bluuebunny/crossref_metadata_2025_split huggingface dataset:
Customized Color Settings of Digitally Assisted Vitreoretinal Surgery to Enable Use of Lower Dye Concentrations During Macular Surgery
Authors: Park Su Jin , Do Jae Rock , Shin Jae Pil , Park Dong Ho 
Published: January 2022

PurposeThis study evaluated the color contrast ratio (CCR) of the internal limiting membrane (ILM) using different color settings of digitally assisted vitreoretinal surgery (DAVS) with different indocyanine green (ICG) concentrations.sMethodsThis is a prospective comparative observational study. Consecutive patients that underwent 25G vitrectomy and ILM peeling using a standard operating microscope (SOM) (25 eyes), DAVS Ver. 1.1 (12 eyes), or DAVS Ver. 1.3 (13 eyes) were enrolled. The SOM and DAVS Ver. 1.1 groups used 0.075% ICG, and the DAVS Ver. 1.3 group used 0.025% ICG. In DAVS Ver. 1.1, macular CCR was compared between four different presets in the red, green, and blue channels: Default (Red (R) 100%, Green (G) 100%, and Blue (B) 100%); Preset 1 (R 20%, G 100%, B 100%); Preset 2 (R 80%, G 80%, B 100%), and Preset 3 (R 85%, G 100%, B 90%). In DAVS Ver. 1.3, macular CCR was evaluated using two different customized settings that modified the hue and saturation: Customized Setting 1 (R 86, G 100, B 100%, Hue +2°, Saturation 90%, Gamma 1.2) and Customized Setting 2 (R 90, G 100, B 100%, Hue +20°, Saturation 100%, Gamma 0.9). All patients underwent ophthalmologic examinations including BCVA at baseline and at 12 months.ResultsIn DAVS Ver. 1.1, macular CCR was highest in Preset 3 (P &lt; 0.01). The CCR of Customized Setting 2 of DAVS Ver. 1.3 using 0.025% ICG did not differ from that of Preset 3 in DAVS Ver. 1.1 using 0.075% ICG. Furthermore, there was no significant difference in BCVA between the Customized Setting 2 of DAVS Ver. 1.3 with 0.025% ICG and the Preset 3 of DAVS Ver. 1.1 with 0.075% ICG groups at baseline and at 12 months (P &gt; 0.05, respectively).ConclusionCustomized DAVS settings enabled surgeons to use a 3-fold lower ICG concentration in ILM peeling.
Transcriptome Analysis of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis
Authors: Yoshioka Keiichiro , Sato Hironori , Kawasaki Takeshi , Ishii Daisuke , Imamoto Takuro , Abe Mitsuhiro , Hasegawa Yoshinori , Ohara Osamu , Tatsumi Koichiro , Suzuki Takuji 
Published: January 2022

BackgroundSarcoidosis is a granulomatous systemic disease of unknown etiology. Mononuclear cells such as macrophages or lymphocytes in lung tissue and hilar or mediastinal lymph nodes have been recognized to play an essential role in granuloma formation in pulmonary sarcoidosis. Peripheral blood mononuclear cells (PBMCs) consist of several immunocompetent cells and have been shown to play a mechanistic role in the pathogenesis of sarcoidosis. However, the genetic modifications that occur in bulk PBMCs of sarcoidosis remain to be elucidated.PurposeThis study aimed to explore the pathobiological markers of sarcoidosis in PBMCs by comparing the transcriptional signature of PBMCs from patients with pulmonary sarcoidosis with those of healthy controls by RNA sequencing.MethodsPBMC samples were collected from subjects with pulmonary sarcoidosis with no steroid/immunosuppressant drugs (n= 8) and healthy controls (n= 11) from August 2020 to April 2021, and RNA sequencing was performed with the PBMC samples.ResultsPrincipal component analysis using RNA sequencing datasets comparing pulmonary sarcoidosis with healthy controls revealed that the two groups appeared to be differentiated, in which 270 differentially expressed genes were found in PBMCs between sarcoidosis and healthy controls. Enrichment analysis for gene ontology suggested that some biological processes related to the pathobiology of sarcoidosis, such as cellular response to interleukin (IL)-1 and IFN-γ, regulation of IL-6 production, IL-8 secretion, regulation of mononuclear cell migration, and response to lipopolysaccharide, were involved. Enrichment analysis of the KEGG pathway indicated the involvement of tumor necrosis factor (TNF), toll-like receptor signaling, IL-17 signaling pathways, phagosomes, and ribosomes. Most of the genes involved in TNF and IL-17 signaling pathways and phagosomes were upregulated, while most of the ribosome-related genes were downregulated.ConclusionThe present study demonstrated that bulk gene expression patterns in PBMCs were different between patients with pulmonary sarcoidosis and healthy controls. The changes in the gene expression pattern of PBMCs could reflect the existence of sarcoidosis lesions and influence granuloma formation in sarcoidosis. These new findings are important to strengthen our understanding of the etiology and pathobiology of sarcoidosis and indicate a potential therapeutic target for sarcoidosis.
Rational Design and Synthesis of 3-Morpholine Linked Aromatic-Imino-1H-Indoles as Novel Kv1.5 Channel Inhibitors Sharing Vasodilation Effects
Authors: Qin Wei , Li Yi-Heng , Tong Jing , Wu Jie , Zhao Dong , Li Hui-Jin , Xing Lu , He Chun-Xia , Zhou Xin , Li Peng-Quan , Meng Ge , Wu Shao-Ping , Cao Hui-Ling 
Published: January 2022

Atrial fibrillation (AF) is the most common clinical sustained arrhythmia; clinical therapeutic drugs have low atrial selectivity and might cause more severe ventricle arrhythmias while stopping AF. As an anti-AF drug target with high selectivity on the atrial muscle cells, the undetermined crystal structure of Kv1.5 potassium channel impeded further new drug development. Herein, with the simulated 3D structure of Kv1.5 as the drug target, a series of 3-morpholine linked aromatic amino substituted 1H-indoles as novel Kv1.5 channel inhibitors were designed and synthesized based on target–ligand interaction analysis. The synthesis route was practical, starting from commercially available material, and the chemical structures of target compounds were characterized. It was indicated that compounds T16 and T5 (100 μM) exhibited favorable inhibitory activity against the Kv1.5 channel with an inhibition rate of 70.8 and 57.5% using a patch clamp technique. All compounds did not exhibit off-target effects against other drug targets, which denoted some selectivity on the Kv1.5 channel. Interestingly, twelve compounds exhibited favorable vasodilation activity on pre-contracted arterial rings in vitro using KCl or phenylephrine (PE) by a Myograph. The vasodilation rates of compounds T16 and T4 (100 μM) even reached over 90%, which would provide potential lead compounds for both anti-AF and anti-hypertension new drug development.
A Computer-Aided Approach for the Discovery of D-Peptides as Inhibitors of SARS-CoV-2 Main Protease
Authors: Hernández González Jorge E. , Eberle Raphael J. , Willbold Dieter , Coronado Mônika A. 
Published: January 2022

The SARS-CoV-2 main protease, also known as 3-chymotrypsin-like protease (3CLpro), is a cysteine protease responsible for the cleavage of viral polyproteins pp1a and pp1ab, at least, at eleven conserved sites, which leads to the formation of mature nonstructural proteins essential for the replication of the virus. Due to its essential role, numerous studies have been conducted so far, which have confirmed 3CLpro as an attractive drug target to combat Covid-19 and have reported a vast number of inhibitors and their co-crystal structures. Despite all the ongoing efforts, D-peptides, which possess key advantages over L-peptides as therapeutic agents, have not been explored as potential drug candidates against 3CLpro. The current work fills this gap by reporting an in silico approach for the discovery of D-peptides capable of inhibiting 3CLpro that involves structure-based virtual screening (SBVS) of an in-house library of D-tripeptides and D-tetrapeptides into the protease active site and subsequent rescoring steps, including Molecular Mechanics Generalized-Born Surface Area (MM-GBSA) free energy calculations and molecular dynamics (MD) simulations. In vitro enzymatic assays conducted for the four top-scoring D-tetrapeptides at 20 μM showed that all of them caused 55–85% inhibition of 3CLpro activity, thus highlighting the suitability of the devised approach. Overall, our results present a promising computational strategy to identify D-peptides capable of inhibiting 3CLpro, with broader application in problems involving protein inhibition.
Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma
Authors: Mo Meile , Liu Bihu , Luo Yihuan , Tan Jennifer Hui Juan , Zeng Xi , Zeng Xiaoyun , Huang Dongping , Li Changhua , Liu Shun , Qiu Xiaoqiang 
Published: January 2022

Background: Circular RNAs (circRNAs) have been demonstrated to be closely related to the carcinogenesis of human cancer in recent years. However, the molecular mechanism of circRNAs in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. We aimed to identify critical circRNAs and explore their potential regulatory network in HCC.Methods: The robust rank aggregation (RRA) algorithm and weighted gene co-expression network analysis (WGCNA) were conducted to unearth the differentially expressed circRNAs (DEcircRNAs) in HCC. The expression levels of DEcircRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). A circRNA-miRNA-mRNA regulatory network was constructed by computational biology, and protein-protein interaction (PPI) network, functional enrichment analysis, survival analysis, and infiltrating immune cells analysis were performed to uncover the potential regulatory mechanisms of the network.Results: A total of 22 DEcircRNAs were screened out from four microarray datasets (GSE94508, GSE97332, GSE155949, and GSE164803) utilizing the RRA algorithm. Meanwhile, an HCC-related module containing 404 circRNAs was identified by WGCNA analysis. After intersection, only four circRNAs were recognized in both algorithms. Following qRT-PCR validation, three circRNAs (hsa_circRNA_091581, hsa_circRNA_066568, and hsa_circRNA_105031) were chosen for further analysis. As a result, a circRNA-miRNA-mRNA network containing three circRNAs, 17 miRNAs, and 222 mRNAs was established. Seven core genes (ESR1, BUB1, PRC1, LOX, CCT5, YWHAZ, and DDX39B) were determined from the PPI network of 222 mRNAs, and a circRNA-miRNA-hubgene network was also constructed. Functional enrichment analysis suggested that these seven hub genes were closely correlated with several cancer related pathways. Survival analysis revealed that the expression levels of the seven core genes were significantly associated with the prognosis of HCC patients. In addition, we also found that these seven hub genes were remarkably related to the infiltrating levels of immune cells.Conclusion: Our research identified three pivotal HCC-related circRNAs and provided novel insights into the underlying mechanisms of the circRNA-miRNA-mRNA regulatory network in HCC.
Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Authors: Ren Junwei , Qian Dongxi , Wu Jiaming , Ni Lingyan , Qian Wei , Zhao Guozheng , Huang Chuanjun , Liu Xing , Zou Yu , Xing Weikang 
Published: January 2022

BackgroundIn recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients.MethodsPubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose.ResultsTen RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81–1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39–0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13–1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02–1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99–1.23); long-term: RR 1.22 (95% CI 0.99–1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89–1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79–1.25); long-term: RR 1.38 (95% CI 0.86–2.21)]. Results in the daily dose group were consistent with those in the TXA duration group.ConclusionsTranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.
Neck Management in cT1N0 Tongue Squamous Cell Carcinoma as Determined by Sonographic Depth of Invasion
Authors: Wu Yao , Zhang Xu , Dai Liyuan , Fang Qigen , Du Wei 
Published: January 2022

ObjectivesTo compare the oncologic outcomes in patients with cT1N0 tongue squamous cell carcinoma (SCC) who underwent different neck management strategies stratified by sonographic depth of invasion (DOI).MethodsThe included patients were retrospectively enrolled, and divided into two groups: observation (OBS) and elective neck dissection (END). The regional control (RC) and disease-specific survival (DSS) rates were compared and stratified by sonographic DOI.ResultsThe mean sonographic and pathologic DOIs were 3.8 and 3.7 mm, respectively; the two DOIs were significantly correlated (Spearman correlation coefficient 0.974. p &lt;0.001). In patients with sonographic DOI &lt;4.0 mm, the 5-year RC rates were 73 and 89% in the OBS and END groups, respectively, and were not significantly different. However, in patients with sonographic DOI ≥4.0 mm, the 5-year RC rate was significantly different between the OBS (57%) and END (80%) groups (p = 0.031). In patients with sonographic DOI &lt;4.0 mm, the 5-year DSS rates were 79 and 89% in OBS and END groups, respectively, and were not significantly different. However, in patients with sonographic DOI ≥4.0 mm, the 5-year DSS rate was significantly different between the OBS (67%) and END (86%) groups (p = 0.033).ConclusionsSonographic DOI was notably correlated with pathologic DOI. Moreover, there was a significant survival difference between the OBS and END groups in cT1N0 tongue SCC patients with sonographic DOI ≥4.0 mm but not in those with sonographic DOI &lt;4.0 mm. Our study provides a useful method to aid decision-making in the clinical setting for this patient group.
Identification of a Hypoxia-Related Gene Model for Predicting the Prognosis and Formulating the Treatment Strategies in Kidney Renal Clear Cell Carcinoma
Authors: Ning Xiang-hui , Li Ning-yang , Qi Yuan-yuan , Li Song-chao , Jia Zhan-kui , Yang Jin-jian 
Published: January 2022

PurposeThe present study aimed to establish a hypoxia related genes model to predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data accessed from The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database.MethodsPatients’ data were downloaded from the TCGA and ICGC databases, and hypoxia related genes were accessed from the Molecular Signatures Database. The differentially expressed genes were evaluated and then the differential expressions hypoxia genes were screened. The TCGA cohort was randomly divided into a discovery TCGA cohort and a validation TCGA cohort. The discovery TCGA cohort was used for constructing the hypoxia genes risk model through Lasso regression, univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were used to assess the reliability and sensitivity of our model. Then, we established a nomogram to predict the probable one-, three-, and five-year overall survival rates. Lastly, the Tumor Immune Dysfunction and Exclusion (TIDE) score of patients was calculated.ResultsWe established a six hypoxia-related gene prognostic model of KIRC patients in the TCGA database and validated in the ICGC database. The patients with high riskscore present poorer prognosis than those with low riskscore in the three TCGA cohorts and ICGC cohort. ROC curves show our six-gene model with a robust predictive capability in these four cohorts. In addition, we constructed a nomogram for KIRC patients in the TCGA database. Finally, the high risk-group had a high TIDE score than the patients with low riskscore.ConclusionsWe established a six hypoxia-related gene risk model for independent prediction of the prognosis of KIRC patients was established and constructed a robust nomogram. The different riskscores might be a biomarker for immunotherapy strategy.
Association Between NT-proBNP and Prolonged Length of Stay in Hospital Among Preterm Infants Born at 28–31 Weeks' Gestation
Authors: Ge Jian , Luo Chenghan , Lei Mengyuan , Shi Zanyang , Cheng Xinru , Zhao Min , Zhao Yanting , Song Min , Ding Wenqian , Wang Mengmeng , Cao Wenjun , Mao Fengxia , Han Suge , Xu Qianya , Wang Junbo , Qin Haoqi , Wang Li , Zhang Qian 
Published: January 2022

ObjectiveIn the early life of preterm infants, the relationship between heart function and length of hospitalization is unclear. This study aims to examine the association between serum NT-proBNP level on the 7th day (NT-proBNP7) after birth and length of hospitalization among preterm infants.MethodsA retrospective cohort study was conducted. Patients included 709 preterm infants born at 28–31 weeks' gestational age (GA) admitted to the NICU of the First Affiliated Hospital of Zhengzhou University between December 20, 2016, to April 31, 2021. Main outcome: Late discharge (postmenstrual age at discharge was in the fourth quartile (highest) among infants born at the same GA). Exposure factor: NT-proBNP7.ResultsWe observed increased prevalence ratios for late discharge among the tertile of logarithm of NT-proBNP7 level (LnNT-proBNP7) which was positive. Compared with the lowest tertile, infants in the highest tertile of LnNT-proBNP7 had an 8.4-fold increased probability of late discharge, and the results were consistent for the subgroups. Next, a non-linear (S-shaped) relationship between LnNT-proBNP7 and late discharge was observed, whose turning points were 7.5 and 9. The effect sizes and the confidence intervals on the left of the first turning point, between two turning points and on the right of the second turning point, were 0.6 (95% CI, 0.2–1.6), 5.0 (95% CI, 2.4–10.6), and 1.1 (95% CI, 0.2–6.1), respectively. In addition, the prevalence of BPD, NEC, nosocomial infection, or any of them was highest in the group of LnNT-proBNP7 ≥ 9, lowest in the group of LnNT-proBNP7 &lt; 7.5.ConclusionHigher NT-proBNP7 levels were associated with longer hospitalization. The relationship between LnNT-proBNP7 and late discharge was S-shaped. LnNT-proBNP7 was positively related with late discharge when LnNT-proBNP7 was between 7.5 and 9.
Perceived Social Support Partially Mediates the Impact of Temperament and Character on Postpartum Depression
Authors: Nakamura Yukako , Takahashi Nagahide , Yamauchi Aya , Morikawa Mako , Okada Takashi , Ozaki Norio 
Published: January 2022

IntroductionTemperament and character of pregnant women, especially harm avoidance (HA) and self-directedness (SD) have been identified as risk factors for postpartum depression, in addition to poor social support. However, the relationship between these personality traits and social support for depressive symptoms after delivery has not been examined.MethodsData were extracted from a prospective cohort survey on pregnant women conducted in Nagoya, Japan that included the Temperament and Character Inventory (TCI), the Social Support Questionnaire (J-SSQ), and the Edinburgh Postnatal Depression Scale (EPDS) at approximately week 25 and 1 month postpartum. A mediation analysis using structural equation modeling (SEM) was used to test if social support in pregnancy is a mediator between personality traits and postpartum depressive symptoms.ResultsThousand five hundred and fifty-nine women were included in the analysis. Both harm avoidance and SD were significantly associated with depressive symptoms (total effect: β [SE], 0.298 [0.041], P &lt; 0.001 for harm avoidance; total effect: β [SE], −0.265 [0.067], P &lt; 0.001 for SD). Mediation analysis showed that the effect of harm avoidance on depressive symptoms was partially mediated by low social support (direct effect: β [SE], 0.193 [0.004], P &lt; 0.001; indirect effect: β [SE], 0.082 [0.034], P = 0.015). Self-directedness on depressive symptoms was not found to be mediated by low social support.ConclusionResults indicate that poor social support worsens depressive symptoms in women with high HA during pregnancy. Limitations include a possible selection bias due to the limited target facilities; most variables being evaluated based on self-report questionnaires, and different number of samples available for analysis between harm avoidance and SD.
Radiometric Stability Assessment of the DSCOVR EPIC Visible Bands Using MODIS, VIIRS, and Invariant Targets as Independent References
Authors: Haney Conor , Doelling David R. , Su Wenying , Bhatt Rajendra , Gopalan Arun , Scarino Benjamin 
Published: January 2022

The DSCOVR mission was designed to take advantage of the first Lagrangian position (L1) to continuously observe the Earth sunlit disk. To facilitate EPIC V03 data product validation and fusion, the EPIC V03 navigation and calibration stability is assessed. The Aqua-MODIS, NPP-VIIRS, and N20-VIIRS based radiometric scaling factors are also provided. The V03 navigation error was 15.5 km, a 50% improvement over V02 and within what can be achieved by an objective image alignment algorithm. Both the navigation accuracy and precision were improved in V03 and were found to be comparable across all EPIC visible channels. The all-sky tropical ocean and deep convective cloud ray-matched MODIS- and VIIRS-referenced EPIC inter-calibration gains are within 0.4% of one-another, and are also within 0.4% of a previous study’s NPP-VIIRS-referenced gains. The inter-calibration study reveals that EPIC bands 5 and 6 degraded mostly within the first year of operation and becoming stable thereafter, whereas bands 7 and 10 were stable during the 6-years record. The capability of the V03 navigation allowed EPIC stability to be monitored using DCC and Libya-4 invariant targets. The EPIC V03 calibration was mostly stable within 0.3% over the 6-years record, as determined from inter-calibration and invariant target monitoring methods. Remarkably, both the DCC- and Libya-4-based methods were able to confirm the stability of the E-8 and E-9 oxygen absorptions—a stability comparable to that of the E-7 and E-10 reference bands. No significant change in the navigation accuracy or calibration stability was observed after the DSCOVR 2019 safe mode incident. The impressive stability of the DSCOVR EPIC L1B V03 channel radiances can greatly benefit the Earth remote sensing community by providing diurnally complete daytime radiative flux and environmental retrievals for future sensors located at L1.