bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Use of Regression Calibration in a Complex Sampling Design With Application to the Hispanic Community Health Study/Study of Latinos
Authors: Baldoni Pedro L , Sotres-Alvarez Daniela , Lumley Thomas , Shaw Pamela A 
Published: January 2021

AbstractRegression calibration is the most widely used method to adjust regression parameter estimates for covariate measurement error. Yet its application in the context of a complex sampling design, for which the common bootstrap variance estimator can be less straightforward, has been less studied. We propose 2 variance estimators for a multistage probability-based sampling design, a parametric and a resampling-based multiple imputation approach, where a latent mean exposure needed for regression calibration is the target of imputation. This work was motivated by the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) data from 2008 to 2011, for which relationships between several outcomes and diet, an error-prone self-reported exposure, are of interest. We assessed the relative performance of these variance estimation strategies in an extensive simulation study built on the HCHS/SOL data. We further illustrate the proposed estimators with an analysis of the cross-sectional association of dietary sodium intake with hypertension-related outcomes in a subsample of the HCHS/SOL cohort. We have provided guidelines for the application of regression models with regression-calibrated exposures. Practical considerations for implementation of these 2 variance estimators in the setting of a large multicenter study are also discussed. Code to replicate the presented results is available online.
Assessment of Conflicts of Interest in Studies of Breast Implants and Breast Implant Mesh
Authors: Tian Tina , Sekigami Yurie , Char Sydney , Bloomenthal Molly , Aalberg Jeffrey , Chen Lilian , Chatterjee Abhishek 
Published: January 2021

Abstract

Background
With increased collaboration between surgeons and industry, there has been a push towards improving transparency of conflicts of interest (COI).

Methods
A literature search identified all articles published between 2016 – 2018 involving breast implants/implantable mesh from three major United States plastic surgery journals. Industry payment data from 8 breast implant/implantable mesh companies was collected using the CMS Open Payments database. COI discrepancies were identified by comparing author declaration statements with payments &gt;$100.00 found for the year of publication and year prior. Risk factors for discrepancy were determined at study and author levels.

Results
A total of 162 studies (548 authors) were identified. 126 (78%) studies had at least one author receive undisclosed payments. 295 (54%) authors received undisclosed payments. Comparative studies were significantly more likely to have COI discrepancy than non- comparative studies (83% vs 69%, p &lt; 0.05). Multivariate analysis showed no association between COI discrepancy and final product recommendation. Authors who accurately disclosed payments received higher payments compared to authors who did not accurately disclose payments (median $40,349 IQR 7278-190,413 vs median $1300 IQR 429-11,1544, p &lt;0.001).

Conclusions
The majority of breast implant-based studies had undisclosed COIs. Comparative studies were more likely to have COI discrepancy. Authors who accurately disclosed COIs received higher payments than authors with discrepancies. This study highlights the need for increased efforts to improve the transparency of industry sponsorship for breast implant-based studies.
Aerobic bioconversion of C-glycoside mangiferin into its aglycone norathyriol by an isolated mouse intestinal bacterium
Authors: Hasanah Uswatun , Miki Kasumi , Nitoda Teruhiko , Kanzaki Hiroshi 
Published: January 2021

ABSTRACT
Norathyriol is an aglycone of a xanthonoid C-glycoside mangiferin that possesses different bioactive properties useful for humans compared to mangiferin. Mangiferin is more readily available in nature than norathyriol; thus, efficient mangiferin conversion into norathyriol is desirable. There are a few reports regarding mangiferin C-deglycosylation because of the C–C bond resistance toward acid, alkaline, and enzyme hydrolysis. In this study, we isolated a mangiferin-deglycosylating bacterium strain KM7-1 from the mouse intestine. 16S rDNA sequencing indicated that KM7-1 belongs to the Bacillus genus. Compared to the taxonomically similar bacteria, the growth characteristic of facultative anaerobic and thermophilic resembled, yet only Bacillus sp. KM7-1 was able to convert mangiferin into norathyriol. Resting cells of Bacillus sp. KM7-1 obtained from aerobic cultivation at 50 °C showed high norathyriol formation from 1 m m of mangiferin. Norathyriol formation can be conducted either under aerobic or anaerobic conditions, and the reaction depended on time and bacterial amount.
From mutation to mechanism: deciphering the molecular function of genetic variants linked to human ageing
Authors: Baghdadi Maarouf , Hinterding Helena M , Partridge Linda , Deelen Joris 
Published: January 2021

Abstract
Many of the leading causes of death in humans, such as cardiovascular disease, type 2 diabetes and Alzheimer’s disease are influenced by biological mechanisms that become dysregulated with increasing age. Hence, by targeting these ageing-related mechanisms, we may be able to improve health in old age. Ageing is partly heritable and genetic studies have been moderately successful in identifying genetic variants associated with ageing-related phenotypes (lifespan, healthspan and longevity). To decipher the mechanisms by which the identified variants influence ageing, studies that focus on their functional validation are vital. In this perspective, we describe the steps that could be taken in the process of functional validation: (1) in silico characterisation using bioinformatic tools; (2) in vitro characterisation using cell lines or organoids; and (3) in vivo characterisation studies using model organisms. For the in vivo characterisation, it is important to focus on translational phenotypes that are indicative of both healthspan and lifespan, such as the frailty index, to inform subsequent intervention studies. The depth of functional validation of a genetic variant depends on its location in the genome and conservation in model organisms. Moreover, some variants may prove to be hard to characterise due to context-dependent effects related to the experimental environment or genetic background. Future efforts to functionally characterise the (newly) identified genetic variants should shed light on the mechanisms underlying ageing and will help in the design of targeted interventions to improve health in old age.
Network-adjusted Kendall’s Tau Measure for Feature Screening with Application to High-dimensional Survival Genomic Data
Authors: Wang Jie-Huei , Chen Yi-Hau 
Published: January 2021

Abstract

Motivation
In high-dimensional genetic/genomic data, the identification of genes related to clinical survival trait is a challenging and important issue. In particular, right-censored survival outcomes and contaminated biomarker data make the relevant feature screening difficult. Several independence screening methods have been developed, but they fail to account for gene–gene dependency information, and may be sensitive to outlying feature data.

Results
We improve the inverse probability-of-censoring weighted (IPCW) Kendall’s tau statistic by using Google’s PageRank Markov matrix to incorporate feature dependency network information. Also, to tackle outlying feature data, the nonparanormal approach transforming the feature data to multivariate normal variates are utilized in the graphical lasso procedure to estimate the network structure in feature data. Simulation studies under various scenarios show that the proposed network-adjusted weighted Kendall’s tau approach leads to more accurate feature selection and survival prediction than the methods without accounting for feature dependency network information and outlying feature data. The applications on the clinical survival outcome data of diffuse large B-cell lymphoma and of The Cancer Genome Atlas lung adenocarcinoma patients demonstrate clearly the advantages of the new proposal over the alternative methods.

Supplementary information
Supplementary data are available at Bioinformatics online.
Extraordinary diversification of the “bristle flies” (Diptera: Tachinidae) and its underlying causes
Authors: Stireman John O , Cerretti Pierfilippo , O’hara James E , Moulton John K 
Published: January 2021

AbstractThe family Tachinidae (“bristle flies”) is the most diverse and ecologically important group of insect parasitoids outside the parasitic wasps. It is among the most species rich families of flies (Diptera) and has experienced a recent adaptive radiation across the globe. We make use of a molecular phylogeny of the family to examine its rapid radiation and explore the traits of tachinid lineages that may have contributed to variation in their diversification. We apply a range of diversification analyses to assess the consistency and robustness of effects. We find that the Tachinidae are among the most rapidly diversifying families of animals. Six to eight clades of bristle flies, distributed across the phylogeny, exhibit strong evidence of accelerated diversification. Our results suggest that the use of holometabolous insect larvae, and specifically caterpillars (Lepidoptera), as hosts, is associated with increased diversification rates. However, these effects were inconsistent across analyses. We detected little influence of oviposition strategy (egg type) or host feeding habit, and we recovered evidence that unmeasured “hidden” traits may explain greater variance in diversification. We evaluated the strengths and weaknesses of different Maximum Likelihood and Bayesian approaches for analysing diversification and the potential for extrinsic factors, such as geography, to influence patterns of richness and diversification. In general, we conclude that although certain traits may provide opportunities for diversification, whether this is capitalized on may depend on additional traits and/or historical contingency.
Capillary Electrophoresis Separation of Artepillin C: Determination in Brazilian Green Propolis
Authors: Galeotti Fabio , Capitani Federica , Maccari Francesca , Mantovani Veronica , Volpi Nicola 
Published: January 2021

Abstract
Propolis is important in complementary and alternative medicine having well-known therapeutic applications. Artepillin C, a main component of Brazilian (green) propolis, has attracted great attention for its anticancer action. Consequently, the synthesis of artepillin C has been reported but, due to the limited yield and elevated costs, this biomolecule is largely produced from Brazilian propolis. We report the capillary electrophoresis (CE) separation of artepillin C in Brazilian propolis also comparing the results with those of HPLC-UV-MS. Optimal separation was obtained with a simple buffer constituted of sodium tetraborate 30 mM pH 9.2 and detection at 210 nm. Artepillin C and the polyphenols of propolis were fully separated with a voltage gradient of 30 to 8 kV and a current of 300 μA for a total run of 50 min. The sensitivity of CE-UV was 22 times greater than HPLC-UV and 100 times more than HPLC-MS with also a stronger reduction in the run time and a greater robustness and reproducibility. The development of CE as an effective and reliable method for the analysis of artepillin C is desired as the standardized quality controls are essential before propolis or its biomolecules can be adopted routinely in nutraceuticals, food ingredients and therapeutic applications.
Simultaneous Estimation of Apremilast and Betamethasone Dipropionate in Microsponge-Based Topical Formulation using a Stability Indicating RP-HPLC Method: A Quality-by-Design Approach
Authors: Mullick Prashansha , Mutalik Sadhana P , Hegde Aswathi R , Pandey Abhijeet , Jagadish P C , Kini Suvarna G , Jain Sanyog , Mutalik Srinivas 
Published: January 2021

Abstract
A stability-indicating reverse phase high-performance liquid chromatography method was developed and validated for simultaneous quantification of apremilast (APL) and betamethasone dipropionate (BD) in bulk as well as drug loaded microsponges. Various mobile phase systems were screened to check the system suitability followed by force degradation analysis to determine APL and BD stability under varying stress conditions. A central composite design model was used to optimize the column temperature and flow rate using Design Expert® (9.0.1). One factor at a time approach with five independent factors were used to validate the robustness of the method. Finally, APL and BD were precisely and accurately quantified from drug loaded microsponges using the validated method. A favorable separation of APL and BD was obtained on a Phenomenex® Luna C18 column using a mixture of 50 mM phosphate buffer containing 0.1% triethylamine (pH 6.1) and acetonitrile (60:40%v/v) as mobile phase. Both the drugs were found to be stable when exposed to stressors such as heat-, light-, alkali-, acid- and peroxide-induced degradation. The calibration curves were found to be linear with appreciable limit of detection and limit of quantification. Recovery and percentage relative standard deviation of peak areas for APL and BD were found to be &lt; 2.0% and 99–100% in bulk drug solution and &lt;2.0% and 99–103% in microsponge formulation, respectively. Statistical analysis using analysis of variance indicated that the model was significant (P &lt; 0.001). Hence, the developed method can be effectively used to quantify APL and BD, both in bulk as well as microsponge formulations.
Effectiveness of the 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-Serotype Otitis Media
Authors: Dagan Ron , Van Der Beek Bart Adriaan , Ben-Shimol Shalom , Pilishvili Tamara , Givon-Lavi Noga 
Published: January 2021

Abstract

Background
Despite the demonstrated impact of pneumococcal vaccine (PCV) implementation on otitis media (OM), demonstration of real-life serotype-specific effectiveness of the 7-valent and 13-valent PCVs (PCV7 and PCV13) is lacking owing to the paucity of culture-positive cases. Furthermore, prelicensure PCV13 efficacy against OM was not studied.

Methods
The study was conducted from October 2009 to July 2013. Case patients were children aged 5–35 months with OM (mostly complex OM [recurrent/nonresponsive, spontaneously draining, chronic with effusion]) from whom middle-ear fluid culture was obtained; controls were contemporary children with rotavirus-negative gastroenteritis in a prospective population-based rotavirus surveillance, from the same age group with similar ethnic distribution and geographic location. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio using unconditional logistic regression, adjusting for time since PCV implementation, age, and ethnicity.

Results
A total of 223 case patients and 1370 controls were studied. Serotypes 19F and 19A together caused 56.1% of all vaccine-type (VT) OM. VE of ≥2 PCV doses in children aged 5–35 months was demonstrated as follows: PCV7 against OM due to PCV7 serotypes, 57.2% (95% confidence interval, 6.0%–80.5%); PCV13 against OM due to PCV13 serotypes, 77.4% (53.3%–92.1%); PCV13 against OM due to the 6 additional non-PCV7 serotypes 67.4% (17.6%–87.1%); PCV13 against OM due to serotype 19F, 91.3% (1.4%–99.2%); and PCV13 against OM due to serotype 3, 89.0% (23.9%–98.4%). PCV7 and PCV13 VE against OM due to serotype 19A in children aged 12–35 months was 72.4% (95% confidence interval, 6.2%–91.9%) and 94.6% (33.9%–99.6%), respectively.

Conclusions
PCV7 and PCV13 were effective against complex OM caused by the targeted serotypes.
Transcontinental Dissemination of the L2b/D-Da Recombinant Chlamydia trachomatis Lymphogranuloma venereum (LGV) Strain: Need of Broad Multi-Country Molecular Surveillance
Authors: Borges Vítor , Isidro Joana , Correia Cristina , Cordeiro Dora , Vieira Luís , Lodhia Zohra , Fernandes Cândida , Rodrigues Ana Maria , Azevedo Jacinta , Alves João , Roxo João , Rocha Miguel , Côrte-Real Rita , Toscano Cristina , Pessanha Maria Ana , Nissan Israel , Pilo Shlomo , Rorman Efrat , Dveyrin Zeev , Paitan Yossi , Paran Haim , Wagner-Kolasko Gal , Beirnes Jennifer , Gibbons Suzanne , Severini Alberto , Borrego Maria José , Gomes João Paulo 
Published: January 2021

Abstract
Previously, we identified a Chlamydia trachomatis lymphogranuloma venereum (LGV) recombinant strain possessing a non-LGV ompA genotype. Here, culture-independent genome sequencing confirms its circulation in Europe, Middle East, and North America, and unveils emergence of antibiotic resistance. Broad surveillance is needed.
Adverse clinical outcomes associated with RAAS inhibitor discontinuation: analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD)
Authors: Humphrey Toby J L , James Glen , Wittbrodt Eric T , Zarzuela Donna , Hiemstra Thomas F 
Published: January 2021

AbstractBackgroundUsers of guideline-recommended renin–angiotensin–aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database.MethodsThis exploratory, retrospective analysis utilized data from the UK’s Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed.ResultsAmong 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8–75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure.ConclusionsThese findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.
Clonotypic Features of Rearranged Immunoglobulin Genes Yield Personalized Biomarkers for Minimal Residual Disease Monitoring in Multiple Myeloma
Authors: Langerhorst Pieter , Brinkman Arie B , VanDuijn Martijn M , Wessels Hans J C T , Groenen Patricia J T A , Joosten Irma , van Gool Alain J , Gloerich Jolein , Scheijen Blanca , Jacobs Joannes F M 
Published: January 2021

Abstract

Background
Due to improved treatment, more patients with multiple myeloma (MM) reach a state of minimal residual disease (MRD). Different strategies for MM MRD monitoring include flow cytometry, allele-specific oligonucleotide–quantitative PCR, next-generation sequencing, and mass spectrometry (MS). The last 3 methods rely on the presence and the stability of a unique immunoglobulin fingerprint derived from the clonal plasma cell population. For MS-MRD monitoring it is imperative that MS-compatible clonotypic M-protein peptides are identified. To support implementation of molecular MRD techniques, we studied the presence and stability of these clonotypic features in the CoMMpass database.

Methods
An analysis pipeline based on MiXCR and HIGH-VQUEST was constructed to identify clonal molecular fingerprints and their clonotypic peptides based on transcriptomic datasets. To determine the stability of the clonal fingerprints, we compared the clonal fingerprints during disease progression for each patient.

Results
The analysis pipeline to establish the clonal fingerprint and MS-suitable clonotypic peptides was successfully validated in MM cell lines. In a cohort of 609 patients with MM, we demonstrated that the most abundant clone harbored a unique clonal molecular fingerprint and that multiple unique clonotypic peptides compatible with MS measurements could be identified for all patients. Furthermore, the clonal immunoglobulin gene fingerprints of both the light and heavy chain remained stable during MM disease progression.

Conclusions
Our data support the use of the clonal immunoglobulin gene fingerprints in patients with MM as a suitable MRD target for MS-MRD analyses.
The complex network of mTOR signalling in the heart
Authors: Sciarretta Sebastiano , Forte Maurizio , Frati Giacomo , Sadoshima Junichi 
Published: January 2021

Abstract
The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.
Extraction of causal relations based on SBEL and BERT model
Authors: Shao Yifan , Li Haoru , Gu Jinghang , Qian Longhua , Zhou Guodong 
Published: January 2021

AbstractExtraction of causal relations between biomedical entities in the form of Biological Expression Language (BEL) poses a new challenge to the community of biomedical text mining due to the complexity of BEL statements. We propose a simplified form of BEL statements [Simplified Biological Expression Language (SBEL)] to facilitate BEL extraction and employ BERT (Bidirectional Encoder Representation from Transformers) to improve the performance of causal relation extraction (RE). On the one hand, BEL statement extraction is transformed into the extraction of an intermediate form—SBEL statement, which is then further decomposed into two subtasks: entity RE and entity function detection. On the other hand, we use a powerful pretrained BERT model to both extract entity relations and detect entity functions, aiming to improve the performance of two subtasks. Entity relations and functions are then combined into SBEL statements and finally merged into BEL statements. Experimental results on the BioCreative-V Track 4 corpus demonstrate that our method achieves the state-of-the-art performance in BEL statement extraction with F1 scores of 54.8% in Stage 2 evaluation and of 30.1% in Stage 1 evaluation, respectively.Database URL: https://github.com/grapeff/SBEL_datasets