bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS
Authors: Lone Museer A. , Zeng Sen , Bourquin Florence , Wang Mengli , Huang Shunxiang , Lin Zhiqiang , Tang Beisha , Zhang Ruxu , Hornemann Thorsten 
Published: February 2022

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease. Recently, several gain-of-function mutations in SPTLC1 were associated with juvenile ALS. SPTLC1 encodes for a subunit of the serine-palmitoyltransferase (SPT) - the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL).Here we identified a novel SPTLC1p.L38R mutation in a young Chinese girl with a signature of juvenile ALS. The patient presented with muscular weakness and atrophy, tongue tremor and fasciculation, breathing problems and positive pyramidal signs. A blood lipid analysis showed overall increased SL levels and particularly a pronounced increase in dihydro-SL species. Increased SL de novo synthesis was confirmed in an SPTLC1 deficient HEK cell model that expressed the mutant form. An experimental therapy based on extracts of the fungus C. cicadae resulted in a significant lowering of plasma sphingolipids. A subsequent metabolomics analysis identified Myriocin, a potent SPT inhibitor as an active component of the extract. The inhibitory effect of the C. cicadae extract on SL de novo synthesis was confirmed in a HepG2 cell model. These results suggest that a pharmacological inhibition of SPT could be a therapeutic option for this form of ALS.
A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens
Authors: Pacheco Gaspar A. , Gálvez Nicolás M. S. , Andrade Catalina A. , Vázquez Yaneisi , Rodríguez-Guilarte Linmar , González Pablo A. , Bueno Susan M. , Kalergis Alexis M. 
Published: February 2022

ABSTRACTBACKGROUNDThe human respiratory syncytial virus (hRSV) is a respiratory pathogen responsible for most cases of acute lower respiratory tract infections in infants worldwide. Although this virus represents a significant social and economic burden, there are no safe and effective available vaccines. rBCG-N-hRSV is a vaccine candidate consisting of a recombinant attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) expressing the nucleoprotein of hRSV (N-hRSV).METHODSrBCG-N-hRSV was applied intradermally in three different doses (5×103, 5×104, or 1×105 CFU) to healthy adults enrolled in a randomized, double-blind, dose-escalating phase 1 clinical trial (NCT03213405). Blood samples were taken before and at various time points after immunization. Cellular and humoral immune parameters were assessed by analyzing circulating immune cells and sera, respectively.RESULTSPerforin- and Granzyme B-producing PBMCs recognizing viral or mycobacterial antigens were found to increase after immunization with rBCG-N-hRSV. These cells also upregulated IFN-γ and IL-10 secretion in response to N-hRSV and upregulated IFN-γ, IL-6, and TNF-α secretion in response to mycobacterial proteins. While naïve T cell populations contracted over time, no specific memory T cell subset expanded significantly. Although binding to C1q by anti-N-hRSV or anti-mycobacterial antibodies decreased slightly after immunization, no apparent changes were found in the concentration of IgG subclasses against N-hRSV or mycobacterial antigens.CONCLUSIONSThe immune response elicited by immunization with rBCG-N-hRSV consists mainly of antigen-specific T cells. The data reported here provide novel information about the characteristics of the immune response elicited after immunization with rBCG-N-hRSV, supporting the safety and immunogenicity of this vaccine.
Genotypic Sex Determination Systems could be Adaptations to Extreme Temperature Environments in Reptiles and to Endothermy in Mammals and Birds
Authors: Ferrando-Bernal Manuel , Lao Óscar 
Published: February 2022

AbstractIn some vertebrates species, environmental temperatures (TSD) determine their sex determination. In others, it is controlled by genomic mechanisms (GSD). One hypothesis suggests that GSD systems could have evolved in ectothermic TSD species to escape the geographical limitation imposed by environmental temperatures. Recently, it has been found that TSD reptiles species tend to breed at warmer temperatures than GSD species, especially in habitat with four months of warm temperatures. Here we obtain the pivotal temperature (the one that generates equal ratios of male and females) in 53 reptiles species (from four orders: sphenodontia, crocodilia, testudines and squamata) and compare it with the environmental temperature in the nest during the breeding season in 100 TSD reptiles species and 78 GSD reptiles species. Our results show that GSD species statistically breed in temperatures that would cause a sex bias if they had TSD systems, whereas species with TSD breed in a similar range of temepratrues to the pivotal ones. Additionally, we also found that the body temperature of more than 1,200 endothermic species statistically exceeds the pivotal temperature suggesting that GSD is necessary for endotherms to avoid sex bias that could lead to extinction. Finally, we observed that one of the 100 most invasive species worldwide,Trachemys scripta elegans, a turtle species with TSD, has never been able to establish in countries with less than four months of warm temperatures, confirming a restriction in the geographic range in TSD species caused by extreme temperatures. Altogether, these results suggest that GSD could have evolved as an adaptation to avoid the biased sex ratios that extreme temperature may cause in species with a TSD system.
Heterogeneity of Irritability: Psychometrics of The Irritability and Dysregulation of Emotion Scale (TIDES-13)
Authors: Dissanayake Andrew S. , Dupuis Annie , Arnold Paul D. , Burton Christie , Crosbie Jennifer , Schachar Russell J. , Levy Tomer 
Published: February 2022

ABSTRACTObjectiveWe designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to test whether irritability consisted of several sub-dimensions that would correlate differentially with internalizing/externalizing psychopathology, age, and gender.MethodParent-report (n = 3935, mean age = 8.9) and youth self-report (n = 579, mean age = 15.1) versions of TIDES-13 were administered to a population-based sample. Exploratory and confirmatory factor analyses were conducted on separate sub-samples. We fit multivariable regression models between TIDES-13 sub-dimensions and age, gender, anxiety, depression, ODD and ADHD trait levels.ResultsA higher order model with a global irritability dimension and Proneness to Anger, Internalized Negative Emotional Reactivity, Externalized Negative Emotional Reactivity and Reactive Aggression sub-dimensions showed good to excellent fit in both parent-report and self-report. The global irritability dimension had a strong influence on all item variance (ωHierarchical; parent report = .0.94, ωHierarchical; self report = .90). Proneness to Anger, Externalized Negative Emotional Reactivity and Reactive Aggression decreased with age in males, whereas Internal Negative Emotional Reactivity increased with age in females. Internalized Negative Emotional Reactivity was associated with internalizing traits, over and above global irritability. ODD and ADHD were predicted primarily by the global irritability.ConclusionAlthough irritability can be estimated as an essentially unidimensional construct, differential associations of Internalized Negative Emotional Reactivity with gender and age, and internalizing psychopathology warrant examination in clinical populations. These results support TIDES-13 as a reliable and valid multidimensional measure of irritability and thus may be useful for research and clinical purposes.
Anabolic Factors and Myokines Improve Differentiation of Human Embryonic Stem Cell Derived Skeletal Muscle Cells
Authors: Ruan Travis , Harney Dylan , Koay Yen Chin , Loo Lipin , Larance Mark , Caron Leslie 
Published: February 2022

AbstractSkeletal muscle weakness is linked to many adverse health outcomes. Current research to identify new drugs has often been inconclusive due to lack of adequate cellular models. We have previously developed a scalable monolayer system to differentiate human embryonic stem cell (hESC) into mature skeletal muscle cells (SkMC) within 26 days without cell sorting or genetic manipulation. Here, building on our previous work, we show that differentiation and fusion of myotubes can be further enhanced using the anabolic factors testosterone (T) and follistatin (F) in combination with a cocktail of myokines (C). Importantly, combined TFC treatment significantly enhanced both hESC-SkMC fusion index and expression of various skeletal muscle markers including the motor protein Myosin Heavy Chain (MyHC). Transcriptomic and proteomic analysis revealed oxidative phosphorylation as the most up-regulated pathway and a significantly higher level of ATP and increased mitochondrial mass were also observed in TFC-treated hESC-SkMCs, suggesting enhanced energy metabolism is coupled to improved muscle differentiation. This cellular model will be a powerful tool for studying in vitro myogenesis and for drug discovery to further enhance muscle development or treat muscle diseases.
8-Furylimidazolo-2′-deoxycytidine: crystal structure, packing, atropisomerism and fluorescence
Authors: Budow-Busse Simone , Jana Sunit K. , Kondhare Dasharath , Daniliuc Constantin , Seela Frank 
Published: February 2022

8-Furylimidazolo-2′-deoxycytidine (furImidC), C14H14N4O5, is a fluorescent analogue of 2′-deoxycytidine, also displaying the same recognition face. As a constituent of DNA, furImidC forms extraordinarily strong silver-mediated self-pairs. Crystal structure determination revealed that furImidC adopts two types of disordered residues: the sugar unit and the furyl moiety. The disorder of the sugar residue amounts to an 87:13 split. The disorder of the furyl ring results from axial chirality at the C8—C2′′ bond connecting the nucleobase to the heterocycle. The two atropisomers are present in unequal proportions [occupancies of 0.69 (2) and 0.31 (2)], and the nucleobase and the furyl moiety are coplanar. Considering the atomic sites with predominant occupancy, an anti conformation with χ = − 147.2 (7)° was found at the glycosylic bond and the 2′-deoxyribosyl moiety shows a C2′-endo (S, 2
T
1) conformation, with P = 160.0°. A 1H NMR-based conformational analysis of the furanose puckering revealed that the S conformation predominates also in solution. In the solid state, two neighbouring furImidC molecules are arranged in a head-to-tail fashion, but with a notable tilt of the molecules with respect to each other. Consequently, one N—H...N hydrogen bond is found for neighbouring molecules within one layer, while a second N—H...N hydrogen bond is formed to a molecule of an adjacent layer. In addition, hydrogen bonding is observed between the nucleobase and the sugar residue. A Hirshfeld surface analysis was performed to visualize the intermolecular interactions observed in the X-ray study. In addition, the fluorescence spectra of furImidC were measured in solvents of different polarity and viscosity. furImidC responds to microenvironmental changes (polarity and viscosity), which is explained by a hindered rotation of the furyl residue in solvents of high viscosity.
Establishing the relationship between population aging and health care expenditure in India
Authors: Mohapatra Geetilaxmi , Arora Rahul , Giri Arun Kumar 
Published: February 2022

PurposeThe main purpose of this paper is to examine the role of population aging in determining the health care expenditure (HCE) in India over the period 1981 to 2018.Design/methodology/approachWhile establishing the linkage between population aging and HCE, the study has used economic growth, urbanization and CO2 emissions as control variables and used the autoregressive distributed lag (ARDL) approach to cointegration and VECM based Granger causality approach to estimate both the long-run and short-run relationships among the variables.FindingsThe results of the ARDL bounds test showed that there is a stable and long-run relationship among the variables. The long-run and short-run coefficients reveal that population aging and income per capita exert a statistically significant and positive effect on per capita HCE in India. The VECM causality evidence shows that there is a presence of short-run causality from economic growth and population aging to per capita HCE, urbanization to environmental degradation and further from aging to urbanization. However, the long-run causality evidence confirms unidirectional causality from population aging to the per capita HCE.Research limitations/implicationsThe research findings could be improved by considering the changes in mortality rate over time because of other environmental factors such as air pollution, among others as control variables. Various other variables affecting the health of an aged person could be considered for better research outcome which is not included in the present study because of the paucity of data. However, the present research findings would certainly serve effective policy instrument aiming at maximizing health gains that are highly associated with the elderly population and economic growth towards achieving sustainable development in India.Originality/valueThe uniqueness of the present study lies in its estimation where the relationship between population aging and HCE is looked at while considering the impact of other environmental factors separately. The causal relationship is shown among the variables using updated econometrics time-series techniques. The study tried to resolve the ambiguity associated with the relationship between aging and HCE at a macro level.
High-cycle fatigue properties of curved-surface AlSi10Mg parts fabricated by powder bed fusion additive manufacturing
Authors: Zhou Yue , Abbara El Mehdi , Jiang Dayue , Azizi Arad , Poliks Mark D. , Ning Fuda 
Published: February 2022

Purpose
This study aims to uncover the multiscale relations among geometry, surface finish, microstructure and fatigue properties of curved-surface AlSi10Mg parts fabricated by powder bed fusion (PBF) additive manufacturing.

Design/methodology/approach
This paper investigated the high-cycle tensile and bending fatigue behaviors of PBF-built AlSi10Mg parts with curved surfaces. Besides, the surface finish, porosity and microstructure around various curvatures were characterized. Meanwhile, the stress distributions of the fatigue specimens with curved surfaces under the dynamic tensile/bending loading were analyzed via theoretical analysis and ANSYS simulation.

Findings
The results showed that the as-built specimens with the smallest curvature exhibited the best surface quality, smallest grain sizes and thinnest grain boundaries. In addition, the tensile fatigue fracture occurred around the largest curvature position of fatigue specimens, which was consistent with the simulated fatigue safety factor results. Moreover, the bending fatigue specimens with the largest curvature presented the shortest fatigue life due to the highest bending and shear stresses along the loading direction.

Originality/value
So far, most studies have focused on the fatigue behavior of as-built AlSi10Mg parts with planar structures only. The investigation on fatigue properties of as-built AlSi10Mg parts with curved surfaces remains unexplored. This study provides new insights into the characterization and quantification of the fatigue performance of PBF-built metal parts with complex geometries, the knowledge of which can promote their adoption in real industries.
Injecting drug use opportunities and reasons for choosing not to inject: A population‐based study of Australian young adults who use stimulants
Authors: Casey Luke Edward , Pourmarzi Davoud , Wessel Ellen Leslie , Kemp Robert , Smirnov Andrew 
Published: February 2022

AbstractIntroductionUnderstanding reasons for choosing not to inject drugs, among those who have never injected before, may be helpful for reducing transitions to injecting drug use. This study examines opportunities to inject and reasons for never injecting in young adults who used stimulants.MethodsData are from a population‐based study of young adults who used ecstasy and methamphetamine (n = 313), recruited in Queensland, Australia in 2008/2009. At the follow‐up, participants who had never injected (n = 293) completed a 13‐item instrument on reasons for never injecting. We conducted a principal components analysis to identify types of reasons (scored 0–100) and multivariate regression to predict endorsement of these reasons.ResultsApproximately one‐in‐five of all participants ever had an opportunity to inject and there was no gender difference in the propensity to accept an opportunity. Four types of reasons, labelled risk perception, subjective effects, social environment and aversion, were identified. Male gender was associated with lower endorsement of risk perception (β = −7.94; 95% confidence interval [CI] −13.37, −2.51) and social environment (β = −7.35; 95% CI −13.15, −1.54). Having friends who injected was associated with lower endorsement of the social environment (β = −8.88; 95% CI −14.83, −2.94), and higher endorsement of aversion (β = 7.67; 95% CI 1.44, 13.89).Discussion and ConclusionsOur findings suggest that injecting drug use opportunities are common among young adults engaged in recreational drug use, with males and females equally likely to accept an opportunity. A strong aversion to injecting and a hedonic preference for non‐injecting drug use may reduce the likelihood of accepting these opportunities.
Changing perspectives on poverty and inequality: The contributions of the International Labour Review
Authors: RODGERS Gerry 
Published: February 2022

AbstractThis introduction presents a selection of articles from the International Labour Review that illustrate how research on poverty and inequality has evolved over the past century. Receiving only occasional attention in the early decades of the journal's history, these topics acquired more prominence in articles published from the 1970s onwards, especially in relation to research carried out under the ILO's World Employment Programme. In the 1990s, articles looked into concepts of poverty and social exclusion and the impact of economic reform. More recent publications have treated economic and social inequality within wider analyses of growth and development. Scope remains for closer integration of different approaches to poverty and inequality.
A numerical model to predict the powder–binder separation during micro‐powder injection molding
Authors: Islam Sk Tanbir , Samanta Sudip K. , Das Santanu , Chattopadhyay Himadri 
Published: February 2022

AbstractThe micro‐powder injection molding (micro‐PIM) process has the potential to bridge the gap between the design and manufacturing of micro‐components that are often used in small and handy devices. Numerical modeling helps to analyze and overcome various difficulties of micro‐PIM. In the present work, a numerical model is developed to predict the powder–binder separation (a common defect in PIM and especially severe in micro‐PIM) during the injection of an alumina feedstock. A powder–binder separation criterion is proposed dealing with applied injection pressure and friction force between the powder and binder. An indirect comparison of feedstock travel time between two locations is used to validate the model. The predicted segregation from the simulated result is supported by a qualitative experimental measurement. The developed model can be used to optimize injection parameters to get a defect‐free product.
Selection and evaluation of suitable reference genes for quantitative gene expression analysis during infection ofCucumis sativuswithPectobacterium brasiliense
Authors: Yuan Lifang , Zhao Yurong , Xie Hua , Shi Yanxia , Xie Xuewen , Chai Ali , Li Lei , Li Baoju 
Published: February 2022

AbstractAimsBacterial soft rot caused by Pectobacterium brasiliense (Pbr) has resulted in severe economic losses of cucumber production in northern China. Quantitative reverse transcription PCR (RT-qPCR) is widely used to determine the fold change in the expression of genes of interest, and an appropriate reference gene played a critical role in the evaluation of genes expression. However, the suitable reference genes for transcript normalization during the interaction between cucumber and Pbr have not yet been systematically validated. In this study, we aimed to identify the suitable reference genes for accurate and reliable normalization of cucumber and Pbr RT-qPCR data.Methods and ResultsWe selected 14 candidate reference genes for cucumber and 10 candidate reference genes for Pbr were analysed by using four algorithms (the deltaCt method, BestKeeper, NormFinder and geNorm). Furthermore, five genes in cucumber involved in plant resistance and five genes in Pbr related to the virulence were selected to confirm the reliability of the reference genes by RT-qPCR. CsARF (ADP-ribosylation factor 1) and pgi (glucose-6-phosphate isomerase) were suggested as the most suitable reference genes for cucumber and Pbr respectively.ConclusionOur results suggested that CsARF (ADP-ribosylation factor 1) and pgi (glucose-6-phosphate isomerase) could be as the reference genes to normalize expression data for cucumber and Pbr during the process of pathogen–host interaction respectively.Significance and Impact of the StudyTo our knowledge, this is the first systematic study of the optimal reference genes specific to cucumber and Pbr, which could help advance the molecular interactions research in Cucurbitaceae vegetables and Pectobacterium species pathosystems.