bluuebunny/crossref_metadata_2025 huggingface dataset:
GCAT|Panel, a comprehensive structural variant haplotype map of the Iberian population from high-coverage whole-genome sequencing
Authors: Valls-Margarit Jordi , Galván-Femenía Iván , Matías-Sánchez Daniel , Blay Natalia , Puiggròs Montserrat , Carreras Anna , Salvoro Cecilia , Cortés Beatriz , Amela Ramon , Farre Xavier , Lerga-Jaso Jon , Puig Marta , Sánchez-Herrero Jose Francisco , Moreno Victor , Perucho Manuel , Sumoy Lauro , Armengol Lluís , Delaneau Olivier , Cáceres Mario , de Cid Rafael , Torrents David
Published: February 2022

The combined analysis of haplotype panels with phenotype clinical cohorts is a common approach to explore the genetic architecture of human diseases. However, genetic studies are mainly based on single nucleotide variants (SNVs) and small insertions and deletions (indels). Here, we contribute to fill this gap by generating a dense haplotype map focused on the identification, characterization, and phasing of structural variants (SVs). By integrating multiple variant identification methods and Logistic Regression Models (LRMs), we present a catalogue of 35 431 441 variants, including 89 178 SVs (≥50 bp), 30 325 064 SNVs and 5 017 199 indels, across 785 Illumina high coverage (30x) whole-genomes from the Iberian GCAT Cohort, containing a median of 3.52M SNVs, 606 336 indels and 6393 SVs per individual. The haplotype panel is able to impute up to 14 360 728 SNVs/indels and 23 179 SVs, showing a 2.7-fold increase for SVs compared with available genetic variation panels. The value of this panel for SVs analysis is shown through an imputed rare Alu element located in a new locus associated with Mononeuritis of lower limb, a rare neuromuscular disease. This study represents the first deep characterization of genetic variation within the Iberian population and the first operational haplotype panel to systematically include the SVs into genome-wide genetic studies.
Consciousness explained or described?
Authors: Schurger Aaron , Graziano Michael
Published: February 2022

Consciousness is an unusual phenomenon to study scientifically. It is defined as a subjective, first-person phenomenon, and science is an objective, third-person endeavor. This misalignment between the means—science—and the end—explaining consciousness—gave rise to what has become a productive workaround: the search for ‘neural correlates of consciousness’ (NCCs). Science can sidestep trying to explain consciousness and instead focus on characterizing the kind(s) of neural activity that are reliably correlated with consciousness. However, while we have learned a lot about consciousness in the bargain, the NCC approach was not originally intended as the foundation for a true explanation of consciousness. Indeed, it was proposed precisely to sidestep the, arguably futile, attempt to find one. So how can an account, couched in terms of neural correlates, do the work that a theory is supposed to do: explain consciousness? The answer is that it cannot, and in fact most modern accounts of consciousness do not pretend to. Thus, here, we challenge whether or not any modern accounts of consciousness are in fact theories at all. Instead we argue that they are (competing) laws of consciousness. They describe what they cannot explain, just as Newton described gravity long before a true explanation was ever offered. We lay out our argument using a variety of modern accounts as examples and go on to argue that at least one modern account of consciousness, attention schema theory, goes beyond describing consciousness-related brain activity and qualifies as an explanatory theory.
Susceptibility to auditory hallucinations is associated with spontaneous but not directed modulation of top-down expectations for speech
Authors: Alderson-Day Ben , Moffatt Jamie , Lima César F , Krishnan Saloni , Fernyhough Charles , Scott Sophie K , Denton Sophie , Leong Ivy Yi Ting , Oncel Alena D , Wu Yu-Lin , Gurbuz Zehra , Evans Samuel
Published: February 2022

Auditory verbal hallucinations (AVHs)—or hearing voices—occur in clinical and non-clinical populations, but their mechanisms remain unclear. Predictive processing models of psychosis have proposed that hallucinations arise from an over-weighting of prior expectations in perception. It is unknown, however, whether this reflects (i) a sensitivity to explicit modulation of prior knowledge or (ii) a pre-existing tendency to spontaneously use such knowledge in ambiguous contexts. Four experiments were conducted to examine this question in healthy participants listening to ambiguous speech stimuli. In experiments 1a (n = 60) and 1b (n = 60), participants discriminated intelligible and unintelligible sine-wave speech before and after exposure to the original language templates (i.e. a modulation of expectation). No relationship was observed between top-down modulation and two common measures of hallucination-proneness. Experiment 2 (n = 99) confirmed this pattern with a different stimulus—sine-vocoded speech (SVS)—that was designed to minimize ceiling effects in discrimination and more closely model previous top-down effects reported in psychosis. In Experiment 3 (n = 134), participants were exposed to SVS without prior knowledge that it contained speech (i.e. naïve listening). AVH-proneness significantly predicted both pre-exposure identification of speech and successful recall for words hidden in SVS, indicating that participants could actually decode the hidden signal spontaneously. Altogether, these findings support a pre-existing tendency to spontaneously draw upon prior knowledge in healthy people prone to AVH, rather than a sensitivity to temporary modulations of expectation. We propose a model of clinical and non-clinical hallucinations, across auditory and visual modalities, with testable predictions for future research.
Comparative Analysis of Mortality From Coronavirus Disease 2019 Across the European Union Countries and the Effects of Vaccine Coverage
Authors: Ziakas Panayiotis D , Kourbeti Irene S , Mylonakis Eleftherios
Published: February 2022

Background

Mortality is a critical measure of disease impact. The European Union (EU) countries share the same regulatory framework but different implementation policies.

Methods

We extracted cumulative COVID-19 mortality data across the EU countries. We evaluated the 27 member states using the location quotient (LQ) to adjust for the expected mortality in the whole EU region, where an LQ <1 signifies a more and an LQ >1 a less favorable outcome. We categorized EU members into 3 distinct profiles based on their LQ estimates: favorable profile, LQ ≤0.9; unfavorable profile, LQ >1.10; and average profile, LQ between 0.9 and 1.10. We compared LQ estimates and profiles with the prevaccination era that ended in December 2020 with the COVID-19 vaccine rollout.

Results

Twelve member states had a favorable profile, 4 had an average profile, and 11 had an unfavorable profile. In quantitative analysis, an improvement (negative LQ difference) was noted across countries with higher vaccination coverage (median, 71% fully vaccinated vs 57% for countries with positive LQ differences). There was a significant negative association between the share of fully vaccinated and LQ changes (ρ = –0.62, P < .001) and a significant 4-month lag effect. After COVID-19 vaccines became available, 4 countries improved their profile and 5 moved to a worse profile.

Conclusions

There is significant variability in mortality and impact of COVID-19 between countries, even if they share the same regulatory framework. Extending immunization coverage may lead the transition to a more favorable profile, and alter the trajectory of COVID-19 mortality.
Olfactomedin 4 Is a Biomarker for the Severity of Infectious Diseases
Authors: Liu Wenli , Rodgers Griffin P
Published: February 2022

Biomarkers of infectious diseases are essential tools for patient monitoring, diagnostics, and prognostics. Here we review recent advances in our understanding of olfactomedin 4 (OLFM4) in neutrophil biology and of OLFM4 as a new biomarker for certain infectious diseases. OLFM4 is a neutrophil-specific granule protein that is expressed in a subset of human and mouse neutrophils. OLFM4 expression is upregulated in many viral and bacterial infections, as well as in malaria. OLFM4 appears to play an important role in regulating host innate immunity against bacterial infection. Further, higher expression of OLFM4 is associated with severity of disease for dengue virus, respiratory syncytial virus, and malaria infections. In addition, higher expression of OLFM4 or a higher percentage of OLFM4 + neutrophils is associated with poorer outcomes in septic patients. OLFM4 is a promising biomarker and potential therapeutic target in certain infectious diseases.
Long-Term Efficacy, Safety, and Durability of Cabotegravir and Rilpivirine as 2-Drug Oral Maintenance Therapy After 6 Years of Study
Authors: Sutton Kenneth C , De Vente Jerome , Leblanc Roger , Dejesus Edwin , Smith Graham , Mills Anthony , Baril Jean-Guy , St. Clair Marty , Stancil Britt S , Vandermeulen Kati , Spreen William R
Published: February 2022

Background

In the LATTE study, daily oral cabotegravir + rilpivirine demonstrated higher rates of efficacy than efavirenz + 2 nucleoside reverse-transcriptase inhibitors (NRTIs) through Week 96 in antiretroviral therapy (ART)-naive adults with human immunodeficiency virus (HIV)-1. We present the results from 6 years of continued treatment with oral cabotegravir + rilpivirine.

Methods

LATTE was a phase IIb, randomized, multicenter, partially blinded, dose-ranging study in ART-naive adults with HIV-1. After a 24-week induction phase with cabotegravir + 2 NRTIs, participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL were randomized to receive cabotegravir (10, 30, or 60 mg) + rilpivirine (25 mg) in the maintenance phase through Week 96 and switched to cabotegravir 30 mg + rilpivirine 25 mg in the open-label phase through Week 312.

Results

Of 160 participants who entered the maintenance phase, 111 completed the study at Week 312. At Week 312, 105 (66%) participants maintained HIV-1 RNA <50 copies/mL, 15 (9%) had HIV-1 RNA ≥50 copies/mL, and 40 (25%) had no virologic data. Eight participants met protocol-defined virologic failure criteria through Week 312, 2 of whom met protocol-defined virologic failure criteria after Week 144. Six participants developed treatment-emergent resistance to 1 or both agents during the study, 3 of whom developed integrase inhibitor resistance substitutions. Two participants (1%) reported drug-related serious adverse events. Few adverse events led to withdrawal during the open-label phase (n = 5, 3%).

Conclusions

Oral cabotegravir + rilpivirine demonstrated efficacy in the majority of participants and an acceptable safety profile through 6 years of treatment, demonstrating its durability as maintenance therapy for HIV-1.
Prevalence of Latent Tuberculous Infection in Patients With Nontuberculous Mycobacterial Lung Disease and Colonization: A Prospective Study in an Intermediate Tuberculosis Burden Country
Authors: Lee Ho-Sheng , Wei Yu-Feng , Tsai Yi-Jung , Wang Ping-Huai , Chen Chung-Yu , Pan Sheng-Wei , Shu Chin-Chung
Published: February 2022

Background

Controlling latent tuberculosis infection (LTBI) is important in eliminating tuberculosis (TB); however, the prevalence of LTBI has rarely been studied in patients with nontuberculous mycobacterial (NTM) lung disease (LD) and colonization (LC).

Methods

We prospectively recruited subjects with NTM isolated from sputum mycobacterial cultures from December 2011 to June 2019. NTM-LD and NTM-LC were defined according to the American Thoracic Society guidelines. Patients with negative cultures were recruited as controls. Patients with a history of active TB or positive TB cultures were excluded. LTBI was confirmed using a QuantiFERON-TB Gold In-tube test. The prevalence and factors associated with LTBI were analyzed.

Results

A total of 406 participants were enrolled, including 171 in the NTM-LD group, 153 in the NTM-LC group, and 82 in the control group. The prevalence of LTBI was higher in the NTM-LD and NTM-LC groups than in the controls (21.6%, 20.9%, and 6.1%; P = .006). Multivariable analysis showed that old age (adjusted odds ratio [aOR], 1.021, per year increment; P = .042), NTM-LD (aOR, 4.030; P = .005), NTM-LC (aOR, 3.610; P = .011, compared with the controls), and pulmonary cavitary lesions (aOR, 3.393; P = .034) were independently associated with LTBI.

Conclusions

The prevalence of LTBI was higher in the patients with NTM-LD and NTM-LC than in the controls. Old age, pulmonary cavitation, and NTM isolated from sputum were associated with a higher risk of LTBI.
Mother–Father Parity in Work–Family Conflict? The Importance of Selection Effects and Nonresponse Bias
Authors: Young Marisa , Milkie Melissa A , Schieman Scott
Published: February 2022

Do mothers experience worse work–family conflicts compared with fathers? Yes, according to trenchant and influential qualitative studies that illuminate mothers’ deeply felt problems from work demands that intrude into family life. No, suggest studies employing representative samples of employed parents that show mothers’ and fathers’ have similar work-to-family conflict. We assess these paradoxical depictions of parents’ lives using panel data from the national Canadian Work, Stress and Health study (2011–2019). We argue that comparable reports from men and women are misleading because they overlook mothers’ adjustment of work hours in the face of high conflict. As evidence, we reveal a gender suppression effect whereby mothers report higher conflict than fathers when adjusting for work hours in the baseline sample. Next, we show that mothers are more likely to leave paid work because of conflict. In fact, they are three times more likely than fathers to leave because of conflict’s focal predictor—having young children. These findings reflect mothers’ adjustment to the conflict they might already experience or anticipate. We use pooled person-year data and fixed-effects regression with logit specification to estimate the hazard of not working at the next wave by gender. We underscore the selection of some mothers into surveys or subsequent waves because it excludes those who systematically dropped out due to higher conflict and its primary predictor of having young children. We argue the observed “gender symmetry” of conflict is an artifact and illustrate the importance of theorizing stress processes over time to understand contradictory work–family conflict scholarship.
Analyzing Phylogenetic Trees with a Tree Lattice Coordinate System and a Graph Polynomial
Authors: Liu Pengyu , Biller Priscila , Gould Matthew , Colijn Caroline
Published: February 2022

Phylogenetic trees are a central tool in many areas of life science and medicine. They demonstrate evolutionary patterns among species, genes, and patterns of ancestry among sets of individuals. The tree shapes and branch lengths of phylogenetic trees encode evolutionary and epidemiological information. To extract information from tree shapes and branch lengths, representation and comparison methods for phylogenetic trees are needed. Representing and comparing tree shapes and branch lengths of phylogenetic trees are challenging, for a tree shape is unlabeled and can be displayed in numerous different forms, and branch lengths of a tree shape are specific to edges whose positions vary with respect to the displayed forms of the tree shape. In this article, we introduce representation and comparison methods for rooted unlabeled phylogenetic trees based on a tree lattice that serves as a coordinate system for rooted binary trees with branch lengths and a graph polynomial that fully characterizes tree shapes. We show that the introduced tree representations and metrics provide distance-based likelihood-free methods for tree clustering, parameter estimation, and model selection and apply the methods to analyze phylogenies reconstructed from virus sequences. [Graph polynomial; likelihood-free inference; phylogenetics; tree lattice; tree metrics.]
Ascending Aortic Aneurysm and Dissection Secondary to Bicuspid Aortic Valve with Concomitant Coarctation of Descending Aorta Successfully Repaired with Extracorporeal Membrane Oxygenation Support: A Case Report
Authors: Jiang Qin , Du Juan , Yu Tao , Huang Xiaobo , Zuo Mingliang , Huang Keli
Published: February 2022

Type A aortic aneurysm and dissection secondary to bicuspid aortic valve (BAV) with untreated coarctation of the aorta (CoA) in adults is a rare finding because there are almost no “abnormalities” in these patients’ medical histories. Here, we report on a 47-year-old man with unexplained weakness followed by unconsciousness. He was diagnosed with cardiogenic shock and underwent venoarterial extracorporeal membrane oxygenation (VA-ECMO). BAV, ascending aortic aneurysm and dissection (based on bedside echocardiography) and concomitant CoA (based on computed tomography angiography) were confirmed. The patient then underwent emergency surgery including aortic root replacement with a composite mechanical valve conduit, additional ascending-to-descending aortic bypass, and coronary artery bypass grafting with a saphenous vein graft to the right coronary artery. After treatment, he recovered uneventfully. Thus, here we present a case involving a patient in a critical condition with ascending aortic aneurysm and dissection secondary to complex congenital heart defects, who was successfully treated with composite surgical procedures combined with life-saving VA-ECMO.
Impact of liver disease severity on outcomes of patients undergoing endourological procedures for urolithiasis
Authors: Sharma Anil , Sindwani Gaurav , Arora Vinod , Bhardwaj Ankit
Published: February 2022

Objectives:

This study is aimed to determine the impact of liver disease severity on the outcome of patients undergoing endourological procedures for urolithiasis, and to understand the factors that are helpful in improving the outcome.

Materials and methods:

We retrospectively analyzed the records of patients with chronic liver disease who underwent endourological procedures between January 2014 and February 2020. Inpatient records and charts were assessed for age, sex, height, weight, body mass index, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh score, type of procedure and anesthesia, intensive care unit (ICU) stay, duration of hospitalization, number, size, and position of stones, and postoperative complications such as hematuria, sepsis, and secondary procedures. Data are presented as mean ± standard deviation or frequency. The chi-square test was applied to determine the exact association between categorical data and Student t-test or Mann-Whitney U test as appropriate for continuous data. Statistical significance was set at p < 0.05.

Results:

Hospital and ICU stay as well as administration of different blood products were significantly longer in the Child C than in the Child A and B categories (p < 0.001). Two patients in the Child C category died, while 3 left the hospital against medical advice. The duration of ICU stay and blood products administered increased with augmenting MELD scores. The durations of hospitalization and blood product administration were significantly higher in patients with an MELD score ≥20 than in the group with MELD score <20.

Conclusions:

Hospital and ICU stay and blood product administration were significantly higher in Child C than in Child A and B class patients. Hospitalization duration and blood product administration were significantly higher in patients with an MELD score ≥20.
Gender and botany in early nineteenth-century Portugal: the circle of the Marquise of Alorna
Authors: da Costa Palmira Fontes
Published: February 2022

An ample number of studies have shown that during the late eighteenth century and the first half of the nineteenth century, botany attracted the attention and involvement of women not only as readers of literature on the subject but also as participants in botanical activities and as authors. However, women are still largely absent from the historiography of Portuguese botany in this period. This article contributes to filling this gap by focusing on the translation of Jean-Jacques Rousseau's
Letters on the elements of botany
(1800) by the Marquise of Alorna (1750–1839) and her long poem
Botanical recreations
(1844). It addresses the issue of women's participation in science and looks not only at the importance of gender but also genre and social status in the dissemination of botany in Portugal. This article shows that in the period, the cultivation of science by women was associated with the upper classes while exchanges within circles of sociability through salons offered them an alternative to the public male-centred world of publication.
Seasonal variations of serotonin in the visual system of an ant revealed by immunofluorescence and a machine learning approach
Authors: Bolder Maximilian F. , Jung Klaus , Stern Michael
Published: February 2022

Hibernation, as an adaptation to seasonal environmental changes in temperate or boreal regions, has profound effects on mammalian brains. Social insects of temperate regions hibernate as well, but despite abundant knowledge on structural and functional plasticity in insect brains, the question of how seasonal activity variations affect insect central nervous systems has not yet been thoroughly addressed. Here, we studied potential variations of serotonin-immunoreactivity in visual information processing centres in the brain of the long-lived ant speciesLasius niger. Quantitative immunofluorescence analysis revealed stronger serotonergic signals in the lamina and medulla of the optic lobes of wild or active laboratory workers than in hibernating animals. Instead of statistical inference by testing, differentiability of seasonal serotonin-immunoreactivity was confirmed by a machine learning analysis using convolutional artificial neuronal networks (ANNs) with the digital immunofluorescence images as input information. Machine learning models revealed additional differences in the third visual processing centre, the lobula. We further investigated these results by gradient-weighted class activation mapping. We conclude that seasonal activity variations are represented in the ant brain, and that machine learning by ANNs can contribute to the discovery of such variations.
A case of severe diarrhoea caused by Cyclospora cayetanensis in an immunocompromised patient in northern Spain
Authors: Alkorta Miriam , Manzanal Ayla , Zeberio Izaskun
Published: February 2022

Cyclospora cayetanensis is a parasite that causes intestinal disease that can be especially severe in immunocompromised patients. Most cases occur in tropical and subtropical areas, and in industrialized countries their diagnosis is mostly linked to international travel or the ingestion of imported food. We describe this case of severe diarrhoea in a patient with diffuse large B cell lymphoma and no epidemiological risk factors that was successfully treated with trimethoprim–sulfamethoxazole (TMP–STX). C. cayetanensis is a pathogen that should be taken into account in patients with chronic diarrhoea, especially immunocompromised patients, even when no epidemiological risk factors are present.
Unsupervised encoding selection through ensemble pruning for biomedical classification
Authors: Spänig Sebastian , Michel Alexander , Heider Dominik
Published: February 2022

Background

Owing to the rising levels of multi-resistant pathogens, antimicrobial peptides, an alternative strategy to classic antibiotics, got more attention. A crucial part is thereby the costly identification and validation. With the ever-growing amount of annotated peptides, researchers leverage artificial intelligence to circumvent the cumbersome, wet-lab-based identification and automate the detection of promising candidates. However, the prediction of a peptide’s function is not limited to antimicrobial efficiency. To date, multiple studies successfully classified additional properties, e.g., antiviral or cell-penetrating effects. In this light, ensemble classifiers are employed aiming to further improve the prediction. Although we recently presented a workflow to significantly diminish the initial encoding choice, an entire unsupervised encoding selection, considering various machine learning models, is still lacking.

Results

We developed a workflow, automatically selecting encodings and generating classifier ensembles by employing sophisticated pruning methods. We observed that the Pareto frontier pruning is a good method to create encoding ensembles for the datasets at hand. In addition, encodings combined with the Decision Tree classifier as the base model are often superior. However, our results also demonstrate that none of the ensemble building techniques is outstanding for all datasets.

Conclusion

The workflow conducts multiple pruning methods to evaluate ensemble classifiers composed from a wide range of peptide encodings and base models. Consequently, researchers can use the workflow for unsupervised encoding selection and ensemble creation. Ultimately, the extensible workflow can be used as a plugin for the PEPTIDE REACToR, further establishing it as a versatile tool in the domain.
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

Amyotrophic 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

BACKGROUND

The 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).

METHODS

rBCG-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.

RESULTS

Perforin- 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.

CONCLUSIONS

The 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

In 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

Objective

We 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.

Method

Parent-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.

Results

A 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.

Conclusion

Although 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

Skeletal 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

Purpose

The 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/approach

While 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.

Findings

The 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/implications

The 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/value

The 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

Introduction

Understanding 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.

Methods

Data 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.

Results

Approximately 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 Conclusions

Our 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

This 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

The 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

Aims

Bacterial 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 Results

We 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.

Conclusion

Our 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 Study

To 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.