bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflux aspiration in lungs of dogs with respiratory disease and in healthy West Highland White Terriers
Authors: Määttä O. L. Merita , Laurila Henna P. , Holopainen Saila , Lilja‐Maula Liisa , Melamies Marika , Viitanen Sanna J. , Johnson L. R. , Koho Ninna , Neuvonen Mikko , Niemi Mikko , Rajamäki Minna M.
Published: October 2018

Background

Gastroesophageal reflux and microaspiration (MA) of gastric juice are associated with various human respiratory diseases but not in dogs.

Objective

To detect the presence of bile acids in bronchoalveolar lavage fluid (BALF) of dogs with various respiratory diseases.

Animals

Twenty‐seven West Highland White Terriers (WHWTs) with canine idiopathic pulmonary fibrosis (CIPF), 11 dogs with bacterial pneumonia (BP), 13 with chronic bronchitis (CB), 9 with eosinophilic bronchopneumopathy (EBP), 19 with laryngeal dysfunction (LD), 8 Irish Wolfhounds (IWHs) with previous BPs, 13 healthy WHWTs, all privately owned dogs, and 6 healthy research colony Beagles

Methods

Prospective cross‐sectional observational study with convenience sampling of dogs. Bile acids were measured by mass spectrometry in BALF samples. Total bile acid (TBA) concentration was calculated as a sum of 17 different bile acids.

Results

Concentrations of TBA were above the limit of quantification in 78% of CIPF, 45% of BP, 62% of CB, 44% of EBP, 68% of LD, and 13% of IWH dogs. In healthy dogs, bile acids were detected less commonly in Beagles (0/6) than in healthy WHWTs (10/13). Concentrations of TBA were significantly higher in CIPF (median 0.013 μM, range not quantifiable [n.q.]‐0.14 μM, P < .001), healthy WHWTs (0.0052 μM, n.q.‐1.2 μM, P = .003), LD (0.010 μM, n.q.‐2.3 μM, P = .015), and CB (0.0078 μM, n.q.‐0.073 μM, P = .018) groups compared to Beagles (0 μM, n.q.).

Conclusion and Clinical Importance

These results suggest that MA occurs in various respiratory diseases of dogs and also in healthy WHWTs.
Gesture and Vocabulary Learning in a Second Language
Authors: Huang Xiaoyi , Kim Nayoung , Christianson Kiel
Published: October 2018

When introducing new words in a second language (L2), presenting vocabulary with concurrent gestures might facilitate learners’ recollection of new words. Previous research has suggested that this gestural advantage might hold only for gestures that overlap with the semantics of the words. Dual coding theory predicts that learners should learn input better when multiple sensory routes act as aids to retrieval. Our research replicated and extended previous studies examining the limits of gestures in learning L2 vocabulary. A within‐participant design directly compared the effects of pairing low idiosyncratic gestures (gestures traditionally iconic with word meanings) versus high idiosyncratic gestures (gestures that likely need to be idiosyncratically paired with word meanings) with L2 vocabulary presentation, relative to using no gestures. Results supported dual coding theory: All gestures were helpful if they were not confusable with other to‐be‐learned words and if the number of words presented was limited.

Open Practices

This article has been awarded an Open Data badge. All data are publicly accessible via the Open Science Framework at https://osf.io/4awze. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
Nursing schools on the increase as the 18 year old population decreases in Japan
Authors: Yamashita Mineko , Miyatake Yoko
Published: October 2018

Baccalaureate nursing programs have been on the increase in Japan in the past few decades. However, the 18 year old population is on the decline. While nursing programs have been increasing, the number of high school graduates has decreased. The paradoxical phenomenon has started to affect nursing education, including shortages in faculty members and in clinical sites. The purpose of the present study was to identify actual or potential problems as a result of so many nursing schools having opened in the past few decades, and to make recommendations for nurse educators in Japan.
Enteric RET inhibition attenuates gastrointestinal secretion and motility via cholinergic signaling in rat colonic mucosal preparations
Authors: Russell John P. , Mohammadi Ehsan , Ligon Casey , Latorre Rocco , Johnson Anthony C. , Hoang Bao , Krull David , Ho Melisa W.‐Y. , Eidam Hilary S. , DeMartino Michael P. , Cheung Mui , Oliff Allen I. , Kumar Sanjay , Greenwood‐Van Meerveld Beverley
Published: October 2018

Background

The expression of RET in the developing enteric nervous system (ENS) suggests that RET may contribute to adult intestinal function. ENS cholinergic nerves play a critical role in the control of colonic function through the release of acetylcholine (ACh). In the current study, we hypothesized that a RET‐mediated mechanism may regulate colonic ion transport and motility through modulation of cholinergic nerves.

Methods

The effect of RET inhibition on active ion transport was assessed electrophysiologically in rat colonic tissue mounted in Ussing chambers via measurements of short circuit current (Isc) upon electrical field stimulation (EFS) or pharmacologically with cholinergic agonists utilizing a gastrointestinal (GI)‐restricted RET inhibitor. We assessed the effect of the RET inhibitor on propulsive motility via quantification of fecal pellet output (FPO) induced by the acetylcholinesterase inhibitor neostigmine.

Key Results

We found that enteric ganglia co‐expressed RET and choline acetyltransferase (ChAT) transcripts. In vitro, the RET kinase inhibitor GSK3179106 attenuated the mean increase in Isc induced by either EFS or carbachol but not bethanechol. In vivo, GSK3179106 significantly reduced the prokinetic effect of neostigmine.

Conclusion and Inferences

Our findings provide evidence that RET‐mediated mechanisms regulate colonic function by maintaining cholinergic neuronal function and enabling ACh‐evoked chloride secretion and motility. We suggest that modulating the cholinergic control of the colon via a RET inhibitor may represent a novel target for the treatment of intestinal disorders associated with increased secretion and accelerated GI transit such as irritable bowel syndrome with diarrhea (IBS‐D).
Models, movements, and minds: bridging the gap between decision making and action
Authors: Wispinski Nathan J. , Gallivan Jason P. , Chapman Craig S.
Published: October 2018

Decision making is a fundamental cognitive function, which not only determines our day‐to‐day choices but also shapes the trajectories of our movements, our lives, and our societies. While immense progress has been made in recent years on our understanding of the mechanisms underlying decision making, research on this topic is still largely split into two halves. Good‐based models largely state that decisions are made between representations of abstract value associated with available options; while action‐based models largely state that decisions are made at the level of action representations. These models are further divided between those that state that a decision is made before an action is specified, and those that regard decision making as an evolving process that continues until movement completion. Here, we review computational models, behavioral findings, and results from neural recordings associated with these frameworks. In synthesizing this literature, we submit that decision making is best understood as a continuous, graded, and distributed process that traverses a landscape of behaviorally relevant options, from their presentation until movement completion. Identifying and understanding the intimate links between decision making and action processing has important implications for the study of complex, goal‐directed behaviors such as social communication, and for elucidating the underlying mechanisms by which decisions are formed.
Pediatric asthma: An unmet need for more effective, focused treatments
Authors: Papadopoulos Nikolaos G. , Čustović Adnan , Cabana Michael D. , Dell Sharon D. , Deschildre Antoine , Hedlin Gunilla , Hossny Elham , Le Souëf Peter , Matricardi Paolo M. , Nieto Antonio , Phipatanakul Wanda , Pitrez Paulo M. , Pohunek Petr , Gavornikova Marcela , Jaumont Xavier , Price David B.
Published: October 2018

Background

Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma.

Methods

A two‐day, face‐to‐face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma.

Results

These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non‐steroid‐based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients.

Conclusions

There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real‐world evidence studies assessing anti‐immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti‐IgE and non‐steroid‐based alternative therapies may delay disease progression, leading to improved clinical outcomes.
The WRKY transcription factor, WRKY13, activates PDR8 expression to positively regulate cadmium tolerance in Arabidopsis
Authors: Sheng Yibao , Yan Xingxing , Huang Ying , Han Yangyang , Zhang Cheng , Ren Yongbing , Fan Tingting , Xiao Fangming , Liu Yongsheng , Cao Shuqing
Published: October 2018

Cadmium (Cd) extrusion is an important mechanism conferring Cd tolerance by decreasing its accumulation in plants. Previous studies have identified an Arabidopsis ABC transporter, PDR8, as a Cd extrusion pump conferring Cd tolerance. However, the regulation of PDR8 in response to Cd stress is still largely unknown. In this study, we identified an Arabidopsis cadmium‐tolerant dominant mutant, designated xcd3‐D, from the XVE‐tagging T‐DNA insertion lines by a gain‐of‐function genetic screen. The corresponding gene was cloned and shown to encode a nuclear WRKY transcription factor WRKY13. Expression of WRKY13 was induced by Cd stress. Overexpression of WRKY13 resulted in decreased Cd accumulation and enhanced Cd tolerance, whereas loss‐of‐function of WRKY13 led to increased Cd accumulation and sensitivity. Further analysis showed that WRKY13 activates the transcription of PDR8 by directly binding to its promoter. Genetic analysis indicated that WRKY13 acts upstream of PDR8 to positively regulate Cd tolerance. Our results provide evidence that WRKY13 directly targets PDR8 to positively regulate Cd tolerance in Arabidopsis.
Skin cancer phototype: A new classification directly related to skin cancer and based on responses from 2869 individuals
Authors: Holm‐Schou Ann‐Sofie Sonne , Philipsen Peter Alshede , Wulf Hans Christian
Published: October 2018

Background/purpose

Fitzpatrick phototype (FST) classification (based on ability to tan and tendency to burn) is widely used for evaluating skin cancer risk; however, it was not developed for that purpose and has been criticised scientifically. The purpose of the present study was a first approach in establishing a new skin cancer phototype (SCP) classification with direct relation to skin cancer risk, based on the questions originally proposed by Fitzpatrick. However, contrary to Fitzpatrick, the questions are in the present study kept separate.

Methods

Validated information on skin cancer and answers about participants’ tendency to burn (4 answers) and ability to tan (4 answers) were obtained from 2869 Danes. The 16 (4 × 4 answers) possible answers formed a matrix, on which a logistic regression was carried out. Successively, the matrix neighbours which were insignificantly different were identified; of which the neighbours with the mutual lowest difference were merged. The merging resulted in four different SCP classes.

Results

There was a linear relationship between SCP classes and skin cancer risk. Further, SCP was as good a predictor of skin cancer as objectively measured skin phototype.

Conclusion

As skin phototype is an important factor in skin cancer research, SCP has great potential in investigative studies of skin cancer risk.
Narrative Intervention in Interethnic Conflict
Authors: Garagozov Rauf , Gadirova Rana
Published: October 2018

This article is rooted in a narrative approach to interethnic conflict which treats them principally as competing stories. On this basis, we examine experimental strategies for narrative intervention in interethnic conflict and potential tools for their reconciliation. Narrative intervention is understood here as a set of actions to identify and disseminate narratives that can reduce negative emotions and attitudes and promote reconciliation between members of conflicting groups. In terms of new solutions, we suggest a method of “Progressive Narrative Transformation” whose key element is the establishment of common points of contact between conflicting narratives and their gradual transformation such that they may converge into a new narrative accepted and shared by both sides. We present different kinds of narratives to evaluate attitudes and emotions among Azerbaijanis, including people displaced from their homes by conflict. Analyzing responses to a “common suffering” narrative, we registered that individuals and groups are able to keep sympathetic attitudes, even implicitly, toward their opponents. Results might enable scholars in conflict resolution and reconciliation to learn how to develop strategies that take advantage of these attributes of the human mind.
Do exemptions undermine environmental policy support? An experimental stress test on the odd‐even road space rationing policy in India
Authors: Bernauer Thomas , Prakash Aseem , Beiser‐McGrath Liam F.
Published: October 2018

Policies sometimes exempt particular categories of regulatees for reasons of equity and political feasibility. Will the non‐exempt oppose the policy because they shoulder all of the policy costs? We outline an analytic framework for “stress testing” public support among the non‐exempt when they are provided negative information about exemptions and reduced policy effectiveness. Empirically, we study public support for the odd‐even road space rationing policy in India. Using a survey experiment with 2,182 car owners in Bangalore, we find considerable baseline support for this policy. While support among the non‐exempt erodes when they are told about exemptions, there is no additional erosion when they are told that exemptions reduce policy effectiveness. This suggests that the perception of fairness, not policy efficacy, drives the erosion of support among the non‐exempt. Yet the policy survives the stress test because the majority of respondents continue to support it, in spite of support erosion among the non‐exempt.
The Statistical Analysis of Acoustic Phonetic Data: Exploring Differences Between Spoken Romance Languages
Authors: Pigoli Davide , Hadjipantelis Pantelis Z. , Coleman John S. , Aston John A. D.
Published: October 2018

The historical and geographical spread from older to more modern languages has long been studied by examining textual changes and in terms of changes in phonetic transcriptions. However, it is more difficult to analyse language change from an acoustic point of view, although this is usually the dominant mode of transmission. We propose a novel analysis approach for acoustic phonetic data, where the aim will be to model the acoustic properties of spoken words statistically. We explore phonetic variation and change by using a time–frequency representation, namely the log-spectrograms of speech recordings. We identify time and frequency covariance functions as a feature of the language; in contrast, mean spectrograms depend mostly on the particular word that has been uttered. We build models for the mean and covariances (taking into account the restrictions placed on the statistical analysis of such objects) and use these to define a phonetic transformation that models how an individual speaker would sound in a different language, allowing the exploration of phonetic differences between languages. Finally, we map back these transformations to the domain of sound recordings, enabling us to listen to the output of the statistical analysis. The approach proposed is demonstrated by using recordings of the words corresponding to the numbers from 1 to 10 as pronounced by speakers from five different Romance languages.
Critical discursive psychology and relational ethics: An uneasy tension?
Authors: McMullen Linda M.
Published: October 2018

The debate over the ethicality of discourse analysis, particularly against the backdrop of relational ethics and the use of interview‐generated data, has recently intensified (see Hammersley, , ; Smith, ; Taylor, ). By way of extending this debate beyond the issue of what constitutes informed consent in discourse analytic research, I focus on the question of harm that might come to participants who provide data that are analysed through the lens of critical discursive psychology and who are subsequently privy to our analyses. Through the use of an actual example from my participation in a project on different ways of analysing qualitative data, I consider the ramifications of critical discursive analytic processes and goals for the ethical obligation to minimize harm to participants that might result from our analyses and for the practice of sharing qualitative analyses with participants. I conclude that choosing to reside in an uneasy tension that can exist between critical discursive psychology and relational ethics, particularly at the stages of writing, analysis, and dissemination of our work, raises questions that require further conversation.
Two novel alleles, HLA‐A*32:01:01:09 and 32:01:01:10, identified by Pacific Bioscience's SMRT sequencing
Authors: Cambridge Charlotte A. , Turner Thomas R. , Georgiou Xenia , Marsh Steven G. E. , Mayor Neema P.
Published: October 2018

Pacific Bioscience's SMRT DNA sequencing was used to identify two novel intronic variants of HLA‐A*32:01:01:01.
Three Waves of State‐led Gentrification in China
Authors: He Shenjing
Published: October 2018

Gentrification in China, as in any other contexts, is an innate process embedded in the dynamic urban metamorphosis, thus requires a provincialised lens to understand its ‘home grown’ mechanism and periodisation, while not losing sight of the macro politico‐economic changes. Hence I propose an analytical framework of ‘state‐centred triangular embedment’ to enable a holistic yet nuanced examination of the delicate entanglements of the state, market and society amidst the surging waves of gentrification in China: The first wave of sporadic gentrification in the 1990s, the second wave of widespread gentrification in the 2000s, and the third wave of reactivated gentrification under state‐led financialisation after 2010. Gentrification has become an integral part of the making of the modern competitive state in China, joining force with the state’s endeavour in extracting values from land/housing redevelopment through market operation, imposing modern (western) values to its society while intermittently responding to social contestations.
Comparison between manufacturing sites shows differential adhesion, activation, and GPIbα expression of cryopreserved platelets
Authors: Six Katrijn R. , Delabie Willem , Devreese Katrien M.J. , Johnson Lacey , Marks Denese C. , Dumont Larry J. , Compernolle Veerle , Feys Hendrik B.
Published: October 2018

BACKGROUND

Transfusion of cryopreserved platelets (cryoplatelets) is not common but may replace standard liquid‐preserved platelets (PLTs) in specific circumstances. To better understand cryoplatelet function, frozen concentrates from different manufacturing sites were compared.

STUDY DESIGN AND METHODS

Cryoplatelets from Denver, Colorado (DEN); Sydney, Australia (SYD); and Ghent, Belgium (GHE) were compared (n = 6). A paired noncryopreserved control was included in Ghent. Microfluidic‐flow chambers were used to study PLT adhesion and fibrin deposition in reconstituted blood. Receptor expression was measured by flow cytometry. Coagulation in static conditions was evaluated by rotational thromboelastometry (ROTEM).

RESULTS

Regardless of the manufacturing site, adhesion of cryoplatelets under shear flow (1000/sec) was significantly (p < 0.05) reduced compared to control. Expression of GPIbα was decreased in a subpopulation of cryoplatelets comprising 45% ± 11% (DEN), 63% ± 9% (GHE), and 94% ± 6% (SYD). That subpopulation displayed increased annexin V binding and decreased integrin activation. PLT adhesion, agglutination, and aggregation were moreover decreased in proportion to that subpopulation. Fibrin deposition under shear flow was normal but initiated faster (546 ± 163 sec GHE) than control PLTs (631 ± 120 sec, p < 0.01), only in the absence of tissue factor. In static conditions, clotting time was faster, but clot firmness decreased compared to control. Coagulation was not different between manufacturing sites.

CONCLUSION

Cryopreservation results in a subset of PLTs with enhanced GPIbα shedding, increased phosphatidylserine expression, reduced integrin response, and reduced adhesion to collagen in microfluidic models of hemostasis. The proportion of this phenotype is different between manufacturing sites. The clinical effects, if any, will need to be verified.
The efficacy of extracorporeal photopheresis to arrest bronchiolitis obliterans in lung allograft recipients was compared between two automated photopheresis instruments
Authors: Chionis Lisa , Grossman Brenda J. , Hachem Ramsey , Commean Paul , Derfler Mary Clare , Vedantham Suresh , Dodds Kathy , Spitznagel Edward , Atkinson Jeff , Despotis George
Published: October 2018

Background

The most common instruments used for extracorporeal photopheresis (ECP) treatment in the United States are the UVAR XTS and the CELLEX devices (Therakos, West Chester, PA). When compared to the UVAR XTS instrument, the efficacy of the CELLEX instrument to arrest the decline in lung function in patients with chronic lung allograft dysfunction (CLAD) related to bronchiolitis obliterans (BOS) has not been previously evaluated.

Methods

The relative efficacy of the CELLEX vs UVAR XTS ECP instruments was assessed by comparing the difference in rates of FEV1 decline before and after ECP treatment and survival in two series of lung allograft recipients with BOS who had been treated with these instruments.

Results

Similar Slope Difference values for change in rate of decline (6 months Post ECP ‐ Pre ECP) were observed between the two cohorts (UVAR XTS: 85 ± 109 mL/month vs CELLEX: 76 ± 128 mL/month, p=0.72). A similar percentage of patients responded to ECP (UVAR XTS: 77% vs CELLEX: 89%; p=0.36) i.e., as defined as a positive difference in slope between the rate of decline of FEV1 before and 6 months after ECP. Survival at either 6 (p=0.89) or 12 (p=0.8) months after the start of ECP was not associated with instrument used despite a trend in higher early mortality (34% vs 17%, p=0.054) in the patients who were predominately treated with the CELLEX.

Conclusions

Our data support the use of the CELLEX for prospective studies designed to evaluate the merits of ECP in this population.
Incidence of immune thrombocytopenia in Taiwan: a nationwide population‐based study
Authors: Hung Giun‐Yi , Lee Chih‐Ying , Yen Hsiu‐Ju , Lin Li‐Yih , Horng Jiun‐Lin
Published: October 2018

BACKGROUND

The incidence of immune thrombocytopenia (ITP) is not well known in Asians. The aims of this study were to survey incidences and clinical features of ITP in Taiwan.

STUDY DESIGN AND METHODS

This study identified 4855 incident ITP cases from the population‐based National Health Insurance Research Database from mid‐2006 to mid‐2013, and compared incidences, patient characteristics, and clinical manifestations of ITP by age.

RESULTS

Respective ITP incidence rates among those aged <15, 15 to 59, and ≥60 years were 4.0, 2.0, and 5.4 per 100,000 person‐years. A male predominance was noted in children, and a female predominance was found in adults. The most common causes of secondary ITP were systemic lupus erythematosus (21.8%), viral hepatitis C (16.9%), and viral hepatitis B (13.4%). The rate of secondary ITP in children was less than one fifth that in adults (4.2% vs. 23.8%). Rates of central nervous system (1.1%) and gastrointestinal tract bleeding (3.3%) were rare, with variations by age. The rate of splenectomies in children (0.4%) was only one tenth that in adults (4.1%). The disease in 25% of children and 30% of adults became persistent or chronic. A decreasing trend in the ITP incidence was found (annual percentage change, −4.9%), and it was confined to those aged >15 years.

CONCLUSION

Incidence estimates of ITP in Taiwan were close to those of Western countries, with age‐specific variations in sex ratio, comorbidity, splenectomy, secondary causes, and incidence trends. The results suggest no racial variations in ITP incidences, but a geographical difference in causes of secondary ITP.
Methylation of protein aspartates and deamidated asparagines as a function of blood bank storage and oxidative stress in human red blood cells
Authors: Reisz Julie A. , Nemkov Travis , Dzieciatkowska Monika , Culp‐Hill Rachel , Stefanoni Davide , Hill Ryan C. , Yoshida Tatsuro , Dunham Andrew , Kanias Tamir , Dumont Larry J. , Busch Michael , Eisenmesser Elan Z. , Zimring James C. , Hansen Kirk C. , D'Alessandro Angelo
Published: October 2018

BACKGROUND

Being devoid of de novo protein synthesis capacity, red blood cells (RBCs) have evolved to recycle oxidatively damaged proteins via mechanisms that involve methylation of dehydrated and deamidated aspartate and asparagine residues. Here we hypothesize that such mechanisms are relevant to routine storage in the blood bank.

STUDY DESIGN AND METHODS

Within the framework of the REDS‐III RBC‐Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell‐Omics) study, packed RBC units (n = 599) were stored under blood bank conditions for 10, 23, and 42 days and profiled for oxidative hemolysis and time‐dependent metabolic dysregulation of the trans‐sulfuration pathway.

RESULTS

In these units, methionine consumption positively correlated with storage age and oxidative hemolysis. Mechanistic studies show that this phenomenon is favored by oxidative stress or hyperoxic storage (sulfur dioxide >95%), and prevented by hypoxia or methyltransferase inhibition. Through a combination of proteomics approaches and 13C‐methionine tracing, we observed oxidation‐induced increases in both Asn deamidation to Asp and formation of methyl‐Asp on key structural proteins and enzymes, including Band 3, hemoglobin, ankyrin, 4.1, spectrin beta, aldolase, glyceraldehyde 3‐phosphate dehydrogenase, biphosphoglycerate mutase, lactate dehydrogenase and catalase. Methylated regions tended to map proximal to the active site (e.g., N316 of glyceraldehyde 3‐phosphate dehydrogenase) and/or residues interacting with the N‐terminal cytosolic domain of Band 3.

CONCLUSION

While methylation of basic amino acid residues serves as an epigenetic modification in nucleated cells, protein methylation at carboxylate side chains and deamidated asparagines is a nonepigenetic posttranslational sensor of oxidative stress and refrigerated storage in anucleated human RBCs.
Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project
Authors: Montemayor‐Garcia Celina , Karagianni Panagiota , Stiles David A. , Reese Erika M. , Smellie Danielle A. , Loy Debrean A. , Levy Kimberly Y. , Nwokocha Magdalene , Bueno Marina U. , Miller Jeffery L. , Klein Harvey G.
Published: October 2018

BACKGROUND

The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance.

STUDY DESIGN AND METHODS

The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next‐generation sequencing output files into a predicted red blood cell (RBC) phenotype.

RESULTS

Forty‐two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull‐down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious.

CONCLUSION

Next‐generation sequencing has known potential for high‐throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.
Anti‐D quantification in relation to anti‐D titre, middle cerebral artery Doppler measurement and clinical outcome in RhD‐immunized pregnancies
Authors: Wikman Agneta , Jalkesten Elisabeth , Ajne Gunilla , Höglund Petter , Mörtberg Anette , Tiblad Eleonor
Published: October 2018

Background

The optimal strategy to monitor RhD‐immunized pregnancies is not evident. Whether a quantitative analysis of anti‐D antibodies adds valuable information to anti‐D titre is unclear. The aim of this study was to evaluate the relevance of anti‐D quantification in routine monitoring of RhD‐immunized pregnancies.

Materials and methods

In a retrospective study, 64 consecutive pregnancies in 61 immunized women with anti‐D titre ≥128 at any time during pregnancy were included. According to routine, at titre ≥128, anti‐D quantification was performed by flow cytometry and the peak systolic velocity in the middle cerebral artery was measured by ultrasound. Decisions for treatment with intrauterine blood transfusion were based on increased peak systolic velocity in the middle cerebral artery.

Results

Increasing anti‐D concentrations correlated well to increasing anti‐D titres, but at each titre value, there was a large interindividual variation, in the determined anti‐D concentration. Intrauterine transfusions were initiated in 35 pregnancies according to algorithms based on ultrasound measurements, at anti‐D concentrations of 2·4–619 IU/ml and titre 128–16 000. Sixty pregnancies resulted in a live‐born child, three in miscarriage and one in termination of pregnancy. During the perinatal care in the neonatal intensive care unit, thirty‐one of the neonates were treated with blood exchange transfusions and/or red cell transfusions and 47 were treated with phototherapy.

Conclusion

Anti‐D quantification does not add further information compared to anti‐D titre, in defining a critical level to start monitoring RhD‐immunized pregnancies with Doppler ultrasound.
A quality assessment of public water fountains and relation to human health: a case study from Yozgat, Turkey
Authors: Birgin Iritas Servet , Ali Turksoy Vugar , Deniz Serdar , Kocoglu Serhat , Kirat Gullu , Can Demirkesen Ali , Baba Alper
Published: October 2018

Public fountains are very common and everyday people appreciate the benefits a water fountain can bring. However, consumption of public fountain water in some country has decreased because of growing concerns that constituents in fountain water may have adverse effects on health. A few studies have examined the safety of public fountains, proposing only limited evidence of fountain‐related health issues in Turkey. Most of these public fountains are sourced from natural springs in Turkey. In this study, a 177 fountain water and 32 rock samples were analysed for source and quality of water. The geology of the region has the direct impact on the quality of the public fountain water. The results indicate that the level of some elements exceeded the limit values determined by WHO and US.EPA. The most striking high values were observed for iron (Fe), nickel (Ni), aluminum (Al), arsenic (As) and bromine (Br) concentrations.
Porcine signal regulatory protein alpha binds to human CD47 to inhibit phagocytosis: Implications for human hematopoietic stem cell transplantation into severe combined immunodeficient pigs
Authors: Boettcher Adeline N. , Cunnick Joan E. , Powell Ellis J. , Egner Timothy K. , Charley Sara E. , Loving Crystal L. , Tuggle Christopher K.
Published: October 2018

Background

Severe combined immunodeficient (SCID) pigs are an emerging animal model being developed for biomedical and regenerative medicine research. SCID pigs can successfully engraft human‐induced pluripotent stem cells and cancer cell lines. The development of a humanized SCID pig through xenotransplantation of human hematopoietic stem cells (HSCs) would be a further demonstration of the value of such a large animal SCID model. Xenotransplantation success with HSCs into non‐obese diabetic (NOD)‐derived SCID mice is dependent on the ability of NOD mouse signal regulatory protein alpha (SIRPA) to bind human CD47, inducing higher phagocytic tolerance than other mouse strains. Therefore, we investigated whether porcine SIRPA binds human CD47 in the context of developing a humanized SCID pig.

Methods

Peripheral blood mononuclear cells (PBMCs) were collected from SCID and non‐SCID pigs. Flow cytometry was used to assess whether porcine monocytes could bind to human CD47. Porcine monocytes were isolated from PBMCs and were subjected to phagocytosis assays with pig, human, and mouse red blood cell (RBC) targets. Blocking phagocytosis assays were performed by incubating human RBCs with anti‐human CD47 blocking antibody B6H12, non‐blocking antibody 2D3, and nonspecific IgG1 antibody and exposing to human or porcine monocytes.

Results

We found that porcine SIRPA binds to human CD47 in vitro by flow cytometric assays. Additionally, phagocytosis assays were performed, and we found that porcine monocytes phagocytose human and porcine RBCs at significantly lower levels than mouse RBCs. When human RBCs were preincubated with CD47 antibodies B6H12 or 2D3, phagocytosis was induced only after B6H12 incubation, indicating the lower phagocytic activity of porcine monocytes with human cells requires interaction between porcine SIRPA and human CD47.

Conclusions

We have shown the first evidence that porcine monocytes can bind to human CD47 and are phagocytically tolerant to human cells, suggesting that porcine SCID models have the potential to support engraftment of human HSCs.
Dynamic structural rearrangements and functional regulation of voltage‐sensing phosphatase
Authors: Sakata Souhei , Okamura Yasushi
Published: October 2018

The voltage‐sensing phosphatase (VSP) consists of a voltage sensor domain (VSD) and a cytoplasmic catalytic region. The latter contains a phosphatase domain and a C2 domain, showing remarkable similarity to the tumour suppressor enzyme PTEN. In VSP, membrane depolarization induces a conformational change in the VSD, which activates the phosphoinositide phosphatase. The final outcome in VSP is enzymatic activity in the cytoplasmic region, unlike in voltage‐gated ion channels where conformational change of the transmembrane pore is induced by the VSD. Therefore, it is crucial to detect structural change in the cytoplasmic catalytic region to gain insights into the operating mechanisms of VSP. This review summarizes a recent study in which a method of genetic incorporation of a non‐canonical amino acid, Anap, was used to detect dynamic membrane voltage‐controlled rearrangements of the structure of the catalytic region of sea squirt VSP (Ci‐VSP). Upon membrane depolarization, both the phosphatase domain and the C2 domain move in a similar time frame, suggesting that the two regions are coupled to each other. Measurement of Förster resonance energy transfer (FRET) between Anap introduced into the C2 domain of Ci‐VSP and dipicrylamine in the cell membrane suggested no large movement of the enzyme towards the membrane. Fluorescence changes in Anap induced by different membrane potentials indicate the presence of multiple conformations of the active enzyme.
A hybrid method to simulate elastic wave scattering of three-dimensional objects
Authors: Li Zhen , Su Yuanda , Tang Xiaoming , Li Huanran , Liu Qing Huo
Published: October 2018

A hybrid method based on the finite-difference method and equivalence principle to simulate elastic wave scattering of three-dimensional objects is proposed. In this method, the near fields are first calculated in a rectangular volume containing the object by the finite-difference method. Then the displacements and tractions on a virtual surface are transformed to the far field by the application of the equivalence principle in elastodynamics. The feasibility is verified by comparing modeling results with the analytical solution for the canonical point force source radiation problem. Modeling for complex scatterer structures shows the advantage of this method in handling multi-scale scattering problems.
It Takes a Village Coach: Cost-Effectiveness of an Intervention to Improve Diet and Physical Activity Among Minority Women
Authors: Buder Iris , Zick Cathleen , Waitzman Norman , Simonsen Sara , Sunada Grant , Digre Kathleen
Published: October 2018

Background: This study gauged the cost-effectiveness of a community-based health coaching intervention aimed at improving diet and physical activity among women in culturally diverse communities. Methods: The Coalition for a Healthier Community for Utah Women and Girls recruited women from 5 cultural and ethnic groups and randomized them to receive quarterly versus monthly health coaching. Coaching was performed by trained community health workers from the targeted communities. Cost-effectiveness ratios were estimated to gauge the cost-effectiveness of the intervention. Results: Estimated quality-adjusted life years gained from both increased physical activity and improved diet were positive. Cost-effectiveness ratios varied by intervention arm, but all ratios fell within the favorable range described in the literature. Conclusions: This culturally adapted health coaching intervention was deemed to be cost-effective. Our findings suggest that to achieve the highest level of cost-effectiveness, programs should focus on enrolling at-risk women who do not meet recommended physical activity standards and/or dietary guidelines.
Tracking time with ricequakes in partially soaked brittle porous media
Authors: Einav Itai , Guillard François
Published: October 2018

Timing your breakfast? Soak cereal in milk, apply pressure, and get recurring collapses whose sound resembles a slowing metronome.
A high-entropy alloy with hierarchical nanoprecipitates and ultrahigh strength
Authors: Fu Zhiqiang , Jiang Lin , Wardini Jenna L. , MacDonald Benjamin E. , Wen Haiming , Xiong Wei , Zhang Dalong , Zhou Yizhang , Rupert Timothy J. , Chen Weiping , Lavernia Enrique J.
Published: October 2018

HEAs’ compositional space allows the design of hierarchical microstructures that contribute to the exceptional strength values.
Pathway-Directed Screen for Inhibitors of the Bacterial Cell Elongation Machinery
Authors: Buss Jackson A. , Baidin Vadim , Welsh Michael A. , Flores-Kim Josué , Cho Hongbaek , Wood B. McKay , Uehara Tsuyoshi , Walker Suzanne , Kahne Daniel , Bernhardt Thomas G.
Published: October 2018

New antibiotics are needed to combat the growing problem of resistant bacterial infections. An attractive avenue toward the discovery of such next-generation therapies is to identify novel inhibitors of clinically validated targets, like cell wall biogenesis.
A Novel Actin Binding Drug withIn VivoEfficacy
Authors: Ravichandran Akshaya , Geng Mengxin , Hull Kenneth G. , Li Jing , Romo Daniel , Lu Shi-En , Albee Aaron , Nutter Christopher , Gordon Donna M. , Ghannoum Mahmoud A. , Lockless Steve W. , Smith Leif
Published: October 2018

Occidiofungin is produced by the soil bacteriumBurkolderia contaminansMS14 and is structurally similar or identical to the burkholdines, xylocandins, and cepacidines. This study identified the primary cellular target of occidiofungin, which was determined to be actin.
Controlled Infection Immunization Using Delayed Death Drug Treatment Elicits Protective Immune Responses to Blood-Stage Malaria Parasites
Authors: Low Leanne M. , Ssemaganda Aloysious , Liu Xue Q. , Ho Mei-Fong , Ozberk Victoria , Fink James , Sundac Lana , Alcorn Kylie , Morrison Amy , O’Callaghan Kevin , Gerrard John , Stanisic Danielle I. , Good Michael F.
Published: October 2018

Naturally acquired immunity to malaria is robust and protective against all strains of the same species ofPlasmodium. This develops as a result of repeated natural infection, taking several years to develop.
Pyrimidine Biosynthesis Regulates the Small-Colony Variant and Mucoidy in Pseudomonas aeruginosa through Sigma Factor Competition
Authors: Al Ahmar Roy , Kirby Brandon D. , Yu Hongwei D.
Published: October 2018

Chronic lung infections with
P. aeruginosa
are the main cause of morbidity and mortality in patients with cystic fibrosis. This bacterium overproduces a capsular polysaccharide called alginate (also known as mucoidy), which aids in bacterial persistence in the lungs and in resistance to therapeutic regimens and host immune responses. The current study explores a previously unknown link between pyrimidine biosynthesis and mucoidy at the level of transcriptional regulation. Identifying/characterizing this link could provide novel targets for the control of bacterial growth and mucoidy. Inhibiting mucoidy may improve antimicrobial efficacy and facilitate host defenses to clear the noncapsulated
P. aeruginosa
bacteria, leading to improved prognosis for patients with cystic fibrosis.
Human MxB Inhibits the Replication of Hepatitis C Virus
Authors: Yi Dong-Rong , An Ni , Liu Zhen-Long , Xu Feng-Wen , Raniga Kavita , Li Quan-Jie , Zhou Rui , Wang Jing , Zhang Yong-Xin , Zhou Jin-Ming , Zhang Lei-Liang , An Jing , Qin Cheng-Feng , Guo Fei , Li Xiao-Yu , Liang Chen , Cen Shan
Published: October 2018

Viruses of the
Flaviviridae
family cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of the
Flaviviridae
, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics.
Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths
Authors: Qian Ying , Song Mohan , Jiang Xi , Xia Ming , Meller Jarek , Tan Ming , Chen Yutao , Li Xuemei , Rao Zihe
Published: October 2018

Our understanding of the molecular bases behind the interplays between human noroviruses and their host glycan ligands, as well as their evolutionary changes over time with alterations in their host ligand binding capability and host susceptibility, remains limited. By solving the crystal structures of the glycan ligand binding protruding (P) domains with or without glycan ligands of three representative noroviruses of the GII.17/13/21 genetic lineage, we elucidated the molecular bases of the human norovirus-glycan interactions of this special genetic lineage. We present solid evidence on how noroviruses of this genetic lineage evolved via different evolutionary paths to (i) optimize their glycan binding site for higher glycan binding function and (ii) acquire a completely new glycan binding site for new ligands. Our data shed light on the mechanism of the structural adaptations of human noroviruses through different evolutionary paths, facilitating our understanding of human norovirus adaptations, evolutions, and epidemiology.
Refractive error and visual impairment in Ireland schoolchildren
Authors: Harrington Siofra Christine , Stack Jim , Saunders Kathryn , O’Dwyer Veronica
Published: October 2018

Aim

To report refractive error prevalence and visual impairment in Republic of Ireland (henceforth 'Ireland') schoolchildren.

Methods

The Ireland Eye Study examined 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), in Ireland between June 2016 and January 2018. Participating schools were selected by stratified random sampling, representing a mix of school type (primary/postprimary), location (urban/rural) and socioeconomic status (disadvantaged/advantaged). Examination included monocular logarithm of the minimum angle of resolution (logMAR) presenting visual acuity (with spectacles if worn) and cycloplegic autorefraction (1% Cyclopentolate Hydrochloride). Parents completed a questionnaire to ascertain participants’ lifestyle.

Results

The prevalence of myopia (spherical equivalent refraction (SER): ≤−0.50 D), hyperopia (SER: ≥+2.00 D) and astigmatism (≤−1.00 DC) among participants aged 6–7 years old was 3.3%, 25% and 19.2%, respectively, and among participants aged 12–13 years old was 19.9%, 8.9% and 15.9%, respectively. Astigmatic axes were predominately with-the-rule. The prevalence of ‘better eye’ presenting visual impairment (≥0.3 logMAR, with spectacles, if worn) was 3.7% among younger and 3.4% among older participants. Participants in minority groups (Traveller and non-white) were significantly more likely to present with presenting visual impairment in the ‘better eye’.

Conclusions

The Ireland Eye Study is the first population-based study to report on refractive error prevalence and visual impairment in Ireland. Myopia prevalence is similar to comparable studies of white European children, but the levels of presenting visual impairment are markedly higher than those reported for children living in Northern Ireland, suggesting barriers exist in accessing eye care.