bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative methylome analysis reveals conservation and divergence of DNA methylation patterns and functions in vertebrates
Authors: Al Adhami Hala , Bardet Anaïs Flore , Dumas Michael , Cleroux Elouan , Guibert Sylvain , Fauque Patricia , Acloque Hervé , Weber Michael 
Published: March 2022

Abstract
Background
Cytosine DNA methylation is a heritable epigenetic mark present in most eukaryotic groups. While the patterns and functions of DNA methylation have been extensively studied in mouse and human, their conservation in other vertebrates remains poorly explored. In this study, we interrogated the distribution and function of DNA methylation in primary fibroblasts of seven vertebrate species including bio-medical models and livestock species (human, mouse, rabbit, dog, cow, pig, and chicken).

Results
Our data highlight both divergence and conservation of DNA methylation patterns and functions. We show that the chicken genome is hypomethylated compared to other vertebrates. Furthermore, compared to mouse, other species show a higher frequency of methylation of CpG-rich DNA. We reveal the conservation of large unmethylated valleys and patterns of DNA methylation associated with X-chromosome inactivation through vertebrate evolution and make predictions of conserved sets of imprinted genes across mammals. Finally, using chemical inhibition of DNA methylation, we show that the silencing of germline genes and endogenous retroviruses (ERVs) are conserved functions of DNA methylation in vertebrates.

Conclusions
Our data highlight conserved properties of DNA methylation in vertebrate genomes but at the same time point to differences between mouse and other vertebrate species.
An international consensus on the essential and desirable criteria for an ‘organized’ cancer screening programme
Authors: Zhang Li , Carvalho André L. , Mosquera Isabel , Wen Tianmeng , Lucas Eric , Sauvaget Catherine , Muwonge Richard , Arbyn Marc , Weiderpass Elisabete , Basu Partha 
Published: March 2022

Abstract
Background
High variability in the definition and interpretation of organized cancer screening needs to be addressed systematically. Moreover, the relevance of the current practice of categorizing screening programmes dichotomously into organized or non-organized needs to be revisited in the context of considerable heterogeneity that exists in the delivery of cancer screening in the real world. We aimed to identify the essential and desirable criteria for organized cancer screening that serve as a charter of best practices in cancer screening.

Methods
We first did a systematic review of literature to arrive at an exhaustive list of criteria used by various publications to describe or define organized cancer screening, based on which, a consolidated list of criteria was generated. Next, we used a Delphi process comprising of two rounds of online surveys to seek agreement of experts to categorize each criterion into essential, desirable, or neither. Consensus was considered to have been achieved based on a predetermined criterion of agreement from at least 80% of the experts. The outcomes were presented before the experts in a virtual meeting for feedbacks and clarifications.

Results
A total of 32 consolidated criteria for an organized screening programme were identified and presented to 24 experts from 20 countries to select the essential criteria in the Delphi first round. Total 16 criteria were selected as essential with the topmost criteria (based on the agreement of 96% of experts) being the availability of a protocol/guideline describing at least the target population, screening intervals, screening tests, referral pathway, management of positive cases and a system being in place to identify the eligible populations. In the second round of Delphi, the experts selected eight desirable criteria out of the rest 16. The most agreed upon desirable criterion was existence of a specified organization or a team responsible for programme implementation and/or coordination.

Conclusions
We established an international consensus on essential and desirable criteria, which screening programmes would aspire to fulfil to be better-organized. The harmonized criteria are a ready-to-use guide for programme managers and policymakers to prioritize interventions and resources rather than supporting the dichotomous and simplistic approach of categorizing programmes as organized or non-organized.
Telomerase deficiency reflects age-associated changes in CD4+ T cells
Authors: Matthe Diana M. , Thoma Oana-Maria , Sperka Tobias , Neurath Markus F. , Waldner Maximilian J. 
Published: March 2022

AbstractBackgroundAmongst other systemic changes, aging leads to an immune dysfunction. On the molecular level, a hallmark of aging is telomere shortening. The functional relevance of telomerase, an enzyme capable of elongating telomeres in T cells upon antigen stimulation, is not fully understood. Studying the impact of telomere shortening on CD4+ T cells and especially Th1 effector function can provide a better understanding on immune dysfunctions in elderly.ResultsWe investigated T cell numbers and differentiation in telomerase-deficient (mTerc−/−) mice under steady-state conditions and the functional role of telomerase in CD4+ T cells using in vitro stimulation and Th1 polarization protocols by comparing T cells from mTerc−/− and control mice. We report reduced relative CD4+ T cell numbers in blood and secondary lymphoid organs and a relative decline in the naïve T cell population in thymus, blood and spleen of mTerc−/− mice compared to control mice. Importantly, after in vitro polarization, mTerc−/− G3 CD4+ T cells showed higher numbers of IFNγ-producing cells and reduced expression of CD28. Notably, telomerase-deficient T cells were more susceptible to inhibition of Th1 polarization by IL-6 in vitro. These results demonstrate that telomerase deficiency recapitulates several changes of CD4+ T cells seen in aged humans regarding the naïve T cell population, expression of CD28 and cytokine production.ConclusionOur data suggest that telomere shortening could play a key role in the aging of T cell immunity, with clinical implications for immune diseases and tumor development and that mTerc−/− mice are a suitable model to study aging-related defects of adaptive immunity.
Association of Keap1 (rs11085735) polymorphism and lncRNA MEG3 hypermethylation status with the risk of preeclampsia
Authors: Zangeneh Maryam , Heydarian Sara , Seifi Zahra , Kohsari Maryam , Rahimi Zohreh 
Published: March 2022

Abstract
Background
Preeclampsia (PE) is one of the complications of pregnancy. The pathogenesis of PE has not been completely understood. The aims of the present study were to investigate the role of Keap1 (rs11085735) variants and the methylation status of long non-coding RNA (lncRNA) MEG3 in the risk of PE.

Methods
In a case–control study, 150 pregnant women, including 75 PE patients and 75 healthy pregnant women recruited from Western Iran with Kurdish ethnic background, were studied for Keap1 variants using polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP). The methylation status of lncRNA MEG3 was investigated using methylation-specific PCR (MSP) among 50 preeclamptic patients and 50 controls.

Results
The frequency of Keap1 A allele was significantly lower (5.3%) in preeclamptic patients compared to controls (12.7%, p = 0.024). The frequencies of hemimethylated (UM) and full methylated (MM) lncRNA MEG3 were 94 and 6% (p = 0.04), respectively, in all patients, 86.4, and 13.6% (p = 0.04), respectively, in patients with severe preeclampsia and 98 and 0% in controls. The frequency of full methylated lncRNA MEG3 was 14.3% in early-onset preeclampsia and 2.8% in late-onset preeclampsia (p = 0.12). Patients with PE had significantly higher levels of liver biomarkers (including ALT, AST, ALP, and total bilirubin) and lower PLT counts compared to healthy pregnant women.

Conclusion
The present study suggests the presence of hypermethylation status of lncRNA MEG3 in preeclampsia that might contribute to the pathogenesis and development of preeclampsia. Also, Keap1 rs11085735 polymorphism might be involved in the risk of preeclampsia.
Combined effect of orthotic intervention and conventional exercise training on balance and gait performance in cerebral palsy: a randomized controlled trial
Authors: El-Shamy Shamekh Mohamed , El-Kafy Ehab Mohamed Abd 
Published: March 2022

Abstract
Background
This study aimed to examine the combined effect of orthotic intervention and conventional therapeutic exercise training on balance and gait performance in children with cerebral palsy. This study was a randomized control trial. Forty children with dyskinetic cerebral palsy of both genders with ages ranged from 12 to 16 years were included. Participants in the control and study groups received a conventional therapeutic exercise training program for two 2 h ours per session. The treatment program was conducted three sessions per week, for twelve 12 successive weeks. Children in the study group additionally wore TheraTogs orthotic undergarment with the strapping system. Pediatric Balance Scale score and postural stability indices (overall, anteroposterior , and mediolateral) evaluated by the Biodex Balance System were assessed (in both groups) at baseline and after 12 weeks of treatment. The changes of step length, gait cycle time, cadence, and velocity were also measured by an electronic walkway.

Results
Children in the study group showed significant improvements in the scores of all the measured variables post-treatment compared to the control group (P < 0.05). The P -values for overall, anteroposterior and mediolateral postural stability indices were 0.011, 0.014, and 0.021, respectively. The P -values for Pediatric Balance Scale score, step length, gait cycle time, cadence, and velocity were 0.001, 0.023, 0.041, 0.011, and 0.013 respectively.

Conclusions
Conventional therapeutic exercise training combined with orthotic intervention were more effective in improving balance and gait performance in children with dyskinetic cerebral palsy.

Trial registration
The ClinicalTrial.gov PRS (NCT04990193).
Registered 4 August 2021 - Retrospectively registered.
Effective medium theory of random regular networks
Authors: Damavandi O. K. , Manning M. L. , Schwarz J. M. 
Published: March 2022

Abstract
Disordered spring networks can exhibit rigidity transitions, due to either the removal of material in over-constrained networks or the application of strain in under-constrained ones. While an effective medium theory (EMT) exists for the former, there is none for the latter. We, therefore, formulate an EMT for random regular, under-constrained spring networks with purely geometrical disorder to predict their stiffness via the distribution of tensions. We find a linear dependence of stiffness on strain in the rigid phase and a nontrivial dependence on both the mean and standard deviation of the tension distribution. While EMT does not yield highly accurate predictions of shear modulus due to spatial heterogeneities, it requires only the distribution of tensions for an intact system, therefore making it an ideal starting point for experimentalists quantifying the mechanics of such networks.
Safety and Efficacy of the Off-Label Use of Pipeline Embolization Device Based on the 2018 Food and Drug Administration-Approved Indications for Intracranial Aneurysms: A Single-Center Retrospective Cohort Study
Authors: Enriquez-Marulanda Alejandro , Penumaka Anirudh , Ogilvy Christopher S. , Thomas Ajith J. , Moore Justin M. 
Published: March 2022

BACKGROUND:
The pipeline embolization device (PED; ev3/Covidien) has proven safe and effective for treating selected intracranial aneurysms. This device's versatility and popularity have driven increased interest in expanding the latest 2018 Food and Drug Administration–approved indications.

OBJECTIVE:
To compare “off-label” and “on-label” PED treatment.

METHODS:
Retrospective analysis of aneurysms treated with PED at a single center from 2013 to 2019. Comparisons were made based on the 2018 Food and Drug Administration–approved indications.

RESULTS:
A total of 492 treated aneurysms were included (65.2% on-label and 34.8% off-label). Aneurysm complete and near-complete occlusion rate was nonsignificantly lower in the off-label group (80.9% vs 85.7%; P = .19). Off-label treatment had higher rate of poor functional outcomes (modified Rankin Scale [mRS] >2: 10.3% vs 3.5%; P = .002). Although pretreatment mRS was already higher in the off-label group (5.3% vs 0.3%; P < .001) and there were no differences in mRS worsening during follow-up (5.5% vs 2.9%; P = .15). We also found a trend to a higher rate of intracranial hemorrhagic complications in the off-label group (4.7% vs 1.6%; P = .05), but there were no differences in hemorrhages requiring surgical intervention (1.8% vs 1.3%; P = .65). There were no differences in retreatment, thromboembolic complications, and mortality rates.

CONCLUSION:
Off-label PED treatment may be considered for select aneurysms, which are challenging to treat with other techniques. These cases have similar complete and near-complete occlusion rates compared with on-label cases. There are, however, higher risks of poor functional outcomes despite similar rates of thromboembolic and hemorrhagic complications. This is partly explained by the significantly higher pretreatment mRS score in the off-label group.
Stereotactic Radiosurgery Compared With Active Surveillance for Asymptomatic, Parafalcine, and Parasagittal Meningiomas: A Matched Cohort Analysis From the IMPASSE Study
Authors: Pikis Stylianos , Mantziaris Georgios , Bunevicius Adomas , Islim Abdurrahman I. , Peker Selcuk , Samanci Yavuz , Nabeel Ahmed M. , Reda Wael A. , Tawadros Sameh R. , El-Shehaby Amr M. N. , Abdelkarim Khaled , Emad Reem M. , Delabar Violaine , Mathieu David , Lee Cheng-chia , Yang Huai-che , Liscak Roman , May Jaromir , Alvarez Roberto Martinez , Patel Dev N. , Kondziolka Douglas , Bernstein Kenneth , Moreno Nuria Martinez , Tripathi Manjul , Speckter Herwin , Albert Camilo , Bowden Greg N. , Benveniste Ronald J. , Lunsford L. Dade , Jenkinson Michael D. , Sheehan Jason 
Published: March 2022

BACKGROUND:
The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial.

OBJECTIVE:
To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas.

METHODS:
Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts.

RESULTS:
There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P < .001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%).

CONCLUSION:
Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death.
In vitro culture of ovine embryos up to early gastrulating stages
Authors: Ramos-Ibeas Priscila , González-Brusi Leopoldo , Used María Torres , Cocero María Jesús , Marigorta Pilar , Alberio Ramiro , Bermejo-Álvarez Pablo 
Published: March 2022

ABSTRACT
Developmental failures occurring shortly after blastocyst hatching from the zona pellucida constitute a major cause of pregnancy losses in both humans and farm ungulates. The developmental events occurring following hatching in ungulates include the proliferation and maturation of extra-embryonic membranes – trophoblast and hypoblast – and the formation of a flat embryonic disc, similar to that found in humans, which initiates gastrulation prior to implantation. Unfortunately, our understanding of these key processes for embryo survival is limited because current culture systems cannot sustain ungulate embryo development beyond hatching. Here, we report a culture system that recapitulates most developmental landmarks of gastrulating ovine embryos: trophoblast maturation, hypoblast migration, embryonic disc formation, disappearance of the Rauber's layer, epiblast polarization and mesoderm differentiation. Our system represents a highly valuable platform for exploring the cell differentiation, proliferation and migration processes governing gastrulation in a flat embryonic disc and for understanding pregnancy failures during the second week of gestation.
This article has an associated ‘The people behind the papers’ interview.
Naphthoquinone-induced arylation inhibits Sirtuin 7 activity
Authors: Sirri Valentina , Berthelet Jérémy , Brookes Oliver , Roussel Pascal 
Published: March 2022

ABSTRACT
Natural or synthetic naphthoquinones have been identified to interfere with biological systems and, in particular, exhibit anticancer properties. As redox cyclers, they generate reactive oxygen species in cells and, as electrophiles, they react with nucleophiles, mainly thiols, and form covalent adducts. To further decipher the molecular mechanism of action of naphthoquinones in human cells, we analyzed their effects in HeLa cells. First, we demonstrated that the naphthoquinones menadione and plumbagin inhibited the nucleolar NAD+-dependent deacetylase Sirtuin 7 in vitro. As assessed by their inhibition of rDNA transcription, pre-rRNA processing and formation of etoposide-induced 53BP1 foci, menadione and plumbagin also inhibited Sirtuin 7 catalytic activity in vivo. Second, we established that when sulfhydryl arylation by menadione or plumbagin was prevented by the thiol reducing agent N-acetyl-L-cysteine, the inhibition of Sirtuin 7 catalytic activity was also blocked. Finally, we discuss how inhibition of Sirtuin 7 might be crucial in defining menadione or plumbagin as anti-tumor agents that can be used in combination with other anti-tumor strategies.
Vertical Loading Rate Is Not Associated with Running Injury, Regardless of Calculation Method
Authors: SCHMIDA ELIZABETH A. , WILLE CHRISTA M. , STIFFLER-JOACHIM MIKEL R. , KLIETHERMES STEPHANIE A. , HEIDERSCHEIT BRYAN C. 
Published: March 2022

ABSTRACT

Introduction
Loading rate (LR), the slope of the vertical ground reaction force (vGRF), is commonly used to assess running-related injury risk. However, the relationship between LR and running-related injuries, including bone stress injuries (BSI), is unclear. Inconsistent findings may result from the numerous LR calculation methods that exist and their application across different running speeds.

Purpose
This study aimed to assess the influence of calculation method and running speed on LR values and to determine the association of LR during healthy running with subsequent injury.

Methods
Healthy preseason running data and subsequent injury records from Division I cross-country athletes (n = 79) over four seasons (2015–2019) at 2.68 m·s−1, preferred training pace, and 4.47 m·s−1 were collected. LR at each speed was calculated four ways: 1) maximum and 2) average slope from 20% to 80% of vGRF magnitude at impact peak (IP), 3) average slope from initial contact to IP, and 4) average slope from 3% to 12% of stance time. Linear mixed effects models and generalized estimation equations were used to assess LR associations.

Results
LR values differed depending on speed and calculation method (P value <0.001). The maximum slope from 20% to 80% of the vGRF at 4.47 m·s−1 produced the highest LR estimate and the average slope from initial contact to IP at 2.68 m·s−1 produced the lowest. Sixty-four injuries (20 BSI) were observed. No significant association was found between LR and all injuries or BSI across any calculation method (P values ≥0.13).

Conclusions
Calculation method and running speed result in significantly different LR values. Regardless of calculation method, no association between LR and subsequent injury was identified. Thus, healthy baseline LR may not be useful to prospectively assess running-related injury risk.
Πρόθεση εμβολιασμού κατά του Covid-19 σε συνθήκες εγκλεισμού: πηγές πληροφόρησης και πεποιθήσεις για τον εμβολιασμό ως προβλεπτικοί παράγοντες
Authors: Αργυρούδη Ανθή , Γαρδικιώτης Αντώνης 
Published: March 2022

Η παρούσα μελέτη διερευνά την πρόθεση των πολιτών να εμβολιαστούν κατά του COVID-19 σε συνθήκες εγκλεισμού, κατά τη διάρκεια του πρώτου κύματος της πανδημίας. Εστιάζει σε ορισμένους από τους παράγοντες που την προβλέπουν, αντλώντας από το πεδίο της επικοινωνίας υγείας, τις πηγές πληροφόρησης που χρησιμοποιούν και εμπιστεύονται για την ενημέρωσή τους οι συμμετέχοντες, και από το πεδίο της ψυχολογικής έρευνας, τις πεποιθήσεις των συμμετεχόντων (απέναντι στον εμβολιασμό κατά του COVID-19, τις θεωρίες συνωμοσίας, την αναμενόμενη μεταμέλεια και τις προσλαμβανόμενες κοινωνικές νόρμες). Στην παρούσα έρευνα, η οποία πραγματοποιήθηκε διαδικτυακά, συμμετείχαν 325 άτομα (Mηλικίας = 41,58 έτη). Ένα μεγάλο ποσοστό των συμμετεχόντων δήλωσε αρνητική πρόθεση ή διστακτικότητα ως προς τον εμβολιασμό (53,9%). Οι θετικές πεποιθήσεις για τα εμβόλια συσχετίστηκαν θετικά με την πρόθεση για εμβολιασμό. Με θετικό τρόπο συσχετίστηκαν, επίσης, οι πεποιθήσεις για την αναμενόμενη μεταμέλεια και τις κοινωνικές νόρμες, ενώ οι συνωμοσιολογικές και οι αρνητικές πεποιθήσεις συσχετίστηκαν με αρνητικό τρόπο. Επιβεβαιώθηκε η σύνδεση της πρόθεσης εμβολιασμού με την επιστημονική και επίσημη πληροφόρηση, καθώς η τελευταία αναγνωρίστηκε ως πηγή αυξημένης εμπιστοσύνης. Ωστόσο, τα Μέσα Κοινωνικής Δικτύωσης (ΜΚΔ) αποδείχτηκε ότι αποτελούν πηγές ενημέρωσης για τον COVID-19, περισσότερο από τα παραδοσιακά μέσα ενημέρωσης, αν και αναγνωρίστηκαν ως πηγές ενημέρωσης χαμηλής εμπιστοσύνης. Αναλύσεις ιεραρχικής παλινδρόμησης έδειξαν ότι οι πεποιθήσεις των συμμετεχόντων/-ουσών προβλέπουν πέρα και πάνω από τις πηγές πληροφόρησης την πρόθεση για εμβολιασμό. Συμπερασματικά, για την ενίσχυση της πρόθεσης εμβολιασμού χρειάζεται να δοθεί έμφαση σε εκστρατείες για τη σπουδαιότητα της έγκυρης πληροφόρησης, την αμφισβήτηση συνωμοσιολογικών θεωριών και αρνητικών πεποιθήσεων σχετικά με τον εμβολιασμό και στην ενίσχυση της εμπιστοσύνης στις επίσημες και επιστημονικές πηγές ενημέρωσης.