bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current understanding and future perspectives of the roles of sirtuins in the reprogramming and differentiation of pluripotent stem cells
Authors: Hsu Yi-Chao , Wu Yu-Ting , Tsai Chia-Ling , Wei Yau-Huei 
Published: March 2018

In mammalian cells, there are seven members of the sirtuin protein family (SIRT1–7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a–SIRT1–p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells. SIRT4 has no direct role in regulating reprogramming but may have the potential to prevent senescence of somatic cells and to facilitate the reprogramming of iPSCs. SIRT5 can deacetylate STAT3, which is an important transcription factor in regulating pluripotency and differentiation of stem cells. SIRT6 can enhance the reprogramming efficiency of iPSCs from aged skin fibroblasts through miR-766 and increase the expression levels of the reprogramming genes including Sox2, Oct4, and Nanog through acetylation of histone H3 lysine 56. SIRT7 plays a regulatory role in the process of mesenchymal-to-epithelial transition (MET), which has been suggested to be a crucial process in the generation of iPSCs from fibroblasts. In this review, we summarize recent findings of the roles of sirtuins in the metabolic reprogramming and differentiation of stem cells and discuss the bidirectional changes in the gene expression and activities of sirtuins in the commitment of differentiation of mesenchymal stem cells (MSCs) and reprogramming of somatic cells to iPSCs, respectively. Thus, understanding the molecular basis of the interplay between different sirtuins and mitochondrial function will provide new insights into the regulation of differentiation of stem cells and iPSCs formation, respectively, and may help design effective stem cell therapies for regenerative medicine.Impact statementThis is an extensive review of the recent advances in our understanding of the roles of some members of the sirtuins family, such as SIRT1, SIRT2, SIRT3, and SIRT6, in the regulation of intermediary metabolism during stem cell differentiation and in the reprogramming of somatic cells to form induced pluripotent stem cells (iPSCs). This article provides an updated integrated view on the mechanisms by which sirtuins-mediated posttranslational protein modifications regulate mitochondrial biogenesis, bioenergetics, and antioxidant defense in the maintenance and differentiation of stem cells and in iPSCs formation, respectively.
Spectrin and its interacting partners in nuclear structure and function
Authors: Lambert Muriel W 
Published: March 2018

Nonerythroid αII-spectrin is a structural protein whose roles in the nucleus have just begun to be explored. αII-spectrin is an important component of the nucleoskelelton and has both structural and non-structural functions. Its best known role is in repair of DNA ICLs both in genomic and telomeric DNA. αII-spectrin aids in the recruitment of repair proteins to sites of damage and a proposed mechanism of action is presented. It interacts with a number of different groups of proteins in the nucleus, indicating it has roles in additional cellular functions. αII-spectrin, in its structural role, associates/co-purifies with proteins important in maintaining the architecture and mechanical properties of the nucleus such as lamin, emerin, actin, protein 4.1, nuclear myosin, and SUN proteins. It is important for the resilience and elasticity of the nucleus. Thus, αII-spectrin’s role in cellular functions is complex due to its structural as well as non-structural roles and understanding the consequences of a loss or deficiency of αII-spectrin in the nucleus is a significant challenge. In the bone marrow failure disorder, Fanconi anemia, there is a deficiency in αII-spectrin and, among other characteristics, there is defective DNA repair, chromosome instability, and congenital abnormalities. One may speculate that a deficiency in αII-spectrin plays an important role not only in the DNA repair defect but also in the congenital anomalies observed in Fanconi anemia , particularly since αII-spectrin has been shown to be important in embryonic development in a mouse model. The dual roles of αII-spectrin in the nucleus in both structural and non-structural functions make this an extremely important protein which needs to be investigated further. Such investigations should help unravel the complexities of αII-spectrin’s interactions with other nuclear proteins and enhance our understanding of the pathogenesis of disorders, such as Fanconi anemia , in which there is a deficiency in αII-spectrin.Impact statementThe nucleoskeleton is critical for maintaining the architecture and functional integrity of the nucleus. Nonerythroid α-spectrin (αIISp) is an essential nucleoskeletal protein; however, its interactions with other structural and non-structural nuclear proteins and its functional importance in the nucleus have only begun to be explored. This review addresses these issues. It describes αIISp’s association with DNA repair proteins and at least one proposed mechanism of action for its role in DNA repair. Specific interactions of αIISp with other nucleoskeletal proteins as well as its important role in the biomechanical properties of the nucleus are reviewed. The consequences of loss of αIISp, in disorders such as Fanconi anemia, are examined, providing insights into the profound impact of this loss on critical processes known to be abnormal in FA, such as development, carcinogenesis, cancer progression and cellular functions dependent upon αIISp’s interactions with other nucleoskeletal proteins.
Racial and Socioeconomic Disparities After Carotid Procedures
Authors: Vogel Todd R. , Kruse Robin L. , Kim Ryan J. , Dombrovskiy Viktor Y. 
Published: March 2018

Background: Race has been associated with inferior outcomes after multiple procedures, but the association of socioeconomic status with procedures for cerebrovascular disease is not well established. Materials and Methods: Elective carotid artery stenting (CAS) and carotid endarterectomy (CEA) procedures were identified in the National Inpatient Sample, 2012 to 2014. Median household income was estimated from patient ZIP codes. Chi-square and multivariable logistic regression analysis evaluated outcomes, accounting for age, race, gender, comorbidities, procedure, income, insurance, and hospital characteristics. Results: We identified 234 825 carotid procedures (205 835 CEA and 28 990 CAS). Blacks and Hispanics were more likely to be among the lowest quartile income patients (LQIPs) compared to whites (53.5% and 38.7% vs 27.0%, respectively; P < .0002). Compared to highest income quartile patients, LQIP had lower rates of private insurance (16.3% vs 22.0%) and higher Medicaid use (4.7% vs 2.0%; all P < .0002). Lowest quartile income patients were more likely to receive CAS (odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.27-1.37), as were blacks and Hispanics (OR = 1.09, 95% CI: 1.02-1.26; OR = 1.31, 95% CI: 1.24-1.40, respectively). In multivariable regression, postoperative stroke was associated with LQIP, black race, and Hispanic ethnicity (OR = 1.16, 95% CI: 1.06-1.28; OR = 1.52, 95% CI: 1.33-1.73; OR = 1.43, 95% CI: 1.24-1.64, respectively). Subgroup analysis demonstrated that whites also had higher odds of stroke in the lower income quartile (OR = 1.2, 95% CI: 1.1-1.4). Mortality was associated with LQIP (OR = 1.6, 95% CI: 1.2-2.1), black race (OR = 1.8, 95% CI: 1.4-2.5), and CAS (OR = 1.3, 95% CI: 1.1-1.6). Length of stay in the lowest income quartile was longer than in patients with the highest income ( P < .0001). Conclusions: Race was associated with increased hospital mortality, postoperative stroke, and overall complications after carotid procedures. Lower income was significantly associated with increased stroke and mortality irrespective of race. Disparate utilization and outcomes for carotid procedures are multifactorial. Efforts to reduce disparities will need to focus on race and other socioeconomic factors.
The impact of relocation of chronic pain service from hospital setting to community centre on patient experience: a single-centre audit
Authors: Tsui Jonathan Jenkin , Davey Veronica , Colvin Lesley 
Published: March 2018

Background and aims: The Lothian Chronic Pain Service relocated from a university teaching hospital (Western General Hospital (WGH)) to a community centre (Leith Community Treatment Centre (LCTC)) in 2015. Transportation and geographical location were noted by staff to be potential challenges that could negatively impact on the patient experience. The objective of this study is to evaluate how relocating pain clinic from an urban-based hospital to a peripheral community centre on patient experience. Methods: An assessment and audit of the impact of the relocation on the Patient-Reported Experience Measure (PREM) of pain services was conducted. Using a nationally developed questionnaire, the patient-reported experience from LCTC was prospectively collected in 2016 and was compared to historical data obtained from WGH in 2014 by National Health Service (NHS) Scotland. All patients attending Lothian Chronic Pain Service clinics were deemed eligible for the audit. Patient demographics were compared between the two data sets. The impact of patient deprivation on patient experience was investigated using the Scottish Index of Multiple Deprivation (SIMD16). Results: Data from 111 patients from LCTC were compared to 206 patients from WGH. Percentage of patients rating care as ‘excellent’ was found to be significantly greater at LCTC than WGH (0.0049). However, overall patient rating of care from LCTC was not significantly different from WGH data and ratings were higher at LCTC. No correlation was found between patient deprivation and PREM. Conclusion: There is no clear evidence that PREM was negatively affected by the move from a university teaching hospital to a community setting. As this only reported experiences of patients who attended the service, further studies may be warranted to investigate the impact of patient nonattendance.
Quantifying performance metrics of cervical spine mobilization for improved education and clinical outcomes: Early experience with a novel wearable device
Authors: Kope Ryan , O’Brien Jordan , Sadi Jackie , Walton David M. , Ferreira Louis M 
Published: March 2018

Introduction Evaluation of manual skills training for spinal rehabilitation has been stagnant for 40 years. Observation and mimicry are coupled with feedback from “expert” observers to train and evaluate learners, relying on rater experience to discern speed and force. Spinal manipulation is a controlled act under the Regulated Health Professions Act (1991) as it is not without risk. The discordance between current methods for evaluating proficiency and the potential risks of inadequate application is a critical gap. Methods This work reports a novel wearable device that measures finger forces via microstrain bending of the physiotherapist’s nail. The device leaves the tactile finger pad unobstructed and does not interfere with treatment application. Five expert-level physiotherapists performed a standard postero-anteriorly directed spinal segmental mobilization treatment for 1 min at 1–1.5 Hz rhythm. Results The device successfully measured all treatment forces (0.2–27.3 N). Physiotherapists applied a maximum force rate of 0.03 ± 0.01 N/s with a rhythm of 1.76 ± 0.38 Hz. In 15 trials, there were no device failures. The device was easily applied and removed, and physiotherapists were able to walk about and interact normally with patients. Conclusions These results indicate that this technology can be integrated into a skills training program to provide quantitative feedback for objective assessments.
Role of Rotational Kinematics in Minimizing Elbow Varus Torques for Professional Versus High School Pitchers
Authors: Luera Micheal J. , Dowling Brittany , Magrini Mitchel A. , Muddle Tyler W.D. , Colquhoun Ryan J. , Jenkins Nathaniel D.M. 
Published: March 2018

Background: Elbow injury rates among baseball pitchers are rapidly rising. However, this increase has been most dramatic among high school (HS) pitchers. Purpose: To examine pitch velocity and the kinetic and kinematic characteristics of HS versus professional (PRO) pitchers to identify potential differences that may play a role in the increased risk of ulnar collateral ligament injury in youth pitchers. Study Design: Controlled laboratory study. Methods: A total of 37 HS (mean ± SD: age, 16 ± 1 years) and 40 PRO (age, 21 ± 2 years) baseball pitchers completed maximal-effort baseball pitches during a single testing session, from which pitch velocity (PV), absolute and normalized elbow varus torque (EVTA and EVTN, respectively) during arm cocking and at maximum shoulder external rotation (MER), and 8 other elbow and shoulder torques or forces and rotational kinematics of the pelvis and trunk were analyzed, recorded, and compared. Results: PV was greater in PRO than HS athletes; EVTA was greater in PRO than HS athletes during arm cocking and at MER; but EVTN was similar during arm cocking and greater in HS than PRO athletes at MER. In PRO athletes, PV was not related to EVTA during arm cocking or MER ( r = 0.01-0.05). Furthermore, in PRO athletes, EVTA during arm cocking and at MER were inversely related to upper trunk rotation at hand separation and foot contact and to pelvis rotation at elbow extension ( r = –0.30 to –0.33). In contrast, in HS athletes, PV was strongly related to EVTA during arm cocking and MER ( r = 0.76-0.77). Furthermore, in HS athletes, PV and EVTA during arm cocking and at MER were moderately or strongly related to the other elbow and shoulder torques and forces ( r = 0.424-0.991), and EVTA was not related to upper trunk rotation or pelvis rotation throughout the throwing motion ( r = –0.16 to 0.15). Conclusion: The kinetic and rotational kinematic differences observed between PRO and HS pitchers in this study may help explain the greater performance of PRO pitchers while allowing them to minimize EVT during pitching. HS pitchers, however, do not appear to be as capable of utilizing the forces generated by rotation of their trunk and pelvis to aid in pitching, and those who throw the hardest generate the greatest forces at the shoulder and elbow. As a result, they experience higher EVTs relative to their body size, which may place them at an increased risk of injury. Clinical Relevance: HS pitchers throw harder primarily by generating larger forces in the arm and shoulder. Thus, owing to the relative physical immaturity of HS versus PRO pitchers, these factors may place them at an increased risk of injury. Coaches may first wish to focus on improving the rotational kinematics of HS pitchers rather than first focusing on achieving greater pitch velocities.
Dynamics of chromatin marks and the role of JMJD3 during pancreatic endocrine cell fate commitment
Authors: Yu Xin-Xin , Qiu Wei-Lin , Yang Liu , Li Lin-Chen , Zhang Yu-Wei , Xu Cheng-Ran 
Published: March 2018

ABSTRACT
Pancreatic endocrine lineages are derived from pancreatic progenitors that undergo a cell fate transition requiring a switch from low to high Ngn3 expression. However, the underlying chromatin regulatory mechanisms are unclear. Here, we performed epigenomic analysis of gene regulatory loci featuring histone marks in cells with low or high level of Ngn3 expression. In combination with transcriptomic analysis, we discovered that in Ngn3-high cells, the removal of H3K27me3 was associated with the activation of key transcription factors and the establishment of primed and active enhancers. Deletion of Jmjd3, a histone demethylase for H3K27me3, at the pancreatic progenitor stage impaired the efficiency of endocrine cell fate transition and thereafter islet formation. Curiously, single-cell RNA-seq revealed that the transcriptome and developmental pathway of Ngn3-high cells were not affected by the deletion of Jmjd3. Our study indicates sequential chromatin events and identifies a crucial role for Jmjd3 in regulating the efficiency of the transition from Ngn3-low to Ngn3-high cells.
Adolescent girls’ attitudes toward female genital mutilation: a study in seven African countries
Authors: Dalal Koustuv , Kalmatayeva Zhanna , Mandal Sourav , Ussatayeva Gainel , Lee Ming Shinn , Biswas Animesh 
Published: March 2018

Background: The study’s aim is to examine adolescent girls’ attitudes toward the continuation or discontinuation of female genital mutilation (FGM) in association with their demographics in seven different countries in Africa. Methods: Data from the women’s survey of the Demographic and Health Surveys (DHS) conducted by the respective ministries (of Health and Family Welfare) in Egypt, Guinea, Kenya, Mali, Niger, Senegal and Sierra Leone were used. Adolescent girls (15–19 years) were included in the current analysis: Egypt (N=636), Guinea (N=1994), Kenya (N= 1767), Mali (N=2791), Niger (N=1835), Senegal (N=3604), Sierra Leone (N=1237). Results: Prevalence of supporting the continuation of FGM among adolescent girls was in Egypt 58%, Guinea 63%, Kenya 16%, Mali 72%, Niger 3%, Senegal 23%, and Sierra Leone 52%. Being Muslim and having low economic status were significantly associated with supporting the continuation of FGM in five of the participating countries. Girls having no education or only primary education in Guinea, Kenya, Mali and Sierra Leone exhibited a higher likelihood of supporting FGM than girls with secondary or higher education. In Egypt, Niger and Senegal there was no association between education and supporting FGM. The girls who stated that they had no exposure to media showed the higher likelihood of supporting FGM in Guinea, Kenya, and Senegal than those with exposure to media. Conclusions: The current study argues that increasing media coverage and education, and reducing poverty are of importance for shifting adolescent girls’ attitudes in favor of discontinuation of FGM.
Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial
Authors: Donovan Joseph , Phu Nguyen Hoan , Mai Nguyen Thi Hoang , Dung Le Tien , Imran Darma , Burhan Erlina , Ngoc Lam Hong Bao , Bang Nguyen Duc , Giang Do Chau , Ha Dang Thi Minh , Day Jeremy , Thao Le Thi Phuong , Thuong Nguyen TT , Vien Nguyen Nang , Geskus Ronald B. , Wolbers Marcel , Hamers Raph L , van Crevel Reinout , Nursaya Mugi , Maharani Kartika , Hien Tran Tinh , Baird Kevin , Lan Nguyen Huu , Kestelyn Evelyne , Chau Nguyen Van Vinh , Thwaites Guy E. 
Published: March 2018

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.
Protest und Demokratisierung in Myanmar: Erste Erkenntnisse aus dem „Myanmar Protest Event Dataset“
Authors: Buschmann Andy 
Published: March 2018

Abstract
Myanmar has been perceived to be in a sociopolitical and economic transition since the semi-civilian government under President Thein Sein took office in 2011. Amongst other things, for a representative democracy to function, citizens have to have the freedom to express their opinions and deliberate them with fellow citizens. This requires the secure granting of fundamental civil liberties, as prescribed in the freedom of expression, association, and assembly. Hence, once in the process of democratization, a formerly authoritarian state has to make significant improvements in the granting and protection of these rights too. To empirically test whether Myanmar has made such improvements since 2011 is the goal of a greater research project I am working on. This research note introduces the project and summarizes first findings. By combining knowledge on legal reforms and protest data from the Myanmar Protest Event Dataset, it is suggested that, in Myanmar, the de jure exercisability and de facto exercise of fundamental civil liberties have significantly improved from 2011 to 2015. Informal methods of suppressing the right to protest, such as arbitrary violence, have increasingly descended while methods that are formally in accordance with the rule of law but still lack compliance with international human rights standards have ascended.
How similar are Heimskringla and Egils saga? An application of Burrows’ delta to Icelandic texts
Authors: Þorgeirsson Haukur 
Published: March 2018

Abstract
Recent methodological and technological developments greatly facilitate the use of stylometry for authorship attribution. Burrows’ delta method, proposed in 2002, has been shown to yield good results for a variety of corpora in different languages. The present article demonstrates that this method is highly effective in analysing 19th century Icelandic fiction. The method is then applied to the classical question of the stylistic affinity between two 13th century texts: Heimskringla and Egils saga. Heimskringla proves to be more similar to Egils saga than it is to a variety of contemporary texts, including other kings’ sagas. This supports the theory that the two texts have the same author.