bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key transcription factors in endometrial cancer by systems bioinformatics analysis
Authors: Song Yong , Chen Qiu‐Tong , He Qi‐Qiang 
Published: May 2019

AbstractEndometrial cancer (EC) is one of the most common malignant diseases worldwide. Although many studies have been performed on EC, a systems analysis between transcription factors (TFs) and EC relationship remains poorly characterized. Here, we present a systems bioinformatics analysis of TFs in EC patient samples to identify key TFs in EC. First, dysregulated and survival‐related TFs were identified in EC using data from The Cancer Genome Atlas database and Gene Expression Omnibus. Second, we investigated the mechanisms of dysregulated TFs and tested whether their expression is correlated with prognosis of EC. Finally, we addressed new perspectives in EC biomarker research, including comprehensive knowledge of previously suggested candidate biomarkers in conjunction with novel mass spectrometry‐based proteomic technologies with enhanced sensitivity and specificity not yet applied to EC studies, enabling a directed clinical perspective of the study design. Our study identified three promising TFs, E2F1, HMGA1, and PGR, which closely correlate with EC. Although treatments targeting TFs are not always efficient, these TFs may be useful as biomarkers for the diagnosis and prognosis of EC. Furthermore, we found that these dysregulated TFs and their target genes are primarily involved in the cell cycle and may promote endometrial carcinoma occurrence and development. Using integrated bioinformatic analysis, we identified candidate genes and pathways in EC, which could improve our understanding of the etiology and underlying molecular events of EC. Furthermore, these candidate genes and pathways could be therapeutic targets for EC.
The association between three AXIN2 variants and cancer risk
Authors: Dai Feng , Zhu Li‐Jie , Zhang Wei , Mi Yuan‐Yuan , Sun He‐Yun , Zhang Li‐Feng , Yue Chuang , Wu Xing‐Yu , Zuo Li , Bai Yu 
Published: May 2019

AbstractPlenty of epidemiological studies have assessed the effects of AXIN2 polymorphisms on the risk of developing cancer, but the available results were somewhat inconclusive. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the relationship between three AXIN2 variants (rs2240308 C/T, rs1133683 C/T, and rs4791171 A/G) and overall cancer susceptibility. In silico tools were undertaken to investigate the correlation of AXIN2 expression with cancer risk and survival time. Furthermore, we explored the serum expression of AXIN2 by enzyme‐linked immunosorbent assay. A total of 4167 cancer patients and 3515 control subjects were evaluated. The overall results demonstrated that there was no major association of these polymorphisms on cancer risk. However, stratified analysis by cancer type showed evidence that rs2240308 C/T polymorphism had a lower risk in lung cancer (OR, 0.76; 95% CI, 0.63‐0.92; Pheterogeneity = 0.865) and prostate cancer (OR, 0.54; 95% CI, 0.35‐0.84; Pheterogeneity = 0.088) by heterozygote comparison. Similar results were indicated in Asian descendants and population‐based studies. In silico analysis showed evidence that AXIN2 expressions in lung cancer and prostate cancer were lower than that in normal counterpart. High expression of AXIN2 may have longer overall survival time than low expression group for lung cancer participants. In addition, individuals who were CC/TC carriers had a higher serum expression level than TT carriers. In conclusion, this pooled analysis suggested that AXIN2 rs2240308 C/T variant may decrease both lung and prostate cancer susceptibility, particularly in Asian descendants and population‐based studies. Future large scale and well‐designed research are required to validate these effects in more detail.
From red vegetables to sexuality: Resymbolizing the meaning of concrete thought in eating disorders
Authors: Pearlman Barbara 
Published: May 2019

AbstractThis paper introduces and describes the theory and practice of a novel treatment approach to eating disorders—internal language enhancement therapy (ILET)—illustrated with a case study. This treatment approach is informed by the neurobiology of emotional processing integrated with elements of psychoanalytic theory and practice, early maternal preoccupation, development of the self, early right hemisphere language development, and techniques from cognitive behavioral therapy. ILET is based on the Discontinuous Model of Neural Emotional Processing, which means that emotions are processed in the brain either symbolically or concretely. The aim of ILET is to open up and reinforce the underused brain pathway to the symbolic functions by forensically working back to and accurately identifying the emotional material that triggers the concrete state. When the emotional trigger is identified it is explored using symbolic and metaphoric language that reconnects the patient to the symbolic state. ILET posits that eating disorders only appear in the concrete state.
The role of therapist MI skill and client change talk class membership predicting dual alcohol and sex risk outcomes
Authors: Janssen Tim , Magill Molly , Mastroleo Nadine R. , Laws M. Barton , Howe Chanelle J. , Walthers Justin W. , Monti Peter M. , Kahler Christopher W. 
Published: May 2019

AbstractObjectiveWe investigated the technical model of motivational interviewing (MI) in a dual‐outcome intervention (i.e., alcohol, sexual risk; N = 164; 57% female).MethodWe identified latent classes of client change statements, based on the proportion of change talk (CT) over the session. We then examined whether outcomes were related to CT class, and whether the relations between MI skill and outcomes varied by CT class.ResultsWe found three classes of alcohol‐CT and two classes of sexual risk‐CT. While CT class membership did not predict outcomes directly, greater therapist MI‐consistent skill was associated with fewer heavy drinking days in the increasing alcohol‐CT class. For sexual risk outcomes, therapist MI‐consistent skill was associated with reduced odds of condomless sex for the low sexual risk‐CT class.ConclusionsThe relation of therapist MI consistency to outcomes appears to be a function of client CT during the session.
Overview of established and emerging immunohistochemical biomarkers and their role in correlative studies in MRI
Authors: Alvi Emaan , Gupta Rajarsi , Borok Raphael Z. , Escobar‐Hoyos Luisa , Shroyer Kenneth R. 
Published: May 2019

Clinical practice in radiology and pathology requires professional expertise and many years of training to visually evaluate and interpret abnormal phenotypic features in medical images and tissue sections to generate diagnoses that guide patient management and treatment. Recent advances in digital image analysis methods and machine learning have led to significant interest in extracting additional information from medical and digital whole‐slide images in radiology and pathology, respectively. This has led to significant interest and research in radiomics and pathomics to correlate phenotypic features of disease with image analytics in order to identify image‐based biomarkers. The expanding role of big data in radiology and pathology parallels the development and role of immunohistochemistry (IHC) in the daily practice of pathology. IHC methods were initially developed to provide additional information to help classify tumors and then transformed into an indispensable tool to guide treatment in many types of cancer. IHC markers are used in daily practice to identify specific types of cells and highlight their distributions in tissues in order to distinguish benign from neoplastic cells, determine tumor origin, subclassify neoplasms, and support and confirm diagnoses. In this regard, radiomics, pathomics, and IHC methods are very similar since they enable the extraction of image‐based features to characterize various properties of diseases. Due to the dramatic advancements in recent radiomics research, we provide a brief overview of the role of established and emerging IHC biomarkers in various tumor types that have been correlated with radiologic biomarkers to improve diagnostic accuracy, predict prognosis, guide patient management, and select treatment strategies.Level of Evidence: 5Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2020;51:341–354.
Cerebral circulation time derived from fMRI signals in large blood vessels
Authors: Yao Jinxia (Fiona) , Wang James H. , Yang Ho‐Ching (Shawn) , Liang Zhenhu , Cohen‐Gadol Aaron A. , Rayz Vitaliy L. , Tong Yunjie 
Published: May 2019

BackgroundThe systemic low‐frequency oscillation (sLFO) functional (f)MRI signals extracted from the internal carotid artery (ICA) and the superior sagittal sinus (SSS) are found to have valuable physiological information.Purpose1) To further develop and validate a method utilizing these signals to measure the delay times from the ICAs and the SSS. 2) To establish the delay time as an effective perfusion biomarker that associates with cerebral circulation time (CCT). 3) To explore within subject variations, and the effects of gender and age on the delay times.Study TypeProspective.SubjectsIn all, 100 healthy adults (Human Connectome Project [HCP], age range 22–36 years, 54 females and 46 males), 56 healthy children (Adolescent Brain Cognitive Development project) were included.Field Strength/SequenceEcho planar imaging (EPI) sequence at 3T.AssessmentThe sLFO fMRI signals from the ICAs and the SSSs were extracted from the resting state fMRI data. The maximum cross‐correlation coefficients and their corresponding delay times were calculated. The gender and age differences of delay times were assessed statistically.Statistical Tests
T‐tests were conducted to measure the gender differences. The Kruskal–Wallis test was used to detect age differences.ResultsConsistent and robust results were found from 80% of the 400 HCP scans included. Negative correlations (–0.67) between the ICA and the SSS signals were found with the ICA signal leading the SSS signal by ∼5 sec. Within subject variation was 2.23 sec at the 5% significance level. The delay times were not significantly different between genders (P = 0.9846, P = 0.2288 for the left and right ICA, respectively). Significantly shorter delay times (4.3 sec) were found in the children than in the adults (P < 0.01).Data ConclusionWe have shown that meaningful perfusion information (ie, CCT) can be derived from the sLFO fMRI signals of the large blood vessels.Level of Evidence: 1Technical Efficacy Stage: 1J. Magn. Reson. Imaging 2019;50:1504–1513.
Changes in extreme temperature and precipitation indices: Using an innovative daily homogenized database in Israel
Authors: Yosef Yizhak , Aguilar Enric , Alpert Pinhas 
Published: May 2019

AbstractThis study examines the 1950–2017 temporal changes in climate extremes in Israel, which is located in the East Mediterranean (EM), a region which suffers from a scarcity of long and reliable datasets. It is well known that most long‐term records are affected by artificial shifts most commonly caused by station relocation, instrumental modification and local environmental changes. Therefore, for the first time, a thorough homogenization (detection and correction) routine was developed and implemented in the long‐term records. Consequently, a new daily adjusted dataset has been generated, including 34 temperature stations and 60 precipitation stations. Based on this comprehensive dataset, 38 extreme indices recommended by the Expert Team on Climate Change Detection and the Expert Team on Sector‐specific Climate Indices have been calculated. These indices will help various sectors to plan properly mitigation actions and adaptation for climate change, in addition to facilitating future studies for the EM. The results showed highly significant changes in temperature extremes associated with warming, especially for those indices derived from the daily minimum temperature (TN, 1950–2017), whereas the maximum temperature (TX) exhibited a similar increasing magnitude of the TN (~0.55°C/decade) in the last 30 years. The warming trends, which are non‐monotonic, seem to have been particularly strong since the early 1990s. The coastal area is characterized by higher heat stress during the nighttime, while mountains exhibit a strong tendency towards increasing temperatures during the noon hours. A reduction in the total precipitation amount and in the number of wet days with a tendency towards more intense wet days was found. Although all the regional trends of the precipitation indices were not statistically significant (p≤ .05), they showed a fine spatial coherence.
Patient‐Specific Functional Analysis: The Key to the Next Revolution Towards the Treatment of Hip and Knee Osteoarthritis
Authors: Astephen Wilson Janie L. , Lamontagne Mario , Wilson David R. , Beaulé Paul E. , Mwale Fackson , Yee Albert 
Published: May 2019

ABSTRACTLower extremity joint arthroplasty surgery remains one of the most successful interventions in orthopaedics. While improvements in patient mobility and physical functioning following surgery are well‐documented, there remains significant post‐operative functional deficits in many patients. This highlights a need and an opportunity towards improving functional and patient‐reported outcomes of arthroplasty surgery. This review summarizes key opportunities arising from the recent 2018 Orthopaedic Research Society Meeting in New Orleans, USA. In this review, the Canadian Orthopaedic Research Society (i.e., CORS) highlights key research advances, case examples, scientific messages, and personalized medical care approaches toward improving physical functioning in our knee and hip joint arthroplasty patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1754–1759, 2019
Effects of Surgical Angiogenesis on Segmental Bone Reconstruction With Cryopreserved Massive‐Structural Allografts in a Porcine Tibia Model
Authors: Visser Noortje J. , Rezaie Elisa S. , Friedrich Patricia F. , Kotsougiani Dimitra , Shin Alexander Y. , Bishop Allen T. 
Published: May 2019

ABSTRACTCryopreserved bone allografts (CBA) used to reconstruct segmental bone defects provide immediate structural stability, but are vulnerable to infection, non‐union and late stress fracture as the majority of the allograft remains largely avascular. We sought to improve the bone vascularity and bone formation of CBAs by surgical angiogenesis with an implanted arteriovenous (AV) bundle, using a porcine tibial defect model. Cryopreserved tibial bone allografts were transplanted in swine leukocyte antigen (SLA) mismatched Yucatan minipigs to reconstruct a 3.5 cm segmental tibial defect. A cranial tibial AV‐bundle was placed within its intramedullary canal to induce angiogenesis. The AV bundle was patent in eight pigs and ligated in a control group of eight pigs. At 20 weeks neo‐angiogenesis was evaluated by micro‐angiography. Bone formation was measured by quantitative histomorphometry and micro‐computed tomography. Seven of eight AV‐bundles in the revascularized group were patent. One had thrombosed due to allograft displacement. Total vascular volume was higher in the revascularized allografts compared to the ligated group (p = 0.015). Revascularized allografts had increased levels of bone formation on the allograft endosteal surface compared to the ligated control group (p = 0.05). Surgical angiogenesis of porcine tibial CBAs by intramedullary implantation of an AV‐bundle creates an enhanced autogenous neoangiogenic circulation and accelerates active bone formation on allograft endosteal surfaces. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1698–1708, 2019
Urinary Bladder Matrix Does Not Improve Tenogenesis in an In Vitro Equine Model
Authors: Khatibzadeh Sarah M. , Menarim Bruno C. , Nichols Anne E. C. , Werre Stephen R. , Dahlgren Linda A. 
Published: May 2019

ABSTRACTExtracellular matrix (ECM) is responsible for tendon strength and elasticity. Healed tendon ECM lacks structural integrity, leading to reinjury. Porcine urinary bladder matrix (UBM) provides a scaffold and source of bioactive proteins to improve tissue healing, but has received limited attention for treating tendon injuries. The objective of this study was to evaluate the ability of UBM to induce matrix organization and tenogenesis using a novel in vitro model. We hypothesized that addition of UBM to tendon ECM hydrogels would improve matrix organization and cell differentiation. Hydrogels seeded with bone marrow cells (n = 6 adult horses) were cast using rat tail tendon ECM ± UBM, fixed under static tension and harvested at 7 and 21 days for construct contraction, cell viability, histology, biochemistry, and gene expression. By day 7, UBM constructs contracted significantly from baseline, whereas control constructs did not. Both control and UBM constructs contracted significantly by day 21. In both groups, cells remained viable over time and changed from round and randomly oriented to elongated along lines of tension with visible compaction of the ECM. There were no differences over time or between treatments for nuclear aspect ratio, DNA, or glycosaminoglycan content. Decorin, matrix metalloproteinase 13, and scleraxis expression increased significantly over time, but not in response to UBM treatment. Mohawk expression was constant over time. Cartilage oligomeric matrix protein expression decreased over time in both groups. Using a novel ECM hydrogel model, substantial matrix organization and cell differentiation occurred; however, the addition of UBM failed to induce greater matrix organization than tendon ECM alone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1848–1859, 2019
Scaffold‐Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair
Authors: Kelly Domhnall C. , Raftery Rosanne M. , Curtin Caroline M. , O’Driscoll Caitriona M. , O’Brien Fergal J. 
Published: May 2019

ABSTRACTRecent advances in tissue engineering have made progress toward the development of biomaterials capable of the delivery of growth factors, such as bone morphogenetic proteins, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localized area is a significant challenge and the associated high costs and side effects of uncontrolled delivery have proven increasingly problematic in clinical orthopedics. Gene therapy may be a valuable tool to avoid the limitations of local delivery of growth factors. Following a series of setbacks in the 1990s, the field of gene therapy is now seeing improvements in safety and efficacy resulting in substantial clinical progress and a resurgence in confidence. Biomaterial scaffold‐mediated gene therapy provides a template for cell infiltration and tissue formation while promoting transfection of cells to engineer therapeutic proteins in a sustained but ultimately transient fashion. Additionally, scaffold‐mediated delivery of RNA‐based therapeutics can silence specific genes associated with orthopedic pathological states. This review will provide an overview of the current state‐of‐the‐art in the field of gene‐activated scaffolds and their use within orthopedic tissue engineering applications. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1671–1680, 2019
Platelet‐Rich Plasma (PRP) From Older Males With Knee Osteoarthritis Depresses Chondrocyte Metabolism and Upregulates Inflammation
Authors: O’Donnell Christian , Migliore Eleonora , Grandi Fiorella Carla , Koltsov Jayme , Lingampalli Nithya , Cisar Cecilia , Indelli Pier F. , Sebastiano Vittorio , Robinson William H. , Bhutani Nidhi , Chu Constance R. 
Published: May 2019

ABSTRACTThere is intense clinical interest in the potential effects of platelet‐rich plasma (PRP) for the treatment of osteoarthritis (OA). This study tested the hypotheses that (i) “lower” levels of the inflammatory mediators (IMs), interleukin‐1β, and tumor necrosis factor α (TNF‐α) and (ii) “higher” levels of the growth factors (GFs), insulin‐like growth factor 1, and transforming growth factor β1 within leukocyte‐poor PRP correlate with more favorable chondrocyte and macrophage responses in vitro. Samples were collected from 10 “healthy” young male (23–33 years old) human subjects (H‐PRP) and nine older (62–85 years old) male patients with severe knee OA (OA‐PRP). The samples were separated into groups of “high” or “low” levels of IM and GF based on multiplex cytokine and enzyme‐linked immunosorbent assay data. Three‐dimensional (3D) alginate bead chondrocyte cultures and monocyte‐derived macrophage cultures were treated with 10% PRP from donors in different groups. Gene expression was analyzed by quantitative polymerase chain reaction. Contrary to our hypotheses, the effect of PRP on chondrocytes and macrophages was mainly influenced by the age and disease status of the PRP donor as opposed to the IM or GF groupings. While H‐PRP showed similar effects on expression of chondrogenic markers (Col2a1 and Sox9) as the negative control group (p > 0.05), OA‐PRP decreased chondrocyte expression of Col2a1 and Sox‐9 messenger RNA by 40% and 30%, respectively (Col2a1, p = 0.015; Sox9, p = 0.037). OA‐PRP also upregulated TNF‐α and matrix metallopeptidase 9 (p < 0.001) gene expression in macrophages while H‐PRP did not. This data suggests that PRP from older individuals with OA contain factors that may suppress chondrocyte matrix synthesis and promote macrophage inflammation in vitro. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1760–1770, 2019
Associations Between Intervertebral Disc Degeneration Grading Schemes and Measures of Disc Function
Authors: Zehra Uruj , Noel‐Barker Natasha , Marshall John , Adams Michael A. , Dolan Patricia 
Published: May 2019

ABSTRACTDisc degeneration is a major cause of spinal dysfunction and pain, but grading schemes concentrate on tissue changes rather than altered function. The aim of this study was to compare disc degeneration grading systems with each other, and with biomechanical measures of disc function. Sixty‐six motion segments (T8–9 to L5–S1) were dissected from cadavers aged 48–98 years. Disc function was assessed by measuring nucleus pressure (IDP) and maximum stresses in the annulus under 1 kN of compression. Detailed “scores” of disc degeneration were based on independent radiographic, macroscopic, and microscopic evaluations. For each evaluation, scores were used to assign a degeneration “grade” (I–IV), and functional measures were then correlated with degeneration scores and grades. Results showed that all measures were reliable (intraclass correlation coefficients: 0.82–0.99). Macroscopic and microscopic assessments were highly correlated with each other (r: 0.57–0.89, p < 0.001) but only weakly correlated with radiographic features. The overall macroscopic and microscopic scores of degeneration increased significantly with age and at lower spinal levels, although the influence of age was less marked in the case of the microscopic scores. IDP decreased with age and at lower spinal levels, but annulus stresses were more variable. Importantly, IDP and annulus stresses decreased consistently with all measures of disc degeneration, and these associations remained strong after controlling for age, gender, and spinal level. We conclude that radiographic and tissue‐based assessments of disc degeneration are consistent with each other, and are more closely related to mechanical (dys)function than to age or spinal level. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1946–1955, 2019