bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natriuretic peptides and Forkhead O transcription factors act in a cooperative manner to promote cardiomyocyte cell cycle re-entry in the postnatal mouse heart
Authors: Ali Mir , Liccardo Daniela , Cao Tongtong , Tian Ying 
Published: February 2021

AbstractBackgroundCardiomyocytes proliferate rapidly during fetal life but lose their ability of proliferation soon after birth. However, before terminal withdrawal from the cell cycle, cardiomyocytes undergo another round of cell cycle during early postnatal life in mice. While a transient wave of increased DNA synthesis in cardiomyocyte has been observed in postnatal mouse hearts, the molecular mechanisms describing cardiomyocyte cell cycle re-entry remain poorly understood. Atrial and B-type natriuretic peptides (ANP and BNP) are abundantly expressed in embryonic heart ventricles. After birth, the expression of both genes is strongly reduced in the ventricular myocardium. Forkhead O (FOXO) transcription factors are expressed in both embryonic and postnatal heart ventricles. Their transcriptional activity negatively affects cardiomyocyte proliferation. Upon phosphorylation, FOXO is translocated to the cytoplasm and is transcriptionally inactive. Despite these important findings, it remains largely unknown whether natriuretic peptides and FOXO cooperatively play a role in regulating cardiomyocyte cell cycle activity during early postnatal life.ResultsWe observed that the expression of ANP and BNP and the level of phosphorylated FOXO were transiently increased in the postnatal mouse heart ventricles, which coincided with the burst of cardiomyocyte cell cycle re-entry during early postnatal life in mice. Cell culture studies showed that ANP/BNP signaling and FOXO cooperatively promoted cell cycle activity in neonatal mouse cardiomyocytes. The enhanced cell cycle activity observed in combined treatment of ANP/BNP and dominant-negative FOXO (DN-FOXO), which can bind FOXO recognition sites on DNA but cannot activate transcription, was primarily mediated through natriuretic peptide receptor 3 (Npr3). In mice, simultaneous application of ANP and DN-FOXO in postnatal hearts reactivated cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction.ConclusionsOur data demonstrate the cooperative effects of natriuretic peptide and DN-FOXO on promoting cardiomyocyte cell cycle activity and mouse cardiac repair and regeneration after injury.
The influence of QTL allelic diversity on QTL detection in multi-parent populations: a simulation study in sugar beet
Authors: Garin Vincent , Wimmer Valentin , Borchardt Dietrich , Malosetti Marcos , van Eeuwijk Fred 
Published: February 2021

AbstractBackgroundMulti-parent populations (MPPs) are important resources for studying plant genetic architecture and detecting quantitative trait loci (QTLs). In MPPs, the QTL effects can show various levels of allelic diversity, which can be an important factor influencing the detection of QTLs. In MPPs, the allelic effects can be more or less specific. They can depend on an ancestor, a parent or the combination of parents in a cross. In this paper, we evaluated the effect of QTL allelic diversity on the QTL detection power in MPPs.ResultsWe simulated: a) cross-specific QTLs; b) parental and ancestral QTLs; and c) bi-allelic QTLs. Inspired by a real application in sugar beet, we tested different MPP designs (diallel, chessboard, factorial, and NAM) derived from five or nine parents to explore the ability to sample genetic diversity and detect QTLs. Using a fixed total population size, the QTL detection power was larger in MPPs with fewer but larger crosses derived from a reduced number of parents. The use of a larger set of parents was useful to detect rare alleles with a large phenotypic effect. The benefit of using a larger set of parents was however conditioned on an increase of the total population size. We also determined empirical confidence intervals for QTL location to compare the resolution of different designs. For QTLs representing 6% of the phenotypic variation, using 1600F2offspring individuals, we found average 95% confidence intervals over different designs of 49 and 25 cM for cross-specific and bi-allelic QTLs, respectively.ConclusionsMPPs derived from less parents with few but large crosses generally increased the QTL detection power. Using a larger set of parents to cover a wider genetic diversity can be useful to detect QTLs with a reduced minor allele frequency when the QTL effect is large and when the total population size is increased.
Authoritative subspecies diagnosis tool for European honey bees based on ancestry informative SNPs
Authors: Momeni Jamal , Parejo Melanie , Nielsen Rasmus O. , Langa Jorge , Montes Iratxe , Papoutsis Laetitia , Farajzadeh Leila , Bendixen Christian , Căuia Eliza , Charrière Jean-Daniel , Coffey Mary F. , Costa Cecilia , Dall’Olio Raffaele , De la Rúa Pilar , Drazic M. Maja , Filipi Janja , Galea Thomas , Golubovski Miroljub , Gregorc Ales , Grigoryan Karina , Hatjina Fani , Ilyasov Rustem , Ivanova Evgeniya , Janashia Irakli , Kandemir Irfan , Karatasou Aikaterini , Kekecoglu Meral , Kezic Nikola , Matray Enikö Sz. , Mifsud David , Moosbeckhofer Rudolf , Nikolenko Alexei G. , Papachristoforou Alexandros , Petrov Plamen , Pinto M. Alice , Poskryakov Aleksandr V. , Sharipov Aglyam Y. , Siceanu Adrian , Soysal M. Ihsan , Uzunov Aleksandar , Zammit-Mangion Marion , Vingborg Rikke , Bouga Maria , Kryger Per , Meixner Marina D. , Estonba Andone 
Published: February 2021

Abstract
Background
With numerous endemic subspecies representing four of its five evolutionary lineages, Europe holds a large fraction of Apis mellifera genetic diversity. This diversity and the natural distribution range have been altered by anthropogenic factors. The conservation of this natural heritage relies on the availability of accurate tools for subspecies diagnosis. Based on pool-sequence data from 2145 worker bees representing 22 populations sampled across Europe, we employed two highly discriminative approaches (PCA and FST) to select the most informative SNPs for ancestry inference.

Results
Using a supervised machine learning (ML) approach and a set of 3896 genotyped individuals, we could show that the 4094 selected single nucleotide polymorphisms (SNPs) provide an accurate prediction of ancestry inference in European honey bees. The best ML model was Linear Support Vector Classifier (Linear SVC) which correctly assigned most individuals to one of the 14 subspecies or different genetic origins with a mean accuracy of 96.2% ± 0.8 SD. A total of 3.8% of test individuals were misclassified, most probably due to limited differentiation between the subspecies caused by close geographical proximity, or human interference of genetic integrity of reference subspecies, or a combination thereof.

Conclusions
The diagnostic tool presented here will contribute to a sustainable conservation and support breeding activities in order to preserve the genetic heritage of European honey bees.
Triple null mutations in starch synthase SSIIa gene homoeologs lead to high amylose and resistant starch in hexaploid wheat
Authors: Schoen Adam , Joshi Anupama , Tiwari Vijay , Gill Bikram S. , Rawat Nidhi 
Published: February 2021

Abstract
Background
Lack of nutritionally appropriate foods is one of the leading causes of obesity in the US and worldwide. Wheat (Triticum aestivum) provides 20% of the calories consumed daily across the globe. The nutrients in the wheat grain come primarily from the starch composed of amylose and amylopectin. Resistant starch content, which is known to have significant human health benefits, can be increased by modifying starch synthesis pathways. Starch synthase enzyme SSIIa, also known as starch granule protein isoform-1 (SGP-1), is integral to the biosynthesis of the branched and readily digestible glucose polymer amylopectin. The goal of this work was to develop a triple null mutant genotype for SSIIa locus in the elite hard red winter wheat variety ‘Jagger’ and evaluate the effect of the knock-out mutations on resistant starch content in grains with respect to wild type.

Results
Knock-out mutations in SSIIa in the three genomes of wheat variety ‘Jagger’ were identified using TILLING. Subsequently, these loss-of function mutations on A, B, and D genomes were combined by crossing to generate a triple knockout mutant genotype Jag-ssiia-∆ABD. The Jag-ssiia-∆ABD had an amylose content of 35.70% compared to 31.15% in Jagger, leading to ~ 118% increase in resistant starch in the Jag-ssiia-∆ABD genotype of Jagger wheat. The single individual genome mutations also had various effects on starch composition.

Conclusions
Our full null Jag-ssiia-∆ABD mutant showed a significant increase in RS without the shriveled grain phenotype seen in other ssiia knockouts in elite wheat cultivars. Moreover, this study shows the potential for developing nutritionally improved foods in a non-GM approach. Since all the mutants have been developed in an elite wheat cultivar, their adoption in production and supply will be feasible in future.
Clinical characteristics of hospitalized mild/moderate COVID-19 patients with a prolonged negative conversion time of SARS-CoV-2 nucleic acid detection
Authors: Yang Ya , Hu Xiaogang , Xiong Lirong , Fu Peishu , Feng Wei , Li Wei , Zhang Liwen , Sun Fengjun 
Published: February 2021

Abstract
Background
The impact of COVID-19 has been devastating on a global scale. The negative conversion time (NCT) of SARS-CoV-2 RNA is closely related to clinical manifestation and disease progression in COVID-19 patients. Our study aimed to predict factors associated with prolonged NCT of SARS-CoV-2 RNA in mild/moderate COVID-19 patients.

Methods
The clinical features, laboratory data and treatment outcomes of COVID-19 patients were retrospectively analyzed. Then univariate and multivariate analysis were used to screen out risk factors of influencing prolonged NCT of SARS-CoV-2 RNA.

Results
Thirty-two hospitalized mild/moderate COVID-19 patients were enrolled. The general clinical symptoms were cough (78.1%), fever (75%), diarrhea (68.8%), expectoration (56.3%), and nausea (37.5%). More than 40% of the patients had decreased erythrocyte, hemoglobin and leucocyte and 93.8% patients were detected in abnormalities of chest CT. The median NCT of SARS-CoV-2 RNA was 19.5 days (IQR: 14.25–25). Univariate analysis found fever, nausea, diarrhea and abnormalities in chest CTs were positively associated with prolonged NCT of viral RNA (P< 0.05). The multivariate Cox proportional hazard model revealed that fever [Exp (B), 0.284; 95% CI, 0.114–0.707; P<0.05] and nausea [Exp (B), 0.257; 95%CI, 0.096–0.689; P<0.05] were two significant independent factors.

Conclusions
Fever and nausea were two significant independent factors in prolonged NCT of viral RNA in mild/moderate COVID-19 patients, which provided a useful references for disease progression and treatment of COVID-19.
Differentiation of Pseudoprogression from True Progressionin Glioblastoma Patients after Standard Treatment: A Machine Learning Strategy Combinedwith Radiomics Features from T1-weighted Contrast-enhanced Imaging
Authors: Sun Ying-Zhi , Yan Lin-Feng , Han Yu , Nan Hai-Yan , Xiao Gang , Tian Qiang , Pu Wen-Hui , Li Ze-Yang , Wei Xiao-Cheng , Wang Wen , Cui Guang-Bin 
Published: February 2021

Abstract
Background
Based on conventional MRI images, it is difficult to differentiatepseudoprogression from true progressionin GBM patients after standard treatment, which isa critical issue associated with survival. The aim of this study was to evaluate the diagnostic performance of machine learning using radiomics modelfrom T1-weighted contrast enhanced imaging(T1CE) in differentiating pseudoprogression from true progression after standard treatment for GBM.

Methods
Seventy-sevenGBM patients, including 51 with true progression and 26 with pseudoprogression,who underwent standard treatment and T1CE, were retrospectively enrolled.Clinical information, including sex, age, KPS score, resection extent, neurological deficit and mean radiation dose, were also recorded collected for each patient. The whole tumor enhancementwas manually drawn on the T1CE image, and a total of texture 9675 features were extracted and fed to a two-step feature selection scheme. A random forest (RF) classifier was trained to separate the patients by their outcomes.The diagnostic efficacies of the radiomics modeland radiologist assessment were further compared by using theaccuracy (ACC), sensitivity and specificity.

Results
No clinical features showed statistically significant differences between true progression and pseudoprogression.The radiomic classifier demonstrated ACC, sensitivity, and specificity of 72.78%(95% confidence interval [CI]: 0.45,0.91), 78.36%(95%CI: 0.56,1.00) and 61.33%(95%CI: 0.20,0.82).The accuracy, sensitivity and specificity of three radiologists’ assessment were66.23%(95% CI: 0.55,0.76), 61.50%(95% CI: 0.43,0.78) and 68.62%(95% CI: 0.55,0.80); 55.84%(95% CI: 0.45,0.66),69.25%(95% CI: 0.50,0.84) and 49.13%(95% CI: 0.36,0.62); 55.84%(95% CI: 0.45,0.66), 69.23%(95% CI: 0.50,0.84) and 47.06%(95% CI: 0.34,0.61), respectively.

Conclusion
T1CE–based radiomics showed better classification performance compared with radiologists’ assessment.The radiomics modelwas promising in differentiating pseudoprogression from true progression.
Subcortical and brainstem hemiatrophy accompanied by iron deposition in a patient with hemiparkinsonism-hemiatrophy syndrome: a case report
Authors: Chung Su Jin 
Published: February 2021

Abstract
Background
There is no established pathogenesis of hemiparkinsonism-hemiatrophy syndrome (HPHA), and the varied clinical presentations have been reported in several case studies. To the best of our knowledge, the present report describes the first case of HPHA with unusual brain imaging findings.

Case presentation
A 20-year-old man presented with a 6-month history of weakness and clumsiness in his right limbs. He showed right-sided parkinsonism with dystonic hand posture; however, body asymmetry was not noted. Brain imaging revealed hemiatrophy of the left hemisphere subcortical structures and brainstem, and iron deposition in the left globus pallidus and substantia nigra. In addition, dopamine transporter imaging demonstrated normal presynaptic dopaminergic function. The patient was treated with levodopa, which had little to no effect.

Conclusions
This case demonstrates the unique imaging characteristics of HPHA associated with widespread brain hemiatrophy and iron deposition. Further studies are needed to elucidate the diagnostic criteria for this heterogeneous syndrome.
The aquaporin4-IgG status and how it affects the clinical features and treatment response in NMOSD patients in Egypt
Authors: Kishk Nirmeen A. , Abdelfattah Walaa , Shalaby Nevin M. , Shehata Hatem S. , Hassan Amr , Hegazy Mohamed I. , Abokrysha Noha T. , Abdellatif Doaa , Shawky Shereen M. , Abdo Sarah S. , Taha Noha , Fouad Amr M. , Elmazny Alaa , Ragab Amany H. 
Published: February 2021

Abstract
Background
In Egypt, the characterization of Neuromyelitis Optica Spectrum Disorder (NMOSD) is lacking.

Objectives
To determine the demographics, clinical features, aquaporin4 antibodies (AQP4-IgG) status, and neuroimaging of Egyptian NMOSD patients.

Methods
Retrospective analysis of 70 NMOSD patients’ records from the MS clinic, Kasr Alainy hospital, between January 2013 and June 2018.

Results
Patients’ mean age was 34.9 ± 9.2 years, and the mean at disease onset was 28.9 ± 10.5 years. Fifty-nine patients had an initial monosymptomatic presentation. AQP4-IgG was measured using either enzyme-linked immunosorbent assay (ELISA) (22 patients) or cell-based assay (CBA) (34 patients). Six and 29 patients had positive results, respectively (p < 0.001). 84% had typical NMOSD brain lesions. Longitudinally extensive myelitis was detected in 49 patients, and 9 had either short segments or normal cords. Treatment failure was higher in seropositive patients. Rituximab significantly reduced the annualized relapse rate (ARR) compared to Azathioprine with a percentage reduction of (76.47 ± 13.28) and (10.21 ± 96.07), respectively (p = 0.04). Age at disease onset was the only independent predictor for disability (p < 0.01).

Conclusion
Treatment failure was higher in seropositive patients. However, there was no difference in clinical or radiological parameters between seropositive and seronegative patients. Patients, who are polysymptomatic or with older age of onset, are predicted to have higher future disability regardless of the AQP4-IgG status.
Trends in the utilization of youth primary healthcare services and psychological distress
Authors: Potrebny Thomas , Wiium Nora , Haugstvedt Anne , Sollesnes Ragnhild , Wold Bente , Thuen Frode 
Published: February 2021

Abstract
Background
Psychological distress among young people is increasing in Northern Europe. According to established healthcare utilization theory, this will create a greater need for youth primary healthcare and subsequently lead to more help-seeking behavior by distressed young people. The aim of this study was to investigate the association between the use of youth primary healthcare services and psychological distress in times of increasing mental health problems and increased service need.

Methods
This study consisted of five waves of repeated annual cross-sectional data collected from young people (aged 13–19) living in Norway between 2014 and 2018 (n = 368,579). Population-weighted and design-adjusted generalized linear regression with a log-link was used to examine the use of youth primary healthcare services over time.

Results
We found that a large proportion of young people use primary healthcare services and that young people with high levels of psychological distress use primary healthcare services twice as much as their peers with low levels of psychological distress. In addition, between 2014 and 2018 both psychological distress and primary healthcare service utilization increased: psychological distress increased by 5% and total primary healthcare service use increased by 500 consultations per 1000 young people. Overall, psychological distress had a conditional association with youth primary healthcare service use and could account for between 16 and 66% of the change in the use of services between 2014 and 2018, depending on the service type. However, the absolute increase seen in the use of primary healthcare services was mainly driven by young people with low levels of psychological distress as opposed to young people with high psychological distress. This suggest a converging trend.

Conclusions
Our findings suggest that there might be serious barriers between need and help-seeking behavior for young people with high levels of psychological distress and that the pattern of utilization among young people with lower distress may indicate overuse, possibly as an inadvertent consequence of a newly introduced school absence policy. While further research is needed to confirm these findings, our work may inform healthcare providers and policy makers about primary healthcare utilization trends among young people.
Comparison of robotic and laparoscopic rectal cancer surgery: a meta-analysis of randomized controlled trials
Authors: Tang Bo , Lei Xiong , Ai Junhua , Huang Zhixiang , Shi Jun , Li Taiyuan 
Published: February 2021

Abstract
Objective
Robotic and laparoscopic surgery for rectal cancer has been applied in the clinic for decades; nevertheless, which surgical approach has a lower rate of postoperative complications is still inconclusive. Therefore, the aim of this meta-analysis was to compare the postoperative complications within 30 days between robotic and laparoscopic rectal cancer surgery based on randomized controlled trials.

Methods
Randomized controlled trials (until May 2020) that compared robotic and laparoscopic rectal cancer surgery were searched through PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and China Biology Medicine disc (CBMdisc). Data regarding sample size, clinical and demographic characteristics, and postoperative complications within 30 days, including overall postoperative complications, severe postoperative complications (Clavien-Dindo score ≥ III), anastomotic leakage, surgical site infection, bleeding, ileus, urinary complications, respiratory complications, conversion to open surgery, unscheduled reoperation, perioperative mortality, and pathological outcomes, were extracted. The results were analyzed using RevMan v5.3.

Results
Seven randomized controlled trials that included 507 robotic and 516 laparoscopic rectal cancer surgery cases were included. Meta-analysis showed that the overall postoperative complications within 30 days [Z = 1.1, OR = 1.18, 95% CI (0.88–1.57), P = 0.27], severe postoperative complications [Z = 0.22, OR = 1.12, 95% CI (0.41–3.07), P = 0.83], anastomotic leakage [Z = 0.96, OR = 1.27, 95% CI (0.78–2.08), P = 0.34], surgical site infection [Z = 0.18, OR = 1.05, 95% CI (0.61–1.79), P = 0.86], bleeding [Z = 0.19, OR = 0.89, 95% CI (0.27–2.97), P = 0.85], ileus [Z = 1.47, OR = 0.66, 95% CI (0.38–1.15), P = 0.14], urinary complications [Z = 0.66, OR = 1.22, 95% CI (0.67–2.22), P = 0.51], respiratory complications [Z = 0.84, OR = 0.64, 95% CI (0.22–1.82), P = 0.40], conversion to open surgery [Z = 1.73, OR = 0.61, 95% CI (0.35–1.07), P = 0.08], unscheduled reoperation [Z = 0.14, OR = 0.91, 95% CI (0.26–3.20), P = 0.89], perioperative mortality [Z = 0.28, OR = 0.79, 95% CI (0.15–4.12), P = 0.78], and pathological outcomes were similar between robotic and laparoscopic rectal surgery.

Conclusion
Robotic surgery for rectal cancer was comparable to laparoscopic surgery with respect to postoperative complications within 30 days.
Pretreatment with melatonin improves ovarian tissue cryopreservation for transplantation
Authors: Shiroma Marcos Eiji , Damous Luciana Lamarão , Cotrim Fernanda Pereira , Roa Cristiane Lima , Cipolla-Neto José , Reiter Russel Joseph , Baracat Edmund Chada , Soares José Maria 
Published: February 2021

Abstract
Backgroud
Melatonin has anti-inflammatory and antioxidative actions at the mitochondrial level. This indole-containing molecule may protect ovarian grafts during the process of cryopreservation. Therefore, we aimed to determine whether melatonin pretreatment improves rat ovarian graft quality.

Methods
Twenty-six female rats were allocated to two study groups of thirteen animals each: 1) control group: ovaries cryopreserved using the standard protocol; and 2) melatonin group: ovaries cryopreserved in a medium with melatonin. Ten rats of each group were submitted to 24-h freezing, and whole ovaries autologous and avascular transplantation with retroperitoneal placement. After postoperative (PO) day 15, daily vaginal smears were obtained for estrous cycle characterization. Between PO days 30 and 35, the animals were euthanized and ovarian grafts were recovered for histological and immunohistochemical (Ki-67, cleaved caspase-3, TUNEL, von Willebrand factor, estrogen, and progesterone receptors) analyses. The ovaries of the three remaining rats from each group were studied immediately after thawing to assess the effects of cryopreservation. ANOVA and Tukey’s tests were used and the rejection level of the null hypothesis was set at 0.05 or 5% (p < 0.05).

Results
Melatonin promoted faster restart of the estrous cycle and increased the expression of mature follicles, collagen type I, von Willebrand factor, Ki-67, and cleaved caspase-3 on corpora lutea and estrogen receptors in the ovaries as compared to control. There was a reduction in apoptosis by TUNEL on follicles, corpora lutea, and collagen type III.

Conclusion
Based on the evaluated parameters, melatonin may promote the quality of ovarian grafts. Reproductive function enhancement should be further studied.