bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Value of KDM5C Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer
Authors: Chen Xiao-Juan , Ren Ai-Qun , Zheng Liang , Zheng En-Dian
Published: April 2021

Lysine (K)-specific demethylase 5C (KDM5C) plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of KDM5C alterations and the association between KDM5C alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of KDM5C alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. KDM5C alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, P<0.0001) than those without. However, in ICI-treated group, patients with KDM5C alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, P=0.0041). The predictive value of KDM5C alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (P=0.2875). Intriguingly, patients with non-small-cell lung cancer and KDM5C alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, P=0.0762). Mechanistically, KDM5C altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, KDM5C alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs.
A Glycolysis-Related Five-Gene Signature Predicts Biochemical Recurrence-Free Survival in Patients With Prostate Adenocarcinoma
Authors: Xu Zijun , Xu Lijuan , Liu Liping , Li Hai , Jin Jiewen , Peng Miaoguan , Huang Yanrui , Xiao Haipeng , Li Yanbing , Guan Hongyu
Published: April 2021

Prostate cancer (PCa) is one of the most frequently diagnosed cancers in males worldwide. Approximately 25% of all patients experience biochemical recurrence (BCR) after radical prostatectomy (RP) and BCR indicates increased risk for metastasis and castration resistance. PCa patients with highly glycolytic tumors have a worse prognosis. Thus, this study aimed to explore glycolysis-based predictive biomarkers for BCR. Expression data and clinical information of PCa samples were retrieved from three publicly available datasets. One from The Cancer Genome Atlas (TCGA) dataset was used as the training cohort, and two from the Gene Expression Omnibus (GEO) dataset (GSE54460 and GSE70769) were used as validation cohorts. Using the training cohort, univariate Cox regression survival analysis, robust likelihood-based survival model, and stepwise multiply Cox analysis were sequentially applied to explore predictive glycolysis-related candidates. A five-gene risk score was then constructed based on the Cox coefficient as the following: (−0.8367*GYS2) + (0.3448*STMN1) + (0.3595*PPFIA4) + (−0.1940*KDELR3) + (0.4779*ABCB6). Receiver operating characteristic curve (ROC) analysis was used to identify the optimal cut-off point, and patients were divided into low risk and high risk groups. Kaplan–Meier analysis revealed that high risk group had significantly shorter BCR free survival time as compared with that in low risk group in training and validation cohorts. In conclusion, our data support the glycolysis-based five-gene signature as a novel and robust signature for predicting BCR of PCa patients.
Galectin-3 Mediated Inflammatory Response Contributes to Neurological Recovery by QiShenYiQi in Subacute Stroke Model
Authors: Wang Yule , He Shuang , Liu Xinyan , Li Zhixiong , Zhu Lin , Xiao Guangxu , Du Xiaoli , Du Hongxia , Zhang Wen , Zhang Yiqian , Orgah John , Feng Yuxin , Zhang Boli , Zhu Yan
Published: April 2021

Effective therapies for stroke are still limited due to its complex pathological manifestations. QiShenYiQi (QSYQ), a component-based Chinese medicine capable of reducing organ injury caused by ischemia/reperfusion, may offer an alternative option for stroke treatment and post-stroke recovery. Recently, we reported a beneficial effect of QSYQ for acute stroke via modulation of the neuroinflammatory response. However, if QSYQ plays a role in subacute stroke remains unknown. The pharmacological action of QSYQ was investigated in experimental stroke rats which underwent 90 min ischemia and 8 days reperfusion in this study. Neurological and locomotive deficits, cerebral infarction, brain edema, and BBB integrity were assessed. TMT-based quantitative proteomics were performed to identify differentially expressed proteins following QSYQ treatment. Immunohistochemistry, western blot analysis, RT-qPCR, and ELISA were used to validate the proteomics data and to reveal the action mechanisms. Therapeutically, treatment with QSYQ (600 mg/kg) for 7 days significantly improved neurological recovery, attenuated infarct volume and brain edema, and alleviated BBB breakdown in the stroke rats. Bioinformatics analysis indicated that protein galectin-3 and its mediated inflammatory response was closely related to the beneficial effect of QSYQ. Specially, QSYQ (600 mg/kg) markedly downregulated the mRNA and protein expression levels of galectin-3, TNF-α, and IL-6 in CI/RI brain as well as serum levels of TNF-α and IL-6. Overall, our findings showed that the effective action of QSYQ against the subacute phase of CI/RI occurs partly via regulating galectin-3 mediated inflammatory reaction.
Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance
Authors: Xiao Huan , Zheng Yongcheng , Ma Lingling , Tian Lili , Sun Qiu
Published: April 2021

Multiple drug resistance (MDR), referring to the resistance of cancer cells to a broad spectrum of structurally and mechanistically unrelated drugs across membranes, severely impairs the response to chemotherapy and leads to chemotherapy failure. Overexpression of ATP binding cassette (ABC) transporters is a major contributing factor resulting in MDR, which can recognize and mediate the efflux of diverse drugs from cancer cells, thereby decreasing intracellular drug concentration. Therefore, modulators of ABC transporter could be used in combination with standard chemotherapeutic anticancer drugs to augment the therapeutic efficacy. This review summarizes the recent advances of important cancer-related ABC transporters, focusing on their physiological functions, structures, and the development of new compounds as ABC transporter inhibitors.
Effects of Nervilia fordii Extract on Pulmonary Fibrosis Through TGF-β/Smad Signaling Pathway
Authors: Yao Yufeng , Yuan Yue , Lu Zenghui , Ma Yunxia , Xie Yuanyuan , Wang Meiqi , Liu Fangle , Zhu Chenchen , Lin Chaozhan
Published: April 2021

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease with a poor prognosis. The extract of Nervilia fordii (NFE) has shown remarkable benefit in the treatment of acute lung injury, lung cancer, and severe acute respiratory syndrome (SARS). However, the potential mechanism and efficacy of NFE in the treatment of IPF remain unknown. In this study, a systematic network pharmacology analysis was used to predict the mechanism and efficacy of NFE in the treatment of IPF, based on the major components of NFE elucidated by UPLC-TOF-MS/MS. The potential molecular interactions between the compounds and potential targets were predicted using molecular docking. In vivo, rats with pulmonary fibrosis induced by a single intratracheal injection of bleomycin (BLM) were orally administered NFE for 14 days. Lung index and biochemical levels were determined, and histopathological analysis using hematoxylin and eosin (H&E) and Masson staining was performed. The effects of NFE on fibroblast proliferation in Lipopolysaccharide (LPS) and TGF-β1-induced mouse 3T6 fibroblasts were evaluated in vitro. In total, 20 components were identified in NFE, and 102 potential targets for IPF treatment were predicted. These targets potentially participate in processes regulated by transmembrane receptor protein tyrosine kinase, ERBB2, and et al. Molecular docking results predicted high affinity interactions between three components (rhamnazin, rhamnetin, and rhamnocitrin) and the potential targets, suggesting that TGF-β is the most important potential target of NFE in the treatment of pulmonary fibrosis. NFE significantly decreased the lung index and alleviated BLM-induced pulmonary fibrosis in rats. Histopathological observation of lung tissues showed that NFE alleviated inflammation and collagen deposition in BLM-induced rats. NFE inhibited the migration of LPS- and TGF-β1-induced 3T6 fibroblasts, reduced the contents of hydroxyproline and collagen, and contributed to anti-inflammation and anti-oxidation. With the intervention of NFE, the protein and RNA expression of TGF-β1, a-SMA, Smad3/4, p-Smad3/4, CTGF, and p-ERK1/2 were significantly downregulated, while Smad7 and ERK1/2 were upregulated significantly in vivo and in vitro. These findings indicated that NFE may exert therapeutic effects on pulmonary fibrosis by alleviating inflammation, oxidation, and collagen deposition. The mechanism related to the inhibition of the TGF-β/Smad signaling pathway.
Home Textile Pattern Emotion Labeling Using Deep Multi-View Feature Learning
Authors: Yang Juan , Zhang Yuanpeng
Published: April 2021

Different home textile patterns have different emotional expressions. Emotion evaluation of home textile patterns can effectively improve the retrieval performance of home textile patterns based on semantics. It can not only help designers make full use of existing designs and stimulate creative inspiration but also help users select designs and products that are more in line with their needs. In this study, we develop a three-stage framework for home textile pattern emotion labeling based on artificial intelligence. To be specific, first of all, three kinds of aesthetic features, i.e., shape, texture, and salient region, are extracted from the original home textile patterns. Then, a CNN (convolutional neural network)-based deep feature extractor is constructed to extract deep features from the aesthetic features acquired in the previous stage. Finally, a novel multi-view classifier is designed to label home textile patterns that can automatically learn the weight of each view. The three-stage framework is evaluated by our data and the experimental results show its promising performance in home textile patterns labeling.
Transcriptome Analysis Identified Gene Regulation Networks in Soybean Leaves Perturbed by the Coronatine Toxin
Authors: Zhang Xiong , He Bin , Sun Sheng , Zhang Zhipeng , Li Tian , Wang Hehe , Liu Zhicheng , Afzal Ahmed Jawaad , Geng Xueqing
Published: April 2021

The non-host specific Pseudomonas syringae phytotoxin Coronatine (COR) causes chlorosis and promotes toxicity by inducing physiological changes in plants. We performed transcriptome analysis to better understand plants' transcriptional and metabolic response to COR. Toward this end, mock-treated and COR-treated soybean plants were analyzed by RNA-Seq. A total of 4,545 genes were differentially expressed between the two treatments, of which 2,170 were up-regulated whereas 2,375 were down-regulated in COR treated samples. Gene annotation and pathway analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases revealed that the differential genes were involved in photosynthesis, jasmonic acid (JA) synthesis, signal transduction, and phenylpropane metabolism. This study will provide new insights into COR mediated responses and extend our understanding of COR function in plants.
Diversification of Morphological Features of the Dark European Honey Bee of the ‘Augustow M’ Line
Authors: Madras-Majewska Beata , Skonieczna Lucja
Published: April 2021

The aim of this study was to investigate the diversification of morphological features of the Dark European honey bee of the Augustow M line. The authors studied the proboscis length and cubital index, as features determining the affiliation to the species; the width of tergite 4 and the sum of widths of tergites 3 + 4, as indicators of the bee body size; and the length and width of the right forewing. They compared bees sampled from (1) the “lead apiary”, (2) “associate apiaries” and (3) “conservation area apiaries”—apiaries situated in the conservation area established by the national program for the conservation of genetic resources of this bee line. The conclusion was that it is possible to protect bees of the Augustow M line under the existing program, based on resources available to the lead, associate and conservation area apiaries. The bees studied have the essential features of the Dark European honey bee and the values of parameters tested are consistent with the morphological feature references valid for Apis m. mellifera. On the other hand, based on the authors’ research and on other studies described in literature of 1960s, there is a dwarfing trend in the Dark European honey bee of the Augustow M line.
The Genomic Landscape of Lobular Breast Cancer
Authors: McCart Reed Amy E. , Foong Samuel , Kutasovic Jamie R. , Nones Katia , Waddell Nicola , Lakhani Sunil R. , Simpson Peter T.
Published: April 2021

Invasive lobular carcinoma (ILC) is the second most common breast cancer histologic subtype, accounting for approximately 15% of all breast cancers. It is only recently that its unique biology has been assessed in high resolution. Here, we present a meta-analysis of ILC sequencing datasets, to provide a long-awaited ILC-specific resource, and to confirm the prognostic value and strength of association between a number of clinico-pathology features and genomics in this special tumour type. We consider panel (n = 684), whole exome (n = 215) and whole genome sequencing data (n = 48), and review histology of The Cancer Genome Atlas cases to assign grades and determine whether the ILC is of classic type or a variant, such as pleomorphic, prior to performing statistical analyses. We demonstrate evidence of considerable genomic heterogeneity underlying a broadly homogeneous tumour type (typically grade 2, estrogen receptor (ER)-positive); with genomes exhibiting few somatic mutations or structural alterations, genomes with a hypermutator phenotype, and tumours with highly rearranged genomes. We show that while CDH1 (E-cadherin) and PIK3CA mutations do not significantly impact survival, overall survival is significantly poorer for patients with a higher tumour mutation burden; this is also true for grade 3 tumours, and those carrying a somatic TP53 mutation (and these cases were more likely to be ER-negative). Taken together, we have compiled a meta-dataset of ILC with molecular profiling, and our analyses show that the genomic landscape significantly impacts the tumour’s variable natural history and overall survival of ILC patients.
Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance
Authors: Zarychta Elżbieta , Ruszkowska-Ciastek Barbara , Bielawski Kornel , Rhone Piotr
Published: April 2021

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.
The Pan-Immune-Inflammation-Value Predicts the Survival of Patients with Human Epidermal Growth Factor Receptor 2 (HER2)—Positive Advanced Breast Cancer Treated with First-Line Taxane-Trastuzumab-Pertuzumab
Authors: Ligorio Francesca , Fucà Giovanni , Zattarin Emma , Lobefaro Riccardo , Zambelli Luca , Leporati Rita , Rea Carmen , Mariani Gabriella , Bianchi Giulia V. , Capri Giuseppe , de Braud Filippo , Vernieri Claudio
Published: April 2021

Different peripheral blood parameters have emerged as prognostic biomarkers in breast cancer (BC), but their predictive role in Human Epidermal growth factor Receptor 2 positive (HER2+) advanced BC (aBC) patients receiving dual anti-HER2 blockade remains unclear. We evaluated the impact of the Pan-Immune-Inflammatory Value (PIV), defined as the product of peripheral blood neutrophil, platelet, and monocyte counts divided by lymphocyte counts, on the prognosis of HER2+ aBC patients treated with first line trastuzumab-pertuzumab-based biochemotherapy. We also evaluated the association between the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte to lymphocyte ratio (MLR) and clinical outcomes. Cox regression models were used to estimate the impact of these variables, as well as of other clinically relevant covariates, on patient survival. We included 57 HER2+ aBC patients treated with taxane-trastuzumab-pertuzumab in our Institution. High baseline MLR, PLR, and PIV were similarly predictive of worse PFS at univariate analysis, but only high PIV was associated with a trend toward worse PFS at multivariable analysis. Regarding OS, both high PIV and MLR were associated with significantly worse patient survival at univariate analysis, but only the PIV was statistically significantly associated with worse overall survival at multivariable analysis (HR 7.96; 95% CI: 2.18–29.09). Our study reveals the PIV as a new and potent predictor of OS in HER2+ aBC patients treated with first line trastuzumab-pertuzumab-containing biochemotherapy. Prospective studies are needed to validate this new prognostic parameter in HER2+ aBC.
Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease
Authors: Veiga Camilla Bertuzzo , Lawrence Erin M. , Murphy Andrew J. , Herold Marco J. , Dragoljevic Dragana
Published: April 2021

The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease.
The Modulating Effect of Ethanol on the Morphology of a Zr-Based Metal–Organic Framework at Room Temperature in a Cosolvent System
Authors: Li Yunzhuo , Tang Zirong , Chen Chen
Published: April 2021

We report that ethanol, used together with water, plays a crucial role in tuning the structures of a zirconium-based metal–organic framework and the 12-connected MOF-801, as well as the possible mechanisms of this modulating effect. By employing a cosolvent system of ethanol and water at just under room temperature without the presence of a monotopic carboxylic acid as the modulator, MOF-801 in various morphologies of different sizes could be synthesized. A linear correlation between the ethanol/water ratio and the crystal sizes is also demonstrated. The growth mechanism is mainly explained by ethanol’s bonding with the metal ion clusters and the Marangoni flow effect. Ethanol competes with the linker molecules in coordinating with the Zr metal clusters, a role similar to that of the modulators. The Marangoni flow effect, which dominates at a certain solvent ratio, further promotes the 1D alignment of the MOF-801 crystals.
Soil Respiration in Alder Swamp (Alnus glutinosa) in Southern Taiga of European Russia Depending on Microrelief
Authors: Glukhova Tamara V. , Ilyasov Danil V. , Vompersky Stanislav E. , Golovchenko Alla V. , Manucharova Natalia A. , Stepanov Alexey L.
Published: April 2021

Swamp forests have been insufficiently studied yet in comparison with thoroughly examined carbon pools and greenhouse gas fluxes of peat bogs. This is primarily since the GHGs in swamp forests have huge spatial (due to the developed microrelief) and temporal variations (due to strong fluctuations in the groundwater level (GWL)). This significantly complicates their study, producing ambiguous results, especially in short-term field research. From June to October 2013–2016, we measured soil respiration (Rsoil) in an alder swamp using the static chamber method at five microsites: depression (DEP), flat surface (FL), elevations (EL), tussocks (TUS), and near-stem tussocks (STUS). We carried out a computer simulation of the total Rsoil for the season based on Rsoil measurements, monitoring of GWL, and soil temperature. In 2013–2016, the average Rsoil values (mgC m−2 h−1 ± σ) on DEP, FL, EL, TUS and STUS comprised 54 ± 50, 94 ± 72, 146 ± 89, 193 ± 96, and 326 ± 183, respectively, whereas the total Rsoil values for the season (tC ha−1 season−1 ± σ) comprised 2.0 ± 0.5, 3.5 ± 0.5, 5.3 ± 1.6, 5.4 ± 2.7, and 12.6 ± 3.2. According to the results of observations, GWL was at the level of several cm below the soil surface for most of the season. In 2014 and 2015, there were extra dry periods that led to a drop in GWL to a mark of 30–40 cm below the soil surface. Despite their short duration (2–3 weeks), these dry periods can lead to an increase in the total Rsoil for the season from 9 to 45% in the TUS–EL–STUS–FL–DEP sequence.
Comparing Strengths and Weaknesses of Three Approaches in Estimating Social Demands for Local Forest Ecosystem Services in South Korea
Authors: Jo Jang-Hwan , Choi Moongi , Lee Chang-Bae , Lee Kyeong-hak , Kim Oh Seok
Published: April 2021

This study is aimed to compare the strengths and weaknesses of three approaches—analytic hierarchy process analysis, sentiment analysis, and floating population analysis—in estimating the social demands for local forest ecosystem services (ES) in South Korea: Gariwangsan and Yeoninsan. The results were as follows: First, the survey respondents of Gariwangsan and Yeoninsan believed that the cultural ES category was the most fundamental one that should be maintained, whereas they thought the supporting ES category needed the least maintenance. Second, both forests had a high frequency of sentiment words related to the cultural ES category, followed by the regulating ES category, such as air and water quality improvement. Third, the spatiotemporal distribution of the floating populations in both forests was concentrated in their valleys and mountainous areas, indicating the finer-scale demands for the cultural and regulating ES category. Fourth, the research shows the areas that are high in demand and those that are not; this result helps forest management. In conclusion, none of the three methodologies was superior to the other two, as they each captured distinct ES demands. To investigate ES demands in a multifaceted way, we suggest applying the three approaches in tandem.
Niche Selection by Soil Bacterial Community of Disturbed Subalpine Forests in Western Sichuan
Authors: Sheng Zheliang , Zhu Wanze , Yao Huaiying , Shu Shumiao , Li Xia , Ma Shenglan , Li Yaying , Xiong Jinbo
Published: April 2021

Soil bacterial microbial communities are important in the ecosystem function and succession of forests. Using high-throughput 16S rRNA gene sequencing and relative importance for linear regression, we explored how the structures of soil bacterial community were influenced by the environmental factors and restoration succession of secondary forests in the Miyaluo Mountains of western Sichuan, China. Using a space-for-time approach, field measurements and sampling were conducted in four stands at different stages of natural restoration. Results of distance-based multivariate analysis showed that soil pH, organic carbon, available phosphorus, and C/N ratio were the predominant environmental factors that collectively explained a 46.9% variation in the bacterial community structures. The community compositions were jointly controlled by the direct and indirect effects of the rehabilitation stages. The changes in soil environmental factors coincided with restoration succession could lead to the shifts in the relative abundance of different soil bacterial taxa. We screened 13 successional discriminant taxa that could quantitatively indicate the secondary succession subalpine stage. Collectively, our findings show that soil bacteria in different taxa are governed by different local soil variables and rehabilitation ages, which can lead to shifts in the relative abundance of different taxa in successional stages, ultimately changing the entire soil bacterial community with the succession of secondary forest.
Coronary Centerline Extraction from CCTA Using 3D-UNet
Authors: Dorobanțiu Alexandru , Ogrean Valentin , Brad Remus
Published: April 2021

The mesh-type coronary model, obtained from three-dimensional reconstruction using the sequence of images produced by computed tomography (CT), can be used to obtain useful diagnostic information, such as extracting the projection of the lumen (planar development along an artery). In this paper, we have focused on automated coronary centerline extraction from cardiac computed tomography angiography (CCTA) proposing a 3D version of U-Net architecture, trained with a novel loss function and with augmented patches. We have obtained promising results for accuracy (between 90–95%) and overlap (between 90–94%) with various network training configurations on the data from the Rotterdam Coronary Artery Centerline Extraction benchmark. We have also demonstrated the ability of the proposed network to learn despite the huge class imbalance and sparse annotation present in the training data.
Further Delineation of Phenotype and Genotype of Primary Microcephaly Syndrome with Cortical Malformations Associated with Mutations in the WDR62 Gene
Authors: Slezak Ryszard , Smigiel Robert , Obersztyn Ewa , Pollak Agnieszka , Dawidziuk Mateusz , Wiszniewski Wojciech , Bekiesinska-Figatowska Monika , Rydzanicz Malgorzata , Ploski Rafal , Gawlinski Pawel
Published: April 2021

Type 2 congenital microcephaly (MCPH2) is a brain development disorder characterized by primary microcephaly with or without brain malformations. MCPH2 is caused by mutations in the WDR62 gene. We present three new patients with MCPH2 and compound heterozygous mutations in the WDR62 gene. In all the cases, the parents were healthy and unrelated. All children were clinically diagnosed with congenital microcephaly and retardation of motor and speech development. Sequencing results in the presented patients revealed five new variants in the WDR62 gene (c.4273C>T, c.1711_1712insTA, c.1777_1778delGA, c.1642+2T>G, c.194T>A) and one previously described in the German population (c.2864_2867delACAG). In two of the presented cases, variants in the SMAD4, DKC1, and ATRX genes were also found with unknown effects on the course of the disease. Moreover, in the article we collected and compared the most common clinical symptoms, dysmorphic features, and changes in radiographic examinations of the brain observed in 120 patients with recessive primary microcephaly type 2 caused by mutations in the WDR62 gene.
MicroRNA Changes in Gastric Carcinogenesis: Differential Dysregulation during Helicobacter pylori and EBV Infection
Authors: Prinz Christian , Mese Kemal , Weber David
Published: April 2021

Despite medical advances, gastric-cancer (GC) mortality remains high in Europe. Bacterial infection with Helicobacter pylori (H. pylori) and viral infection with the Epstein–Barr virus (EBV) are associated with the development of both distal and proximal gastric cancer. Therefore, the detection of these infections and the prediction of further cancer development could be clinically significant. To this end, microRNAs (miRNAs) could serve as promising new tools. MiRNAs are highly conserved noncoding RNAs that play an important role in gene silencing, mainly acting via translational repression and the degradation of mRNA targets. Recent reports demonstrate the downregulation of numerous miRNAs in GC, especially miR-22, miR-145, miR-206, miR-375, and miR-490, and these changes seem to promote cancer-cell invasion and tumor spreading. The dysregulation of miR-106b, miR-146a, miR-155, and the Let-7b/c complex seems to be of particular importance during H. pylori infection or gastric carcinogenesis. In contrast, many reports describe changes in host miRNA expression and outline the effects of bamHI-A region rightward transcript (BART) miRNA in EBV-infected tissue. The differential regulation of these miRNA, acting alone or in close interaction when both infections coexist, may therefore enable us to detect cancer earlier. In this review, we focus on the two different etiologies of gastric cancer and outline the molecular pathways through which H. pylori- or EBV-induced changes might synergistically act via miR-155 dysregulation to potentiate cancer risk. The three markers, namely, H. pylori presence, EBV infection, and miR-155 expression, may be checked in routine biopsies to evaluate the risk of developing gastric cancer.
Accurate Quantification of AAV Vector Genomes by Quantitative PCR
Authors: Martinez-Fernandez de la Camara Cristina , McClements Michelle , MacLaren Robert
Published: April 2021

The ability to accurately determine the dose of an adeno-associated viral (AAV) therapeutic vector is critical to the gene therapy process. Quantitative PCR (qPCR) is one of the common methods to quantify the AAV vector titre, but different variables can lead to inconsistent results. The aim of this study was to analyze the influence of the conformation of the DNA used as the standard control, and the enzymatic digestion was performed to release the viral genome from the protein capsid on the physical genome titration of a clinically relevant AAV8.RPGR vector, made to good laboratory practice standards in an academic setting. The results of this study showed that the conformation of the DNA used as standard has a significant impact on the accuracy of absolute quantification by qPCR. The use of supercoiled undigested plasmid DNA template generated a higher apparent titer, as compared to the use of linearized plasmid as the standard. In contrast to previous studies, the pre-treatment of the samples with Proteinase K, in addition to the high temperature step used after DNase I digestion, resulted in a reduction on AAV titers. Ideally, all AAV documentation should state which form of reference plasmid and which pre-treatment of the samples have been used to calculate titers, so that appropriate comparisons relating to dose toxicity and transduction efficacy can be made in the clinical scenario.
Impact of COVID-19 Confinement on Adolescent Patients with Anorexia Nervosa: A Qualitative Interview Study Involving Adolescents and Parents
Authors: Zeiler Michael , Wittek Tanja , Kahlenberg Leonie , Gröbner Eva-Maria , Nitsch Martina , Wagner Gudrun , Truttmann Stefanie , Krauss Helene , Waldherr Karin , Karwautz Andreas
Published: April 2021

COVID-19-related restrictions may have a serious impact on patients with eating disorders. We conducted semistructured interviews with female adolescent patients with anorexia nervosa (AN) (n = 13, 13–18 years) currently receiving inpatient or outpatient treatment and their parents (n = 10). We asked for their experiences during COVID-19 confinement regarding everyday life, AN symptoms, and treatment. We used thematic analysis to interpret the data. The main themes identified from the patients’ interviews involved restrictions of personal freedom (i.e., leading to tension between patients and family members, reduced motivation to work on recovery), interruption of the treatment routine (emerging risks through self-monitored weight, challenges/opportunities of teletherapy), changes in AN symptoms (more exposure to triggering situations), COVID-19-related fears, and compulsions but also potential opportunities (less stress, better family relationships). The parents discussed changes in daily routines as negative (challenges in maintaining day structures) and positive (more family time, “slowing down”). They expressed reservations about reduced outpatient monitoring and increased teletherapy and discussed challenges in keeping contact with the child and clinicians during inpatient treatment. Moreover, the parents discussed deteriorations and improvements in the patients’ psychopathology. Clinical implications from these in-depth insights include the importance of strengthening communication between changing staff cohorts, patients, and parents; motivational work; and joint weight monitoring with the therapist.
How to Identify Future Priority Areas for Urban Development: An Approach of Urban Construction Land Suitability in Ecological Sensitive Areas
Authors: Liu Xiaobo , Wang Yukuan , Li Ming
Published: April 2021

The suitability of urban construction land (SUCL) is key to the appropriate utilization of land resources and represents an important foundation for regional exploration and land management. This study explores the SUCL conceptual framework by considering the theory of human-land relationships. The upper reaches of the Yangtze River were studied, a typical ecologically-sensitive area of China. The spatial pattern and control of the SUCL were determined using the improved entropy method. The results show that an area of 91 × 104 km2 was categorized as prohibited or restricted, and these categories account for 28.61% and 50.66% of the total area, respectively. Priority areas and suitable areas are mainly located in the Chengdu Plain, the urban agglomeration of southern Sichuan Province, Chongqing, and the economic corridor in the west, and the surrounding cities of Guiyang and Kunming. SUCL hotspots feature obvious spatial heterogeneity and are concentrated in Sichuan Basin and Guizhou Plateau. The SUCL is obviously constrained by the physical geography of this region. In addition, towns affected by the pole–axis effect have stronger suitability for development and construction. These findings will be very useful for land managers as they provide relevant information about urban development in mountainous areas.
Uncertainty and Nursing Needs of Parents with Pediatric Cancer Patients in Different Treatment Phases: A Cross-Sectional Study
Authors: Park Mijeong , Suh Eunyoung E. , Yu Soo-Young
Published: April 2021

The survival rate of pediatric cancer has increased to 80%, but long-term treatment is required. During treatment, parents experience uncertainty, which affects parents’ quality of life and, even worse, their children’s health; however, the variation of that uncertainty remains under-studied. Thus, it is crucial to understand parents’ nursing needs in each distinct treatment phase to develop relevant educational content. This study investigated the uncertainty level and nursing needs of parents according to their children’s treatment phase. This cross-sectional comparative descriptive study collected survey data from 119 people at a tertiary hospital from December 2017 to April 2018. Nursing needs were ascertained using open-ended questions, and data were analyzed using quantitative content analysis. The uncertainty levels of parents of pediatric cancer patients showed statistically significant differences across treatment phases (F = 8.209, p < 0.001). Parents’ uncertainty was higher in the treatment initiation phase (87.77 ± 13.43) and when treatment was ongoing (83.33 ± 15.10) than in the post-treatment phase (75.35 ± 12.82). All three groups had nursing needs regarding infection control, diet, daily activities of living, and prognosis. Parents’ uncertainty levels and nursing needs differed across treatment phases, suggesting a need for tailored education programs to provide practical support to parents of pediatric cancer patients in each phase.
Biopollution by Invasive Marine Non-Indigenous Species: A Review of Potential Adverse Ecological Effects in a Changing Climate
Authors: Occhipinti-Ambrogi Anna
Published: April 2021

Biopollution by alien species is considered one of the main threats to environmental health. The marine environment, traditionally less studied than inland domains, has been the object of recent work that is reviewed here. Increasing scientific evidence has been accumulated worldwide on ecosystem deterioration induced by the development of massive non-indigenous population outbreaks in many coastal sites. Biopollution assessment procedures have been proposed, adopting criteria already used for xenochemical compounds, adjusting them to deal with alien species invasions. On the other hand, prevention and mitigation measures to reduce biopollution impact cannot always mimic the emission countermeasures that have been successfully applied for chemical pollutants. Nevertheless, in order to design comprehensive water-quality criteria, risk assessment and management strategies, based on scientific knowledge, have been developed in a similar way as for chemical pollution. The Mediterranean Sea is a well-known case of alien species invasion, mainly linked to the opening of the Suez Canal. Non-indigenous species have caused well-documented changes in many coastal ecosystems, favoured by concomitant changes induced by global warming and by the heavy load of nutrients and pollutants by various anthropogenic activities. Naval commercial traffic and leisure boats are among the most active vectors of spread for alien species inside the Mediterranean, and also towards other ocean regions. The scientific evidence gathered and summarized in this review suggests that effective management actions, under a precautionary approach, should be put in place in order to control introductions of species in new areas. These management measures are already established in international treaties and national legislations, but should be enforced to prevent the disruption of the dynamic ecological equilibria in the receiving environment and to control the direct adverse effects of alien species.
The Psychometric Properties of the Meaning of Home and Housing-Related Control Beliefs Scales among 67–70 Year-Olds in Sweden
Authors: Boonyaratana Yadanuch , Hansson Eva Ekvall , Granbom Marianne , Schmidt Steven M.
Published: April 2021

Background: The housing environment is important for health and well-being among older people, and it is important to consider both physical and perceived aspects of housing. Psychometrically sound scales are necessary to assess perceived housing. This study evaluated the psychometric properties of two instruments that measure perceived aspects of housing among a younger cohort of older adults in Sweden. Methods: A random sample of 371 participants aged 67 to 70 years (mean 67.9 (SD = 0.98)) was used. Participants lived in ordinary housing in the south of Sweden. Data on perceived aspects of housing were collected with the Meaning of Home Questionnaire (MOH) and the Housing-Related Control Beliefs Questionnaire (HCQ). Internal consistency, corrected item–total correlations, floor and ceiling effects, and construct validity were analyzed. Results: Cronbach’s alphas for all four subscales of MOH and two of three subscales of HCQ had acceptable levels (α > 0.50). Some items from both scales had low item–total correlations. All subscales, except for one from HCQ, had good construct validity. Conclusion: While both instruments had some limitations, all subscales with one exception had adequate psychometric properties. When used in different national contexts, further development may be necessary to achieve conceptual equivalence.
Can Male Patient’s Age Affect the Cortical Bone Thickness of Jawbone for Dental Implant Placement? A Cohort Study
Authors: Wang Shiuan-Hui , Ko Yi-Chun , Tsai Ming-Tzu , Fuh Lih-Jyh , Huang Heng-Li , Shen Yen-Wen , Hsu Jui-Ting
Published: April 2021

Dental implants are among the most common treatments for missing teeth. The thickness of the crestal cortical bone at the potential dental implant site is a critical factor affecting the success rate of dental implant surgery. However, previous studies have predominantly focused on female patients, who are at a high risk of osteoporosis, for the discussion of bone quality and quantity at the dental implant site. This study aimed to investigate the effect of male patients’ age on the crestal cortical bone of the jaw at the dental implant site by using dental cone-beam computed tomography (CBCT). This study performed dental CBCT on 84 male patients of various ages to obtain tomograms of 288 dental implant sites at the jawbone (41 sites in the anterior maxilla, 95 in the posterior maxilla, 59 in the anterior mandible, and 93 in the posterior mandible) for measuring the cortical bone thickness. A one-way analysis of variance and Scheffe’s test were performed on the measurement results to compare the cortical bone thickness at implant sites in the four jaw areas. The correlation between male patient age and cortical bone thickness at the dental implant site was determined. The four jaw areas in order of the cortical bone thickness were as follows: posterior mandible (1.07 ± 0.44 mm), anterior mandible (0.99 ± 0.30 mm), anterior maxilla (0.82 ± 0.32 mm), and posterior maxilla (0.71 ± 0.27 mm). Apart from dental implant sites in the anterior and posterior mandibles, no significant correlation was observed between male patients’ age and the cortical bone thickness at the dental implant site.
The Impact of the COVID-19 Pandemic on the Cognition of People with Dementia
Authors: Tondo Giacomo , Sarasso Barbara , Serra Paola , Tesser Fabiana , Comi Cristoforo
Published: April 2021

(1) Background: To limit the COVID-19 outbreak, the Italian government implemented social restrictions that may have had psychological and cognitive repercussions on people with dementia. We aimed to analyze cognitive decline during the pandemic year in people evaluated in a memory clinic in northern Italy, the epicenter of COVID-19 spread. (2) Methods: A single-center retrospective study was carried out, including individuals with annual follow-up evaluated in three different years (2020-GROUP, 2019-GROUP, 2018-GROUP). We performed an intergroup comparison of cognitive decline over a one-year follow-up, and an intragroup comparison in the 2020-GROUP to analyze the five-year cognitive decline trajectory, as measured by the MMSE. (3) Results: The 2020-GROUP showed a significant loss of MMSE points per year in the considered follow-up period compared with the 2019-GROUP and 2018-GROUP (p = 0.021). Demographics, clinical features, and the other analyzed variables, including rate of diagnosis, therapy, and comorbidities, did not significantly differ between groups. The five-year cognitive decline trajectory confirmed a significant worsening of cognitive decline between 2019 and 2020 (p < 0.001), while the decrease in MMSE scores was not statistically significant between previous time points. (4) Conclusions: COVID-19 pandemic measures have induced a significant worsening of cognitive decline in people with dementia, needing more careful assistance to minimize the adverse effects of social isolation in case of future lockdowns.
Racial Difference in the Association of Long-Term Exposure to Fine Particulate Matter (PM2.5) and Cardiovascular Disease Mortality among Renal Transplant Recipients
Authors: Dehom Salem , Knutsen Synnove , Bahjri Khaled , Shavlik David , Oda Keiji , Ali Hatem , Pompe Lance , Spencer-Hwang Rhonda
Published: April 2021

Ambient air pollutants are known risk factors for cardiovascular disease (CVD) morbidity and mortality with significant racial disparities. However, few studies have explored racial differences among highly susceptible subpopulations, such as renal transplant recipients (RTRs). Despite improvements in quality of life after transplantation, CVD remains the major cause of mortality, especially among Black recipients. This study aimed to evaluate potential racial differences in the association between long-term levels of PM2.5 and the risk of all-cause, total CVD, and coronary heart disease (CHD) mortality among RTRs. This retrospective study consists of 93,857 non-smoking adults who received a renal transplant between 2001 and 2015. Time-dependent Cox regression was used to assess the association between annual concentrations of PM2.5 and mortality risk. In the multivariable-adjusted models, a 10 μg/m3 increase in ambient PM2.5 levels found increased risk of all-cause (HR = 3.45, 95% CI: 3.08–3.78), CVD (HR = 2.38, 95% CI: 1.94–2.92), and CHD mortality (HR = 3.10, 95% CI: 1.96–4.90). Black recipients had higher risks of all-cause (HR = 4.09, 95% CI: 3.43–4.88) and CHD mortality (HR = 6.73, 95% CI: 2.96–15.32). High levels of ambient PM2.5 were associated with all-cause, CVD, and CHD mortality. The association tended to be higher among Black recipients than non-Blacks.