEThe current study aimed to compare fusion rates of different graft materials used in MIS-TLIF, via meta-analysis of the published literature.METHODSA Medline search was performed and a database was created including patient's type of graft, clinical outcome, fusion rate, fusion assessment modality, and duration of follow-up. Meta-analysis of the fusion rate was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United Kingdom).RESULTSA total of 1533 patients from 40 series were included. Fusion rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion rate was seen with isolated use of autologous local bone (91.8%). The highest fusion rate was observed with combination of autologous local bone with bone extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was seen with autologous local bone + bone extender (93.1%). The reported complication rate ranged from 0% to 35.71%. Clinical improvement was observed in all studies.CONCLUSIONFusion rates are generally high with MIS-TLIF regardless of the graft material used. Given the potential complications of iliac bone harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable. The highest fusion rate without the use of rhBMP was seen with autologous local bone plus bone extender (93.1%).
Streptobacillus moniliformis Bacteremia in a Pet Shop Employee: Case Report and Literature Review
Authors: Suzuki Kiyozumi , Hirai Yuji , Morita Fujiko , Nakamura Ayako , Uehara Yuki , Naito Toshio 
Published: March 2017

Abstract
A 39-year-old pet shop employee who sustained a bite from one of his store’s rats developed fever and arthritis. Streptobacillus moniliformis was cultured from the patient’s blood, confirming a diagnosis of rat-bite fever. Treatment with standard antibiotics was successful. Although rat-bite fever is commonly considered a zoonosis transmitted by wild or laboratory rats, our case emphasizes that it may be transmitted by pet animals as well.
Pulmonary Histoplasma Infection After Allogeneic Hematopoietic Stem Cell Transplantation: Case Report and Review of the Literature
Authors: Natarajan Mukil , Swierzbinski Matthew J. , Maxwell Sandra , Zelazny Adrian M. , Fahle Gary A. , Quezado Martha , Barrett John , Battiwalla Minoo , Lionakis Michail S. 
Published: March 2017

Abstract
Histoplasmosis causes a wide spectrum of clinical illness, including disseminated infection in the immunocompromised. We report a case of pulmonary histoplasmosis in an allogeneic stem cell transplant recipient and review the literature on this topic. Histoplasmosis in this patient population is uncommon, but it is associated with poor outcome.
Expanding Local Cancer Clinical Trial Options: Analysis of the Economic Impact of the Midwest Cancer Alliance in Kansas
Authors: Gafford J. Atlee , Gurley-Calvez Tami , Krebill Hope , Lai Sue Min , Christiadi  , Doolittle Gary C. 
Published: March 2017

Purpose
Patients benefit from receiving cancer treatment closer to home when possible and at high-volume regional centers when specialized care is required. The purpose of this analysis was to estimate the economic impact of retaining more patients in-state for cancer clinical trials and care, which might offset some of the costs of establishing broader cancer trial and treatment networks.

Method
Kansas Cancer Registry data were used to estimate the number of patients retained in-state for cancer care following the expansion of local cancer clinical trial options through the Midwest Cancer Alliance based at the University of Kansas Medical Center. The 2014 economic impact of this enhanced local clinical trial network was estimated in four parts: Medical spending was estimated on the basis of National Cancer Institute cost-of-care estimates. Household travel cost savings were estimated as the difference between in-state and out-of-state travel costs. Trial-related grant income was calculated from administrative records. Indirect and induced economic benefits to the state were estimated using an economic impact model.

Results
The authors estimated that the enhanced local cancer clinical trial network resulted in approximately $6.9 million in additional economic activity in the state in 2014, or $362,000 per patient retained in-state. This estimate includes $3.6 million in direct spending and $3.3 million in indirect economic activity. The enhanced trial network also resulted in 45 additional jobs.

Conclusions
Retaining patients in-state for cancer care and clinical trial participation allows patients to remain closer to home for care and enhances the state economy.