bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Collaborative Effort to Define Classification Criteria forATMVariants in Hereditary Cancer Patients
Authors: Feliubadaló Lidia , Moles-Fernández Alejandro , Santamariña-Pena Marta , Sánchez Alysson T , López-Novo Anael , Porras Luz-Marina , Blanco Ana , Capellá Gabriel , de la Hoya Miguel , Molina Ignacio J , Osorio Ana , Pineda Marta , Rueda Daniel , de la Cruz Xavier , Diez Orland , Ruiz-Ponte Clara , Gutiérrez-Enríquez Sara , Vega Ana , Lázaro Conxi 
Published: October 2020

AbstractBackgroundGene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene.MethodsSix independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants.ResultsAmid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%.ConclusionsOur results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.
A tool for assessment of risk of bias in studies of adverse effects of orthodontic treatment applied in a systematic review on external root resorption
Authors: Johansson Kristina , Lindh Christina , Paulsson Liselotte , Rohlin Madeleine 
Published: October 2020

Summary

Background and aims
Systematic reviews (SRs) are considered to provide reliable estimates, but flaws in designs, methods of monitoring effects, and outcomes have the potential to bias results. There are several tools for assessing risk of bias (RoB), most of them designed for SRs of beneficial effects. To our knowledge, there is no tool that is adapted specifically to assess RoB in studies of adverse effects associated with orthodontic treatment. To address this, the aim of this study was first to introduce a tool for assessment of RoB in studies of adverse effects associated with orthodontic treatment and, second, to apply it in an SR of external root resorption (ERR) associated with orthodontic treatment with fixed appliance.

Materials and methods
The approach with domains supported by signalling questions was used for the tool. Domains and signalling questions were tailored to the review questions of the SR of studies of ERR after orthodontic treatment using periapical radiography or cone beam computed tomography. Duplicate study selection, data extraction, and RoB assessment using the tool, followed by meta-analyses, were performed.

Results
Using the tool for the assessment of RoB identified shortcomings and report deficiencies of primary studies concerning the presentation of orthodontic treatment, identification of ERR, and analysis of outcomes. RoB assessment resulted in 12 of 32 studies read in full text being included. Reported severe ERR varied across studies between 2 and 14 per cent for all incisors and 10 and 29 per cent for maxillary incisors. Results of ERR related to patients’ age and sex, orthodontic diagnosis, and treatment were contradictory. Quality of evidence evaluated by GRADE was low due to study limitations, imprecision, and inconsistency of study results.

Conclusions
As the tool and its application highlight important issues to consider when planning, conducting, and reporting research, the tool may have a valuable role for quality enhancement of future studies of outcomes of orthodontic treatment. The tool may also serve for authors when planning SRs. Our SR identified a need for studies that use rigorous methodology and transparent reporting.

Registration
PROSPERO (ID = CRD42018084725).
Functional characterization of the adenine transporter EaAdeP from the fire blight pathogenErwinia amylovoraand its effect on disease establishment in apples and pears
Authors: Alexander Candace R , Huntley Regan B , Schultes Neil P , Mourad George S 
Published: October 2020

ABSTRACTErwinia amylovora is the causal agent of fire blight, an economically important disease of apples and pears. As part of the infection process, Er. amylovora propagates on different plant tissues each with distinct nutrient environments. Here, the biochemical properties of the Er. amylovora adenine permease (EaAdeP) are investigated. Heterologous expression of EaAdeP in nucleobase transporter-deficient Escherichia coli strains, coupled with radiolabel uptake studies, revealed that EaAdeP is a high affinity adenine transporter with a Km of 0.43 ± 0.09 μM. Both Es. coli and Er. amylovora carrying extra copies of EaAdeP are sensitive to growth on the toxic analog 8-azaadenine. EaAdeP is expressed during immature pear fruit infection. Immature pear and apple fruit virulence assays reveal that an E. amylovora ΔadeP::Camr mutant is still able to cause disease symptoms, however, with growth at a lower level, indicating that external adenine is utilized in disease establishment.
Evolutionary and Comparative Analysis of Bacterial Nonhomologous End Joining Repair
Authors: Sharda Mohak , Badrinarayanan Anjana , Seshasayee Aswin Sai Narain 
Published: October 2020

Abstract
DNA double-strand breaks (DSBs) are a threat to genome stability. In all domains of life, DSBs are faithfully fixed via homologous recombination. Recombination requires the presence of an uncut copy of duplex DNA which is used as a template for repair. Alternatively, in the absence of a template, cells utilize error-prone nonhomologous end joining (NHEJ). Although ubiquitously found in eukaryotes, NHEJ is not universally present in bacteria. It is unclear as to why many prokaryotes lack this pathway. Toward understanding what could have led to the current distribution of bacterial NHEJ, we carried out comparative genomics and phylogenetic analysis across ∼6,000 genomes. Our results show that this pathway is sporadically distributed across the phylogeny. Ancestral reconstruction further suggests that NHEJ was absent in the eubacterial ancestor and can be acquired via specific routes. Integrating NHEJ occurrence data for archaea, we also find evidence for extensive horizontal exchange of NHEJ genes between the two kingdoms as well as across bacterial clades. The pattern of occurrence in bacteria is consistent with correlated evolution of NHEJ with key genome characteristics of genome size and growth rate; NHEJ presence is associated with large genome sizes and/or slow growth rates, with the former being the dominant correlate. Given the central role these traits play in determining the ability to carry out recombination, it is possible that the evolutionary history of bacterial NHEJ may have been shaped by requirement for efficient DSB repair.
Evolutionary History of Alpha Satellite DNA Repeats Dispersed within Human Genome Euchromatin
Authors: Feliciello Isidoro , Pezer Željka , Kordiš Dušan , Bruvo Mađarić Branka , Ugarković Đurđica 
Published: October 2020

Abstract
Major human alpha satellite DNA repeats are preferentially assembled within (peri)centromeric regions but are also dispersed within euchromatin in the form of clustered or short single repeat arrays. To study the evolutionary history of single euchromatic human alpha satellite repeats (ARs), we analyzed their orthologous loci across the primate genomes. The continuous insertion of euchromatic ARs throughout the evolutionary history of primates starting with the ancestors of Simiformes (45–60 Ma) and continuing up to the ancestors of Homo is revealed. Once inserted, the euchromatic ARs were stably transmitted to the descendant species, some exhibiting copy number variation, whereas their sequence divergence followed the species phylogeny. Many euchromatic ARs have sequence characteristics of (peri)centromeric alpha repeats suggesting heterochromatin as a source of dispersed euchromatic ARs. The majority of euchromatic ARs are inserted in the vicinity of other repetitive elements such as L1, Alu, and ERV or are embedded within them. Irrespective of the insertion context, each AR insertion seems to be unique and once inserted, ARs do not seem to be subsequently spread to new genomic locations. In spite of association with (retro)transposable elements, there is no indication that such elements play a role in ARs proliferation. The presence of short duplications at most of ARs insertion sites suggests site-directed recombination between homologous motifs in ARs and in the target genomic sequence, probably mediated by extrachromosomal circular DNA, as a mechanism of spreading within euchromatin.
Worse outcomes after conversion of thoracoscopic lobectomy for lung cancer
Authors: Gabryel Piotr , Piwkowski Cezary , Kasprzyk Mariusz , Zieliński Paweł , Roszak Magdalena , Dyszkiewicz Wojciech 
Published: October 2020

Abstract

OBJECTIVES
Conversion of thoracoscopic lobectomy for lung cancer to thoracotomy can adversely affect short-term outcomes, but the impact on long-term outcomes is unknown. This study aimed to identify the risk factors for conversion and to determine the influence of conversion on the outcomes of lung cancer treatment.

METHODS
This retrospective study included 1002 consecutive patients with lung cancer who underwent thoracoscopic lobectomy between 7 June 1999 and 17 July 2018. The groups of patients with and without conversion were compared in terms of possible risk factors and the short- and long-term outcomes. The survival of patients was analysed by the Kaplan–Meier method.

RESULTS
Conversion was done in 105 patients (10.5%). On multivariable logistic regression analysis, the independent risk factors for conversion were pleural adhesions (P &lt; 0.001) and mediastinal lymph node metastases (P &lt; 0.001). Compared with the non-conversion group, the conversion group had longer chest drainage time (4 vs 3 days, P &lt; 0.001) and hospital stay (8 vs 6 days, P &lt; 0.001); more frequent complications (38.1% vs 27.1%, P = 0.018), including red blood cell transfusion (10.5% vs 2%, P &lt; 0.001) and supraventricular arrhythmia (13.3% vs 7.5%, P = 0.037); and lower 5-year survival rate in patients with stage I lung cancer (70% vs 87%, P = 0.014). Conversion did not increase in-hospital mortality.

CONCLUSIONS
Pleural adhesions and lymph node metastases increased the probability of conversion to thoracotomy. Conversion adversely affected the short-term outcomes of thoracoscopic lobectomy. Long-term outcomes of treatment of non-small-cell lung cancer could be worse in patients after conversion, but definitive conclusions cannot be made in this regard because of the absence of control of selection bias.
Patient-reported outcome measures after mitral valve repair: a comparison between minimally invasive and sternotomy
Authors: Whiteley Jennifer , Toolan Caroline , Shaw Matthew , Perin Giordano , Palmer Kenneth , Al-Rawi Omar , Modi Paul 
Published: October 2020

Abstract

OBJECTIVES
To compare patient-reported outcome measures of minimally invasive (MI) to sternotomy (ST) mitral valve repair.

METHODS
We included all patients undergoing isolated mitral valve surgery via either a right mini-thoracotomy (MI) or ST over a 36-month period. Patients were asked to complete a modified Composite Physical Function questionnaire. Intraoperative and postoperative outcomes, and patient-reported outcome measures were compared between 2 propensity-matched groups (n = 47/group), assessing 3 domains: ‘Recovery Time’, ‘Postoperative Pain’ (at day 2 and 1, 3, 6 and 12 weeks) and ‘Treatment Satisfaction’. Composite scores for each domain were subsequently constructed and multivariable analysis was used to determine whether surgical approach was associated with domain scores.

RESULTS
The response rate was 79%. There was no mortality in either group. In the matched groups, operative times were longer in the MI group (P &lt; 0.001), but postoperative outcomes were similar. Composite scores for Recovery Time [ST 51.7 (31.8–62.1) vs MI 61.7 (43.1–73.9), P = 0.03] and Pain [ST 65.7 (40.1–83.1) vs MI 79.1 (65.5–89.5), P = 0.02] significantly favoured the MI group. Scores in the Treatment Satisfaction domain were high for both surgical approaches [ST 100 (82.5–100) vs MI 100 (95.0–100), P = 0.15]. The strongest independent predictor of both faster recovery parameter estimate 12.0 [95% confidence interval (CI) 5.7–18.3, P &lt; 0.001] and less pain parameter estimate 7.6 (95% CI 0.7–14.5, P = 0.03) was MI surgery.

CONCLUSIONS
MI surgery was associated with faster recovery and less pain; treatment satisfaction and safety profiles were similar.
Maternal Epstein-Barr Virus-Specific Antibodies and Risk of Infection in Ugandan Infants
Authors: Minab Rana , Bu Wei , Nguyen Hanh , Wall Abigail , Sholukh Anton M , Huang Meei-Li , Ortego Michael , Krantz Elizabeth M , Irvine Michael , Casper Corey , Orem Jackson , McGuire Andrew T , Cohen Jeffrey I , Gantt Soren 
Published: October 2020

AbstractBackgroundEpstein-Barr virus (EBV) infection is a major cause of malignancy worldwide. Maternal antibody is thought to prevent EBV infection because it is uncommon in early infancy. Maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants, which we hypothesized results from impaired transfer of EBV-neutralizing maternal antibodies.MethodsAmong Ugandan infants followed for EBV acquisition from birth, we measured antibody binding to EBV glycoproteins (gp350, gH/gL) involved in B-cell and epithelial-cell entry, as well as viral neutralization and antibody-dependent cellular cytotoxicity (ADCC) activity in plasma samples prior to infection. These serologic data were analyzed for differences between HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) infants, and for associations with incident infant EBV infection.ResultsHEU infants had significantly higher titers than HUU infants for all EBV-binding and neutralizing antibodies measured (P &lt; .01) but not ADCC activity, which was similar between groups. No antibody measure was associated with a decreased risk of EBV acquisition in the cohort.ConclusionsOur findings indicate that in this cohort maternal antibody did not protect infants against EBV infection through viral neutralization. The identification of protective nonneutralizing antibody functions would be invaluable for the development of an EBV vaccine.
HIV-1 Transcription but Not Intact Provirus Levels are Associated With Systemic Inflammation
Authors: Olson Alex , Coote Carolyn , Snyder-Cappione Jennifer E , Lin Nina , Sagar Manish 
Published: October 2020

Abstract
Individuals infected with human immunodeficiency virus (HIV) 1 have increased inflammation, which has been associated with age-associated diseases. Plasma markers, cell-associated virus levels, and ability to stimulate RNA transcription in latently infected cell lines was examined in younger and older HIV-1–infected individuals with suppressed virus. Cell-associated RNA, but not intact provirus level, had positive correlation with plasma D-dimer levels. Compared with the younger group, the older group had higher D-dimer levels and a trend toward more cell-associated RNA but similar levels of intact proviruses. Even though all measured inflammatory markers were relatively higher in the older group, this greater inflammation did not induce more HIV-1 transcription in latently infected cell lines. Inflammation and HIV-1 RNA expression increase with age despite similar levels of intact infectious HIV DNA. While plasma inflammation is correlated with HIV-1 RNA expression in peripheral blood mononuclear cells, it does not induce HIV-1 transcription in latently infected cell lines.
Associations Between Genetically Predicted Protein Levels and COVID-19 Severity
Authors: Zhu Jingjing , Wu Chong , Wu Lang 
Published: October 2020

Abstract
It is critical to identify potential causal targets for SARS-CoV-2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from the COVID-19 Host Genetics Initiative comparing 6492 hospitalized COVID-19 patients and 1 012 809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of &lt;0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, 6 showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity.
Sharing patient-generated data with healthcare providers: findings from a 2019 national survey
Authors: Turner Kea , Jo Ara , Wei Grace , Tabriz Amir Alishahi , Clary Alecia , Jim Heather S L 
Published: October 2020

Abstract

Objective
Our study estimates the prevalence and predictors of wearable device adoption and data sharing with healthcare providers in a nationally representative sample.

Materials and Methods
Data were obtained from the 2019 Health Information National Trend Survey. We conducted multivariable logistic regression to examine predictors of device adoption and data sharing.

Results
The sample contained 4159 individuals, 29.9% of whom had adopted a wearable device in 2019. Among adopters, 46.3% had shared data with their provider. Individuals with diabetes (odds ratio [OR], 2.39; 95% CI, 1.66–3.45; P &lt; .0001), hypertension (OR, 2.80; 95% CI, 2.12–3.70; P &lt; .0001), and multiple chronic conditions (OR, 1.55; 95% CI, 1.03–2.32; P &lt; .0001) had significantly higher odds of wearable device adoption. Individuals with a usual source of care (OR, 2.44; 95% CI, 1.95–3.04; P &lt; .0001), diabetes (OR, 1.66; 95% CI, 1.32–2.08; P &lt; .0001), and hypertension (OR, 1.78; 95% CI, 1.44–2.20; P &lt; .0001) had significantly higher odds of sharing data with providers.

Discussion
A third of individuals adopted a wearable medical device and nearly 50% of individuals who owned a device shared data with a provider in 2019. Patients with certain conditions, such as diabetes and hypertension, were more likely to adopt devices and share data with providers. Social determinants of health, such as income and usual source of care, negatively affected wearable device adoption and data sharing, similarly to other consumer health technologies.

Conclusions
Wearable device adoption and data sharing with providers may be more common than prior studies have reported; however, digital disparities were noted. Studies are needed that test implementation strategies to expand wearable device use and data sharing into care delivery.
Chemical composition and in vitro fermentation characteristics of ancient grains using canine fecal inoculum
Authors: Traughber Zachary T , He Fei , Hoke Jolene M , Davenport Gary M , de Godoy Maria R C 
Published: October 2020

Abstract
Human interest in ancient grains replacing traditional carbohydrate sources has reached the pet food market; however, chemical composition of these grains and their digestive properties in the canine model, specifically the fermentative characteristics, have not been established. Five ancient grain varieties were analyzed: amaranth (AM), white proso millet (WPM), oat groats (OG), quinoa (QU), and red millet (RM). Cellulose (CEL) was used as a negative control, and beet pulp (BP) was used as a positive control. Substrates were analyzed for macronutrient composition as well as free and hydrolyzed sugar profiles in addition to their in vitro fermentative characteristics. Substrates were allocated into 2 sets to allow for quantification of pH, short-chain fatty acids, and branched-chain fatty acids, as well as gas volume and composition. Samples were digested for 6 and 18 h with pepsin and pancreatin, respectively, prior to inoculation with fecal bacteria for 0, 3, 6, 9, or 12 h. Detectable levels of cereal β-glucans were observed solely in OG (3.5%), with all other substrate containing &lt;0.35% cereal β-glucans. All test substrates had fairly similar macronutrient and starch profiles with the exception of RM that contained the highest resistant starch content (2.4%), with all other test substrates containing &lt;0.5% resistant starch. However, the analyzed pseudocereals, AM and QU, had the highest concentrations of free glucose while the minor cereal grains, WPM, OG, and RM, contained the highest concentrations of hydrolyzed glucose. All test substrates had propionate production values similar or greater than BP after 3, 6, 9, and 12 h of fermentation, and similar or greater butyrate production values than BP after 6, 9, and 12 h. All substrates had greater (P &lt; 0.05) changes in pH than CEL after 6, 9, and 12 h, with AM, WPM, OG, and RM having greater (P &lt; 0.05) changes in pH than BP after 9 and 12 h. These data suggest select ancient grains have similar fermentation characteristics as BP, a moderately fermentable fiber considered the gold standard in terms of fiber sources in the pet food market today, and that OG and AM may be more fermentable during longer fermentation periods.
Confronting Colonial Amnesia
Authors: Stahn Carsten 
Published: October 2020

Abstract
Colonial injustice has suffered from the effects of amnesia in international law. Law has served as an instrument to justify injustice in the past and to silence its contemporary effects. The rise of the ‘Black Lives Matter’ movement, TWAIL scholarship and the current debate on racism, slavery and return of cultural colonial objects illustrate the ongoing effects of colonialism. Some seemingly neutral principles and institutions of international law contribute to colonial amnesia. This contribution argues that it is time to revisit this status quo. It draws on emerging case law, scholarship and practices to identify news ways of relational engagement with the past. It suggests a re-reading of three fundamental dimensions of post-colonial engagement with colonial injustice: intertemporality, legal subjectivity and the approach towards cultural colonial objects. It claims that international criminal law has only a modest role in relation to colonial crimes. However, some wider lessons and methods from the field of transitional justice may help to mitigate contemporary dilemmas and contribute to a more post-colonial international law.