bluuebunny/crossref_metadata_2025 huggingface dataset:
IVIM Parameters on MRI Could Predict ISUP Risk Groups of Prostate Cancers on Radical Prostatectomy
Authors: Chang Chun-Bi , Lin Yu-Chun , Wong Yon-Cheong , Lin Shin-Nan , Lin Chien-Yuan , Lin Yu-Han , Sheng Ting-Wen , Huang Chen-Chih , Yang Lan-Yan , Wang Li-Jen
Published: July 2021

Purpose

To elucidate the usefulness of intravoxel incoherent motion (IVIM)/apparent diffusion coefficient (ADC) parameters in preoperative risk stratification using International Society of Urological Pathology (ISUP) grades.

Materials and Methods

Forty-five prostate cancer (PCa) patients undergoing radical prostatectomy (RP) after prostate multiparametric magnetic resonance imaging (mpMRI) were included. The ISUP grades were categorized into low-risk (I-II) and high-risk (III-V) groups, and the concordance between the preoperative and postoperative grades was analyzed. The largest region of interest (ROI) of the dominant tumor on each IVIM/ADC image was delineated to obtain its histogram values (i.e., minimum, mean, and kurtosis) of diffusivity (D), pseudodiffusivity (D*), perfusion fraction (PF), and ADC. Multivariable logistic regression analysis of the IVIM/ADC parameters without and with preoperative ISUP grades were performed to identify predictors for the postoperative high-risk group.

Results

Thirty-two (71.1%) of 45 patients had concordant preoperative and postoperative ISUP grades. Dmean, D*kurtosis, PFkurtosis, ADCmin, and ADCmean were significantly associated with the postoperative ISUP risk group (all p < 0.05). Dmean and D*kurtosis (model I, both p < 0.05) could predict the postoperative ISUP high-risk group with an area under the curve (AUC) of 0.842 and a 95% confidence interval (CI) of 0.726–0.958. The addition of D*kurtosis to the preoperative ISUP grade (model II) may enhance prediction performance, with an AUC of 0.907 (95% CI 0.822–0.992).

Conclusions

The postoperative ISUP risk group could be predicted by Dmean and D*kurtosis from mpMRI, especially D*kurtosis. Obtaining the biexponential IVIM parameters is important for better risk stratification for PCa.
Deep Neural Network Analysis of Pathology Images With Integrated Molecular Data for Enhanced Glioma Classification and Grading
Authors: Pei Linmin , Jones Karra A. , Shboul Zeina A. , Chen James Y. , Iftekharuddin Khan M.
Published: July 2021

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel glioma analytical method that, for the first time in the literature, integrates a cellularity feature derived from the digital analysis of brain histopathology images integrated with molecular features following the latest WHO criteria. We first propose a novel over-segmentation strategy for region-of-interest (ROI) selection in large histopathology whole slide images (WSIs). A Deep Neural Network (DNN)-based classification method then fuses molecular features with cellularity features to improve tumor classification performance. We evaluate the proposed method with 549 patient cases from The Cancer Genome Atlas (TCGA) dataset for evaluation. The cross validated classification accuracies are 93.81% for lower-grade glioma (LGG) and high-grade glioma (HGG) using a regular DNN, and 73.95% for LGG II and LGG III using a residual neural network (ResNet) DNN, respectively. Our experiments suggest that the type of deep learning has a significant impact on tumor subtype discrimination between LGG II vs. LGG III. These results outperform state-of-the-art methods in classifying LGG II vs. LGG III and offer competitive performance in distinguishing LGG vs. HGG in the literature. In addition, we also investigate molecular subtype classification using pathology images and cellularity information. Finally, for the first time in literature this work shows promise for cellularity quantification to predict brain tumor grading for LGGs with IDH mutations.
Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias
Authors: Bhingarkar Aboli , Vangapandu Hima V. , Rathod Sanjay , Hoshitsuki Keito , Fernandez Christian A.
Published: July 2021

Amino acid (AA) metabolism plays an important role in many cellular processes including energy production, immune function, and purine and pyrimidine synthesis. Cancer cells therefore require increased AA uptake and undergo metabolic reprogramming to satisfy the energy demand associated with their rapid proliferation. Like many other cancers, myeloid leukemias are vulnerable to specific therapeutic strategies targeting metabolic dependencies. Herein, our review provides a comprehensive overview and TCGA data analysis of biosynthetic enzymes required for non-essential AA synthesis and their dysregulation in myeloid leukemias. Furthermore, we discuss the role of the general control nonderepressible 2 (GCN2) and-mammalian target of rapamycin (mTOR) pathways of AA sensing on metabolic vulnerability and drug resistance.
Prognostic and Therapeutic Value of Apolipoprotein A and a New Risk Scoring System Based on Apolipoprotein A and Adenosine Deaminase in Chronic Lymphocytic Leukemia
Authors: Yun Xiaoya , Sun Xiang , Hu Xinting , Zhang Huimin , Yin Zixun , Zhang Xin , Liu Ming , Zhang Ya , Wang Xin
Published: July 2021

Lipid metabolism is related to lymphomagenesis, and is a novel therapeutic target in some hematologic tumors. Apolipoprotein A (ApoA), the major protein of high-density lipoprotein (HDL), plays a crucial role in lipid transportation and protecting against cardiovascular disease, and takes effect on anti-inflammation and anti-oxidation. It is correlated with the prognosis of some solid tumors. Yet, there is no investigation involving the role of ApoA plays in chronic lymphocytic leukemia (CLL). Our retrospective study focuses on the prognostic value of ApoA in CLL and its therapeutic potential for CLL patients. Herein, ApoA is a favorable independent prognostic factor for both overall survival (OS) and progression-free survival (PFS) of CLL patients. ApoA is negatively associated with β2-microglobulin (β2-MG) and advanced stage, which are poor prognostic factors in CLL. Age, Rai stage, ApoA, and adenosine deaminase (ADA) are included in a new risk scoring system named ARAA-score. It is capable of assessing OS and PFS of CLL patients. Furthermore, cell proliferation assays show that the ApoA-I mimetic L-4F can inhibit the proliferation of CLL cell lines and primary cells. In conclusion, ApoA is of prognostic value in CLL, and is a potential therapy for CLL patients. The ARAA-score may optimize the risk stratification of CLL patients.
Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis
Authors: Lv Liwei , Sun Xuefei , Wu Yuchen , Cui Qu , Chen Yuedan , Liu Yuanbo
Published: July 2021

Background

Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Studies investigating primary CNSL determined that the Bruton tyrosine kinase (BTK) played an important role in pathogenesis. Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL. The purpose of this meta-analysis was to clarify the effectiveness and safety of ibrutinib in the treatment of CNSL.

Methods

A systematic search of PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure databases was conducted through to 31 October 2019. Studies involving patients with CNSL who received ibrutinib that reported the overall response (OR), complete remission (CR), and partial response (PR) were included. The random-effects or fixed-effects model with double arcsine transformation was used for the pooled rates and 95% confidence intervals (CI) were determined for all outcomes.

Results

Eight studies including 162 patients were identified and included in the meta-analysis. The pooled OR rate after treatment with ibrutinib was 69% (95% CI, 61–79%, I2 = 47.57%, p = 0.06), while the pooled CR and PR was 52% (95% CI, 35–68%, I2 = 74.95%, p = 0.00) and 17% (95% CI, 7–30%, I2 = 67.85%, p = 0.00), respectively. Among PCNSL patients, including new diagnoses PCNSL and R/R PCNSL, the pooled OR rate was 72% (95% CI, 63–80%, I2 = 49.20%, p = 0.06) while the pooled CR and PR rates were 53% (95% CI, 33–73%, I2 = 75.04%, p = 0.00) and 22% (95% CI, 14–30%, I2 = 46.30%, p = 0.07), respectively. Common adverse events above grade 3 included cytopenia and infections.

Conclusions

The ibrutinib-containing therapy was well tolerated and offered incremental benefit to patients with CNSL. However, randomized-controlled studies that directly compare efficacy and adverse events of ibrutinib are still needed.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42020218974.
Case Report: Pansynostosis, Chiari I Malformation and Syringomyelia in a Child With Frontometaphyseal Dysplasia 1
Authors: Kim Jaewon , Lee Dong-Woo , Jang Dae-Hyun
Published: July 2021

Frontometaphyseal dysplasia 1 (FMD1) is a rare otopalatodigital spectrum disorder (OPDSD) that is inherited as an X-linked trait and it is caused by gain-of-function mutations in theFLNA. It is characterized by generalized skeletal dysplasia, and craniofacial abnormalities including facial dysmorphism (supraorbital hyperostosis, hypertelorism, and down-slanting palpebral fissures). The involvement of the central nervous system in patients with OPDSD is rare. Herein, we present the case of a 12-year-old boy with facial dysmorphism, multiple joint contractures, sensorineural hearing loss, scoliosis, craniosynostosis, and irregular sclerosis with hyperostosis of the skull. Brain and whole-spine magnetic resonance imaging revealed Chiari I malformation with extensive hydrosyringomyelia from the C1 to T12 levels. Targeted next-generation sequencing identified a hemizygous pathologic variant (c.3557C>T/p.Ser1186Leu) in theFLNA, confirming the diagnosis of FMD1. This is the first report of a rare case of OPDSD with pansynostosis and Chiari I malformation accompanied by extensive syringomyelia.
Management and Clinical Outcome of Posterior Reversible Encephalopathy Syndrome in Pediatric Oncologic/Hematologic Diseases: A PRES Subgroup Analysis With a Large Sample Size
Authors: Hun Marady , Xie Min , She Zhou , Abdirahman Amin S. , Li Cuifang , Wu Feifeng , Luo Senlin , Han Phanna , Phorn Rithea , Wu Pan , Luo Haiyan , Chen Keke , Tian Jidong , Wan Wuqing , Wen Chuan
Published: July 2021

This study investigated the management and clinical outcomes along with associated factors of posterior reversible encephalopathy syndrome (PRES) in childhood hematologic/oncologic diseases. We present data from children with hematologic/oncologic diseases who developed PRES after treatment of the primary disease with chemotherapy and hematopoietic stem cell transplantation (HSCT) at 3 medical centers in Changsha, China from 2015 to 2020, and review all previously reported cases with the aim of determining whether this neurologic manifestation affects the disease prognosis. In the clinical cohort of 58 PRES patients, hypertension [pooled odds ratio (OR) = 4.941, 95% confidence interval (CI): 1.390, 17.570; P = 0.001] and blood transfusion (OR = 14.259, 95% CI: 3.273, 62.131; P = 0.001) were significantly associated with PRES. Elevated platelet (OR = 0.988, 95% CI: 0.982, 0.995; P < 0.001), hemoglobin (OR = 0.924, 95% CI: 0.890, 0.995; P < 0.001), and blood sodium (OR = 0.905, 95% CI: 0.860, 0.953; P < 0.001), potassium (OR = 0.599, 95% CI: 0.360, 0.995; P = 0.048), and magnesium (OR = 0.093, 95% CI: 0.016, 0.539; P = 0.008) were protective factors against PRES. Data for 440 pediatric PRES patients with hematologic/oncologic diseases in 21 articles retrieved from PubMed, Web of Science, and Embase databases and the 20 PRES patients from our study were analyzed. The median age at presentation was 7.9 years. The most common primary diagnosis was leukemia (62.3%), followed by solid tumor (7.7%) and lymphoma (7.5%). Most patients (65.0%) received chemotherapy, including non-induction (55.2%) and induction (44.8%) regimens; and 86.5% used corticosteroids before the onset of PRES. Although 21.0% of patients died during follow-up, in most cases (93.2%) this was not attributable to PRES but to severe infection (27.3%), underlying disease (26.1%), graft-vs.-host disease (14.8%), multiple organ dysfunction syndrome (8.0%), and respiratory failure (3.4%). PRES was more common with HSCT compared to chemotherapy and had a nearly 2 times higher mortality rate in patients with oncologic/hematologic diseases than in those with other types of disease. Monitoring neurologic signs and symptoms in the former group is therefore critical for ensuring good clinical outcomes following treatment of the primary malignancy.
Authentication of Three Source Spices of Arnebiae Radix Using DNA Barcoding and HPLC
Authors: Xu Haiyan , Li Ping , Ren Guangxi , Wang Yanjiao , Jiang Dan , Liu Chunsheng
Published: July 2021

Arnebia decumbens (Vent.) Coss. et Kralik, A. euchroma (Royle) Johnst and A. guttata Bunge, three commonly used traditional Chinese medicinal plants have been widely used for the clinical treatment of inflammatory diseases caused by fungal, bacterial, oxidation, and other related pathogens. However, precise identification at the similar species level is usually challenging due to the influence of the source of medicinal materials, traditional ethnic medicine and medicinal habits. Here we developed a comprehensive and efficient identification system for three source spices of Arnebiae Radix based on DNA barcoding and HPLC fingerprinting. A total of 599 samples from thirty-five wild populations were collected and identified by using DNA barcodes of ITS2 regions, and the chemotypes of seven naphthoquinoneswere revealed by HPLC quantitative analysis including principal component analysis and hierarchical clustering analysis. Our results showed that the ITS2 sequences can distinguish three source spices of Arnebiae Radix from adulterants. However, it was difficult to identify them by HPLC-specific chromatograms combined with chemometric analysis. These results indicated that DNA barcoding was a more powerful method than HPLC fingerprinting for the identification of related species that were genetically similar. DNA barcoding analysis could be a promising and reliable tool to accurately confirm the identities of medicinal materials, especially for those whose sources are multiple and difficult to be identified by conventional chromatography.
Evaluation of a Pharmacist-Led Remote Warfarin Management Model Using a Smartphone Application (Yixing) in Improving Patients’ Knowledge and Outcomes of Anticoagulation Therapy
Authors: Jiang Shudan , He Qiuyi , Yan Jiajia , Zhao Liyan , Zheng Yifan , Chen Pan , Chen Xiao
Published: July 2021

Background: The management of warfarin-treated patients has been recognized as a challenge due to narrow therapeutic range and food and drug interactions in warfarin therapy. We aim to evaluate the effect of a pharmacist-led remote warfarin management model using a smartphone application (app) on anticoagulation therapy.

Methods: Eligible patients who had received warfarin therapy after mechanical heart valve replacement were enrolled. The intervention group was offered a pharmacist-led remote warfarin management model using the app named Yixing. Yixing incorporates functions including automatic daily reminder, personal health record, educational program, and online counseling. The control group received traditional pharmacy services without Yixing. Co-primary outcomes were patients’ awareness score of warfarin therapy obtained from questionnaire, the medication adherence measured by the percentage of the correct-warfarin-taken days in the monitored period, the fraction of time in therapeutic range (FTTR), and the incidence of anticoagulation-related complications. The needed information of the patients was acquired via electronic medical records from the hospital, Yixing system and telephone follow-up when necessary.

Results: 64 and 66 patients were initially in the intervention and control groups respectively. After propensity score matching, 50 patients were assigned in each group. The intervention group had a median age of 51.0 years, in which 27 (54%) were male. The control group had a median age of 50.5 years, in which 28 (56%) were male. Patient awareness score in the intervention group was 8.00 (2.00), which was higher than that in the control group, with score at 6.50 (2.50) (p = 0.001). No significant difference was found in the percentage of the correct-warfarin-taken days between the two groups (p = 0.520). The median (interquartile range) value of FTTR was 80.3% (21.9%) and 72.1% (17.7%) in the intervention and control groups respectively (p = 0.033), and no significant differences in the incidence of anticoagulation-related complications were observed (p = 0.514).

Conclusion: The pharmacist-led remote warfarin management model using Yixing improves patients’ awareness of warfarin therapy and increases FTTR, but may not have significant improvements on medication adherence and safety.
Deep Shape Features for Predicting Future Intracranial Aneurysm Growth
Authors: Bizjak Žiga , Pernuš Franjo , Špiclin Žiga
Published: July 2021

Introduction: Intracranial aneurysms (IAs) are a common vascular pathology and are associated with a risk of rupture, which is often fatal. Aneurysm growth is considered a surrogate of rupture risk; therefore, the study aimed to develop and evaluate prediction models of future artificial intelligence (AI) growth based on baseline aneurysm morphology as a computer-aided treatment decision support.

Materials and methods: Follow-up CT angiography (CTA) and magnetic resonance angiography (MRA) angiograms of 39 patients with 44 IAs were classified by an expert as growing and stable (25/19). From the angiograms vascular surface meshes were extracted and the aneurysm shape was characterized by established morphologic features and novel deep shape features. The features corresponding to the baseline aneurysms were used to predict future aneurysm growth using univariate thresholding, multivariate random forest and multi-layer perceptron (MLP) learning, and deep shape learning based on the PointNet++ model.

Results: The proposed deep shape feature learning method achieved an accuracy of 0.82 (sensitivity = 0.96, specificity = 0.63), while the multivariate learning and univariate thresholding methods were inferior with an accuracy of up to 0.68 and 0.63, respectively.

Conclusion: High-performing classification of future growing IAs renders the proposed deep shape features learning approach as the key enabling tool to manage rupture risk in the “no treatment” paradigm of patient follow-up imaging.
Predictive Modeling of Secondary Pulmonary Hypertension in Left Ventricular Diastolic Dysfunction
Authors: Harrod Karlyn K. , Rogers Jeffrey L. , Feinstein Jeffrey A. , Marsden Alison L. , Schiavazzi Daniele E.
Published: July 2021

Diastolic dysfunction is a common pathology occurring in about one third of patients affected by heart failure. This condition may not be associated with a marked decrease in cardiac output or systemic pressure and therefore is more difficult to diagnose than its systolic counterpart. Compromised relaxation or increased stiffness of the left ventricle induces an increase in the upstream pulmonary pressures, and is classified as secondary or group II pulmonary hypertension (2018 Nice classification). This may result in an increase in the right ventricular afterload leading to right ventricular failure. Elevated pulmonary pressures are therefore an important clinical indicator of diastolic heart failure (sometimes referred to as heart failure with preserved ejection fraction, HFpEF), showing significant correlation with associated mortality. However, accurate measurements of this quantity are typically obtained through invasive catheterization and after the onset of symptoms. In this study, we use the hemodynamic consistency of a differential-algebraic circulation model to predict pulmonary pressures in adult patients from other, possibly non-invasive, clinical data. We investigate several aspects of the problem, including the ability of model outputs to represent a sufficiently wide pathologic spectrum, the identifiability of the model's parameters, and the accuracy of the predicted pulmonary pressures. We also find that a classifier using the assimilated model parameters as features is free from the problem of missing data and is able to detect pulmonary hypertension with sufficiently high accuracy. For a cohort of 82 patients suffering from various degrees of heart failure severity, we show that systolic, diastolic, and wedge pulmonary pressures can be estimated on average within 8, 6, and 6 mmHg, respectively. We also show that, in general, increased data availability leads to improved predictions.
Epigenetic Regulation of Hepatic Stellate Cell Activation and Macrophage in Chronic Liver Inflammation
Authors: Shi Chun-xia , Wang Yao , Jiao Fang-zhou , Chen Qian , Cao Pan , Pei Mao-hua , Zhang Lu-yi , Guo Jin , Deng Wei , Wang Lu-wen , Gong Zuo-jiong
Published: July 2021

Chronic liver inflammation is a complex pathological process under different stress conditions, and the roles of stellate cells and macrophages in chronic liver inflammation have been widely reported. Moderate liver inflammation can protect the liver from damage and facilitate the recovery of liver injury. However, an inflammatory response that is too intense can result in massive death of hepatocytes, which leads to irreversible damage to the liver parenchyma. Epigenetic regulation plays a key part in liver inflammation. This study reviews the regulation of epigenetics on stellate cells and macrophages to explore the new mechanisms of epigenetics on liver inflammation and provide new ideas for the treatment of liver disease.
Inflammatory Cytokines, Immune Cells, and Organ Interactions in Heart Failure
Authors: Li Huihui , Chen Chen , Wang Dao Wen
Published: July 2021

Despite mounting evidence demonstrating the significance of inflammation in the pathophysiological mechanisms of heart failure (HF), most large clinical trials that target the inflammatory responses in HF yielded neutral or even worsening outcomes. Further in-depth understanding about the roles of inflammation in the pathogenesis of HF is eagerly needed. This review summarizes cytokines, cardiac infiltrating immune cells, and extracardiac organs that orchestrate the complex inflammatory responses in HF and highlights emerging therapeutic targets.
Activation of Orexin System Stimulates CaMKII Expression
Authors: Fan Yuanyuan , Jiang Enshe , Gao Huanjia , Bigalke Jeremy , Chen Bojun , Yu Chunxiu , Chen Qinghui , Shan Zhiying
Published: July 2021

Hyperactivity of the orexin system within the paraventricular nucleus (PVN) has been shown to contribute to increased sympathetic nerve activity (SNA) and blood pressure (BP) in rodent animals. However, the underlying molecular mechanisms remain unclear. Here, we test the hypothesis that orexin system activation stimulates calcium/calmodulin-dependent kinase II (CaMKII) expression and activation, and stimulation of CaMKII expressing PVN neurons increases SNA and BP. Real-time PCR and/or western blot were carried out to test the effect of orexin-A administration on CaMKII expression in the PVN of normal Sprague Dawley (SD) rats and orexin receptor 1 (OX1R) expressing PC12 cells. Immunostaining was performed to assess OX1R cellular localization in the PVN of SD rats as well as orexin-A treatment on CaMKII activation in cultured hypothalamic neurons. In vivo sympathetic nerve recordings were employed to test the impact of optogenetic stimulation of CaMKII-expressing PVN neurons on the renal SNA (RSNA) and BP. The results showed that intracerebroventricular injection of orexin-A into the SD rat increases mRNA expression of CaMKII subunits in the PVN. In addition, Orexin-A treatment increases CaMKII expression and its phosphorylation in OX1R-expressing PC12 cells. Furthermore, Orexin-A treatment increases CaMKII activation in cultured hypothalamic neurons from neonatal SD rats. Finally, optogenetic excitation of PVN CaMKII-expressing neurons results in robust increases in RSNA and BP in SD rats. Our results suggest that increased orexin system activity activates CaMKII expression in cardiovascular relevant regions, and this may be relevant to the downstream cardiovascular effects of CaMKII.
L-Leucine Improves Metabolic Disorders in Mice With in-utero Cigarette Smoke Exposure
Authors: Zeng Yunxin , Huang Taida , Wang Nan , Xu Yi , Sun Chunhui , Huang Min , Chen Chun , Oliver Brian G. , Yi Chenju , Chen Hui
Published: July 2021

Objectives: Maternal cigarette smoke exposure (SE) causes intrauterine undernutrition, resulting in increased risk for metabolic disorders and type 2 diabetes in the offspring without sex differences. L-leucine supplementation has been shown to reduce body weight and improve glucose metabolism in both obese animals and humans. In this study, we aimed to determine whether postnatal L-leucine supplementation in female offspring can ameliorate the detrimental impact of maternal SE.

Methods: Female Balb/c mice (6-week) were exposed to cigarette smoke (SE, 2 cigarettes/day) prior to mating for 5 weeks until the pups weaned. Sham dams were exposed to air during the same period. Half of the female offspring from the SE and SHAM dams were supplied with L-leucine via drinking water (1.5% w/w) after weaning (21-day) for 10 weeks and sacrificed at 13 weeks (adulthood).

Results: Maternal SE during pregnancy resulted in smaller body weight and glucose intolerance in the offspring. L-leucine supplement in Sham offspring reduced body weight, fat mass, and fasting blood glucose levels compared with their untreated littermates; however somatic growth was not changed. L-leucine supplement in SE offspring improved glucose tolerance and reduced fat mass compared with untreated littermates.

Conclusions: Postnatal L-leucine supplement could reduce fat accumulation and ameliorate glucose metabolic disorder caused by maternal SE. The application of leucine may provide a potential strategy for reducing metabolic disorders in offspring from mothers who continued to smoke during pregnancy.
The Conservation of Chloroplast Genome Structure and Improved Resolution of Infrafamilial Relationships of Crassulaceae
Authors: Chang Hong , Zhang Lei , Xie Huanhuan , Liu Jianquan , Xi Zhenxiang , Xu Xiaoting
Published: July 2021

Crassulaceae are the largest family in the angiosperm order Saxifragales. Species of this family are characterized by succulent leaves and a unique photosynthetic pathway known as Crassulacean acid metabolism (CAM). Although the inter- and intrageneric relationships have been extensively studied over the last few decades, the infrafamilial relationships of Crassulaceae remain partially obscured. Here, we report nine newly sequenced chloroplast genomes, which comprise several key lineages of Crassulaceae. Our comparative analyses and positive selection analyses of Crassulaceae species indicate that the overall gene organization and function of the chloroplast genome are highly conserved across the family. No positively selected gene was statistically supported in Crassulaceae lineage using likelihood ratio test (LRT) based on branch-site models. Among the three subfamilies of Crassulaceae, our phylogenetic analyses of chloroplast protein-coding genes support Crassuloideae as sister to Kalanchoideae plus Sempervivoideae. Furthermore, within Sempervivoideae, our analyses unambiguously resolved five clades that are successively sister lineages, i.e., Telephium clade, Sempervivum clade, Aeonium clade, Leucosedum clade, and Acre clade. Overall, this study enhances our understanding of the infrafamilial relationships and the conservation of chloroplast genomes within Crassulaceae.
Wild Olive Genotypes as a Valuable Source of Resistance to Defoliating Verticillium dahliae
Authors: Díaz-Rueda Pablo , Aguado Ana , Romero-Cuadrado Laura , Capote Nieves , Colmenero-Flores José M.
Published: July 2021

Resistance to the defoliating pathotype of Verticillium dahliae has been evaluated in a pool of 68 wild genotypes of olive belonging to the SILVOLIVE collection. Resistance was evaluated by assessing symptom severity using a 0–4 rating scale, estimating the relative area under the disease progress curve (RAUDPC), determining the percentage of dead plants (PDP), and measuring the evolution of morphological parameters in inoculated plants over time. In addition, the density levels of V. dahliae in the stem of root-inoculated genotypes have been quantified by means of quantitative real-time PCR at 35 and 120 days after inoculation (dai). Fifteen genotypes (22%) were cataloged as resistant to V. dahliae (i.e., disease parameters did not significantly differ from those of the resistant cultivar Frantoio, or were even lower). Resistant genotypes are characterized by presenting fewer symptoms and a lower amount of V. dahliae DNA at 120 dai than at 35 dai, indicating their ability to control the disease and reduce the density of the pathogen. The rest of the evaluated genotypes showed variable levels of susceptibility. Overall analysis of all genotypes showed high correlation between symptomatology and the amount of V. dahliae DNA in the stem of inoculated genotypes at 120 dai, rather than at 35 dai. However, correlation at 120 dai was not observed in the set of resistant genotypes, suggesting that resistance to defoliating V. dahliae in olive is based on the occurrence of different mechanisms such as avoidance or tolerance. These mechanisms are valuable for designing breeding programs and for the identification of target genes and resistant rootstocks to better control Verticillium wilt in the olive grove.
New Insights on the Regulation of Glucosinolate Biosynthesis via COP1 and DELLA Proteins in Arabidopsis Thaliana
Authors: Frerigmann Henning , Hoecker Ute , Gigolashvili Tamara
Published: July 2021

The biosynthesis of defensive secondary metabolites, such as glucosinolates (GSLs), is a costly process, which requires nutrients, ATP, and reduction equivalents, and, therefore, needs well-orchestrated machinery while coordinating defense and growth. We discovered that the key repressor of light signaling, the CONSTITUTIVE PHOTOMORPHOGENIC 1/SUPPRESSOR OF PHYTOCHROME A-105 (COP1/SPA) complex, is a crucial component of GSL biosynthesis regulation. Various mutants in this COP1/SPA complex exhibited a strongly reduced level of GSL and a low expression of jasmonate (JA)-dependent genes. Furthermore, cop1, which is known to accumulate DELLA proteins in the dark, shows reduced gibberellin (GA) and JA signaling, thereby phenocopying other DELLA-accumulating mutants. This phenotype can be complemented by a dominant gain-of-function allele of MYC3 and by crossing with a mutant having low DELLA protein levels. Hence, SPA1 interacts with DELLA proteins in a yeast two-hybrid screen, whereas high levels of DELLA inhibit MYC function and suppress JA signaling. DELLA accumulation leads to reduced synthesis of GSL and inhibited growth. Thus, the COP1/SPA-mediated degradation of DELLA not only affects growth but also regulates the biosynthesis of GSLs.
The GB4.0 Platform, an All-In-One Tool for CRISPR/Cas-Based Multiplex Genome Engineering in Plants
Authors: Vazquez-Vilar Marta , Garcia-Carpintero Víctor , Selma Sara , Bernabé-Orts Joan M. , Sanchez-Vicente Javier , Salazar-Sarasua Blanca , Ressa Arianna , de Paola Carmine , Ajenjo María , Quintela Jose Carlos , Fernández-del-Carmen Asun , Granell Antonio , Orzáez Diego
Published: July 2021

CRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy. Furthermore, multiplexing enhances dCas-based programmable gene expression and enables cascade-like gene regulation. However, the design and assembly of multiplex constructs comprising tandemly arrayed guide RNAs (gRNAs) requires scarless cloning and is still troublesome due to the presence of repetitive sequences, thus hampering a more widespread use. Here we present a comprehensive extension of the software-assisted cloning platform GoldenBraid (GB), in which, on top of its multigene cloning software, we integrate new tools for the Type IIS-based easy and rapid assembly of up to six tandemly-arrayed gRNAs with both Cas9 and Cas12a, using the gRNA-tRNA-spaced and the crRNA unspaced approaches, respectively. As stress tests for the new tools, we assembled and used for Agrobacterium-mediated stable transformation a 17 Cas9-gRNAs construct targeting a subset of the Squamosa-Promoter Binding Protein-Like (SPL) gene family in Nicotiana tabacum. The 14 selected genes are targets of miR156, thus potentially playing an important role in juvenile-to-adult and vegetative-to-reproductive phase transitions. With the 17 gRNAs construct we generated a collection of Cas9-free SPL edited T1 plants harboring up to 9 biallelic mutations and showing leaf juvenility and more branching. The functionality of GB-assembled dCas9 and dCas12a-based CRISPR/Cas activators and repressors using single and multiplexing gRNAs was validated using a Luciferase reporter with the Solanum lycopersicum Mtb promoter or the Agrobacterium tumefaciens nopaline synthase promoter in transient expression in Nicotiana benthamiana. With the incorporation of the new web-based tools and the accompanying collection of DNA parts, the GB4.0 genome edition turns an all-in-one open platform for plant genome engineering.
Elicitor Application in Strawberry Results in Long-Term Increase of Plant Resilience Without Yield Loss
Authors: Mouden Sanae , Bac-Molenaar Johanna A. , Kappers Iris F. , Beerling Ellen A. M. , Leiss Kirsten A.
Published: July 2021

For a first step integrating elicitor applications into the current IPM strategy increasing plant resilience against pests, we investigated repeated elicitor treatments in a strawberry everbearer nursery and cropping cycle under glass. During nursery methyl-jasmonate (MeJA), testing induction of defenses with plant bioassays was applied every 3 weeks. Thrips damage and reproduction by spider mites, whitefly and aphids were strongly reduced upon elicitor treatment. Subsequently, we applied MeJA every 3 weeks or based on scouting pests during a whole cropping cycle. Thrips leaf bioassays and LC-MS leaf metabolomics were applied to investigate the induction of defenses. Leaf damage by thrips was lower for both MeJA application schemes compared to the control except for the last weeks. While elicitor treatments after scouting also reduced damage, its effect did not last. Thrips damage decreased from vegetative to mature plants during the cropping cycle. At the end of the nursery phase, plants in the elicitor treatment were smaller. Surprisingly, growth during production was not affected by MeJA application, as were fruit yield and quality. LC-MS leaf metabolomics showed strong induction of vegetative plants decreasing during the maturation of plants toward the end of cultivation. Concurrently, no increase in the JA-inducible marker PPO was observed when measured toward the end of cultivation. Mostly flavonoid and phenolic glycosides known as plant defense compounds were induced upon MeJA application. While induced defense decreased with the maturation of plants, constitutive defense increased as measured in the leaf metabolome of control plants. Our data propose that young, relatively small plant stages lack constitutive defense necessitating an active JA defense response. As plants, mature constitutive defense metabolites seem to accumulate, providing a higher level of basal resistance. Our results have important implications for but are not limited to strawberry cultivation. We demonstrated that repeated elicitor application could be deployed as part of an integrated approach for sustainable crop protection by vertical integration with other management tactics and horizontal integration to control multiple pests concurrently. This approach forms a promising potential for long-term crop protection in greenhouses.
A Dual Path Model of Work-Related Well-Being in Healthcare and Social Work Settings: The Interweaving Between Trait Emotional Intelligence, End-User Job Demands, Coworkers Related Job Resources, Burnout, and Work Engagement
Authors: Tesi Alessio
Published: July 2021

Framing the job demands-resources (JD-R) model, the present study deepened how trait emotional intelligence (TEI, i.e., perception about one's own emotional realm) contributes to the work-related well-being of healthcare professionals. A total of 302 healthcare professionals were involved in the study and completed an anonymous self-report questionnaire. The results of the structural equation modeling revealed that TEI was directly and indirectly—mediated by end-user job demands—negatively associated with burnout, and directly and indirectly—mediated by coworkers related job resources— associated with work engagement. According to the health impairment and motivational processes of JD-R, the present study highlights that TEI could targets burnout and work engagement through different paths. The first path revealed that TEI would reduce burnout protecting by the insurgence harmful relationships with service end-users and the second showed that TEI would support work engagement sustaining the development of positive relationship with coworkers.
Motivation and Perceived Learning of Secondary Education History Students. Analysis of a Programme on Initial Teacher Training
Authors: Gómez Carrasco Cosme J. , Rodríguez-Medina Jairo , Miralles-Martínez Pedro , López-Facal Ramón
Published: July 2021

This paper presents the results of research on the initial teacher training in Spain. The aim is to verify whether the development of a training program for teachers based on methodological and epistemological aspects has a positive repercussion on the learning of secondary school pupils. We evaluated to what degree this training was reflected in secondary education pupils (n = 467, Mage = 14.74, SD = 1.97) taught by the participating trainee teachers during their period of teaching practice. A pretest and a postest were employed to obtain data on the methodology and the motivation and perceived learning on the part of the pupils. A confirmatory factor analysis was carried out to verify the validity and internal consistency of the tools and, later, the longitudinal invariance in each of the dimensions analyzed. The results confirm the internal consistency and validity of the tools employed and the improvement in the pupils' evaluation regarding methodology, motivation, and learning.
Study on Consumer Preference for Traceable Pork With Animal Welfare Attribute
Authors: Chen Mo , Hu Enhua , Kuen Lin Lin , Wu Linhai
Published: July 2021

We determined consumer preferences for traceable pork attributes in 328 consumers in Wuxi City, Jiangsu Province, China, based on a traceable pork attribute system composed of traceability, animal welfare, place of origin, and price attributes. Preference was studied using a Choice Experiment and Bayesian inference analysis. Results showed that the marginal utility of health welfare was lower than that of high-level traceability information and similar to that of place of origin but was higher than that of middle-level traceability information. A complementary relationship existed between dietary animal welfare and high-level traceability information and between health welfare and non-indigenous production. A substitution relationship existed between health welfare and indigenous production and between environmental animal welfare and non-indigenous production. The marginal utilities of health welfare and dietary welfare were higher than those of all price levels, and consumers accept a higher price as a result of increased production costs due to the inclusion of animal welfare information. Due to the harsh realities of COVID-19, China has recently approved the animal welfare attribute to be integrated into traceability market systems of new animal-derived food. The government should encourage manufacturers to produce diverse traceable animal-derived food not only to protect animal welfare and promote the construction of an ecological civilization, but also to develop new animal-derived food markets to satisfy different levels of consumer demand.
Exploring Emotion Regulation and Perceived Control as Antecedents of Anxiety and Its Consequences During Covid-19 Full Remote Learning
Authors: Zhao Ting , Fu Zongmei , Lian Xi , Ye Linning , Huang Wei
Published: July 2021

Maintaining the emotional well-being of learners during a pandemic is important. This study explored the effects of two emotion regulation strategies (cognitive reappraisal, expressive suppression) and perceived control on full remote learners' anxiety during Covid-19, and their relationship to perceived learning. Structural equation modeling was used to analyze 239 questionnaires completed by Chinese graduate students taking a course remotely from home for 13 weeks. This study showed that reappraisal was positively related to perceived control, whereas suppression was negatively related to perceived control. Reappraisers perceived more learning, whereas suppressors experienced more anxiety. Anxiety was significantly and negatively related to perceived learning. Mediation analyses showed the existence of different patterns of mediation in the pathways from the two types of emotion regulation to perceived learning. These findings are discussed in relation to relevant studies conducted during non-pandemic periods and Covid-19, and based on the results we highlight the need for interventions aimed at developing adaptive emotion regulation strategies and reducing anxiety in emergency remote learning.
Predicting Individual Function During COVID-19 Lockdown: Depression, Fear of COVID-19, Age, and Employment
Authors: Levy Inna , Cohen-Louck Keren
Published: July 2021

This study aims to identify the significance of age and employment to individual function during COVID-19. An online survey included 509 Israeli citizens, ages 18–78, who reported individual function, depression, fears related to COVID-19 and demographic characteristics. Structural Equation Modeling (SEM) analysis showed a good fit between our model and the data. Age and employment were negatively associated with depression and economic fears related to COVID-19 that, in turn, were negatively associated with individual function. The effect of age and employment on individual function was fully mediated via depression and economic fears related to COVID-19. The discussion addresses our findings in the context of the victimization paradox. Although COVID-19 related health complications are more frequent among older adults, our results suggest that practitioners responsible for public mental health during viral pandemics should consider young age and unemployment as risk factors for depression and low individual function.
Barriers and Motivators to Opioid Treatment Among Suburban Women Who Are Pregnant and Mothers in Caregiver Roles
Authors: Boeri Miriam , Lamonica Aukje K. , Turner Jeffrey M. , Parker Amanda , Murphy Grace , Boccone Carly
Published: July 2021

Women of childbearing age who misuse opioids are a particularly vulnerable population, and their barriers to treatment are unique because of their caregiver roles. Research on treatment for opioid use generally draws from urban and rural areas. This study fills a gap in research that focuses on barriers and motivators to opioid treatment in suburban areas. The aim of this study was to give voice to suburban pregnant women and mothers caring for children while using opioids. Ethnographic methods were used for recruitment, and 58 in-depth interviews were analyzed using a modified grounded theory approach. Barriers to medication-assisted treatment (MAT) included stigma, staff attitudes, and perceptions the women had about MAT treatment. Barriers associated with all types of treatment included structural factors and access difficulties. Relationships with partners, friends, family, and providers could be barriers as well as motivators, depending on the social context of the women’s situation. Our findings suggest increasing treatment-seeking motivators for mothers and pregnant women by identifying lack of resources, more empathetic consideration of social environments, and implementing structural changes to overcome barriers. Findings provide a contemporary understanding of how suburban landscapes affect mothers’ treatment-seeking for opioid dependence and suggest the need for more focus on emotional and structural resources rather than strict surveillance of women with opioid dependence who are pregnant or caring for children.
The Downstream Effects of Teacher Well-Being Programs: Improvements in Teachers' Stress, Cognition and Well-Being Benefit Their Students
Authors: Carroll Annemaree , York Ashley , Fynes-Clinton Sam , Sanders-O'Connor Emma , Flynn Libby , Bower Julie M. , Forrest Kylee , Ziaei Maryam
Published: July 2021

Quality interventions addressing the important issue of teacher stress and burnout have shown promising outcomes for participating teachers in terms of decreased distress, improved well-being and increased commitment to their jobs. Less is known however about whether such interventions also benefit students. The present study investigated the downstream effects for a completer sample of 226 primary and high school students after their teachers (n = 17) completed one of two 8-week stress reduction interventions. The relationships between change in teacher self-reported distress and burnout after completing the interventions, and change in students' self-reported well-being, academic self-perceptions, and perceptions of classroom environment were explored. A secondary aim of this study was to assess whether changes in teachers' cognitive flexibility mediated the relationship between teacher and student self-report outcomes. Results of correlational and multi-level mediation analyses showed that changes to teachers' self-reported distress and burnout affected multiple facets of students' well-being and the academic environment. Specifically, reductions in teachers' self-reported distress and burnout were related to students' improved perceptions of their teachers' support in the classroom. Reductions in teachers' personal and work-related burnout correlated with greater increases of academic self-perception in students. Contrary to predictions, cognitive flexibility in teachers did not mediate the relationship between these student and teacher measures. These findings indicate important downstream benefits for students and highlight the broader value of stress-reduction and well-being programs for teachers.