bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resonance Risk and Mode Shape Management in the Frequency Domain to Prevent Squeak and Rattle
Authors: Bayani Mohsen , Wickman Casper , Krishnaswamy Aswin Dhananjai , Sathappan Chidambaram , Söderberg Rikard 
Published: June 2021

Abstract
Avoiding quality problems in passenger cars, such as squeak and rattle (S&R), has been a remarkable cost-saving consideration. The introduction of electric engines and autonomous driving is expected to further stress the need for quieter cabins. However, the complexity of S&R events has obstructed the practical treatment of these quality issues in the pre-design-freeze phases of product development. In this study, new quantified frequency-domain metrics are proposed to measure the risk of S&R generation in car subsystems. The proposed metrics measure the resonance risk and the mode shape similarity in the critical interfaces for S&R. The calculations are done based on the system response in the frequency domain. Compared with the time-domain evaluation methods, the knowledge about the system excitation levels is not essential and the calculations are more time-efficient. The proposed metrics can be used in design optimization processes to involve S&R attributes in the pre-design-freeze attribute trade-off activities besides other attributes. In this work, these metrics were used in a previously developed two-stage optimization approach to determine the connection configuration in two industrial cases. As compared with the baseline design, the risk for S&R was reduced by improving the system behavior in terms of resonance risk and mode shape similarity. This was achieved by applying adjustments to the location of the fasteners while maintaining the same general connection configuration concept.
The Association of Family, Friends, and Teacher Support With Girls’ Sport and Physical Activity on the Island of Ireland
Authors: O’Brien Wesley , Coppinger Tara , Hogan Irene , Belton Sarahjane , Murphy Marie H. , Powell Cormac , Woods Catherine 
Published: June 2021

Background: The current study was the largest physical activity (PA) surveillance assessment of youth undertaken in Ireland in recent years. The purpose of this research was to assess the impact of social support, while controlling for age and screen time, on PA and sport participation, across a representative sample of Irish female youth.Methods: A total of 3503 children (mean age: 13.54 [2.05] y) across the island of Ireland participated. Participants completed a previously validated electronic questionnaire while supervised in a classroom setting, which investigated their (1) levels of PA; (2) screen time; (3) community sport participation; and (4) social support (friend, family, and teacher) to be physically active/partake in sport.Results: There were significant differences, with medium and large effect sizes, for social support from friends and family across types of sports participation. Specifically, girls who participated in the most popular team sports, when compared with the most popular individual sports, reported higher social support scores for friends and family structures.Conclusions: Findings from this study confirm the contributing influence of friends and family as sport and PA support networks for girls. Interventions should consider the importance of culturally relevant team sports for PA engagement in female youth.
Exploring Preschoolers’ Physical Activity and Sedentary Time During Outdoor Play at Childcare: A Cross-Sectional Analysis of the Supporting Physical Activity in the Childcare Environment Study
Authors: Bruijns Brianne A. , Vanderloo Leigh M. , Timmons Brian W. , Tucker Patricia 
Published: June 2021

Background: Moderate-to-vigorous physical activity (MVPA) offers many health benefits for preschoolers (2.5–5 y). In childcare, MVPA is predominantly accumulated outdoors, with higher rates purported among children within the first few minutes outside. The Supporting Physical Activity in the Childcare Environment intervention included shorter, more frequent outdoor play sessions; this study sought to explore children’s activity levels during various outdoor play schedules. Methods: During the final week of the Supporting Physical Activity in the Childcare Environment intervention, preschoolers wore an Actical™ accelerometer for 5 days during childcare and staff logged outdoor times. Separate linear mixed effects models were run to explore the effect of the intervention on preschoolers’ physical activity (total and MVPA) and sedentary time during outdoor play. Sex was entered as an interaction effect. Results: Preschoolers (n = 292) were significantly more active in the first 10 minutes outdoors compared with remaining time (P < .0083). For total outdoor time, children in the experimental group engaged in significantly less sedentary time than those in the control group (P < .017), and experimental group boys and girls engaged in higher MVPA than boys and girls in the control group (P < .017). Conclusions: Findings support scheduling more frequent outdoor play sessions in childcare to increase physical activity participation among young children.
Klotho prevents epithelial–mesenchymal transition through Egr-1 downregulation in diabetic kidney disease
Authors: Li Yang , Xue Meng , Hu Fang , Jia Yijie , Zheng Zongji , Yang Yanlin , Liu Xiaolian , Yang Yuelian , Wang Yanjing 
Published: June 2021

IntroductionAs a key event leading to tubulointerstitial fibrosis in diabetic kidney disease (DKD), epithelial–mesenchymal transition (EMT) has drawn increasing attention from researchers. The antiaging protein Klotho attenuates renal fibrosis in part by inhibiting ERK1/2 signaling in DKD. Early growth response factor 1 (Egr-1), which is activated mainly by ERK1/2, has been shown to play an important role in EMT. However, whether Klotho prevents EMT by inhibiting ERK1/2-dependent Egr-1 expression in DKD is unclear.The aim of this study was to investigate whether Klotho prevents EMT through Egr-1 downregulation by inhibiting the ERK1/2 signaling pathway in DKD.Research design and methodsMale C57BL/6J mice fed an high-fat diet for 4 weeks received 120 mg/kg streptozotocin (STZ), which was injected intraperitoneally. Klotho and Egr-1 expression was detected in the renal cortices of these mice on their sacrifice at 6 and 12 weeks after STZ treatment. In In vitro studies, we incubated HK2 cells under high-glucose (HG) or transforming growth factor-β1 (TGF-β1) conditions to mimic DKD. We then transfected the cells with an Klotho-containing plasmid, Klotho small interfering RNA.ResultsKlotho expression was significantly decreased in the renal cortices of mice with diabetes mellitus (DM) compared with the renal cortices of control mice at 6 weeks after treatment and even more significantly decreased at 12 weeks. In contrast, Egr-1 expression was significantly increased in mice with DM compared with control mice only at 12 weeks. We also found that Klotho overexpression downregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Conversely, Klotho silencing upregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Moreover, the effects of si-Klotho were abolished by the ERK1/2 inhibitor PD98059.ConclusionsKlotho prevents EMT during DKD progression, an effect that has been partially attributed to Egr-1 downregulation mediated by ERK1/2 signaling pathway inhibition.
Exploring support needs of people living with diabetes during the coronavirus COVID-19 pandemic: insights from a UK survey
Authors: Sauchelli Sarah , Bradley Julia , England Clare , Searle Aidan , Whitmarsh Alex 
Published: June 2021

IntroductionThe coronavirus COVID-19 pandemic has radically compromised healthcare for people living with chronic conditions such as diabetes. Government-imposed restrictions to contain the spread of the virus have forced people to suddenly adjust their lifestyle. This study aimed to capture the impact of the pandemic on people living with diabetes and the views of these individuals on ways in which the information, advice and support they are receiving could be improved.Research design and methodsAn online anonymous survey was distributed across the UK during the first lockdown and initial easing. The survey comprised questions about confidence in diabetes self-management, resources used to obtain information, advice and support, and opinions on how these could be improved. Open-ended questions captured subjective experiences.ResultsThe survey was completed by 773 adults with diabetes (69.2% type 1, 28.5% type 2). There was notable variability in the impact of the pandemic on confidence in self-management, with confidence having deteriorated most commonly in the ability to take care of own mental well-being (37.0% respondents) and improved most commonly in maintaining a healthy weight (21.1% respondents). 41.2% of respondents living alone reported not receiving any outside support. The quality of information, advice and support received from the healthcare team was rated poorly by 37.2%. Respondents sought greater communication and tailored advice from their care team, clear and consistent information from the government and news channels, and improved understanding of diabetes and its challenges from their personal networks and employers.ConclusionAdjusting to the COVID-19 pandemic has strained the mental health and well-being of people living with diabetes. Diabetes care teams must receive assistance to support these individuals without risking further inequalities in access to healthcare. Equipping personal networks and employers with knowledge on diabetes and skills to support self-management may reduce the burden on the National Health Service.
Feasibility and efficacy of a multicomponent exercise medicine programme in patients with pancreatic cancer undergoing neoadjuvant therapy (the EXPAN trial): study protocol of a dual-centre, two-armed phase I randomised controlled trial
Authors: Luo Hao , Galvão Daniel A , Newton Robert U , Tang Colin , Dean Andrew , Jasas Kevin , Johansson Mikael , Yusoff Ian , Spry Nigel , Taaffe Dennis R 
Published: June 2021

IntroductionExercise is emerging as a therapy in oncology for its physical and psychosocial benefits and potential effects on chemotherapy tolerability and efficacy. However, evidence from randomised controlled trials (RCTs) supporting exercise in patients with borderline resectable or locally advanced pancreatic cancer (PanCa) undergoing neoadjuvant therapy (NAT) are lacking.Methods and analysisThe EXPAN trial is a dual-centre, two-armed, phase I RCT. Forty patients with borderline resectable or locally advanced PanCa undergoing NAT will be randomised equally to an exercise intervention group (individualised exercise+standard NAT) or a usual care control group (standard NAT). The exercise intervention will be supervised and consist of moderate to vigorous intensity resistance and aerobic-based training undertaken two times a week for 45–60 min per session for a maximum period of 6 months. The primary outcome is feasibility. Secondary outcomes are patient-related and treatment-related endpoints, objectively measured physical function, body composition, psychological health and quality of life. Assessments will be conducted at baseline, prior to potential alteration of treatment (~4 months postbaseline), at completion of the intervention (maximum 6 months postbaseline) and 3-month and 6-month postintervention (maximum 9 and 12 months postbaseline).Ethics and disseminationThe EXPAN trial has been approved by Edith Cowan University (reference no.: 2020-02011-LUO), Sir Charles Gairdner Hospital (reference no.: RGS 03956) and St John of God Subiaco Hospital (reference no.: 1726). The study results will be presented at national/international conferences and submitted for publications in peer-reviewed journals.Trial registration numberACTRN12620001081909.
Assessment, outcomes and implications of multiple anthropometric deficits in children
Authors: Kundan Idzes , Nair Rajalakshmi , Kulkarni Shashwat , Deshpande Aparna , Jotkar Raju , Phadke Mrudula 
Published: June 2021

BackgroundMalnutrition in children is widely prevalent around the world. It has been observed that malnourished children with multiple anthropometric deficits have higher mortality. However, adequate studies are not available on the outcome and recovery of these children.Nandurbar, a tribal district from Maharashtra, India, shows high prevalence of all three forms of malnutrition, often occurring simultaneously. A project previously undertaken in Nandurbar from July 2014 to June 2016 studied the effect of various therapeutic feeds in treatment of children with uncomplicated severe acute malnutrition (SAM). In this study, we analyse secondary data from it to correlate effects of stunting, wasting and underweight on treatment recovery.MethodsAnalysis was done on 5979 children with SAM using linear and logistic regression on R software for recovery rates and weight gain in children with SAM with single versus multiple anthropometric deficits, their relation to age, sex, and recovery from severe stunting by gain in height.ResultsThe mean age of children was 35 months and 53.1% of the children were males. 2346 (39.2%) children recovered at the end of the 8-week treatment. 454 (7.6%) had single anthropometric deficit (SAM only), 3164 (52.9%) had two anthropometric deficits (SAM and severe underweight (SUW)) and 2355 (39.4%) children had three anthropometric deficits (SAM, SUW and severe stunting). Out of the 5979 children with SAM, only 52 (0.9%) of children were not underweight (severe or moderate).44.94% of children with SAM who were severely stunted recovered, compared with 35.52% of children who were not (p<0.001). After controlling for confounders, severe stunting was found to increase the odds of recovery by 1.49. Severely stunted children with SAM also showed faster recovery and weight gain by 1.93 days (p<0.012) and 0.29 g/kg/day (p<0.001), respectively. Recovery was higher in females and younger age group. Recovery was also found to depend on the therapeutic feed, with children receiving medical nutrition therapy showing better recovery for severely stunted children.ConclusionOur findings corroborate previous literature that stunting is a way for the body to deal with chronic stress of nutritional deprivation and provides a survival advantage to a child.
Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework
Authors: Pandolfo Alyssa M , Horne Robert , Jani Yogini , Reader Tom W , Bidad Natalie , Brealey David , Enne Virve I , Livermore David M , Gant Vanya , Brett Stephen J 
Published: June 2021

BackgroundAntibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians’ antibiotic prescribing.MethodsWe conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs. Focus groups explored factors influencing prescribing, whereas interviews examined decision-making processes using two clinical vignettes. Data were analysed using thematic analysis, applying the Necessity Concerns Framework.ResultsClinicians’ antibiotic decisions were influenced by their judgement of the necessity for prescribing/not prescribing, relative to their concerns about potential adverse consequences. Antibiotic necessity perceptions were strongly influenced by beliefs that antibiotics would protect patients from deterioration and themselves from the ethical and legal consequences of undertreatment. Clinicians also reported concerns about prescribing antibiotics. These generally centred on antimicrobial resistance; however, protecting the individual patient was prioritised over these societal concerns. Few participants identified antibiotic toxicity concerns as a key influencer. Clinical uncertainty often complicated balancing antibiotic necessity against concerns. Decisions to start or continue antibiotics often represented ‘erring on the side of caution’ as a protective response in uncertainty. This approach was reinforced by previous experiences of negative consequences (‘being burnt’) which motivated prescribing ‘just in case’ of an infection. Prescribing decisions were also context-dependent, exemplified by a lower perceived threshold to prescribe antibiotics out-of-hours, input from external team members and local prescribing norms.ConclusionEfforts to improve antibiotic stewardship should consider clinicians’ desire to protect with a prescription. Rapid molecular microbiology, with appropriate communication, may diminish clinicians’ fears of not prescribing or of using narrower-spectrum antibiotics.
Association of body pain and chronic disease: evidence from a 7-year population-based study in China
Authors: Luo Yaxin , Liu Zheran , Yang Lianlian , Li Juejin , Zhang Qiang , Peng Xingchen , Hu Xiaolin 
Published: June 2021

Background
Evidence is limited on the risk impact of body pain on future chronic disease. The present study aimed to investigate the association between body pain and chronic diseases.

Methods
Data were analyzed using four waves of the China Health and Retirement Longitudinal Study with 17 708 individual respondents aged 45 years and older. The association between body pain and chronic disease was estimated in both a cross-sectional cohort (2011) and a longitudinal cohort (2011–2018). The key outcomes include the incidence of overall and any specific chronic diseases. The associations among different body pain sites and 10 independent chronic disease risks were also assessed.

Findings
A total of 17 128 participants in 2011 were included in the cross-sectional cohort and 5611 participants were included in the 2011–2018 longitudinal cohort. Body pain showed an association with overall chronic disease in both the cross-sectional models (OR 2.71, 95% CI 2.47 to 2.98) and longitudinal model (risk ratio (RR) 1.21, 95% CI 1.07 to 1.35). Moreover, body pain was found to be associated with an increased risk of chronic respiratory disease (RR 1.43, 95% CI 1.06 to 1.92), heart disease (RR 1.45, 95% CI 1.12 to 1.89), kidney disease (RR 1.83, 95% CI 1.28 to 2.6), and digestive disease (RR 1.48, 95% CI 1.17 to 1.88).

Conclusion
Body pain is associated with major disease and mortality. Future clinical research should be targeted to whether or not improved pain control can mitigate this population-level disease burden.
MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING
Authors: Zhang Yong , Yang Qifan , Zeng Xiangyu , Wang Manxiang , Dong Shuang , Yang Bin , Tu Xinyi , Wei Ting , Xie Wenzhuan , Zhang Chao , Guo Qiang , Kloeber Jake A. , Cao Yueyu , Guo Guijie , Zhou Qin , Zhao Fei , Huang Jinzhou , Liu Li , Zhang Kai , Wang Mingwei , Yin Ping , Luo Kuntian , Deng Min , Kim Wootae , Hou Jing , Shi Yu , Zhu Qian , Chen Lifeng , Hu Sheng , Yue Junqiu , Pi Guoliang , Lou Zhenkun 
Published: June 2021

Abstract

Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 patients with lung cancer under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progression-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T-cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20,000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted natural killer (NK) cells and decreased CD8+ T-cell and NK-cell populations in patients with MET amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3′-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET.

Significance:
We suggest that the combination of MET inhibitor together with ICB will overcome ICB resistance induced by MET amplification. Our report reveals much-needed information that will benefit the treatment of patients with primary MET amplification or EGFR–tyrosine kinase inhibitor resistant-related MET amplification.
This article is highlighted in the In This Issue feature, p. 2659
A Computational Study on Synaptic Plasticity Regulation and Information Processing in Neuron-Astrocyte Networks
Authors: Vuillaume Roman , Lorenzo Jhunlyn , Binczak Stéphane , Jacquir Sabir 
Published: June 2021

Abstract
Postsynaptic ionotropic receptors critically shape synaptic currents and underpin their activity-dependent plasticity. In recent years, regulation of expression of these receptors by slow inward and outward currents mediated by gliotransmitter release from astrocytes has come under scrutiny as a potentially important mechanism for the regulation of synaptic information transfer. In this study, we consider a model of astrocyte-regulated synapses to investigate this hypothesis at the level of layered networks of interacting neurons and astrocytes. Our simulations hint that gliotransmission sustains the transfer function across layers, although it decorrelates the neuronal activity from the signal pattern. Overall, our results make clear how astrocytes could transform neuronal activity by inducing a lowfrequency modulation of postsynaptic activity.
Experimental size- and sex-specific predation on dung flies by amphibian and arthropod predators
Authors: Blanckenhorn Wolf U. , Cozzi Gabriele , Jäggli Gregory , Busso Juan Pablo 
Published: June 2021

Abstract
Because predator-prey interactions in nature are multifarious, linking phenomenological predation rates to underlying behavioral or ecological mechanisms is challenging. Size- and sex-specific predation has been implicated as a major selective force keeping animals small, directing the evolution of body size and sexual size dimorphism. We experimentally assessed predation by 4 amphibian and 3 arthropod species (bug, fly, spider) on 3 species of dung flies with similar ecology but contrasting body sizes, sexual size dimorphism, and coloration. Predators were offered a size range of male and/or female individuals of one prey species. As expected based on optimal foraging theory, some anurans (Bufo bufo) preferred larger prey individuals, others (Bombina variagata, Rana esculenta) showed no preference. Small juvenile Rana temporaria metamorphs preferred small prey, as did all arthropod predators, a pattern that may be explained by gape limitation or larger prey escaping better. Presumably more mobile males were not preyed upon more frequently or faster than cryptic females, even when conspicuously colored. Contrary to expectation, predation rates on flies in mixed groups facilitating mating activity were not higher, nor was predation generally sex-specific, hence contributing little to sexual dimorphism. We conclude that the size-selectivity of predators, and hence the viability selection pattern exerted on their prey, depends foremost on the relative body sizes of the two in a continuous fashion, in addition to any specific prey defense mechanisms. Therefore, the mechanistic study of predation requires integration of both the predator and prey perspectives, and phenomenological field studies of predation remain indispensable.