bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why don’t long-finned pilot whales have a widespread postreproductive lifespan? Insights from genetic data
Authors: Nichols Hazel J , Arbuckle Kevin , Fullard Karen , Amos William 
Published: December 2019

AbstractIn a handful of mammals, females show an extended postreproductive lifespan (PRLS), leading to questions over why they spend a substantial portion of their lifespan nonreproductive. Theoretical and empirical studies suggest that PRLS may evolve when 1) demographic patterns lead to increasing local relatedness as females age, and 2) females come into reproductive competition with their daughters, as these conditions lead to high relative benefits of helping kin versus reproducing in later life. However, evolutionary pathways to PRLS are poorly understood and empirical studies are scarce. Here, we use a dataset of 1522 individuals comprising 22 pods to investigate patterns of reproduction and relatedness in long-finned pilot whales Globicephala melas; a toothed whale without species-wide PRLS. We find a similar relatedness structure to whales with PRLS: pods appear composed of related matrilines, and relatedness of females to their pod increases with age, suggesting that this species could benefit from late-life help. Furthermore, females with a large number of philopatric adult daughters are less likely to reproduce, implying intergenerational reproductive competition between females. This suggests that individuals may display a plastic cessation of reproduction, switching to investing in existing offspring when they come into competition with their daughters. To the best of our knowledge, this is the first time such a relationship has been described in relation to PRLS, and it raises questions about whether this represents a step towards evolving PRLS or is a stable alternative strategy to widespread postreproductive periods.
Applications and explorations of CRISPR/Cas9 in CAR T-cell therapy
Authors: Li Chenggong , Mei Heng , Hu Yu 
Published: December 2019

AbstractChimeric antigen receptor(CAR) T-cell therapy has shown remarkable effects and promising prospects in patients with refractory or relapsed malignancies, pending further progress in the next-generation CAR T cells with more optimized structure, enhanced efficacy and reduced toxicities. The clustered regulatory interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) technology holds immense promise for advancing the field owing to its flexibility, simplicity, high efficiency and multiplexing in precise genome editing. Herein, we review the applications and explorations of CRISPR/Cas9 technology in constructing allogenic universal CAR T cells, disrupting inhibitory signaling to enhance potency and exploration of safer and more controllable novel CAR T cells.
A framework for exhaustive modelling of genetic interaction patterns using Petri nets
Authors: Jacobsen Annika , Ivanova Olga , Amini Saman , Heringa Jaap , Kemmeren Patrick , Feenstra K Anton 
Published: December 2019

Abstract

Motivation
Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs.

Results
In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets.

Availability and implementation
The framework is available at http://www.ibi.vu.nl/programs/ExhMod.

Supplementary information
Supplementary data are available at Bioinformatics online.
Auditory Processing Deficits Are Selectively Associated with Medial Temporal Lobe Mnemonic Function and White Matter Integrity in Aging Macaques
Authors: Gray Daniel T , Umapathy Lavanya , De La Peña Nicole M , Burke Sara N , Engle James R , Trouard Theodore P , Barnes Carol A 
Published: December 2019

Abstract
Deficits in auditory function and cognition are hallmarks of normative aging. Recent evidence suggests that hearing-impaired individuals have greater risks of developing cognitive impairment and dementia compared to people with intact auditory function, although the neurobiological bases underlying these associations are poorly understood. Here, a colony of aging macaques completed a battery of behavioral tests designed to probe frontal and temporal lobe-dependent cognition. Auditory brainstem responses (ABRs) and visual evoked potentials were measured to assess auditory and visual system function. Structural and diffusion magnetic resonance imaging were then performed to evaluate the microstructural condition of multiple white matter tracts associated with cognition. Animals showing higher cognitive function had significantly better auditory processing capacities, and these associations were selectively observed with tasks that primarily depend on temporal lobe brain structures. Tractography analyses revealed that the fractional anisotropy (FA) of the fimbria-fornix and hippocampal commissure were associated with temporal lobe-dependent visual discrimination performance and auditory sensory function. Conversely, FA of frontal cortex-associated white matter was not associated with auditory processing. Visual sensory function was not associated with frontal or temporal lobe FA, nor with behavior. This study demonstrates significant and selective relationships between ABRs, white matter connectivity, and higher-order cognitive ability.
Renal involvement and Strømme syndrome
Authors: Caridi Gianluca , Lugani Francesca , Lerone Margherita , Divizia Maria Teresa , Ghiggeri Gian Marco , Verrina Enrico 
Published: December 2019

Abstract
Strømme syndrome is a rare autosomal recessive congenital disorder involving multiple systems. Centromeric protein F (CENPF) is the causative gene of the disease, and variants are usually linked to lethal outcomes either during the foetal stage or in early life. We present a young adult with a genetic diagnosis of Strømme syndrome who—in addition to classic microcephalia, microphthalmia and intestinal atresia (apple peel-type)—experienced slow and unexpected evolution to end-stage renal disease (ESRD). In conclusion, Strømme syndrome is a complex multiorgan disease that needs multidisciplinary clinical management, and potential evolution to ESRD should be taken into account.
Primary Emotions and Recognition of Their Intensities
Authors: Afdhal Rim , Ejbali Ridha , Zaied Mourad 
Published: December 2019

AbstractThe emotion recognition field has two major issues. On the one hand, it is difficult to find the same emotion state in different persons since they may express the same emotion state in various ways. On the other hand, it is also hard to seek the difference between expressions of the same person because some emotion states are too subtle to discriminate. The focus of this work is to solve these two problems by proposing a new approach of emotion recognition. This novel approach allows our emotion recognition system to classify 18 emotions (primary emotions and their intensities). First, we proposed textual definitions of the intensity emotions. Then, we created our emotion recognition system, which is composed of three stages: pre-treatment, feature extraction and classification. We used the deep learning for the feature extraction and the fuzzy logic for the classification. The experimental test demonstrates the efficiency of our system for primary emotions and their intensities’ classification compared to other methods.
“Passwords protect my stuff”—a study of children’s password practices
Authors: Choong Yee-Yin , Theofanos Mary F , Renaud Karen , Prior Suzanne 
Published: December 2019

AbstractChildren use technology from a very young age and often have to authenticate. The goal of this study is to explore children’s practices, perceptions, and knowledge regarding passwords. Given the limited work to date and that the world’s cyber posture and culture will be dependent on today’s youth, it is imperative to conduct cyber-security research with children. We conducted surveys of 189 3rd to 8th graders from two Midwest schools in the USA. We found that children have on average two passwords for school and three to four passwords for home. They kept their passwords private and did not share with others. They created passwords with an average length of 7 (3rd to 5th graders) and 10 (6–8th graders). But, only about 13% of the children created very strong passwords. Generating strong passwords requires mature cognitive and linguistic capabilities which children at this developmental stage have not yet mastered. They believed that passwords provide access control, protect their privacy and keep their “stuff” safe. Overall, children had appropriate mental models of passwords and demonstrated good password practices. Cyber-security education should strive to reinforce these positive practices while continuing to provide and promote age-appropriate developmental security skills. Given the study’s sample size and limited generalizability, we are expanding our research to include children from 3rd to 12th graders across multiple US school districts.
Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms
Authors: Miller Lloyd S , Fowler Vance G , Shukla Sanjay K , Rose Warren E , Proctor Richard A 
Published: December 2019

ABSTRACT
Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread emergence of virulent and multi-drug resistant methicillin-resistant S. aureus strains. There is an urgent and unmet clinical need for non-antibiotic immune-based approaches to treat these infections as the increasing antibiotic resistance is creating a serious threat to public health. However, all vaccination attempts aimed at preventing S. aureus invasive infections have failed in human trials, especially all vaccines aimed at generating high titers of opsonic antibodies against S. aureus surface antigens to facilitate antibody-mediated bacterial clearance. In this review, we summarize the data from humans regarding the immune responses that protect against invasive S. aureus infections as well as host genetic factors and bacterial evasion mechanisms, which are important to consider for the future development of effective and successful vaccines and immunotherapies against invasive S. aureus infections in humans. The evidence presented form the basis for a hypothesis that staphylococcal toxins (including superantigens and pore-forming toxins) are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis.
Comparative Plastome Analysis of Root- and Stem-Feeding Parasites of Santalales Untangle the Footprints of Feeding Mode and Lifestyle Transitions
Authors: Chen Xiaoli , Fang Dongming , Wu Chenyu , Liu Bing , Liu Yang , Sahu Sunil Kumar , Song Bo , Yang Shuai , Yang Tuo , Wei Jinpu , Wang Xuebing , Zhang Wen , Xu Qiwu , Wang Huafeng , Yuan Langxing , Liao Xuezhu , Chen Lipeng , Chen Ziqiang , Yuan Fu , Chang Yue , Lu Lihua , Yang Huanming , Wang Jian , Xu Xun , Liu Xin , Wicke Susann , Liu Huan 
Published: December 2019

AbstractIn plants, parasitism triggers the reductive evolution of plastid genomes (plastomes). To disentangle the molecular evolutionary associations between feeding on other plants below- or aboveground and general transitions from facultative to obligate parasitism, we analyzed 34 complete plastomes of autotrophic, root- and stem-feeding hemiparasitic, and holoparasitic Santalales. We observed inexplicable losses of housekeeping genes and tRNAs in hemiparasites and dramatic genomic reconfiguration in holoparasitic Balanophoraceae, whose plastomes have exceptionally low GC contents. Genomic changes are related primarily to the evolution of hemi- or holoparasitism, whereas the transition from a root- to a stem-feeding mode plays no major role. In contrast, the rate of molecular evolution accelerates in a stepwise manner from autotrophs to root- and then stem-feeding parasites. Already the ancestral transition to root-parasitism coincides with a relaxation of selection in plastomes. Another significant selectional shift in plastid genes occurs as stem-feeders evolve, suggesting that this derived form coincides with trophic specialization despite the retention of photosynthetic capacity. Parasitic Santalales fill a gap in our understanding of parasitism-associated plastome degeneration. We reveal that lifestyle-genome associations unfold interdependently over trophic specialization and feeding mode transitions, where holoparasitic Balanophoraceae provide a system for exploring the functional realms of plastomes.
“We Are Like Any Other People, but We Don’t Cry Much Because Nobody Listens”: The Need to Strengthen Aging Policies and Service Provision for Minorities in Canada
Authors: Salma Jordana , Salami Bukola 
Published: December 2019

Abstract

Background and Objectives
This study explores the aging experiences and needs of immigrant Muslim communities in an urban center in Alberta, Canada. Over one million Muslims live in Canada, with the majority being immigrants and visible minorities. Aging-focused policies and services have yet to address the needs of this population as larger cohorts begin to enter older age.

Research Design and Methods
A community-based participatory research approach was adopted with a community advisory committee co-leading all aspects of the research process. Sixty-seven older adults and stakeholders from diverse ethnocultural immigrant Muslim communities participated in either individual interviews or one of the seven focus groups (2017–2018). Data were transcribed verbatim and thematically analyzed with a focus on factors that support or hinder positive aging experiences in this population.

Results
Participants not only described the benefits of growing old in Canada but also identified unique challenges stemming from their social positioning as religious minorities, immigrants, and older adults. We highlight these experiences in three themes: (a) aging while living across places, (b) negotiating access to aging-supportive resources in a time of scarcity, and (c) re-envisioning Islamic approaches to eldercare.

Discussion and Implications
Immigrant Muslim communities report inequities experienced by older community members. There is a need for an in-depth analysis of the ways aging and migration policies intersect to influence the resources that immigrant minorities have access to as they grow old in Canada.
Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial
Authors: Turner Dan , Bishai Jason , Reshef Leah , Abitbol Guila , Focht Gili , Marcus Dana , Ledder Oren , Lev-Tzion Raffi , Orlanski-Meyer Esther , Yerushalmi Baruch , Aloi Marina , Griffiths Anne M , Albenberg Lindsey , Kolho Kaija-Leena , Assa Amit , Cohen Shlomi , Gophna Uri , Vlamakis Hera , Lurz Eberhard , Levine Arie 
Published: December 2019

AbstractBackgroundAlterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC).MethodsHospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome.ResultsTwenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (&gt;33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm.ConclusionPatients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408).
Baloxavir Marboxil Treatment of Nude Mice Infected With Influenza A Virus
Authors: Kiso Maki , Yamayoshi Seiya , Murakami Jurika , Kawaoka Yoshihiro 
Published: December 2019

Abstract

Background
Immunocompromised patients infected with influenza virus require prolonged treatment with neuraminidase inhibitors, because these patients are not able to eradicate the virus from the respiratory tract, leading to the emergence of drug-resistant mutant viruses.

Methods
In this study, we examined the efficacy of baloxavir marboxil in nude mice that were immunologically deficient.

Results
Daily treatment with a suboptimal dose of baloxavir marboxil increased the survival time of the virus-infected nude mice but did not clear the virus from their respiratory organs, resulting in gradual body weight loss after termination of treatment.

Conclusions
Despite the prolonged baloxavir marboxil treatment, few resistant mutants were detected.
Gradual, Cooperative, Coordinated: Effective Support for Peace and Democracy in Conflict-Affected States
Authors: Fiedler Charlotte , Grävingholt Jörn , Leininger Julia , Mross Karina 
Published: December 2019

AbstractThis article analyzes the success factors for external engagement aimed at fostering peace in conflict-affected states. It focuses on a set of three factors that have been under-researched so far: the strategic prioritization between stability and democracy, the degree of coordination, and the mode of interaction. We compare international engagement in six countries—Burundi, Kenya, Kyrgyzstan, Nepal, Senegal, and Timor-Leste. These countries all struggled with violent conflict and experienced a democratic transition in the period 2000–2014. We use an innovative approach to assess the impact of external engagement by analyzing twenty critical junctures in the domestic political processes of these countries mainly linked to elections, constitution-writing processes, and peace agreements, as well as disarmament, demobilization, and reintegration. Based on over 300 interviews, we find that prioritizing stability over democratization is problematic, good international coordination has positive effects, and preferring cooperative forms of interaction over coercion is mostly but not always useful. In discussing these general features of international support, this article contributes to the broader discussion of factors that explain the impact external actors can have on transformative political processes after conflict.
Regulation of the transcription factor E2F1 mRNA in ovarian granulosa cells of cattle
Authors: Morrell Breanne C , Perego M Chiara , Maylem Excel Rio S , Zhang Lingna , Schütz Luis F , Spicer Leon J 
Published: December 2019

Abstract
The E2F family of transcription factors plays an important role in the control of the cell cycle, cell proliferation, and differentiation, and their role in ovarian function is just emerging. Although some evidence suggests a possible role of E2F1 in ovarian follicular development, what regulates its production in ovarian cells is unknown. Objectives of this study were to determine whether: (i) E2F1 gene expression in granulosa cells (GCs) and theca cells (TCs) change with follicular development and (ii) E2F1 mRNA abundance in TC and GC is hormonally regulated. Using real-time PCR, E2F1 mRNA abundance in GC was 5.5-fold greater (P &lt; 0.05) in small (SM; 1 to 5 mm) than large (LG; &gt;8 mm) follicles, but in TC, E2F1 expression did not differ among follicle sizes. SM-follicle GC had 2.1-fold greater (P &lt; 0.05) E2F1 mRNA than TC. In SM-follicle GC, FGF9 induced a 7.6-fold increase in E2F1 mRNA abundance; however, FGF9 did not affect (P &gt; 0.10) abundance of E2F1 mRNA in LG-follicle TC or GC. Follicle-stimulating hormone (FSH) had no effect (P &gt; 0.10) on E2F1 gene expression in SM- or LG-follicle GC. SM-follicle GC were concomitantly treated with insulin-like growth factor 1 (30 ng/mL), FSH (30 ng/mL), and either 0 or 30 ng/mL of FGF9 with or without 50 µM of an E2F inhibitor (E2Fi; HLM0064741); FGF9 alone increased (P &lt; 0.05) GC numbers, whereas E2Fi alone decreased (P &lt; 0.05) GC numbers, and concomitant treatment of E2Fi with FGF9 blocked (P &lt; 0.05) this stimulatory effect of FGF9. Estradiol production was inhibited (P &lt; 0.05) by FGF9 alone and concomitant treatment of E2Fi with FGF9 attenuated (P &lt; 0.05) this inhibitory effect of FGF9. SM-follicle GC treated with E2Fi decreased (P &lt; 0.05) E2F1 mRNA abundance by 70%. Collectively, our studies show that GC E2F1 mRNA is developmentally and hormonally regulated in cattle. Inhibition of E2F1 reduced FGF9-induced GC proliferation and attenuated FGF9-inhibited estradiol production, indicating that E2F1 may be involved in follicular development in cattle.
LC-MS Quantification of Malondialdehyde-Dansylhydrazine Derivatives in Urine and Serum Samples
Authors: Kartavenka Kostya , Panuwet Parinya , Yakimavets Volha , Jaikang Churdsak , Thipubon Kanitarin , D’Souza Priya Esilda , Barr Dana Boyd , Ryan P Barry 
Published: December 2019

Abstract
We developed a robust analytical method for quantification of malondialdehyde (MDA) in urine and serum samples using dansylhydrazine (DH) as a derivatizing reagent. The derivatization procedure was partially carried out using an autosampler injection program to minimize errors associated with the low-volume addition of reagents and was optimized to yield a stable hydrazone derivative of MDA and its labeled d2-MDA analogue. The target MDA-DH derivatives were separated on an Agilent Zorbax Eclipse Plus Phenyl-Hexyl (3.0 × 100 mm, 3.5 μm) column. The mass-to-charge ratios of the target derivatives [(M+H)+ of 302 and 304 for MDA-DH and d2-MDA-DH, respectively] were analyzed in single ion monitoring mode using a single quadrupole mass spectrometer operated under positive electrospray ionization. The method limits of quantification were 5.63 nM (or 0.405 ng/mL) for urine analysis and 5.68 nM (or 0.409 ng/mL) for serum analysis. The quantification range for urine analysis was 5.63–500 nM (0.405–36.0 ng/mL) while the quantification range for serum analysis was 5.68–341 nM (0.409–24.6 ng/mL). The method showed good relative recoveries (98–103%), good accuracies (92–98%), and acceptable precisions (relative standard deviations 1.8–7.3% for inter-day precision; 1.8–6.1% for intra-day precision) as observed from the repeat analysis of quality control samples prepared at different concentrations. The method was used to measure MDA in individual urine samples (n = 287) and de-identified archived serum samples (n = 22) to assess the overall performance of the method. The results demonstrated that our method is capable of measuring urinary and serum levels of MDA, allowing its future application in epidemiologic investigations.