bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust estimation of the effect of an exposure on the change in a continuous outcome
Authors: Ning Yilin , Støer Nathalie C. , Ho Peh Joo , Kao Shih Ling , Ngiam Kee Yuan , Khoo Eric Yin Hao , Lee Soo Chin , Tai E-Shyong , Hartman Mikael , Reilly Marie , Tan Chuen Seng 
Published: June 2020

AbstractBackgroundThe change in two measurements of a continuous outcome can be modelled directly with a linear regression model, or indirectly with a random effects model (REM) of the individual measurements. These methods are susceptible to model misspecifications, which are commonly addressed by applying monotonic transformations (e.g., Box-Cox transformation) to the outcomes. However, transforming the outcomes complicates the data analysis, especially when variable selection is involved. We propose a robust alternative through a novel application of the conditional probit (cprobit) model.MethodsThe cprobit model analyzes the ordered outcomes within each subject, making the estimate invariant to monotonic transformation on the outcome. By scaling the estimate from the cprobit model, we obtain the exposure effect on the change in the observed or Box-Cox transformed outcome, pending the adequacy of the normality assumption on the raw or transformed scale.ResultsUsing simulated data, we demonstrated a similar good performance of the cprobit model and REM with and without transformation, except for some bias from both methods when the Box-Cox transformation was applied to scenarios with small sample size and strong effects. Only the cprobit model was robust to skewed subject-specific intercept terms when a Box-Cox transformation was used. Using two real datasets from the breast cancer and inpatient glycemic variability studies which utilize electronic medical records, we illustrated the application of our proposed robust approach as a seamless three-step workflow that facilitates the use of Box-Cox transformation to address non-normality with a common underlying model.ConclusionsThe cprobit model provides a seamless and robust inference on the change in continuous outcomes, and its three-step workflow is implemented in an R package for easy accessibility.
The effect of physical activity on cognition relative to APOE genotype (PAAD-2): study protocol for a phase II randomized control trial
Authors: Park Kyoung Shin , Ganesh Alexis B. , Berry Nathaniel T. , Mobley Yashonda P. , Karper William B. , Labban Jeffrey D. , Wahlheim Christopher N. , Williams Tomika M. , Wideman Laurie , Etnier Jennifer L. 
Published: June 2020

Abstract
Background
By 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is critical to identify preventive strategies that can reduce the risk of or delay the onset of AD. Physical activity (PA) has potential in this regard. This randomized clinical trial aims to (a) test the causal relationship between PA and AD-associated cognitive function for persons with a family history of AD (FH+), (b) determine the moderating role of apolipoprotein epsilon 4 (APOE4) carrier status on cognition, and (c) assess cerebral structure, cerebral function, and putative biomarkers as mediators of the effects of PA on cognition.

Methods
We are recruiting cognitively normal, middle aged (40–65 years) sedentary adults with FH+. Participants are randomly assigned to a 12-month PA intervention for 3 days/week or to a control group maintaining their normal lifestyle. Saliva samples are taken at pre-test to determine APOE genotype. At pre-, mid-, and post-tests, participants complete a series of cognitive tests to assess information-processing speed, verbal and visual episodic memory, constructional praxis, mnemonic discrimination, and higher-order executive functions. At pre- and post-tests, brain imaging and blood biomarkers are assessed.

Discussion
We hypothesize that 1) the PA group will demonstrate improved cognition compared with controls; 2) PA-derived cognitive changes will be moderated by APOE4 status; and 3) PA-induced changes in neural and blood biomarkers will contribute to cognitive changes and differ as a function of APOE4 status. Our results may provide important insights into the potential of PA to preserve neurocognitive function in people with a heightened risk of AD due to FH+ and as moderated by APOE4 status. By using sophisticated analytic techniques to assess APOE as a moderator and neurobiological mechanisms as mediators across trajectories of cognitive change in response to PA, we will advance our understanding of the potential of PA in protecting against AD.

Trial registration
ClinicalTrials.gov NCT03876314. Registered March 15, 2019.
The effect of interictal epileptiform discharges on cognitive and academic performance in children with idiopathic epilepsy
Authors: Cheng Dazhi , Yan Xiuxian , Xu Keming , Zhou Xinlin , Chen Qian 
Published: June 2020

Abstract
Background
Interictal epileptiform discharges (IEDs) have been proven to impair cognitive function. However, it is not clear whether IEDs disrupt academic performance in children with idiopathic epilepsy, and the contribution of cognitive function deficits to impaired academic performance has not been clarified. This study aimed to examine the cognitive deficits and academic impairment in childhood idiopathic epilepsy with IEDs.

Methods
Ninety-seven childhood idiopathic epilepsy with IEDs, 77 childhood idiopathic epilepsy without IEDs, and 71 healthy controls completed a series of cognitive tests. We analyzed the cognitive performance in several domains including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention and executive functioning. Analysis of variance was conducted to compare the performance on all tests between the three groups.

Results
Childhood idiopathic epilepsy with IEDs exhibited not only general cognitive deficits in processing speed, spatial ability, and attention, but also arithmetic impairment. Furthermore, general cognitive deficits could account for the impaired arithmetic performance in childhood idiopathic epilepsy with IEDs.

Conclusions
Our study suggested that IEDs in children with idiopathic epilepsy affected both cognitive function and academic performance, and that the cognitive deficits may be responsible for arithmetic performance impairment.
Complications of bone transport technique using the Ilizarov method in the lower extremity: a retrospective analysis of 282 consecutive cases over 10 years
Authors: Liu Yanshi , Yushan Maimaiaili , Liu Zhenhui , Liu Jialin , Ma Chuang , Yusufu Aihemaitijiang 
Published: June 2020

AbstractBackgroundThe treatment of large bone defects in lower limbs is a serious challenge for orthopedic surgeons and patients. The bone transport technique using the Ilizarov method has become the main treatment option for the reconstruction of bone defect. However, inevitable difficulties and complications related to bone transport technique have been reported by many studies. The purpose of this study was to evaluate the effectiveness and complications of bone transport technique using Ilizarov method in the treatment of bone defect of lower extremity.MethodsThe study was conducted on 282 patients who underwent bone transport procedures using Ilizarov method at our institution from January 2007 to June 2017. Patient’s demographic data, complications and clinical outcomes at minimum of 2 years follow-up were collected and retrospectively analyzed. All difficulties that related to bone transport were documented according to Paley’s classification. The clinical outcomes were evaluated using Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at last clinical visit.ResultsThere were 243 male and 39 females with a mean age of 40 years (range 18–65 years). The mean defect was 6.56 ± 2.15 cm, whereas single level transport in 221 cases and double level transport in 61 cases. There were 189 problems, 166 obstacles and 406 complications (257 minor and 149 major complications), and the average complication rate per patients consists of 0.91 minor and 0.53 major complications. The top five complications were pin-site infection (65.96%), axial deviation (40.78%), joint stiffness (23.76%), soft tissue incarceration (22.34%) and delayed union of the docking site (13.48%).The ASAMI bony result was excellent in 233 patients, good in 32, fair in 5 and poor in 12. The ASAMI functional result was excellent in 136 patients, good in 88, fair in 47, poor in 11.ConclusionBone transport is a reliable method for reconstruction of bone defects in the femur and tibia. Awareness of predictable complications is beneficial to prevent or early detection of the expected complication which can improve the risk-benefit balance.
Supportive and palliative care indicators tool (SPICT™): content validity, feasibility and pre-test of the Italian version
Authors: Casale Giuseppe , Magnani Caterina , Fanelli Renato , Surdo Laura , Goletti Mauro , Boyd Kirsty , D’Angelo Daniela , Mastroianni Chiara ,   the SPICT-IT™ study group, Cancian Maurizio , Colotto Marco , Di Giacomo Antonella , Fucito Giuseppe , Gentili Giorgio , Latorre Patrizia , Aprile Pierangelo Lora , Massaro Michele , Pace Andrea , Savarese Antonella , Scarlata Simone , Stefanelli Maria Consiglia , Turriziani Adriana 
Published: June 2020

Abstract
Background
Difficulties in identifying patients at risk of clinical deterioration or death represent one of the main barriers to Palliative Care (PC) development in the community. Currently, no specific Italian tools aimed at identifying patients with PC needs are available. Of the different European tools available, the SPICT™ can be used easily in any kind of setting and does not include the Surprise Question. The purpose of the study was to translate, cross-culturally adapt and pre-test the Italian version of the SPICT™.

Methods
The Beaton recommendations for the cross-cultural adaptation of instruments were followed. Content validity was assessed using the Lynn method. A sample of Italian General Practitioners (GPs) assessed the SPICT-IT™ for feasibility and tested it.

Results
During the cross-cultural adaptation, some issues regarding semantic, experiential, idiomatic and conceptual equivalences were raised and resolved. The Scale-Content Validity Index/Ave was 0.86. Of the 907 GPs included in the sample, 71 (7.8%) agreed to test the SPICT-IT™ and to assess its feasibility. The participants provided care for 73,526 people in the community. Of these people, 1.7% (N = 1303) were identified as being in need of PC according to the SPICT-IT™. Sixty-six (93.0%) GPs stated they would use the SPICT-IT™ in their daily clinical practice.

Conclusions
The SPICT-IT™ demonstrated acceptable content validity. The percentage of patients identified through the SPICT-IT™ was comparable to findings from literature. The next phase of this project will investigate the impact of a proactive training programme aimed at supporting GPs in identifying patients with PC needs and delivering appropriate Primary Palliative Care (PPC).
Schedule feasibility and workflow for additive manufacturing of titanium plates for cranioplasty in canine skull tumors
Authors: James J. , Oblak M. L. , zur Linden A. R. , James F. M. K. , Phillips J. , Parkes M. 
Published: June 2020

Abstract
Background
Additive manufacturing has allowed for the creation of a patient-specific custom solution that can resolve many of the limitations previously reported for canine cranioplasty. The purpose of this pilot study was to determine the schedule feasibility and workflow in manufacturing patient-specific titanium implants for canines undergoing cranioplasty immediately following craniectomy.

Results
Computed tomography scans from patients with tumors of the skull were considered and 3 cases were selected. Images were imported into a DICOM image processing software and tumor margins were determined based on agreement between a board-certified veterinary radiologist and veterinary surgical oncologist. Virtual surgical planning was performed and a bone safety margin was selected. A defect was created to simulate the planned intraoperative defect. Stereolithography format files of the skulls were then imported into a plate design software. In collaboration with a medical solution centre, a custom titanium plate was designed with the input of an applications engineer and veterinary surgery oncologist. Plates were printed in titanium and post-processed at the solution centre. Total planning time was approximately 2 h with a manufacturing time of 2 weeks.

Conclusions
Based on the findings of this study, with access to an advanced 3D metal printing medical solution centre that can provide advanced software and printing, patient-specific additive manufactured titanium implants can be planned, created, processed, shipped and sterilized for patient use within a 3-week turnaround.
Long noncoding RNA SNHG6 mainly functions as a competing endogenous RNA in human tumors
Authors: Wang Hui-shan , Zhang Wen , Zhu Han-long , Li Quan-peng , Miao Lin 
Published: June 2020

AbstractIncreased expression of the small nucleolar RNA host gene 6 (SNHG6) has been reported in different cancers, such as hepatocellular carcinoma, colorectal cancer, and lung cancer. The high expression level of SNHG6 is associated with tumor progression and poor prognosis. This paper provides an overview of recent studies on the oncogenic role and potential clinical utilities of SNHG6. Upregulated SNHG6 arrests tumor cell cycle and reduces apoptosis but promotes migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), and chemoresistance in tumors. Mechanically, SNHG6 primarily sponges tumor suppressor microRNA (miRNA), functioning as a competing endogenous RNA. Once sponged, miRNA is unable to degrade, silence, or hamper the translation of its downstream, mostly oncogenic genes, ultimately driving cancer-related processes. Thus, SNHG6 might serve as a biomarker for cancer diagnosis and prognosis.
Nomogram to predict multidrug-resistant tuberculosis
Authors: Wang Saibin , Tu Junwei 
Published: June 2020

Abstract
Background
Multidrug-resistant tuberculosis (MDR-TB) is burgeoning globally, and has been a serious challenge in TB management. Clinically, the ability to identify MDR-TB is still limited, especially in smear-negative TB. The aim of this study was to develop a nomogram for predicting MDR-TB.

Methods
Demographics and clinical characteristics of both MDR-TB and drug-susceptible TB patients were utilized to develop a nomogram for predicting MDR-TB. The LASSO regression method was applied to filter variables and select predictors, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). Moreover, calibration analysis and decision curve analysis (DCA) of the model were performed. This study involved a second analysis of a completed prospective cohort study conducted in a country with a high TB burden.

Results
Five variables of TB patients were selected through the LASSO regression method, and a nomogram was built based on these variables. The predictive model yielded an AUC of 0.759 (95% CI, 0.719–0.799), and in the internal validation, the AUC was 0.757 (95% CI, 0.715–0.793). The predictive model was well-calibrated, and DCA showed that if the threshold probability of MDR-TB was between 70 and 90%, using the proposed nomogram to predict MDR-TB would obtain a net benefit.

Conclusions
In this study, a nomogram was constructed that incorporated five demographic and clinical characteristics of TB patients. The nomogram may be of great value for the prediction of MDR-TB in patients with sputum-free or smear-negative TB.
Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol
Authors: Fonseca Liliana , Paredes Sílvia , Ramos Helena , Oliveira José Carlos , Palma Isabel 
Published: June 2020

Abstract
Background
Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target.

Methods
A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets.

Results
In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588).

Conclusions
These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients’ evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.
The effects of social integration and hometown identity on the life satisfaction of Chinese rural migrants: the mediating and moderating effects of a sense of belonging in the host city
Authors: Chen Hongsheng , Zhu Zhenjun , Chang Jiang , Gao Yinbao 
Published: June 2020

Abstract
Background
Many developing countries are rapidly urbanising because of large migration flows from rural to urban areas. However, migrants’ socio-cultural transitions might be challenging, and their extent of social integration and sense of hometown identity might impede resettlement and quality of life. Although a sense of belonging in the host city and a sense of attachment to the hometown might be important to migrants’ ability to assimilate, adapt and succeed in a new place, these factors have not adequately been studied in China.

Methods
The data were derived from the 2014 China Migrants Dynamic Survey, a large-scale questionnaire survey of Chinese migrants. This study’s sample comprised 15,990 individuals in eight Chinese cities. Life satisfaction was measured with the Satisfaction with Life Scale, and the key independent variables (social integration, sense of hometown identity and sense of belonging in the host city) were measured using multi-item constructs. Cronbach’s alpha coefficients on the four main variables were 0.76 to 0.90. A multivariable linear regression analysis was applied to a path model that assessed the mediating and moderating effects of sense of belonging in the host city on direct relationships with life satisfaction (social integration ⇢ life satisfaction and hometown identity ⇢ life satisfaction).

Results
Social integration positively related to life satisfaction (B = 0.267) and sense of belonging in the host city (B = 0.912). A weak hometown identity related to higher life satisfaction and stronger sense of belonging in the host city (B = 0.087 and B = 0.176, respectively). Sense of belonging in the host city significantly mediated the relationships between social integration and life satisfaction (B = 0.267 decreased to B = 0.085) and between hometown identity and life satisfaction (B = 0.087 decreased to B = 0.048). Last, sense of belonging in the host city significantly moderated the relationship between social integration and life satisfaction.

Conclusion
A sense of belonging to a place is important to migrants’ life satisfaction regarding the hometown and the host city. Promoting migrants’ sense that they are part of the new living environment is important to China’s sustainable urban development.
Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment
Authors: Schram Sarah , Loeb Jeffrey A. , Song Fei 
Published: June 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS can start focally at a single limb, but then segmentally spread up and down the spinal cord as well as in the motor cortex and cortex of frontal and temporal lobes until respiratory muscles fail. With or without a clear genetic etiology, often there is no explanation as to why it starts in one region of the body versus another. Similarly, once the disease starts the mechanisms by which the neurodegenerative process spreads are not known. Here, we summarize recent work in animal models that support the hypothesis that critical environmental contributions, such as a nerve injury, can initiate the disease process. We also propose that pathological axoglial signaling by the glial growth factor neuregulin-1 leads to the slow propagation of neuroinflammation resulting in neurodegeneration up and down the spinal cord and that locally applied drugs that block neuregulin-1 signaling could slow or halt the spread of disease.
Neuroprotective effects of miR-142-5p downregulation against isoflurane-induced neurological impairment
Authors: Xie Cuili , Wang Hongyue , Zhang Yu , Wei Yanhua 
Published: June 2020

Abstract
Background
Isoflurane can lead to neuron damage to the developing brain, resulting in learning and memory disability. The aim of this study was to investigate the role of miR-142-5p on isoflurane-induced neurological impairment.

Methods
The Morris water maze (MWM) test was performed to evaluate spatial learning and memory of rats. The expression level of miR-142-5p was measured using qRT-PCR. MTT assay was used to calculate the viability of hippocampal neuronal cells. The cell apoptosis was analyzed using Flow cytometric assay.

Results
Isoflurane treatment led to the increase of neurological function score and escape latency, and the reduction of time spent in the original quadrant in rats. The expression level of miR-142-5p was increased significantly in isoflurane-treated rats. MiR-142-5p downregulation protected against isoflurane-induced neurological impairment, which was reflected by the decrease of neurological function score and escape latency, and the increase of time spent in the original quadrant. In vitro, downregulation of miR-142-5p alleviated isoflurane-induced neuron cell viability inhibition, and relieved isoflurane-induced cell apoptosis.

Conclusions
MiR-142-5p downregulation plays a neuroprotective role in protecting against isoflurane-induced neurological impairment through regulating neuron cell viability and apoptosis. It provides a theoretical basis for the investigation of the mechanism underlying the effect on isoflurane-induced neurological impairment.