bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZAP70, too little, too much can lead to autoimmunity*
Authors: Ashouri Judith F. , Lo Wan‐Lin , Nguyen Trang T. T. , Shen Lin , Weiss Arthur 
Published: December 2021

AbstractEstablishing both central and peripheral tolerance requires the appropriate TCR signaling strength to discriminate self‐ from agonist‐peptide bound to self MHC molecules. ZAP70, a cytoplasmic tyrosine kinase, directly interacts with the TCR complex and plays a central and requisite role in TCR signaling in both thymocytes and peripheral T cells. By studying ZAP70 hypomorphic mutations in mice and humans with a spectrum of hypoactive or hyperactive activities, we have gained insights into mechanisms of central and peripheral tolerance. Interestingly, both hypoactive and hyperactive ZAP70 can lead to the development of autoimmune diseases, albeit through distinct mechanisms. Immature thymocytes and mature T cells rely on normal ZAP70 function to complete their development in the thymus and to modulate T cell responses in the periphery. Hypoactive ZAP70 function compromises key developmental checkpoints required to establish central tolerance, allowing thymocytes with potentially self‐reactive TCRs a greater chance to escape negative selection. Such ‘forbidden clones’ may escape into the periphery and may pose a greater risk for autoimmune disease development since they may not engage negative regulatory mechanisms as effectively. Hyperactive ZAP70 enhances thymic negative selection but some thymocytes will, nonetheless, escape negative selection and have greater sensitivity to weak and self‐ligands. Such cells must be controlled by mechanisms involved in anergy, expansion of Tregs, and upregulation of inhibitory receptors or signaling molecules. However, such potentially autoreactive cells may still be able to escape control by peripheral negative regulatory constraints. Consistent with findings in Zap70 mutants, the signaling defects in at least one ZAP70 substrate, LAT, can also lead to autoimmune disease. By dissecting the similarities and differences among mouse models of patient disease or mutations in ZAP70 that affect TCR signaling strength, we have gained insights into how perturbed ZAP70 function can lead to autoimmunity. Because of our work and that of others on ZAP70, it is likely that perturbations in other molecules affecting TCR signaling strength will be identified that also overcome tolerance mechanisms and cause autoimmunity. Delineating these molecular pathways could lead to the development of much needed new therapeutic targets in these complex diseases.
Acceptability of medical immobilization: Results from a pilot international survey
Authors: Townsend Janice A. , Peng Jin , McDaniel Jodee C. , Casamassimo Paul S. 
Published: December 2021

AbstractBackgroundControversy exists on the acceptability of medical immobilization (MI).AimTo identify regulations, professional conventions, and opinions on the acceptability of MI and to identify practice patterns through a pilot study of members of the International Association of Paediatric Dentistry (IAPD) and their colleagues.DesignA 22‐item questionnaire was developed and electronically distributed to 1191 members of the IAPD.ResultsResponses were received from 182 dentists in 45 countries. The majority (74.9%) of respondents use MI, and 29.1% use an immobilization device. MI with an immobilization device was reported as professionally acceptable (58.1%) and permitted by medicolegal regulations (70.8%) in their countries of practice. Dentists rated acceptability of MI higher than they perceived parents would overall and perceived MI to be more acceptable by parents for emergency situations and for children with special healthcare needs but 19.8% of respondents found it totally unacceptable in all scenarios. Use and opinions of acceptability varied by geographical location with respondents from North America being more accepting of MI. Most dentists felt that the use of an immobilization device could lead to lasting psychological trauma (72.3%) and violation of the rights of the child (55.4%) but that it improves access to care (58.5%).ConclusionThe acceptability of MI remains an area of controversy for paediatric dentists internationally.
Dynamics of the bacterial communities and predicted functional profiles in wilted alfalfa silage
Authors: Wang Siran , Li Junfeng , Zhao Jie , Dong Zhihao , Dong Dong , Shao Tao 
Published: December 2021

Abstract

Aims
To investigate the fermentation characteristics, bacterial community and predicted functional profiles during the ensiling of wilted alfalfa (Medicago sativa L.).

Methods and Results
First-cutting alfalfa was harvested at the early bloom stage, wilted for 6 h, and ensiled in laboratory-scale silos (1 L capacity). Triplicate silos were sampled after 1, 3, 7, 15, 30 and 60 days of ensiling, respectively. The bacterial communities of wilted alfalfa and silages on day 3 and 60 were assessed through high throughput sequencing technology, and their functional characteristics were evaluated according to the Kyoto Encyclopedia of Genes and Genomes using Tax4Fun. After 60 days of ensiling, alfalfa silage showed a moderate fermentation quality, indicated by high lactic acid (56.7 g kg−1 dry matter [DM]) and acetic acid (39.4 g kg−1 DM) contents, and low concentrations of butyric acid (2.12 g kg−1 DM) and ammonia nitrogen (128 g kg−1 total nitrogen). Lactobacillus rapidly became predominant on day 3 and increased to 60.4% on day 60. Results of functional prediction analyses showed that the metabolism of amino acid, energy, cofactors and vitamins were reduced, while metabolism of nucleotide and carbohydrate were increased during ensiling. Fructokinase, 1-phosphofructokinase and pyruvate kinase played important roles in producing lactic acid. The production of acetic acid may be correlated with the enhancement of 6-phosphogluconate dehydrogenase and acetyl-CoA synthetase.

Conclusions
Knowledge regarding bacterial dynamics and their metabolic pathways during alfalfa ensiling is important for understanding the fermentation process and may contribute to the production of nutritious and stable alfalfa silage.

Significance and Impact of the Study
High throughput sequencing technology combined with 16S rRNA gene-predicted functional analyses could provide a new and comprehensive insight into bacterial community dynamics and functional profiles to further improve the silage quality.
Factors influencing the detection of antibacterial-resistant Escherichia coli in faecal samples from individual cattle
Authors: Turner Andrea , Schubert Hannah , Puddy Emma F. , Sealey Jordan E. , Gould Virginia C. , Cogan Tristan A. , Avison Matthew B. , Reyher Kristen K. 
Published: December 2021

Abstract

Aims
To investigate whether on-farm antibacterial usage (ABU), environmental antibacterial-resistant (ABR) Escherichia coli prevalence, sampling and sample handling methodologies are associated with ABR E. coli positivity in individual faecal samples from dairy heifers.

Methods and Results
Three hundred and sixty-four heifers from 37 farms were sampled via rectal or faecal pat sampling. Samples were stored at −80°C for variable periods before microbiological analysis. Data analysis was done through a multilevel, multivariable logistic regression approach. Individual rectal samples had increased odds of positivity for amoxicillin-, cefalexin- and tetracycline-resistant E. coli. Sample storage for 6–12 months was associated with decreased odds of finding amoxicillin- and tetracycline-resistant E. coli. On-farm ABU had little influence, and environmental ABR E. coli prevalence had no significant influence on the odds of sample-level positivity for ABR E. coli.

Conclusions
Sampling methodology and sample handling have a greater association than on-farm factors with the detection of ABR E. coli in individual faecal samples from dairy heifers.

Significance and Impact of the Study
Sampling and storage methodologies should be considered carefully at the point of designing ABR surveillance studies in livestock and their environments and, where possible, these methodologies should be standardized between and within future studies.
Cycling and reciprocity in weighted food webs and economic networks
Authors: Iskrzyński Mateusz , Janssen Freek , Picciolo Francesco , Fath Brian , Ruzzenenti Franco 
Published: December 2021

AbstractNetworks of mass flows describe the basic structure of ecosystems as food webs, and of economy as input–output tables. Matter leaving a node in these networks can return to it immediately as part of a reciprocal flow, or completing a longer, multi‐node cycle. Previous research comparing cycling of matter in ecosystems and economy was limited by relying on unweighted or few networks. Overcoming this limitation, we study mass cycling in large datasets of weighted real‐world networks: 169 mostly aquatic food webs and 155 economic networks. We quantify cycling as the portion of all flows that is due to cycles, known as the Finn Cycling Index (FCI). We find no correlation between FCI and the largest eigenvalues of unweighted adjacency matrices used as a cycling proxy in the past. Unweighted networks ignore the actual flow values that in reality can differ by even 10 orders of magnitude. FCI can be decomposed into a sum of contributions of individual nodes. This enables us to quantify how organisms recycling dead organic matter dominate mass cycling in weighted food webs. FCI of food webs has a geometric mean of 5%. We observe lower average mass cycling in the economic networks. The global production network had an FCI of 3.7% in 2011. Cycling in economic networks (input–output tables and trade relationships) and food webs strongly correlates with reciprocity. Encouraging reciprocity could enhance cycling in the economy by acting locally, without the need to perfectly know its global structure.
The validity of the higher‐order structure of effortful control as defined by inhibitory control, attention shifting, and focusing: A longitudinal and multi‐informant study
Authors: Alessandri Guido , Perinelli Enrico , Filosa Lorenzo , Eisenberg Nancy , Valiente Carlos 
Published: December 2021

AbstractObjectiveEffortful control (EC) has been conceptualized as a higher‐order construct defined by a class of self‐regulatory mechanisms. However, the developmental higher‐order structure of EC has seldom been investigated with a thorough psychometric analysis. To begin to fill this gap in the literature, data were obtained from parents and teachers of 185 children (age at T1: M = 9.43 y/o, SD = 1.17) every 2 years for 8 years.MethodWe used a structural equation modeling approach for assessing if EC develops as a higher‐order factor superordinate to three commonly studied self‐regulatory mechanisms, namely inhibitory control (IC), attention focusing (AF), and attention shifting (AS).ResultsResults showed that (a) IC, AF, and AS followed a similar pattern of growth, (b) EC displayed an acceptable degree of scalar longitudinal invariance when operationalized as a latent variable indicated by IC, AF, and AS, (c) a higher‐order structure explained the co‐development of IC, AF, and AS, and (d) stability and change in EC negatively predicted externalizing symptoms, much better than the stability and change of IC, AF, and AS, but only for parents' reports.ConclusionOverall, the higher‐order structure of EC was supported, but our results also indicated that there is a certain degree of uniqueness in its facets.
Safety of higher doses of melatonin in adults: A systematic review and meta‐analysis
Authors: Menczel Schrire Zoe , Phillips Craig L. , Chapman Julia L. , Duffy Shantel L. , Wong Grace , D’Rozario Angela L. , Comas Maria , Raisin Isabelle , Saini Bandana , Gordon Christopher J. , McKinnon Andrew C. , Naismith Sharon L. , Marshall Nathaniel S. , Grunstein Ronald R. , Hoyos Camilla M. 
Published: December 2021

AbstractMelatonin is commonly used for sleep and jetlag at low doses. However, there is less documentation on the safety of higher doses, which are being increasingly used for a wide variety of conditions, including more recently COVID‐19 prevention and treatment. The aim of this review was to investigate the safety of higher doses of melatonin in adults. Medline, Scopus, Embase and PsycINFO databases from inception until December 2019 with convenience searches until October 2020. Randomised controlled trials investigating high‐dose melatonin (≥10 mg) in human adults over 30 years of age were included. Two investigators independently abstracted articles using PRISMA guidelines. Risk of bias was assessed by a committee of three investigators. 79 studies were identified with a total of 3861 participants. Studies included a large range of medical conditions. The meta‐analysis was pooled data using a random effects model. The outcomes examined were the number of adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs. A total of 29 studies (37%) made no mention of the presence or absence of AEs. Overall, only four studies met the pre‐specified low risk of bias criteria for meta‐analysis. In that small subset, melatonin did not cause a detectable increase in SAEs (Rate Ratio = 0.88 [0.52, 1.50], p = .64) or withdrawals due to AEs (0.93 [0.24, 3.56], p = .92), but did appear to increase the risk of AEs such as drowsiness, headache and dizziness (1.40 [1.15, 1.69], p < .001). Overall, there has been limited AE reporting from high‐dose melatonin studies. Based on this limited evidence, melatonin appears to have a good safety profile. Better safety reporting in future long‐term trials is needed to confirm this as our confidence limits were very wide due to the paucity of suitable data.
Impact of emergency management in a simulated home environment for caregivers of children who are tracheostomy dependent
Authors: Brooks Malorie , Jacobs Linda , Cazzell Mary 
Published: December 2021

AbstractPurposeChildren who are tracheostomy dependent require comprehensive caregiver preparation for safe hospital‐to‐home transition. Although a structured discharge education program successfully trained caregivers to provide routine daily tracheostomy care, emergency response training was limited, lacking realistic experiences. Initiation of simulated emergency training for caregivers indicated performance confusion related to tracheostomy cardiopulmonary resuscitation (CPR). This study evaluated the effectiveness of an evidence‐based tracheostomy CPR education intervention via caregiver participation in a high‐fidelity simulation of a home‐based emergency scenario on the performance of essential behaviors, comfort, and satisfaction.Design and MethodsThe study utilized a prospective descriptive pre‐ and post interventional design; 44 caregivers of children who were tracheostomy dependent participated. All caregiver participants completed: video‐ and instructor‐assisted specialized tracheostomy CPR class, high‐fidelity simulation performance of a home‐based emergency (respiratory failure with cardiac arrest), postsimulation video debriefing, performance assessment with an objective scoring rubric, and pre‐ and post simulation surveys on levels of comfort and satisfaction.ResultsOn the performance of essential emergency management behaviors, 86.4% of caregivers performed all four behaviors, but only 36.4% performed these essential behaviors in order. Post simulation caregiver comfort with emergency management significantly increased from pre simulation (p = .001). All caregivers were satisfied with this training and would recommend simulation of home‐based emergencies for all caregivers. Qualitative feedback from caregivers revealed themes of gratitude and the importance of hands‐on practice with guided debriefing/feedback. Study power was 0.98.Practice ImplicationsObjective evaluation of caregiver performance demonstrated specialized tracheostomy CPR education prepared caregivers to respond in a home emergency. Caregivers viewed simulation as an opportunity to gain hands‐on experience and improve emergency responses. It may be beneficial for other similar programs to include specialized tracheostomy CPR and emergency scenario simulation in their discharge education protocols and subsequently compare this program to other similar programs to establish best practice guidelines.
Teachers’ preference for later school start times
Authors: Albrecht Joëlle N. , Werner Helene , Yaw Mei Ling , Jenni Oskar G. , Huber Reto 
Published: December 2021

SummaryEarly morning school start times conflict with biologically determined sleep phase preference and thus contribute to common sleep deficits. This conflict is most pronounced in adolescents, and numerous studies have confirmed that later school start times are beneficial for their sleep and health. However, the conflict continues to exist beyond adolescence and, accordingly, also teachers might benefit from later school start times, but this has gained little attention so far. Importantly, teachers’ resistance to delay school start time is one of the key barriers for a successful implementation and, therefore, teachers’ school start time preferences and influencing factors are important to consider. To this end, we conducted an online survey. Teachers (n = 694, 56.1% female) from 17 high schools in Zurich, Switzerland, participated in the study. They indicated their school start time preference. In addition, four predictor blocks were assessed: sociodemographic, school‐/work‐related, and sleep characteristics, as well as teachers’ perception of students in the first morning lesson. Mixed models were applied to predict the preference. The majority (51%) endorsed later school start times (median preferred delay 25.2 min). School start time, sleep characteristics and perception of students in the first morning lesson were significant predictors for the preference. Thus, teachers with more misaligned sleep and higher awareness for students’ issues in the early morning were more likely to report a preference. This suggests psychoeducation about sleep biology throughout life span to be an effective measure to increase teachers’ support to delay school start time, especially because also they themselves are likely to benefit from later school start times.
Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTSMan and Mga
Authors: Woo Jerry K. K. , McIver Kevin S. , Federle Michael J. 
Published: December 2021

AbstractStreptococcus pyogenes, also known as group A Streptococcus or GAS, is a human‐restricted pathogen causing a diverse array of infections. The ability to adapt to different niches requires GAS to adjust gene expression in response to environmental cues. We previously identified the abundance of biometals and carbohydrates led to natural induction of the Rgg2/3 cell–cell communication system (quorum sensing, QS). Here we determined the mechanism by which the Rgg2/3 QS system is stimulated exclusively by mannose and repressed by glucose, a phenomenon known as carbon catabolite repression (CCR). Instead of carbon catabolite protein A, the primary mediator of CCR in Gram‐positive bacteria; CCR of Rgg2/3 requires the PTS regulatory domain (PRD)‐containing transcriptional regulator Mga. Deletion of Mga led to carbohydrate‐independent activation of Rgg2/3 by down‐regulating rgg3, the QS repressor. Through phosphoablative and phosphomimetic substitutions within Mga PRDs, we demonstrated that selective phosphorylation of PRD1 conferred repression of the Rgg2/3 system. Moreover, given the carbohydrate specificity mediating Mga‐dependent governance over Rgg2/3, we tested mannose‐specific PTS components and found the EIIA/B subunit ManL was required for Mga‐dependent repression. These findings provide newfound connections between PTSMan, Mga, and QS, and further demonstrate that Mga is a central regulatory nexus for integrating nutritional status and virulence.
An unconventionally secreted effector from the root knot nematode Meloidogyne incognita, Mi‐ISC‐1, promotes parasitism by disrupting salicylic acid biosynthesis in host plants
Authors: Qin Xin , Xue Bowen , Tian Haiyang , Fang Chenjie , Yu Jiarong , Chen Cong , Xue Qing , Jones John , Wang Xuan 
Published: December 2021

AbstractPlant‐parasitic nematodes need to deliver effectors that suppress host immunity for successful parasitism. We have characterized a novel isochorismatase effector from the root‐knot nematode Meloidogyne incognita, named Mi‐ISC‐1. The Mi‐isc‐1 gene is expressed in the subventral oesophageal glands and is up‐regulated in parasitic‐stage juveniles. Tobacco rattle virus‐induced gene silencing targeting Mi‐isc‐1 attenuated M. incognita parasitism. Enzyme activity assays confirmed that Mi‐ISC‐1 can catalyse hydrolysis of isochorismate into 2,3‐dihydro‐2,3‐dihydroxybenzoate in vitro. Although Mi‐ISC‐1 lacks a classical signal peptide for secretion at its N‐terminus, a yeast invertase secretion assay showed that this protein can be secreted from eukaryotic cells. However, the subcellular localization and plasmolysis assay revealed that the unconventional secretory signal present on the Mi‐ISC‐1 is not recognized by the plant secretory pathway and that the effector was localized within the cytoplasm of plant cells, but not apoplast, when transiently expressed in Nicotiana benthamiana leaves by agroinfiltration. Ectopic expression of Mi‐ISC‐1 in N. benthamiana reduced expression of the PR1 gene and levels of salicylic acid (SA), and promoted infection by Phytophthora capsici. The cytoplasmic localization of Mi‐ISC‐1 is required for its function. Moreover, Mi‐ISC‐1 suppresses the production of SA following the reconstitution of the de novo SA biosynthesis via the isochorismate pathway in the cytoplasm of N. benthamiana leaves. These results demonstrate that M. incognita deploys a functional isochorismatase that suppresses SA‐mediated plant defences by disrupting the isochorismate synthase pathway for SA biosynthesis to promote parasitism.
Nursing students’ insights of learning evidence‐based practice skills using interactive online technology: Scoping review
Authors: Shorey Shefaly , Chua Joelle Yan Xin 
Published: December 2021

AbstractThis scoping review aims to explore nursing students' insights of learning evidence‐based practice skills through the use of interactive online technology. Studies were obtained from seven electronic databases (PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, and ProQuest Dissertations and Theses Global) until May 2021. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis extension for Scoping Reviews and was guided by the Arksey and O'Malley framework (Scoping studies: Towards a methodological framework. International Journal of Social Research Methodology, 2005, 8(1), 19–32). Findings were analyzed using thematic analysis. Three themes were derived from the 22 included studies: (1) embracing new changes, (2) challenges to tackle, and (3) towards future improvement. Many nursing students reported positive learning experiences of evidence‐based practice skills using interactive online technology. The challenges faced by students and suggestions for improvement were discussed. Future online evidence‐based practice courses should consider blended pedagogies, providing students with effective scaffolding (step‐by‐step guidance) and allowing students to choose their preferred instructional strategies. Thorough planning, testing, and orientation should be conducted before the programs’ implementation. Lastly, future studies should aim to achieve higher study rigor to obtain more accurate results.