bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the effects of meteorological factors on COVID-19 prevalence by the distributed lag nonlinear model
Authors: Ai Hongjing , Nie Rongfang , Wang Xiaosheng 
Published: April 2022

Abstract
Background
Although numerous studies have explored the impact of meteorological factors on the epidemic of COVID-19, their relationship remains controversial and needs to be clarified.

Methods
We assessed the risk effect of various meteorological factors on COVID-19 infection using the distributed lag nonlinear model, based on related data from July 1, 2020, to June 30, 2021, in eight countries, including Portugal, Greece, Egypt, South Africa, Paraguay, Uruguay, South Korea, and Japan, which are in Europe, Africa, South America, and Asia, respectively. We also explored associations between COVID-19 prevalence and individual meteorological factors by the Spearman’s rank correlation test.

Results
There were significant non-linear relationships between both temperature and relative humidity and COVID-19 prevalence. In the countries located in the Northern Hemisphere with similar latitudes, the risk of COVID-19 infection was the highest at temperature below 5 ℃. In the countries located in the Southern Hemisphere with similar latitudes, their highest infection risk occurred at around 15 ℃. Nevertheless, in most countries, high temperature showed no significant association with reduced risk of COVID-19 infection. The effect pattern of relative humidity on COVID-19 depended on the range of its variation in countries. Overall, low relative humidity was correlated with increased risk of COVID-19 infection, while the high risk of infection at extremely high relative humidity could occur in some countries. In addition, relative humidity had a longer lag effect on COVID-19 than temperature.

Conclusions
The effects of meteorological factors on COVID-19 prevalence are nonlinear and hysteretic. Although low temperature and relative humidity may lower the risk of COVID-19, high temperature or relative humidity could also be associated with a high prevalence of COVID-19 in some regions.
Mitigated suppressive function of regulatory T cells (Treg) upon Th17-inducing cytokines in oligo- and polyarticular Juvenile Idiopathic Arthritis (JIA) patients
Authors: Holzer Marie-Therese , Almanzar Giovanni , Woidich Robert , Hügle Boris , Haas Johannes-Peter , Prelog Martina 
Published: April 2022

Abstract
Background
The plasticity of T helper-17 (Th17) and regulatory T (Treg) cells may be a clue to pathogenesis of Juvenile Idiopathic Arthritis (JIA). It is still unclear, whether targeted suppression of Interleukin (IL)-17 is able to influence regulatory function of Treg to control pro-inflammatory effectors in JIA. This study aimed to assess the effect of a Th17-stimulating cytokine environment and of IL-17A-inhibition on phenotype plasticity and suppressive function of Treg derived from JIA patients.

Methods
Th17 and Treg characteristics of CD4+ helper T cells were investigated in blood samples of JIA patients with oligo- and polyarticular pattern and healthy controls (HC). Isolated CD4+CD25+CD127− cells defined as Treg were cultivated with Th17-inducing cytokine environment as well as with IL-17A-inhibitors and analyzed for plasticity of phenotype by flow cytometry. Furthermore, inhibitory function of Treg on autologous effectors after cultivation with these stimuli was determined by suppression assays.

Results
Our findings demonstrated significantly elevated proportions of Th17 and Th17-like Treg in JIA compared to HC. After incubation with Th17-inducing stimuli, increased FoxP3 expression in separated Treg in JIA and an impaired suppressive capacity in JIA and HC were found. Blockade of IL-17A resulted in adjustment of FoxP3-expression in JIA to proportions found in controls and in regular suppressive function.

Conclusions
Our results demonstrate an induction of FoxP3 expressing Treg by Th17-inducing cytokines with concomitant mitigated suppressive function. In contrast, specific IL-17A blockade maintains suppressive Treg function and adjusted FoxP3-expression in JIA to levels found in controls. These findings may help to provide experimental evidence for the successful clinical use of IL-17A inhibition in JIA patients.
Real-world data reveals the complexity of disease modifying anti-rheumatic drug treatment patterns in juvenile idiopathic arthritis: an observational study
Authors: Grazziotin Luiza R. , Currie Gillian , Twilt Marinka , Ijzerman Maarten J. , Kip Michelle M. A. , Koffijberg Hendrik , Benseler Susanne M. , Swart Joost F. , Vastert Sebastiaan J. , Wulffraat Nico M. , Yeung Rae S. M. , Marshall Deborah A. 
Published: April 2022

Abstract
Objective
Pharmacological treatment is a cornerstone of care for children with juvenile idiopathic arthritis (JIA). The objective of this study is to evaluate prescription patterns of conventional and biologic disease modifying anti-rheumatic drugs (c-DMARDs and b-DMARDs) for patients with JIA.

Methods
We conducted a retrospective cohort study of children diagnosed with JIA at a rheumatology pediatric clinic. Eligibility criteria were defined as children and youth newly diagnosed with enthesis-related arthritis, polyarticular, or oligoarticular JIA between 2011 and 2019, with at least one year of observation. Data on c-DMARDs and b-DMARDs prescriptions were obtained from electronic medical charts. We used descriptive statistics, Kaplan–Meier survival methods, and Sankey diagrams to describe treatment prescription patterns.

Results
A total of 325 patients with JIA were included, with a median observation time of 3.7 years. The most frequently prescribed c-DMARD and b-DMARD were methotrexate and etanercept, respectively. Within the first year of rheumatology care, 62% and 21% of patients had a c-DMARD and a b-DMARD prescribed, respectively. These proportions varied greatly by JIA subtype. Among the 147 (147/325, 45%) patients that had at least one b-DMARD prescribed, 24% were prescribed a second, and 7% a third-line of b-DMARD. A total of 112 unique treatment sequences were observed, with c-DMARD monotherapy followed by the addition of either a b-DMARD (56%) or another c-DMARD (30%) being the two most prevalent patterns in this cohort.

Conclusion
We observed a variety of treatment trajectories, with many patients experiencing multiple treatment lines, illustrating the complexity of the overall JIA treatment path.
Integrated pond aquaculture and regional identity: ethnobiology of the golden humped tench of Poirino highlands, Northwest Italy
Authors: Delpero Alessandro , Volpato Gabriele 
Published: April 2022

AbstractBackgroundSocial–ecological systems are based on particular species and on their direct and human-mediated interactions. The ‘golden humped tench’ ortinca gobba dorata, a variety of tench—Tinca tinca(L., 1758)—traditionally bred in artificial ponds calledpeschierein Poirino highlands, northwest Italy, is one of such species. The aim of the study is to investigate the traditional farming of the golden humped tench, the associated knowledge, practices, and gastronomy, and to discuss the changes that the tench, the ponds, and their role in the local social–ecological system are going through.MethodsThe data analyzed were collected in different locations of Poirino highlands during May–September 2021. Fieldwork included semi-structured interviews (n = 23) with current and former tench farmers about the breeding and gastronomy of the tench and the management of thepeschiere. The interviewees’ selection occurred through an exponential non-discriminative snowball sampling, and interview transcripts were qualitatively analyzed through inductive thematic content analysis.ResultsThe golden humped tench has been farmed for centuries in ponds used also to water livestock and to irrigate cultivated fields, and managed by every peasant household in the area. This integrated aquaculture system is underpinned by detailed knowledge on thepeschieraecosystem and on the tench life cycle and supports a gastronomic knowledge that is part of the local heritage. The ongoing process of gastronomic valorization of the tench is sustaining the role of the fish in locals’ livelihoods and as a marker of regional identity, but it is also transforming tench farming, already threatened by livelihood change, pesticides, and invasive species, in controversial ways.ConclusionsWe argue that ponds and tenches are core elements of the local social–ecological system, defining the cultural landscape and engendering a form of regional identity around them. Studying integrated aquaculture systems and associated knowledge and practices is relevant to design sustainable systems of food production and to address possibilities of conservation of biodiversity and livelihoods in aquatic environments.
Quantitative monitoring of paramagnetic contrast agents and their allocation in plant tissues via DCE-MRI
Authors: Mayer Simon , Munz Eberhard , Hammer Sebastian , Wagner Steffen , Guendel Andre , Rolletschek Hardy , Jakob Peter M. , Borisjuk Ljudmilla , Neuberger Thomas 
Published: April 2022

AbstractBackgroundStudying dynamic processes in living organisms with MRI is one of the most promising research areas. The use of paramagnetic compounds as contrast agents (CA), has proven key to such studies, but so far, the lack of appropriate techniques limits the application of CA-technologies in experimental plant biology. The presented proof-of-principle aims to support method and knowledge transfer from medical research to plant science.ResultsIn this study, we designed and tested a new approach for plant Dynamic Contrast Enhanced Magnetic Resonance Imaging (pDCE-MRI). The new approach has been applied in situ to a cereal crop (Hordeum vulgare). The pDCE-MRI allows non-invasive investigation of CA allocation within plant tissues. In our experiments, gadolinium-DTPA, the most commonly used contrast agent in medical MRI, was employed. By acquiring dynamic T1-maps, a new approach visualizes an alteration of a tissue-specific MRI parameter T1(longitudinal relaxation time) in response to the CA. Both, the measurement of local CA concentration and the monitoring of translocation in low velocity ranges (cm/h) was possible using this CA-enhanced method.ConclusionsA novel pDCE-MRI method is presented for non-invasive investigation of paramagnetic CA allocation in living plants. The temporal resolution of the T1-mapping has been significantly improved to enable the dynamic in vivo analysis of transport processes at low-velocity ranges, which are common in plants. The newly developed procedure allows to identify vascular regions and to estimate their involvement in CA allocation. Therefore, the presented technique opens a perspective for further development of CA-aided MRI experiments in plant biology.
The enduring consequences of conflict-related sexual violence: a qualitative study of women survivors in northern Uganda
Authors: Woldetsadik Mahlet A. , Acan Grace , Odiya Okwir Isaac 
Published: April 2022

Abstract
Background
One in three women in northern Uganda report having suffered from conflict-related sexual violence (CRSV), including forced marriage and rape. Research on the long-term effects of CRSV on the health and social well-being of survivors is scant, but crucial to informing policy and improving programs tailored to conflict-affected communities. Understanding women’s perceptions of and experiences with CRSV, especially related to the persistent health and social challenges they continue to face, is critical for developing effective and targeted interventions.

Methods
We worked with a local, survivor-led organization to recruit participants purposively from three post-conflict districts in northern Uganda: Gulu, Lira, and Pader. Women who had experienced CRSV and who were 18 years of age or older were eligible to participate. We asked participants open-ended questions about their experience with CRSV, including how it continues to affect their health and social well-being, any impact it had on their relationships, and if they faced barriers to accessing services. We transcribed, translated, and uploaded interview responses to the qualitative data analysis software MAXQDA and analyzed data thematically using a modified approach to grounded theory.

Results
We conducted 30 interviews between October 2016 and March 2017. All participants reported experiencing forced marriage, rape, or forced pregnancy. Over two-thirds of participants said they continued to face physical and psychological issues, including untreated sexually transmitted infections, anxiety, and depression. Almost half of the women faced challenges with maintaining links with family members, stigma related to their experiences during abduction that also extended to their children born in captivity, and difficulty with accessing and affording health care. Barriers to seeking care included fear of disclosure and being unable to find services. Women identified peer-support from other survivors as a key coping mechanism.

Conclusions
Women survivors continue to face multifaceted health and social problems in the post-conflict period. Most health-related programs that were set up at the end of the war in northern Uganda are no longer available. Increasing access to care, particularly services tailored to treating chronic reproductive health issues and mental health, is paramount for women survivors in northern Uganda and other conflict-affected regions.
Selective sorting and secretion of hY4 RNA fragments into extracellular vesicles mediated by methylated YBX1 to promote lung cancer progression
Authors: Li Chuang , Wang Wei , Sun Yuting , Ni Yifan , Qin Fang , Li Xiaolu , Wang Tao , Guo Mingxiong , Sun Guihong 
Published: April 2022

Abstract
Background
Extracellular vesicles (EVs) are emerging mediators of intercellular communication that have been shown to play important roles in tumor progression. YRNA fragments, a type of small non-coding RNA, are dysregulated in non-small cell lung cancer (NSCLC) cell-derived EVs, suggesting that they may be an effective biomarker for cancer diagnosis and treatment strategies.

Methods
Differentially expressed YRNA hY4 fragments (hY4F) in EVs from NSCLC cells and normal lung fibroblasts were isolated by differential ultra-centrifugation. RNA-binding proteins that interacted with hY4F were identified by screening with an RNA pulldown assay and mass spectrometry. The molecular mechanism of hY4F and the RNA-binding protein Y box binding protein 1 (YBX1) was demonstrated by qRT-PCR, western blot, RNA pulldown, and rescue experiments. Transcriptome sequencing, qRT-PCR validation, bioinformatics analysis and NF-κB pathway inhibitor assays elucidate the mechanism of YBX1 and hY4F inhibiting lung cancer. A peptide pulldown assay was performed to screen and identify a potential methyltransferase for YBX1. The roles of hY4F, YBX1, and SET domain containing 3 in biological functions, such as proliferation, migration, invasion, and apoptosis, in lung cancer cells were also examined by EdU incorporation assay, Transwell assay, flow cytometry, and other methods. Lastly, a mouse xenograft assay was used to assess the clinical relevance of YBX1 and hY4F in vivo.

Results
Our data demonstrate that hY4 RNA fragments were upregulated in lung cancer- derived EVs, hY4F inhibits tumor progression through downregulating MAPK/NF-κB signaling, and then the selective sorting and secretion of hY4F into lung cancer EVs is regulated by the RNA-binding protein YBX1. Furthermore, we identified lysine K264 within the YBX1 C-terminal domain as the necessary site for its interaction with hY4Fs. K264 is modified by methylation, which affects its binding to hY4F and subsequent selective sorting into EVs in lung cancer cells.

Conclusion
Our findings demonstrate that hY4F acts as a tumor suppressor and is selectively sorted into lung cancer cell-derived EVs by interacting with methylated YBX1, which in turn promotes lung cancer progression. hY4F is a promising circulating biomarker for non-small cell lung cancer diagnosis and prognosis and an exceptional candidate for further therapeutic exploration.
Peripheral lymphocyte populations in ovarian cancer patients and correlations with clinicopathological features
Authors: Ye Shuang , Chen Wei , Zheng Yuwei , Wu Yutuan , Xiang Libing , Li Teng , Ping Bo , Zhang Xiaoming , Yang Huijuan 
Published: April 2022

Abstract
Background
To investigate the alterations of peripheral lymphocyte subpopulations in ovarian cancer patients compared to benign or borderline counterparts. The possible clinicopathological implications were also evaluated.

Methods
We enrolled 112 treatment-naive ovarian cancer patients, 14 borderline tumor patients and 44 benign tumor patients between 09/2016 and 01/2019. Flow cytometry was used to measure the peripheral lymphocyte subsets consisting of T cells (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+), regulatory T cells (Tregs, CD4+CD25+CD127−), natural killer cells (NK cells, CD3−CD56+) and B cells (CD19+).

Results
Most ovarian cancer patients were high-grade serous carcinoma (84.8%), followed by clear cell carcinoma (8.03%). Late-stage tumor (FIGO III + IV) accounted for 82.1%. The study showed that the proportions of peripheral lymphocyte subsets underwent apparent changes in ovarian cancer patients. We observed elevated levels of Treg cells in patients with both ovarian borderline and malignant tumor compared to those with benign tumors, which achieved statistic significance. In contrast, CD3+CD8+ T and CD8+CD28+ T cells were significantly lower in ovarian cancer patients. Interestingly, low level of B cells was correlated to clear cell carcinoma (P = 0.024), advanced tumor (P = 0.028) and platinum-resistant recurrence (P = 0.014). Regarding the changes of lymphocyte subsets after surgery, CD8+CD28+ T cells had a significant decreasing tendency (P = 0.007) while B cells were the opposite (P < 0.001).

Conclusions
Ovarian cancer patients have altered circulating lymphocyte profile (elevated Treg cell, depressed CD3+CD8+ T and CD8+CD28+ T cells). Low level of B cells might be related to disease aggressiveness, and it recovered after the removal of tumor, which merits further study.
The Positive Choices trial: update to study protocol for a phase-III RCT trial of a whole-school social-marketing intervention to promote sexual health and reduce health inequalities
Authors: Ponsford Ruth , Meiksin Rebecca , Allen Elizabeth , Melendez-Torres G. J. , Morris Steve , Mercer Catherine , Campbell Rona , Young Honor , Lohan Maria , Coyle Karin , Bonell Chris 
Published: April 2022

Abstract
Background
Positive Choices is a whole-school social-marketing intervention to promote sexual health among secondary school students. Intervention comprises the following: school health promotion council involving staff and students coordinating delivery, student survey to inform local tailoring, teacher-delivered classroom curriculum, student-run campaigns, parent information and review of sexual/reproductive health services to inform improvements. This trial builds on an optimisation/pilot-RCT study which met progression criteria, plus findings from another pilot RCT of the Project Respect school-based intervention to prevent dating and relationship violence which concluded such work should be integrated within Positive Choices. Young people carry a disproportionate burden of adverse sexual health; most do not report competence at first sex. Relationships and sex education in schools can contribute to promoting sexual health but effects are small, inconsistent and not sustained. Such work needs to be supplemented by ‘whole-school’ (e.g. student campaigns, sexual health services) and ‘social marketing’ (harnessing commercial marketing to social ends) approaches for which there is good review-level evidence but not from the UK.

Methods
We will conduct a cluster RCT across 50 schools (minimum 6440, maximum 8500 students) allocated 1:1 to intervention/control assessing outcomes at 33 months. Our primary outcome is non-competent first sex. Secondary outcomes are non-competent last sex, age at sexual debut, non-use of contraception at first and last sex among those reporting heterosexual intercourse, number of sexual partners, dating and relationship violence, sexually transmitted infections and pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys. We will recruit 50 school and undertake baseline surveys by March 2022, implement the intervention over the 2022–2024 school years and conduct the economic and process evaluations by July 2024; undertake follow-up surveys by December 2024; complete analyses, all patient and policy involvement and draft the study report by March 2025 and engage in knowledge exchange from December 2024.

Discussion
This trial is one of a growing number focused on whole-school approaches to public health in schools. The key scientific output will be evidence about the effectiveness, costs and potential scalability and transferability of Positive Choices.

Trial registration
ISRCTN No: ISRCTN16723909. Registered on 3 September 2021.
Using a modified nominal group technique to develop complex interventions for a randomised controlled trial in children with symptomatic pes planus
Authors: Backhouse Michael R. , Parker Daniel J. , Morison Stewart C. , Anderson Jenny , Cockayne Sarah , Adamson Joy A. 
Published: April 2022

Abstract
Background
Children with symptomatic flat feet (pes planus) frequently present for care but there remains uncertainty about how best to manage their condition. There is considerable variation in practice between and within professions. We intend to conduct a three-arm trial to evaluate three frequently used interventions for pes planus (exercise and advice, exercise and advice plus prefabricated orthoses, and exercise and advice plus custom made orthoses). Each of these interventions are complex and required developing prior to starting the trial. This paper focusses on the development process undertaken to develop the interventions.

Methods
We used a modified Nominal Group Technique combining an electronic survey with two face-to-face meetings to achieve consensus on the final logic model and menu of options for each intervention. Using the Nominal Group Technique across consecutive meetings in combination with a questionnaire is novel, and enabled us to develop complex interventions that reflect contemporary clinical practice.

Results
In total 16 healthcare professionals took part in the consensus. These consisted of 11 podiatrists, two orthotists, two physiotherapists, and one orthopaedic surgeon.
Both meetings endorsed the logic model with amendments to reflect the wider psychosocial impact of pes planus and its treatment, as well as the increasing use of shared decision making in practice. Short lists of options were agreed for prefabricated and custom made orthoses, structures to target in stretching and strengthening exercises, and elements of health education and advice.

Conclusions
Our novel modification of the nominal group technique produced a coherent logic model and shortlist of options for each of the interventions that explicitly enable adaptability. We formed a consensus on the range of what is permissible within each intervention so that their integrity is kept intact and they can be adapted and pragmatically applied. The process of combining survey data with face-to-face meetings has ensured the interventions mirror contemporary practice and may provide a template for other trials.