bluuebunny/crossref_metadata_2025 huggingface dataset:
PredictProtein - Predicting Protein Structure and Function for 29 Years
Authors: Bernhofer Michael , Dallago Christian , Karl Tim , Satagopam Venkata , Heinzinger Michael , Littmann Maria , Olenyi Tobias , Qiu Jiajun , Schütze Konstantin , Yachdav Guy , Ashkenazy Haim , Ben-Tal Nir , Bromberg Yana , Goldberg Tatyana , Kajan Laszlo , O’Donoghue Sean , Sander Chris , Schafferhans Andrea , Schlessinger Avner , Vriend Gerrit , Mirdita Milot , Gawron Piotr , Gu Wei , Jarosz Yohan , Trefois Christophe , Steinegger Martin , Schneider Reinhard , Rost Burkhard
Published: May 2021

Since 1992 PredictProtein (https://predictprotein.org) is a one-stop online resource for protein sequence analysis with its main site hosted at the Luxembourg Centre for Systems Biomedicine (LCSB) and queried monthly by over 3,000 users in 2020. PredictProtein was the first Internet server for protein predictions. It pioneered combining evolutionary information and machine learning. Given a protein sequence as input, the server outputs multiple sequence alignments, predictions of protein structure in 1D and 2D (secondary structure, solvent accessibility, transmembrane segments, disordered regions, protein flexibility, and disulfide bridges) and predictions of protein function (functional effects of sequence variation or point mutations, Gene Ontology (GO) terms, subcellular localization, and protein-, RNA-, and DNA binding). PredictProtein's infrastructure has moved to the LCSB increasing throughput; the use of MMseqs2 sequence search reduced runtime five-fold (apparently without lowering performance of prediction methods); user interface elements improved usability, and new prediction methods were added. PredictProtein recently included predictions from deep learning embeddings (GO and secondary structure) and a method for the prediction of proteins and residues binding DNA, RNA, or other proteins. PredictProtein.org aspires to provide reliable predictions to computational and experimental biologists alike. All scripts and methods are freely available for offline execution in high-throughput settings.
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

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

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

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

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

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

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

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

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.
Potential Value of the Insights and Lived Experiences of Addiction Researchers With Addiction
Authors: Stull Samuel W. , Smith Kirsten E. , Vest Noel A. , Effinger Devin P. , Epstein David H.
Published: May 2021

People in remission from substance use disorders (SUDs) have a history of using their own experience (also referred to as “experiential knowledge” or “expertise”) to support those in or seeking SUD remission. In recent years, people with this experiential knowledge are being incorporated into research protocols to better guide research questions and inform the real-world uptake of SUD treatments and recovery supports. In these research contexts, however, those with research expertise and addiction rarely speak freely about these overlapping perspectives. The aim of this commentary is to increase awareness regarding the existence of this group (addiction researchers with addiction) and to explore the possibility that their expertise may help advance addiction science while helping to reduce stigma.
Implementation of a virtual learning and simulation curriculum for orthopaedic resident training during COVID and beyond
Authors: Hoyt Benjamin W. , Clark DesRaj M. , Roach William B. , Rodkey Daniel L. , Eckel Tobin T.
Published: May 2021

The recent coronavirus disease of 2019 pandemic has resulted in unprecedented limitations in person-to-person contact, elective surgeries, and even traumatic injuries, leaving potential gaps in training and skill development. Surgical programs have had to adapt with the rapid implementation of surgical simulation curricula, collaborative lecture series, and greater focus on online learning. Using models, simulation, and virtual learning, we have accommodated for restrictions and operative volume from coronavirus disease of 2019. The goal was to establish a durable system of extra-clinical training that would increase patient safety and collaborative knowledge sharing. From our simulated interventions, we noted maintenance of skills despite low operative volumes, low temporal or monetary commitment especially when compared with operating room time, and engagement from both learners (medical students and junior residents) and teachers (senior residents and staff physicians). Our experience with transition to a virtual curriculum with involvement of multiple institutions has also resulted in greater diversity of lectures, increased frequency of academics, and high levels of participation. In this article, we discuss our department’s experience with these alterations and the path for surgical training moving forward. We have seen multiple benefits to advancement of nonclinical specialty-specific simulation and virtual didactics. While some of these efforts may require some early expenditure, both monetary and temporal, to establish the program infrastructure, they are easy to apply, confer substantial added value, and appear durable.
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.

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.

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.
One Hundred Top Cited Articles in Cervical Myelopathy
Authors: Sinha Amit , Dheerendra Sujay , Munigangaiah Sudarshan
Published: May 2021

Study Design.

A bibliometric review of the literature.

Objectives.

The aim of this study was to identify the most highly cited articles relating to cervical myelopathy and to analyze the most influential articles.

Summary of Background Data.

Over the past several decades, a lot of research has been conducted regarding the subject of cervical myelopathy. Although there are a large number of articles on this topic, to our knowledge, this is the first bibliometric analysis.

Methods.

A selection of search terms and keywords were inputted into the “Dimensions” database and the most highly cited articles in cervical myelopathy were selected from high impact factor journals. The top 100 articles were analyzed for year of publication, authorship, publishing journals, institution and country of origin, subject matter, article type, and level of evidence.

Results.

The 100 most cited articles in the topic of cervical myelopathy were published from 1956 to 2015. These articles, their corresponding authors, and number of citations are shown in Table 1. The number of citations ranged from 121 times for the 100th article to 541 times for the top article in a total of 20 journals. The most common topic was operative technique, whereas the journals which contributed the most articles were the Spine journal and the Journal of Neurosurgery.

Conclusion.

Our study provided an extensive list of the most historically significant articles regarding cervical myelopathy, acknowledging the key contributions made to the advancement of this field.

Level of Evidence: 5
What is the standard indication of adjuvant or neoadjuvant chemotherapy in localized soft-tissue sarcoma?
Authors: Hindi Nadia , Martin-Broto Javier
Published: May 2021

Purpose of review

The aim is to bring latest evidence of the role of perioperative chemotherapy in localized soft-tissue sarcomas (STS) of limbs and to review the risk classification systems of retroperitoneal and extremity STS.

Recent findings

High-risk subset of localized STS of limbs and trunk-wall, defined with classic prognostic factors, consistently obtained 5-year overall survival ranging from 69 to 76% in randomized patients treated with full-dose of anthracycline and ifosfamide. Validated nomograms accurately predict, on individual basis, the risk of death and recurrence in localized STS of retroperitoneum and limbs, enabling a better selection of high-risk patients (usually those with death risk of ≥40%) that potentially could benefit with perioperative systemic treatment. Nomograms have virtually converted a negative large perioperative trial into a positive, favouring chemotherapy arm in the high-risk selection.

Perioperative three cycles of full-dose of anthracycline and ifosfamide should be proposed on an individual basis, in reference sarcoma centres, to high-risk localized STS of limbs or trunk-wall in certain histologies.
The active human immunodeficiency virus reservoir during antiretroviral therapy: emerging players in viral persistence
Authors: Astorga-Gamaza Antonio , Buzon Maria J.
Published: May 2021

Purpose of review

To discuss the role of CD4+ T cells with active Human immunodeficiency virus (HIV), meaning infected cells with transcriptional and/or translational viral activity during antiretroviral therapy (ART), focusing on new technologies for its detection, potential cell markers for its characterization, and evidences on the contribution of the active HIV reservoir to long-term viral persistence.

Recent findings

HIV-infected cells expressing viral ribonucleic acid are systematically detected in subjects on long-term ART. In recent years, powerful new tools have provided significant insights into the nature, quantification, and identification of cells with active HIV, including the identification of new cell markers, and the presence of viral activity in specific cell populations located in different cellular and anatomical compartments. Moreover, studies on viral sequence integrity have identified cell clones with intact viral genomes and active viral transcription that could potentially persist for years. Together, new investigations support the notion that the active reservoir could represent a relevant fraction of long-term infected cells, and therefore, the study of its cell sources and mechanisms of maintenance could represent a significant advance in our understanding of viral persistence and the development of new curative strategies.

The presence of HIV-infected cells with viral expression during ART has been traditionally overlooked for years. Based on recent investigations, this active viral reservoir could play an important role in HIV persistence.
Prenatal and childhood exposure to air pollution and traffic and the risk of liver injury in European children
Authors: Garcia Erika , Stratakis Nikos , Valvi Damaskini , Maitre Léa , Varo Nerea , Aasvang Gunn Marit , Andrusaityte Sandra , Basagana Xavier , Casas Maribel , de Castro Montserrat , Fossati Serena , Grazuleviciene Regina , Heude Barbara , Hoek Gerard , Krog Norun Hjertager , McEachan Rosemary , Nieuwenhuijsen Mark , Roumeliotaki Theano , Slama Rémy , Urquiza Jose , Vafeiadi Marina , Vos Miriam B. , Wright John , Conti David V. , Berhane Kiros , Vrijheid Martine , McConnell Rob , Chatzi Lida
Published: May 2021

Background:

Nonalcoholic fatty liver disease is the most prevalent pediatric chronic liver disease. Experimental studies suggest effects of air pollution and traffic exposure on liver injury. We present the first large-scale human study to evaluate associations of prenatal and childhood air pollution and traffic exposure with liver injury.

Methods:

Study population included 1,102 children from the Human Early Life Exposome project. Established liver injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and cytokeratin-18, were measured in serum between ages 6–10 years. Air pollutant exposures included nitrogen dioxide, particulate matter <10 μm (PM10), and <2.5 μm. Traffic measures included traffic density on nearest road, traffic load in 100-m buffer, and inverse distance to nearest road. Exposure assignments were made to residential address during pregnancy (prenatal) and residential and school addresses in year preceding follow-up (childhood). Childhood indoor air pollutant exposures were also examined. Generalized additive models were fitted adjusting for confounders. Interactions by sex and overweight/obese status were examined.

Results:

Prenatal and childhood exposures to air pollution and traffic were not associated with child liver injury biomarkers. There was a significant interaction between prenatal ambient PM10 and overweight/obese status for alanine aminotransferase, with stronger associations among children who were overweight/obese. There was no evidence of interaction with sex.

Conclusion:

This study found no evidence for associations between prenatal or childhood air pollution or traffic exposure with liver injury biomarkers in children. Findings suggest PM10 associations maybe higher in children who are overweight/obese, consistent with the multiple-hits hypothesis for nonalcoholic fatty liver disease pathogenesis.
The association between prenatal concentrations of polybrominated diphenyl ether and child cognitive and psychomotor function
Authors: Solazzo Giulia , Wu Haotian , Laue Hannah E. , Brennan Kasey , Knox Julia M. , Gillet Virginie , Bovin Amélie , Abdelouahab Nadia , Posner Jonathan , Raffanello Elizabeth , Pieper Sarah , Bowman Fredrick DuBois , Drake Daniel , Baccarelli Andrea A. , Takser Larissa
Published: May 2021

Background:

Previous studies suggest a negative association between prenatal polybrominated diphenyl ethers (PBDEs) exposure and child cognitive and psychomotor development. However, the timing of the relationship between PBDE exposure and neurodevelopment is still unclear. We examined the association between PBDE concentration at two different prenatal times (early and late pregnancy) and cognitive function in children 6–8 years of age.

Methods:

Eight hundred pregnant women were recruited between 2007 and 2009 from Sherbrooke, Canada. Four PBDE congeners (BDE-47, -99, -100, and -153) were measured in maternal plasma samples collected during early pregnancy (12 weeks of gestation) and at delivery. At 6–8 years of age, 355 children completed a series of subtests spanning multiple neuropsychologic domains: verbal and memory skills were measured using the Wechsler Intelligence Scale for Children, Fourth Edition; visuospatial processing using both Wechsler Intelligence Scale for Children, Fourth Edition and Neuropsychological Assessment second edition; and attention was assessed through the Test of Everyday Attention for Children. Additionally, parents completed subtests from the Developmental Coordination Disorder Questionnaire to measure child motor control. We used linear regression and quantile g-computation models to estimate associations of PBDE congener concentrations and psychologic test scores.

Results:

In our models, no significant associations were detected between PBDE mixture and any of the child psychologic scores. BDE-99 concentration at delivery was nominally associated with higher scores on short-term and working memory while a decrease in spatial perception and reasoning was nominally associated with higher BDE-100 concentration at delivery.

Conclusion:

Overall, our results did not show a significant association between PBDEs and child cognitive and motor development.
Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women
Authors: Jiang Xuezhi , Bossert Anna , Parthasarathy K. Nathan , Leaman Kristine , Minassian Shahab S. , Schnatz Peter F. , Woodland Mark B.
Published: May 2021

Objective:

To assess the safety and serum estradiol (E2) and total testosterone (T) concentrations in postmenopausal women treated with Pellet Hormonal Therapy (PHT) and Food and Drug Administration approved Hormonal Therapy (FHT).

Methods:

A total of 539 postmenopausal women were identified, including 384 on PHT and 155 on FHT. Data extracted from medical records include demographics, indication for hormone therapy, treatment duration, side effects, serum E2 and T levels, and frequency of laboratory follow-up.

Results:

The incidence of overall side effects was significantly higher in PHT compared with FHT (221 [57.6%] vs 23 [14.8%], P < 0.00001, odds ratio [95% CI] =8.0[4.5-14.2]). When examining women with an intact uterus prior to hormone therapy initiation, 55.3% (136/246) on PHT vs 15.2% (12/79) on FHT had at least one episode of abnormal uterine bleeding (P < 0.0001, odds ratio [95% CI] = 7.9[3.6-17.0]). Furthermore, a significantly higher proportion of women on PHT (20.3% [50/246]), compared with 6.3% (5/79) on FHT, had a hysterectomy (P = 0.036, odds ratio [95% CI] = 3.2[1.1-9.3]). Both mean (SD, Min-Max) peak E2 (pg/mL) and peak T (ng/dL) are significantly higher in the PHT group than those in the FHT group (E2: 237.70 [168.55, 10-1,111] vs 93.45 [130.77, 5.5-465.8], T: 194.04 [84.94, 4.3-599] vs 15.59 [19.52, 0.2-70], P < 0.00001). Of those on PHT, four women had E2 level > 1,000 pg/mL and nine women with T level > 400 ng/dL.

Conclusion:

Women on PHT had a significantly higher incidence of side effects than FHT as well as a significantly higher supraphysiological level of peak E2 and T during the treatment.
Predictive and criterion validity of the Cervantes-SF menopause quality of life questionnaire
Authors: Coronado Pluvio J. , Monroy Manuel , Fasero María , Baquedano Laura , Mendoza Nicolás , Llaneza Plácido , Rejas Javier , Ruiz Miguel A.
Published: May 2021

Objectives:

To determine the predictive and criterion-based validity of the Cervantes-SF scale that measures the impact of menopause on Health-Related Quality of Life.

Methods:

We recruited a noninstitutionalized sample of peri/postmenopausal women aged 40 to 65 years, who had their last menstrual cycle 12+ months prior to inclusion in the study of the psychometric validity of the Cervantes-SF scale. Predictive validity of the scale was confirmed for various health outcome measures administered concomitantly (years of disability-free life expectancy, work productivity and impact on daily activities, economic impact arising from loss of work productivity, hours of undisturbed sleep each day, and the utilization of healthcare facilities), whilst criterion validity was determined by the likelihood of identifying a moderate-to-severe vasomotor or genital syndrome requiring specific treatment.

Results:

A sample of 308 peri/postmenopausal women with a mean age of 55.7 years (SD: 5.3 y) was analyzed in this study. A score >25 points on the dimension of vasomotor problems (or menopausal health) showed values of sensitivity and specificity > 80% for identifying women with moderate-severe vasomotor syndrome requiring pharmacological treatment. Predictive validity was confirmed for menopause-related health outcomes. A change of 6.7 points in the scale score, equivalent to the value of its minimal difference, is indicative of a significant increase in the degree of disability regarding work/day-to-day activities, greater economic loss due to decreased work productivity, fewer years of life expectancy without disability, fewer hours of undisturbed sleep, and more visits to the physician per year due to menopausal symptoms.

Conclusions:

These results confirm the criterion and predictive validity of the Cervantes-SF scale in peri/postmenopausal women.
First Trimester Abortion Care in Low- and Middle-Income Countries
Authors: HENKEL ANDREA , SHAW KATE A.
Published: May 2021

Access to first trimester abortions has increased significantly in the past few decades in low and middle-income countries. Manual vacuum aspiration is now standard of care for procedural abortion and postabortion care. Medication abortion has shifted abortions to being performed earlier in pregnancy and is becoming more widely available with new service delivery strategies to broaden access. Widespread availability of misoprostol has made abortions induced outside of the formal medical sector overall safer. In both legally restrictive and supportive environments, there is increased interested in self-managed abortions as part of a shift towards demedicalizing abortion through task-sharing.
Abortion Care Beyond 13 Weeks’ Gestation: A Global Perspective
Authors: COHEN MEGAN A. , KAPP NATHALIE , EDELMAN ALISON
Published: May 2021

The majority of abortions are performed early in pregnancy, but later abortion accounts for a large proportion of abortion-related morbidity and mortality. People who need this care are often the most vulnerable–the poor, the young, those who experience violence, and those with significant health issues. In settings with access to safe care, studies demonstrate significant declines in abortion-related morbidity and mortality. This review focuses on evidence-based practices for induced abortion beyond 13 weeks’ gestation and post-abortion care in both high- and low-resource settings. We also highlight key programmatic issues to consider when expanding the gestational age for abortion services.
Relationships between cardiovascular risk factors and white-coat hypertension diagnosed by home blood pressure recordings in a middle-aged population
Authors: Johansson Martina A.K. , Östgren Carl Johan , Engvall Jan , Swahn Eva , Wijkman Magnus , Nystrom Fredrik H.
Published: May 2021

Objective:

To study risk in white-coat hypertension (WCH) by measurement of coronary artery calcium score (CACS), carotid--femoral pulse-wave velocity (PWV) and carotid plaques.

Methods:

Cross-sectional population-based cohort with randomized selection of participants from Linköping, Sweden. An Omron m10-IT oscillometric device was used for clinic and home blood pressures (HBP) in the morning and evening for 1 week.

Results:

We recruited 5029 middle-aged and mainly defined WCH as SBP at least 140 mmHg and/or DBP at least 90 mmHg with HBP less than 135/85 mmHg. There were 2680 normotensive participants and 648 had WCH after exclusion of treated participants. More women (59.5%) than men (42.8%, P < 0.001) had WCH. We found higher prevalence of CACS greater than 100 compared with less than 100 (12.4 vs. 7.2%, P < 0.001), PWV (11.5 ± 1.5 vs. 10.4 ± 1.3 m/s, P < 0.001) and a higher prevalence of one or more carotid plaques (59.5 vs. 48%, P < 0.001) in participants with WCH than in normotension. Participants with WCH also had more dyslipidemia and higher glucose levels. Normotensive women scored lower on nervousness than women with WCH (P = 0.022). After matching of 639 participants with WCH to normotensive participants according to age, gender and systolic HBP the prevalence of a high CACS (12.1 vs. 8.6%, P = 0.003,) PWV (11.0 ± 0.068 vs. 11.5 ± 0.068 m/s, estimated marginal means ± SE, P < 0.001 by ANOVA) but not more carotid plaques (59.5 vs. 55.6%, P = 0.23), remained in the participants with WCH compared with the matched normotensive participants.

Conclusion:

WCH is particularly common in middle-aged women, and it displays metabolic dysfunction and increased prevalence of arteriosclerotic manifestations in both genders. As markers of increased cardiovascular risk were present also after matching normotensive and WCH participants according to systolic HBP, age and gender, the presence of WCH signals an increased cardiovascular risk burden that is not fully explained by elevated BP levels at home.
Abnormalities in emotional and motor reactions among young prehypertensive individuals: employing continuous blood pressure analysis
Authors: Wiener Avigail , Goldstein Pavel , Doenyas Keren , Okon-Singer Hadas
Published: May 2021

Background:

Essential hypertension is an important risk factor for cerebrovascular diseases and a major cause of premature death in industrialized societies. A predisposing factor for essential hypertension is prehypertension: blood pressure (BP) values at rest that are at the higher end of the normal range. Abnormally enhanced cardiovascular responses to motor and emotional tasks have been found as predictors of essential hypertension. Yet, knowledge regarding the BP reaction to aversive stimuli and motor reaction in prehypertension is limited.

Methods:

We compared the reaction to aversive and neutral stimuli inducing an emotional response (experiment 1) and to the isometric handgrip exercise (IHE) inducing a motor response (experiment 2), between prehypertensive and normotensive controls. BP reactions were measured and analyzed in a continuous fashion, in contrast to previous studies that averaged BP responses across blocks. We applied a multilevel B-spline model, a continuous analysis that enabled a better understanding of the BP time course and the detection of subtle differences between groups.

Results:

In both tasks, we found that prehypertensive individuals showed enhanced DBP reactions compared with normotensive controls; prehypertensive individuals exhibited lower BP responses to aversive pictures and higher BP responses to the IHE. These results are in line with previous studies with healthy or hypertensive participants and suggest abnormalities already in the prehypertensive stage.

Conclusion:

Considering the high frequency and health risks related to prehypertension, understanding the autonomic reactions to emotional and motor stimuli in this population is of clinical and theoretical importance and could serve as a behavioural marker to identify at-risk groups.