bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing phosphorylation regulatory networks during embryogenesis of honey bee worker and drone (Apis mellifera)
Authors: Ma Beibei , Ma Chuan , Li Jianke , Fang Yu 
Published: September 2022

Protein phosphorylation is known to regulate a comprehensive scenario of critical cellular processes. However, phosphorylation-mediated regulatory networks in honey bee embryogenesis are mainly unknown. We identified 6342 phosphosites from 2438 phosphoproteins and predicted 168 kinases in the honey bee embryo. Generally, the worker and drone develop similar phosphoproteome architectures and major phosphorylation events during embryogenesis. In 24 h embryos, protein kinases A play vital roles in regulating cell proliferation and blastoderm formation. At 48–72 h, kinase subfamily dual-specificity tyrosine-regulated kinase, cyclin-dependent kinase (CDK), and induced pathways related to protein synthesis and morphogenesis suggest the centrality to enhance the germ layer development, organogenesis, and dorsal closure. Notably, workers and drones formulated distinct phosphoproteome signatures. For 24 h embryos, the highly phosphorylated serine/threonine-protein kinase minibrain, microtubule-associated serine/threonine-protein kinase 2 (MAST2), and phosphorylation of mitogen-activated protein kinase 3 (MAPK3) at Thr564 in workers, are likely to regulate the late onset of cell proliferation; in contrast, drone embryos enhanced the expression of CDK12, MAPK3, and MAST2 to promote the massive synthesis of proteins and cytoskeleton. In 48 h, the induced serine/threonine-protein kinase and CDK12 in worker embryos signify their roles in the construction of embryonic tissues and organs; however, the highly activated kinases CDK1, raf homolog serine/threonine-protein kinase, and MAST2 in drone embryos may drive the large-scale establishment of tissues and organs. In 72 h, the activated pathways and kinases associated with cell growth and tissue differentiation in worker embryos may promote the configuration of rudimentary organs. However, kinases implicated in cytoskeleton organization in drone embryos may drive the blastokinesis and dorsal closure. Our hitherto most comprehensive phosphoproteome offers a valuable resource for signaling research on phosphorylation dynamics in honey bee embryos.
The optimal timing for non-culprit percutaneous coronary intervention in patients with multivessel coronary artery disease: A pairwise and network meta-analysis of randomized trials
Authors: Feng Yujia , Li Shu , Hu Sihan , Wan Jing , Shao Hua 
Published: September 2022

Background and aimsRecently, several randomized trials have shown that patients with multivessel disease (MVD) often pursue complete revascularization during percutaneous coronary intervention (PCI) to improve their prognosis. However, the optimal time for the non-culprit artery has been controversial. This study aimed to determine the optimal strategy for revascularization in ST-segment elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease (CAD).MethodsRandomized controlled trials (RCTs) comparing three revascularization strategies [i.e., complete revascularization at the index procedure (CR), complete revascularization as a staged procedure (SR), or culprit-only revascularization (COR)] in STEMI patients with multivessel coronary artery disease were included. We performed both pairwise and network meta-analyses. Network meta-analysis was performed using mixed treatment comparison models.Results17 trials with 8568 patients were included. In the network meta-analysis, the most interesting finding was that staged revascularization increased the risk of major adverse cardiac events (MACE) compared with complete revascularization at the index procedure [odds ratio (OR): 1.93; 95% confidence interval (CI): 1.07–3.49]. In the pairwise meta-analysis, complete revascularization reduced the incidence of MACE [risk ratio (RR): 0.62, 95% CI: 0.48–0.79, p &lt; 0.001], mainly because it reduced the probability of unplanned repeat revascularization (RR: 0.49, 95% CI: 0.33–0.75, p = 0.001). There were no significant differences in all-cause mortality, cardiac mortality, or nonfatal re-myocardial infarction (MI).ConclusionOur analysis suggests that complete revascularization should be performed in STEMI patients with multivessel coronary artery disease, and complete revascularization at the index procedure is superior to staged revascularization in reducing the risk of MACE events.
Fully automatic cardiac four chamber and great vessel segmentation on CT pulmonary angiography using deep learning
Authors: Sharkey Michael J. , Taylor Jonathan C. , Alabed Samer , Dwivedi Krit , Karunasaagarar Kavitasagary , Johns Christopher S. , Rajaram Smitha , Garg Pankaj , Alkhanfar Dheyaa , Metherall Peter , O'Regan Declan P. , van der Geest Rob J. , Condliffe Robin , Kiely David G. , Mamalakis Michail , Swift Andrew J. 
Published: September 2022

IntroductionComputed tomography pulmonary angiography (CTPA) is an essential test in the work-up of suspected pulmonary vascular disease including pulmonary hypertension and pulmonary embolism. Cardiac and great vessel assessments on CTPA are based on visual assessment and manual measurements which are known to have poor reproducibility. The primary aim of this study was to develop an automated whole heart segmentation (four chamber and great vessels) model for CTPA.MethodsA nine structure semantic segmentation model of the heart and great vessels was developed using 200 patients (80/20/100 training/validation/internal testing) with testing in 20 external patients. Ground truth segmentations were performed by consultant cardiothoracic radiologists. Failure analysis was conducted in 1,333 patients with mixed pulmonary vascular disease. Segmentation was achieved using deep learning via a convolutional neural network. Volumetric imaging biomarkers were correlated with invasive haemodynamics in the test cohort.ResultsDice similarity coefficients (DSC) for segmented structures were in the range 0.58–0.93 for both the internal and external test cohorts. The left and right ventricle myocardium segmentations had lower DSC of 0.83 and 0.58 respectively while all other structures had DSC &gt;0.89 in the internal test cohort and &gt;0.87 in the external test cohort. Interobserver comparison found that the left and right ventricle myocardium segmentations showed the most variation between observers: mean DSC (range) of 0.795 (0.785–0.801) and 0.520 (0.482–0.542) respectively. Right ventricle myocardial volume had strong correlation with mean pulmonary artery pressure (Spearman's correlation coefficient = 0.7). The volume of segmented cardiac structures by deep learning had higher or equivalent correlation with invasive haemodynamics than by manual segmentations. The model demonstrated good generalisability to different vendors and hospitals with similar performance in the external test cohort. The failure rates in mixed pulmonary vascular disease were low (&lt;3.9%) indicating good generalisability of the model to different diseases.ConclusionFully automated segmentation of the four cardiac chambers and great vessels has been achieved in CTPA with high accuracy and low rates of failure. DL volumetric biomarkers can potentially improve CTPA cardiac assessment and invasive haemodynamic prediction.
A study on the effect of site response on California seismic hazard map assessment
Authors: Gallahue Molly M. , Salditch Leah , Lucas Madeleine C. , Neely James , Stein Seth , Abrahamson Norman , Williams Tessa , Hough Susan E. 
Published: September 2022

Prior studies have repeatedly shown that probabilistic seismic hazard maps from several different countries predict higher shaking than that observed. Previous map assessments have not, however, considered the influence of site response on hazard. Seismologists have long acknowledged the influence of near-surface geology, in particular low-impedance sediment layers, on earthquake ground-motion at frequencies of engineering concern. Although the overall effects of site response are complex, modern ground-motion models (GMMs) account for site effects using terms based on VS30, the time-averaged shear-wave velocity in the upper 30 m of the Earth’s surface. In this study, we consider general implications of incorporating site terms from modern GMMs using site-specific VS30 as a proxy in probabilistic seismic hazard maps for California. At the long periods (1–5 s) that affect tall buildings, site terms amplify the mapped hazard by factors of 1–3 at many sites relative to maps calculated for the standard reference soft-rock site condition, VS30 = 760 m/s. However, at the short periods of ground-motion that are the main contributors to peak ground acceleration (PGA) and thus affect smaller structures, only negligible effects occur due to nonlinear deamplification of strong ground-motion at high frequencies. Nonlinear deamplification increases as the shaking level increases. For very strong shaking, deamplification can overcome the linear amplification, yielding net deamplification. We explore the implications of these results for the evaluation of hazard maps. Because site effects do not change the maps appreciably at short periods, we can exclude site response as an explanation for why the maps overpredict historically observed shaking as captured by the California Historical Intensity Mapping Project (CHIMP) dataset. The results are expected to be generalizable to regions that are comparable to California in terms of structure and seismicity rates. In low-to-moderate-seismicity regions where the hazard reflects weaker shaking, nonlinear site response is expected to be less important for the hazard.
Daily requirement of softgel thyroxine is independent from gastric juice pH
Authors: Virili Camilla , Capriello Silvia , Stramazzo Ilaria , Brusca Nunzia , Santaguida Maria Giulia , Gargano Lucilla , Bagaglini Maria Flavia , Bruno Giovanni , Severi Carola , Centanni Marco 
Published: September 2022

BackgroundSoftgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better performance of softgel LT4 preparation in patients with gastric disorders but whether this finding is related to gastric juice pH variation in vivo is not known.MethodsTwenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 µg/kg/day) and with stable thyroid stimulating hormone (TSH) values on target (&lt;0.8-2.5&gt; mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar individual serum TSH value. All subjects followed a specific treatment schedule, taking LT4 in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent endoscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gastric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients.ResultsUpon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly reduced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction &gt;20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p&lt;0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p&lt;0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman’s ρ =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman’s ρ =1.952; p = 0.3194).ConclusionsThese findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with increased LT4 requirement, owed to disorders impairing the gastric acidic output.
Experimental investigation of the film cooling performance by triangular-shaped thin plates on inclined cylindrical holes
Authors: Choi Jaemun , Choi Jaehun , Kwon Hwabhin , Jang Hoyong , Park Heesung 
Published: September 2022

Experimental investigations have been conducted to improve the cooling effectiveness of film-cooling technology. A multiple row of cylindrical holes at the flat surface was considered by inclining the holes at 35° along the streamwise direction. A low-speed wind tunnel with the main flow speed of 10 m/s was devised to create a cross flow at a Reynolds number of 196,167 and five blowing ratios of 0.3, 0.5, 0.7, 1, and 2. The proposed triangular-shaped thin plate and flop at the cylindrical film cooling hole were investigated using flow visualization and thermographic techniques. The resulting cooling performances were also experimentally evaluated and compared with respect to the different film-cooling hole configurations. The typical film cooling hole configuration of cylindrical hole shape shows the cooling effectiveness of 0.1 at blowing ration of 1.0. It should be denoted that this cooling effectiveness is exemplary value of wide range of gas turbine applications. We also experimentally evaluates the cooling effectiveness in order to valid our experimental method. Meanwhile, with triangular-shaped thin plate-flop, the flow detachment is successfully prevented with requiring 8% increase of discharge coefficient. In addition, the film flow is stable even at the distant downstream, resulting in enhanced cooling performance compared to the cylindrical and triangular-shaped thin plate. Consequently, a 242.7% improvement in film cooling effectiveness can be achieved with a triangular-shaped thin plate-flop than with a cylindrical hole owing to its enhanced film coverage.
Case Report: How whole-genome sequencing-based cell-free DNA prenatal testing can help identify a marker mhromosome
Authors: Kleinfinger Pascale , Brechard Marie , Luscan Armelle , Trost Detlef , Boughalem Aicha , Mylene Valduga  , Serero DR Stéphane , Costa Jean-Marc , Lohmann Laurence 
Published: September 2022

A supernumerary marker chromosome (SMC) is a structurally abnormal chromosome that cannot be characterized by conventional banding cytogenetics. Marker chromosomes are present in 0.075% of prenatal cases. They are associated with variable phenotypes, ranging from normal to severely abnormal, and the prognosis is largely dependent on the results of further cytogenomic analysis. Here, we report the identification and characterization of a marker chromosome following prenatal screening in a 39-year-old pregnant patient. The patient had a normal first trimester ultrasound but was high-risk for fetal chromosome anomalies based on the results of maternal serum parameters. Chorionic villus sampling was performed, and analysis of chorionic villi revealed the presence of two identical marker chromosomes. In the interest of a rapid identification of the markers, we performed noninvasive prenatal testing (NIPT) together with chorionic villus sampling. A pericentromeric 29 Mb duplication of chromosome 20: dup (20) (p13q11.21) was identified and thereafter confirmed by targeted metaphasic FISH. Whole-genome sequencing-based NIPT was instrumental in rapid characterization of the SMCs and allowed us to obviate the need for multiple expensive and time-consuming FISH analyses.
Differential expression of circRNAs of testes with high and low sperm motility in Yili geese
Authors: Wu Yingping , Li Haiying , Zhao Xiaoyu , Baki Gulnar , Ma Chen , Yao Yingying , Li Jiahui , Yao Yang , Wang Lin 
Published: September 2022

The aim of this study was to explore the potential biological function of circular RNAs (circRNAs) in the sperm motility traits of Xinjiang Yili geese, and to provide a reference for analyzing the mechanism of regulation of Yili geese sperm motility. The 10 selected Xinjiang Yili Geese with high or low sperm motility (five for each group) were 3 years old, in good health, and were kept in the same feeding conditions. Yili geese were slaughtered for the collection of testicular tissue and high-throughput sequencing technology was used to screen differentially expressed circRNAs for bioinformatics analysis. Combined with the previously screened miRNAs related to the sperm motility of Yili geese, the circRNAs miRNAs regulatory network was constructed. The results showed that a total of 26,311 circRNAs were obtained from testicular tissues with high and low sperm motility, and 173 DECs were screened between the two groups (p &lt; 0.05, |log2Foldchange|&gt;0), of which 82 were up-regulated and 91 were down-regulated. Functional analysis of the source genes of these DECs showed that the source genes were mainly involved in biological processes. KEGG enrichment analysis showed that the source genes of DECs were mainly enriched in autophagy-animal, ubiquinone and other terpenoid-quinone biosynthesis, progesterone-mediated oocyte maturation, regulation of the actin cytoskeleton and other pathways. Furthermore, the visual regulatory network of differential circRNA-miRNA-mRNA was constructed, including 20 circRNAs, 18 miRNAs and 177 mRNAs, and nine core regulatory circRNAs were screened, including novell_circ_0045314, novel_circ_0019994 and novel_circ_0020422, etc., targeting ppy-mir-16, hsa-mir-221–3p, gga-mir-499–5p, etc. The results suggest that circRNAs may interact with miRNAs to further regulate mRNA to regulate sperm motility in Yili geese, so as to provide a reference for analyzing the molecular mechanism of sperm motility regulation.
Comprehensive analysis of somatic mutator-derived and immune infiltrates related lncRNA signatures of genome instability reveals potential prognostic biomarkers involved in non-small cell lung cancer
Authors: Yang Cai-Zhi , Yang Ting , Liu Xue-Ting , He Can-Feng , Guo Wei , Liu Shan , Yao Xiao-Hui , Xiao Xi , Zeng Wei-Ran , Lin Li-Zhu , Huang Zhong-Yu 
Published: September 2022

Background: The function and features of long non-coding RNAs (lncRNAs) are already attracting attention and extensive research on their role as biomarkers of prediction in lung cancer. However, the signatures that are both related to genomic instability (GI) and tumor immune microenvironment (TIME) have not yet been fully explored in previous studies of non-small cell lung cancer (NSCLC).Method: The clinical characteristics, RNA expression profiles, and somatic mutation information of patients in this study came from The Cancer Genome Atlas (TCGA) database. Cox proportional hazards regression analysis was performed to construct genomic instability-related lncRNA signature (GIrLncSig). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential functions of lncRNAs. CIBERSORT was used to calculate the proportion of immune cells in NSCLC.Result: Eleven genomic instability-related lncRNAs in NSCLC were identified, then we established a prognostic model with the GIrLncSig ground on the 11 lncRNAs. Through the computed GIrLncSig risk score, patients were divided into high-risk and low-risk groups. By plotting ROC curves, we found that patients in the low-risk group in the test set and TCGA set had longer overall survival than those in the high-risk group, thus validating the survival predictive power of GIrLncSig. By stratified analysis, there was still a significant difference in overall survival between high and low risk groups of patients after adjusting for other clinical characteristics, suggesting the prognostic significance of GIrLncSig is independent. In addition, combining GIrLncSig with TP53 could better predict clinical outcomes. Besides, the immune microenvironment differed significantly between the high-risk and the low-risk groups, patients with low risk scores tend to have upregulation of immune checkpoints and chemokines. Finally, we found that high-risk scores were associated with increased sensitivity to chemotherapy.Conclusion: we provided a new perspective on lncRNAs related to GI and TIME and revealed the worth of them in immune infiltration and immunotherapeutic response. Besides, we found that the expression of AC027288.1 is associated with PD-1 expression, which may be a potential prognostic marker in immune checkpoint inhibitor response to improve the prediction of clinical survival in NSCLC patients.
Understanding efficacy-safety balance of biologics in moderate-to-severe pediatric psoriasis
Authors: Golhen Klervi , Winskill Carolyn , Theiler Martin , Buettcher Michael , Yeh Yu-Hsin , Zhang Nancy , Welzel Tatjana , Pfister Marc 
Published: September 2022

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease affecting both adults and children. To better understand the efficacy-safety profile of biologics in children with moderate-to-severe psoriasis, this study aimed to analyze efficacy and safety data of randomized controlled trials (RCTs) performed in pediatric psoriasis and to compare efficacy outcomes in children with those in adults.MethodsRCTs investigating biologics in children with moderate-to-severe psoriasis were identified in a systematic literature review. PASI75/90 treatment responses at weeks 11/12 were analyzed comparing biologics with control arms. Serious adverse events (SAEs) were analyzed at the end of each study. Efficacy data from RCTs in adults with psoriasis were selected for the same biologics. Risk ratios (RR) of selected RCTs were pooled together in a statistical random effects model using the inverse variance method.ResultsFor children, there were 1 etanercept, 2 secukinumab, 1 ixekizumab and 1 ustekinumab placebo-controlled RCTs and 1 adalimumab RCT using methotrexate as reference arm at weeks 11/12. For adults, out of 263 RCTs, 7 adalimumab and 15 etanercept (TNF inhibitors) and 4 ixekizumab and 12 ustekinumab (IL-17 and IL-12/23 inhibitors) RCTs reported PASI75/90 efficacy responses at weeks 11/12. Regarding efficacy, all biologics showed improved PASI responses over control arms. RRs ranges were 2.02–7.45 in PASI75 and 4.10–14.50 in PASI90. The highest PASI75 responses were seen for ustekinumab 0.375 mg/kg (RR = 7.25, 95% CI 2.83–18.58) and ustekinumab 0.75 mg/kg (RR = 7.45, 95% CI 2.91–19.06) in the CADMUS study. The highest PASI90 response was seen for ixekizumab (RR = 14.50, 95% CI 4.82–43.58) in the IXORA-PEDS study. SAE incidences in pediatric and adult arms with biologics were 0 to 3% except for a pediatric arm with adalimumab 0.40 mg/kg (8%). For adults, pooled RR also showed improved PASI responses over placebo for all biologics, with highest PASI75 response observed for ixekizumab (pooled RR = 16.18, 95% CI 11.83–22.14).ConclusionBoth adults and children with psoriasis show superior efficacy with biologics compared to control arms after 3 months of treatment with SAE incidences in the low percentages. Additional longer-term clinical studies are warranted to fully understand the overall efficacy-safety profile of biologics in children with moderate-to-severe psoriasis.