bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient and proxies’ attitudes towards deferred consent in randomised trials of acute treatment for stroke: A qualitative survey
Authors: van den Bos Noa , van den Berg Sophie A , Caupain Catalina MM , Pols Jeannette AJ , van Middelaar Tessa , Chalos Vicky , Dippel Diederik WJ , Roos Yvo BWEM , Kappelhof Manon , Nederkoorn Paul J 
Published: November 2021

Introduction Deferral of consent for participation in a clinical study is a relatively novel procedure, in which informed consent is obtained after randomisation and study treatment. Deferred consent can be used in emergency situations, where small therapeutic time windows limit possibilities for patients to provide informed consent. We aimed to investigate patients’ or their proxies’ experiences and opinions regarding deferred consent in acute stroke randomised trials. Patients and methods For this qualitative study, Dutch Collaboration for New Treatments of Acute Stroke (CONTRAST) trial participants were selected. Study participants were either patients or their proxies who provided consent and were selected with theoretical sampling based on patient characteristics. Semi-structured interviews were conducted face-to-face or by telephone. Themes and subthemes were iteratively defined. Results Twenty of the 23 interviewed participants (16 patients and 7 proxies) considered deferred consent acceptable. The received study treatment and consent conversation were remembered by 18 participations, although the concept of randomisation and treatment comparison were generally not well understood. Sixteen participants felt capable of overseeing the decision to give deferred consent. Distress in the first days after stroke, lack of understanding and neurological deficits were reasons for feeling incapable of providing consent. Four participants would have preferred a different timing of the consent conversation, of whom two prior to treatment. Conclusion Our study found that deferred consent was considered acceptable by most study participants who provided consent for acute stroke randomised trials. Though they felt capable, the recall and comprehension of consent were overall limited.
Micro-embolic signal monitoring in stroke subtypes: A systematic review and meta-analysis of 58 studies
Authors: Sudheer Pachipala , Misra Shubham , Nath Manabesh , Kumar Pradeep , Vibha Deepti , Srivastava M.V.Padma , Tripathi Manjari , Bhatia Rohit , Pandit Awadh Kishor , Singh Rajesh K 
Published: November 2021

Introduction Micro-embolic signals (MESs) detected using transcranial Doppler (TCD) help in risk stratification in stroke patients. A systematic review and meta-analysis were performed to estimate the prevalence of MES and its association with stroke recurrence, functional outcome, and mortality in different stroke subtypes. Methods A comprehensive literature search was conducted before 26th January 2021 in PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov . Studies were identified that used TCD to detect MES in stroke/TIA patients. Pooled prevalence and odds ratio (OR) along with 95% confidence interval (95% CI) were calculated for different outcome measures. The entire statistical analysis was conducted in R version 3.6.2. Findings Fifty-eight studies involving 5123 patients (1329 MES+, 3794 MES−) were included in our meta-analysis. The pooled prevalence of MES among all acute stroke/TIA patients was 30% (95% CI 25-34%). The pooled prevalence adjusted after the trim-and-fill analysis among all acute stroke/TIA patients was 18% (95% CI 14-23%). The prevalence of MES was high among all stroke subtypes except in patients with small vessel disease (SVD). In patients with new-onset stroke/TIA, the presence of MES was associated with a high risk of recurrence of cerebral ischemia (OR 4.03; 95% CI 2.38-6.82). Although no significant association was observed for the presence of MES with increased mortality (OR 2.37; 95% CI 0.75-7.50) and poor functional outcome (OR 2.11; 95% CI 0.20-22.50) among patients with new-onset stroke/TIA, this could only be determined in a smaller sample size of 477 patients. Conclusions Our meta-analysis showed a 30% prevalence of MES following acute stroke/TIA. The presence of MES increased the chance of recurrence of cerebral ischemia but was not associated with poor functional outcomes and mortality in the studied subgroup.
Safety assessment of β-fructofuranosidase from Aspergillus brunneoviolaceus
Authors: Vo Trung Duc , Meetro Jwar , Lynch Barry , Tafazoli Shahrzad , Ichihara Akio , Chikamatsu Go 
Published: November 2021

β-Fructofuranosidase (β-D-fructofuranoside fructohydrolase; EC 3.2.1.26) is used in the production of fructo-oligosaccharides that are commonly used by the food industry as prebiotics for their purported health benefits. The β-fructofuranosidase discussed herein is obtained from a novel source organism that is a non-genetically modified strain of Aspergillus brunneoviolaceus, which phylogenetically belongs to the Aspergillus section Nigri. The safety of β-fructofuranosidase was evaluated in a series of toxicology studies as prescribed by Tier 1 toxicity testing by the European Food Safety Authority, including an evaluation of the mutagenicity and genotoxicity potential using the in vitro bacterial reverse mutation and mammalian chromosomal aberration assays, as well as systemic toxicity in a 90-day oral subchronic toxicity study in Sprague-Dawley rats. β-Fructofuranosidase was demonstrated to lack mutagenic or genotoxic potential based on the results of the in vitro assays due to absence of increased revertant colonies in the bacterial reverse mutation test and incidence of chromosome aberrations in the chromosomal aberration assay. Administration of β-fructofuranosidase by gavage at doses up to 1200 mg total organic solids (TOS)/kg body weight/day for 90 days did not elicit any systemic toxic effects in rats based on a lack of adverse effect in any study parameter, and therefore the no-observed-adverse-effect level of β-fructofuranosidase was concluded to be 1200 mg TOS/kg body weight/day, the highest dose tested. The results of the toxicology studies on β-fructofuranosidase from A. brunneoviolaceus demonstrate this species to be a safe and suitable source of enzymes for use by the food industry.
Antibody Response to BNT162b2 Vaccine in Immune Modifiers–Treated Psoriatic Patients
Authors: Pavlotsky Felix , Segal Zvi , Barzilai Aviv 
Published: November 2021

Background Data regarding anti–COVID-19 vaccination efficacy in psoriasis patients treated with immune-modulatory medications are scarce. Objective This study aims to examine the rate of positive antibody response following BNT162b2 vaccine in those patients. Methods BNT162b2-vaccinated and immune modifier–treated psoriatic patients were assigned to serological testing of IgG antibodies to protein S of SARS-CoV-2 after the second vaccination dose by Abbott Architect or Beckman Coulter. Levels ≥ 1 S1 units/mL (S/ml) and > 150 arbitrary units/ml (AU/ml) are considered a positive antibody response, respectively. The antibody levels further analyzed according to the patient’s characteristics and compared to health workers’ controls. Results Forty-nine of the 51 patients had a positive antibody response. Overall, patients treated with immune-modulatory medications had antibody levels similar to the control group. Conclusions Immune modifier–treated psoriasis patients seem to develop a positive antibody response to the full BNT162b2 vaccination in the vast majority of cases.
TET2 mutations as a part of DNA dioxygenase deficiency in myelodysplastic syndromes
Authors: Gurnari Carmelo , Pagliuca Simona , Guan Yihong , Adema Vera , Hershberger Courtney E. , Ni Ying , Awada Hassan , Kongkiatkamon Sunisa , Zawit Misam , Coutinho Diego F. , Zalcberg Ilana R. , Ahn Jae-Sook , Kim Hyeoung-Joon , Kim Dennis Dong Hwan , Minden Mark D. , Jansen Joop H. , Meggendorfer Manja , Haferlach Claudia , Jha Babal K. , Haferlach Torsten , Maciejewski Jaroslaw P. , Visconte Valeria 
Published: November 2021

Abstract
Decrease in DNA dioxygenase activity generated by TET2 gene family is crucial in myelodysplastic syndromes (MDS). The general downregulation of 5-hydroxymethylcytosine (5-hmC) argues for a role of DNA demethylation in MDS beyond TET2 mutations, which albeit frequent, do not convey any prognostic significance. We investigated TETs expression to identify factors which can modulate the impact of mutations and thus 5-hmC levels on clinical phenotypes and prognosis of MDS patients. DNA/RNA-sequencing and 5-hmC data were collected from 1665 patients with MDS and 91 controls. Irrespective of mutations, a significant fraction of MDS patients exhibited lower TET2 expression, whereas 5-hmC levels were not uniformly decreased. In searching for factors explaining compensatory mechanisms, we discovered that TET3 was upregulated in MDS and inversely correlated with TET2 expression in wild-type cases. Although TET2 was reduced across all age groups, TET3 levels were increased in a likely feedback mechanism induced by TET2 dysfunction. This inverse relationship of TET2 and TET3 expression also corresponded to the expression of L-2-hydroxyglutarate dehydrogenase, involved in agonist/antagonist substrate metabolism. Importantly, elevated TET3 levels influenced the clinical phenotype of TET2 deficiency whereby the lack of compensation by TET3 (low TET3 expression) was associated with poor outcomes of TET2 mutant carriers.
Antithrombin protects againstPlasmodium falciparumhistidine-rich protein II-mediated inflammation and coagulation
Authors: Biswas Indranil , Panicker Sumith R. , Giri Hemant , Cai Xiaofeng S. , Rezaie Alireza R. 
Published: November 2021

AbstractPlasmodium falciparum-derived histidine-rich protein II (HRPII) has been shown to inhibit heparin-dependent anticoagulant activity of antithrombin (AT) and induce inflammation in vitro and in vivo. In a recent study, we showed that HRPII interacts with the AT-binding vascular glycosaminoglycans (GAGs) not only to disrupt the barrier-permeability function of endothelial cells but also to inhibit the antiinflammatory signaling function of AT. Here we investigated the mechanisms of the proinflammatory function of HRPII and the protective activity of AT in cellular and animal models. We found that AT competitively inhibits the GAG-dependent HRPII-mediated activation of NF-κB and expression of intercellular cell adhesion molecule 1 (ICAM1) in endothelial cells. Furthermore, AT inhibits HRPII-mediated histone H3 citrullination and neutrophil extracellular trap (NET) formation in HL60 cells and freshly isolated human neutrophils. In vivo, HRPII induced Mac1 expression on blood neutrophils, MPO release in plasma, neutrophil infiltration, and histone H3 citrullination in the lung tissues. HRPII also induced endothelial cell activation as measured by increased ICAM1 expression and elevated vascular permeability in the lungs. AT effectively inhibited HRPII-mediated neutrophil infiltration, NET formation, and endothelial cell activation in vivo. AT also inhibited HRPII-meditated deposition of platelets and fibrin(ogen) in the lungs and circulating level of von Willebrand factor in the plasma. We conclude that AT exerts protective effects against pathogenic effects of P falciparum-derived HRPII in both cellular and animal models.
ADSCs enhance VEGFR3-mediated lymphangiogenesis via METTL3-mediated VEGF-C m6A modification to improve wound healing of diabetic foot ulcers
Authors: Zhou Jie , Wei Tianhong , He Zhiyou 
Published: November 2021

Abstract
Background
Adipose-derived mesenchymal stem cells (ADSCs) are an important focus in regenerative medicine. However, the biological function of ADSCs in the wound repair of diabetic foot ulcers (DFUs) remains unclear. This study aimed to determine the underlying mechanisms of ADSCs involved in the wound healing of DFUs.

Methods
The cell surface markers cluster of differentiation 34 (CD34), stromal cell antigen 1 (Stro-1), cluster of differentiation 90 (CD90) and cluster of differentiation 105 (CD105) on ADSCs were identified by flow cytometry. Oil Red O staining and Alizarin Red S staining were performed to identify the multipotential differentiation of ADSCs into adipocytes and bone. The levels of Methyltransferase-like 3 (METTL3), vascular endothelial growth factor C (VEGF-C) and insulin-like growth factor 2 binding protein 2 (IGF2BP2) were assessed by RT-qPCR. CCK-8, Transwell and tubule formation assays were conducted to assess lymphatic endothelial cell (LEC) viability, migration and tubule formation ability, respectively. RIP and RNA pulldown assays were conducted to assess the interaction between IGF2BP2 and VEGF-C. The levels of VEGF-C, VEGFR3, LYVE-1 and IGF2BP2 proteins were assessed by Western blotting. The levels of VEGF-C in LECs were measured by ELISA.

Results
Our findings illustrated that ADSCs accelerate LEC proliferation, migration and lymphangiogenesis via the METTL3 pathway and regulate VEGF-C expression via the METTL3/IGF2BP2-m6A pathway VEGF-C-mediated lymphangiogenesis via the METTL3/IGF2BP2-m6A pathway in DFU mice.

Conclusion
ADSCs enhance VEGFR3-mediated lymphangiogenesis via METTL3-mediated VEGF-C m6A modification to improve wound healing in DFUs, indicating that ADSCs may be regarded as a promising therapeutic strategy to promote wound healing in DFUs.
Patient-reported results of simultaneous direct anterior approach and posterolateral approach total hip arthroplasties performed in the same patients
Authors: Yang Zhi , Feng Shuo , Guo Kai-Jin , Zha Guo-Chun 
Published: November 2021

Abstract
Background
Several studies have compared clinical results of the direct anterior approach (DAA) and the posterolateral approach (PLA) in total hip arthroplasty (THA); however, the effect of the surgical approach on outcome of THA remains controversial. Most of these studies used two distinct groups of patients, and THAs were performed by different surgeons, using different designs of prosthesis. These confounding factors may limit the strength of the conclusions. The purpose of this prospective, simultaneous bilateral randomized study was to investigate whether patients would perceive the difference between the direct anterior approach (DAA) and the posterolateral approach (PLA) after THA.

Materials and methods
Among 20 patients scheduled to undergo same-day bilateral THA between October 2017 and August 2019, one hip was randomly assigned to DAA and the other to PLA. Patient-reported outcome measures [Hip disability and Osteoarthritis Outcome Score (HOOS), patients’ hip pain on mobilization] and physician-assessed measures [Harris Hip Score (HHS), operative time, intraoperative blood loss, cup abduction, cup anteversion, stem orientation, and incidence of complications (intraoperative fracture, nerve damage, incisional problem, or postoperative dislocation)] were compared.

Results
All patients were followed up for 12 months. Hip pain was significantly less with DAA-THA compared with PLA-THA at postoperative 1, 3, and 7 days (p < 0.05). There was no clinical difference between DAA-THA and PLA-THA in terms of the VAS, HOOS, or HSS at 6 weeks and 3, 6, and 12 months postoperatively (p > 0.05). DAA-THA had a longer operative time and shorter length of incision compared with PLA-THA. There was no statistical difference between DAA-THA and PLA-THA in terms of intraoperative blood loss, cup abduction, cup anteversion, stem orientation, and perioperative complications (p > 0.05).

Conclusions
This study demonstrates that DAA-THA and PLA-THA could provide comparable HHS and HOOS at all follow-ups. Compared with PLA-THA, DAA-THA is associated with less hip pain within postoperative 7 days and shorter incision length, but longer operative time.

Level of evidence
Level I, therapeutic study.
Trial registration Chinese Clinical Trail Registry, ChiCTR1800019816. Registered 30 November 2018—retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=30863
Pleiotropy between language impairment and broader behavioral disorders—an investigation of both common and rare genetic variants
Authors: Nudel Ron , Appadurai Vivek , Buil Alfonso , Nordentoft Merete , Werge Thomas 
Published: November 2021

AbstractBackgroundLanguage plays a major role in human behavior. For this reason, neurodevelopmental and psychiatric disorders in which linguistic ability is impaired could have a big impact on the individual’s social interaction and general wellbeing. Such disorders tend to have a strong genetic component, but most past studies examined mostly the linguistic overlaps across these disorders; investigations into their genetic overlaps are limited. The aim of this study was to assess the potential genetic overlap between language impairment and broader behavioral disorders employing methods capturing both common and rare genetic variants.MethodsWe employ polygenic risk scores (PRS) trained on specific language impairment (SLI) to evaluate genetic overlap across several disorders in a large case-cohort sample comprising ~13,000 autism spectrum disorder (ASD) cases, including cases of childhood autism and Asperger’s syndrome, ~15,000 attention deficit/hyperactivity disorder (ADHD) cases, ~3000 schizophrenia cases, and ~21,000 population controls. We also examine rare variants in SLI/language-related genes in a subset of the sample that was exome-sequenced using the SKAT-O method.ResultsWe find that there is little evidence for genetic overlap between SLI and ADHD, schizophrenia, and ASD, the latter being in line with results of linguistic analyses in past studies. However, we observe a small, significant genetic overlap between SLI and childhood autism specifically, which we do not observe for SLI and Asperger’s syndrome. Moreover, we observe that childhood autism cases have significantly higher SLI-trained PRS compared to Asperger’s syndrome cases; these results correspond well to the linguistic profiles of both disorders. Our rare variant analyses provide suggestive evidence of association for specific genes with ASD, childhood autism, and schizophrenia.ConclusionsOur study provides, for the first time, to our knowledge, genetic evidence for ASD subtypes based on risk variants for language impairment.
Identification of an Elite Core Panel as a Key Breeding Resource to Accelerate the Rate of Genetic Improvement for Irrigated Rice
Authors: Juma Roselyne U. , Bartholomé Jérôme , Thathapalli Prakash Parthiban , Hussain Waseem , Platten John D. , Lopena Vitaliano , Verdeprado Holden , Murori Rosemary , Ndayiragije Alexis , Katiyar Sanjay Kumar , Islam Md Rafiqul , Biswas Partha S. , Rutkoski Jessica E. , Arbelaez Juan D. , Mbute Felister N. , Miano Douglas W. , Cobb Joshua N. 
Published: November 2021

AbstractRice genetic improvement is a key component of achieving and maintaining food security in Asia and Africa in the face of growing populations and climate change. In this effort, the International Rice Research Institute (IRRI) continues to play a critical role in creating and disseminating rice varieties with higher productivity. Due to increasing demand for rice, especially in Africa, there is a strong need to accelerate the rate of genetic improvement for grain yield. In an effort to identify and characterize the elite breeding pool of IRRI’s irrigated rice breeding program, we analyzed 102 historical yield trials conducted in the Philippines during the period 2012–2016 and representing 15,286 breeding lines (including released varieties). A mixed model approach based on the pedigree relationship matrix was used to estimate breeding values for grain yield, which ranged from 2.12 to 6.27 t·ha−1. The rate of genetic gain for grain yield was estimated at 8.75 kg·ha−1 year−1(0.23%) for crosses made in the period from 1964 to 2014. Reducing the data to only IRRI released varieties, the rate doubled to 17.36 kg·ha−1 year−1(0.46%). Regressed against breeding cycle the rate of gain for grain yield was 185 kg·ha−1 cycle−1(4.95%). We selected 72 top performing lines based on breeding values for grain yield to create an elite core panel (ECP) representing the genetic diversity in the breeding program with the highest heritable yield values from which new products can be derived. The ECP closely aligns with the indica 1B sub-group ofOryza sativathat includes most modern varieties for irrigated systems. Agronomic performance of the ECP under multiple environments in Asia and Africa confirmed its high yield potential. We found that the rate of genetic gain for grain yield found in this study was limited primarily by long cycle times and the direct introduction of non-improved material into the elite pool. Consequently, the current breeding scheme for irrigated rice at IRRI is based on rapid recurrent selection among highly elite lines. In this context, the ECP constitutes an important resource for IRRI and NAREs breeders to carefully characterize and manage that elite diversity.
Immobilization of mercury in contaminated soils through the use of new carbon foam amendments
Authors: Janeiro-Tato I. , Lopez-Anton M. A. , Baragaño D. , Antuña-Nieto C. , Rodríguez E. , Peláez A. I. , Gallego J. R. , Martínez-Tarazona M. R. 
Published: November 2021

Abstract
Background
Mercury (Hg) is recognized as one of the 10 most toxic elements in nature and is much more persistent in soils than in other environmental compartments. However, an effective, environmentally friendly, economical, and large-scale applicable technology for the remediation of soils contaminated by Hg has not yet been established. This study evaluates the feasibility of a new carbon foam-based product for the remediation of three soils contaminated with Hg, and infers the mobilization or immobilization mechanism through a detailed study of Hg speciation.

Results
Soil treatment with carbon foams, one of them impregnated with goethite, reduced Hg availability by 75–100%. The proportion of mercury associated to humic acids (Hg–HA) determined the mobility and the availability of Hg when soils were treated with carbon foams. The drop of pH promotes changes in the structure of HA, a consequence of which is that Hg–HA becomes part of the unavailable fraction of the soil along with HgS. The carbon foam impregnated with goethite did not mobilize Fe as occurred with zero valence iron nanoparticles. The presence of acidic groups on the surface of the foam (carboxyl, quinone and phenolic groups) can strongly improve the binding of metal cations, enhancing Fe immobilization.

Conclusions
A novel carbon foam-based amendment was efficient in immobilizing Hg in all the soils studied. The carbon foam impregnated with goethite, in addition to not mobilizing Fe, had the additional advantage of its low effect on the electrical conductivity of the soil. This novel approach could be considered as a potential amendment for other industrial and/or abandoned mining areas contaminated with Hg and/or other metal(loid)s.