bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of preoperative segmental range of motion on patient outcomes in cervical disc arthroplasty
Authors: Wu Ting-kui , Liu Hao , Ding Chen , Rong Xin , He Jun-bo , Huang Kang-kang , Hong Ying , Wang Bei-yu 
Published: July 2020

Abstract
Background
Cervical disc arthroplasty (CDA) has been demonstrated, in clinical trials, as an effective and safe treatment for patients diagnosed with radiculopathy and/or myelopathy. However, the current CDA indication criteria, based on the preoperative segmental range of motion (ROM), comprises a wide range of variability. Although the arthroplasty level preserved ROM averages 7°-9° after CDA, there are no clear guidelines on preoperatively limited or excessive ROM at the index level, which could be considered as suitable for CDA.

Methods
This was a retrospective study of patients who underwent CDA between January 2008 and October 2018 using Prestige-LP discs in our hospital. They were divided into the small-ROM (≤5.5°) and the large-ROM (> 12.5°) groups according to preoperatively index-level ROM. Clinical outcomes, including the Japanese Orthopedics Association (JOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) scores, were evaluated. Radiological parameters, including cervical lordosis, disc angle (DA), global and segmental ROM, disc height (DH), and complications were measured.

Results
One hundred and twenty six patients, with a total of 132 arthroplasty segments were analyzed. There were 64 patients in the small-ROM and 62 in the large-ROM group. There were more patients diagnosed with cervical spondylosis in the small-ROM than in the large-ROM group (P = 0.046). Patients in both groups had significantly improved JOA, NDI, and VAS scores after surgery, but the intergroup difference was not significant. Patients in the small-ROM group had dramatic postoperative increase in cervical lordosis, global and segmental ROM (P < 0.001). However, there was a paradoxical postoperative decrease in global and segmental ROM in the large-ROM group postoperatively (P < 0.001). Patients in the small-ROM group had lower preoperative DH (P = 0.012), and a higher rate of postoperative heterotopic ossification (HO) (P = 0.037).

Conclusion
Patients with preoperatively limited segmental ROM had severe HO, and achieved similar postoperative clinical outcomes as patients with preoperatively excessive segmental ROM. Patients with preoperatively limited segmental ROM showed a postoperative increase in segmental mobility, which decreased in patients with preoperatively excessive segmental ROM.
Long non-coding RNA CCHE1 participates in postoperative distant recurrence but not local recurrence of osteosarcoma possibly by interacting with ROCK1
Authors: Zhang Zhi , Yu Tao , Geng Wei 
Published: July 2020

Abstract
Background
Clinical treatment of osteosarcoma suffers from high recurrence rate. Therefore, is of great clinical values to develop predictive markers for recurrent osteosarcoma. Cervical carcinoma high-expressed lncRNA 1 (lncRNA CCHE1) participates in several types of malignancies, while its functionality in osteosarcoma is unknown. This study was therefore carried out to explore the involvement of lncRNA CCHE1 in recurrent osteosarcoma.

Methods
A total of 87 osteosarcoma patients received surgical resection and 38 healthy volunteers were included in this study. The 87 osteosarcoma patients were followed up for 5 years to record the recurrence of osteosarcoma. Plasma levels of lncRNA CCHE1 and ROCK1 on the day of discharge and during follow-up were measured by real-time quantitative PCR and ELISA, respectively. The effects of CCHE1 siRNA silencing on ROCK1 expression were analyzed by real-time quantitative PCR and western blot. Transwell assay was performed to analyze the role of lncRNA CCHE1 and ROCK1 in regulating cell invasion and migration.

Results
We observed that, on the day of discharge, plasma lncRNA CCHE1 was upregulated in osteosarcoma patients who developed distant recurrence (DR) during follow-up than in osteosarcoma patients who developed local recurrence (LR), patients with non-recurrence (NR) and healthy controls. On the day of discharge, plasma levels of ROCK1 were higher in DR, LR and NR groups in comparison to healthy controls. On the day of discharge, plasma levels of lncRNA CCHE1 were positively correlated with plasma levels of ROCK1 only in patients who developed DR during follow-up, but not in patients who developed LR, NR and control groups. During follow-up, plasma levels of lncRNA CCHE1 were further increased in DR group but slightly decreased in LR and NR groups. LncRNA CCHE1 siRNA silencing inhibited, while ROCK1 overexpression promoted osteosarcoma cell invasion and migration. ROCK1 overexpression attenuated the role of CCHE1. LncRNA CCHE1 siRNA silencing led to inhibited ROCK1 expression in cancer cells.

Conclusion
Therefore, lncRNA CCHE1 may participate in postoperative distant recurrence of osteosarcoma caner possibly by interacting with ROCK1 to promote cancer cell invasion and migration.
Survival analysis in gastric cancer: a multi-center study among Iranian patients
Authors: Talebi Atefeh , Mohammadnejad Afsaneh , Akbari Abolfazl , Pourhoseingholi Mohamad Amin , Doosti Hassan , Moghimi-Dehkordi Bijan , Agah Shahram , Bahardoust Mansour 
Published: July 2020

Abstract
Background
Gastric cancer (GC) has been considered as the 5th most common type of cancer and the third leading cause of cancer-associated death worldwide. The aim of this historical cohort study was to evaluate the survival predictors for all patients with GC using the Cox proportional hazards, extended Cox, and gamma-frailty models.

Methods
This historical cohort study was performed according to documents of 1695 individuals having GC referred to three medical centers in Iran from 2001 to 2018. First, most significant prognostic risk factors on survival were selected, Cox proportional hazards, extended Cox, gamma-frailty models were applied to evaluate the effects of the risk factors, and then these models were compared with the Akaike information criterion.

Results
The age of patients, body mass index (BMI), tumor size, type of treatment and grade of the tumor increased the hazard rate (HR) of GC patients in both the Cox and frailty models (P < 0.05). Also, the size of the tumor and BMI were considered as time-varying variables in the extended Cox model. Moreover, the frailty model showed that there is at least an unknown factor, genetic or environmental factors, in the model that is not measured (P < 0.05).

Conclusions
Some prognostic factors, including age, tumor size, the grade of the tumor, type of treatment and BMI, were regarded as indispensable predictors in patients of GC. Frailty model revealed that there are unknown or latent factors, genetic and environmental factors, resulting in the biased estimates of the regression coefficients.
A hospital-based study on complementary and alternative medicine use among diabetes patients in Rajshahi, Bangladesh
Authors: Rafi Md. Abdur , Azad Dewan Tasnia , Bhattacharjee Mridula , Rahman Nikita , Mubin Kazi Abdul , Rahman Md. Ajijur , Hossain Md. Golam 
Published: July 2020

Abstract
Background
The use of complementary and alternative medicine (CAM) among type 2 diabetes mellitus (T2DM) patients is increasing worldwide. It can affect optimum glycemic management. This study was to determine the rate and influencing factors of CAM use among diabetes patients as well as their effect on glycemic control.

Methods
This cross-sectional study was conducted among T2DM patients attending the outpatient department of Rajshahi Medical College Hospital. It is a tertiary hospital in the northern part of Bangladesh. A face-to-face interview with a pretested structured questionnaire was used for data collection. Chi-square (χ2) test and multivariate logistic regression model were used in this study for data analysis.

Results
Out of 244 T2DM patients, 86 (35.2%) used CAM. Multivariate logistic regression model showed that lower family income group (AOR = 8.7, 95% CI: 2.15–35.22, p-value 0.002), having no institutional education (AOR = 3.4, 95% CI: 1.17–9.87, p-value 0.025) and having diabetes for more than five years (AOR = 2.821, 95% CI: 1.34–5.94, p-value 0.006) were the most influential predictors of CAM use. The most commonly used CAMs were herbal products (67.4%) and homeopathic medicine (37.2%). Most of the CAM users (72%) were influenced by friends, neighbors, and family members. The most common reasons behind CAM use were reported to be the belief that CAM helped control diabetes better (44.2%) and easy availability and lower cost (27.9%). More than half of the users reported the efficacy of CAM as ‘nothing significant’, while others reported as somewhat good. 14% of CAM users experienced side-effects, especially gastrointestinal upset. It was observed that using CAM was associated with poor glycemic control (AOR = 2.25, 95% CI: 1.14–4.44, p-value 0.018).

Conclusion
Our study demonstrated that some modifiable factors are associated with the use of CAM, and it cannot maintain good glycemic control. So, patients should be made aware of the ineffectiveness and bad effects of CAM by enhancing educational and poverty-alleviating programs.
Caregivers' role in using a personal electronic health record: a qualitative study of cancer patients and caregivers in Germany
Authors: Weis Aline , Pohlmann Sabrina , Poss-Doering Regina , Strauss Beate , Ullrich Charlotte , Hofmann Helene , Ose Dominik , Winkler Eva C. , Szecsenyi Joachim , Wensing Michel 
Published: July 2020

Abstract
Background
Particularly in the context of severe diseases like cancer, many patients wish to include caregivers in the planning of treatment and care. Many caregivers like to be involved but feel insufficiently enabled. This study aimed at providing insight into patients’ and caregivers’ perspectives on caregivers’ roles in managing the patient portal of an electronic personal health record (PHR).

Methods
A descriptive qualitative study was conducted comprising two study phases: (1) Usability tests and interviews with patients with cancer and caregivers (2) additional patient interviews after a 3-month-pilot-testing of the PHR. For both study parts, a convenience sample was selected, focusing on current state of health and therapy process and basic willingness to participate and ending up with a mixed sample as well as saturation of data. All interviews were audio-recorded, pseudonymized, transcribed verbatim and qualitatively analyzed.

Results
Two main categories emerged from qualitative data: ‘Caregivers’ role’ and ‘Graduation of access rights’ – consisting of four subcategories each. The interviewed patients (n = 22) and caregivers (n = 9) felt that the involvement of caregivers is central to foster the acceptance of a PHR for cancer patients. However, their role varied from providing technical support to representing patients, e.g. if the patient’s state of health made this necessary. Heterogeneous opinions emerged regarding the question whether caregivers should receive full or graduated access on a patient’s PHR.

Conclusions
In order to support the patient and to participate in the care process, caregivers need up-to-date information on the patient’s health and treatment. Nevertheless, some patients do not want to share all medical data with caregivers, which might strain the patient-caregiver relationship. This needs to be considered in development and implementation of personal health records. Generally, in the debate on patient portals of a personal health record, paying attention to the role of caregivers is essential. By appreciating the important relationship between patients and caregivers right from the beginning, implementation, of a PHR would be enhanced.

Trial registration
ISRCTN85224823. Date of registration: 23/12/2015 (retrospectively registered).
Drug switching in the Netherlands: a cohort study of 20 active substances
Authors: Glerum Pieter J. , Maliepaard Marc , de Valk Vincent , Burger David M. , Neef Kees 
Published: July 2020

Abstract
Background
For a patient, drug switches are not desirable (either between a brand-name drug and a generic drug, or between two generic drugs of the same active substance). Research into the causes of drug switches, and related adverse drug reactions, is hampered by the absence of quantitative data on drug switches.

Methods
We describe the frequency of drug switches in the Netherlands for a selection of active substances. A retrospective cohort study was conducted using the Drug Information System of the National Health Care Institute in the Netherlands. We studied the Dutch patient population from mid-2009 to 2016. The selection of active substances (n = 20) was made based on a report by Lareb, the Netherlands Pharmacovigilance Centre, on adverse drug reactions related to drug switching, and we used qualitative and quantitative descriptive analyses. A drug switch is defined as the replacement of a patient’s prescribed drug with a similar drug from a different manufacturer.

Results
We identified 23.8 million drug switches on a total of 206 million (11.6%) similar drug dispenses. The frequency of drug switches demonstrated a yearly peak in the period from January to March. In some months, for atorvastatin, losartan, pantoprazole, and irbesartan, more than 60% of similar drug dispenses were drug switches. Most drug switches (80.3%) were between two generic drugs, and 0.12% of these involved a drug from a European parallel import. The proportion of drug switches between two brand-name drugs decreased from 14.5 to 5.53% during our study period, and of these, 86.5% involved a drug from a European parallel import.

Conclusions
Drug switching is common in the Netherlands, and most of the drug switches we studied are between generic drugs. The observed annual peak of drug switches is most likely explained by a specific Dutch reimbursement policy. Not only are the data valuable as is, but they also serve as a first step towards elucidating the reasons for the occurrence of these drug switches. In addition, these data can be used to put into perspective the adverse drug reactions associated with drug switching.
Prognostic value of an autophagy-related gene expression signature for endometrial cancer patients
Authors: Wang Hui , Ma Xiaoling , Liu Jinhui , Wan Yicong , Jiang Yi , Xia Yankai , Cheng Wenjun 
Published: July 2020

AbstractBackgroundAutophagy is associated with cancer development. Autophagy-related genes play significant roles in endometrial cancer (EC), a major gynecological malignancy worldwide, but little was known about their value as prognostic markers. Here we evaluated the value of a prognostic signature based on autophagy-related genes for EC.MethodsFirst, various autophagy-related genes were obtained via the Human Autophagy Database and their expression profiles were downloaded from The Cancer Genome Atlas. Second, key prognostic autophagy-related genes were identified via univariate, LASSO and multivariate Cox regression analyses. Finally, a risk score to predict the prognosis of EC was calculated and validated by using the test and the entire data sets. Besides, the key genes mRNA expression were validated using quantitative real-time PCR in clinical tissue samples.ResultsA total of 40 differentially expressed autophagy-related genes in EC were screened and five of them were prognosis-related (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1). A prognostic signature was constructed based on these five genes using the train set, which stratified EC patients into high-risk and low-risk groups (p < 0.05). In terms of overall survival, the analyses of the test set and the entire set yielded consistent results (test set: p < 0.05; entire set: p < 0.05). Time-dependent ROC analysis suggested that the risk score predicted EC prognosis accurately and independently (0.674 at 1 year, 0.712 at 3 years and 0.659 at 5 years). A nomogram with clinical utility was built. Patients in the high-risk group displayed distinct mutation signatures compared with those in the low-risk group. For clinical sample validation, we found that EIF4EBP1and ERBB2 had higher level in EC than that in normal tissues while CDKN1B, DLC1 and GRID1 had lower level, which was consistent with the results predicted.ConclusionsBased on five autophagy-related genes (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1), our model can independently predict the OS of EC patients by combining molecular signature and clinical characteristics.
Norepinephrine transporter-derived homing peptides enable rapid endocytosis of drug delivery nanovehicles into neuroblastoma cells
Authors: Haddad Yazan , Charousova Marketa , Zivotska Hana , Splichal Zbynek , Merlos Rodrigo Miguel Angel , Michalkova Hana , Krizkova Sona , Tesarova Barbora , Richtera Lukas , Vitek Petr , Stokowa-Soltys Kamila , Hynek David , Milosavljevic Vedran , Rex Simona , Heger Zbynek 
Published: July 2020

Abstract
Background
Currently, the diagnosis and treatment of neuroblastomas—the most frequent solid tumors in children—exploit the norepinephrine transporter (hNET) via radiolabeled norepinephrine analogs. We aim to develop a nanomedicine-based strategy towards precision therapy by targeting hNET cell-surface protein with hNET-derived homing peptides.

Results
The peptides (seq. GASNGINAYL and SLWERLAYGI) were shown to bind high-resolution homology models of hNET in silico. In particular, one unique binding site has marked the sequence and structural similarities of both peptides, while most of the contribution to the interaction was attributed to the electrostatic energy of Asn and Arg (< − 228 kJ/mol). The peptides were comprehensively characterized by computational and spectroscopic methods showing ~ 21% β-sheets/aggregation for GASNGINAYL and ~ 27% α-helix for SLWERLAYGI. After decorating 12-nm ferritin-based nanovehicles with cysteinated peptides, both peptides exhibited high potential for use in actively targeted neuroblastoma nanotherapy with exceptional in vitro biocompatibility and stability, showing minor yet distinct influences of the peptides on the global expression profiles. Upon binding to hNET with fast binding kinetics, GASNGINAYLC peptides enabled rapid endocytosis of ferritins into neuroblastoma cells, leading to apoptosis due to increased selective cytotoxicity of transported payload ellipticine. Peptide-coated nanovehicles significantly showed higher levels of early apoptosis after 6 h than non-coated nanovehicles (11% and 7.3%, respectively). Furthermore, targeting with the GASNGINAYLC peptide led to significantly higher degree of late apoptosis compared to the SLWERLAYGIC peptide (9.3% and 4.4%, respectively). These findings were supported by increased formation of reactive oxygen species, down-regulation of survivin and Bcl-2 and up-regulated p53.

Conclusion
This novel homing nanovehicle employing GASNGINAYLC peptide was shown to induce rapid endocytosis of ellipticine-loaded ferritins into neuroblastoma cells in selective fashion and with successful payload. Future homing peptide development via lead optimization and functional analysis can pave the way towards efficient peptide-based active delivery of nanomedicines to neuroblastoma cells.
Changes in peripheral mitochondrial DNA copy number in metformin-treated women with polycystic ovary syndrome: a longitudinal study
Authors: Yang Po-Kai , Chou Chia-Hong , Chang Chin-Hao , Chen Shee-Uan , Ho Hong-Nerng , Chen Mei-Jou 
Published: July 2020

Abstract
Background
Patients with polycystic ovarian syndrome (PCOS) are associated with known alterations in mitochondria DNA copy number (mtDNA-CN). The aim of this study is to study the change in mtDNA-CN in patients with PCOS who were treated with metformin.

Methods
This is a prospective cohort of patients with PCOS, who received metformin for one year. From 2009 to 2015, 88 women diagnosed with PCOS, based on the Rotterdam criteria, were enrolled. Serial measurements of mtDNA-CN, 8-hydroxydeoxyguanosine (8-OHdG), anthropometric, metabolic, endocrine, and inflammatory markers were obtained before and after 3, 6, and 12 months of treatment.

Results
A significant decrease in mtDNA-CN was seen over the course of one year. Other markers, including 8-OHdG, testosterone, free androgen index, blood pressure and liver enzymes, also decreased in the same interval. On regression analysis, there was a significant association between the change in mtDNA-CN and serum total testosterone, and no association between mtDNA-CN and metabolic factors.

Conclusions
Treatment with metformin is associated with a time-dependent decrease in mtDNA-CN in patients with PCOS who are treated over the course of one year. This may signify a reduction in mitochondria dysfunction. The change in mtDNA-CN corresponds to a similar change in serum total testosterone, and suggests a possible relationship between mtDNA-CN and testosterone.

Trial registration
ClinicalTrials.gov, NCT00172523. Registered September 15, 2005
Validity and reliability of an accelerometer-based assessgame to quantify upper limb selective voluntary motor control
Authors: Keller Jeffrey W. , Fahr Annina , Balzer Julia , Lieber Jan , van Hedel Hubertus J. A. 
Published: July 2020

Abstract
Introduction
Current clinical assessments measure selective voluntary motor control (SVMC) on an ordinal scale. We introduce a playful, interval-scaled method to assess SVMC in children with brain lesions and evaluate its validity and reliability.

Methods
Thirty-one neurologically intact children (median [1st-3rd quartile]: 11.6 years [8.5–13.9]) and 33 patients (12.2 years [8.8–14.9]) affected by upper motor neuron lesions with mild to moderate impairments participated. Using accelerometers, they played a movement tracking game (assessgame) with isolated joint movements (shoulder, elbow, lower arm [pro−/supination], wrist, and fingers), yielding an accuracy score. Involuntary movements were recorded simultaneously and resulted in an involuntary movement score. Both scores were normalized to the performance of 33 neurologically intact adults (32.5 years [27.9; 38.3]), which represented physiological movement patterns.
We correlated the assessgame outcomes with the Manual Ability Classification System, Selective Control of the Upper Extremity Scale, and a therapist rating of involuntary movements. Furthermore, a robust ANCOVA was performed with age as covariate, comparing patients to their healthy peers at the age levels of 7.5, 9, 10.5, 12, and 15 years.
Intraclass correlation coefficients and smallest real differences indicated relative and absolute reliability.

Results
Correlations (Kendall/Spearman) for the accuracy score were τ = 0.29 (p = 0.035; Manual Ability Classification System), ρ = − 0.37 (p = 0.035; Selective Control of the Upper Extremity Scale), and ρ = 0.64 (p < 0.001; therapist rating). Correlations for the involuntary movement metric were τ = 0.37 (p = 0.008), ρ = − 0.55 (p = 0.001), and ρ = 0.79 (p < 0.001), respectively. The robust ANCOVAs revealed that patients performed significantly poorer than their healthy peers in both outcomes and at all age levels except for the dominant/less affected arm, where the youngest age group did not differ significantly. Robust intraclass correlation coefficients and smallest real differences were 0.80 and 1.02 (46% of median patient score) for the accuracy and 0.92 and 2.55 (58%) for involuntary movements, respectively.

Conclusion
While this novel assessgame is valid, the reliability might need to be improved. Further studies are needed to determine whether the assessgame is sensitive enough to detect changes in SVMC after a surgical or therapeutic intervention.