bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of coronavirus disease 2019 on urological surgery services and training up to the peak of the pandemic in South East England
Authors: Folkard Samuel Stephen , Sturch Paul , Mahesan Tharani , Garnett Stephen 
Published: November 2020

Introduction: The coronavirus disease 2019 (COVID-19) pandemic is having significant effects on health services globally, including on urological surgery for which the British Association of Urological Surgeons (BAUS) has provided national guidance. Kent, Surrey and Sussex (KSS) is one of the regions most affected by COVID-19 in the UK to date. Methods: An anonymous online survey of all KSS urology trainees was conducted. The primary outcome was to assess the effects on urology services, both malignant and benign, across the region in the acceleration phase and at the peak of the pandemic compared to standard care. The second was to quantify the effects on urology training, especially regarding operative exposure. Results: There were significant decreases in urological services provided at the peak of the pandemic across KSS compared to standard care ( p<0.0001). Only 22% of urology units were able to continue operating for low-risk cancer and to continue cystoscopy for two-week wait non-visible haematuria referrals in line with BAUS escalation guidelines. A third (33%) did not complete any prostate biopsies at the peak. The majority of urology units continued clinics by telephone. Urology trainees reported completing substantially fewer operating procedures and workplace-based assessments. A third (33%) had moved to consultant-only operating by the peak. Conclusions: The COVID-19 pandemic has caused significant changes to urological surgery services and training in KSS, with heterogeneity across the region. We suggest further work to quantify the effects nationally. Level of evidence: 4.
Visualisation of fetal meconium on post-mortem magnetic resonance imaging scans: a retrospective observational study
Authors: Hyde Georgia , Fry Andrew , Raghavan Ashok , Whitby Elspeth 
Published: November 2020

Background Less invasive techniques for fetal post-mortems are increasingly used to correlate with parental wishes. With the use of post-mortem magnetic resonance imaging (MRI), normal appearance of the organs must be established. Purpose To investigate the after death appearance of the fetal meconium throughout gestation using the hyperintense appearance of meconium on T1 weighted MRI. Material and Methods This was a retrospective study that took place in a tertiary referral centre radiology department. Sixty-two fetal body post-mortem MRI scans (January 2014 to May 2018) between 12 and 41 weeks gestation were reviewed. Signal intensity of meconium at the rectum, sigmoid colon, splenic flexure and hepatic flexure was evaluated and correlated with gestational age. Interrater reliability was calculated. Results Meconium did not consistently have high signal intensity on T1 scans and was not always obvious. Rectal meconium had the highest intensity, and the more proximal the bowel the lower the intensity. The meconium had higher intensity at earlier gestations. Interrater reliability for rectal meconium gradings was excellent. Conclusion This study provides the first published primary research on the appearance of fetal meconium on post-mortem MRI. Overall, results were variable and suggest an alteration of bowel contents after death, but further investigation is needed to effectively inform practice.
Long-term Stress Distribution Patterns Across the Ankle Joint in Soccer Players: A Computed Tomography Osteoabsorptiometry Study
Authors: Shiota Junki , Momma Daisuke , Yamaguchi Takayoshi , Iwasaki Norimasa 
Published: November 2020

Background: The distribution pattern of subchondral bone density is considered to accurately reflect the stress distribution over a joint under long-term physiologic loading. The biomechanical characteristics of the surface of the ankle joint in soccer players can be determined by measuring this distribution pattern under long-term loading. Purpose: To evaluate the distribution of subchondral bone density across the ankle joint in soccer players and to determine the effects of soccer activities, including kicking motion, on the ankle joint surface under long-term loading conditions by computed tomography (CT) osteoabsorptiometry (CTOAM). Study Design: Cross-sectional study; Level of evidence, 3. Methods: CT imaging data were obtained from both ankles of 10 soccer players (soccer group) and 10 nonathletic volunteers (control group). The distribution patterns of subchondral bone density across the articular surface of the ankle joints were assessed by CTOAM. Quantitative analysis was performed of the locations and percentages of high-density areas on the articular surface. Results: Stress distribution patterns over the ankle joint differed between the soccer players and controls. In the soccer players, the high-density areas were found in the anterior part of the distal tibia and proximal talus as well as the distal fibula. The percentages of high-density areas were greater in the soccer players compared with controls ( P < .0001). Conclusion: Stress distribution over the articular surface of the ankle joint was affected by soccer activities. A high stress concentration was seen in soccer players in the anterior part of the tibia and talus and in the fibula; such excessive stress may lead to anterior impingement.
Incidence of Medial and Lateral Meniscal Tears After Delayed Anterior Cruciate Ligament Reconstruction in Pediatric Patients
Authors: Kawashima Itaru , Hiraiwa Hideki , Ishizuka Shinya , Kawai Ryosuke , Kusaka Yoshiaki , Ohtomo Katsuyuki , Tsukahara Takashi 
Published: November 2020

Background: The treatment of pediatric anterior cruciate ligament (ACL) injuries is controversial, and no clear management guidelines have been established. Purpose: To evaluate the association between elapsed time from ACL injury to surgery and the incidence of meniscal tears and chondral injuries in patients aged ≤16 years. Study Design: Cohort study; Level of evidence, 3. Methods: Between December 2012 and April 2019, a total of 207 consecutive knees in 207 patients aged ≤16 years underwent primary ACL reconstruction and were included in this study. Patients were divided into 1 of 2 groups (early group [≤150 days] and delayed group [>150 days]) based on the time between injury and surgery. Patient records, including arthroscopic findings identified by 2 experienced knee surgeons at the time of surgery, were reviewed for demographic information, incidence and types of medial and lateral meniscal tears, and chondral injuries and their locations in each group. Results: There were 180 knees in the early group and 27 knees in the delayed group. The delayed group showed a significantly higher rate of medial meniscal tears than the early group: 16 of 27 (59.2%) and 46 of 180 (25.6%), respectively (odds ratio [OR], 4.24 [95% CI, 1.83-9.33]; P = .0011). The delayed group had a significantly lower rate of lateral meniscal tears than the early group: 6 of 27 (22.2%) and 90 of 180 (50.0%), respectively (OR, 0.29 [95% CI, 0.11-0.70]; P = .007). The delayed group had significantly higher rates of chondral injuries in the medial femoral condyle and the medial tibial plateau than the early group: 8 of 27 (29.6%) and 25 of 180 (13.9%), respectively (OR, 2.61 [95% CI, 1.03-6.62]; P = .049), and 2 of 27 (7.4%) and 1 of 180 (0.6%), respectively (OR, 14.32 [95% CI, 1.58-208.10]; P = .045). Conclusion: Delayed ACL reconstruction was associated with an increased incidence of medial chondral injuries and medial meniscal tears but with a decreased incidence of lateral meniscal tears.
Genomic and transcriptomic correlates of Richter transformation in chronic lymphocytic leukemia
Authors: Klintman Jenny , Appleby Niamh , Stamatopoulos Basile , Ridout Katie , Eyre Toby A. , Robbe Pauline , Pascua Laura Lopez , Knight Samantha J. L. , Dreau Helene , Cabes Maite , Popitsch Niko , Ehinger Mats , Martín-Subero Jose I. , Campo Elías , Månsson Robert , Rossi Davide , Taylor Jenny C. , Vavoulis Dimitrios V. , Schuh Anna 
Published: November 2020

Abstract
The transformation of chronic lymphocytic leukemia (CLL) to high-grade B-cell lymphoma is known as Richter syndrome (RS), a rare event with dismal prognosis. In this study, we conducted whole-genome sequencing (WGS) of paired circulating CLL (PB-CLL) and RS biopsies (tissue-RS) from 17 patients recruited into a clinical trial (CHOP-O). We found that tissue-RS was enriched for mutations in poor-risk CLL drivers and genes in the DNA damage response (DDR) pathway. In addition, we identified genomic aberrations not previously implicated in RS, including the protein tyrosine phosphatase receptor (PTPRD) and tumor necrosis factor receptor–associated factor 3 (TRAF3). In the noncoding genome, we discovered activation-induced cytidine deaminase–related and unrelated kataegis in tissue-RS affecting regulatory regions of key immune-regulatory genes. These include BTG2, CXCR4, NFATC1, PAX5, NOTCH-1, SLC44A5, FCRL3, SELL, TNIP2, and TRIM13. Furthermore, differences between the global mutation signatures of pairs of PB-CLL and tissue-RS samples implicate DDR as the dominant mechanism driving transformation. Pathway-based clonal deconvolution analysis showed that genes in the MAPK and DDR pathways demonstrate high clonal-expansion probability. Direct comparison of nodal-CLL and tissue-RS pairs from an independent cohort confirmed differential expression of the same pathways by RNA expression profiling. Our integrated analysis of WGS and RNA expression data significantly extends previous targeted approaches, which were limited by the lack of germline samples, and it facilitates the identification of novel genomic correlates implicated in RS transformation, which could be targeted therapeutically. Our results inform the future selection of investigative agents for a UK clinical platform study. This trial was registered at www.clinicaltrials.gov as #NCT03899337.
A validated pediatric disease risk index for allogeneic hematopoietic cell transplantation
Authors: Qayed Muna , Ahn Kwang Woo , Kitko Carrie L. , Johnson Mariam H. , Shah Nirali N. , Dvorak Christopher , Mellgren Karin , Friend Brian D. , Verneris Michael R. , Leung Wing , Toporski Jacek , Levine John , Chewning Joseph , Wayne Alan , Kapoor Urvi , Triplett Brandon , Schultz Kirk R. , Yanik Gregory A. , Eapen Mary 
Published: November 2020

AbstractA disease risk index (DRI) that was developed for adults with hematologic malignancy who were undergoing hematopoietic cell transplantation is also being used to stratify children and adolescents by disease risk. Therefore, to develop and validate a DRI that can be used to stratify those with AML and ALL by their disease risk, we analyzed 2569 patients aged &lt;18 years with acute myeloid (AML; n = 1224) or lymphoblastic (ALL; n = 1345) leukemia who underwent hematopoietic cell transplantation. Training and validation subsets for each disease were generated randomly with 1:1 assignment to the subsets, and separate prognostic models were derived for each disease. For AML, 4 risk groups were identified based on age, cytogenetic risk, and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2, 3, 5), high (7, 8), and very high (&gt;8) risk groups was 78%, 53%, 40%, and 25%, respectively (P &lt; .0001). For ALL, 3 risk groups were identified based on age and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2-4), and high (≥5) risk groups was 68%, 51%, and 33%, respectively (P &lt; .0001). We confirmed that the risk groups could be applied to overall survival, with 5-year survival ranging from 80% to 33% and 73% to 42% for AML and ALL, respectively (P &lt; .0001). This validated pediatric DRI, which includes age and residual disease status, can be used to facilitate prognostication and stratification of children with AML and ALL for allogeneic transplantation.
Obstructive sleep apnoea and the progression of thoracic aortic aneurysm: a prospective cohort study
Authors: Gaisl Thomas , Rejmer Protazy , Roeder Maurice , Baumgartner Patrick , Sievi Noriane A. , Siegfried Sandra , Stämpfli Simon F. , Thurnheer Robert , Stradling John R. , Tanner Felix C. , Kohler Malcolm 
Published: November 2020

BackgroundObstructive sleep apnoea (OSA) is associated with an increased prevalence of aortic aneurysms and it has also been suggested that severe OSA furthers aneurysm expansion in the abdomen. We evaluated whether OSA is a risk factor for the progression of ascending thoracic aortic aneurysm (TAA).MethodsPatients with TAA underwent yearly standardised echocardiographic measurements of the ascending aorta over 3 years and two level III sleep studies. The primary outcome was the expansion rate of TAA in relation to the apnoea–hypopnoea index (AHI). Secondary outcomes included surveillance for aortic events (composite end-points of rupture/dissection, elective surgery or death).ResultsBetween July 2014 and March 2020, 230 patients (median age 70 years, 83.5% male) participated in the cohort. At baseline, 34.8% of patients had AHI ≥15 events·h−1. There was no association between TAA diameter and AHI at baseline. After 3 years, mean±sdexpansion rates were 0.55±1.25 mm at the aortic sinus and 0.60±1.12 mm at the ascending aorta. In the regression analysis, after controlling for baseline diameter and cardiovascular risk factors, there was strong evidence for a positive association of TAA expansion with AHI (aortic sinus estimate 0.025 mm, 95% CI 0.009–0.040 mm; p<0.001 and ascending aorta estimate 0.026 mm, 95% CI 0.011–0.041 mm; p=0.001). 20 participants (8%) experienced an aortic event; however, there was no association with OSA severity.ConclusionOSA may be a modest but independent risk factor for faster TAA expansion and thus potentially contributes to life-threatening complications in aortic disease.
DNA methylation at birth is associated with lung function development until age 26 years
Authors: Mukherjee Nandini , Arathimos Ryan , Chen Su , Kheirkhah Rahimabad Parnian , Han Luhang , Zhang Hongmei , Holloway John W. , Relton Caroline , Henderson A. John , Arshad Syed Hasan , Ewart Susan , Karmaus Wilfried 
Published: November 2020

Little is known about whether DNA methylation (DNAm) of cytosine–phosphate–guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (forced expiratory volume in 1 s, forced vital capacity, their ratio, and forced expiratory flow at 25–75% of forced vital capacity) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm.Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys and 390 girls of IOWBC-F1. Replication in ALSPAC focussed on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2).Differential DNAm of eight CpGs on genesGLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6,andWNT11involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, aged 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs onLHX1andCOL18A1were linked to gene expression in IOWBC-F2.In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.
Revisiting the mechanism of β-O-4 bond cleavage during acidolysis of lignin VII: acidolyses of non-phenolic C6-C2-type model compounds using HBr, HCl and H2SO4, and a proposal on the characteristic action of Br− and Cl−
Authors: Ye Qiaoqiao , Yokoyama Tomoya 
Published: November 2020

AbstractA non-phenolic C6-C2-type lignin model compound with theβ-O-4 bond, 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)ethanol (I), was acidolyzed in aqueous 82% 1,4-dioxane containing HBr, HCl, or H2SO4with a concentration of 0.2 mol/L at 85 ℃ to examine the differences between these acidolyses. Compound Iprimarily converted to an enol ether compound, 1-(2-methoxyphenoxy)-2-(3,4-dimethoxyphenyl)ethene (II), via the benzyl cation followed by acidolyticβ-O-4 bond cleavage regardless of the acid-type, although the disappearance rates of compoundIwere remarkably different (HBr > HCl >> H2SO4). Acidolyses of compoundIIusing these acids under the same conditions showed a similar tendency, but the rate differences were much smaller than in the acidolyses of compound I. Acidolyses of theα-methyl-etherified derivative of compoundI(I-α-OMe) using these acids under the same conditions suggested that the formation rates of the benzyl cation from compoundI-α-OMe (also from compoundI) are not largely different between the acidolyses using these acids, but those of compoundIIfrom the benzyl cation are remarkably different. Acidolysis of theα-bromo-substituting derivative of compoundI(I-α-Br) using HBr under the same conditions showed a characteristic action of Br¯ in the acidolysis. Br¯ adds to the benzyl cation generated from compoundIorI-α-OMe to afford unstable compoundI-α-Br, resulting in acceleration of the formation of compound IIand of the whole acidolysis reaction.
Labour mobility as an adjustment mechanism to asymmetric shocks in Europe: evidence from the Czech Republic, Hungary, Poland and Slovakia
Authors: Nchor Dennis 
Published: November 2020

AbstractThis paper assesses the nature and correlation of shocks in Visegrad countries and investigates the role of labour mobility in the process of adjustment to the effects of asymmetric shocks. Structural vector autoregression (SVAR) models are employed to assess the nature and correlation of shocks while dynamic cointegrated panel autoregressive distributed lag (ARDL) models are used to determine the role of labour mobility in the adjustment process. The dataset for the SVAR models is quarterly time series and covers the period 2000–2020. The dataset for the cointegrated panel ARDL models is annual and covers the period 2000–2019. The results show more asymmetries in external supply, domestic supply, demand and monetary shocks before the financial crisis. The findings also show that more symmetries occurred in Visegrad countries after the financial crisis in relation to external and domestic supply shocks. Asymmetries persisted with regard to demand and monetary shocks after the financial crisis. With labour mobility as an adjustment mechanism to asymmetric shocks, the paper finds that the capacity of labour mobility is very low. The percentage of net migration in the total population is less than 1% in the four countries compared to 15% in the United States. The size of the adjustment coefficients shows that it takes 3–5 years for countries to adjust to asymmetric shocks through labour mobility.
Targeted mutagenesis of ∆5 and ∆6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar)
Authors: Jin Yang , Datsomor Alex K. , Olsen Rolf E. , Vik Jon Olav , Torgersen Jacob S. , Edvardsen Rolf B. , Wargelius Anna , Winge Per , Grammes Fabian 
Published: November 2020

AbstractBackgroundWith declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with other genes involved in lipid metabolism. Several key genes of LC-HUFA synthesis in salmon belong to the fatty acid desaturases 2 (fads2) family. The present study applied whole transcriptome analysis on two CRISPR-mutated salmon strains (crispants), 1)Δ6abc/5Mtwith mutations inΔ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-cgenes,and 2)Δ6bcMtwith mutations inΔ6fads2-b and Δ6fads2-cgenes. Our purpose is to evaluate the genetic effectfads2mutations have on other lipid metabolism pathways in fish, as well as to investigate mosaicism in a commercial species with a very long embryonal period.ResultsBothΔ6abc/5MtandΔ6bcMtcrispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. TheΔ6abc/5Mtfish displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation ofsrebp1genes which are known key transcription regulators of lipid metabolism as well as a number of down-stream genes involved in fatty acidde-novosynthesis, fatty acidβ-oxidation and lipogenesis. Bothelovl5andelovl2genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation ofΔ6bcMtsurprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability.ConclusionsCRISPR-Cas9 can efficiently mutate multiplefads2genes simultaneously in salmon. The results of the present study have provided new information on the transcriptional regulations of lipid metabolism genes after reduction of LC-HUFA synthesis pathways in salmon.
Sex and FOXP3 gene rs2232365 polymorphism may be associated with the clinical and pathological aspects of chronic viral diseases
Authors: Pereira Leonn Mendes Soares , da Silva Madureira Max Willy , de Castro Renata Bezerra Hermes , Abreu Isabella Nogueira , da Silva Conde Simone Regina Souza , Demachki Sâmia , de Sousa Maisa Silva , Queiroz Maria Alice Freitas , Rangel da Silva Andrea Nazaré M. , Lima Sandra Souza , de Oliveira Guimarães Ishak Marluísa , Ishak Ricardo , Vallinoto Antonio Carlos Rosário 
Published: November 2020

AbstractBackgroundThe forkhead box protein 3 (FOXP3) transcription factor is one of the main markers of immunological suppression in different pathological profiles, and the presence of polymorphic variants may alter the gene expression of this factor. Despite descriptions of an association between the presence of the rs2232365 polymorphism and chronic diseases, the role of the sex variant in this context has not yet been elucidated, as theFOXP3gene is located on the human sex chromosome X.ResultsTo contribute to this topic, 323 women and 373 men were enrolled in the study, of which 101 were diagnosed with chronic viral liver diseases (39 women and 62 men), 67 with HTLV-1 infection (44 women and 23 men), 230 with coronary artery disease (91 women and 139 men) and 298 healthy and uninfected blood donors (149 women and men). They were genotyped for the rs2232365 polymorphism. The rs2232365 polymorphism was associated with clinical and pathological aspects and biomarkers of viral infections only in men, with functional differences between different infections.ConclusionsA relationship is suggested between sex andFOXP3rs2232365 polymorphism, resulting in different biological repercussions.