bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yellow-y Functions in Egg Melanization and Chorion Morphology of the Asian Tiger Mosquito, Aedes albopictus
Authors: Noh Mi Young , Mun Seulgi , Kramer Karl J. , Muthukrishnan Subbaratnam , Arakane Yasuyuki 
Published: December 2021

The Asian tiger mosquito, Aedes albopictus, is one of the most serious public health pests, which can transmit various vector-borne diseases. Eggs from this mosquito species become dark black shortly after oviposition and exhibit high desiccation resistance. Some of the Yellow proteins that act as dopachrome conversion enzymes (DCEs) are involved in the tyrosine-mediated tanning (pigmentation and sclerotization) metabolic pathway that significantly accelerates melanization reactions in insects. In this research, we analyzed the function of one of the yellow genes, yellow-y (AalY-y), in eggshell/chorion melanization of Ae. albopictus eggs. Developmental and tissue-specific expression measured by real-time PCR showed that AalY-y transcripts were detected at all stages of development analyzed, with significantly higher levels in the ovaries from blood-fed adult females. Injection of double-stranded RNA for AalY-y (dsAalY-y) had no significant effect on fecundity. However, unlike dsEGFP-treated control eggs that become black by 2–3 h after oviposition (HAO), dsAalY-y eggs were yellow-brown at 2 HAO, and reddish-brown even at 48 HAO. dsEGFP eggs exhibited resistance to desiccation at 48 HAO, whereas approximately 50% of the dsAalY-y eggs collapsed when they were moved to a low humidity condition. In addition, TEM analysis revealed an abnormal morphology and ultrastructure of the outer-endochorion in the dsAalY-y eggs. These results support the hypothesis that AalY-y is involved in the tyrosine-induced melanin biosynthetic pathway, plays an important role in black melanization of the chorion and functions in conferring proper morphology of the outer-endochorion, a structure that is presumably required for egg desiccation resistance in Ae. albopictus.
Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19
Authors: Valdés-Aguayo José J. , Garza-Veloz Idalia , Vargas-Rodríguez José R. , Martinez-Vazquez María C. , Avila-Carrasco Lorena , Bernal-Silva Sofia , González-Fuentes Carolina , Comas-García Andreu , Alvarado-Hernández Diana E. , Centeno-Ramirez Alba S. H. , Rodriguez-Sánchez Iram P. , Delgado-Enciso Ivan , Martinez-Fierro Margarita L. 
Published: December 2021

IntroductionDuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient’s outcome.MethodsA total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene.ResultsThere were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/μl ± 0.30) and controls (3.3 ng/μl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/μl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/μl) were also observed (p = 0.037).ConclusionHigh levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.
Driveline Features as Risk Factor for Infection in Left Ventricular Assist Devices: Meta-Analysis and Experimental Tests
Authors: Kranzl Melanie , Stoiber Martin , Schaefer Anne-Kristin , Riebandt Julia , Wiedemann Dominik , Marko Christiane , Laufer Günther , Zimpfer Daniel , Schima Heinrich , Schlöglhofer Thomas 
Published: December 2021

Background: Risk factors for driveline infection (DLI) in patients with left ventricular assist devices are multifactorial. The aim of this study was to analyze the correlation between mechanical driveline features and DLI occurrence.Methods: A meta-analysis was conducted that included studies reporting DLI rates at 6 months after implantation of any of three contemporary devices (HVAD with Pellethane or Carbothane driveline, HeartMate II, and HeartMate 3). Further, outer driveline diameter measurements and ex-vivo experimental three-point bending and torsion tests were performed to compare the stiffness of the four different driveline types.Results: 21 studies with 5,393 patients were included in the meta-analysis. The mean weighted DLI rates ranged from 7.2% (HeartMate II) to 11.9% (HeartMate 3). The HeartMate II driveline had a significantly lower maximal bending force (Loadmax) (4.52 ± 0.19 N) compared to the Carbothane HVAD (8.50 ± 0.08 N), the HeartMate 3 (11.08 ± 0.3 N), and the Pellethane HVAD driveline (15.55 ± 0.14 N) (p &lt; 0.001). The maximal torque (Torquemax) of the HeartMate II [41.44 (12.61) mNm] and the Carbothane HVAD driveline [46.06 (3.78) mNm] were significantly lower than Torquemax of the Pellethane HVAD [46.06 (3.78) mNm] and the HeartMate 3 [95.63 (26.60) mNm] driveline (p &lt; 0.001). The driveline of the HeartMate 3 had the largest outer diameter [6.60 (0.58) mm]. A relationship between the mean weighted DLI rate and mechanical driveline features (Torquemax) was found, as the the HeartMate II driveline had the lowest Torquemax and lowest DLI rate, whereas the HeartMate 3 driveline had the highest Torquemax and highest DLI rate.Conclusions: Device-specific mechanical driveline features are an additional modifiable risk factor for DLI and may influence clinical outcomes of LVAD patients.
Atherogenic Index of Plasma and Coronary Artery Disease in the Adult Population: A Meta-Analysis
Authors: Wu Jing , Zhou Qiang , Wei Zhouxia , Wei Jinying , Cui Meizi 
Published: December 2021

Background: The atherogenic index of plasma (AIP), which is the logarithm of the ratio between the triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) concentrations in molar units, is correlated with the burden of atherosclerosis. This study aimed to evaluate the association between the AIP and coronary artery disease (CAD) in the adult population by performing a meta-analysis.Methods: Observational studies relevant for this meta-analysis were identified by searching the PubMed, Embase, and Web of Science databases. Only studies using multivariate analysis were considered. A random-effects model, which incorporates potential intra-study heterogeneity, was applied to combine the results.Results: Ten observational studies were included. In studies with the AIP analyzed as a continuous variable, a higher AIP was associated with a higher odds of CAD (adjusted risk ratio [RR] per 1-standard deviation [SD] increment of AIP: 2.10, 95% confidence interval [CI]: 1.51–2.93, P &lt; 0.001, I2 = 90%). Further analysis of studies with the AIP analyzed as a categorical variable showed a higher odds of CAD (adjusted RR: 2.35, 95% CI: 1.88–2.93, P &lt; 0.001, I2 = 37%) in the participants with the highest versus the lowest AIP value. Subgroup analyses demonstrated consistent results in asymptomatic and symptomatic populations as well as in male and female participants (all between-group P values &gt; 0.05).Discussion: Current evidence, mostly from cross-sectional studies, suggests that a higher AIP value may be independently associated with CAD in the adult population.
Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome
Authors: Lukovic Jelena , Petrovic Irina , Liu Zijin , Armstrong Susan M. , Brierley James D. , Tsang Richard , Pasternak Jesse D. , Gomez-Hernandez Karen , Liu Amy , Asa Sylvia L. , Mete Ozgur 
Published: December 2021

ObjectiveThe main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population.MethodsPatients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome.ResultsIn total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p&lt;0.001), extra-thyroidal extension (HR 24.95; p&lt;0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p&lt;0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease.ConclusionWe present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.
Identification and Mechanism of the PD-1/PD-L1 Genomic Signature SORL1 as Protective Factor in Bladder Cancer
Authors: Xu Yajing , Chen Didi , Shen Lanxiao , Huang Xiaowei , Chen Yi , Su Huafang 
Published: December 2021

Background: Immunotherapy has recently shown remarkable efficacy for advanced bladder cancer patients. Accordingly, identifying a biomarker associated with the programmed cell death protein 1 (PD-1)/its ligand (PD-L1) genomic signature to predict patient prognosis is necessary.Methods: In this study, we used mutation data and RNA-seq data of bladder cancer samples acquired from The Cancer Genome Atlas (TCGA) database to combine PD-1/PD-L1-associated mutational signatures with PD-1/PD-L1-associated differentially expressed genes (DEGs). Then, we performed a Kaplan-Meier analysis on the corresponding clinical data of the TCGA bladder urothelial carcinoma (BLCA) cohort to identify prognostic genes, and the results were validated using the GSE48075 cohort. The online platform UCSC Xena was used to analyze the relationship between the candidate genes and clinical parameters. We utilized the Human Protein Atlas (HPA) database to validate the protein expression levels. Then, correlation analysis, cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) analysis, and gene set enrichment analysis (GSEA) were used to clarify the mechanism.Results: We identified one prognostic gene, sortilin related receptor 1 (SORL1), whose downregulation was associated with a comparatively advanced BLCA stage. While further exploring this finding, we found that SORL1 expression was negatively correlated with PD-1/PD-L1 expression and M2 macrophage levels. Furthermore, we found that the downregulation of SORL1 expression was significantly associated with a higher epithelial-mesenchymal transition (EMT) score.Conclusion: We described a novel PD-1/PD-L1-associated signature, SORL1, that predicts favorable outcomes in bladder cancer. SORL1 might reduce immune suppression and inhibit the M2 macrophage-induced EMT phenotype of tumor cells.
MRI-Based Radiomics for Differentiating Orbital Cavernous Hemangioma and Orbital Schwannoma
Authors: Chen Liang , Shen Ya , Huang Xiao , Li Hua , Li Jian , Wei Ruili , Yang Weihua 
Published: December 2021

Aim: The purpose of this work was to develop and evaluate magnetic resonance imaging (MRI)-based radiomics for differentiation of orbital cavernous hemangioma (OCH) and orbital schwannoma (OSC).Methods: Fifty-eight patients (40 OCH and 18 OSC, confirmed pathohistologically) screened out from 216 consecutive patients who presented between 2015 and 2020 were divided into a training group (28 OCH and 12 OSC) and a validation group (12 OCH and 6 OSC). Radiomics features were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). T-tests, the least absolute shrinkage and selection operator (LASSO), and principal components analysis (PCA) were used to select features for use in the classification models. A logistic regression (LR) model, support vector machine (SVM) model, decision tree (DT) model, and random forest (RF) model were constructed to differentiate OCH from OSC. The models were evaluated according to their accuracy and the area under the receiver operator characteristic (ROC) curve (AUC).Results: Six features from T1WI, five features from T2WI, and eight features from combined T1WI and T2WI were finally selected for building the classification models. The models using T2WI features showed superior performance on the validation data than those using T1WI features, especially the LR model and SVM model, which showed accuracy of 93% (85–100%) and 92%, respectively, The SVM model showed high accuracy of 93% (91–96%) on the combined feature group with an AUC of 98% (97–99%). The DT and RF models did not perform as well as the SVM model.Conclusion: Radiomics analysis using an SVM model achieved an accuracy of 93% for distinguishing OCH and OSC, which may be helpful for clinical diagnosis.
Circadian Clock Genes Modulate Immune, Cell Cycle and Apoptosis in the Diagnosis and Prognosis of Pan-Renal Cell Carcinoma
Authors: Liu Shuwen , Cheng Yongxian , Wang Shaoxiang , Liu Huiyu 
Published: December 2021

Background: Pan-renal cell carcinoma (pan-RCC) is mainly divided into renal clear cell carcinoma (KIRC), renal papillary cell carcinoma (KIRP), and chromophobe cell carcinoma (KICH). Pan-RCC is a common malignant neoplasm with a high incidence and poor prognosis. Several studies have demonstrated a close association between cancer development and circadian rhythms; however, the clinical significance and molecular mechanism of the clock gene remain unclear in pan-RCC.Methods: In this study, we systematically characterized the alterations of 15 well-known clock genes of three types of kidney cancer. Bioinformatics methods, including differential expression analysis, survival analysis, signing pathway analysis, co-expression network analysis, and drug sensitivity analysis were used to study the diagnosis, prognostic role, and mechanism of clock genes.Results: Thirteen rhythmic genes fluctuated in circadian rhythm in the kidney tissue of mice, and the opposite trend of these rhythm phases was also found in baboons. There are twelve clock genes that were differentially expressed in at least two types of RCC, of which NR1D1, DBP, BHLHE40, CRY1, and CLOCK had the same trend in RCC. Changes in clock control genes may be regulated through methylation, copy number, and mutations. Five rhythmic genes, including PER2, DBP, PER3, CRY2, and RORA, have significant prognostic role in patient survival in at least two types of kidney cancer. Immune infiltration analysis showed that the expression of these rhythmic genes related to prognosis was positively correlated with the infiltration levels of CD4 and CD8 T cells. Pathway analysis suggests that the clock genes is widely related to cancer-related signaling pathways, such as apoptosis, cell cycle, and other pathways. The PPI network showed that circadian genes are closely linked to cancer-related genes such as HIF-1A, TP53, and ERBB2. Moreover, clock gene expression is correlated with the sensitivity of anticancer drugs such as bleomycin and methotrexate in pan-RCC.Conclusion: Taken together, the abnormal expression of biological clock genes plays an important role in the clinical prognosis of RCC through immunity, cell cycle, and apoptosis. These findings provide a reliable basis for the diagnosis, prognosis, and drug guidance for RCC.
Design and Development of a Mobile Health (mHealth) Platform for Dementia Prevention in the Prevention of Dementia by Mobile Phone Applications (PRODEMOS) Project
Authors: Hafdi Melanie , Eggink Esmé , Hoevenaar-Blom Marieke P. , Witvliet M. Patrick , Andrieu Sandrine , Barnes Linda , Brayne Carol , Brooks Rachael , Coley Nicola , Georges Jean , van der Groep Abraham , van Marwijk Harm , van der Meijden Mark , Song Libin , Song Manshu , Wang Youxin , Wang Wenzhi , Wang Wei , Wimo Anders , Ye Xiaoyan , Moll van Charante Eric P. , Richard Edo 
Published: December 2021

Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China.Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China.Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities.Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes.
Stroke Epidemiology, Care, and Outcomes in Kenya: A Scoping Review
Authors: Waweru Peter , Gatimu Samwel Maina 
Published: December 2021

Background: Stroke is a leading cause of death and disability in sub-Saharan Africa with increasing incidence. In Kenya, it is a neglected condition with a paucity of evidence despite its need for urgent care and hefty economic burden. Therefore, we reviewed studies on stroke epidemiology, care, and outcomes in Kenya to highlight existing evidence and gaps on stroke in Kenya.Methods: We reviewed all published studies on epidemiology, care, and outcomes of stroke in Kenya between 1 January 1990 to 31 December 2020 from PubMed, Web of Science, EBSCOhost, Scopus, and African journal online. We excluded case reports, reviews, and commentaries. We used the Newcastle-Ottawa scale adapted for cross-sectional studies to assess the quality of included studies.Results: Twelve articles were reviewed after excluding 111 duplicates and 94 articles that did not meet the inclusion criteria. Five studies were of low quality, two of medium quality, and five of high quality. All studies were hospital-based and conducted between 2003 and 2017. Of the included studies, six were prospective and five were single-center. Stroke patients in the studies were predominantly female, in their seventh decade with systemic hypertension. The mortality rate ranged from 5 to 27% in-hospital and 23.4 to 26.7% in 1 month.Conclusions: Our study highlights that stroke is a significant problem in Kenya, but current evidence is of low quality and limited in guiding policy development and improving stroke care. There is thus a need for increased investment in hospital- and community-based stroke care and research.
3D U-Net Improves Automatic Brain Extraction for Isotropic Rat Brain Magnetic Resonance Imaging Data
Authors: Hsu Li-Ming , Wang Shuai , Walton Lindsay , Wang Tzu-Wen Winnie , Lee Sung-Ho , Shih Yen-Yu Ian 
Published: December 2021

Brain extraction is a critical pre-processing step in brain magnetic resonance imaging (MRI) analytical pipelines. In rodents, this is often achieved by manually editing brain masks slice-by-slice, a time-consuming task where workloads increase with higher spatial resolution datasets. We recently demonstrated successful automatic brain extraction via a deep-learning-based framework, U-Net, using 2D convolutions. However, such an approach cannot make use of the rich 3D spatial-context information from volumetric MRI data. In this study, we advanced our previously proposed U-Net architecture by replacing all 2D operations with their 3D counterparts and created a 3D U-Net framework. We trained and validated our model using a recently released CAMRI rat brain database acquired at isotropic spatial resolution, including T2-weighted turbo-spin-echo structural MRI and T2*-weighted echo-planar-imaging functional MRI. The performance of our 3D U-Net model was compared with existing rodent brain extraction tools, including Rapid Automatic Tissue Segmentation, Pulse-Coupled Neural Network, SHape descriptor selected External Regions after Morphologically filtering, and our previously proposed 2D U-Net model. 3D U-Net demonstrated superior performance in Dice, Jaccard, center-of-mass distance, Hausdorff distance, and sensitivity. Additionally, we demonstrated the reliability of 3D U-Net under various noise levels, evaluated the optimal training sample sizes, and disseminated all source codes publicly, with a hope that this approach will benefit rodent MRI research community.Significant Methodological Contribution: We proposed a deep-learning-based framework to automatically identify the rodent brain boundaries in MRI. With a fully 3D convolutional network model, 3D U-Net, our proposed method demonstrated improved performance compared to current automatic brain extraction methods, as shown in several qualitative metrics (Dice, Jaccard, PPV, SEN, and Hausdorff). We trust that this tool will avoid human bias and streamline pre-processing steps during 3D high resolution rodent brain MRI data analysis. The software developed herein has been disseminated freely to the community.