bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of BZW2 by LINC00174 through miR-4500 inhibition enhances proliferation and apoptosis evasion in laryngeal papilloma
Authors: Liu Jiajia , Yang Tao , Zhang Ying , Wang Shuhui 
Published: September 2020

Abstract
Background
We aimed to explore the roles of basic leucine zipper and W2 domains (BZW) 2 in the human papillomavirus-infected laryngeal papillomatosis.

Methods
In the present study, BZW 2 knockdown and overexpressed cell lines were constructed. CCK-8 and colony formation assays were used to determine cell proliferation. Caspase-3 activity and nucleosomes fragmentation assays were used to determine cell apoptosis. qRT-PCR and Western blot were employed to evaluate the mRNA and protein levels of target genes, respectively. Luciferase and biotin-coupled miRNA pulldown assays were used to examine the interactions between mRNA and mRNA.

Results
We observed the levels of BZW2 were up-regulated in the laryngeal papilloma (LP) tissues as compared with adjacent tissues. The knockdown of BZW2 significantly inhibited cell proliferation and promoted cell apoptosis in the LP cells. Additionally, we identified the expressions of BZW2 negatively regulated by miR-4500. Luciferase and biotin-coupled miRNA pulldown assays demonstrated that LINC00174 competed with the BZW2 for binding with miR-4500. Moreover, the results showed that LINC00174/miR-4500/BZW2 axis regulated cell proliferation and apoptosis.

Conclusion
Our results demonstrated that the regulation of LINC00174/miR-4500/BZW2 axis might be used as an effective strategy for treatment of human papillomavirus-infected laryngeal papillomatosis.
Autologous bone-marrow mononuclear stem cell therapy in patients with stroke: a meta-analysis of comparative studies
Authors: Chumnanvej Sorayouth , Chumnanvej Siriluk 
Published: September 2020

Abstract
Background
There is a need to promote recovery after stroke with novel therapeutic interventions. Of them, bone-marrow mononuclear cell (BM-MNC) therapy offers promising outcomes in preclinical and clinical models.

Aims
To investigate the efficacy and safety of BM-MNCs versus traditional medical care of stroke patients.

Summary of review
A meta-analysis was conducted involving controlled prospective studies and randomized clinical trials (RCTs) which investigated the changes in the scores of neurological functions (the National Institutes of Health Stroke Scale [NIHSS]), the indices of functional recovery (the Barthel Index [BI] and the modified Rankin scale [mRS]) at 3 and 6 month post-transplantation. A total of nine studies (five RCTs) recruited 469 stroke patients (65.5% males, 49.25% received the intervention). There were no significant differences in NIHSS, BI, or mRS scores after 3 months of follow-up. However, the BI indices of BM-MNCs-receiving patients improved significantly after 6 months (standardized mean difference = 1.17, 95% confidence interval, 0.23 to 2.10, P = 0.01) as compared to traditional treatment. The risk of mortality and adverse events and the proportion of patients with favorable outcomes (mRS ≤ 3) were similar in both groups.

Conclusion
Both the BM-MNCs and medical stroke treatment have similar outcomes in terms of safety and short-term efficacy, while the effect of therapy is significant only after 6 months. More well-designed, large sized RCTs are needed to confirm the efficacy of stem cell therapy over long periods of follow-up.
Neutrophils mediated multistage nanoparticle delivery for prompting tumor photothermal therapy
Authors: Ye Bo , Zhao Bao , Wang Kun , Guo Yilong , Lu Qinguo , Zheng Longpo , Li Ang , Qiao Jianou 
Published: September 2020

Abstract
Background
Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer.

Results
Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro. Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days).

Conclusions
Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising.
Impact of maternal and child dental anxiety on oral health-related quality of life of 5–6-year-old preschool children
Authors: Esa Rashidah , Jamaludin Marhazlinda , Yusof Zamros Yuzadi Mohd 
Published: September 2020

AbstractBackgroundThere is a lack of evidence with regards to the association between both maternal and child dental anxiety and the mother’s perception of her child’s oral health-related quality of life (COHRQoL). The aim of this study was to investigate the association of maternal and child dental anxiety with COHRQoL and the effect of demographic factors as moderators in this relationship. In addition, the association between child’s dental caries experience and the COHRQoL was also assessed.MethodsA cross-sectional study was conducted involving 1150, 5–6 year-old preschool children in Selangor, Malaysia. Mothers answered a questionnaire on socio-economic status, the Malay-Modified Dental Anxiety Scale to assess maternal dental anxiety, and the Malay-Early Childhood Oral Health Impact Scale to assess COHRQoL. Child's dental anxiety was assessed using the Malay-Modified Child Dental Anxiety Scale via a face-to-face interview prior to oral examination to assess dental caries. Data were analysed using structural equation modelling to assess the relationship between maternal and child dental anxiety and COHRQoL.ResultsOverall, complete data on 842 mother–child dyads were analysed. The mean scores of total ECOHIS, the child impacts section (CIS), and the family impacts section (FIS) were 17.7 (SD = 4.9), 12.6 (SD = 3.7), and 5.1 (SD = 1.9), respectively. The mean dental anxiety scores for mothers and children were 11.8 (SD = 4.5) and 16.9 (SD = 4.3), respectively. Maternal dental anxiety was associated with the CIS (b = 0.08,p < 0.001), the FIS (b = 0.01,p = 0.001), and the total ECOHIS (b = 0.14,p < 0.001). Maternal education level, income, urban/rural location, and kindergarten type were moderators to the relationship. In addition, there was also a significant relationship between child’s dental caries experience and COHRQoL (p < 0.001).ConclusionsMaternal dental anxiety and child’s dental caries experience have significantly impacted the COHRQoL, the CIS, and the FIS domains. Demographic factors such as maternal education, income, urban/rural location, and kindergarten type acted as moderators that can strengthen or weaken the relationship between maternal dental anxiety and COHRQoL of 5–6-year-old preschool children.
Impact of oral health conditions on the quality of life of quilombola and non-quilombola rural adolescents in the countryside of Bahia, Brazil: a cross-sectional study
Authors: da Silva Etna Kaliane Pereira , de Medeiros Danielle Souto 
Published: September 2020

AbstractBackgroundThis study aimed to estimate the prevalence of negative impacts of oral health conditions on the quality of life ofquilombolaand non-quilombolarural adolescents and identify associated factors.MethodsThis cross-sectional study was carried out in a rural area in the countryside of Bahia, Brazil, in 2015. Participants were asked to complete the Oral Impacts on Daily Performance Questionnaire. Prevalence and prevalence ratios (PR) were estimated together with their respective 95% confidence intervals. Multiple analysis was conducted using Poisson regression with robust error variance and hierarchical entry of variables.ResultsOf the 390 rural adolescents who took part in the study, 42.8% werequilombolas, and 45.6% of all participants reported a negative impact of their oral health conditions on their quality of life. The most prevalent impact was difficulty eating (32.6%). After adjusted analysis, the following factors were found to be associated with the negative impact of oral health conditions on quality of life: age (PR = 1.04), feeling lonely (PR = 1.42), worst evaluation of oral health (PR = 1.52), need of dental care (PR = 1.33), and occurrence of toothache in the last 6 months (PR = 1.83).Quilombolasand non-quilombolaspresented with a different prevalence of discomfort when brushing their teeth and had different factors associated with the negative impact of oral health conditions on their quality of life. Bothquilombolaand non-quilombolarural adolescents showed a high prevalence of negative impact of oral health conditions on their quality of life.ConclusionsThese results support the need for improved oral healthcare for specific populations like thequilombolas. Furthermore, the results illustrate the importance of incorporating oral healthcare strategies that take into consideration the sociocultural context of adolescents.
Curcumin derivative C212 inhibits Hsp90 and
eliminates both growing and quiescent leukemia cells in deep dormancy
Authors: Liu Bi , Shen Yunzhu , Huang Huafang , Croce Kimiko Della , Wu Min , Fan Yingjuan , Liu Yang , Xu Jianhua , Yao Guang 
Published: September 2020

Abstract
Background
Relapsed leukemia following initial therapeutic response and
remission is difficult to treat and causes high patient mortality. Leukemia
relapse is due to residual quiescent leukemia cells that escape conventional
therapies and later reemerge. Eliminating not only growing but quiescent
leukemia cells is critical to effectively treating leukemia and preventing its
recurrence. Such dual targeting therapeutic agents, however, are lacking in the
clinic. To start tackling this problem, encouraged by the promising anticancer
effects of a set of curcumin derivatives in our earlier studies, we examined in
this work the effects of a 4-arylmethyl curcumin derivative (C212) in
eliminating both growing and quiescent leukemia cells.

Methods
We analyzed the effects of C212 on the growth and viability of
growing and quiescent leukemia cells using MTS, apoptosis, cell cycle and cell
tracking assays. The effects of C212 on the quiescence depth of leukemia cells
were measured using EdU incorporation assay upon growth stimulation. The
mechanisms of C212-induced apoptosis and deep dormancy, particularly associated
with its inhibition of Hsp90 activity, were studied using molecular docking,
protein aggregation assay, and Western blot of client proteins.

Results
C212, on the one hand, inhibits growing leukemia cells at a higher
efficacy than curcumin by inducing apoptosis and G2/M accumulation; it, on the
other hand, eliminates quiescent leukemia cells that are resistant to
conventional treatments. Furthermore, C212 drives leukemia cells into and kills
them at deep quiescence. Lastly, we show that C212 induces apoptosis and drives
cells into deep dormancy at least partially by binding to and inhibiting Hsp90,
leading to client protein degradation and protein aggregation.

Conclusion
C212 effectively eliminates both growing and quiescent leukemia
cells by inhibiting Hsp90. The property of C212 to kill quiescent leukemia cells
in deep dormancy avoids the risk associated with awaking therapy-resistant
subpopulation of quiescent leukemia cells during treatments, which may lead to
the development of novel therapies against leukemia relapse.
Different neighborhood walkability indexes for active commuting to school are necessary for urban and rural children and adolescents
Authors: Molina-García Javier , Campos Sergio , García-Massó Xavier , Herrador-Colmenero Manuel , Gálvez-Fernández Patricia , Molina-Soberanes Daniel , Queralt Ana , Chillón Palma 
Published: September 2020

Abstract
Background
Literature focusing on youth has reported limited evidence and non-conclusive associations between neighborhood walkability measures and active commuting to and from school (ACS). Moreover, there is a lack of studies evaluating both macro- and micro-scale environmental factors of the neighborhood when ACS is analyzed. Likewise, most studies on built environment attributes and ACS focus on urban areas, whereas there is a lack of studies analyzing rural residential locations. Moreover, the relationship between built environment attributes and ACS may differ in children and adolescents. Hence, this study aimed to develop walkability indexes in relation to ACS for urban and rural children and adolescents, including both macro- and micro-scale school-neighborhood factors.

Methods
A cross-sectional study of 4593 participants from Spain with a mean age of 12.2 (SD 3.6) years was carried out. Macro-scale environmental factors were evaluated using geographic information system data, and micro-scale factors were measured using observational procedures. Socio-demographic characteristics and ACS were assessed with a questionnaire. Several linear regression models were conducted, including all the possible combinations of six or less built environment factors in order to find the best walkability index.

Results
Analyses showed that intersection density, number of four-way intersections, and residential density were positively related to ACS in urban participants, but negatively in rural participants. In rural children, positive streetscape characteristics, number of regulated crossings, traffic calming features, traffic lanes, and parking street buffers were also negatively related to ACS. In urban participants, other different factors were positively related to ACS: number of regulated crossings, positive streetscape characteristics, or crossing quality. Land use mix acted as a positive predictor only in urban adolescents. Distance to the school was a negative predictor on all the walkability indexes. However, aesthetic and social characteristics were not included in any of the indexes.

Conclusions
Interventions focusing on improving built environments to increase ACS behavior need to have a better understanding of the walkability components that are specifically relevant to urban or rural samples.
The study of the association between immune monitoring and pneumonia in kidney transplant recipients through machine learning models
Authors: Peng Bo , Gong Hang , Tian Han , Zhuang Quan , Li Junhui , Cheng Ke , Ming Yingzi 
Published: September 2020

Abstract
Background
Kidney transplantation is the optimal treatment to cure the patients with end-stage renal disease (ESRD). However, the infectious complication, especially pneumonia, is the main cause of mortality in the early stage. Immune monitoring by relevant biomarkers provides direct evidence of immune status. We aimed to study the association between immune monitoring and pneumonia in kidney transplant patients through machine learning models.

Methods
A total of 146 patients receiving the immune monitoring panel in our center, including 46 pneumonia recipients and 100 stable recipients, were retrospectively reviewed to develop the models. All the models were validated by external data containing 10 pneumonia recipients and 32 stable recipients. The immune monitoring panel consisted of the percentages and absolute cell counts of CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and natural killer (NK) cells, and median fluorescence intensity (MFI) of human leukocyte antigen (HLA)-DR on monocytes and CD64 on neutrophils. The machine learning models including support vector machine (SVM), logistic regression (LR), multi-layer perceptron (MLP) and random forest (RF) were applied for analysis.

Results
The pneumonia and stable groups showed significant difference in cell counts of each subpopulation and MFI of monocyte HLA-DR and neutrophil CD64. The SVM model by monocyte HLA-DR (MFI), neutrophil CD64 (MFI), CD8+ T cells (cells/μl), NK cells (cell/μl) and TBNK (T cells, B cells and NK cells, cells/μl) had the best performance with the average area under the curve (AUC) of 0.940. The RF model best predicted the patients who would progress into severe pneumonia, with the average AUC of 0.760. All the models had good performance validated by external data.

Conclusions
The immune monitoring panel was tightly associated with pneumonia in kidney transplant recipients. The models developed by machine learning techniques identified patients at risk and predicted the prognosis. Based on the results of immune monitoring, better individualized therapy might be achieved.
Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer’s disease
Authors: Robison Lisa S. , Gannon Olivia J. , Thomas Melissa A. , Salinero Abigail E. , Abi-Ghanem Charly , Poitelon Yannick , Belin Sophie , Zuloaga Kristen L. 
Published: September 2020

AbstractBackgroundHypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are often observed years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high-fat diet and metabolic disease (e.g., obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex.MethodsWT and 3xTg-AD male and female mice were fed a control (10% fat) or high-fat (HF 60% fat) diet from ~ 3–7 months of age, then tested for metabolic and hypothalamic disturbances.ResultsOn control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group.ConclusionsThese findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.
Kinematic parameters obtained with the ArmeoSpring for upper-limb assessment after stroke: a reliability and learning effect study for guiding parameter use
Authors: Brihmat Nabila , Loubinoux Isabelle , Castel-Lacanal Evelyne , Marque Philippe , Gasq David 
Published: September 2020

AbstractBackgroundAfter stroke, kinematic measures obtained with non-robotic and robotic devices are highly recommended to precisely quantify the sensorimotor impairments of the upper-extremity and select the most relevant therapeutic strategies. Although the ArmeoSpring exoskeleton has demonstrated its effectiveness in stroke motor rehabilitation, its interest as an assessment tool has not been sufficiently documented. The aim of this study was to investigate the psychometric properties of selected kinematic parameters obtained with the ArmeoSpring in post-stroke patients.MethodsThis study involved 30 post-stroke patients (mean age = 54.5 ± 16.4 years; time post-stroke = 14.7 ± 26.7 weeks; Upper-Extremity Fugl-Meyer Score (UE-FMS) = 40.7 ± 14.5/66) who participated in 3 assessment sessions, each consisting of 10 repetitions of the ‘horizontal catch’ exercise. Five kinematic parameters (taskandmovement time, hand path ratio, peak velocity, number of peak velocity) anda globalScorewere computed from raw ArmeoSpring’ data. Learning effect and retention were analyzed using a 2-way repeated-measures ANOVA, and reliability was investigated using the intra-class correlation coefficient (ICC) and minimal detectable change (MDC).ResultsWe observed significant inter- and intra-session learning effects for most parameters except peak velocity. The measures performed in sessions 2 and 3 were significantly different from those of session 1. No additional significant difference was observed after the first 6 trials of each session and successful retention was also highlighted for all the parameters. Relative reliability was moderate to excellent for all the parameters, and MDC values expressed in percentage ranged from 42.6 to 102.8%.ConclusionsAfter a familiarization session, the ArmeoSpring can be used to reliably and sensitively assess motor impairment and intervention effects on motor learning processes after a stroke.Trial registrationThe study was approved by the local hospital ethics committee in September 2016 and was registered under number 05-0916.
Rugged landscapes: complexity and implementation science
Authors: Ornstein Joseph T. , Hammond Ross A. , Padek Margaret , Mazzucca Stephanie , Brownson Ross C. 
Published: September 2020

Abstract
Background
Mis-implementation—defined as failure to successfully implement and continue evidence-based programs—is widespread in public health practice. Yet the causes of this phenomenon are poorly understood.

Methods
We develop an agent-based computational model to explore how complexity hinders effective implementation. The model is adapted from the evolutionary biology literature and incorporates three distinct complexities faced in public health practice: dimensionality, ruggedness, and context-specificity. Agents in the model attempt to solve problems using one of three approaches—Plan-Do-Study-Act (PDSA), evidence-based interventions (EBIs), and evidence-based decision-making (EBDM).

Results
The model demonstrates that the most effective approach to implementation and quality improvement depends on the underlying nature of the problem. Rugged problems are best approached with a combination of PDSA and EBI. Context-specific problems are best approached with EBDM.

Conclusions
The model’s results emphasize the importance of adapting one’s approach to the characteristics of the problem at hand. Evidence-based decision-making (EBDM), which combines evidence from multiple independent sources with on-the-ground local knowledge, is a particularly potent strategy for implementation and quality improvement.