bluuebunny/crossref_metadata_2025_split huggingface dataset:
hPMSCs inhibit the expression of PD-1 in CD4+IL-10+ T cells and mitigate liver damage in a GVHD mouse model by regulating the crosstalk between Nrf2 and NF-κB signaling pathway
Authors: Zhang Aiping , Zhang Jiashen , Li Xiaohua , Zhang Hengchao , Xiong Yanlian , Wang Zhuoya , Zhao Nannan , Wang Feifei , Luan Xiying 
Published: June 2021

Abstract
Background
The activation of T cells and imbalanced redox metabolism enhances the development of graft-versus-host disease (GVHD). Human placenta-derived mesenchymal stromal cells (hPMSCs) can improve GVHD through regulating T cell responses. However, whether hPMSCs balance the redox metabolism of CD4+IL-10+ T cells and liver tissue and alleviate GVHD remains unclear. This study aimed to investigate the effect of hPMSC-mediated treatment of GVHD associated with CD4+IL-10+ T cell generation via control of redox metabolism and PD-1 expression and whether the Nrf2 and NF-κB signaling pathways were both involved in the process.

Methods
A GVHD mouse model was induced using 6–8-week-old C57BL/6 and Balb/c mice, which were treated with hPMSCs. In order to observe whether hPMSCs affect the generation of CD4+IL-10+ T cells via control of redox metabolism and PD-1 expression, a CD4+IL-10+ T cell culture system was induced using human naive CD4+ T cells. The percentage of CD4+IL-10+ T cells and their PD-1 expression levels were determined in vivo and in vitro using flow cytometry, and Nrf2, HO-1, NQO1, GCLC, GCLM, and NF-κB levels were determined by western blotting, qRT-PCR, and immunofluorescence, respectively. Hematoxylin-eosin, Masson’s trichrome, and periodic acid-Schiff staining methods were employed to analyze the changes in hepatic tissue.

Results
A decreased activity of superoxide dismutase (SOD) and a proportion of CD4+IL-10+ T cells with increased PD-1 expression were observed in GVHD patients and the mouse model. Treatment with hPMSCs increased SOD activity and GCL and GSH levels in the GVHD mouse model. The percentage of CD4+IL-10+ T cells with decreased PD-1 expression, as well as Nrf2, HO-1, NQO1, GCLC, and GCLM levels, both in the GVHD mouse model and in the process of CD4+IL-10+ T cell generation, were also increased, but NF-κB phosphorylation and nuclear translocation were inhibited after treatment with hPMSCs, which was accompanied by improvement of hepatic histopathological changes.

Conclusions
The findings suggested that hPMSC-mediated redox metabolism balance and decreased PD-1 expression in CD4+IL-10+ T cells were achieved by controlling the crosstalk between Nrf2 and NF-κB, which further provided evidence for the application of hPMSC-mediated treatment of GVHD.
Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury
Authors: Chen Yen-Ta , Chuang Fei-Chi , Yang Chih-Chao , Chiang John Y. , Sung Pei-Hsun , Chu Yi-Ching , Huang Chi-Ruei , Huang Kuan-Hui , Yip Hon-Kan 
Published: June 2021

Abstract
Background
This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.

Methods and results
Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001).

Conclusion
Mel-ADMSCs effectively protected the testis against TTIR injury.
LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels
Authors: Zhao Chen-Guang , Qin Jie , Li Jia , Jiang Shan , Ju Fen , Sun Wei , Ren Zhen , Ji Yu-Qiang , Wang Rui , Sun Xiao-Long , Mou Xiang , Yuan Hua 
Published: June 2021

Abstract
Background
Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells.

Methods
sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and β-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0–35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test.

Results
We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery.

Conclusions
LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.
MicroRNAs: emerging driver of cancer perineural invasion
Authors: Zhang Mei , Xian Hong-chun , Dai Li , Tang Ya-ling , Liang Xin-hua 
Published: June 2021

AbstractThe perineural invasion (PNI), which refers to tumor cells encroaching on nerve, is a clinical feature frequently occurred in various malignant tumors, and responsible for postoperative recurrence, metastasis and decreased survival. The pathogenesis of PNI switches from ‘low-resistance channel’ hypothesis to ‘mutual attraction’ theory between peripheral nerves and tumor cells in perineural niche. Among various molecules in perineural niche, microRNA (miRNA) as an emerging modulator of PNI through generating RNA-induced silencing complex (RISC) to orchestrate oncogene and anti-oncogene has aroused a wide attention. This article systematically reviewed the role of microRNA in PNI, promising to identify new biomarkers and offer cancer therapeutic targets.
An effective localization algorithm for moving sources
Authors: Wang Hao , Li Liping 
Published: June 2021

AbstractBy utilizing the time difference of arrival (TDOA), the frequency difference of arrival (FDOA), and the differential Doppler rate (DDR) measurements from sensors, this paper proposes an effective moving source localization algorithm with closed solutions. Instead of employing the traditional two-step weighted least squares (WLS) process, the Lagrange multiplier technique is employed in the first step to obtain the initial solution. This initial solution yields a better solution than the existing solution because the dependence among the variables are taken into account. The initial solution is further refined in the second step. The simulation results verify the effectiveness of the proposed algorithm when compared with the relevant existing algorithms.
Event-triggered H-infinity finite-time consensus control for nonlinear second-order multi-agent systems with disturbances
Authors: Luo Yiping , Zhu Wanling 
Published: June 2021

AbstractThe study considers the problem of finite-time event-triggered H-infinity consensus for second-order multi-agent systems (MASs) with intrinsic nonlinear dynamics and external bounded disturbances. Based on the designed triggering function, a distributed event-triggered control strategy is presented on the basis of the designed triggering function to ensure consensus in the system, which effectively reduces the data transmission. Then, sufficient conditions for the finite-time consensus with H-infinity performance level of the resulting event-triggered MAS are derived by utilizing the Lyapunov function and finite-time stability theory. Furthermore, Zeno behavior is proven to be excluded under the proposed event-triggered scheme. Finally, the validity of the proposed results is verified by numerical simulation.
Reimagining brief interventions for alcohol: towards a paradigm fit for the twenty first century?
Authors: McCambridge Jim 
Published: June 2021

Abstract
Background
There is no longer support for the idea that brief intervention programmes alone can contribute meaningfully to the improvement of population health relating to alcohol. As a result, calls for major innovations and paradigm shifts grow, notably among research leaders.

Main text
This paper briefly examines the history of the development of the evidence-base from the landmark World Health Organisation projects on Screening and Brief Intervention (SBI) in the 1980s onwards. Particular attention is given to weaknesses in the theorisation of social influence and interventions design, and declining effect sizes over time. Although the old SBI paradigm may be exhausted where it has been applied, it has not been replaced by a new paradigm. Alcohol marketing encourages heavy drinking and today may have more powerful effects on thinking about alcohol, and about alcohol problems, than previously. The nature of the societal challenge being faced in an alcogenic environment in which alcohol is widely promoted and weakly regulated underpins consideration of the possibilities for contemporary evidence-informed public health responses. Evidence-informed perspectives in discourses on alcohol problems need to be strengthened in redeveloping rationales for brief interventions. This process needs to move away from sole reliance on a model based on a two-person discussion of alcohol, which is divorced from wider concerns the person may have. Reimagining the nature of brief interventions involves incorporating digital content, emphasising meso-level social processes based on material that people want to share, and seeking synergies with macro-level population and media issues, including alcohol policy measures.

Conclusions
Current versions of brief interventions may be simply too weak to contend with the pressures of an alcogenic environment. A new generation of brief interventions could have a key role to play in developing multi-level responses to the problems caused by alcohol.
Plausibility of patient-centred care in high-intensity methadone treatment: reflections of providers and patients
Authors: Marshall Kerry , Maina Geoffrey , Sherstobitoff Jordan 
Published: June 2021

Abstract
Background
Patients with opioid use disorder (OUD) often have complex health care needs. Methadone is one of the medications for opioid use disorder (MOUD) used in the management of OUDs. Highly restrictive methadone treatment—which requires patient compliance with many rules of care—often results in low retention, especially if there is inadequate support from healthcare providers (HCPs). Nevertheless, HCPs should strive to offer patient-centred care (PCC) as it is deemed the gold standard to care. Such an approach can encourage patients to be actively involved in their care, ultimately increasing retention and yielding positive treatment outcomes.

Methods
In this secondary analysis, we aimed to explore how HCPs were applying the principles of PCC when caring for patients with OUD in a highly restrictive, biomedical and paternalistic setting. We applied Mead and Bower’s PCC framework in the secondary analysis of 40 in-depth, semi-structured interviews with both HCPs and patients.

Results
We present how PCC's concepts of; (a) biopsychosocial perspective; (b) patient as a person; (c) sharing power and responsibility; (d) therapeutic alliance and (e) doctor as a person—are applied in a methadone treatment program. We identified both opportunities and barriers to providing PCC in these settings.

Conclusion
In a highly restrictive methadone treatment program, full implementation of PCC is not possible. However, implementation of some aspects of PCC are possible to improve patient empowerment and engagement with care, possibly leading to increase in retention and better treatment outcomes.
Characterisation of mobile colistin resistance genes (mcr-3 and mcr-5) in river and storm water in regions of the Western Cape of South Africa
Authors: Snyman Yolandi , Whitelaw Andrew C. , Barnes Jo M. , Maloba Motlatji R. B. , Newton-Foot Mae 
Published: June 2021

Abstract
Background
Colistin is regarded as a last-resort antimicrobial against multi-drug resistant Gram-negative bacteria (GNB), therefore the dissemination of colistin resistance in the environment is of great concern. Horizontal transfer of mobile colistin resistance (mcr) genes to potential pathogens poses a serious problem. This study aimed to describe the presence of colistin resistant GNB and mcr genes in river and storm water in regions of the Western Cape.

Methods
Water samples were collected from three rivers during May 2019 and January 2020 and two storm water samples were collected in November 2019. Colistin resistant GNB were cultured on MacConkey agar containing colistin and identified by MALDI-TOF. Colistin resistance was confirmed using broth microdilution (BMD). mcr-1-5 genes were detected by PCR performed directly on the water samples and on the colistin resistant isolates. mcr functionality was assessed by BMD after cloning the mcr genes into pET-48b(+) and expression in SHuffle T7 E. coli.

Results
mcr-5.1 and various mcr-3 gene variants were detected in the Plankenburg-, Eerste- and Berg rivers and in storm water from Muizenberg, and only mcr-5.1 was detected in storm water from Fish Hoek. Colistin resistant GNB were isolated from all of the water sources. Aeromonas spp. were the most common colistin resistant organisms detected in the water sources; 25% (6/24) of colistin resistant Aeromonas spp. isolated from the Berg river contained novel mcr-3 variants; mcr-3.33 (n = 1), mcr-3.34 (n = 1) mcr-3.35 (n = 1) mcr-3.36 (n = 2) and mcr-3.37 (n = 1), which were confirmed to confer colistin resistance.

Conclusions
The mcr-5.1 and mcr-3 colistin resistance gene variants were present in widely dispersed water sources in regions of the Western Cape. The mcr genes were only detected in water sampled downstream of and alongside communities, suggesting that their presence is driven by human influence/contamination. This is the first documentation of mcr-3 and mcr-5 gene variants in any setting in South Africa. Spill-over of these genes to communities could result in horizontal gene transfer to pathogenic bacteria, exacerbating the challenge of controlling multidrug resistant GNB infections.
The effects of transcranial direct current stimulation on gait in patients with Parkinson’s disease: a systematic review
Authors: Pol Fateme , Salehinejad Mohammad Ali , Baharlouei Hamzeh , Nitsche Michael A. 
Published: June 2021

Abstract
Background
Gait problems are an important symptom in Parkinson’s disease (PD), a progressive neurodegenerative disease. Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention that can modulate cortical excitability of the gait-related regions. Despite an increasing number of gait-related tDCS studies in PD, the efficacy of this technique for improving gait has not been systematically investigated yet. Here, we aimed to systematically explore the effects of tDCS on gait in PD, based on available experimental studies.

Methods
Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, PubMed, Web of Science, Scopus, and PEDro databases were searched for randomized clinical trials assessing the effect of tDCS on gait in patients with PD.

Results
Eighteen studies were included in this systematic review. Overall, tDCS targeting the motor cortex and supplementary motor area bilaterally seems to be promising for gait rehabilitation in PD. Studies of tDCS targeting the dorosolateral prefrontal cortex or cerebellum showed more heterogeneous results. More studies are needed to systematically compare the efficacy of different tDCS protocols, including protocols applying tDCS alone and/or in combination with conventional gait rehabilitation treatment in PD.

Conclusions
tDCS is a promising intervention approach to improving gait in PD. Anodal tDCS over the motor areas has shown a positive effect on gait, but stimulation of other areas is less promising. However, the heterogeneities of methods and results have made it difficult to draw firm conclusions. Therefore, systematic explorations of tDCS protocols are required to optimize the efficacy.
Feasibility of controlling hepatitis E in Jiangsu Province, China: a modelling study
Authors: Yang Meng , Cheng Xiao-Qing , Zhao Ze-Yu , Li Pei-Hua , Rui Jia , Lin Sheng-Nan , Xu Jing-Wen , Zhu Yuan-Zhao , Wang Yao , Liu Xing-Chun , Luo Li , Deng Bin , Liu Chan , Huang Jie-Feng , Yang Tian-Long , Li Zhuo-Yang , Liu Wei-Kang , Liu Wen-Dong , Zhao Ben-Hua , He Yue , Yin Qi , Mao Si-Ying , Su Yan-Hua , Zhang Xue-Feng , Chen Tian-Mu 
Published: June 2021

Abstract
Background
Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province.

Methods
We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness.

Results
From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R2 = 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days).

Conclusions
HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.

Graphic Abstract
Deterministic, random, or in between? Inferring the randomness level of wildlife movements
Authors: Goicolea Teresa , Gastón Aitor , Cisneros-Araujo Pablo , García-Viñas Juan Ignacio , Mateo-Sánchez M. Cruz 
Published: June 2021

AbstractBackgroundWhen assessing connectivity, it is crucial to rely on accurate modeling frameworks that consider species movement preferences and patterns. One important aspect is the level of randomness or unpredictability in the route selection. In this respect, traditional approaches (based on least-cost path or circuit theory) consider species movements unrealistically as totally deterministic or as totally random. A recent approach (randomized shortest path) advocates for choosing intermediate levels of randomness through a single parameter. This parameter may be optimized by validating connectivity surfaces developed from different levels of randomness against observed movement data. However, connectivity models are seldom validated, and it is still unclear how to approach this task. To address this knowledge gap, this paper aims at comparing different validation methods to infer the optimal randomness level in connectivity studies. Additionally, we aimed to disentangle the practical consequences of applying traditional connectivity approaches versus using an optimized level of movement randomness when delineating corridors.MethodsThese objectives were accomplished through the study case of the Iberian lynx, an endangered species whose maintenance and recovery depend on the current connectivity among its population nuclei. We firstly determined a conductance surface based on point selection functions accounting for the behavioral state (territorial or exploratory) of individuals. Secondly, we identified the level of randomness that better fits lynxes’ movements with independent GPS locations and different validation techniques. Lastly, we delineated corridors between lynx population nuclei through a) the randomized shortest path approach and the extreme and optimal levels of randomness of each validation method, and b) the traditional connectivity approaches.ResultsAccording to all used validation methodologies, models with intermediate levels of randomness outperformed those with extreme randomness levels representing totally deterministic or random movements. We found differences in the optimal randomness level among validation methods but similar results in the delineation of corridors. Our results also revealed that models with extreme randomness levels (deterministic and random walk) of the randomized path approach provided equivalent corridor networks to those from traditional approaches. Moreover, these corridor networks calculated with traditional approaches showed notable differences in patterns from the corridor network calculated with an optimized randomness level.ConclusionsHere we presented a connectivity model with a solid biological basis that calibrates the level of movement randomness and is supported by comprehensive validation methods. It is thus a step forward in the search and evaluation of connectivity approaches that lead to improved, efficient, and successful management actions.