bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of total hip and total knee arthroplasty and vitamin D homeostasis
Authors: Brambilla Lorenzo , Peretti Giuseppe Maria , Sirtori Paolo , Maffulli Nicola , Mangiavini Laura 
Published: June 2020

Abstract

Background
Low levels of vitamin D are common in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), but it is still unclear whether the outcome of such surgery is related to vitamin D levels.

Sources of data
Publicly available electronic databases were systematically reviewed to update knowledge about the role of vitamin D in THA and TKA patients, and to appraise the correlation between vitamin D levels before surgery and post-surgical outcomes. Eight studies were included in our review: six employed prospective observational designs, two reported retrospective database interrogations. Six prospective observational studies and two retrospective database interrogations matched inclusion and exclusion criteria.

Areas of agreement
Patients undergoing THA and TKA have a high prevalence of hypovitaminosis D. Five of eight studies (62.5%) report a statistically significant association between low vitamin D status and worse outcomes after THA and TKA.

Areas of controversy
Different explanations have been proposed for vitamin D insufficiency, but some authors have questioned the correctness of the methods used to measure the vitamin D levels.

Growing points
A trial focusing on the role of vitamin D supplementation on safety and outcomes of patients undergoing THA and TKA with low vitamin D status is ongoing.

Areas timely for developing research
Further studies should explore the possible causal relationship between vitamin D status and outcomes of THA and TKA and verify the laboratory methods to analyse it.
Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by Severe acute respiratory syndrome coronavirus 2
Authors: Gonfiotti Alessandro , Gatteschi Lavinia , Salvicchi Alberto , Bongiolatti Stefano , Lavorini Federico , Voltolini Luca 
Published: June 2020

Abstract

OBJECTIVES
There is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2.

METHODS
We retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported.

RESULTS
All patients were men with a mean age of 74.0 years (range 67–80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8–22); mean hospital stay was 33.8 days (range 21–60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively.

CONCLUSIONS
Lung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.
Comparison of pain perception, anxiety, and impacts on oral health-related quality of life between patients receiving clear aligners and fixed appliances during the initial stage of orthodontic treatment
Authors: Gao Meiya , Yan Xinyu , Zhao Rui , Shan Yue , Chen Yiyin , Jian Fan , Long Hu , Lai Wenli 
Published: June 2020

Abstract

Background and Objectives
Clear aligner is an advanced orthodontic method with benefits of comfort, aesthetics, and convenience. This study aimed to compare pain perception, anxiety, and impacts on oral health-related quality of life (OHRQoL) between adult patients receiving clear aligners and fixed appliances during the initial stage of orthodontic treatments.

Material and Methods
The two groups were well matched by ages, gender, and levels of malocclusion severity. Pain perception, anxiety, and OHRQoL were assessed through visual analogue scale, state-trait anxiety inventory, and oral health impact profile-14 (OHIP-14), respectively. And the comparison of above scores was performed by two-way analysis of variance.

Results
A total of 110 patients (55 pairs) were enrolled in this study. Orthodontic pain levels peaked on the first day and decreased gradually afterwards in both groups, which were significantly higher in the fixed group on the first, second, fourth, and fifth days. Likewise, anxiety levels peaked on the first day and decreased thereafter, with significant difference on the 1st, 3d, 5th, 7th, and 14th days. Moreover, the OHIP-14 scores increased and peaked on the first day and then gradually decreased for both groups, which were also significantly higher in the fixed group on the 1st, 7th, and 14th days.

Limitations
More malocclusion types should be used for group matching. The effect of exclusion of small groups should be taken into consideration in sample size calculation. Income was significantly unbalanced between two groups due to higher cost of clear aligners, and random assignment of treatment modalities was unfeasible.

Conclusions
Patients treated with clear aligners experienced lower pain levels, less anxiety, and higher OHRQoL as compared to those receiving fixed appliances.
Cell wall homeostasis in lactic acid bacteria: threats and defences
Authors: Martínez Beatriz , Rodríguez Ana , Kulakauskas Saulius , Chapot-Chartier Marie-Pierre 
Published: June 2020

ABSTRACTLactic acid bacteria (LAB) encompasses industrially relevant bacteria involved in food fermentations as well as health-promoting members of our autochthonous microbiota. In the last years, we have witnessed major progresses in the knowledge of the biology of their cell wall, the outermost macrostructure of a Gram-positive cell, which is crucial for survival. Sophisticated biochemical analyses combined with mutation strategies have been applied to unravel biosynthetic routes that sustain the inter- and intra-species cell wall diversity within LAB. Interplay with global cell metabolism has been deciphered that improved our fundamental understanding of the plasticity of the cell wall during growth. The cell wall is also decisive for the antimicrobial activity of many bacteriocins, for bacteriophage infection and for the interactions with the external environment. Therefore, genetic circuits involved in monitoring cell wall damage have been described in LAB, together with a plethora of defence mechanisms that help them to cope with external threats and adapt to harsh conditions. Since the cell wall plays a pivotal role in several technological and health-promoting traits of LAB, we anticipate that this knowledge will pave the way for the future development and extended applications of LAB.
Macular Ganglion Cell-Inner Plexiform Layer as a Marker of Cognitive and Sensory Function in Midlife
Authors: Merten Natascha , Paulsen Adam J , Pinto A Alex , Chen Yanjun , Dillard Lauren K , Fischer Mary E , Huang Guan-Hua , Klein Barbara E K , Schubert Carla R , Cruickshanks Karen J 
Published: June 2020

Abstract

Background
Neurodegenerative diseases are public health challenges in aging populations. Early identification of people at risk for neurodegeneration might improve targeted treatment. Noninvasive, inexpensive screening tools are lacking but are of great potential. Optical coherence tomography (OCT) measures the thickness of nerve cell layers in the retina, which is an anatomical extension of the brain and might be indicative of common underlying neurodegeneration. We aimed to determine the association of macular ganglion cell-inner plexiform layer (mGCIPL) thickness with cognitive and sensorineural function in midlife.

Method
This cross-sectional study included 1,880 Beaver Dam Offspring Study participants (aged 27–93 years, mean 58) who participated in the 10-year follow-up examination. We assessed cognitive function and impairment, hearing sensitivity thresholds and impairment, central auditory processing, visual impairment, and olfactory impairment. We measured mGCIPL using the Cirrus 5000 HD-OCT Macular Cube Scan. Multivariable linear and logistic regression models adjusted for potential confounders were used to determine associations between mGCIPL thickness and cognitive and sensorineural functions, as well as for comparing participants with a thin mGCIPL (1 SD below average) to the remainder in those functions.

Results
Thinner mGCIPL was associated with worse cognitive function, worse central auditory function, and visual impairment. We found an association of mGCIPL thickness with hearing sensitivity in women only and no association with impairment in hearing, olfaction, and cognition. Results on the thin group comparisons were consistent.

Conclusions
mGCIPL thickness is associated with cognitive and sensorineural function and has the potential as a marker for neurodegeneration in middle-aged adults.
Influenza Infection has Fiber Type-Specific Effects on Cellular and Molecular Skeletal Muscle Function in Aged Mice
Authors: Straight Chad R , Ringham Olivia R , Bartley Jenna M , Keilich Spencer R , Kuchel George A , Haynes Laura , Miller Mark S 
Published: June 2020

Abstract
Skeletal muscle myopathies represent a common non-pulmonary manifestation of influenza infection, leading to reduced physical function and hospitalization in older adults. However, underlying mechanisms remain poorly understood. Our study examined the effects of influenza virus A pulmonary infection on contractile function at the cellular (single fiber) and molecular (myosin-actin interactions and myofilament properties) levels in soleus and extensor digitorum longus muscles of aged (20 months) C57BL/6 male mice that were healthy or flu-infected for 7 (7-days post-infection; 7-DPI) or 12 days (12-DPI). Cross-sectional area (CSA) of myosin heavy chain (MHC) IIA and IIB fibers was reduced at 12-DPI relative to 7-DPI and healthy. Maximal isometric force in MHC IIA fibers was also reduced at 12-DPI relative to 7-DPI and healthy, resulting in no change in specific force (maximal isometric force divided by CSA). In contrast, MHC IIB fibers produced greater isometric force and specific force at 7-DPI compared to 12-DPI or healthy. The increased specific force in MHC IIB fibers was likely due to greater myofilament lattice stiffness and/or an increased number or stiffness of strongly bound myosin-actin cross-bridges. At the molecular level, cross-bridge kinetics were slower in MHC IIA fibers with infection, while changes in MHC IIB fibers were largely absent. In both fiber types, greater myofilament lattice stiffness was positively related to specific force. This study provides novel evidence that cellular and molecular contractile function is impacted by influenza infection in a fiber type-specific manner, suggesting potential molecular mechanisms to help explain the impact of flu-induced myopathies.
Iterative hard thresholding in genome-wide association studies: Generalized linear models, prior weights, and double sparsity
Authors: Chu Benjamin B , Keys Kevin L , German Christopher A , Zhou Hua , Zhou Jin J , Sobel Eric M , Sinsheimer Janet S , Lange Kenneth 
Published: June 2020

Abstract

Background
Consecutive testing of single nucleotide polymorphisms (SNPs) is usually employed to identify genetic variants associated with complex traits. Ideally one should model all covariates in unison, but most existing analysis methods for genome-wide association studies (GWAS) perform only univariate regression.

Results
We extend and efficiently implement iterative hard thresholding (IHT) for multiple regression, treating all SNPs simultaneously. Our extensions accommodate generalized linear models, prior information on genetic variants, and grouping of variants. In our simulations, IHT recovers up to 30% more true predictors than SNP-by-SNP association testing and exhibits a 2–3 orders of magnitude decrease in false-positive rates compared with lasso regression. We also test IHT on the UK Biobank hypertension phenotypes and the Northern Finland Birth Cohort of 1966 cardiovascular phenotypes. We find that IHT scales to the large datasets of contemporary human genetics and recovers the plausible genetic variants identified by previous studies.

Conclusions
Our real data analysis and simulation studies suggest that IHT can (i) recover highly correlated predictors, (ii) avoid over-fitting, (iii) deliver better true-positive and false-positive rates than either marginal testing or lasso regression, (iv) recover unbiased regression coefficients, (v) exploit prior information and group-sparsity, and (vi) be used with biobank-sized datasets. Although these advances are studied for genome-wide association studies inference, our extensions are pertinent to other regression problems with large numbers of predictors.
Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features
Authors: Crawford Parks Tara E , Marcellus Kristen A , Péladeau Christine , Jasmin Bernard J , Ravel-Chapuis Aymeric 
Published: June 2020

Abstract
In myotonic dystrophy type 1 (DM1), the CUG expansion (CUGexp) in the 3′ untranslated region of the dystrophia myotonica protein kinase messenger ribonucleic acid affects the homeostasis of ribonucleic acid-binding proteins, causing the multiple symptoms of DM1. We have previously reported that Staufen1 is increased in skeletal muscles from DM1 mice and patients and that sustained Staufen1 expression in mature mouse muscle causes a progressive myopathy. Here, we hypothesized that the elevated levels of Staufen1 contributes to the myopathic features of the disease. Interestingly, the classic DM1 mouse model human skeletal actin long repeat (HSALR) lacks overt atrophy while expressing CUGexp transcripts and elevated levels of endogenous Staufen1, suggesting a lower sensitivity to atrophic signaling in this model. We report that further overexpression of Staufen1 in the DM1 mouse model HSALR causes a myopathy via inhibition of protein kinase B signaling through an increase in phosphatase tensin homolog, leading to the expression of atrogenes. Interestingly, we also show that Staufen1 regulates the expression of muscleblind-like splicing regulator 1 and CUG-binding protein elav-like family member 1 in wild-type and DM1 skeletal muscle. Together, data obtained from these new DM1 mouse models provide evidence for the role of Staufen1 as an atrophy-associated gene that impacts progressive muscle wasting in DM1. Accordingly, our findings highlight the potential of Staufen1 as a therapeutic target and biomarker.
Example of Adverse Outcome Pathway Concept Enabling Genome-to-Phenome Discovery in Toxicology
Authors: Gust Kurt A , Ji Qing , Luo Xiao 
Published: June 2020

Synopsis
The following article represents a mini-review of an intensive 10-year progression of genome-to-phenome (G2P) discovery guided by the adverse outcome pathway (AOP) concept. This example is presented as a means to stimulate crossover of this toxicological concept to enhance G2P discovery within the broader biological sciences community. The case study demonstrates the benefits of the AOP approach for establishing causal linkages across multiple levels of biological organization ultimately linking molecular initiation (often at the genomic scale) to organism-level phenotypes of interest. The case study summarizes a US military effort to identify the mechanism(s) underlying toxicological phenotypes of lethargy and weight loss in response to nitroaromatic munitions exposures, such as 2,4,6-trinitrotoluene. Initial key discoveries are described including the toxicogenomic results that nitrotoluene exposures inhibited expression within the peroxisome proliferator activated receptor α (PPARα) pathway. We channeled the AOP concept to test the hypothesis that inhibition of PPARα signaling in nitrotoluene exposures impacted lipid metabolic processes, thus affecting systemic energy budgets, ultimately resulting in body weight loss. Results from a series of transcriptomic, proteomic, lipidomic, in vitro PPARα nuclear signaling, and PPARα knock-out investigations ultimately supported various facets of this hypothesis. Given these results, we next proceeded to develop a formalized AOP description of PPARα antagonism leading to body weight loss. This AOP was refined through intensive literature review and polished through multiple rounds of peer-review leading to final international acceptance as an Organisation for Economic Cooperation and Development-approved AOP. Briefly, that AOP identifies PPARα antagonist binding as the molecular initiating event (MIE) leading to a series of key events including inhibition of nuclear transactivation for genes controlling lipid metabolism and ketogenesis, inhibition of fatty acid beta-oxidation and ketogenesis dynamics, negative energy budget, and ultimately the adverse outcome (AO) of body-weight loss. Given that the PPARα antagonism MIE represented a reliable indicator of AO progression within the pathway, a phylogenetic analysis was conducted which indicated that PPARα amino acid relatedness generally tracked species relatedness. Additionally, PPARα amino acid relatedness analysis using the Sequence Alignment to Predict Across Species Susceptibility predicted susceptibility to the MIE across vertebrates providing context for AOP extrapolation across species. Overall, we hope this illustrative example of how the AOP concept has benefited toxicology sows a seed within the broader biological sciences community to repurpose the concept to facilitate enhanced G2P discovery in biology.
Remedies for algorithmic tacit collusion
Authors: Beneke Francisco , Mackenrodt Mark-Oliver 
Published: June 2020

Abstract
There is growing evidence that tacit collusion can be autonomously achieved by machine learning technology, at least in some real-life examples identified in the literature and experimental settings. Although more work needs to be done to assess the competitive risks of widespread adoption of autonomous pricing agents, this is still an appropriate time to examine which possible remedies can be used in case competition law shifts towards the prohibition of tacit collusion. This is because outlawing such conduct is pointless unless there are suitable remedies that can be used to address the social harm. This article explores how fines and structural and behavioural remedies can serve to discourage collusive results while preserving the incentives to use efficiency-enhancing algorithms. We find that this could be achieved if fines and remedies can target structural conditions that facilitate collusion. In addition, the problem of unfeasibility of injunctions to remedy traditional price coordination changes with the use of pricing software, which in theory can be programmed to avoid collusive outcomes. Finally, machine-learning methods can be used by the authorities themselves as a tool to test the effects of any given combination of remedies and to estimate a more accurate competitive benchmark for the calculation of the appropriate fine.
Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort
Authors: Lam Emily , Higgins Victoria , Zhang Liyong , Chan Man Khun , Bohn Mary Kathryn , Trajcevski Karin , Liu Peter , Adeli Khosrow , Nathan Paul C 
Published: June 2020

Abstract

Background
Cardiac troponin (cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are increasingly used clinically to evaluate and prognosticate acute myocardial infarction and heart failure, respectively. Pediatric reference intervals and cut-offs have not been established for Roche’s Elecsys Troponin T hs (high sensitive) assay. Although pediatric reference intervals exist for NT-proBNP, cut-off values do not exist. In this study, we report reference intervals and 99th percentile cut-offs in a large, healthy Canadian pediatric population using the CALIPER cohort.

Methods
Blood samples from 484 healthy children and adolescents between 0 and &lt;19 years old were recruited from hospital outpatient clinics and community settings. Serum samples were analyzed using Roche’s Cobas e411 and evaluated for high-sensitivity cTnT (hs-cTnT) and NT-proBNP concentrations. 95% reference intervals and 99th percentile cut-off values were established.

Results
Three hs-cTnT age partitions were established (0 to &lt;6 months, 6 months to &lt;1 year, and 1 to &lt;19 years) with highest concentrations observed in children under 1 year. Two NT-proBNP age partitions were established (0 to &lt;1 year, and 1 to &lt;19 years), also with higher concentrations in infants under 1 year of age. For each of these age partitions, the 99th percentile cut-off, 95% reference interval, and proportion of detectable concentrations were determined.

Conclusions
This is the first study to examine hs-cTnT and NT-proBNP reference values together in a healthy pediatric cohort without other clinical indications. We present 99th percentile cut-offs, which will allow clinicians to appropriately evaluate cardiovascular disease in children and adolescents.
Assessing the enrichment of dietary supplement coverage in the Unified Medical Language System
Authors: Vasilakes Jake , Bompelli Anusha , Bishop Jeffrey R , Adam Terrence J , Bodenreider Olivier , Zhang Rui 
Published: June 2020

AbstractObjectiveWe sought to assess the need for additional coverage of dietary supplements (DS) in the Unified Medical Language System (UMLS) by investigating (1) the overlap between the integrated DIetary Supplements Knowledge base (iDISK) DS ingredient terminology and the UMLS and (2) the coverage of iDISK and the UMLS over DS mentions in the biomedical literature.Materials and MethodsWe estimated the overlap between iDISK and the UMLS by mapping iDISK to the UMLS using exact and normalized strings. The coverage of iDISK and the UMLS over DS mentions in the biomedical literature was evaluated via a DS named-entity recognition (NER) task within PubMed abstracts.ResultsThe coverage analysis revealed that only 30% of iDISK terms can be matched to the UMLS, although these cover over 99% of iDISK concepts. A manual review revealed that a majority of the unmatched terms represented new synonyms, rather than lexical variants. For NER, iDISK nearly doubles the precision and achieves a higher F1 score than the UMLS, while maintaining a competitive recall.DiscussionWhile iDISK has significant concept overlap with the UMLS, it contains many novel synonyms. Furthermore, almost 3000 of these overlapping UMLS concepts are missing a DS designation, which could be provided by iDISK. The NER experiments show that the specialization of iDISK is useful for identifying DS mentions.ConclusionsOur results show that the DS representation in the UMLS could be enriched by adding DS designations to many concepts and by adding new synonyms.