bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variants related to physical activity or sedentary behaviour: a systematic review
Authors: Aasdahl Lene , Nilsen Tom Ivar Lund , Meisingset Ingebrigt , Nordstoga Anne Lovise , Evensen Kari Anne I. , Paulsen Julie , Mork Paul Jarle , Skarpsno Eivind Schjelderup 
Published: January 2021

AbstractBackgroundResearch shows that part of the variation in physical activity and sedentary behaviour may be explained by genetic factors. Identifying genetic variants associated with physical activity and sedentary behaviour can improve causal inference in physical activity research. The aim of this systematic review was to provide an updated overview of the evidence of genetic variants associated with physical activity or sedentary behaviour.MethodsWe performed systematic literature searches in PubMed and Embase for studies published from 1990 to April 2020 using keywords relating to “physical activity”, “exercise”, “sedentariness” and “genetics”. Physical activity phenotypes were either based on self-report (e.g., questionnaires, diaries) or objective measures (e.g., accelerometry, pedometer). We considered original studies aiming to i) identify new genetic variants associated with physical activity or sedentary behaviour (i.e., genome wide association studies [GWAS]), or ii) assess the association between known genetic variants and physical activity or sedentary behaviour (i.e., candidate gene studies). Study selection, data extraction, and critical appraisal were carried out by independent researchers, and risk of bias and methodological quality was assessed for all included studies.ResultsFifty-four out of 5420 identified records met the inclusion criteria. Six of the included studies were GWAS, whereas 48 used a candidate gene approach. Only one GWAS and three candidate gene studies were considered high-quality. The six GWAS discovered up to 10 single nucleotide polymorphisms (SNPs) associated with physical activity or sedentariness that reached genome-wide significance. In total, the candidate gene studies reported 30 different genes that were associated (p < 0.05) with physical activity or sedentary behaviour. SNPs in or close to nine candidate genes were associated with physical activity or sedentary behaviour in more than one study.ConclusionGWAS have reported up to 10 loci associated with physical activity or sedentary behaviour. Candidate gene studies have pointed to some interesting genetic variants, but few have been replicated. Our review highlights the need for high-quality GWAS in large population-based samples, and with objectively assessed phenotypes, in order to establish robust genetic instruments for physical activity and sedentary behaviour. Furthermore, consistent replications in GWAS are needed to improve credibility of genetic variants.Trial registrationProsperoCRD42019119456.
Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
Authors: Recasens Mireia , Almolda Beatriz , Pérez-Clausell Jeús , Campbell Iain L. , González Berta , Castellano Bernardo 
Published: January 2021

AbstractBackgroundWhen the homeostasis of the central nervous system (CNS) is altered, microglial cells become activated displaying a wide range of phenotypes that depend on the specific site, the nature of the activator, and particularly the microenvironment generated by the lesion. Cytokines are important signals involved in the modulation of the molecular microenvironment and hence play a pivotal role in orchestrating microglial activation. Among them, interleukin-6 (IL-6) is a pleiotropic cytokine described in a wide range of pathological conditions as a potent inducer and modulator of microglial activation, but with contradictory results regarding its detrimental or beneficial functions. The objective of the present study was to evaluate the effects of chronic IL-6 production on the immune response associated with CNS-axonal anterograde degeneration.MethodsThe perforant pathway transection (PPT) paradigm was used in transgenic mice with astrocyte-targeted IL6-production (GFAP-IL6Tg). At 2, 3, 7, 14, and 21 days post-lesion, the hippocampal areas were processed for immunohistochemistry, flow cytometry, and protein microarray.ResultsAn increase in the microglia/macrophage density was observed in GFAP-IL6Tg animals in non-lesion conditions and at later time-points after PPT, associated with higher microglial proliferation and a major monocyte/macrophage cell infiltration. Besides, in homeostasis, GFAP-IL6Tg showed an environment usually linked with an innate immune response, with more perivascular CD11b+/CD45high/MHCII+/CD86+macrophages, higher T cell infiltration, and higher IL-10, IL-13, IL-17, and IL-6 production. After PPT, WT animals show a change in microglia phenotype expressing MHCII and co-stimulatory molecules, whereas transgenic mice lack this shift. This lack of response in the GFAP-IL6Tg was associated with lower axonal sprouting.ConclusionsChronic exposure to IL-6 induces a desensitized phenotype of the microglia.
Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration
Authors: Lee Keng Siang , Lin Shuxiao , Copland David A. , Dick Andrew D. , Liu Jian 
Published: January 2021

AbstractAge-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Besides the association of innate immune pathway genes with AMD susceptibility, environmental stress- and cellular senescence-induced alterations in pathways such as metabolic functions and inflammatory responses are also implicated in the pathophysiology of AMD. Cellular senescence is an adaptive cell process in response to noxious stimuli in both mitotic and postmitotic cells, activated by tumor suppressor proteins and prosecuted via an inflammatory secretome. In addition to physiological roles in embryogenesis and tissue regeneration, cellular senescence is augmented with age and contributes to a variety of age-related chronic conditions. Accumulation of senescent cells accompanied by an impairment in the immune-mediated elimination mechanisms results in increased frequency of senescent cells, termed “chronic” senescence. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD.
STeroids Against Radiculopathy (STAR) trial: a statistical analysis plan
Authors: ter Meulen Bastiaan C. , van Dongen Johanna M. , van der Vegt Marinus , Weinstein Henry C. , Ostelo Raymond W. J. G. 
Published: January 2021

AbstractBackgroundTransforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (< 8 weeks).MethodsThe STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (< 8 weeks): (1) TESI combined with levobupivacaine added to oral pain medication (intervention group 1) versus oral pain medication alone (control group), (2) intervention group 1 versus transforaminal epidural injection with levobupivacaine and saline solution added to oral pain medication (intervention group 2), and (3) intervention group 2 versus control group. Co-primary outcomes were physical functioning (Roland Morris Disability Questionnaire), pain intensity (10-point numerical rating scale), and global perceived recovery (7-point Likert scale, dichotomized into ‘recovered’ and ‘not recovered’). For all three comparisons, we defined the following minimal clinically relevant between-group differences: two points for pain intensity (range 0–10), four points for physical functioning (range 0–24) and a 20% difference in recovery rate. Secondary outcomes are health-related quality of life (EQ-5D-5L) and patient satisfaction (7-point Likert scale) and surgery rate. We also collected resource use data to perform an economic evaluation. Analyses will be conducted by intention-to-treat withp < 0.05 (two-tailed) for all three comparisons. Effects will be estimated using mixed models by maximum likelihood. For each comparison, mean differences, or difference in proportions, between groups will be tested per time point and an overall mean difference, or difference in proportions, between groups during the complete duration of follow-up (6 months) will be estimated. In the economic evaluation, Multivariate Imputation by Chained Equations will be used to handle missing data. Cost and effect differences will be estimated using seemingly unrelated regression, and uncertainty will be estimated using bootstrapping techniques.DiscussionThis statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (< 8 weeks).Trial registrationDutch National trial registerNTR4457(6 March 2014)
The pterional approach for the surgical resection of an orbital cholesteatoma: a case report
Authors: Guadarrama-Ortiz Parménides , Choreño-Parra José Alberto , Pacheco-Sánchez Francisco Javier , Rodríguez-Nava Alberto Iván , García-Quintero Gabriela , Rodríguez-Muñoz Patricia Emilia , Sánchez-Garibay Carlos , Ángeles-Castellanos Manuel 
Published: January 2021

Abstract
Background
Cholesteatomas are benign tumors mainly composed of cholesterol crystals that rarely arise within the orbit. However, orbital cholesteatomas require a complete surgical resection due to their recidivating potential. Transcranial approaches offering a broad surgical exposure of the orbital cavity have been scarcely used for the management of these tumors. Here, we provide evidence of the benefits of the pterional craniotomy for the surgical resection of orbital tumors by sharing our experience in the surgical management of a cholesteatoma of the superotemporal orbital wall.

Case presentation
A 45-year-old Hispanic man with a 2-year history of progressive proptosis of the left eye attended to our center complaining of diplopia and migraine. At his arrival, physical examination revealed ptosis, palpebral edema, and exophthalmos of the left eye, as well as the abolishment of the ipsilateral photomotor and consensual responses. Fundoscopy showed mild optic atrophy, whereas a T2-weighted magnetic resonance imaging (MRI) of the head showed a hyperintense mass arising at the superotemporal wall of the orbit that was displacing the eyeball. The tumor was resected using a pterional craniotomy without postoperative complications. The histopathological analysis of the tumor revealed a cholesteatoma. The patient recovered the functionality of the left eye with no visual sensitive deficits nor tumor recurrence 1 year after the surgery.

Conclusions
Our results support the use of the pterional craniotomy as a safe procedure for the surgical resection of cholesteatomas arising at the superotemporal walls of the orbit, with low postoperative morbidity.
SOX4 maintains the stemness of cancer cells via transcriptionally enhancing HDAC1 revealed by comparative proteomics study
Authors: Liu Jingshu , Qiu Jiangfeng , Zhang Zhiqi , Zhou Lei , Li Yunzhe , Ding Dongyan , Zhang Yang , Zou Dongling , Wang Dong , Zhou Qi , Lang Tingyuan 
Published: January 2021

Abstract
Background
Cancer stem cells (CSCs) are the root of human cancer development and the major cause of treatment failure. Aberrant elevation of SOX4, a member of SOX (SRY-related HMG-box) family transcription factors, has been identified in many types of human cancer and promotes cancer development. However, the role of SOX4 in CSCs, especially at a proteome-wide level, has remained elusive. The aim of this study is to investigate the effect of SOX4 on the stemness of CSCs and reveal the underlying mechanisms by identification of SOX4-induced proteome changes through proteomics study.

Results
Overexpression of SOX4 promotes sphere formation and self-renewal of colorectal cancer cells in vitro and in vivo and elevates the expression levels of CSCs markers. Through iTRAQ-based quantitative proteomics analysis, 215 differentially expressed proteins (128 upregulated, 87 downregulated) in SOX4-overexpressing HCT-116 spheres were identified. The bioinformatic analysis highlighted the importance of HDAC1 as the fundamental roles of its impacted pathways in stem cell maintenance, including Wnt, Notch, cell cycle, and transcriptional misregulation in cancer. The mechanistic study showed that SOX4 directly binds to the promoter of HDAC1, promotes HDAC1 transcription, thereby supporting the stemness of colorectal cancer cells. HDAC1 hallmarks colorectal cancer stem cells and depletion of HDAC1 abolished the stimulatory effect of SOX4. Furthermore, SOX4-HDAC1 axis is conserved in multiple types of cancer.

Conclusions
The results of this study reveal SOX4-induced proteome changes in HCT-116 spheres and demonstrates that transcriptional activation of HDAC1 is the primary mechanism underlying SOX4 maintaining CSCs. This finding suggests that HDAC1 is a potential drug target for eradicating SOX4-driven human CSCs.
Comparison between regional citrate anticoagulation and heparin for intermittent hemodialysis in ICU patients: a propensity score-matched cohort study
Authors: Leroy Christophe , Pereira Bruno , Soum Edouard , Bachelier Claire , Coupez Elisabeth , Calvet Laure , Bachoumas Konstantinos , Dupuis Claire , Souweine Bertrand , Lautrette Alexandre 
Published: January 2021

AbstractBackgroundRegional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD.MethodsThis retrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017).ResultsIn total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32;p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%;p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%;p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03–0.18];p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017).ConclusionRCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.
Impulsive noise modeling and robust receiver design
Authors: Clavier Laurent , Peters Gareth W. , Septier François , Nevat Ido 
Published: January 2021

AbstractInterference is an important limitation in many communication systems. It has been shown in many situations that the popular Gaussian approximation is not adequate and interference exhibits an impulsive behavior. This paper surveys the different statistical models proposed for such an interference, that can generally be unified using the class of sub-exponential family of distributions, and its impact on the receiver design. Visualizing the optimal decision boundaries allows one to show the non linear effect induced by impulsive noise models, which explains the significant loss in receiver performance designed under the standard Gaussian approximation. This motivates the need to develop new receivers. We propose a framework to design receivers robust to a variety of interference types, both Gaussian and non-Gaussian. We explore three ways of thinking about such receiver designs: a linear approach; by approximating the noise plus interference distribution; and by mimicking the decision rule distribution directly. Except for the linear approach, the other designs are capable of replicating the non-trivial optimal decision regions to different extents. The new detection algorithms are evaluated via Monte Carlo simulations. We focus on four efficient architectures, including the parameter estimations: Myriad, Normal Inverse Gaussian, p-norm and a direct estimation of the likelihood ratio function. They exhibit good performance, close to the optimal, in a large range of situations demonstrating they may be considered as robust decision rules in the presence of heavy tailed or impulsive interference environments.
Diagnostic efficiency of whole-body 18F-FDG PET/MRI, MRI alone, and SUV and ADC values in staging of primary uterine cervical cancer
Authors: Steiner Aida , Narva Sara , Rinta-Kiikka Irina , Hietanen Sakari , Hynninen Johanna , Virtanen Johanna 
Published: January 2021

Abstract
Background
The use of PET/MRI for gynecological cancers is emerging. The purpose of this study was to assess the additional diagnostic value of PET over MRI alone in local and whole-body staging of cervical cancer, and to evaluate the benefit of standardized uptake value (SUV) and apparent diffusion coefficient (ADC) in staging.

Methods
Patients with histopathologically-proven cervical cancer and whole-body 18F-FDG PET/MRI obtained before definitive treatment were retrospectively registered. Local tumor spread, nodal involvement, and distant metastases were evaluated using PET/MRI or MRI dataset alone. Histopathology or clinical consensus with follow-up imaging were used as reference standard. Tumor SUVmax and ADC were measured and SUVmax/ADC ratio calculated. Area under the curve (AUC) was determined to predict diagnostic performance and Mann-Whitney U test was applied for group comparisons.

Results
In total, 33 patients who underwent surgery (n = 23) or first-line chemoradiation (n = 10) were included. PET/MRI resulted in higher AUC compared with MRI alone in detecting parametrial (0.89 versus 0.73), vaginal (0.85 versus 0.74), and deep cervical stromal invasion (0.96 versus 0.74), respectively. PET/MRI had higher diagnostic confidence than MRI in identifying patients with radical cone biopsy and no residual at hysterectomy (sensitivity 89% versus 44%). PET/MRI and MRI showed equal AUC for pelvic nodal staging (both 0.73), whereas AUC for distant metastases was higher using PET/MRI (0.80 versus 0.67). Tumor SUVmax/ADC ratio, but not SUVmax or ADC alone, was significantly higher in the presence of metastatic pelvic lymph nodes (P < 0.05).

Conclusions
PET/MRI shows higher accuracy than MRI alone for determining local tumor spread and distant metastasis emphasizing the added value of PET over MRI alone in staging of cervical cancer. Tumor SUVmax/ADC ratio may predict pelvic nodal involvement.
Bubbles to Chondrites-II. Chemical fractionations in chondrites
Authors: Hashimoto Akihiko , Nakano Yuki 
Published: January 2021

AbstractWe attempt to develop a possible theory of chemical fractionations in chondrites, that is consistent with various features of chondritic components and current observation of protoplanetary disks (PPD). Combining the 3+2 component fitting calculation that simulates chondrule formation process proposed in paper (I) with additional mixing procedures, we investigate essential causes that made various types of chondrites evolve from the uniform solar system composition, the CI-chondritic composition. Seven chemical types of chondrites (CM, CV, CO, E, LL, L and H) are examined, for which reliable chemical compositions for both bulk chondrites and chondrules therein are known. High vaporization degree of the primordial dust aggregates (dustons) required by the calculation vindicates that the chondrule formation was the driving force for the chemical fractionations in all chondrites examined. Various initial redox states in dustons and different timings of CAIs’ invasion to the chondrule formation zone are identified for different chondrite types. These results, together with a good correlation with the D/H ratios of chondrites measured previously, lead us to the notion that PPD evolved from reducing to oxidizing. We explore the heating mechanism for the chondrule formation and the place it occurred. Only heat source being consistent with our chondrule formation model is lightning discharge. We postulate that large vortices encompassing the snow-line are ideal places for large charge separation to occur between dustons and small ice particles, and that direct strikes on dustons should make them boil for ten seconds and longer and allow a swarm of chondrules released from their surfaces. Chemical fractionations are completed by an aerodynamic separation of dustons from chondrules inside the vortex, in such a way that the dustons fall fast into the vortex center and form a planetesimal immediately, while chondrules with dust mantles fall slow and form a thin veneer on the planetesimal surface. During collisional episodes, the veneers are preferentially fragmented and reassemble themselves by a weak self-gravity to form a rubble-piled chondritic asteroid, i.e. chondrite.