bluuebunny/crossref_metadata_2025 huggingface dataset:
Granular layEr Simulator: Design and Multi-GPU Simulation of the Cerebellar Granular Layer
Authors: Florimbi Giordana , Torti Emanuele , Masoli Stefano , D'Angelo Egidio , Leporati Francesco
Published: March 2021

In modern computational modeling, neuroscientists need to reproduce long-lasting activity of large-scale networks, where neurons are described by highly complex mathematical models. These aspects strongly increase the computational load of the simulations, which can be efficiently performed by exploiting parallel systems to reduce the processing times. Graphics Processing Unit (GPU) devices meet this need providing on desktop High Performance Computing. In this work, authors describe a novel Granular layEr Simulator development implemented on a multi-GPU system capable of reconstructing the cerebellar granular layer in a 3D space and reproducing its neuronal activity. The reconstruction is characterized by a high level of novelty and realism considering axonal/dendritic field geometries, oriented in the 3D space, and following convergence/divergence rates provided in literature. Neurons are modeled using Hodgkin and Huxley representations. The network is validated by reproducing typical behaviors which are well-documented in the literature, such as the center-surround organization. The reconstruction of a network, whose volume is 600 × 150 × 1,200 μm3 with 432,000 granules, 972 Golgi cells, 32,399 glomeruli, and 4,051 mossy fibers, takes 235 s on an Intel i9 processor. The 10 s activity reproduction takes only 4.34 and 3.37 h exploiting a single and multi-GPU desktop system (with one or two NVIDIA RTX 2080 GPU, respectively). Moreover, the code takes only 3.52 and 2.44 h if run on one or two NVIDIA V100 GPU, respectively. The relevant speedups reached (up to ~38× in the single-GPU version, and ~55× in the multi-GPU) clearly demonstrate that the GPU technology is highly suitable for realistic large network simulations.
The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Can Protect Against Cognitive Impairment in Multiple Sclerosis
Authors: Portaccio Emilio , Bellinvia Angelo , Prestipino Elio , Nacmias Benedetta , Bagnoli Silvia , Razzolini Lorenzo , Pastò Luisa , Niccolai Claudia , Goretti Benedetta , Fonderico Mattia , Zimatore Giovanni Bosco , Losignore Nunzia Alessandra , Sorbi Sandro , Amato Maria Pia
Published: March 2021

Introduction: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, involved in neuronal survival and synaptic plasticity. The BDNF Val66Met polymorphism is known to reduce BDNF expression and secretion; its role in multiple sclerosis (MS) is poorly investigated.

Objectives and Methods: In this multicenter, retrospective study, we assessed the role of BDNF Val66Met polymorphism on cognitive and motor disability in MS patients consecutively referred to the University of Florence and the Hospital of Barletta. All patients underwent a genetic analysis for the presence of Val66Met polymorphism and a comprehensive neuropsychological examination on the Rao's Brief Repeatable Battery and the Stroop Color Word Test. Possible predictors of the Expanded Disability Status Scale (EDSS) score and number of failed neuropsychological tests were assessed through linear multivariable regression models.

Results: Ninety-eight patients were recruited. Patients with the BDNF Val66Met polymorphism (35.7%) were more frequently males (p = 0.020), more disabled (p = 0.026) and, marginally, older (p = 0.064). In the multivariable analysis, BDNF Val66Met polymorphism was associated with a better cognitive performance (B = −1.1 ± 0.5, p = 0.027). Higher EDSS score was associated with a progressive disease course (B = 3.4, p < 0.001) and, marginally, with the presence of the BDNF Val66Met polymorphism (B = 0.56, p = 0.066).

Discussion: Our results preliminarily suggest a protective role of BDNF Val66Met polymorphism against cognitive impairment in MS patients, possibly related to a detrimental effect of increased BDNF concentration in a neuroinflammatory environment.
Alteration of N6 -Methyladenosine mRNA Methylation in a Rat Model of Cerebral Ischemia–Reperfusion Injury
Authors: Yi Dazhuang , Wang Qunhui , Zhao Yuhao , Song Yu , You Hong , Wang Jian , Liu Renjie , Shi Zhongqiang , Chen Xuan , Luo Qi
Published: March 2021

Aim

This study was conducted in order to reveal the alterations in the N6-methyladenosine (m6A) modification profile of cerebral ischemia–reperfusion injury model rats.

Materials and Methods

Rats were used to establish the middle cerebral artery occlusion and reperfusion (MCAO/R) model. MeRIP-seq and RNA-seq were performed to identify differences in m6A methylation and gene expression. The expression of m6A methylation regulators was analyzed in three datasets and detected by quantitative real-time polymerase chain reaction, western blot, and immunofluorescence.

Results

We identified 1,160 differentially expressed genes with hypermethylated or hypomethylated m6A modifications. The differentially expressed genes with hypermethylated m6A modifications were involved in the pathways associated with inflammation, while hypomethylated differentially expressed genes were related to neurons and nerve synapses. Among the m6A regulators, FTO was specifically localized in neurons and significantly downregulated after MCAO/R.

Conclusion

Our study provided an m6A transcriptome-wide map of the MACO/R rat samples, which might provide new insights into the mechanisms of cerebral ischemia–reperfusion injury.
Testing the Effects of a Preceding Self-Control Task on Decision-Making in Soccer Refereeing
Authors: Englert Chris , Dziuba Anna , Schweizer Geoffrey
Published: March 2021

The present study tested the assumption that the momentary level of self-control strength affects the accuracy rates in a sports-related judgment and decision-making task. A total ofN= 27 participants rated the veracity of 28 video-taped statements of soccer players who were interviewed by a non-visible referee after a critical game-related situation. In half of the videos, the players were lying, and in the other half, they were telling the truth. Participants were tested twice: once with temporarily depleted self-control strength and once with temporarily available self-control strength (order counterbalanced; measurements separated by exactly 7 days). Self-control strength was experimentally manipulated with the Stroop task. In line with two-process models of information processing, we hypothesized that under ego depletion, information is processed in a rather heuristic manner, leading to lower accuracy rates. Contrary to our expectations, the level of temporarily available self-control strength did not have an effect on accuracy rates. Limitations and implications for future research endeavors are discussed.
Maternal High Fat Diet Consumption Exaggerates Metabolic Disorders in Mice With Cigarette-Smoking Induced Intrauterine Undernutrition
Authors: Huang Taida , Yang Mo , Zeng Yunxin , Huang Xiaomin , Wang Nan , Chen Yun , Li Peng , Yuan Jinqiu , Chen Chun , Oliver Brian G. , Yi Chenju
Published: March 2021

Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption.

Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks.

Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD.

Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring.
Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study
Authors: Xu Ling , Liu Yinhua , Fan Zhimin , Jiang Zefei , Liu Yunjiang , Ling Rui , Zhang Jianguo , Yu Zhigang , Jin Feng , Wang Chuan , Cui Shude , Wang Shu , Mao Dahua , Han Bing , Wang Tao , Zhang Geng , Wang Ting , Guo Baoliang , Yu Lixiang , Xu Yingying , Fu Fangmeng , Liu Zhenzhen , Wang Siyuan , Luo Ke , Xiang Qian , Zhang Zhuo , Liu Qianxin , Zhou Bin , Liu Zhaorui , Ma Chao , Tong Weiwei , Mao Jie , Duan Xuening , Cui Yimin
Published: March 2021

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals’ databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan–Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 vs. 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03437837.
ROS-Mediated Necrosis by Glycolipid Biosurfactants on Lung, Breast, and Skin Melanoma Cells
Authors: Haque Farazul , Khan Mohd Sajjad Ahmad , AlQurashi Naif
Published: March 2021

Cancer is one of the major leading causes of death worldwide. Designing the new anticancer drugs is remained a challenging task due to ensure complexicity of cancer etiology and continuosly emerging drug resistance. Glycolipid biosurfactants are known to possess various biological activities including antimicrobial, anticancer and antiviral properties. In the present study, we sought to decipher the mechanism of action of the glycolipids (lactonic-sophorolipd, acidic-sophorolipid, glucolipid, and bolalipid) against cancer cells using lung cancer cell line (A549), breast cancer cell line (MDA-MB 231), and mouse skin melanoma cell line (B16F10). Scratch assay and fluorescence microscopy revealed that glycolipids inhibit tumorous cell migration possibly by inhibiting actin filaments. Fluorescence activated cell sorter (FACS) analysis exhibited that lactonic sophorolipid and glucolipid both induced the reactive oxygen species, altered the mitochondrial membrane potential (ΔΨ) and finally led to the cell death by necrosis. Furthermore, combinatorial effect of lactonic-sophorolipd and glucolipid demonstrated synergistic interaction on A549 cell line whereas additive effect on MDA-MB 231 and B16F10 cell lines. Our study has highlighted that lactonic-sophorolipd and glucolipid could be useful for developing new anticancer drugs either alone or in combination.
Peripheral Blood Autoantibodies Against to Tumor-Associated Antigen Predict Clinical Outcome to Immune Checkpoint Inhibitor-Based Treatment in Advanced Non-Small Cell Lung Cancer
Authors: Zhou Juan , Zhao Jing , Jia Qingzhu , Chu Qian , Zhou Fei , Chu Xiangling , Zhao Wencheng , Ren Shengxiang , Zhou Caicun , Su Chunxia
Published: March 2021

Background

Peripheral blood biomarkers to immunotherapy have attracted more and more attentions owing to noninvasive nature. This study was designed to identify a panel of tumor associated autoantibodies (TAAbs) in plasma to predict the clinical outcome of ICIs-based treatment in advanced NSCLC patients and correlation between TAAbs and checkpoint inhibitor pneumonitis (CIP) would also be investigated.

Materials and Methods

Baseline plasma was collected from patients with advanced NSCLC before receiving ICIs-based treatment. ELISA was used to detect concentration of autoantibodies. Clinical efficacy was evaluated according to RECIST v1.1.

Results

We have identified a panel of five-TAAbs to predict responses of ICIs-based treatment in a discovery cohort (n = 37), and confirmed its predictive value in a validation cohort (n = 129). In the validation cohort, the positivity of this 5-TAAbs panel was significantly associated with better response (ORR: 44.4% vs. 13.6%, P < 0.001) and longer PFS (7.6 vs. 3.3m, P < 0.001). This significant association was remained in subgroup of patients treated with combination therapy (ORR: 43.8% vs. 13.7%, P = 0.004,PFS: 6.7 vs. 3.7m, P = 0 .017). Furthermore, this 5-TAAs panel worked better in patients who received subsequent-line treatment (ORR: 42.4% vs. 7.7%, P = 0.001, PFS: 6.2 vs. 3.0m, P = 0.004) than those received first-line treatment (ORR: 46.7% vs. 35.7%, P = 0.345, PFS: NR vs. 10.48m, P = 0.146). In addition, the CIP incidence in patients with 5-TAAbs positive was significantly higher comparing to negative patients (20.4% vs. 5.9%, P = 0.015).

Conclusion

Our 5-TAAbs panel is a potential predictive biomarker for responses and toxicities to ICIs-based treatment in patients with advanced NSCLC.
En Bloc Tumor Resection, Optical Molecular Imaging, and the Potential Synergy of the Combination of the Two Techniques in Bladder Cancer
Authors: Yang Yongjun , Liu Chao , Yan Xiaoting , Li Jiawei , Yang Xiaofeng
Published: March 2021

Although transurethral resection of bladder tumor is the golden standard for the treatment of non-muscle invasive bladder cancer, this surgical procedure still has some serious drawbacks. For example, piecemeal resection of tumor tissue results in exfoliated tumor cells dissemination and implantation, and fragmented tumor specimens make it difficult for pathologists to accurately assess the pathological stage and histologic grade. En bloc tumor resection follows the basic principle of oncological surgery and provides an intact tumor specimen containing detrusor muscle for pathologists to make accurate histopathological assessment. However, there is no robust clinical evidence that en bloc tumor resection is superior to conventional resection in terms of oncological outcomes. Considering the high recurrence rate, small or occult tumor lesions may be overlooked and incomplete tumor resection may occur during white light cystoscopy-assisted transurethral resection. Molecular fluorescent tracers have the ability to bind tumor cells with high sensitivity and specificity. Optical molecular imaging mediated by it can detect small or occult malignant lesions while minimizing the occurrence of false-positive results. Meanwhile, optical molecular imaging can provide dynamic and real-time image guidance in the surgical procedure, which helps urologists to accurately determine the boundary and depth of tumor invasion, so as to perform complete and high-quality transurethral tumor resection. Integrating the advantages of these two technologies, optical molecular imaging-assisted en bloc tumor resection shows the potential to improve the positive detection rate of small or occult tumor lesions and the quality of transurethral resection, resulting in high recurrence-free and progression-free survival rates.
Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies
Authors: Allan Katelin M. , Farrow Nigel , Donnelley Martin , Jaffe Adam , Waters Shafagh A.
Published: March 2021

Prognosis of patients with cystic fibrosis (CF) varies extensively despite recent advances in targeted therapies that improve CF transmembrane conductance regulator (CFTR) function. Despite being a multi-organ disease, extensive lung tissue destruction remains the major cause of morbidity and mortality. Progress towards a curative treatment strategy that implements aCFTRgene addition-technology to the patients’ lungs has been slow and not yet developed beyond clinical trials. Improved delivery vectors are needed to overcome the body’s defense system and ensure an efficient and consistent clinical response before gene therapy is suitable for clinical care. Cell-based therapy–which relies on functional modification of allogenic or autologous cellsex vivo, prior to transplantation into the patient–is now a therapeutic reality for various diseases. For CF, pioneering research has demonstrated proof-of-principle for allogenic transplantation of cultured human airway stem cells into mouse airways. However, applying a cell-based therapy to the human airways has distinct challenges. We review CF gene therapies using viral and non-viral delivery strategies and discuss current advances towards autologous cell-based therapies. Progress towards identification, correction, and expansion of a suitable regenerative cell, as well as refinement of pre-cell transplant lung conditioning protocols is discussed.
Competitive Drivers of Atrial Fibrillation: The Interplay Between Focal Drivers and Multiwavelet Reentry
Authors: Carrick Richard T. , Benson Bryce E. , Bates Oliver R. J. , Spector Peter S.
Published: March 2021

Background

There is debate whether human atrial fibrillation is driven by focal drivers or multiwavelet reentry. We propose that the changing activation sequences surrounding a focal driver can at times self-sustain in the absence of that driver. Further, the relationship between focal drivers and surrounding chaotic activation is bidirectional; focal drivers can generate chaotic activation, which may affect the dynamics of focal drivers.

Methods and Results

In a propagation model, we generated tissues that support structural micro-reentry and moving functional reentrant circuits. We qualitatively assessed (1) the tissue’s ability to support self-sustaining fibrillation after elimination of the focal driver, (2) the impact that structural-reentrant substrate has on the duration of fibrillation, the impact that micro-reentrant (3) frequency, (4) excitable gap, and (5) exposure to surrounding fibrillation have on micro-reentry in the setting of chaotic activation, and finally the likelihood fibrillation will end in structural reentry based on (6) the distance between and (7) the relative lengths of an ablated tissue’s inner and outer boundaries. We found (1) focal drivers produced chaotic activation when waves encountered heterogeneous refractoriness; chaotic activation could then repeatedly initiate and terminate micro-reentry. Perpetuation of fibrillation following elimination of micro-reentry was predicted by tissue properties. (2) Duration of fibrillation was increased by the presence of a structural micro-reentrant substrate only when surrounding tissue had a low propensity to support self-sustaining chaotic activation. Likelihood of micro-reentry around the structural reentrant substrate increased as (3) the frequency of structural reentry increased relative to the frequency of fibrillation in the surrounding tissue, (4) the excitable gap of micro-reentry increased, and (5) the exposure of the structural circuit to the surrounding tissue decreased. Likelihood of organized tachycardia following termination of fibrillation increased with (6) decreasing distance and (7) disparity of size between focal obstacle and external boundary.

Conclusion

Focal drivers such as structural micro-reentry and the chaotic activation they produce are continuously interacting with one another. In order to accurately describe cardiac tissue’s propensity to support fibrillation, the relative characteristics of both stationary and moving drivers must be taken into account.
How I See Me—A Meta-Analysis Investigating the Association Between Identities and Pro-environmental Behaviour
Authors: Udall Alina Mia , de Groot Judith I.M. , De Jong Simon B. , Shankar Avi
Published: March 2021

Prolific research suggests identity associates with pro-environmental behaviours (PEBs) that are individual and/or group focused. Individual PEB is personally driven, self-reliant, and are conducted on one's own (e.g., home recycling). Group focused PEB is other people-reliant and completed as part of a group (e.g., attending meetings of an environmental organisation). A wide range of identities have been related to PEBs. For example, a recent systematic qualitative review revealed 99 different types of identities studied in a PEB context. Most studies were correlational, few had an experimental design. However, the relationships between all these identities and PEBs have so far not been tested quantitatively with meta-analytical techniques. As such, a clear overview of this field is currently lacking. Due to the diverse nature of the field,a priorihypotheses were not possible and relatively broad definitions of identity had to be used to encompass all types of identities and the diverse meanings of identity that have been included in PEB research. What prior theory did allow for was to assess the distinction between two main types of identity, namely how people label, describe, and recognise oneself individually (individual identity), or as part of a group (group identity). Our overall goal was thus to assess the current state of knowledge on identities and PEBs. In 104 studies using a meta-regression following the preferred reporting items for systematic reviews and meta-analyses guidelines, our random-effects meta-analysis showed that the overall concept of identity associated with PEB with a medium Pearson'sr(Aim 1). Furthermore, we found that individual identities associated more strongly with PEBs than group identities (Aim 2). The associations between individual and group identities were stronger when the identity and PEB were from the same category (e.g., when both were group-focused; Aim 3). Methodologically, the findings revealed that group identities and group PEBs were most strongly associated for self-reported rather than observed PEBs (Aim 4). Overall identity associated most strongly with group PEBs in the field rather than in the lab (Aim 5) and in student- rather than non-student samples (Aim 6). We discuss the theoretical and practical implications.
Noncompliance With Safety Guidelines as a Free-Riding Strategy: An Evolutionary Game-Theoretic Approach to Cooperation During the COVID-19 Pandemic
Authors: Yong Jose C. , Choy Bryan K. C.
Published: March 2021

Evolutionary game theory and public goods games offer an important framework to understand cooperation during pandemics. From this perspective, the COVID-19 situation can be conceptualized as a dilemma where people who neglect safety precautions act as free riders, because they get to enjoy the benefits of decreased health risk from others’ compliance with policies despite not contributing to or even undermining public safety themselves. At the same time, humans appear to carry a suite of evolved psychological mechanisms aimed at curbing free riding in order to ensure the continued provision of public goods, which can be leveraged to develop more effective measures to promote compliance with regulations. We also highlight factors beyond free riding that reduce compliance rates, such as the emergence of conspiratorial thinking, which seriously undermine the effectiveness of measures to suppress free riding. Together, the current paper outlines the social dynamics that occur in public goods dilemmas involving the spread of infectious disease, highlights the utility and limits of evolutionary game-theoretic approaches for COVID-19 management, and suggests novel directions based on emerging challenges to cooperation.
Impact of the Coronavirus Pandemic (COVID-19) Lockdown on Mental Health and Well-Being in the United Arab Emirates
Authors: Cheikh Ismail Leila , Mohamad Maysm N. , Bataineh Mo'ath F. , Ajab Abir , Al-Marzouqi Amina M. , Jarrar Amjad H. , Abu Jamous Dima O. , Ali Habiba I. , Al Sabbah Haleama , Hasan Hayder , Stojanovska Lily , Hashim Mona , Shaker Obaid Reyad R. , Saleh Sheima T. , Osaili Tareq M. , Al Dhaheri Ayesha S.
Published: March 2021

United Arab Emirates (UAE) has taken unprecedented precautionary measures including complete lockdowns against COVID-19 to control its spread and ensure the well-being of individuals. This study investigated the impact of COVID-19 and societal lockdown measures on the mental health of adults in the UAE. A cross-sectional study was conducted using an English and Arabic online questionnaire between May and June 2020. The psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and the social and family support impact was evaluated using questions from the Perceived Support Scale (PSS). A total of 4,426 participants (3,325 females and 1,101 males) completed the questionnaire. The mean IES-R score was 28.0 ± 14.6, reflecting a mild stressful impact with 27.3% reporting severe psychological impact. Over 36% reported increased stress from work, home and financial matters. Also, 43–63% of the participants felt horrified, apprehensive or helpless due to COVID-19. Females, younger participants, part-timers, and college or University graduates were more likely to have a high IES-R score (p < 0.05). The majority of participants reported receiving increased support from family members, paying more attention to their mental health, and spending more time to rest and relax. The results of this study demonstrate the impact of the COVID-19 pandemic on mental health among the UAE residents and highlight the need to adopt culturally appropriate interventions for the general population and vulnerable groups, such as females and younger adults.
A Smart Tendon Hammer System for Remote Neurological Examination
Authors: Meinhold Waiman , Yamakawa Yoshinori , Honda Hiroshi , Mori Takayuki , Izumi Shin-ichi , Ueda Jun
Published: March 2021

The deep tendon reflex exam is an important part of neurological assessment of patients consisting of two components, reflex elicitation and reflex grading. While this exam has traditionally been performed in person, with trained clinicians both eliciting and grading the reflex, this work seeks to enable the exam by novices. The COVID-19 pandemic has motivated greater utilization of telemedicine and other remote healthcare delivery tools. A smart tendon hammer capable of streaming acceleration measurements wirelessly allows differentiation of correct and incorrect tapping locations with 91.5% accuracy to provide feedback to users about the appropriateness of stimulation, enabling reflex elicitation by laypeople, while survey results demonstrate that novices are reasonably able to grade reflex responses. Novice reflex grading demonstrates adequate performance with a mean error of 0.2 points on a five point scale. This work shows that by assisting in the reflex elicitation component of the reflex exam via a smart hammer and feedback application, novices should be able to complete the reflex exam remotely, filling a critical gap in neurological care during the COVID-19 pandemic.
Exploring the Potential of DSCOVR EPIC Data to Retrieve Clumping Index in Australian Terrestrial Ecosystem Research Network Observing Sites
Authors: Pisek Jan , Arndt Stefan K. , Erb Angela , Pendall Elise , Schaaf Crystal , Wardlaw Timothy J. , Woodgate William , Knyazikhin Yuri
Published: March 2021

Vegetation foliage clumping significantly alters the radiation environment and affects vegetation growth as well as water, carbon cycles. The clumping index (CI) is useful in ecological and meteorological models because it provides new structural information in addition to the effective leaf area index. Previously generated CI maps using a diverse set of Earth Observation multi-angle datasets across a wide range of scales have all relied on the single approach of using the normalized difference hotspot and darkspot (NDHD) method. We explore an alternative approach to estimate CI from space using the unique observing configuration of the Deep Space Climate Observatory Earth Polychromatic Imaging Camera (DSCOVR EPIC) and associated products at 10 km resolution. The performance was evaluated with in situ measurements in five sites of the Australian Terrestrial Ecosystem Research Network comprising a diverse range of canopy structure from short and sparse to dense and tall forest. The DSCOVR EPIC data can provide meaningful CI retrievals at the given spatial resolution. Independent but comparable CI retrievals obtained with a completely different sensor and new approach were encouraging for the general validity and compatibility of the foliage clumping information retrievals from space. We also assessed the spatial representativeness of the five TERN sites with respect to a particular point in time (field campaigns) for satellite retrieval validation. Our results improve our understanding of product uncertainty both in terms of the representativeness of the field data collected over the TERN sites and its relationship to Earth Observation data at different spatial resolutions.
Discriminating Spontaneous From Cigarette Smoke and THS 2.2 Aerosol Exposure-Related Proliferative Lung Lesions in A/J Mice by Using Gene Expression and Mutation Spectrum Data
Authors: Xiang Yang , Luettich Karsta , Martin Florian , Battey James N. D. , Trivedi Keyur , Neau Laurent , Wong Ee Tsin , Guedj Emmanuel , Dulize Remi , Peric Dariusz , Bornand David , Ouadi Sonia , Sierro Nicolas , Büttner Ansgar , Ivanov Nikolai V. , Vanscheeuwijck Patrick , Hoeng Julia , Peitsch Manuel C.
Published: March 2021

Mice, especially A/J mice, have been widely employed to elucidate the underlying mechanisms of lung tumor formation and progression and to derive human-relevant modes of action. Cigarette smoke (CS) exposure induces tumors in the lungs; but, non-exposed A/J mice will also develop lung tumors spontaneously with age, which raises the question of discriminating CS-related lung tumors from spontaneous ones. However, the challenge is that spontaneous tumors are histologically indistinguishable from the tumors occurring in CS-exposed mice. We conducted an 18-month inhalation study in A/J mice to assess the impact of lifetime exposure to Tobacco Heating System (THS) 2.2 aerosol relative to exposure to 3R4F cigarette smoke (CS) on toxicity and carcinogenicity endpoints. To tackle the above challenge, a 13-gene gene signature was developed based on an independent A/J mouse CS exposure study, following by a one-class classifier development based on the current study. Identifying gene signature in one data set and building classifier in another data set addresses the feature/gene selection bias which is a well-known problem in literature. Applied to data from this study, this gene signature classifier distinguished tumors in CS-exposed animals from spontaneous tumors. Lung tumors from THS 2.2 aerosol-exposed mice were significantly different from those of CS-exposed mice but not from spontaneous tumors. The signature was also applied to human lung adenocarcinoma gene expression data (from The Cancer Genome Atlas) and discriminated cancers in never-smokers from those in ever-smokers, suggesting translatability of our signature genes from mice to humans. A possible application of this gene signature is to discriminate lung cancer patients who may benefit from specific treatments (i.e., EGFR tyrosine kinase inhibitors). Mutational spectra from a subset of samples were also utilized for tumor classification, yielding similar results. “Landscaping” the molecular features of A/J mouse lung tumors highlighted, for the first time, a number of events that are also known to play a role in human lung tumorigenesis, such as Lrp1b mutation and Ros1 overexpression. This study shows that omics and computational tools provide useful means of tumor classification where histopathological evaluation alone may be unsatisfactory to distinguish between age- and exposure-related lung tumors.
Az arc-állcsont régióban végzett csontpótló műtétek összehasonlító Cone Beam Computed Tomography (CBCT) vizsgálatára alkalmas mérési módszer definiálása és standardizálása
Authors: Decker Roland , Fábián Zoltán , Decker Iván , Bogdán Sándor , Restár László , Dúcz András , Németh Zsolt , Huszár Tamás
Published: March 2021

Az arc-állcsont régióban végzett csontpótló műtétek eredményességének objektív összehasonlító vizsgálata nem megoldott.Ennek oka, hogy a fogászatban, szájsebészetben alkalmazott képalkotó eljárásokkal különböző időpontokbankészített felvételek objektív összehasonlítása nehézségekbe ütközik. Léteznek software-ek, melyek alkalmasak összehasonlítóvizsgálatokra, de alkalmazásuk nehézkes, az eredmények nem megbízhatók. Az arc-állcsont régióban alkalmazható,standardizált összehasonlító eljárás még nincs kidolgozva.Célkitűzés: 1) Csontpótló műtétek összehasonlító CBCT (Cone Beam Computed Tomography) analízisére alkalmasmódszer létrehozása és ellenőrzése. 2) Módszertani ajánlás készítése.Anyag és módszer: 6 páciens két különböző időpontban készült CBCT felvételeinek összehasonlítása történt HorosTMorvosi képfeldolgozó programmal, illesztési hiba meghatározása alapján. A vizsgálatot 4 független személy végezte.Vizsgálati csoportok: 1) Standard anatómiai pontok alapján végzett mérések, 2) Egyedi radiológiai pontok alapján végzettmérések.Statisztika: minden vizsgáló által 3 mérés/eset. Értékelés: Mann-Whitney U teszt (SD /Standard Deviaton/ p ≤ 0,05).Eredmények: Az illesztési hiba mértéke minden vizsgáló esetében szignifikánsan alacsonyabb volt az egyedi pontokáltal mért esetekben, az anatómiai pontok alapján mért értékekhez képest (vizsgáló 1: 0,463 ± 0,103 vs. 0,283 ± 0,030;vizsgáló 2: 0,499 ± 0,100 vs. 0,318 ± 0,040; vizsgáló 3: 0,647 ± 0,555 vs. 0,291 ± 0,388; vizsgáló 4: 0,607 ± 0,069 vs.0,281 ± 0,033).Következtetések: A HorosTM képfeldolgozó programmal végzett illesztési hiba mérési módszerrel lehetséges objektívösszehasonlító vizsgálatot végezni ugyanazon személy két eltérő időpontban készült CBCT felvételén. Legpontosabbméréseket, a lehető legnagyobb háromszöget körülhatároló, három, egyedi radiológiai mintázatot jelölő pont kijelölésévellehet elérni.
Új terápiás lehetőségek odontomák kezelésében
Authors: Trimmel Bálint , Nagy Zoltán , Gyulai-Gaál Szabolcs
Published: March 2021

Az odontomák benignus, hám- és kötőszöveti elemeket vegyesen tartalmazó odontogén daganatok. Irodalmi adatokalapján teljes exstirpatiójuk mellett recidíva ritkán jelentkezik. Esetünkben két évvel korábban operált, complex odontomarecidívájánakkétlépcsős műtéti ellátását mutatjuk be. A 20 éves páciens jobb oldali angulus mandibulae területérelokalizálódó abscessusszal jelentkezett, képalkotó felvételek alapján az angulus mandibulaenak megfelelő területetodontomának imponáló képlet és az impaktált jobb alsó bölcsességfog töltötte ki. Az állkapocstörés és nervusalveolaris sérülésveszélye miatt kétlépcsős műtéti eljárás mellett döntöttünk intraoralis feltárásból. Az első műtét soránaz odontoma eltávolítását, valamint a csontdefektus marsupialisatióját végeztük. 4 hónappal később a második műtét alkalmávaleltávolítottuk a jobb alsó bölcsességfogat, valamint a csontdefektust fedő hámborítást. A műtét során a nervusalveolaris inferior nem sérült, a keletkezett csontdefektust platelet-rich fibrinnel töltöttük fel, a műtéti területet per primamzártuk. A gyógyulás komplikációmentesen zajlott, három hónap alatt a korábbi műtéti területen az egészséges anatómiaiviszonyok rekonstrukcióját értük el.
The Impact of Crop Diversification on the Economic Efficiency of Small Farms in Poland
Authors: Kurdyś-Kujawska Agnieszka , Strzelecka Agnieszka , Zawadzka Danuta
Published: March 2021

Crop diversification finds an important place in the strategy of dealing with risk and uncertainty related to climate change. It helps to increase the resilience of farmers, significantly improving their income stability, but at the same time, it can lower the economic efficiency of small farms. The aim of the article is to identify the determinants of crop diversification and the impact of crop diversification on the economic efficiency of small farms in Poland. This article first provides a critical review of the literature on crop diversification, its role in stabilizing agricultural income and its impact on economic efficiency in small farms. Secondly, the level of crop diversification was determined and empirical research was conducted considering the economic, social and agronomic characteristics of farms. Thirdly, the economic efficiency of farms diversifying crops was compared with farms focused on one type of production. The research material consisted of small farms participating in the Polish system of collecting and using farm accountancy data (FADN) in 2018. The level of diversification was determined using the Herfindahl-Hirschman Index. The factors influencing crop diversification were identified using the logit regression model. The Mann–Whitney U rank sum test was used to assess the significance of the differences in distributions. The research results indicate an average level of crop diversification in small farms in Poland and its regional differentiation. In addition, a statistically significant positive impact on the probability of crop diversification in small farms in Poland was found of variables such as the level of exposure of agricultural production to atmospheric and agricultural drought and the location of the farm in the frost hardiness zone and a statistically significant negative impact of the variable: value of fixed assets. The existence of significant differences in the level of economic efficiency of farms diversifying crops and farms focused on one profile of agricultural production was proved. The study is an important voice in the discussion on increasing measures to strengthen support for small farms that diversify crops so as to ensure their greater stability and economic efficiency.
Overexpression of DUF538 from Wild Arachis Enhances Plant Resistance to Meloidogyne spp.
Authors: Araujo Ana Claudia Guerra , Guimaraes Patricia Messenberg , Mota Ana Paula Zotta , Guimaraes Larissa Arrais , Pereira Bruna Medeiros , Vinson Christina Cleo , Lacerda Ana Luíza , Martins Andressa Cunha Quintana , Brasileiro Ana Cristina Miranda
Published: March 2021

DUF538 proteins belong to a large group of uncharacterized protein families sharing the highly conserved Domain of Unknown Function (DUF). Attention has been given to DUF538 domain-containing proteins due to changes in their gene expression behavior and protein abundance during plant development and responses to stress. Putative roles attributed to DUF538 in plants under abiotic and biotic constraints include involvement in cell redox balance, chlorophyll breakdown and pectin degradation. Our previous transcriptome studies suggested that DUF538 is also involved in the resistance responses of wild Arachis species against the highly hazardous root-knot nematodes (RKNs). To clarify the role of the AsDUF538 gene from the wild peanut relative Arachis stenosperma in this interaction, we analyzed the effect of its overexpression on RKN infection in peanut and soybean hairy roots and Arabidopsis transgenic plants. AsDUF538 overexpression significantly reduced the infection in all three heterologous plant systems against their respective RKN counterparts. The distribution of AsDUF538 transcripts in RKN-infected Arachis roots and the effects of AsDUF538 overexpression on hormonal pathways and redox system in transgenic Arabidopsis were also evaluated. This is the first time that a DUF538 gene is functionally validated in transgenic plants and the earliest report on its role in plant defense against RKNs.
Successive Harvests Modulate the Productive and Physiological Behavior of Three Genovese Pesto Basil Cultivars
Authors: Formisano Luigi , Ciriello Michele , El-Nakhel Christophe , Kyriacou Marios C. , Rouphael Youssef
Published: March 2021

In the Italian culinary tradition, young and tender leaves of Genovese basil (Ocimum basilicum L.) are used to prepare pesto sauce, a tasty condiment that attracts the interest of the food processing industry. Like other leafy or aromatic vegetables, basil is harvested more than once during the crop cycle to maximize yield. However, the mechanical stress induced by successive cuts can affect crucial parameters associated with pesto processing (leaf/stem ratio, stem diameter, and dry matter). Our research accordingly aimed to evaluate the impact of successive harvests on three field-grown Genovese basil cultivars (“Aroma 2”, “Eleonora” and “Italiano Classico”) in terms of production, physiological behavior, and technological parameters. Between the first and second harvest, marketable fresh yield and shoot dry biomass increased by 148.4% and 172.9%, respectively; by contrast, the leaf-to-stem ratio decreased by 22.5%, while the dry matter content was unchanged. The increased fresh yield and shoot dry biomass at the second harvest derived from improved photosynthetic efficiency, which enabled higher net CO2 assimilation, Fv/Fm and transpiration as well as reduced stomatal resistance. Our findings suggest that, under the Mediterranean environment, “Italiano Classico” carries superior productive performance and optimal technological characteristics in line with industrial requirements. These promising results warrant further investigation of the impact successive harvests may have on the qualitative components of high-yielding basil genotypes with respect to consumer expectations of the final product.
Seroconversion to Brucella spp. and Toxoplasma gondii in Sheep and Goats in Dohuk Province, Iraq and Its Association with Pregnancy Loss
Authors: Al Hamada Ali , Habib Ihab , Bruce Mieghan , Barnes Anne , Robertson Ian D.
Published: March 2021

In this study, sera from 240 small ruminants (192 sheep and 48 goats) belonging to 12 farms in Dohuk Province, northern Iraq, were collected on two occasions to investigate the incidence risk of seroconversion to Brucella spp. and Toxoplasma gondii. All selected animals were confirmed pregnant (approximately 2 months pregnant) by ultrasound examination at the time of the first blood collection. A second ultrasound examination and blood sampling were undertaken two months after the initial scanning/sampling. Antibodies to Brucella were tested using the Rose Bengal Test (RBT) and an indirect enzyme-linked immunosorbent assay (iELISA), and the results were interpreted in series. The Latex Agglutination Test (LAT) and an indirect enzyme-linked immunosorbent assay (iELISA) were also used in series to confirm the presence of antibodies to T. gondii. The seroprevalence for Brucella and Toxoplasma increased significantly between the two sampling times (p = 0.0003 and 0.03 in first and second sampling, respectively). The incidence risk of seroconversion to Brucella over the two months was 10.6% (95% CI: 6.9–15.3) and 7.3% (95% CI: 4.3–11.6) for Toxoplasma. Animals that seroconverted to Brucella were 2.9 times more likely to lose their pregnancy (95% CI: 1.6–5.5) than animals that remained seronegative; however, seroconversion to Toxoplasma had no significant impact on loss of pregnancy. This study is the first reported investigation on the association of seroconversion to Brucella and Toxoplasma with the reproductive outcome of pregnant sheep and goats in northern Iraq. Brucellosis and toxoplasmosis continue to negatively impact small ruminants’ reproductive performance and compromising food security in Iraq. It is hoped that this study will assist the development of a better-informed economic model to estimate Brucella and Toxoplasma burden in small animals in northern Iraq, and such a model could be used to validate the impact of various potential intervention programs in.
Mechanisms Modified by (−)-Epicatechin and Taxifolin Relevant for the Treatment of Hypertension and Viral Infection: Knowledge from Preclinical Studies
Authors: Bernatova Iveta , Liskova Silvia
Published: March 2021

Various studies have shown that certain flavonoids, flavonoid-containing plant extracts, and foods can improve human health. Experimental studies showed that flavonoids have the capacity to alter physiological processes as well as cellular and molecular mechanisms associated with their antioxidant properties. An important function of flavonoids was determined in the cardiovascular system, namely their capacity to lower blood pressure and to improve endothelial function. (−)-Epicatechin and taxifolin are two flavonoids with notable antihypertensive effects and multiple beneficial actions in the cardiovascular system, but they also possess antiviral effects, which may be of particular importance in the ongoing pandemic situation. Thus, this review is focused on the current knowledge of (−)-epicatechin as well as (+)-taxifolin and/or (−)-taxifolin-modified biological action and underlining molecular mechanisms determined in preclinical studies, which are relevant not only to the treatment of hypertension per se but may provide additional antiviral benefits that could be relevant to the treatment of hypertensive subjects with SARS-CoV-2 infection.
Reprograming of Tumor-Associated Macrophages in Breast Tumor-Bearing Mice under Chemotherapy by Targeting Heme Oxygenase-1
Authors: Kim Seung Hyeon , Kim Su-Jung , Park Jeongmin , Joe Yeonsoo , Lee So Eui , Saeidi Soma , Zhong Xiancai , Kim Seong Hoon , Park Sin-Aye , Na Hye-Kyung , Chung Hun Taeg , Surh Young-Joon
Published: March 2021

Tumor-associated macrophages (TAMs) represent one of the most abundant components of the tumor microenvironment and play important roles in tumor development and progression. TAMs display plasticity and functional heterogeneity as reflected by distinct phenotypic subsets. TAMs with an M1 phenotype have proinflammatory and anti-tumoral properties whereas M2-like TAMs exert anti-inflammatory and pro-tumoral functions. Tumor cell debris generated during chemotherapy can stimulate primary tumor growth and recurrence. According to our previous study, phagocytic engulfment of breast tumor cell debris by TAMs attenuated chemotherapeutic efficacy through the upregulation of heme oxygenase-1 (HO-1). To verify the impact of HO-1 upregulation on the profile of macrophage polarization during cytotoxic therapy, we utilized a syngeneic murine breast cancer (4T1) model in which tumor bearing mice were treated with paclitaxel (PTX). PTX treatment markedly downregulated the surface expression of the M1 marker CD86 in infiltrated TAMs. Notably, there were significantly more cytotoxic CD8+ T cells in tumors of mice treated with PTX plus the HO-1 inhibitor, zinc protophorphyrin IX (ZnPP) than in mice treated with PTX alone. Interestingly, the tumor-inhibiting efficacy of PTX and ZnPP co-treatment was abrogated when macrophages were depleted by clodronate liposomes. Macrophage depletion also decreased the intratumoral CD8+ T cell population and downregulated the expression of Cxcl9 and Cxcl10. The expression of the M1 phenotype marker, CD86 was higher in mice injected with PTX plus ZnPP than that in mice treated with PTX alone. Conversely, the PTX-induced upregulation of the M2 marker gene, Il10 in CD11b+ myeloid cells from 4T1 tumor-bearing mice treated was dramatically reduced by the administration of the HO-1 inhibitor. Genetic ablation of HO-1 abolished the inhibitory effect of 4T1 tumor cell debris on expression of M1 marker genes, Tnf and Il12b, in LPS-stimulated BMDMs. HO-1-deficient BMDMs exposed to tumor cell debris also exhibited a diminished expression of the M2 macrophage marker, CD206. These findings, taken all together, provide strong evidence that HO-1 plays a pivotal role in the transition of tumor-inhibiting M1-like TAMs to tumor-promoting M2-like ones during chemotherapy.