bluuebunny/crossref_metadata_2025_split huggingface dataset:
A breakdown in microglial metabolic reprogramming causes internalization dysfunction of α-synuclein in a mouse model of Parkinson’s disease
Authors: Lu Jia , Wang Chenfei , Cheng Xin , Wang Ruizhi , Yan Xuehan , He Pengju , Chen Hongzhuan , Yu Zhihua 
Published: May 2022

Abstract
Background
The α-synuclein released by neurons activates microglia, which then engulfs α-synuclein for degradation via autophagy. Reactive microglia are a major pathological feature of Parkinson’s disease (PD), although the exact role of microglia in the pathogenesis of PD remains unclear. Transient receptor potential vanilloid type 1 (TRPV1) channels are nonselective cation channel protein that have been proposed as neuroprotective targets in neurodegenerative diseases.

Methods
Using metabolic profiling, microglia energy metabolism was measured including oxidative phosphorylation and aerobic glycolysis. The mRFP-GFP-tagged LC3 reporter was introduced to characterize the role of TRPV1 in microglial autophagy. α-synuclein preformed fibril (PFF) TRPV1flox/flox; Cx3cr1Cre mouse model of sporadic PD were employed to study the capacity of TRPV1 activation to attenuate neurodegeneration process.

Results
We found that acute exposure to PFF caused microglial activation as a result of metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis via the AKT–mTOR–HIF-1α pathway. Activated microglia eventually reached a state of chronic PFF-tolerance, ﻿accompanied by broad defects in energy metabolism. We showed that metabolic boosting by treatment with the TRPV1 agonist capsaicin rescued metabolic impairments in PFF-tolerant microglia and also defects in mitophagy caused by disruption of the AKT–mTOR–HIF-1α pathway. Capsaicin attenuated phosphorylation of α-synuclein in primary neurons by boosting phagocytosis in PFF-tolerant microglia in vitro. Finally, we found that behavioral deficits and loss of dopaminergic neurons were accelerated in the PFF TRPV1flox/flox; Cx3cr1Cre mouse model of sporadic PD. We identified defects in energy metabolism, mitophagy and phagocytosis of PFF in microglia from the substantia nigra pars compacta of TRPV1flox/flox; Cx3cr1Cre mice.

Conclusion
The findings suggest that modulating microglial metabolism might be a new therapeutic strategy for PD.
Autistic adults have poorer quality healthcare and worse health based on self-report data
Authors: Weir Elizabeth , Allison Carrie , Baron-Cohen Simon 
Published: May 2022

Abstract
Background
Recent research suggests that autistic individuals have shorter lifespans and experience worse health (greater health burden) than non-autistic individuals. Small, qualitative studies suggest that autistic adults also experience poor self-reported healthcare quality.

Methods
An anonymized, cross-sectional, self-report questionnaire was administered to n = 4158 individuals. The study assessed prevalence of chronic health conditions, healthcare quality, differences in overall health inequality score, and effects of the coronavirus pandemic on healthcare quality. We used Fisher’s exact tests, binomial logistic regression, and predictive machine learning tools, as appropriate.

Results
The final sample included n = 2649 participants (n = 1285 autistic) aged 16–96 years. Autistic adults reported lower quality healthcare than non-autistic adults across 50/51 items, including poorer access to healthcare and poorer communication, alongside increased anxiety, sensory sensitivity, system-level problems, shutdowns, and meltdowns. Differences between groups were stark: aggregated health inequality scores predicted autism diagnosis, even after stratifying by sex. Autistic adults were also more likely to have chronic health conditions than non-autistic adults. There were no significant differences in healthcare quality for autistic adults before and during the pandemic, although they received relatively poorer quality healthcare than non-autistic adults across both periods.

Limitations
The study’s sampling methods are not likely to capture the perspectives of all autistic individuals, especially those with intellectual disability. Both the autistic and control samples are biased towards UK residents, white individuals, those assigned female at birth, and those who completed an undergraduate degree or higher education. As such, these results may limit their generalizability to other groups. Finally, these results relate to self-reported differences in healthcare quality between autistic and non-autistic adults. The observed group differences may in part reflect differences in perception and communication rather than differences in actual healthcare quality.

Conclusions
Autistic adults are more likely to have chronic health conditions alongside self-reported lower quality healthcare than others. Health inequalities between these groups are widespread and dramatic; unfortunately, they existed before and have persisted after the onset of the coronavirus pandemic.
Radiologic and clinical changes after denosumab treatment for giant cell tumors of the mobile spine: a quantitative study
Authors: Yuan Bei , Han Songbo , Yang Shaomin , Zhang Lihua , Jiang Liang , Wei Feng , Yuan Huishu , Liu Xiaoguang , Liu Zhongjun 
Published: May 2022

Abstract
Objectives
To analyze the radiologic and clinical changes after denosumab treatment in patients with giant cell tumors (GCTs) in the mobile spine.

Methods
Clinical data and images by computed tomography and magnetic resonance imaging at a single center were retrospectively reviewed before and after denosumab treatment.

Results
Pre- and post-treatment data from 24 patients were evaluated. On imaging, marginal ossification and/or bone formation was observed in 22 patients (91.7%). The median maximum diameter of the GCT reduced from 52.5 to 48.2 mm (p < 0.001), and the mean proportion of tumor to spinal canal area decreased from 36.8 to 18.5% (p < 0.001). Out of six patients with compression, three patients (50%) showed no compression after treatment. The signal intensity (SI) ratio between the solid part of the tumor and the normal spinal cord on T2-weighted MR images was 0.77 ± 0.22 and decreased to 0.58 ± 0.22 (p = 0.001). On clinical symptoms, the mean visual analog scale scores were reduced from 5.3 to 2.0 (p < 0.001) and the Karnofsky Performance Scale scores increased from a median of 65 to 80 (p < 0.001). Post-treatment, performance scores improved in eight patients (33.3%) (p = 0.003), and the neurological function of four patients improved according to Frankel grade (p = 0.046).

Conclusions
Bone formation, tumor reduction, regression of epidural lesion and the decrease in SI ratio on T2-weighted image should be considered as the effectiveness of denosumab in the treatment of spinal GCT. In clinical application, denosumab can relieve pain, improve neurological function, and improve the quality of life of spinal GCT patients.
Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells
Authors: Tayebi Behnoosh , Babaahmadi Mahnaz , Pakzad Mohammad , Hajinasrollah Mostafa , Mostafaei Farhad , Jahangiri Shahrbanoo , Kamali Amir , Baharvand Hossein , Baghaban Eslaminejad Mohamadreza , Hassani Seyedeh-Nafiseh , Hajizadeh-Saffar Ensiyeh 
Published: May 2022

Abstract
Introduction
Mesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP). Various evaluations should be passed in conjunction with the development of these newly emerging therapeutic products from bench-to-bedside. These evaluations include in vitro characterization, preclinical studies, and clinical trials to ensure product safety and efficacy. Therefore, a robust and well-designed preclinical study is critical to confirm product safety. This study aims to determine the probable toxicity effects of local and systemic injections of cryopreserved human bone marrow-derived clonal MSCs (BM-cMSCs) during subacute and subchronic periods of time.

Methods
BM-cMSCs were characterized according to the International Society for Cell and Gene Therapy (ISCT) criteria for MSCs. Both safety and toxicity of the BM-cMSCs population produced under GMP-compatible conditions were assessed in both sexes of Sprague Dawley (SD) rats via systemic intravenous (IV) administration and local injection in intervertebral disc (IVD). Behavioral changes, clinical signs of toxicity, and changes in body weight, water and food consumption were the important variables for product toxicity testing over 14 consecutive days during the subacute period and 90 consecutive days during the subchronic period. At the end of the assessment periods, the rats were killed for histopathology analysis of the target tissues. The BM-cMSCs potential for tumorigenicity was checked in nude mice.

Results
Single IV and IVD injections of BM-cMSCs did not cause significant signs of clinical toxicity, or changes in laboratory and histopathology data during the subacute (14 day) and subchronic (90 day) periods. Ex vivo-expanded and cryopreserved BM-cMSCs did not induce tumor formation in nude mice.

Conclusion
The results suggest that local and systemic administrations of xenogeneic BM-cMSCs in both sexes of SD rats do not cause toxicity during the subacute and subchronic periods of time. Also, BM-cMSCs were non-tumorigenic in nude mice.
An accelerated common fixed point algorithm for a countable family of G-nonexpansive mappings with applications to image recovery
Authors: Wattanataweekul Rattanakorn , Janngam Kobkoon 
Published: May 2022

AbstractIn this paper, we define a new concept of left and right coordinate affine of a directed graph and then employ it to introduce a new accelerated common fixed point algorithm for a countable family ofG-nonexpansive mappings in a real Hilbert space with a graph. We prove, under certain conditions, weak convergence theorems for the proposed algorithm. As applications, we also apply our results to solve convex minimization and image restoration problems. Moreover, we show that our algorithm provides better convergence behavior than other methods in the literature.
Towards a global One Health index: a potential assessment tool for One Health performance
Authors: Zhang Xiao-Xi , Liu Jing-Shu , Han Le-Fei , Xia Shang , Li Shi-Zhu , Li Odel Y. , Kassegne Kokouvi , Li Min , Yin Kun , Hu Qin-Qin , Xiu Le-Shan , Zhu Yong-Zhang , Huang Liang-Yu , Wang Xiang-Cheng , Zhang Yi , Zhao Han-Qing , Yin Jing-Xian , Jiang Tian-Ge , Li Qin , Fei Si-Wei , Gu Si-Yu , Chen Fu-Min , Zhou Nan , Cheng Zi-Le , Xie Yi , Li Hui-Min , Chen Jin , Guo Zhao-Yu , Feng Jia-Xin , Ai Lin , Xue Jing-Bo , Ye Qian , Grant Liz , Song Jun-Xia , Simm Geoff , Utzinger Jürg , Guo Xiao-Kui , Zhou Xiao-Nong 
Published: May 2022

Abstract
Background
A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed.

Methods
We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators.

Results
The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8–65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible.

Conclusions
GOHI—subject to rigorous validation—would represent the world’s first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Graphical Abstract
Perceived Vulnerability to Disease Questionnaire: psychometric validation with a Portuguese sample
Authors: Ferreira Jacqueline , Magalhães Ana C. , Bem-Haja Pedro , Alho Laura , Silva Carlos F. , Soares Sandra C. 
Published: May 2022

AbstractBackgroundIndividual differences in one’s perceived vulnerability to infectious diseases are implicated in psychological distress, social and behavioral disease avoidance phenomena. The Perceived Vulnerability to Disease Questionnaire (PVD) is the most extensively used measure when it comes to assessing subjective vulnerability to infectious diseases. However, this measure is not yet accessible to the Portuguese population. The present study aimed to adapt and validate the PVD with 136 Portuguese participants.MethodsFactorial, convergent and discriminant validity (of both the scale and between each factor), and reliability analysis were assessed.ResultsA modified bifactorial model, comprised of Perceived Infectability and Germ Aversion factors, was obtained, with acceptable goodness-of-fit indices, adequate convergent and discriminant validity, and good internal consistencies.ConclusionsOverall, the 10-items European-Portuguese PVD appears to be a reliable and valid measure of one’s perceived vulnerability to disease, with potential relevance for application in both research and clinical practice pertaining to disease-avoidance processes.
Fluorescence-aided removal of orthodontic composites: an in vivo comparative study
Authors: Albertini Paolo , Tauro Rosita , Barbara Lorenza , Albertini Enrico , Lombardo Luca 
Published: May 2022

Abstract
Background
To compare the fluorescent properties of 6 different orthodontic adhesives and provide useful information for clinicians in the adhesion choice, in order to remove it easily at the end of orthodontic treatment by using the Fluorescence-aided Identification Technique (FIT).

Methods
Six orthodontic adhesives were included: Ortho Connect, Gradia LoFlo A3.5, Greengloo, Transbond XT, KommonBase Pink, and KommonBase Clear. The same thermoformed template with 1 mm shell thickness on the six anterior teeth was used for adhesive positioning; furthermore, an ultraviolet light-emitting diode flashlight was used for the FIT. The brightness of adhesive area and tooth area (L* color coordinate) were measured on the photographs by using the “color picker” tool of Photoshop software.

Results
GC Ortho Connect, Gradia Direct LoFlo and KommonBase Clear showed the highest differences of brightness (15.5, 16.3 and 13.5, respectively), while Greengloo, Transbond XT and KommonBase Pink registered similar values between resin area and tooth area with FIT (− 0.5, − 0.8 and − 1.0, respectively). The high viscosity adhesive resins, as Greengloo and Transbond XT, showed a similar performance in terms of fluorescence to the KommonBase Pink, the lowest viscous resin adhesive considered.

Conclusions
The most used orthodontic adhesives showed different fluorescence properties. Some resins were brighter with the FIT, facilitating identification and subsequent removal. Other orthodontic adhesives presented no difference between adhesive and tooth. The viscosity of orthodontic adhesives did not influence the brightness emitted with FIT.
Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy
Authors: Su Pei-Pei , Liu Dong-Wei , Zhou Si-Jie , Chen Hang , Wu Xian-Ming , Liu Zhang-Suo 
Published: May 2022

Abstract
Background
LncRNA AK044604 (regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.

Methods
Diabetic db/db mice received Risa-inhibition adeno-associated virus (AAV) via tail vein injection, and intraperitoneal injection of lithium chloride (LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with Risa-inhibition lentivirus (LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy, Periodic Acid-Schiff staining, and immunofluorescence staining.

Results
Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucose-treated MPCs (P < 0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1 (P < 0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527 (P < 0.001, db/db + Risa-AAV vs. db/db, HG + Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes (P < 0.001, db/db + LiCl vs. db/db, HG + LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.

Conclusion
Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.
Sustainability of the rice-crayfish co-culture aquaculture model: microbiome profiles based on multi-kingdom analyses
Authors: Zhu Xue , Ji Lei , Cheng Mingyue , Wei Huimin , Wang Zhi , Ning Kang 
Published: May 2022

AbstractWhile the rice-crayfish culture (RCFP) model, an important aquaculture model in Asia, is generally considered a sustainable model, its sustainability in terms of microbial community profiles has not been evaluated. In this study, multi-kingdom analyses of microbiome profiles (i.e., bacteria, archaea, viruses, and eukaryotes) were performed using environmental (i.e., water and sediment) and animal gut (i.e., crayfish and crab gut) microbial samples from the RCFP and other aquaculture models, including the crab-crayfish co-culture, crayfish culture, and crab culture models, to evaluate the sustainability of the RCFP systematically. Results showed that RCFP samples are enriched with a distinct set of microbes, including Shewanella, Ferroplasma, Leishmania, and Siphoviridae, when compared with other aquaculture models. Additionally, most microbes in the RCFP samples, especially microbes from different kingdoms, were densely and positively connected, which indicates their robustness against environmental stress. Whereas microbes in different aquaculture models demonstrated moderate levels of horizontal gene transfer (HGT) across kingdoms, the RCFP showed relatively lower frequencies of HGT events, especially those involving antibiotic resistance genes. Finally, environmental factors, including pH, oxidation–reduction potential, temperature, and total nitrogen, contributed profoundly to shaping the microbial communities in these aquaculture models. Interestingly, compared with other models, the microbial communities of the RCFP model were less influenced by these environmental factors, which suggests that microbes in the latter have stronger ability to resist environmental stress. The findings collectively reflect the unique multi-kingdom microbial patterns of the RCFP model and suggest that this model is a sustainable model from the perspective of microbiome profiles.
ePortfolio to promote networked learning: an experience in the Latin American context
Authors: Roco Miguel , Barberà Elena 
Published: May 2022

AbstractThis research shows and analyses a pedagogical experience with ePortfolio into the bridge context between higher education and profession in Latin America, particularly Architectural Design Studio (ADS). The objective was to reveal the impacts of ePortfolio use as a tool of Information and Communication Technologies (ICT) on the training process to enhance Networked Learning Principles (NLP) into the particular architectural pedagogy. The research had a descriptive methodology with a qualitative approach through a perception survey applied to a sample of students from eight cohorts of the same training cycle (second year) in a ADS across years 2015–2018. The study kept its design and implementation fidelity stable during this time, allowing data from eight instances. The results allow observing relationships between the training process dimensions and the NLP, with indicators to improve this relationship, throughout to observe transformations linked to the ePortfolio conception, implementation and projection. The conclusions are related to the ePortfolio capacity to close strategic gaps in the training learning process to design, organise and provide feedback to improve the NLP, creating training strategies that promote students’ autonomous learning, connections, identities, needs, aspirations and professional objectives.
Pharmacist knowledge of gout management: impact of an educational intervention
Authors: Dorris Emma R. , Kieran Mariosa , Dalbeth Nicola , McCarthy Geraldine 
Published: May 2022

Abstract
Background
Pharmacists play a key role in community gout education. We investigated pharmacist knowledge of gout management and developed an educational intervention which was assessed in a cohort of Irish pharmacists.

Methods
A ten-question questionnaire about gout management was developed to assess pharmacists’ knowledge. A 14 min 26 s video educational intervention was co-designed by a rheumatologist, a pharmacist, and designer of pharmacy education resources. The effectiveness of this pharmacy-specific intervention was assessed using the same questionnaire in 53 pharmacists (25 in the intervention group; 28 in the control group). Contingency tables were used to analyse differences between groups.

Results
There were 173 pharmacist respondents to the initial survey; 35.3% answered that first-line therapy for gout involves a combination of a xanthine oxidase inhibitor (e.g., allopurinol) combined with a prophylactic agent (e.g., colchicine), and 28.9% of respondents answered that colchicine prophylaxis should be used when initiating urate-lowering therapy. Following the educational intervention, pharmacist’s knowledge about gout management increased across many domains, including serum urate targets when using urate-lowering therapy (p = 0.006), use of colchicine prophylaxis (p = 0.011), and duration of colchicine use (p < 0.001).

Conclusion
Gout management recommendations can be impeded if translation into pharmacy practice is neglected. Pharmacists are a valuable information resource for patients. Co-designing a brief education intervention with pharmacists is an effective, low-cost way to increase pharmacist knowledge on the management of gout.