bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of implant surgical guides fabricated using computer numerical control milling for edentulous jaws: a pilot clinical trial
Authors: Chai Jinyou , Liu Xiaoqian , Schweyen Ramona , Setz Jürgen , Pan Shaoxia , Liu Jianzhang , Zhou Yongsheng 
Published: October 2020

Abstract
Background
To evaluate the accuracy of a computer numerical control (CNC) milled surgical guide for implant placement in edentulous jaws.

Methods
Edentulous patients seeking implants treatment were recruited in this prospective cohort study. Radiographic guides with diagnostic templates were fabricated from wax-up dentures. Patients took cone-beam computed tomography (CBCT) wearing the radiopaque radiographic guides. Implant positions were virtually designed in the planning software based on the CBCT data, and the radiographic templates were converted into surgical guides using CNC milling technique. Forty-four implants were placed into 12 edentulous jaws following guided implant surgery protocol. Post-surgery CBCT scans were made for each jaw, and the deviations between the planned and actual implant positions were measured. Deviation of implant position was compared between maxilla and mandible, and between cases with and without anchor pins using independent t-test.

Results
Nine patients (3 males and 6 females) with 12 edentulous jaws were recruited. The mean age of patients was 59.2 ± 13.9 years old. All 44 implants was placed without complication and survived, the mean three dimensional linear deviation of implant position between virtual planning and actual placement was 1.53 ± 0.48 mm at the implant neck and 1.58 ± 0.49 mm at the apex. The angular deviation was 3.96 ± 3.05 degrees. No significant difference was found in the deviation of implant position between maxilla and mandible (P = 0.28 at neck, 0.08 at apex), nor between cases with and without anchor pins (P = 0.87 at neck, 0.06 at apex).

Conclusions
The guides fabricated using the CNC milling technique provided comparable accuracy as those fabricated by Stereolithography. The displacement of the guides on edentulous arch might be the main contributing factor of deviation.
Trial registration: Chinese Clinical Trial Registry, ChiCTR-ONC-17014159 (July 26, 2017).
Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
Authors: Lawlor Peter G. , McNamara-Kilian Marie T. , MacDonald Alistair R. , Momoli Franco , Tierney Sallyanne , Lacaze-Masmonteil Nathalie , Dasgupta Monidipa , Agar Meera , Pereira Jose L. , Currow David C. , Bush Shirley H. 
Published: October 2020

Abstract
Background
Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC.

Methods
Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative Care Unit (PCU), having a Palliative Performance Scale rating ≥ 30%, and for whom consent was obtained, were included in the study. Patients with delirium on admission were excluded. The main study objectives were to assess the feasibility issues of conducting a double-blind RCT of exogenous melatonin to prevent delirium in PC: recruitment, retention, procedural acceptability, appropriateness of outcome measures, and preliminary efficacy and safety data. Study participants were randomized in a double-blind, parallel designed study to receive daily melatonin 3 mg or placebo orally at 21:00 over 28 days or less if incident delirium, death, discharge or withdrawal occurred earlier. Delirium was diagnosed using the Confusion Assessment Method. Efficacy endpoints in the melatonin and placebo groups were compared using time-to-event analysis: days from study entry to onset of incident delirium.

Results
Over 16 months, 60/616 (9.7%; 95% CI: 7.5–12.4%) screened subjects were enrolled. The respective melatonin (n = 30) vs placebo (n = 30) outcomes were: incident delirium in 11/30 (36.7%; 95%CI: 19.9–56.1%) vs 10/30 (33%; 95% CI: 17.3–52.8%); early discharge (6 vs 5); withdrawal (6 vs 3); death (0 vs 1); and 7 (23%) vs 11 (37%) reached the 28-day end point. The 25th percentile time-to-event were 9 and 18 days (log rank, χ2 = 0.62, p = 0.43) in melatonin and placebo groups, respectively. No serious trial medication-related adverse effects occurred and the core study procedures were acceptable. Compared to those who remained delirium-free during their study participation, those who developed delirium (n = 21) had poorer functional (p = 0.036) and cognitive performance (p = 0.013), and in particular, poorer attentional capacity (p = 0.003) at study entry.

Conclusions
A larger double-blind RCT is feasible, but both subject accrual and withdrawal rates signal a need for multisite collaboration. The apparent trend for shorter time to incident delirium in the melatonin group bodes for careful monitoring in a larger trial.

Trial registration
Registered on July 21st 2014 with ClinicalTrials.gov: NCT02200172.
Adoption rates of electronic health records in Turkish Hospitals and the relation with hospital sizes
Authors: Kose Ilker , Rayner John , Birinci Suayip , Ulgu Mustafa Mahir , Yilmaz Ismayil , Guner Seyma ,   HIMSS Analytics Team, Mahir Suna Kirdag , Aycil Kubra , Elmas Beytiye O. , Volkan Esra , Altinbas Zeynep , Gencyurek Gizem ,   MoH Team, Zehir Esra , Gundogdu Berrin , Ozcan Mert , Vardar Ceyhan , Altinli Behcet , Hasancebi Jale Sungur 
Published: October 2020

Abstract
Background
Nation-wide adoption of electronic health records (EHRs) in hospitals has become a Turkish policy priority in recognition of their benefits in maintaining the overall quality of clinical care. The electronic medical record maturity model (EMRAM) is a widely used survey tool developed by the Healthcare Information and Management Systems Society (HIMSS) to measure the rate of adoption of EHR functions in a hospital or a secondary care setting. Turkey completed many standardizations and infrastructural improvement initiatives in the health information technology (IT) domain during the first phase of the Health Transformation Program between 2003 and 2017. Like the United States of America (USA), the Turkish Ministry of Health (MoH) applied a bottom-up approach to adopting EHRs in state hospitals. This study aims to measure adoption rates and levels of EHR use in state hospitals in Turkey and investigate any relationship between adoption and use and hospital size.

Methods
EMRAM surveys were completed by 600 (68.9%) state hospitals in Turkey between 2014 and 2017. The availability and prevalence of medical information systems and EHR functions and their use were measured. The association between hospital size and the availability/prevalence of EHR functions was also calculated.

Results
We found that 63.1% of all hospitals in Turkey have at least basic EHR functions, and 36% have comprehensive EHR functions, which compares favourably to the results of Korean hospitals in 2017, but unfavorably to the results of US hospitals in 2015 and 2017. Our findings suggest that smaller hospitals are better at adopting certain EHR functions than larger hospitals.

Conclusion
Measuring the overall adoption rates of EHR functions is an emerging approach and a beneficial tool for the strategic management of countries. This study is the first one covering all state hospitals in a country using EMRAM. The bottom-up approach to adopting EHR in state hospitals that was successful in the USA has also been found to be successful in Turkey. The results are used by the Turkish MoH to disseminate the nation-wide benefits of EHR functions.
TNFPred: identifying tumor necrosis factors using hybrid features based on word embeddings
Authors: Nguyen Trinh-Trung-Duong , Le Nguyen-Quoc-Khanh , Ho Quang-Thai , Phan Dinh-Van , Ou Yu-Yen 
Published: October 2020

AbstractBackgroundCytokines are a class of small proteins that act as chemical messengers and play a significant role in essential cellular processes including immunity regulation, hematopoiesis, and inflammation. As one important family of cytokines, tumor necrosis factors have association with the regulation of a various biological processes such as proliferation and differentiation of cells, apoptosis, lipid metabolism, and coagulation. The implication of these cytokines can also be seen in various diseases such as insulin resistance, autoimmune diseases, and cancer. Considering the interdependence between this kind of cytokine and others, classifying tumor necrosis factors from other cytokines is a challenge for biological scientists.MethodsIn this research, we employed a word embedding technique to create hybrid features which was proved to efficiently identify tumor necrosis factors given cytokine sequences. We segmented each protein sequence into protein words and created corresponding word embedding for each word. Then, word embedding-based vector for each sequence was created and input into machine learning classification models. When extracting feature sets, we not only diversified segmentation sizes of protein sequence but also conducted different combinations among split grams to find the best features which generated the optimal prediction. Furthermore, our methodology follows a well-defined procedure to build a reliable classification tool.ResultsWith our proposed hybrid features, prediction models obtain more promising performance compared to seven prominent sequenced-based feature kinds. Results from 10 independent runs on the surveyed dataset show that on an average, our optimal models obtain an area under the curve of 0.984 and 0.998 on 5-fold cross-validation and independent test, respectively.ConclusionsThese results show that biologists can use our model to identify tumor necrosis factors from other cytokines efficiently. Moreover, this study proves that natural language processing techniques can be applied reasonably to help biologists solve bioinformatics problems efficiently.
Pan-cancer analysis of differential DNA methylation patterns
Authors: Shi Mai , Tsui Stephen Kwok-Wing , Wu Hao , Wei Yingying 
Published: October 2020

Abstract
Background
DNA methylation is a key epigenetic regulator contributing to cancer development. To understand the role of DNA methylation in tumorigenesis, it is important to investigate and compare differential methylation (DM) patterns between normal and case samples across different cancer types. However, current pan-cancer analyses call DM separately for each cancer, which suffers from lower statistical power and fails to provide a comprehensive view for patterns across cancers.

Methods
In this work, we propose a rigorous statistical model, PanDM, to jointly characterize DM patterns across diverse cancer types. PanDM uses the hidden correlations in the combined dataset to improve statistical power through joint modeling. PanDM takes summary statistics from separate analyses as input and performs methylation site clustering, differential methylation detection, and pan-cancer pattern discovery. We demonstrate the favorable performance of PanDM using simulation data. We apply our model to 12 cancer methylome data collected from The Cancer Genome Atlas (TCGA) project. We further conduct ontology- and pathway-enrichment analyses to gain new biological insights into the pan-cancer DM patterns learned by PanDM.

Results
PanDM outperforms two types of separate analyses in the power of DM calling in the simulation study. Application of PanDM to TCGA data reveals 37 pan-cancer DM patterns in the 12 cancer methylomes, including both common and cancer-type-specific patterns. These 37 patterns are in turn used to group cancer types. Functional ontology and biological pathways enriched in the non-common patterns not only underpin the cancer-type-specific etiology and pathogenesis but also unveil the common environmental risk factors shared by multiple cancer types. Moreover, we also identify PanDM-specific DM CpG sites that the common strategy fails to detect.

Conclusions
PanDM is a powerful tool that provides a systematic way to investigate aberrant methylation patterns across multiple cancer types. Results from real data analyses suggest a novel angle for us to understand the common and specific DM patterns in different cancers. Moreover, as PanDM works on the summary statistics for each cancer type, the same framework can in principle be applied to pan-cancer analyses of other functional genomic profiles. We implement PanDM as an R package, which is freely available at http://www.sta.cuhk.edu.hk/YWei/PanDM.html.
Risk factors for the critical illness in SARS-CoV-2 infection: a multicenter retrospective cohort study
Authors: Cheng Sijing , Wu Dingfeng , Li Jie , Zou Yifeng , Wan Yunle , Shen Lihan , Zhu Lixin , Shi Mang , Hou Linlin , Xu Tao , Jiao Na , Li Yichen , Huang Yibo , Tang Zhipeng , Xu Mingwei , Jiang Shusong , Li Maokun , Yan Guangjun , Lan Ping , Zhu Ruixin 
Published: October 2020

Abstract
Background
Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection.

Methods
Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness.

Results
Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia < 1.1 × 109/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 μg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 μM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors.

Conclusions
Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.
Designed proteinoid polymers and nanoparticles encapsulating risperidone for enhanced antipsychotic activity
Authors: Lugasi L. , Grinberg I. , Rudnick-Glick S. , Okun E. , Einat H. , Margel S. 
Published: October 2020

AbstractBackgroundNanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood–brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by proteinoid NPs.ResultsProteinoid polymers with high molecular weight and low polydispersity were synthesized froml-amino acids and poly-l-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded proteinoid NPs compared to free RSP.ConclusionsProteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.
Who chooses to enroll in a new national gambling self-exclusion system? A general population survey in Sweden
Authors: Håkansson A. , Henzel V. 
Published: October 2020

AbstractBackgroundSelf-exclusion from gambling is a common method for prevention and harm reduction in hazardous gambling. However, few national self-exclusion programs, involving a large number of gambling operators and activities in a country, have been assessed scientifically. This study aimed to examine characteristics of individuals who chose to enroll in a recently introduced (January, 2019) national self-exclusion system in Sweden.MethodsAdults and adolescents (from age 16 and above) were addressed with an online survey sent to members of the web panel of a market survey company (1940 respondents). Psychological distress, previous history of addictive disorders, sociodemographic data, and recent history of gambling patterns and over-indebtedness were recorded. Logistic regression tested associations with self-exclusion, with unadjusted analyses conducted for the sub-group of moderate-risk or problem gamblers.ResultsFour percent reported having self-excluded using the new national self-exclusion system. In logistic regression, self-exclusion was significantly associated with younger age (OR 0.65 [0.54–0.79] for increasing age groups) and with the highest level of problem gambling (OR 2.84 [1.10–7.37]). In moderate-risk or problem gamblers, in unadjusted analyses, younger age (p < 0.05) and psychological distress (p = 0.02) were associated with self-exclusion. In none- or low-risk gamblers, 3% had self-excluded, which was significantly associated with younger age (p < 0.001) and self-reported over-indebtedness (p < 0.001).ConclusionsIn a national, multi-venue online and land-based self-exclusion system, aiming to reduce the harm of problem gambling, self-exclusion is expectedly more common in problem gamblers, but also occurs among people without recent gambling problems. Further efforts may be needed in order to increase gambling self-exclusion in problem gamblers, and research in reasons for self-excluding, even in non-problem gamblers, is needed.
Assessing the effect of child’s gender on their father–mother perception of the PedsQL™ 4.0 questionnaire: an iterative hybrid ordinal logistic regression/item response theory approach with Monte Carlo simulation
Authors: Doostfatemeh Marziyeh , Ayatollahi Seyyed Mohammad Taghi , Jafari Peyman 
Published: October 2020

AbstractBackgroundThis study aimed at investigating the possible confounding effect of children’s gender on the parents’ dyads perception of their child HRQoL at both item and scale levels of PedsQLTM4.0 questionnaire.MethodsThe PedsQL™ 4.0 Generic Core Scales were completed by 573 children and their father-and-mother dyads. An iterative hybrid ordinal logistic regression/item response theory model with Monte Carlo simulation was used to detect differential item functioning (DIF) invariance across mothers/fathers and daughter/sons.ResultsAssessing DIF across mother–daughter, father–daughter, mother–son, and father–son dyads revealed that although parents and their children perceived the meaning of some items of PedsQLTM4.0 instrument differently, the pattern of fathers’ and mothers’ report does not vary much across daughters and sons.ConclusionIn the Persian version of PedsQLTM4.0, the child’s gender is not a confounding factor in the mothers’ and fathers’ report with respect to their daughters’ and sons’ HRQoL. Hence, paternal proxy-reports can be included in studies, along with maternal proxy-reports, and the reports can be combined short of concerning children gender, when looking at parent–child agreement.
Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-κB signaling pathway
Authors: Lai Tsung-Ching , Fang Chih-Yeu , Jan Yi-Hua , Hsieh Hsiao-Ling , Yang Yi-Fang , Liu Chun-Yu , Chang Peter Mu-Hsin , Hsiao Michael 
Published: October 2020

Abstract
Background
Chemotherapy is currently one of the most effective treatments for advanced breast cancer. Anti-microtubule agents, including taxanes, eribulin and vinca-alkaloids are one of the primary major anti-breast cancer chemotherapies; however, chemoresistance remains a problem that is difficult to solve. We aimed to discover novel candidate protein targets to combat chemoresistance in breast cancer.

Methods
A lentiviral shRNA-based high-throughput screening platform was designed and developed to screen the global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The phenotypes were confirmed with alternative expression in vitro and in vivo. Molecular mechanisms were investigated using global phosphoprotein arrays and expression microarrays. Global microarray analysis was performed to determine TAOK3 and genes that induced paclitaxel resistance.

Results
A serine/threonine kinase gene, TAOK3, was identified from 724 screened kinase genes. TAOK3 shRNA exhibited the most significant reduction in IC50 values in response to paclitaxel treatment. Ectopic downregulation of TAOK3 resulted in paclitaxel-resistant breast cancer cells sensitize to paclitaxel treatment in vitro and in vivo. The expression of TAOK3 also was correlated to sensitivity to two other anti-microtubule drugs, eribulin and vinorelbine. Our TAOK3-modulated microarray analysis indicated that NF-κB signaling played a major upstream regulation role. TAOK3 inhibitor, CP43, and shRNA of NF-κB both reduced the paclitaxel resistance in TAOK3 overexpressed cells. In clinical microarray databases, high TAOK3 expressed breast cancer patients had poorer prognoses after adjuvant chemotherapy.

Conclusions
Here we identified TAOK3 overexpression increased anti-microtubule drug resistance through upregulation of NF-κB signaling, which reduced cell death in breast cancer. Therefore, inhibition of the interaction between TAOK3 and NF-κB signaling may have therapeutic implications for breast cancer patients treated with anti-microtubule drugs.