bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer's Disease
Authors: Hector Audrey , Brouillette Jonathan
Published: January 2021

Soluble amyloid-beta oligomers (Aβo) start to accumulate in the human brain one to two decades before any clinical symptoms of Alzheimer's disease (AD) and are implicated in synapse loss, one of the best predictors of memory decline that characterize the illness. Cognitive impairment in AD was traditionally thought to result from a reduction in synaptic activity which ultimately induces neurodegeneration. More recent evidence indicates that in the early stages of AD synaptic failure is, at least partly, induced by neuronal hyperactivity rather than hypoactivity. Here, we review the growing body of evidence supporting the implication of soluble Aβo on the induction of neuronal hyperactivity in AD animal models, in vitro, and in humans. We then discuss the impact of Aβo-induced hyperactivity on memory performance, cell death, epileptiform activity, gamma oscillations, and slow wave activity. We provide an overview of the cellular and molecular mechanisms that are emerging to explain how Aβo induce neuronal hyperactivity. We conclude by providing an outlook on the impact of hyperactivity for the development of disease-modifying interventions at the onset of AD.
BRAFAMP Frequently Co-occurs With IDH1/2, TP53, and ATRX Mutations in Adult Patients With Gliomas and Is Associated With Poorer Survival Than That of Patients Harboring BRAFV600E
Authors: Da Rong , Wang Maode , Jiang Haitao , Wang Tuo , Wang Wei
Published: January 2021

Abnormal RAS/RAF signaling plays a critical role in glioma. Although it is known that the V600E mutation of v-raf murine viral oncogene homolog B1 (BRAFV600E) and BRAF amplification (BRAFAMP) both result in constitutive activation of the RAS/RAF pathway, whether BRAFV600E and BRAFAMP have different effects on the survival of glioma patients needs to be clarified. Using cBioPortal, we retrieved studies of both mutations and copy number variations of the BRAF gene in CNS/brain tumors and investigated data from 69 nonredundant glioma patients. The BRAF mutation group had significantly more male patients (64.00% vs. 36.84%; P = 0.046) and a higher occurrence of glioblastoma multiforme (66.00% vs. 31.58%; P = 0.013) compared to those in the other group. The BRAFAMP group had significantly more patients with the mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) (73.68% vs. 18.00%; P = 0.000), tumor protein p53 (TP53) (73.68% vs. 30.00%; P = 0.002), and alpha thalassemia/mental retardation syndrome X linked (ATRX) (63.16% vs. 18.00%; P = 0.001) than the mutation group. The BRAFAMP and IDH1/2WT cohort had lower overall survival compared with the BRAFAMP and IDH1/2MT groups (P = 0.001) and the BRAF mutation cohort (P = 0.019), including the BRAFV600E (P = 0.033) and BRAFnon-V600E (P = 0.029) groups, using Kaplan–Meier survival curves and the log rank (Mantel–Cox) test. The BRAFAMP and IDH1/2WT genotype was found to be an independent predictive factor for glioma with BRAF mutation and BRAFAMP using Cox proportional hazard regression analysis (HR = 0.138, P = 0.018). Our findings indicate that BRAFAMP frequently occurs with IDH1/2, TP53, and ATRX mutations. Adult patients with glioma with BRAFAMP and IDH1/2WT had worse prognoses compared with those with BRAF mutation and BRAFAMP and IDH1/2MT. This suggests that the assessment of the status of BRAFAMP and IDH1/2 in adult glioma/glioblastoma patients has prognostic value as these patients have relatively short survival times and may benefit from personalized targeted therapy using BRAF and/or MEK inhibitors.
Quantitative Comparison of Knowledge-Based and Manual Intensity Modulated Radiation Therapy Planning for Nasopharyngeal Carcinoma
Authors: Hu Jiang , Liu Boji , Xie Weihao , Zhu Jinhan , Yu Xiaoli , Gu Huikuan , Wang Mingli , Wang Yixuan , Qi ZhenYu
Published: January 2021

Background and purpose

To validate the feasibility and efficiency of a fully automatic knowledge-based planning (KBP) method for nasopharyngeal carcinoma (NPC) cases, with special attention to the possible way that the success rate of auto-planning can be improved.

Methods and materials

A knowledge-based dose volume histogram (DVH) prediction model was developed based on 99 formerly treated NPC patients, by means of which the optimization objectives and the corresponding priorities for intensity modulation radiation therapy (IMRT) planning were automatically generated for each head and neck organ at risk (OAR). The automatic KBP method was thus evaluated in 17 new NPC cases with comparison to manual plans (MP) and expert plans (EXP) in terms of target dose coverage, conformity index (CI), homogeneity index (HI), and normal tissue protection. To quantify the plan quality, a metric was applied for plan evaluation. The variation in the plan quality and time consumption among planners was also investigated.

Results

With comparable target dose distributions, the KBP method achieved a significant dose reduction in critical organs such as the optic chiasm (p<0.001), optic nerve (p=0.021), and temporal lobe (p<0.001), but failed to spare the spinal cord (p<0.001) compared with MPs and EXPs. The overall plan quality evaluation gave mean scores of 144.59±11.48, 142.71±15.18, and 144.82±15.17, respectively, for KBPs, MPs, and EXPs (p=0.259). A total of 15 out of 17 KBPs (i.e., 88.24%) were approved by our physician as clinically acceptable.

Conclusion

The automatic KBP method using the DVH prediction model provided a possible way to generate clinically acceptable plans in a short time for NPC patients.
Contrast-Enhanced Ultrasound in the Differential Diagnosis of Primary Thyroid Lymphoma and Nodular Hashimoto’s Thyroiditis in a Background of Heterogeneous Parenchyma
Authors: Yang Lulu , Zhao Haina , He Yushuang , Zhu Xianglan , Yue Can , Luo Yan , Ma Buyun
Published: January 2021

Objective

To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the differentiation of primary thyroid lymphoma (PTL) and nodular Hashimoto’s thyroiditis (NHT) in patients with background of heterogeneous diffuse Hashimoto’s thyroiditis (HT).

Methods

Sixty HT patients with 64 thyroid nodules (31 PTL and 33 NHT) who had undergone CEUS examination were included in this study. With histopathological results as the reference, we evaluated the imaging features of each nodule on both conventional ultrasonography (US) and CEUS. Quantitative CEUS parameters including peak intensity (PI), time to peak (TTP), and area under the time–intensity curve (AUC) were gathered in the nodule and background parenchyma. The ratio indexes of theses parameters were calculated by the ratio of the lesion and the corresponding thyroid parenchyma. Logistic regression and receiver operating characteristic (ROC) curves analyses of valuable US indicators were further preformed to evaluate the diagnostic capability of CEUS in discrimination of PTL and NHT.

Results

Among all the observed US imaging features and CEUS parameters, 10 indicators showed significant differences between PTL and NHT (all P < 0.05). All the significant indicators were ranked according to the odds ratios (ORs). Eight of them were CEUS associated including imaging features of enhancement pattern, degree, homogeneity, and quantification parameters of PI, AUC, ratios of PI, AUC, and TTP, while indicators on conventional US, including vascularity and size ranked the last two with ORs less than 3. The five single CEUS parameters showed good diagnostic performance in diagnosis of PTL with areas under ROC curves of 0.72–0.83 and accuracies of 70.3–75.0%. The combination of CEUS imaging features and the ratios of PI, AUC, and TTP demonstrated excellent diagnostic efficiency and achieved area under ROC curve of 0.92, which was significantly higher than any of the five single parameters (all P < 0.05), with a sensitivity of 83.9%, specificity of 87.9%, and accuracy of 85.9%.

Conclusions

CEUS is an efficient diagnostic tool in the differential diagnosis of PTL and NHT for patients with diffuse HT. Conjoint analysis of CEUS imaging features and quantification parameters could improve the diagnostic values.
Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas
Authors: Li Jianyi , Hu Chuan , Du Yukun , Tang Xiaojie , Shao Cheng , Xu Tongshuai , Zhao Zheng , Hu Huiqiang , Sheng Yingyi , Guo Jianwei , Xi Yongming
Published: January 2021

Iron is one of the essential trace elements in the human body. An increasing amount of evidence indicates that the imbalance of iron metabolism is related to the occurrence and development of cancer. Here, we obtained the gene expression and clinical data of sarcoma patients from TCGA and the GEO database. The prognostic value of iron metabolism-related genes (IMRGs) in patients with sarcoma and the relationship between these genes and the immune microenvironment were studied by comprehensive bioinformatics analyses. Two signatures based on IMRGs were generated for the overall survival (OS) and disease-free survival (DFS) of sarcoma patients. At 3, 5, and 7 years, the areas under the curve (AUCs) of the OS signature were 0.708, 0.713, and 0.688, respectively. The AUCs of the DFS signature at 3, 5, and 7 years were 0.717, 0.689, and 0.702, respectively. Kaplan–Meier survival analysis indicated that the prognosis of high-risk patients was worse than that of low-risk patients. In addition, immunological analysis showed that there were different patterns of immune cell infiltration among patients in different clusters. Finally, we constructed two nomograms that can be used to predict the OS and DFS of sarcoma patients. The C-index was 0.766 (95% CI: 0.697–0.835) and 0.763 (95% CI: 0.706–0.820) for the OS and DFS nomograms, respectively. Both the ROC curves and the calibration plots showed that the two nomograms have good predictive performance. In summary, we constructed two IMRG-based prognostic models that can effectively predict the OS and DFS of sarcoma patients.
Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation
Authors: Xu Beili , Li Shuyu , Fang Yong , Zou Yanting , Song Dongqiang , Zhang Shuncai , Cai Yu
Published: January 2021

Objective

To examine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on gastric cancer (GC) progression and prognosis, and to explore the underlying mechanism.

Methods

PCSK9 expression levels in human GC tissues were determined by quantitative real-time PCR, western blotting, and immunohistochemical assay. PCSK9 serum levels were detected by enzyme-linked immunosorbent assay. The relationships of PCSK9 and GC progression and survival were analyzed using the Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards model. The effect of PCSK9 on cell invasion, migration, and apoptosis were determined in human GC cell lines and mouse xenograft model separately using PCSK9 knockdown and overexpression strategies. The PCSK9 interacting molecules, screened by co-immunoprecipitation combined with LC-MS/MS, were identified by immunofluorescence localization and western blotting. Additionally, the mitogen-activated protein kinase (MAPK) pathway was assessed by western blotting.

Results

PCSK9 mRNA and protein levels were significantly elevated in GC tissues compared with the paired normal tissues at our medical center (P < 0.001). Notably, the up-regulation of PCSK9 expression in GC tissues was related to tumor progression and poor survival. GC patients had higher serum levels of PCSK9 than the age-matched healthy controls (P < 0.001); PCSK9 promoted invasive and migratory ability and inhibited apoptosis in GC cells with no apparent affection in cell proliferation. The silencing of PCSK9 reversed these effects, suppressing tumor metastasis in vitro and in vivo. Furthermore, PCSK9 maintained these functions through up-regulating heat shock protein 70 (HSP70), ultimately facilitating the mitogen-activated protein kinase (MAPK) pathway.

Conclusion

Collectively, our data revealed that high PCSK9 expression levels in GC tissue were correlated with GC progression and poor prognosis and that PCSK9 could promote GC metastasis and suppress apoptosis by facilitating MAPK signaling pathway through HSP70 up-regulation. PCSK9 may represent a novel potential therapeutic target in GC.
Respiratory Symptoms in Post-infancy Children. A Dutch Pediatric Cohort Study
Authors: de Vries Esther , van Hout Roeland W. N. M.
Published: January 2021

Aim:To study the pattern of respiratory symptoms in children in the general population.

Method:We followed a cohort of children for up to 2 years through parents completing weekly online questionnaires in the Child-Is-Ill study (“Kind-en-Ziekmeting” in Dutch); the study was running 2012–2015. Inclusion criteria were “an ordinary child” (according to the parents) and <18 years old at inclusion. We especially encouraged participation of post-infancy children. Age at inclusion, sex, smoking exposure, allergy in the family, and frequent infections in the family were noted. Pearson's correlation, principal component analysis, latent class analysis, latent profile analysis, linear regression, and linear mixed effects regression were used in the statistical analyses.

Results:Data were collected on 55,524 childweeks in 755 children (50% girls; median age, 7 years; interquartile range, 4–11 years, 97% ≥2 years at inclusion), with reported symptom(s) in 8,425 childweeks (15%), leading to school absenteeism in 25%, doctor's visits in 12%, and parental sick leave in 8%; symptoms lasting ≥3 weeks were rare (2% of episodes). Linear mixed effects regression showed significant, but only limited, effects of season on the proportion of “symptom(s) reported” per individual child. Only runny nose showed a significant, but very small, age effect. However, the variability between the children was considerable. There were no obvious subgroups of children with specific symptom combinations.

Conclusion:In any randomly chosen week, the vast majority of children (85%) in our—mainly—post-infancy cohort derived from the general population did not have any symptom, even in the younger age group, even in winter. The children showed considerable variability; no clear subgroups of symptom patterns could be identified, underlining the difficult position of healthcare providers. These results support our opinion that post-infancy children in the general population should not be evaluated as if they are infants when they have recurrent respiratory symptoms. If they clearly deviate from the above-described most common pattern, it is wise to keep an eye on potential, maybe even rare, serious underlying causes.
Case Report: Primary Ewing Sarcoma of the Penis With Multiple Metastases
Authors: Zheng Chuanxi , Zhou Yong , Luo Yi , Zhang Hongying , Tu Chongqi , Min Li
Published: January 2021

Background: Ewing sarcoma is the second most common malignant bone tumor in children, but it rarely originates from extra-skeletal sites. The commonly involved sites of soft tissue include paravertebral spaces, lower extremities, the pelvis, head, and neck, while primary extra-skeletal Ewing sarcoma (EES) located in the genitals is extremely rare.

Case Presentation: We report a young patient who presented to our hospital with a painful erection of the penis and limited motion of the left hip. Magnetic resonance imaging showed a hyperintense mass with invasion of adjacent tissue in the penis and a heterogeneously high signal lesion in the left proximal femur. 18F-fluorodeoxyglucose positron-emission tomography detected widespread metastatic lesions in the bilateral lung and multiple skeletons. An incisional biopsy of the penis was performed; the histopathological findings and EWS gene translocation identified by molecular analysis confirmed the diagnosis of Ewing sarcoma. Subsequently, the punch-biopsy specimen from the left femur showed undifferentiated small round cells, a finding consistent with the microscopic presence of Ewing sarcoma metastasis. However, after the first course of multiagent chemotherapy, the penile mass did not obtain stabilization but instead grew progressively with surface ulceration and multidrug resistant bacteria infection. Despite receiving antibiotics and maximal supportive therapy, the patient died from sepsis and lung metastasis complications in the intensive care unit 2 months later.

Conclusion: This case indicates that although EES as a subtype of Ewing sarcoma is rare, it can occur virtually in any soft tissue site, even in the genitals. Therefore, clinicians need to distinguish this entity from other soft tissue sarcomas with rapid progression since early diagnosis and timely treatment of EES are pivotal for a favorable prognosis.
Hydroxychloroquine as a Chemoprophylactic Agent for COVID-19: A Clinico-Pharmacological Review
Authors: Agarwal Mudit , Ranjan Piyush , Baitha Upendra , Mittal Ankit
Published: January 2021

Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical and pharmacological point of view. In vitro studies on Vero cells show that hydroxychloroquine effectively inhibits SARS-CoV-2 by affecting viral entry and viral transport via endolysosomes. However, this efficacy has failed to replicate in in vivo animal models as well as in most clinical observational studies and clinical trials assessing pre-exposure prophylaxis and postexposure prophylaxis in healthcare workers. An analysis of the pharmacology of HCQ in COVID-19 reveals certain possible reasons for this failure—a pharmacokinetic failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells. Currently, many clinical trials on HCQ prophylaxis in HCW are ongoing; these factors should be taken into account. Using higher doses of HCQ for prophylaxis is likely to be associated with increased safety concerns; thus, it may be worthwhile to focus on other possible interventions.
Observability of Complex Systems by Means of Relative Distances Between Homological Groups
Authors: Diaz Ochoa Juan G.
Published: January 2021

It is common to consider using a data-intensive strategy as a way to develop systemic and quantitative analysis of complex systems so that data collection, sampling, standardization, visualization, and interpretation can determine how causal relationships are identified and incorporated into mathematical models. Collecting enough large datasets seems to be a good strategy in reducing bias of the collected data; but persistent and dynamic anomalies in the data structure, generated from variations in intrinsic mechanisms, can actually induce persistent entropy thus affecting the overall validity of quantitative models. In this research, we are introducing a method based on the definition of homological groups that aims at evaluating this persistent entropy as a complexity measure to estimate the observability of the systems. This method identifies patterns with persistent topology, extracted from the combination of different time series and clustering them to identify persistent bias in the data. We tested this method on accumulated data from patients using mobile sensors to measure the response of physical exercise in real-world conditions outside the lab. With this method, we aim to better stratify time series and customize models in complex biological systems.
The Prevalence and Independent Risk Factors of Significant Tricuspid Regurgitation Jets in Maintenance Hemodialysis Patients With ESRD
Authors: Zhang Ying , Ding Xiao-Han , Pang Fang , Zhang Laiping , Wang Yiqin , Wang Weili , Rao Rongsheng , Bian Shi-Zhu
Published: January 2021

Background and Aim

Tricuspid regurgitation (TR) is a frequent complication in various cardiovascular diseases. However, few studies have reported the prevalence of TR especially the moderate to severe or significant TR (ms-TR) maintenance dialysis patients. Thus, we aimed to identify the prevalence of ms-TR and its associated factors.

Methods

A total of 491 maintenance dialysis patients underwent echocardiographic examinations, while a subgroup (n = 283) also received routine blood tests, renal function examinations, and electrolyte analysis. We first compared the differences in abovementioned parameters among groups with various TR areas (TRAs). Finally, univariate and adjusted regression were also used to identify factors that were independently associated with ms-TR.

Results

The incidence of TR jets was 62.6%, which included a mildly increased TRA (47.8%), moderately increased TRA (10.4%), and severely increased TRA (3.5%). Most of the cardiac structures and functional parameters, such as the end-diastolic internal diameters of the left atrium (LA), left ventricle (LVDD), right atrium (RA), right ventricle (RV), left ventricular ejection fraction (LVEF), and fractional shortening (FS), were significantly associated with ms-TR. Among serum ions, only total CO2 (TCO2; r = −0.141, p = 0.047) was negatively correlated with TRA. After adjusted, only Na+ [odds ratio (OR): 0.871 0.888, p = 0.048], RA (OR: 1.370, p < 0.001), and FS (OR: 0.887, p < 0.001) were independently associated with ms-TR.

Conclusion

Tricuspid regurgitation occurs in maintenance hemodialysis patients with ESRD. Na+ FS and RA were independently associated with ms-TR, and these parameters may be potential risk factors/predictors for ms-TR.
Life Cycle of the Cardiac Voltage-Gated Sodium Channel NaV1.5
Authors: Dong Caijuan , Wang Ya , Ma Aiqun , Wang Tingzhong
Published: January 2021

Cardiac voltage-gated sodium channel NaV1.5, encoded by SCN5A, is crucial for the upstroke of action potential and excitation of cardiomyocytes. NaV1.5 undergoes complex processes before it reaches the target membrane microdomains and performs normal functions. A variety of protein partners are needed to achieve the balance between SCN5A transcription and mRNA decay, endoplasmic reticulum retention and export, Golgi apparatus retention and export, selective anchoring and degradation, activation, and inactivation of sodium currents. Subtle alterations can impair NaV1.5 in terms of expression or function, eventually leading to NaV1.5-associated diseases such as lethal arrhythmias and cardiomyopathy.
EEG Functional Connectivity and Cognitive Variables in Premanifest and Manifest Huntington’s Disease: EEG Low-Resolution Brain Electromagnetic Tomography (LORETA) Study
Authors: Delussi Marianna , Nazzaro Virgilio , Ricci Katia , de Tommaso Marina
Published: January 2021

Background

Scientific literature does not offer sufficient data on electroencephalography (EEG) functional connectivity and its correlations with clinical and cognitive features in premanifest and manifest HD.

Aim

This study tries to identify abnormal EEG patterns of functional connectivity, in conditions of “brain resting state” and correlations with motor decline and cognitive variable in Huntington’s disease (HD), in premanifest and manifest phase, looking for a reliable marker measuring disease progression.

Method

This was an observational cross-sectional study; 105 subjects with age ≥18 years submitted to HD genetic test. Each subject underwent a neurological, psychiatric, and cognitive assessment, EEG recording and genetic investigation for detecting the expansion of the CAG trait. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA) in 18 premanifest HD (pHD), 49 manifest HD (mHD), and 38 control (C) subjects.

Results

HD patients showed a Power Spectral Density reduced in the alpha range and increased in delta band compared to controls; no difference was detectable between pHD and mHD; the Global Connectivity in pHD revealed no significant differences if compared to mHD. The Current Source Density was similar among groups. No statistically significant results when comparing pHD with C group, even in comparison of mHD with Controls, and pHD with mHD. mHD compared to Controls showed a significant increase in delta, alpha1, alpha2, beta2, and beta3. Lagged Phase Synchronization in delta, alpha1, alpha2, beta2, and beta3 bands was increased in HD compared to controls (t = −3.921, p < 0.05). A significant correlation was found in Regression Analysis: statistically significant results in pHD for the “Symbol Digit Modality Test and lagged phase synchronization” in the Beta1 (r = −0.806, p < 0.05) in the prefrontal regions. The same correlation was found in mHD for the Stroop Word Reading Test (SWRT) in the Alpha2 band (r = −0.759, p < 0.05).

Conclusion

Increased phase synchronization in main bands characterized EEG in HD patients, as compared to controls. pHD were not dissimilar from mHD as regard to this EEG pattern. Increased phase synchronization correlated to cognitive decline in HD patients, with a similar trend in pHD, suggesting that it would be a potential biomarker of early phenotypical expression.
Physiological, Nutritional and Metabolomic Responses of Tomato Plants After the Foliar Application of Amino Acids Aspartic Acid, Glutamic Acid and Alanine
Authors: Alfosea-Simón Marina , Simón-Grao Silvia , Zavala-Gonzalez Ernesto Alejandro , Cámara-Zapata Jose Maria , Simón Inmaculada , Martínez-Nicolás Juan José , Lidón Vicente , García-Sánchez Francisco
Published: January 2021

Agriculture is facing a great number of different pressures due to the increase in population and the greater amount of food it demands, the environmental impact due to the excessive use of conventional fertilizers, and climate change, which subjects the crops to extreme environmental conditions. One of the solutions to these problems could be the use of biostimulant products that are rich in amino acids (AAs), which substitute and/or complement conventional fertilizers and help plants adapt to climate change. To formulate these products, it is first necessary to understand the role of the application of AAs (individually or as a mixture) in the physiological and metabolic processes of crops. For this, research was conducted to assess the effects of the application of different amino acids (Aspartic acid (Asp), Glutamic acid (Glu), L-Alanine (Ala) and their mixtures Asp + Glu and Asp + Glu + Ala on tomato seedlings (Solanum lycopersicum L.). To understand the effect of these treatments, morphological, physiological, ionomic and metabolomic studies were performed. The results showed that the application of Asp + Glu increased the growth of the plants, while those plants that received Ala had a decreased dry biomass of the shoots. The greatest increase in the growth of the plants with Asp + Glu was related with the increase in the net CO2 assimilation, the increase of proline, isoleucine and glucose with respect to the rest of the treatments. These data allow us to conclude that there is a synergistic effect between Aspartic acid and Glutamic acid, and the amino acid Alanine produces phytotoxicity when applied at 15 mM. The application of this amino acid altered the synthesis of proline and the pentose-phosphate route, and increased GABA and trigonelline.
Network Analysis Combining Proteomics and Metabolomics Reveals New Insights Into Early Responses of Eucalyptus grandis During Rust Infection
Authors: Sekiya Alline , Marques Felipe Garbelini , Leite Thiago Falda , Cataldi Thais Regiani , de Moraes Fabricio Edgar , Pinheiro Ana Lúcia Mendes , Labate Mônica Teresa Veneziano , Labate Carlos Alberto
Published: January 2021

Eucalyptus rust is caused by the biotrophic fungus, Austropuccinia psidii, which affects commercial plantations of Eucalyptus, a major raw material for the pulp and paper industry in Brazil. In this manuscript we aimed to uncover the molecular mechanisms involved in rust resistance and susceptibility in Eucalyptus grandis. Epifluorescence microscopy was used to follow the fungus development inside the leaves of two contrasting half-sibling genotypes (rust-resistance and rust-susceptible), and also determine the comparative time-course of changes in metabolites and proteins in plants inoculated with rust. Within 24 h of complete fungal invasion, the analysis of 709 metabolomic features showed the suppression of many metabolites 6 h after inoculation (hai) in the rust-resistant genotype, with responses being induced after 12 hai. In contrast, the rust-susceptible genotype displayed more induced metabolites from 0 to 18 hai time-points, but a strong suppression occurred at 24 hai. Multivariate analyses of genotypes and time points were used to select 16 differential metabolites mostly classified as phenylpropanoid-related compounds. Applying the Weighted Gene Co-Expression Network Analysis (WGCNA), rust-resistant and rust-susceptible genotypes had, respectively, 871 and 852 proteins grouped into 5 and 6 modules, of which 5 and 4 of them were significantly correlated to the selected metabolites. Functional analyses revealed roles for photosynthesis and oxidative-dependent responses leading to temporal activity of metabolites and related enzymes after 12 hai in rust-resistance; while the initial over-accumulation of those molecules and suppression of supporting mechanisms at 12 hai caused a lack of progressive metabolite-enzyme responses after 12 hai in rust-susceptible genotype. This study provides some insights on how E. grandis plants are functionally modulated to integrate secondary metabolites and related enzymes from phenylpropanoid pathway and lead to temporal divergences of resistance and susceptibility responses to rust.
A Long-Term Terrestrial Laser Scanning Measurement Station to Continuously Monitor Structural and Phenological Dynamics of Boreal Forest Canopy
Authors: Campos Mariana Batista , Litkey Paula , Wang Yunsheng , Chen Yuwei , Hyyti Heikki , Hyyppä Juha , Puttonen Eetu
Published: January 2021

The terrestrial laser scanner (TLS) has become standard technology for vegetation dynamics monitoring. TLS time series have significant underlying application in investigating structural development and dynamics on a daily and seasonal scale. However, the high potential of TLS for the monitoring of long-term temporal phenomena in fully grown trees with high spatial and temporal resolution has not yet been fully explored. Automated TLS platforms for long-term data collection and monitoring of forest dynamics are rare; and long-term TLS time series data is not yet readily available to potential end-user, such as forestry researchers and plant biologists. This work presents an automated and permanent TLS measurement station that collects high frequency and high spatial resolution TLS time series, aiming to monitor short- and long-term phenological changes at a boreal forestry field station (0.006° angular resolution, one scan per hour). The measurement station is the first of its kind considering the scope, accuracy, and length of the time series it produces. The TLS measurement station provides a unique dataset to monitor the 3D physical structure of a boreal forest, enabling new insights into forest dynamics. For instance, the information collected by the TLS station can be used to accurately detect structural changes in tree crowns surrounding the station. These changes and their timing can be linked with the phenological state of plants, such as the start of leaf-out during spring growing season. As the first results of this novel station, we present time series data products collected with the station and what detailed information it provides about the phenological changes in the test site during the leaf sprout in spring.
Cysts of the Snow Alga Chloromonas krienitzii (Chlorophyceae) Show Increased Tolerance to Ultraviolet Radiation and Elevated Visible Light
Authors: Procházková Lenka , Remias Daniel , Bilger Wolfgang , Křížková Heda , Řezanka Tomáš , Nedbalová Linda
Published: January 2021

Melting mountainous snowfields are populated by extremophilic microorganisms. An alga causing orange snow above timberline in the High Tatra Mountains (Poland) was characterised using multiple methods examining its ultrastructure, genetics, life cycle, photosynthesis and ecophysiology. Based on light and electron microscopy and ITS2 rDNA, the species was identified as Chloromonas krienitzii (Chlorophyceae). Recently, the taxon was described from Japan. However, cellular adaptations to its harsh environment and details about the life cycle were so far unknown. In this study, the snow surface population consisted of egg-shaped cysts containing large numbers of lipid bodies filled presumably with the secondary carotenoid astaxanthin. The outer, spiked cell wall was shed during cell maturation. Before this developmental step, the cysts resembled a different snow alga, Chloromonas brevispina. The remaining, long-lasting smooth cell wall showed a striking UV-induced blue autofluorescence, indicating the presence of short wavelengths absorbing, protective compounds, potentially sporopollenin containing polyphenolic components. Applying a chlorophyll fluorescence assay on intact cells, a significant UV-A and UV-B screening capability of about 30 and 50%, respectively, was measured. Moreover, intracellular secondary carotenoids were responsible for a reduction of blue-green light absorbed by chloroplasts by about 50%. These results revealed the high capacity of cysts to reduce the impact of harmful UV and high visible irradiation to the chloroplast and nucleus when exposed at alpine snow surfaces during melting. Consistently, the observed photosynthetic performance of photosystem II (evaluated by fluorometry) showed no decline up to 2100 μmol photons m–2 s–1. Cysts accumulated high contents of polyunsaturated fatty acids (about 60% of fatty acids), which are advantageous at low temperatures. In the course of this study, C. krienitzii was found also in Slovakia, Italy, Greece and the United States, indicating a widespread distribution in the Northern Hemisphere.
Whose Norms, Whose Prejudice? The Dynamics of Perceived Group Norms and Prejudice in New Secondary School Classes
Authors: Váradi Luca , Barna Ildikó , Németh Renáta
Published: January 2021

Ethnic prejudice can lead to exclusion and hinder social integration. Prejudices are formed throughout socialization, and social norms inform individuals about the acceptability of prejudice against certain outgroups. Adolescence is a crucial period for the development of intergroup attitudes, and young people are especially prone to follow the norms they perceive in their reference groups. At the same time, the effect of perceived norms on prejudice in school classes has been rarely studied. In Hungary, where prejudice against the Roma is widespread and there is no clear social norm proscribing prejudiced manifestations, this topic is especially relevant. In the present paper, based on multi-level analyses of panel data from Hungarian ninth-graders, we find that adolescents adjust their attitudes to those they perceive to be dominant among their classmates and that classmates serve as more important reference groups than teachers do. More contact with Roma is found to be associated with less prejudice against them. Looking at school classes, we find that at the beginning of the school year, many students underestimate the rejection of prejudiced expressions in their classes. By the end of the year, many students are found to adjust their own attitudes to the falsely perceived class norm. Based on our findings, we argue that school classes should be treated as important normative contexts for the socialization of intergroup attitudes and should receive special attention from both scholars and practitioners working in the fields of prejudice research and reduction. Furthermore, we suggest that teachers can most successfully hinder prejudices by working on a common, visible, shared class norm rather than “teaching” students that prejudices are not acceptable.
The Digital Transformation of Business Model Innovation: A Structured Literature Review
Authors: Vaska Selma , Massaro Maurizio , Bagarotto Ernesto Marco , Dal Mas Francesca
Published: January 2021

This paper has a two-fold aim: to analyze the development of the digital transformation field, and to understand the impact of digital technologies on business model innovation (BMI) through a structured review of the literature. The results of this research reveal that the field of digital transformation is still developing, with growing interest from researchers since 2014. Results show a need for research in developing countries and for more collaboration between researchers and practitioners. The review highlights that the field is fragmented among disruptive technologies, shared platforms and ecosystems, and new enabling technologies. We conclude that digital transformation has impacted value creation, delivery, and capture in almost every industry. These impacts have led to the employment of a variety of new business models, such as those for frugal innovation and the circular economy.
Fostering Self-Management of Everyday Memory in Older Adults: A New Intervention Approach
Authors: Hertzog Christopher , Pearman Ann , Lustig Emily , Hughes MacKenzie
Published: January 2021

Traditional memory strategy training interventions improve older adults’ performance on tests of episodic memory, but have limited transfer to episodic memory tasks, let alone to everyday memory. We argue that an alternative approach is needed to assist older adults to compensate for age-related cognitive declines and to maintain functional capacity in their own natural ecologies. We outline a set of principles regarding how interventions can successfully train older adults to increase successful goal pursuit to reduce risks of everyday memory failures. We argue that training individuals to use metacognitive self-regulatory strategies to proactively manage formulation and pursuit of daily goals can compensate for age-related cognitive changes and increase the likelihood of goal attainment. We then describe an intervention approach that instantiates these principles in a multi-modal intervention that is unique in its three-phase approach: (1) individualized assessment of an individual’s current approaches to self-regulation; (2) training memory strategies, self-management skills, and new habits of mind in a group training context; and (3) a behavioral shaping period in which individuals receive coaching and feedback on their efforts to use trained procedures to improve everyday cognition. A recently completed study conducted an initial test of the intervention, with highly encouraging results. We advocate further efforts to replicate, extend, and fine-tune this type of intervention. The ultimate goal is to be able to deliver the intervention in a way that increases its potential reach, including to subpopulations of older adults at risk for everyday cognitive impairments.
Representation Wars: Enacting an Armistice Through Active Inference
Authors: Constant Axel , Clark Andy , Friston Karl J.
Published: January 2021

Over the last 30 years, representationalist and dynamicist positions in the philosophy of cognitive science have argued over whether neurocognitive processes should be viewed as representational or not. Major scientific and technological developments over the years have furnished both parties with ever more sophisticated conceptual weaponry. In recent years, an enactive generalization of predictive processing – known as active inference – has been proposed as a unifying theory of brain functions. Since then, active inference has fueled both representationalist and dynamicist campaigns. However, we believe that when diving into the formal details of active inference, one should be able to find a solution to the war; if not a peace treaty, surely an armistice of a sort. Based on an analysis of these formal details, this paper shows how both representationalist and dynamicist sensibilities can peacefully coexist within the new territory of active inference.
The Goal Scale: A New Instrument to Measure the Perceived Exertion in Soccer (Indoor, Field, and Beach) Players
Authors: Polito Luis Felipe Tubagi , Marquezi Marcelo Luis , Marin Douglas Popp , Villas Boas Junior Marcelo , Brandão Maria Regina Ferreira
Published: January 2021

The rating of perceived exertion (RPE) can be used to monitor the exercise intensity during laboratory and specific tests, training sessions, and to estimate the internal training load of the athletes. The aim of the present study was to develop and validate a specific pictorial perceived exertion scale for soccer players (indoor, field, and beach soccer) called GOAL Scale. The pictorial GOAL Scale (six drawings; 1 “low exertion” to 6 “exhaustion”) was validated for twenty under-17 soccer players (16.4 ± 0.68 years; 175.4 ± 9 cm; 66.4 ± 7.7 kg; % fat mass 12.4 ± 3.3). In the validation phase, the athletes were evaluated in a progressive protocol involving stimuluses of 3 min with 1 min for the rest into the stages until the voluntary exhaustion in Maximal Cardiopulmonary Effort Test (MCET), and in the Yo Yo Intermittent Recovery Test – Level 1 (Yo-Yo). The RPE identified by the GOL Scale, by the Borg Scale 6 – 20 and by the Cavasini Scale, as well as the heart rate (HR), perceptual of the heart rate (%HRmax) and the blood lactate concentration ([La]) were immediately evaluated after each stage of both tests. Spearman’s correlation coefficient (p < 0.05) was used. Construct scale validity was examined by regressing GOAL Scale against Borg Scale 6 – 20 and Cavasini Scale and concurrent scale validity was investigated by regressing GOAL Scale against HR, beats/min and blood lactate concentration (mmol/L) during two progressive tests. There was a significant correlation values of the GOAL Scale with Borg Scale (r = 0.93; r = 0.88), Cavasini Scale (r = 0.91; r = 0.90), %HRmax (r = 0.91; r = 0,86), HR (r = 0.87; r = 0.83) and lactate (r = 0.68; r = 0.83) during tests (Maximal Incremental Cardiopulmonary Test and Yo-Yo test, respectively). The results evidenced concurrent and construct validity of the GOAL Scale across a wide range of exercise intensity. The absence of verbal anchors makes the use of this instrument to soccer, futsal and beach soccer athletes of different languages and different literacy levels possible.
Loneliness, Social Isolation and Their Difference: A Cross-Diagnostic Study in Persistent Depressive Disorder and Borderline Personality Disorder
Authors: Nenov-Matt Tabea , Barton Barbara B. , Dewald-Kaufmann Julia , Goerigk Stephan , Rek Stephanie , Zentz Katharina , Musil Richard , Jobst Andrea , Padberg Frank , Reinhard Matthias A.
Published: January 2021

Background:Interpersonal difficulties are a key feature of persistent depressive disorder (PDD) and borderline personality disorder (BPD). Caught in a vicious circle of dysfunctional interpersonal transaction, PDD and BPD patients are at great risk of experiencing prolonged loneliness. Loneliness, in turn, has been associated with the development of mental disorders and chronic illness trajectories. Besides, several factors may contribute to the experience of loneliness across the lifespan, such as social network characteristics, a history of childhood maltreatment (CM), and cognitive-affective biases such as rejection sensitivity (RS). This cross-diagnostic study approached the topic of perceived loneliness by comparing PDD and BPD patients with healthy controls (HC) in its interplay with symptom burden, social network characteristics, RS as well as CM.

Method:Thirty-four PDD patients (DSM-5; 15 female, Mage= 38.2, SD = 12.3), 36 BPD patients (DSM-5; 19 female, Mage= 28.8, SD = 9.2), and 70 age- and gender-matched HC were assessed cross-sectionally using the following self-report measures: UCLA Loneliness Scale, Social Network Index (SNI; size, diversity, and embeddedness), Beck Depression Inventory (BDI-II), Borderline Symptom List (BSL-23), Childhood Trauma Questionnaire (CTQ), and Rejection Sensitivity Questionnaire (RSQ).

Results:Both patient groups reported significantly higher levels of perceived loneliness, symptom severity, and smaller social network characteristics compared to HC. Loneliness was significantly correlated with severity of self-reported clinical symptoms in PDD and at trend level in BPD. Besides, loneliness tended to be related to social network characteristics for all groups except PDD patients. Both PDD and BPD patients showed higher RS as well as CTQ scores than HC. A history of emotional abuse and emotional neglect was associated with loneliness, and this association was mediated by RS as demonstrated by an exploratory mediation analysis.

Discussion:Loneliness is highly prevalent in PDD and BPD patients and contributes to the overall symptom burden. Interestingly, loneliness showed an association with prior experiences of CM as well as current RS. We therefore propose a comprehensive model on how intra- und interpersonal aspects may interplay in the dynamics of loneliness in light of CM. Finally, this model may have further implications for psychotherapeutic interventions.
Effects on Gambling Activity From Coronavirus Disease 2019—An Analysis of Revenue-Based Taxation of Online- and Land-Based Gambling Operators During the Pandemic
Authors: Håkansson Anders
Published: January 2021

Background:Concerns have been raised about increased gambling problems during the coronavirus disease (COVID-19) crisis, particularly in settings with high online gambling and risks of migration from land-based to riskier online-based gambling types. However, few non-self-reported data sources are hitherto available. The present study aimed to assess changes in the online- and land-based gambling markets in Sweden during the first months affected by the societal impact of COVID-19.

Methods:Data were derived from national authority data describing monthly taxations of all licensed Swedish gambling operators, whose monthly tax payments are directly based on gambling revenue. Subdivisions of the gambling market were followed monthly from before COVID-19 onset in Sweden (mainly February 2020) through June 2020, when the sports market was restarted after COVID-19 lockdown.

Results:Overall revenue-based taxations in the licensed gambling decreased markedly from February to March, but stabilized onto an overall modest decrease through June. Commercial online casino/betting, despite some decrease in March, was maintained on a relatively stable level through June. However, within this category, horse betting increased steeply during the pandemic but returned to prepandemic levels later during the period. The state-owned operator in betting/online casino decreased markedly throughout the pandemic. The remaining commercial operators, mainly in online casino and online betting, demonstrated no change during the pandemic and ended on a June level 14% above the February level. Throughout the pandemic, the smaller restaurant casinos decreased markedly, while major state-owned casinos also closed entirely. State-owned lotteries and electronic gambling machines decreased markedly but were rapidly normalized to prepandemic levels.

Conclusions:Commercial online gambling operators' revenues remained stable throughout the pandemic, despite the dramatic lockdown in sports. Thus, chance-based online games may have remained a strong actor in the gambling market despite the COVID-19 crisis, in line with previous self-report data. A sudden increase in horse betting during the sports lockdown and its decrease when sports reopened confirm the picture of possible COVID-19-related migration between gambling types, indicating a volatility with potential impact on gambling-related public health.