bluuebunny/crossref_metadata_2025_split huggingface dataset:
An essential role of the autophagy activating kinase ULK1 in snRNP biogenesis
Authors: Schmitz Katharina , Cox Jan , Esser Lea Marie , Voss Martin , Sander Katja , Löffler Antje , Hillebrand Frank , Erkelenz Steffen , Schaal Heiner , Kähne Thilo , Klinker Stefan , Zhang Tao , Nagel-Steger Luitgard , Willbold Dieter , Seggewiß Sabine , Schlütermann David , Stork Björn , Grimmler Matthias , Wesselborg Sebastian , Peter Christoph 
Published: May 2021

Abstract
The biogenesis of small uridine-rich nuclear ribonucleoproteins (UsnRNPs) depends on the methylation of Sm proteins catalyzed by the methylosome and the subsequent action of the SMN complex, which assembles the heptameric Sm protein ring onto small nuclear RNAs (snRNAs). In this sophisticated process, the methylosome subunit pICln (chloride conductance regulatory protein) is attributed to an exceptional key position as an ‘assembly chaperone’ by building up a stable precursor Sm protein ring structure. Here, we show that—apart from its autophagic role—the Ser/Thr kinase ULK1 (Uncoordinated [unc-51] Like Kinase 1) functions as a novel key regulator in UsnRNP biogenesis by phosphorylation of the C-terminus of pICln. As a consequence, phosphorylated pICln is no longer capable to hold up the precursor Sm ring structure. Consequently, inhibition of ULK1 results in a reduction of efficient UsnRNP core assembly. Thus ULK1, depending on its complex formation, exerts different functions in autophagy or snRNP biosynthesis.
Modeling Public Sentiments About JUUL Flavors on Twitter Through Machine Learning
Authors: Malik Aqdas , Khan Muhammad Irfan , Karbasian Habib , Nieminen Marko , Ammad-Ud-Din Muhammad , Khan Suleiman Ali 
Published: May 2021

Abstract

Introduction
The availability of a variety of e-cigarettes flavors is one of the frequently cited reasons for their adoption. An active stream of discussion about flavoring can be observed online. Analyzing these real-time conversations offers nuanced insights into key factors related to the adoption of flavors, subsequently supporting public health interventions.

Methods
Google’s BERT, a state-of-the-art deep learning method was employed to model the first sentiment corpus on JUUL flavors. BERT, which is pre-trained with the complete English Wikipedia was fine-tuned by integrating a classification model, with human labeled Tweets, as training data. A collection of 30 075 Tweets about JUUL flavors was classified into positive and negative sentiments. Finally, using topic models, we identify and grouped thematic areas into positive and negative Tweets.

Results
With an average of 89% cross-validation precision for classifying Tweets, the fine-tuned BERT model classified 24 114 Tweets as positive and 5961 Tweets as negative. Through the topic modeling approach 10 thematic topics were identified from the predicted positive and negative sentiments expressed in the Tweets.

Conclusions
JUUL flavors, notably mango, mint, and cucumber, provoke overwhelmingly positive sentiments indicating a strong likeness due to favorable taste and odor. Negative discourse about JUUL flavors revolve around addictiveness, high nicotine content, and youth targeted marketing.

Implications
Limiting the content related to flavors and positive perceptions on social media is necessary to minimize exposure to youth. The novel methodology used in this study may be adopted to monitor e-cigarette discourse periodically, as well as other critical public health phenomena online.
Studying the Utility of Using Genetics to Predict Smoking-Related Outcomes in a Population-Based Study and a Selected Cohort
Authors: Bray Michael J , Chen Li-Shiun , Fox Louis , Ma Yinjiao , Grucza Richard A , Hartz Sarah M , Culverhouse Robert C , Saccone Nancy L , Hancock Dana B , Johnson Eric O , McKay James D , Baker Timothy B , Bierut Laura J 
Published: May 2021

Abstract

Introduction
The purpose of this study is to examine the predictive utility of polygenic risk scores (PRSs) for smoking behaviors.

Aims and Methods
Using summary statistics from the Sequencing Consortium of Alcohol and Nicotine use consortium, we generated PRSs of ever smoking, age of smoking initiation, cigarettes smoked per day, and smoking cessation for participants in the population-based Atherosclerosis Risk in Communities (ARIC) study (N = 8638), and the Collaborative Genetic Study of Nicotine Dependence (COGEND) (N = 1935). The outcomes were ever smoking, age of smoking initiation, heaviness of smoking, and smoking cessation.

Results
In the European ancestry cohorts, each PRS was significantly associated with the corresponding smoking behavior outcome. In the ARIC cohort, the PRS z-score for ever smoking predicted smoking (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 1.31, 1.43); the PRS z-score for age of smoking initiation was associated with age of smoking initiation (OR: 0.87; 95% CI: 0.82, 0.92); the PRS z-score for cigarettes per day was associated with heavier smoking (OR: 1.17; 95% CI: 1.11, 1.25); and the PRS z-score for smoking cessation predicted successful cessation (OR: 1.24; 95% CI: 1.17, 1.32). In the African ancestry cohort, the PRSs did not predict smoking behaviors.

Conclusions
Smoking-related PRSs were associated with smoking-related behaviors in European ancestry populations. This improvement in prediction is greatest in the lowest and highest genetic risk categories. The lack of prediction in African ancestry populations highlights the urgent need to increase diversity in research so that scientific advances can be applied to populations other than those of European ancestry.

Implications
This study shows that including both genetic ancestry and PRSs in a single model increases the ability to predict smoking behaviors compared with the model including only demographic characteristics. This finding is observed for every smoking-related outcome. Even though adding genetics is more predictive, the demographics alone confer substantial and meaningful predictive power. However, with increasing work in PRSs, the predictive ability will continue to improve.
Surface engineering of titania nanotubes incorporated with double-layered extracellular vesicles to modulate inflammation and osteogenesis
Authors: Zhao Qingyu , Zhang Yi , Xiao Lan , Lu Haiping , Ma Yaping , Liu Qi , Wang Xin 
Published: May 2021

Abstract
Titania nanotubes (TNT) generated on titanium implant are emerged as important modification technique to facilitate bone regeneration. Mesenchymal stem cells (MSCs)-derived exosomes are membrane bound extracellular vesicles (EVs), which play an important role in tissue regeneration. The objective of this study was to generate an EVs hybrid TNT aiming at regulating inflammation, MSCs recruitment and osteogenesis. We isolated EVs from MSCs (MSCs EVs) and 3-day osteogenically differentiated MSCs (3d EVs). MSC EVs and 3d EVs exhibited round morphology under TEM, which also showed robust internalization by human bone marrow derived MSCs (hBMSCs). Next, we fabricated 3d EVs/MSC EVs hybrid TNT. When inflammatory macrophages were co-cultured with EVs hybrid TNT, the gene and protein expression of inflammatory cytokine were significantly reduced. Macrophage morphology was also examined by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Further migratory ability study using hBMSCs indicated significant enhancement of MSCs migration in EVs hybrid TNT. In addition, we further demonstrated significant increase of osteogenic differentiation of hBMSCs in EVs hybrid TNT. This study suggests that EVs hybrid TNT may serve as a viable therapeutic approach to enhance osteogenesis and bone regeneration.
Development and validation of a prediction model for glucocorticoid-associated osteonecrosis of the femoral head by targeted sequencing
Authors: Jiang Chang , Wang Xinyuan , Huang Kai , Chen Limeng , Ji Zongfei , Hua Bingxuan , Qi Guobin , Yuan Hengfeng , Cao Yuanwu , Jiang Lindi , Peng David Haixiang , Yan Zuoqin 
Published: May 2021

Abstract

Objective
To develop and validate a prediction model based on targeted sequencing for glucocorticoid (GC)-associated osteonecrosis of the femoral head (GA-ONFH) in GC-treated adults.

Methods
This two-centre retrospective study was conducted between July 2015 and April 2019 at Zhongshan Hospital (training set) and the Sixth People’s Hospital (test set) in Shanghai, China. All patients had a history of GC therapy, with a dose exceeding 2000 mg equivalent prednisone within 6 weeks. Patients were divided into two groups according to whether they were diagnosed with GA-ONFH within 2 years after GC initiation. Blood or saliva samples were collected for targeted sequencing of 358 single nucleotide polymorphisms and genetic risk score (GRS) calculating for developing GA-ONFH prediction model. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate and validate the model.

Results
. The training set comprised 117 patients, while the test set comprised 30 patients for external validation. Logistic regression analysis showed that GRS was significantly associated with GA-ONFH (OR 1.87, 95% CI: 1.48, 2.37). The ROC and DCA curves showed that the multivariate model considering GRS, age at GC initial, sex and underlying diseases had a discrimination with area under the ROC curve (AUC) of 0.98 (95% CI: 0.96, 1.00). This model was further externally validated using the test set with an AUC of 0.91 (95% CI: 0.81, 1.00).

Conclusion
Our prediction model comprising GRS, age, sex and underlying diseases yields valid predictions of GA-ONFH incidence. It may facilitate effective screening and prevention strategies of GA-ONFH.
KERMA-AREA PRODUCT, ENTRANCE SURFACE DOSE AND EFFECTIVE DOSE IN ABDOMINAL ENDOVASCULAR ANEURYSM REPAIR
Authors: Efthymiou Fotios O , Metaxas Vasileios I , Dimitroukas Christos P , Kakkos Stavros K , Panayiotakis George S 
Published: May 2021

Abstract
This study aims to evaluate patient radiation dose during fluoroscopically guided endovascular aneurysm repair (EVAR) procedures. Fluoroscopy time (FT) and kerma-area product (KAP) were recorded from 87 patients that underwent EVAR procedures with a mobile C-arm fluoroscopy system. Effective dose (ED) and organs’ doses were calculated utilising appropriate conversion coefficients based on the recorded KAP values. Entrance surface dose (ESD) was calculated based on KAP values and technical parameters. The mean FT was 22.7 min (range 6.4–76.8 min), resulting in a mean KAP of 36.6 Gy cm2 (range 2.0–167.8 Gy cm2), a mean ED of 6.2 mSv (range 0.3–28.5 mSv) and a mean ESD of 458 mGy (range 26–2098 mGy). The corresponding median values were 17.4 min, 25.6 Gy cm2, 4.4 mSv and 320 mGy. The threshold of 2 Gy for skin erythema was exceeded in two procedures for a focus-to-skin distance (FSD) of 40 cm and six procedures when an FSD of 30 cm was considered. The highest doses absorbed by the adrenals, kidneys, spleen and pancreas and ranged between 3.7 and 313.3 mGy (average 66.8 mGy), 3.3 and 285.1 mGy (average 60.8 mGy), 1.3 and 111.1 mGy (average 23.7 mGy), 1.1 and 92.1 mGy (average 19.6 mGy), respectively. A wide range of patient doses was reported in the literature. The radiation dose received by the patients was comparative or lower than most of the previously reported values. However, higher doses can be revealed due to the X-ray system’s non-optimum use and extended FTs, mainly affected by complex clinical conditions, patients’ body habitus and vascular surgeon experience. The large variation of patient doses highlights the potential to optimise the EVAR procedure by considering the balance between the radiation dose and the required image quality. Additional studies need to be conducted in increasing the vascular surgeons’ awareness regarding patient dose and radiation protection issues during EVAR procedures.
Are Skyline Plot-Based Demographic Estimates Overly Dependent on Smoothing Prior Assumptions?
Authors: Parag Kris V , Pybus Oliver G , Wu Chieh-Hsi 
Published: May 2021

Abstract
In Bayesian phylogenetics, the coalescent process provides an informative framework for inferring changes in the effective size of a population from a phylogeny (or tree) of sequences sampled from that population. Popular coalescent inference approaches such as the Bayesian Skyline Plot, Skyride, and Skygrid all model these population size changes with a discontinuous, piecewise-constant function but then apply a smoothing prior to ensure that their posterior population size estimates transition gradually with time. These prior distributions implicitly encode extra population size information that is not available from the observed coalescent data or tree. Here, we present a novel statistic, $\Omega$, to quantify and disaggregate the relative contributions of the coalescent data and prior assumptions to the resulting posterior estimate precision. Our statistic also measures the additional mutual information introduced by such priors. Using $\Omega$ we show that, because it is surprisingly easy to overparametrize piecewise-constant population models, common smoothing priors can lead to overconfident and potentially misleading inference, even under robust experimental designs. We propose $\Omega$ as a useful tool for detecting when effective population size estimates are overly reliant on prior assumptions and for improving quantification of the uncertainty in those estimates.[Coalescent processes; effective population size; information theory; phylodynamics; prior assumptions; skyline plots.]
let-7c-5p regulates CyclinD1 in fluoride-mediated osteoblast proliferation and activation
Authors: Luo Keke , Qin Yu , Ouyang Ting , Wang Xilan , Zhang Aihua , Luo Peng , Pan Xueli 
Published: May 2021

Abstract
Endemic fluorosis is caused by the intake of high environmental fluoride levels, which causes dental and skeletal fluorosis. Osteoblast proliferation and activation is closely related to skeletal fluorosis and is tightly regulated by the cell cycle. Several biological processes, including bone metabolism and osteoblast proliferation and activation, are regulated by a type of non-coding RNA called microRNAs (miRNAs). However, the understanding of miRNA functions in skeletal fluorosis is limited. Based on our previous miRNA sequencing results and bioinformatics analysis, we investigated the function of the miRNA let-7c-5p to regulate CyclinD1 in fluoride-induced osteoblast proliferation and activation. We designed population experiments as well as in vitro studies using EdU, flow cytometry, immunofluorescence, dual-luciferase reporters, and chromatin immunoprecipitation. The population-based analysis showed a decrease in let-7c-5p expression as fluoride exposure increased. In addition, let-7c-5p levels were negatively correlated with CyclinD1 and Wnt9a (another let-7c-5p target). We verified in vitro that let-7c-5p participates in the fluoride-induced proliferation and activation of human osteoblasts by directly targeting CyclinD1. Furthermore, we demonstrated that let-7c-5p regulates CyclinD1 expression via the Wnt/β-catenin signaling pathway. This study demonstrated the participation of let-7c-5p in fluoride-induced proliferation and activation of human osteoblasts by regulation of CyclinD1 expression at the post-transcriptional and transcriptional levels. We report for the first time that the Wnt9a/β-catenin/CyclinD1 axis is involved in fluorosis development.
Provider and Patient-panel Characteristics Associated With Initial Adoption and Sustained Prescribing of Medication for Opioid Use Disorder
Authors: Cochran Gerald , Cole Evan S. , Sharbaugh Michael , Nagy Dylan , Gordon Adam J. , Gellad Walid F. , Pringle Janice , Bear Todd , Warwick Jack , Drake Coleman , Chang Chung-Chou H. , DiDomenico Ellen , Kelley David , Donohue Julie 
Published: May 2021

Objectives:
Limited information is available regarding provider- and patient panel-level factors associated with primary care provider (PCP) adoption/prescribing of medication for opioid use disorder (MOUD).

Methods:
We assessed a retrospective cohort from 2015 to 2018 within the Pennsylvania Medicaid Program. Participants included PCPs who were Medicaid providers, with no history of MOUD provision, and who treated ≥10 Medicaid enrollees annually. We assessed initial MOUD adoption, defined as an index buprenorphine/buprenorphine-naloxone or oral/extended release naltrexone fill and sustained prescribing, defined as ≥1 MOUD prescription(s) for 3 consecutive quarters from the PCP. Independent variables included provider- and patient panel-level characteristics.

Results:
We identified 113 rural and 782 urban PCPs who engaged in initial adoption and 36 rural and 288 urban PCPs who engaged in sustained prescribing. Rural/urban PCPs who issued increasingly larger numbers of antidepressant and antipsychotic medication prescriptions had greater odds of initial adoption and sustained prescribing (P < 0.05) compared to those that did not prescribe these medications. Further, each additional patient out of 100 with opioid use disorder diagnosed before MOUD adoption increased the adjusted odds for initial adoption 2% to 4% (95% confidence interval [CI] = 1.01–1.08) and sustained prescribing by 4% to 7% (95% CI = 1.01–1.08). New Medicaid providers in rural areas were 2.52 (95% CI = 1.04–6.11) and in urban areas were 2.66 (95% CI = 1.94, 3.64) more likely to engage in initial MOUD adoption compared to established PCPs.

Conclusions:
MOUD prescribing adoption was concentrated among PCPs prescribing mental health medications, caring for those with OUD, and new Medicaid providers. These results should be leveraged to test/implement interventions targeting MOUD adoption among PCPs.
Therapy Dose Mediates the Relationship Between Buprenorphine/Naloxone and Opioid Treatment Outcomes in Youth Receiving Medication for Opioid Use Disorder Treatment
Authors: Hammond Christopher J. , Kady Annabel , Park Grace , Vidal Carol , Wenzel Kevin , Fishman Marc 
Published: May 2021

Background:
Evidence-based interventions for treating opioid use disorder (OUD) in youth are limited and little is known about specific and general mechanisms of OUD treatments and how they promote abstinence.

Methods:
The present study used data from the NIDA-CTN-0010 trial to evaluate the mediating effects of psychosocial treatment-related variables (therapy dose and therapeutic alliance) on end-of-treatment opioid abstinence in a sample of youth with OUD (n = 152, 40% female, mean age = 19.7 years) randomized to receive either 12-weeks of treatment with Bup/Nal (“Bup-Nal”) or up to 2 weeks of Bup/Nal detoxification (“Detox”) with both treatment arms receiving weekly individual and group drug counseling ± family therapy.

Results:
Participants in the Bup-Nal group attended more therapy sessions (16 vs 6 sessions), had increased therapeutic alliance at week-4, and had less opioid use by week-12 compared to those in the Detox group. In both treatment arms, youth who attended more therapy sessions were less likely to have a week-12 opioid positive urine. In a multiple mediator model, therapy dose mediated the association between treatment arm and opioid abstinence.

Conclusions:
These findings provide preliminary support for a “dose-response” effect of addiction-focused therapy on abstinence in youth OUD. Further, the results identified a mediating effect of therapy dose on the relationship between treatment assignment and opioid treatment outcomes, suggesting that extended Bup-Nal treatment may enhance abstinence, in part, through a mechanism of therapy facilitation, by increasing therapy dose during treatment.
Intestinal dysbiosis in spondyloarthritis – chicken or egg?
Authors: Breban Maxime , Beaufrère Marie , Glatigny Simon 
Published: May 2021

Purpose of review
The well-established link between intestinal inflammation and spondyloarthritis (SpA) remains largely unexplained. Recent sequencing technologies have given access to a thorough characterization of the gut microbiota in healthy and disease conditions. This showed that inflammatory bowel disease (IBD) is associated with dysbiosis – i.e., disturbed gut microbiota composition – which may contribute to disease pathogenesis. Whether gut dysbiosis exists in SpA and could contribute to disease development or be a bystander consequence of chronic inflammation is a question of major interest.

Recent findings
Several metagenomic studies have been performed in SpA. Most of them concerned faecal samples and showed dysbiosis consisting in a reduction of microbial biodiversity in a way similar to what has been described in IBD. They also highlighted changes in microbial taxa composition that could contribute to the inflammatory process. Likewise, healthy carriers of human leukocyte antigen (HLA)-B27 exhibited gut dysbiosis, indicating that this predisposing allele could exert its pathogenic effect by influencing microbiota composition, and possibly by driving antigen-specific cross-reactive immune response. On the other hand, SpA treatments were associated with a reduction of dysbiosis, showing that it is at least in part a consequence of inflammation.

Summary
Recent insights from metagenomic studies warrant further investigations to identify the mechanisms by which microbial dysbiosis could contribute to SpA development. This would bring novel therapeutic opportunities aiming at correcting detrimental changes.
Inflammatory back pain: a concept, not a diagnosis
Authors: Coath Fiona Louise , Gaffney Karl 
Published: May 2021

Purpose of review
The concept of inflammatory back pain (IBP) describes a cohort of patients with chronic back pain (CBP) who have distinct clinical characteristics, rather than being a diagnosis in and of itself. IBP is a common and important feature of axial spondyloarthritis (axSpA) but this is not the only differential. This review examines the utility of IBP in both primary and secondary care settings.

Recent findings
There are a number of suggested referral strategies for patients with suspected axSpA that include IBP. These strategies attempt to strike a balance between ensuring potential axSpA patients are not overlooked, whilst simultaneously not overwhelming secondary care services. Their success relies on the clinicians who first encounter these patients being familiar with IBP as a concept; however, it is still poorly recognized by many healthcare professionals. IBP may be helpful as part of a referral strategy; however, other clinical features, laboratory investigations and radiology must be incorporated for the final diagnostic outcome in axSpA.

Summary
Delayed diagnosis is a major clinical problem in axSpA and is associated with worse clinical outcomes. When recognized and utilized correctly, IBP can be a useful tool to promote prompt referral to rheumatology services.