bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmental Mandibular Reconstruction Using Tissue Engineering Strategies: A Systematic Review of Individual Patient Data
Authors: Kumar Vinay V. , Rometsch Elke , Thor Andreas , Wolvius Eppo , Hurtado-Chong Anahí 
Published: April 2020

Objective: The aim of the systematic review was to analyze the current clinical evidence concerning the use of tissue engineering as a treatment strategy for reconstruction of segmental defects of the mandible and their clinical outcomes using individual patient data. Methods: A systematic review of the literature was conducted using PubMed and Cochrane Library on May 21, 2019. The eligibility criteria included patients in whom segmental mandibular reconstruction was carried out using tissue engineering as the primary treatment strategy. After screening and checking for eligibility, individual patient data were extracted to the extent it was available. Data extraction included the type of tissue engineering strategy, demographics, and indication for treatment, and outcomes included clinical and radiographic outcome measures, vitality of engineered bone, dental rehabilitation, and patient-reported outcome measures and complications. Results: Out of a total of 408 articles identified, 44 articles reporting on 285 patients were included, of which 179 patients fulfilled the inclusion criteria. The different tissue engineering treatment strategies could be broadly classified into 5 groups: “prefabrication,” “cell culture,” “bone morphogenetic protein (BMP) without autografts,” “BMP with autografts,” and “scaffolds containing autografts.” Most included studies were case reports or case series. A wide variety of components were used as scaffolds, cells, and biological substances. There was not a single outcome measure that was both objective and consistently reported, although most studies reported successful outcome. Discussion: A wide variety of tissue engineering strategies were used for segmental mandibular reconstruction that could be classified into 5 groups. Due to the low number of treated patients, lack of standardized and consistent reporting outcomes, lack of comparative studies, and low evidence of reported literature, there is insufficient evidence to recommend any particular tissue engineering strategy.
Bridging the Unbridged: A Case Study of a U.S. University’s Study Abroad Program in Beijing
Authors: Wang Yong , Li Ke , Zhang Yuan 
Published: April 2020

Purpose: Studying abroad is an important way for universities to cultivate talent with international vision and global competitiveness. Based on its analysis of a U.S. university’s study in China program, this study provides policy recommendations to promote the overseas study and exchange of U.S. students in China. Design/Approach/Methods: This study examines the Beijing Overseas Learning Program of L University to examine the actual operations of a study abroad program in China. More specifically, this study examines the cooperative institution where the U.S. study program is located in China to analyze the operation mechanism and underlying logical framework of the program. Findings: This study provides a comprehensive analysis of the logical factors as well as internal and external reasons behind U.S. students’ decisions to study in China. This study demonstrates that the “peer factor” has a decisive influence on students’ decisions to study in China. Originality/Value: Study abroad programs constitute an integral part of China’s initiatives to enhance people-to-people exchanges with other countries. This study improves our understanding of the practical dynamics of study abroad programs in China, thereby enhancing abilities to attract U.S. students to study in China.
Is There a Role for CT Pan-Scans in the Initial Workup of Fragility Fracture Patients?
Authors: Lepkowsky Eric , Simcox Trevor , Rogoff Hunter , Barzideh Omid , Islam Shahidul 
Published: April 2020

Introduction: Computed tomography (CT) pan-scans have become increasingly commonplace as part of the initial diagnostic workup for patients sustaining traumatic injuries. They have proven effective in improving diagnostic accuracy in those with high-energy mechanisms of injury. However, the utility of pan-scans in the geriatric population sustaining low-energy traumatic injuries remains unproven. Methods: A retrospective review was conducted of patients who sustained a fragility fracture at a level-1 trauma center over a 15-month period. Radiologist interpretations of any CT pan-scans were reviewed for acute findings, and charts were reviewed for resulting changes in orthopedic and nonorthopedic management. Additionally, mechanism of injury, definitive management, time to surgery, length of stay, level of care at discharge, and demographic data were compared against similar patients who did not receive a pan-scan. Results: Of the 109 patients who underwent a CT pan-scan, 1 (0.92%) had a change in orthopedic treatment. Twelve (11.01%) patients had changes to their nonorthopedic management. In addition, 14 other patients had one or more consultations obtained based on pan-scan results that did not result in any change in management. Discussion: This study found that only 1 of the included patients had a change in orthopedic management and 12 had a change in nonorthopedic management, despite over half of the study population being found to have additional findings. Furthermore, patients who underwent a pan-scan did not have expedited surgical intervention or earlier discharges compared to those who were not pan-scanned. Conclusion: This study demonstrates whole-body CT imaging provides little benefit in geriatric patients who sustain fragility fractures and should be utilized judiciously and in a targeted fashion instead of as a routine part of trauma surgery or emergency department protocol in this patient population. Level of Evidence: Level III Retrospective Study.
Mechanistic basis and efficacy of targeting the β-catenin–TCF7L2–JMJD6–c-Myc axis to overcome resistance to BET inhibitors
Authors: Saenz Dyana T. , Fiskus Warren , Mill Christopher P. , Perera Dimuthu , Manshouri Taghi , Lara Bernardo H. , Karkhanis Vrajesh , Sharma Sunil , Horrigan Stephen K. , Bose Prithviraj , Kadia Tapan M. , Masarova Lucia , DiNardo Courtney D. , Borthakur Gautam , Khoury Joseph D. , Takahashi Koichi , Bhaskara Srividya , Lin Charles Y. , Green Michael R. , Coarfa Cristian , Crews Craig M. , Verstovsek Srdan , Bhalla Kapil N. 
Published: April 2020

Abstract
The promising activity of BET protein inhibitors (BETi’s) is compromised by adaptive or innate resistance in acute myeloid leukemia (AML). Here, modeling of BETi-persister/resistance (BETi-P/R) in human postmyeloproliferative neoplasm (post-MPN) secondary AML (sAML) cells demonstrated accessible and active chromatin in specific superenhancers/enhancers, which was associated with increased levels of nuclear β-catenin, TCF7L2, JMJD6, and c-Myc in BETi-P/R sAML cells. Following BETi treatment, c-Myc levels were rapidly restored in BETi-P/R sAML cells. CRISPR/Cas9-mediated knockout of TCF7L2 or JMJD6 reversed BETi-P/R, whereas ectopic overexpression conferred BETi-P/R in sAML cells, confirming the mechanistic role of the β-catenin–TCF7L2–JMJD6–c-Myc axis in BETi resistance. Patient-derived, post-MPN, CD34+ sAML blasts exhibiting relative resistance to BETi, as compared with sensitive sAML blasts, displayed higher messenger RNA and protein expression of TCF7L2, JMJD6, and c-Myc and following BETi washout exhibited rapid restoration of c-Myc and JMJD6. CRISPR/Cas9 knockout of TCF7L2 and JMJD6 depleted their levels, inducing loss of viability of the sAML blasts. Disruption of colocalization of nuclear β-catenin with TBL1 and TCF7L2 by the small-molecule inhibitor BC2059 combined with depletion of BRD4 by BET proteolysis-targeting chimera reduced c-Myc levels and exerted synergistic lethality in BETi-P/R sAML cells. This combination also reduced leukemia burden and improved survival of mice engrafted with BETi-P/R sAML cells or patient-derived AML blasts innately resistant to BETi. Therefore, multitargeted disruption of the β-catenin–TCF7L2–JMJD6–c-Myc axis overcomes adaptive and innate BETi resistance, exhibiting preclinical efficacy against human post-MPN sAML cells.
Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line
Authors: Mengozzi Manuela , Hesketh Andrew , Bucca Giselda , Ghezzi Pietro , Smith Colin P. 
Published: April 2020

AbstractBackgroundVitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it is unclear whether vitamin D supplementation improves the clinical course of MS, and there is uncertainty about the dose and form of vitamin D (D2 or D3) to be used. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with vitamin D3 at 24 h and 72 h following onset of differentiation.MethodsGene expression in differentiating CG4 cells in response to vitamin D2 or D3 was quantified using Agilent DNA microarrays (n = 4 replicates), and the transcriptome data were processed and analysed using the R software environment. Differential expression between the experimental conditions was determined using LIMMA, applying the Benjamini and Hochberg multiple testing correction top-values, and significant genes were grouped into co-expression clusters by hierarchical clustering. The functional significance of gene groups was explored by pathway enrichment analysis using the clusterProfiler package.ResultsDifferentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for Gene Ontology (GO) categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway.ConclusionsThis study shows that vitamin D3, compared with D2, changes the expression of a larger number of genes in OLs. Identification of genes affected by D3 in OLs should help to identify mechanisms mediating its action in MS.
Long non-coding RNA H19, a novel therapeutic target for pancreatic cancer
Authors: Wang Jing , Zhao Lei , Shang Kun , Liu Fang , Che Juanjuan , Li Huihui , Cao Bangwei 
Published: April 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, which threats peoples’ health. Unfortunately, the pathogenesis of PDAC remains unclear. Recent studies have indicated that long non-coding RNAs (lncRNAs) can regulate the development and progression of malignant tumors through varying mechanisms. LncRNA H19 has a unique expression profile and can act as a sponger of specific miRNAs to regulate the pathogenic process of many diseases, including PDAC and several other types of cancers. Here, we review the research approaches to understanding the regulatory role of H19 and potential mechanisms in the progression of PDAC and other types of cancers and diseases. These studies suggest that H19 may be a novel therapeutic target for PDAC and our findings may open new revenues for scientific researches and development of valuable therapies for these diseases in the future.
2D/2D Heterojunction of R-scheme Ti3C2 MXene/MoS2 Nanosheets for Enhanced Photocatalytic Performance
Authors: Yao Ziyu , Sun Huajun , Sui Huiting , Liu Xiaofang 
Published: April 2020

AbstractCombination of two-dimensional (2D) materials and semiconductors is considered to be an effective way for fabricating photocatalysts for solving the environmental pollution and energy crisis. In this work, novel 2D/2D heterojunction of R-scheme Ti3C2 MXene/MoS2 nanosheets is successfully synthesized by hydrothermal reaction. The photocatalytic activity of the Ti3C2 MXene/MoS2 composites is evaluated by photocatalytic degradation and hydrogen evolution reaction. Especially, 0.5 wt% Ti3C2 MXene/MoS2 sample exhibits optimum methyl orange (MO) degradation and H2 evolution rate of 97.4% and H2 evolution rate of 380.2 μmol h−1 g−1, respectively, which is attributed to the enhanced optical absorption ability and increased specific surface area. Additionally, Ti3C2 MXene coupled with MoS2 nanosheets is favorable for improving the photocurrent response and reducing the electrochemical impedance, leading to the enhanced electron transfer of excited semiconductor and inhibition of charge recombination. This work demonstrates that Ti3C2 MXene could be a promising carrier to construct 2D/2D heterojunction in photocatalytic degradation and hydrogen evolution reaction.
Toxo: a library for calculating penetrance tables of high-order epistasis models
Authors: Ponte-Fernández Christian , González-Domínguez Jorge , Carvajal-Rodríguez Antonio , Martín María J. 
Published: April 2020

Abstract
Background
Epistasis is defined as the interaction between different genes when expressing a specific phenotype. The most common way to characterize an epistatic relationship is using a penetrance table, which contains the probability of expressing the phenotype under study given a particular allele combination. Available simulators can only create penetrance tables for well-known epistasis models involving a small number of genes and under a large number of limitations.

Results
Toxo is a MATLAB library designed to calculate penetrance tables of epistasis models of any interaction order which resemble real data more closely. The user specifies the desired heritability (or prevalence) and the program maximizes the table’s prevalence (or heritability) according to the input epistatic model boundaries.

Conclusions
Toxo extends the capabilities of existing simulators that define epistasis using penetrance tables. These tables can be directly used as input for software simulators such as GAMETES so that they are able to generate data samples with larger interactions and more realistic prevalences/heritabilities.
Investigation of sequence features of hinge-bending regions in proteins with domain movements using kernel logistic regression
Authors: Veevers Ruth , Cawley Gavin , Hayward Steven 
Published: April 2020

Abstract
Background
Hinge-bending movements in proteins comprising two or more domains form a large class of functional movements. Hinge-bending regions demarcate protein domains and collectively control the domain movement. Consequently, the ability to recognise sequence features of hinge-bending regions and to be able to predict them from sequence alone would benefit various areas of protein research. For example, an understanding of how the sequence features of these regions relate to dynamic properties in multi-domain proteins would aid in the rational design of linkers in therapeutic fusion proteins.

Results
The DynDom database of protein domain movements comprises sequences annotated to indicate whether the amino acid residue is located within a hinge-bending region or within an intradomain region. Using statistical methods and Kernel Logistic Regression (KLR) models, this data was used to determine sequence features that favour or disfavour hinge-bending regions. This is a difficult classification problem as the number of negative cases (intradomain residues) is much larger than the number of positive cases (hinge residues). The statistical methods and the KLR models both show that cysteine has the lowest propensity for hinge-bending regions and proline has the highest, even though it is the most rigid amino acid. As hinge-bending regions have been previously shown to occur frequently at the terminal regions of the secondary structures, the propensity for proline at these regions is likely due to its tendency to break secondary structures. The KLR models also indicate that isoleucine may act as a domain-capping residue. We have found that a quadratic KLR model outperforms a linear KLR model and that improvement in performance occurs up to very long window lengths (eighty residues) indicating long-range correlations.

Conclusion
In contrast to the only other approach that focused solely on interdomain hinge-bending regions, the method provides a modest and statistically significant improvement over a random classifier. An explanation of the KLR results is that in the prediction of hinge-bending regions a long-range correlation is at play between a small number amino acids that either favour or disfavour hinge-bending regions. The resulting sequence-based prediction tool, HingeSeek, is available to run through a webserver at hingeseek.cmp.uea.ac.uk.
A benchmark study of ab initio gene prediction methods in diverse eukaryotic organisms
Authors: Scalzitti Nicolas , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie D. 
Published: April 2020

Abstract
Background
The draft genome assemblies produced by new sequencing technologies present important challenges for automatic gene prediction pipelines, leading to less accurate gene models. New benchmark methods are needed to evaluate the accuracy of gene prediction methods in the face of incomplete genome assemblies, low genome coverage and quality, complex gene structures, or a lack of suitable sequences for evidence-based annotations.

Results
We describe the construction of a new benchmark, called G3PO (benchmark for Gene and Protein Prediction PrOgrams), designed to represent many of the typical challenges faced by current genome annotation projects. The benchmark is based on a carefully validated and curated set of real eukaryotic genes from 147 phylogenetically disperse organisms, and a number of test sets are defined to evaluate the effects of different features, including genome sequence quality, gene structure complexity, protein length, etc. We used the benchmark to perform an independent comparative analysis of the most widely used ab initio gene prediction programs and identified the main strengths and weaknesses of the programs. More importantly, we highlight a number of features that could be exploited in order to improve the accuracy of current prediction tools.

Conclusions
The experiments showed that ab initio gene structure prediction is a very challenging task, which should be further investigated. We believe that the baseline results associated with the complex gene test sets in G3PO provide useful guidelines for future studies.
Genetic and phenotypic associations between root architecture, arbuscular mycorrhizal fungi colonisation and low phosphate tolerance in strawberry (Fragaria × ananassa)
Authors: Cockerton Helen Maria , Li Bo , Stavridou Eleftheria , Johnson Abigail , Karlström Amanda , Armitage Andrew Douglas , Martinez-Crucis Ana , Galiano-Arjona Lorena , Harrison Nicola , Barber-Pérez Nuria , Cobo-Medina Magdalena , Harrison Richard Jonathan 
Published: April 2020

Abstract
Background
Phosphate is an essential plant macronutrient required to achieve maximum crop yield. Roots are able to uptake soil phosphate from the immediate root area, thus creating a nutrient depletion zone. Many plants are able to exploit phosphate from beyond this root nutrient depletion zone through symbiotic association with Arbuscular Mycorrhizal Fungi (AMF). Here we characterise the relationship between root architecture, AMF association and low phosphate tolerance in strawberries. The contrasting root architecture in the parental strawberry cultivars ‘Redgauntlet’ and ‘Hapil’ was studied through a mapping population of 168 progeny. Low phosphate tolerance and AMF association was quantified for each genotype to allow assessment of the phenotypic and genotypic relationships between traits.

Results
A “phosphate scavenging” root phenotype where individuals exhibit a high proportion of surface lateral roots was associated with a reduction in root system size across genotypes. A genetic correlation between “root system size” traits was observed with a network of pleiotropic QTL found to represent five “root system size” traits. By contrast, average root diameter and the distribution of roots appeared to be under two discrete methods of genetic control. A total of 18 QTL were associated with plant traits, 4 of which were associated with solidity that explained 46% of the observed variation. Investigations into the relationship between AMF association and root architecture found that a higher root density was associated with greater AMF colonisation across genotypes. However, no phenotypic correlation or genotypic association was found between low phosphate tolerance and the propensity for AMF association, nor root architectural traits when plants are grown under optimal nutrient conditions.

Conclusions
Understanding the genetic relationships underpinning phosphate capture can inform the breeding of strawberry varieties with better nutrient use efficiency. Solid root systems were associated with greater AMF colonisation. However, low P-tolerance was not phenotypically or genotypically associated with root architecture traits in strawberry plants. Furthermore, a trade-off was observed between root system size and root architecture type, highlighting the energetic costs associated with a “phosphate scavenging” root architecture.
Ovarian metastases from ileum cancer in a patient with germline EPCAM gene deletion successfully treated with surgical resection and CAPOX chemotherapy: a case report
Authors: Iwata Narushi , Shikama Ayumi , Takao Wataru , Hosokawa Yoshihiko , Itagaki Hiroya , Tasaka Nobutaka , Akiyama Azusa , Ochi Hiroyuki , Minaguchi Takeo , Arita Miwa , Noguchi Emiko , Moriwaki Toshikazu , Satoh Toyomi 
Published: April 2020

Abstract
Background
Despite recent findings that epithelial cell adhesion molecule (EPCAM) deletions can cause Lynch syndrome (LS), its clinical characteristics are still unknown. We present the first case of ileum cancer in a patient with germline EPCAM gene deletion, which was discovered during ovarian tumor surgery.

Case presentation
A 59-year-old woman presented with a history of colon cancer occurring at 38 and 55 years old. Five of her siblings had a history of colon cancer, and an elder sister had confirmed LS. As imaging examination revealed an ovarian tumor, and we performed hysterectomy and bilateral salpingo-oophorectomy. Careful observation during surgery revealed a cherry-sized tumor in the ileum, prompting partial ileal resection. Pathological examination showed the ovarian tumor to be a metastasis of ileum cancer. Genetic testing with blood-relative information using multiplex ligation-dependent probe amplification showed EPCAM exons 8 and 9 deletions, confirming LS. The patient received adjuvant chemotherapy with CAPOX (capecitabine and oxaliplatin) and has remained disease-free for 24 months.

Conclusions
We were fortunate to identify ileum cancer that would have been difficult to find preoperatively through careful observation during ovarian tumor surgery and successfully treated the patient by using surgical resection and CAPOX chemotherapy. When treating patients with hereditary cancer syndromes including LS, we should keep all associated cancers in mind.