bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-perspective qualitative exploration of the reasons for changes in the physical activity among 10–11-year-old children following the easing of the COVID-19 lockdown in the UK in 2021
Authors: Walker Robert , House Danielle , Emm-Collison Lydia , Salway Ruth , Tibbitts Byron , Sansum Kate , Reid Tom , Breheny Katie , Churchward Sarah , Williams Joanna G. , de Vocht Frank , Hollingworth William , Foster Charlie , Jago Russell 
Published: September 2022

Abstract
Background
Active-6 is exploring how the COVID-19 pandemic has impacted physical activity behaviour among Year 6 children (aged 10–11 years) and their parents in Southwest England. Initial findings from the Active-6 project have shown a 7–8 min decrease in moderate-to-vigorous physical activity and an increase in sedentary behaviour among children following the easing of restrictions in the UK in latter half of 2021. This finding suggests that the pandemic has had a persistent impact on child physical activity behaviour. This paper explored the possible mechanisms behind these changes.

Methods
Interviews with parents (n = 21), members of school staff (n = 9) and focus groups with children aged 10–11 years (n = 47) were conducted between August and December 2021 to discuss the impact of the pandemic on child physical activity behaviour. The framework method was used for analysis.

Results
Five themes spanning two key stages of the pandemic were described. Three themes related to the period of lockdowns and fluctuating restrictions (March 2020 – April 2021). These included: Theme 1) Lockdown: A short-lived adventure; Theme 2) Access to facilities during restrictions; and Theme 3) The importance of the parent. A further two themes were identified related to the period following the gradual easing of restrictions in April 2021. These included: Theme 4) An overwhelming return to normal; and Theme 5) Reopening fatigue.

Conclusions
The analysis suggested that feelings of novelty experienced during the initial stages of lockdown waned as restrictions were prolonged, creating an increasingly challenging period for parents and their children. However, during periods of restrictions, the importance of parental encouragement and access to appropriate facilities in the local and home environment helped facilitate physical activity. Following the easing of COVID-19 restrictions, emotional overwhelm and physical fatigue among children, stemming from a sedentary and socially isolated life in lockdown and other restrictions, were key contributors to the decreased moderate to vigorous physical activity and increased sedentary behaviour that was observed in a related quantitative study.
Identification of diagnostic biomarkers and therapeutic targets in peripheral immune landscape from coronary artery disease
Authors: Feng Xiaoteng , Zhang Yifan , Du Min , Li Sijin , Ding Jie , Wang Jiarou , Wang Yiru , Liu Ping 
Published: September 2022

Abstract
Background
Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD.

Methods
We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis.

Results
A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR−/− mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-β, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway.

Conclusions
We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.
TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: a report of two cases
Authors: Aslani Nahid , Asnaashari Kosar , Parvaneh Nima , Shahrooei Mohammad , Sotoudeh-Anvari Maryam , Shahram Farhad , Ziaee Vahid 
Published: September 2022

Abstract
Background
A20 haploinsufficiency (HA20) is a newly introduced autosomal dominant autoinflammatory disorder, also known as Behcet’s-like disease. Some of the most common symptoms of the disease are recurrent oral, genital, and/or gastrointestinal (GI) ulcers, episodic fever, musculoskeletal symptoms, cutaneous lesions, and recurrent infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of multi-organ failure due to excessive immune activation. HLH has been reported in a few HA20 patients. Herein, we report two children with the primary presentation of HLH, with a mutation in TNFAIP3, in favor of HA20.

Case presentations
Our first patient was a 4-month-old boy who presented with fever, irritability, pallor, and hepatosplenomegaly. Pancytopenia, elevated ferritin, and decreased fibrinogen levels were found in laboratory evaluation. He was diagnosed with HLH and was treated with methylprednisolone and cyclosporine. Two years later, whole exome sequencing (WES) indicated a mutation in TNFAIP3 at NM_001270507: exon3: c.C386T, p.T129M, consistent with A20 haploinsufficiency. Etanercept, a TNF inhibitor, was prescribed, but the parents were reluctant to initiate the therapy. The patient passed away with the clinical picture of cerebral hemorrhage.
The second patient was a 3-month-old boy who presented with a fever and hepatosplenomegaly. Laboratory evaluation found pancytopenia, hyperferritinemia, hypoalbuminemia, hypertriglyceridemia, and hypofibrinogenemia. With the establishment of the HLH diagnosis, he was treated with etoposide, dexamethasone, and cyclosporine, and recovered. WES results revealed a heterozygous de novo variant of TNFAIP3 (c. T824C in exon 6, 6q23.3) that leads to a proline to leucine amino acid change (p. L275P). He was treated with etanercept and has been symptom-free afterward.

Conclusions
This report is a hypothesis for developing of the HLH phenotype in the presence of TNFAIP3 mutation. Our results provide a new perspective on the role of TNFAIP3 mutation in HLH phenotypes, but more extensive studies are required to confirm these preliminary results.
Kawasaki disease complicated by peripheral artery thrombosis: a case report and literature review
Authors: Zhang Nanjun , Yu Li , Xiong Zhongxian , Hua Yimin , Duan Hongyu , Qiao Lina , Zhou Kaiyu , Wang Chuan 
Published: September 2022

Abstract
Background
Peripheral gangrene is rarely documented as a possible complication of Kawasaki disease (KD). There are many causes of peripheral gangrene, and the common cause is in situ thrombosis or embolism. Most cases are reported to have regrettable outcomes (amputation or necrotic shedding). Herein, we report the successful management of KD complicated by peripheral artery thrombosis in an older Chinese boy, and a review of all cases of peripheral gangrene in KD in the literature.

Case presentation
We found that most of the children with this complication were under 1 year old, had a heavy inflammatory response combined with the use of cortisol and immunoglobulin, and most children had coronary artery lesions. In addition, Peripheral gangrene mainly occurred in the subacute or chronic stage, and the prognosis is poor.

Conclusions
In the presence of high risk factors, we consider it is necessary to monitor coagulation function and administer prophylactic anticoagulation therapy. When peripheral artery thrombosis or embolism occur, heparin and prostaglandins can be used for treatment.
The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration
Authors: Nortey Andrea , Garces Kimberly , Carmy-Bennun Tal , Hackam Abigail S. 
Published: September 2022

Abstract
Background
Retinal degenerative diseases are a group of conditions characterized by photoreceptor death and vision loss. Excessive inflammation and microglial activation contribute to the pathology of retinal degenerations and a major focus in the field is identifying more effective anti-inflammatory therapeutic strategies that promote photoreceptor survival. A major challenge to developing anti-inflammatory treatments is to selectively suppress detrimental inflammation while maintaining beneficial inflammatory responses. We recently demonstrated that endogenous levels of the IL-27 cytokine were upregulated in association with an experimental treatment that increased photoreceptor survival. IL-27 is a pleiotropic cytokine that regulates tissue reactions to infection, neuronal disease and tumors by inducing anti-apoptotic and anti-inflammatory genes and suppressing pro-inflammatory genes. IL-27 is neuroprotective in the brain, but its function during retinal degeneration has not been investigated. In this study, we investigated the effect of IL-27 in the rd10 mouse model of inherited photoreceptor degeneration.

Methods
Male and female rd10 mice were randomly divided into experimental (IL-27) and control (saline) groups and intravitreally injected at age post-natal day (P) 18. Retina function was analyzed by electroretinograms (ERGs), visual acuity by optomotor assay, photoreceptor death by TdT-mediated dUTP nick-end labeling (TUNEL) assay, microglia/macrophage were detected by immunodetection of IBA1 and inflammatory mediators by cytoplex and QPCR analysis. The distribution of IL-27 in the retina was determined by immunohistochemistry on retina cross-sections and primary Muller glia cultures.

Results
We demonstrate that recombinant IL-27 decreased photoreceptor death, increased retinal function and reduced inflammation in the rd10 mouse model of retinal degeneration. Furthermore, IL-27 injections led to lower levels of the pro-inflammatory proteins Ccl22, IL-18 and IL-12. IL-27 expression was localized to Muller glia and IL-27 receptors to microglia, which are key cell types that regulate photoreceptor survival.

Conclusion
Our results identify for the first time anti-inflammatory and neuroprotective activities of IL-27 in a genetic model of retinal degeneration. These findings provide new insight into the therapeutic potential of anti-inflammatory cytokines as a treatment for degenerative diseases of the retina.
Efficacy of behavioral interventions to improve maternal mental health and breastfeeding outcomes: a systematic review
Authors: Pezley Lacey , Cares Kate , Duffecy Jennifer , Koenig Mary Dawn , Maki Pauline , Odoms-Young Angela , Clark Withington Margaret H. , Lima Oliveira Manoela , Loiacono Bernardo , Prough Jilian , Tussing-Humphreys Lisa , Buscemi Joanna 
Published: September 2022

AbstractBackgroundDespite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor associated with barriers and reduced rates of breastfeeding intent, initiation, and continuation. Given evidence of a bidirectional association between maternal mental health and breastfeeding, it is important to consider both factors when examining the efficacy of interventions to improve these outcomes. The purpose of this manuscript is to review the literature on the efficacy of behavioral interventions focused on both maternal mental health and breastfeeding outcomes, examining the intersection of the two.MethodsThis systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Studies were selected if they were available in English, used primary experimental design, and used a behavioral intervention type to examine maternal mental health and breastfeeding outcomes. Articles were identified from PubMed, CINAHL, Embase, and PsycINFO from database inception to 3 March 2022. Study quality was assessed using the Cochrane Risk of Bias tool. Results were synthesized by intervention success for 1. Mental health and breastfeeding, 2. Breastfeeding only, 3. Mental health only, and 4. No intervention effect. PROSPERO CRD42021224228.ResultsThirty interventions reported in 33 articles were identified, representing 15 countries. Twelve studies reported statistically significant positive effect of the intervention on both maternal mental health and breastfeeding; most showing a decrease in self-report depressive and/or anxiety symptoms in parallel to an increase in breastfeeding duration and/or exclusivity. Common characteristics of successful interventions were a) occurring across pregnancy and postpartum, b) delivered by hospital staff or multidisciplinary teams, c) offered individually, and d) designed to focus on breastfeeding and maternal mental health or on breastfeeding only. Our results are not representative of all countries, persons, experiences, circumstances, or physiological characteristics.ConclusionsInterventions that extend the perinatal period and offer individualized support from both professionals and peers who collaborate through a continuum of settings (e.g., health system, home, and community) are most successful in improving both mental health and breastfeeding outcomes. The benefits of improving these outcomes warrant continued development and implementation of such interventions.Systematic review registrationPROSPERO CRD42021224228.
The role of soluble CD80 in patients with soft tissue tumors
Authors: Matsuyama Yumi , Asanuma Kunihiro , Yoshida Keisuke , Hagi Tomohito , Iino Takahiro , Nakamura Tomoki , Sudo Akihiro 
Published: September 2022

Abstract
Background
Immune checkpoint protein (ICP), which is a central factor group of the immune system, has been reported to have a correlation between the degree of its expression and the prognosis of patients with malignant tumors, and many inhibitors have appeared as therapeutic targets. On the other hand, a soluble form of ICP in circulating blood induced systemic immunosuppression. In this study, we investigated the relationship between the soluble form of CD80 (sCD80) which is a ligand for the inhibitory system CTLA-4, in blood, and clinicopathological parameters in patients with soft tissue tumors.

Methods
A total of 119 patients with primary soft tissue tumors were enrolled in this study. The sCD80 levels were measured by enzyme immunoassay.

Results
There were no significant differences in sCD80 levels between benign (34) and soft tissue sarcoma (STS) patients (85). In STS, the high-sCD80 group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low-sCD80 group at 5 years using the log-rank test (OS: high > 404 pg/mL, low ≤ 404 pg/mL, MS: high > 531 pg/ml, low ≤ 531 pg/ml). On multivariate Cox proportional hazard analysis, the high-sCD80 group had significant differences in 5MS and 5OS compared to the low-sCD80 group.

Conclusions
In conclusion, sCD80 may negatively affect systemic immune circumstances, in STS, and may have potential as a therapeutic target.
Resveratrol protection against IL-1β-induced chondrocyte damage via the SIRT1/FOXO1 signaling pathway
Authors: Liang ChuanCai , Xing Hengte , Wang ChenYu , Xu XiongFeng , Hao Yarong , Qiu Bo 
Published: September 2022

Abstract
Purpose
Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration, synovial inflammation, osteophytes, and subchondral osteosclerosis. This study investigated the effects of resveratrol (RES) on extracellular matrix (ECM), autophagy, and apoptosis in OA pathogenesis via the SIRT1/FOXO1 pathway.

Methods
The microenvironment of OA chondrocytes was stimulated in vitro by adding 10 ng/mL of IL-1β to primary Wistar rat chondrocyte. Western blotting, immunofluorescence, quantitative real-time PCR, and transmission electron microscopy (TEM) were used for analysis.

Results
In the presence of IL-1β, RES increased the expression of silent information regulator (SIR) 1 protein and the phosphorylation level of forkhead transcription factor (FOXO) 1. It also promoted chondrocyte autophagy, increased the expression of SOX9 and aggrecan, inhibited chondrocyte apoptosis and matrix breakdown, and protected chondrocytes from IL-1β damage. After a SIRT1 inhibitor or FOXO1 inhibitor was added, the protective effect of RES on chondrocytes was significantly weakened. Our results suggest that RES regulates the ECM metabolism, autophagy, and apoptosis of OA chondrocytes through the SIRT1/FOXO1 pathway to ameliorate IL-1β-induced chondrocyte injury.

Conclusion
RES protects chondrocytes from IL-1β-induced damage by activating SIRT1/FOXO1 signaling and holds potential in OA treatment.
Social pharmaceutical innovation and alternative forms of research, development and deployment for drugs for rare diseases
Authors: Douglas Conor M. W. , Aith Fernando , Boon Wouter , de Neiva Borba Marina , Doganova Liliana , Grunebaum Shir , Hagendijk Rob , Lynd Larry , Mallard Alexandre , Mohamed Faisal Ali , Moors Ellen , Oliveira Claudio Cordovil , Paterson Florence , Scanga Vanessa , Soares Julino , Raberharisoa Vololona , Kleinhout-Vliek Tineke 
Published: September 2022

AbstractRare diseases are associated with difficulties in addressing unmet medical needs, lack of access to treatment, high prices, evidentiary mismatch, equity, etc. While challenges facing the development of drugs for rare diseases are experienced differently globally (i.e., higher vs. lower and middle income countries), many are also expressed transnationally, which suggests systemic issues. Pharmaceutical innovation is highly regulated and institutionalized, leading to firmly established innovation pathways. While deviating from these innovation pathways is difficult, we take the position that doing so is of critical importance. The reason is that the current model of pharmaceutical innovation alone will not deliver the quantity of products needed to address the unmet needs faced by rare disease patients, nor at a price point that is sustainable for healthcare systems. In light of the problems in rare diseases, we hold that re-thinking innovation is crucial and more room should be provided for alternative innovation pathways. We already observe a significant number and variety of new types of initiatives in the rare diseases field that propose or use alternative pharmaceutical innovation pathways which have in common that they involve a diverse set of societal stakeholders, explicitly address a higher societal goal, or both. Our position is that principles of social innovation can be drawn on in the framing and articulation of such alternative pathways, which we term heresocial pharmaceutical innovation(SPIN), and that it should be given more room for development. As an interdisciplinary research team in the social sciences, public health and law, the cases of SPIN we investigate are spread transnationally, and include higher income as well as middle income countries. We do this to develop a better understanding of the social pharmaceutical innovation field’s breadth and to advance changes ranging from the bedside to system levels. We seek collaborations with those working in such projects (e.g., patients and patient organisations, researchers in rare diseases, industry, and policy makers). We aim to add comparative and evaluative value to social pharmaceutical innovation, and we seek to ignite further interest in these initiatives, thereby actively contributing to them as a part of our work.
The impact of the COVID-19 pandemic on Fabry Disease Patients: an examination of Mood Status, Therapy Adherence, and COVID-19 infection
Authors: Karaca Cebrail , Dincer Mevlut Tamer , Ozcan Seyda Gul , Sarac Betul , Ahmadzada Saffa , Alagoz Selma , Bakir Alev , Kiykim Ertugrul , Trabulus Sinan , Seyahi Nurhan 
Published: September 2022

Abstract
Background
Fabry disease (FD) is a rare metabolic disorder, in which a lifelong enzyme replacement therapy (ERT) constitutes the cornerstone of disease-specific therapy. In this study, we examined the effects of the COVID-19 pandemic and lockdown measures on the management of FD patients.

Methods
We collected data in three main domains; mood status, adherence to ERT, and COVID-19 infection. We used the Hospital Anxiety and Depression Scale (HADS) to evaluate the mood statuses of FD patients and the Morisky Medication Adherence Scale (MMAS) and the Medication Adherence Report Scale (MARS) to assess patients’ adherence to non-disease specific therapy. We also examined a control group to compare the mood status data.

Results
A total of 67 FD patients (males: 47.8%, mean age: 37.0 years) were recruited to the study, of which 58 were receiving ERT. Both the HADS depression and anxiety scores were higher in the control group compared to FD patients. During the first wave of the pandemic, 25 patients reported to have missed an infusion for a mean of 2.3 ± 1.7 doses and half of the patients had adopted a home-based infusion treatment regimen. COVID-19 infection developed in 25 patients, of which one died. The majority of our patients (71.6%) have had at least one shot of the vaccine.

Conclusion
We found that FD patients were more resilient to the negative psychological effects of lockdown. Traumatic growth may be an important factor in explaining this finding. Government-supported home therapy programs might be beneficial for FD patients to increase the therapy adherence.