bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-intensity pulsed ultrasound ameliorates cardiac diastolic dysfunction in mice: a possible novel therapy for heart failure with preserved left ventricular ejection fraction
Authors: Monma Yuto , Shindo Tomohiko , Eguchi Kumiko , Kurosawa Ryo , Kagaya Yuta , Ikumi Yosuke , Ichijo Sadamitsu , Nakata Takashi , Miyata Satoshi , Matsumoto Ayana , Sato Haruka , Miura Masahito , Kanai Hiroshi , Shimokawa Hiroaki 
Published: July 2020

Abstract

Aims
Heart failure with preserved left ventricular ejection fraction (HFpEF) is a serious health problem worldwide, as no effective therapy is yet available. We have previously demonstrated that our low-intensity pulsed ultrasound (LIPUS) therapy is effective and safe for angina and dementia. In this study, we aimed to examine whether the LIPUS therapy also ameliorates cardiac diastolic dysfunction in mice.

Methods and results
Twelve-week-old obese diabetic mice (db/db) and their control littermates (db/+) were treated with either the LIPUS therapy [1.875 MHz, 32 cycles, Ispta (spatial peak temporal average intensity) 117–162 mW/cm2, 0.25 W/cm2] or placebo procedure two times a week for 4 weeks. At 20-week-old, transthoracic echocardiography and invasive haemodynamic analysis showed that cardiac diastolic function parameters, such as e′, E/e′, end-diastolic pressure–volume relationship, Tau, and dP/dt min, were all deteriorated in placebo-treated db/db mice compared with db/+ mice, while systolic function was preserved. Importantly, these cardiac diastolic function parameters were significantly ameliorated in the LIPUS-treated db/db mice. We also measured the force (F) and intracellular Ca2+ ([Ca2+]i) in trabeculae dissected from ventricles. We found that relaxation time and [Ca2+]i decay (Tau) were prolonged during electrically stimulated twitch contractions in db/db mice, both of which were significantly ameliorated in the LIPUS-treated db/db mice, indicating that the LIPUS therapy also improves relaxation properties at tissue level. Functionally, exercise capacity was also improved in the LIPUS-treated db/db mice. Histologically, db/db mice displayed progressed cardiomyocyte hypertrophy and myocardial interstitial fibrosis, while those changes were significantly suppressed in the LIPUS-treated db/db mice. Mechanistically, western blot showed that the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cGMP-protein kinase G (PKG) pathway and Ca2+-handling molecules were up-regulated in the LIPUS-treated heart.

Conclusions
These results indicate that the LIPUS therapy ameliorates cardiac diastolic dysfunction in db/db mice through improvement of eNOS-NO-cGMP-PKG pathway and cardiomyocyte Ca2+-handling system, suggesting its potential usefulness for the treatment of HFpEF patients.
Professionals’ Perspectives on Supporting Deaf Multilingual Learners and Their Families
Authors: Crowe Kathryn , Guiberson Mark 
Published: July 2020

AbstractParents frequently report that advice from professionals is important in making decisions about how their child with hearing loss will communicate. Little is currently known about how professionals support parents raising children with hearing loss in spoken language multilingual environments, children who are described as d/Deaf multilingual learners (DMLs). The purpose of this phenomenological study was to gain insight into professionals’ perspectives and experiences working with such families, particularly in relation to supporting parents in decision-making about multilingualism and language choice. Nineteen professionals discussed their experiences working with DMLs and their families, the role of professionals in decision-making about multilingualism and language choice, and the factors that they considered were important when supporting DMLs and their families. Inductive thematic analysis yielded three themes: child characteristics (language, development), negotiating and supporting language (information, parents’ language, role of language, timing, leadership, language management), and professional issues (knowledge, resources). This paper provides an important insight into professional considerations in supporting DMLs and their families, such as the role and functioning of evidence-based practice.
The Identification and Evolutionary Trends of the Solute Carrier Superfamily in Arthropods
Authors: Denecke Shane M , Driva Olympia , Luong Hang Ngoc Bao , Ioannidis Panagiotis , Linka Marc , Nauen Ralf , Geibel Sven , Vontas John 
Published: July 2020

Abstract
The solute carrier (SLC) transporter superfamily comprises an ancient and ubiquitous group of proteins capable of translocating a range of nutrients, endogenous molecules, and xenobiotics. Although the group has been the subject of intense investigation in both bacteria and mammals, its systematic identification in arthropods has not yet been undertaken. Here, we present a genome-wide identification of all 66 human SLC families in 174 arthropod species. A pipeline (SLC_id) was constructed to identify and group SLCs using a combination of hidden Markov model and BLAST searches followed by filtering based on polypeptide length and the number of transmembrane domains. Comparative analysis of the number of transporters in each family across diverse arthropod lineages was accomplished using one-way analysis of variance (ANOVA) and the Computational Analysis of gene Family Evolution (CAFE). These results suggested that many SLC families have undergone expansions or contractions in particular evolutionary lineages. Notably, the sugar transporting SLC2 family was significantly larger in insects compared with arachnids. This difference may have been complemented by a rapid expansion of the SLC60 family in arachnids which also acts on dietary sugars. Furthermore, the SLC33 family underwent a recent and drastic expansion in aphids, although the biological relevance of this expansion was not possible to infer. Information on specific SLC transporter families across arthropod species can be accessed through an R shiny web application at http://chrysalida.imbb.forth.gr : 3838/Arthropod_SLC_Database/. The present study greatly facilitates further investigation of the diverse group of SLC transporters in arthropods.
Inferring rheology and geometry of subsurface structures by adjoint-based inversion of principal stress directions
Authors: Reuber G S , Holbach L , Popov A A , Hanke M , Kaus B J P 
Published: July 2020

SUMMARY
Imaging subsurface structures, such as salt domes, magma reservoirs or subducting plates, is a major challenge in geophysics. Seismic imaging methods are, so far, the most precise methods to open a window into the Earth. However, the methods may not yield the exact depth or size of the imaged feature and may become distorted by phenomena such as seismic anisotropy, fluid flow, or compositional variations. A useful complementary method is therefore to simulate the mechanical behaviour of rocks on large timescales, and compare model predictions with observations. Recent studies have used the (non-linear) Stokes equations and geometries from seismic studies in combination with an adjoint-based approach to invert for rheological parameters that are consistent with surface observations such as GPS velocities. Nevertheless, it would be useful to use other surface observations, such as principal stress directions, as constraints as well. Here, we derive the adjoint formulation for the case that principal stress directions are used as observables with respect to rheological parameters. Both an algebraic and a discretized derivation of the adjoint equations are described. This thus enables the usage of two data fields - surface velocities and stress directions - as a misfit for the inversion. We test the performance of the inversion for principal stress directions on simplified 3-D test cases.
Finally, we demonstrate how the adjoint approach can be used to compute 3-D geodynamic sensitivity kernels, which highlight the areas in the model domain that have the largest impact on the misfit value of a particular point. This provides a simple, yet powerful, way to visualize which parts of the model domain are of key importance if changing rheological constants.
A synonymous UPF3B variant causing a speech disorder implicates NMD as a regulator of neurodevelopmental disorder gene networks
Authors: Domingo Deepti , Nawaz Urwah , Corbett Mark , Espinoza Josh L , Tatton-Brown Katrina , Coman David , Wilkinson Miles F , Gecz Jozef , Jolly Lachlan A 
Published: July 2020

Abstract
Loss-of-function mutations of the X-chromosome gene UPF3B cause male neurodevelopmental disorders (NDDs) via largely unknown mechanisms. We investigated initially by interrogating a novel synonymous UPF3B variant in a male with absent speech. In silico and functional studies using cell lines derived from this individual show altered UPF3B RNA splicing. The resulting mRNA species encodes a frame-shifted protein with a premature termination codon (PTC) predicted to elicit degradation via nonsense-mediated mRNA decay (NMD). UPF3B mRNA was reduced in the cell line, and no UPF3B protein was produced, confirming a loss-of-function allele. UPF3B is itself involved in the NMD mechanism which degrades both PTC-bearing mutant transcripts and also many physiological transcripts. RNAseq analysis showed that ~1.6% of mRNAs exhibited altered expression. These mRNA changes overlapped and correlated with those we identified in additional cell lines obtained from individuals harbouring other UPF3B mutations, permitting us to interrogate pathogenic mechanisms of UPF3B-associated NDDs. We identified 102 genes consistently deregulated across all UPF3B mutant cell lines. Of the 51 upregulated genes, 75% contained an NMD-targeting feature, thus identifying high-confidence direct NMD targets. Intriguingly, 22 of the dysregulated genes encoded known NDD genes, suggesting UPF3B-dependent NMD regulates gene networks critical for cognition and behaviour. Indeed, we show that 78.5% of all NDD genes encode a transcript predicted to be targeted by NMD. These data describe the first synonymous UPF3B mutation in a patient with prominent speech and language disabilities and identify plausible mechanisms of pathology downstream of UPF3B mutations involving the deregulation of NDD-gene networks.
Neurobiological and Ecological Correlates of Avian Innovation
Authors: Audet Jean-Nicolas 
Published: July 2020

SynopsisIn the wild, particularly in rapidly changing conditions, being capable of solving new problems can increase an animal’s chances of survival and reproduction. In the current context of widespread habitat destruction and increasing urbanization, innovativeness might be a crucial trait. In the past few decades, birds have proven to be a model taxon for the study of innovation, thanks to the abundant literature on avian innovation reports. Innovation databases in birds have been successfully employed to assess associations between innovativeness and other traits such as invasion success, life history, generalism, and brain encephalization. In order to more directly assess the causes of variation in innovation, a complementary approach consists in measuring innovativeness in wild-caught animals using problem-solving tasks that mimic innovations in the field. This method can allow for finer scale evaluation of ecological and neural correlates of innovation. Here, I review some of the most important findings on the correlates of innovation, with a particular focus on neural ones. I conclude by discussing avenues for future research, which I suggest should focus on neurobiology.
Early intervention for children with developmental disabilities in low and middle-income countries – the case for action
Authors: Smythe Tracey , Zuurmond Maria , Tann Cally J , Gladstone Melissa , Kuper Hannah 
Published: July 2020

AbstractIn the last two decades, the global community has made significant progress in saving the lives of children &lt;5 y of age. However, these advances are failing to help all children to thrive, especially children with disabilities. Most early child development research has focussed on the impact of biological and psychosocial factors on the developing brain and the effect of early intervention on child development. Yet studies typically exclude children with disabilities, so relatively little is known about which interventions are effective for this high-risk group. In this article we provide an overview of child development and developmental disabilities. We describe family-centred care interventions that aim to provide optimal stimulation for development in a safe, stable and nurturing environment. We make the case for improving opportunities for children with developmental disabilities to achieve their full potential and thrive, including through inclusive early childhood development intervention. Finally, we call for the global research community to adopt a systematic approach for better evidence for and implementation of early interventions for children with developmental disabilities in low-resource settings.
Exploring the Extra-Virgin Olive Oil Volatilome by Adding Extra Dimensions to Comprehensive Two-Dimensional Gas Chromatography and Time-of-Flight Mass Spectrometry Featuring Tandem Ionization: Validation of Ripening Markers in Headspace Linearity Conditions
Authors: Stilo Federico , Liberto Erica , Reichenbach Stephen E , Tao Qingping , Bicchi Carlo , Cordero Chiara 
Published: July 2020

Abstract

Background
Comprehensive two-dimensional gas chromatography (GC×GC) combined with time-of-flight (TOF) MS is the most informative analytical approach for chemical characterization of the complex food volatilome. Key analytical features include separation power and resolution enhancement, improved sensitivity, and structured separation patterns from chemically correlated analytes.

Objective
In this study, we explore the complex extra-virgin olive oil volatilome by combining headspace (HS) solid-phase microextraction (SPME), applied under HS linearity conditions to GC×GC-TOF MS and featuring hard and soft ionization in tandem.

Method
Multiple analytical dimensions are combined in a single run and evaluated in terms of chemical dimensionality, method absolute and relative sensitivity, identification reliability provided by spectral signatures acquired at 70 and 12 eV, and dynamic and linear range of response provided by soft ionization.

Results
Method effectiveness is validated on a sample set of oils from Picual olives at different ripening stages. Ripening markers [3,4-diethyl-1,5-hexadiene (RS/SR), 3,4-diethyl-1,5-hexadiene (meso), (5Z)-3-ethyl-1,5-octadiene, (5E)-3-ethyl-1,5-octadiene, (E, Z)-3,7-decadiene and (E, E)-3,7-decadiene, (Z)-2-hexenal, (Z)-3-hexenal and (Z)-3-hexenal, (E)-2-pentenal, (Z)-2-pentenal, 1-pentanol, 1-penten-3-ol, 3-pentanone, and 1-penten-3-one] and quality indexes [(Z)-3-hexenal/nonanal, (Z)-3-hexenal/octane, (E)-2-pentenal/nonanal, and (E)-2-pentenal/octane] are confirmed for their validity in HS linearity conditions.

Conclusions
For the complex olive oil volatilome, the proposed approach offers concrete advantages for the validation of the informative role of existing analytes while suggesting new potential markers to be studied in larger sample sets.

Highlights
The accurate fingerprinting of volatiles by HS-SPME operating in HS linearity conditions followed by GC×GC-TOF MS featuring tandem ionization gives the opportunity to improve the quality of analytical data and reliability of results.
The Analysis of Docosahexaenoic Acid (DHA) in Dried Dog Food Enriched with an Aurantiochytrium limacinum Biomass: Matrix Extension Validation and Verification of AOAC Method 996.06
Authors: Dillon Gerald Patrick , Cardinall Cathy , Keegan Jason D , Yiannikouris Alexandros , Brandl Walter , Moran Colm Anthony 
Published: July 2020

Abstract

Background
Docosahexaenoic acid (DHA) plays an important role in brain and retinal development in dogs. However, supranutritional dietary supplementation can result in health issues, including gastrointestinal bleeding, making the accurate analysis of DHA in dog food important for nutritional and welfare regulatory compliance.

Objective
The aim of this study was to conduct a validation and verification of the AOAC 996.06 method, and hence establish its fitness for purpose, for the analysis of DHA in dried dog food supplemented with a heterotrophically grown unextracted DHA-rich Aurantiochytrium limacinum biomass.

Methods
The AOAC 996.06 method, which involves the use of gas chromatography coupled to flame ionization detection (GC-FID), was used to conduct a validation of the analysis of DHA in dried dog food and the results were verified in a second laboratory.

Results
The method was found to be linear over the ranges analyzed and results were found to be within the acceptance criteria for precision and accuracy, verifying the applicability for this matrix. The selectivity and sensitivity of the method were also determined.

Conclusions
The AOAC 996.06 method is fit for purpose for the analysis of DHA in dry dog food kibble.

Highlights
The method can be applied to various dog food samples, supplemented with an unextracted Aurantiochytrium limacinum biomass, using alternative manufacturing methods, i.e. pelleted and extruded with no significant matrix effects being observed.
Technical note: improving the efficiency of generating bovine extraembryonic endoderm cells
Authors: Smith Mary K , Clark Catherine C , McCoski Sarah R 
Published: July 2020

Abstract
The formation of extraembryonic endoderm (XEN) occurs early in embryonic development. The cell types that develop from the XEN remain poorly studied in ruminant species because of the lack of suitable cell culture model systems. The goal of this work was to establish a protocol for producing XEN cell cultures from bovine blastocysts. Previous work identified fibroblast growth factor 2 (FGF2) as a facilitator of bovine XEN development. Further refinements in culture conditions studied here included exposure to 20% fetal bovine serum and FGF2 replenishment. These modifications yielded an endoderm outgrowth formation incidence of 81.6% ± 5.5% compared with 33.3% ± 5.5% in bovine serum albumin (BSA)-supplemented controls. These cells resembled XEN when examined morphologically and contained XEN transcripts (GATA binding protein 4 [GATA4] and GATA binding protein 6 [GATA6]) as well as transcripts present in visceral (BCL2 interacting protein 1 [BNIP1] and vascular endothelial growth factor A [VEGFA]) and parietal (C-X-C motif chemokine receptor 4 [CXCR4], thrombomodulin [THBD], and hematopoietically expressed homeobox [HHEX]) XEN. Two XEN cell lines were maintained for prolonged culture. Both lines continued to proliferate for approximately 6 wk before becoming senescent. These cultures maintained an XEN-like state and continued to express GATA4 and GATA6 until senescence. An increase in the abundance of visceral and parietal XEN transcripts was observed with continued culture, suggesting that these cells either undergo spontaneous differentiation or retain the ability to form various XEN cell types. Stocks of cultured cells exposed to a freeze-thaw procedure possessed similar phenotypic and genotypic behaviors as nonfrozen cells. To conclude, a procedure for efficient production of primary bovine XEN cell cultures was developed. This new protocol may assist researchers in exploring this overlooked cell type for its roles in nutrient supply during embryogenesis.
Severe Hypothermia and Frostbite Requiring ECMO and Four Limb Amputations
Authors: Lumbard Derek C , Lacey Alex M , Endorf Frederick W , Gayken Jon R , Fey Ryan M , Schmitz Kyle R , Deisler Ryan F , Calcaterra Domenico , Prekker Matthew , Nygaard Rachel M 
Published: July 2020

Abstract
Severe hypothermia and frostbite can result in significant morbidity and mortality. We present a case of a patient with severe hypothermia and frostbite due to cold exposure after a snowmobile crash. He presented in cardiac arrest with a core temperature of 19°C requiring prolonged cardiopulmonary resuscitation, active internal rewarming, venoarterial extracorporeal membrane oxygenation, and subsequently amputations of all four extremities. Although severe hypothermia and frostbite can be a fatal condition, the quick action of Emergency Medical Services, emergency physicians, trauma surgeons, cardiothoracic surgeons, intensivists, and the burn team contributed to a successful recovery for this patient including a good neurological outcome. This case highlights the importance of a strong interdisciplinary team in treating this condition.
Long-term Outcomes of Patients Surgically Treated for Hirschsprung Disease
Authors: Nasr Ahmed , Grandpierre Viviane , Sullivan Katrina J , Wong Coralie A , Benchimol Eric I 
Published: July 2020

Abstract

Background
The only curative treatment for Hirschsprung disease (HD) is surgical repair. However, some patients experience poor postoperative outcomes. We determined long-term outcomes of all HD patients in Ontario, Canada’s most populous province.

Methods
We conducted a retrospective cohort study including all children with HD born between April 1, 1991 and March 31, 2014 in Ontario using linked health administrative data. Each HD case was matched to five non-HD controls on sex, date of birth, region of residence and income and followed to March 31, 2016. Chronic diarrhea and constipation were identified using combinations of outpatient physician billing codes in both HD patients and non-HD residents of the province. We determined risk factors associated with diarrhea and constipation, including surgery type and sociodemographic characteristics, using multivariable conditional logistic regression, and reported adjusted odds ratios (aORs).

Results
There were 3,265,172 children born in the study period, of whom 673 had HD. Compared to controls, chronic constipation was more common in HD patients (27.5% versus 2.1%; aOR 17.2, 95% CI 12.6 to 23.4), as was chronic diarrhea (29.9% versus 6.9%, aOR 5.22, 95% CI 4.19 to 6.50). In HD patients, older age at surgery was associated with increased risk of chronic constipation (OR 2.71, 95% CI 1.75 to 4.20). Surgery type, sex, rural/urban residence and income were not associated with risk of chronic constipation or diarrhea.

Conclusion
Chronic constipation and diarrhea were common following surgery for HD. Older age at surgery was associated with subsequent risk of chronic constipation. Surgery type was not associated with increased risk of chronic constipation or diarrhea.