bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical Assessment of the Validity of Sheep as a Preclinical Model for Testing Mandibular Fracture Fixation Devices
Authors: Orassi Vincenzo , Duda Georg N. , Heiland Max , Fischer Heilwig , Rendenbach Carsten , Checa Sara
Published: May 2021

Mandibular fracture fixation and reconstruction are usually performed using titanium plates and screws, however, there is a need to improve current fixation techniques. Animal models represent an important step for the testing of new designs and materials. However, the validity of those preclinical models in terms of implant biomechanics remains largely unknown. In this study, we investigate the biomechanics of the sheep mandible as a preclinical model for testing the mechanical strength of fixation devices and the biomechanical environment induced on mandibular fractures. We aimed to assess the comparability of the biomechanical conditions in the sheep mandible as a preclinical model for human applications of fracture fixation devices and empower analyses of the effect of such defined mechanical conditions on bone healing outcome. We developed 3D finite element models of the human and sheep mandibles simulating physiological muscular loads and three different clenching tasks (intercuspal, incisal, and unilateral). Furthermore, we simulated fractures in the human mandibular body, sheep mandibular body, and sheep mandibular diastema fixated with clinically used titanium miniplates and screws. We compared, at the power stroke of mastication, the biomechanical environment (1) in the healthy mandibular body and (2) at the fracture sites, and (3) the mechanical solicitation of the implants as well as the mechanical conditions for bone healing in such cases. In the healthy mandibles, the sheep mandibular body showed lower mechanical strains compared to the human mandibular body. In the fractured mandibles, strains within a fracture gap in sheep were generally not comparable to humans, while similar or lower mechanical solicitation of the fixation devices was found between the human mandibular body fracture and the sheep mandibular diastema fracture scenarios. We, therefore, conclude that the mechanical environments of mandibular fractures in humans and sheep differ and our analyses suggest that the sheep mandibular bone should be carefully re-considered as a model system to study the effect of fixation devices on the healing outcome. In our analyses, the sheep mandibular diastema showed similar mechanical conditions for fracture fixation devices to those in humans.
Monetary Dynamics With Proof of Stake
Authors: Dimitri Nicola
Published: May 2021

In recent years blockchain consensus mechanisms based on Proof of Stake gained increasing attention as an alternative to Proof of Work, which requires high energy consumption. In its original version Proof of Stake hinges on the idea that, for a user, the likelihood to confirm the next block is positively related to the amount of currency units held in the wallet, and possibly also on the time length which the money has been unspent for. In a simple framework with risk neutral users we provide some early insights on the monetary equilibrium of Proof of Stake based platforms. In particular, we find that the aggregate demand and supply of currency may not coincide, which implies that users could hold suboptimal quantities of the currency. Furthermore, we also discuss how symmetric stationary states of the system could be implausible. As a consequence, a long run uniform distribution of money would seem unlikely unless appropriate measures are introduced.
Epigenetics and Heart Development
Authors: George Rajani M. , Firulli Anthony B.
Published: May 2021

Epigenetic control of gene expression during cardiac development and disease has been a topic of intense research in recent years. Advances in experimental methods to study DNA accessibility, transcription factor occupancy, and chromatin conformation capture technologies have helped identify regions of chromatin structure that play a role in regulating access of transcription factors to the promoter elements of genes, thereby modulating expression. These chromatin structures facilitate enhancer contacts across large genomic distances and function to insulate genes from cis-regulatory elements that lie outside the boundaries for the gene of interest. Changes in transcription factor occupancy due to changes in chromatin accessibility have been implicated in congenital heart disease. However, the factors controlling this process and their role in changing gene expression during development or disease remain unclear. In this review, we focus on recent advances in the understanding of epigenetic factors controlling cardiac morphogenesis and their role in diseases.
Molecular Markers Reveal Epidemiological Patterns and Evolutionary Histories of the Human Pathogenic Cryptococcus
Authors: Hong Nan , Chen Min , Xu Jianping
Published: May 2021

The human pathogenic Cryptococcus species are the main agents of fungal meningitis in humans and the causes of other diseases collectively called cryptococcosis. There are at least eight evolutionary divergent lineages among these agents, with different lineages showing different geographic and/or ecological distributions. In this review, we describe the main strain typing methods that have been used to analyze the human pathogenic Cryptococcus and discuss how molecular markers derived from the various strain typing methods have impacted our understanding of not only cryptococcal epidemiology but also its evolutionary histories. These methods include serotyping, multilocus enzyme electrophoresis, electrophoretic karyotyping, random amplified polymorphic DNA, restriction fragment length polymorphism, PCR-fingerprinting, amplified fragment length polymorphism, multilocus microsatellite typing, single locus and multilocus sequence typing, matrix-assisted laser desorption/ionization time of flight mass spectrometry, and whole genome sequencing. The major findings and the advantages and disadvantages of each method are discussed. Together, while controversies remain, these strain typing methods have helped reveal (i) the broad phylogenetic pattern among these agents, (ii) the centers of origins for several lineages and their dispersal patterns, (iii) the distributions of genetic variation among geographic regions and ecological niches, (iv) recent hybridization among several lineages, and (v) specific mutations during infections within individual patients. However, significant challenges remain. Multilocus sequence typing and whole genome sequencing are emerging as the gold standards for continued strain typing and epidemiological investigations of cryptococcosis.
Deinococcus radiodurans UWO298 Dependence on Background Radiation for Optimal Growth
Authors: Castillo Hugo , Li Xiaoping , Smith Geoffrey B.
Published: May 2021

Ionizing radiation is a major environmental variable for cells on Earth, and so organisms have adapted to either prevent or to repair damages caused by it, primarily from the appearance and accumulation of reactive oxygen species (ROS). In this study, we measured the differential gene expression in Deinococcus radiodurans UWO298 cultures deprived of background ionizing radiation (IR) while growing 605 m underground at the Waste Isolation Pilot Plant (WIPP), reducing the dose rate from 72.1 to 0.9 nGy h–1 from control to treatment, respectively. This reduction in IR dose rate delayed the entry into the exponential phase of the IR-shielded cultures, resulting in a lower biomass accumulation for the duration of the experiment. The RNASeq-based transcriptome analysis showed the differential expression of 0.2 and 2.7% of the D. radiodurans genome after 24 and 34 h of growth in liquid culture, respectively. Gene expression regulation after 34 h was characterized by the downregulation of genes involved in folding newly synthesized and denatured/misfolded proteins, in the assimilation of nitrogen for amino acid synthesis and in the control of copper transport and homeostasis to prevent oxidative stress. We also observed the upregulation of genes coding for proteins with transport and cell wall assembly roles. These results show that D. radiodurans is sensitive to the absence of background levels of ionizing radiation and suggest that its transcriptional response is insufficient to maintain optimal growth.
Tumor Immune Microenvironment Characterization Identifies Prognosis and Immunotherapy-Related Gene Signatures in Melanoma
Authors: Liu Dan , Yang Xue , Wu Xiongzhi
Published: May 2021

Background

The tumor microenvironment (TME) involves infiltration of multiple immune cell subsets, which could influence the prognosis and clinical characteristics. The increasing evidence on the role of tumor-infiltrating lymphocytes (TILs) in primary and metastatic melanomas supports that the immune system is involved in the progression and outcomes of melanoma. However, the immune infiltration landscape in melanoma has not been systematically elucidated.

Methods

In this study, we used CIBERSORT and ESTIMATE algorithms to analyze immune infiltration pattern of 993 melanoma samples. Then we screened differential expression genes (DEGs) related to immune subtypes and survival. The immune cell infiltration (ICI) score was constructed by using principal-component analysis (PCA) based on immune signature genes from DGEs. Gene set enrichment analysis (GSEA) was applied to explore high and low ICI score related pathways. Finally, the predictive ability of ICI score was evaluated in survival prognosis and immunotherapy benefit.

Result

We identified three ICI clusters and three gene clusters associated with different immune subtypes and survival outcomes. Then the ICI score was constructed, and we found that high ICI score exhibited activated immune characteristics and better prognosis. High ICI score was significantly enriched in immune pathways and highly expressed immune signature genes. More importantly, we confirmed that melanoma patients with high ICI score had longer overall survival and rate of response to immunotherapy.

Conclusion

We presented a comprehensive immune infiltration landscape in melanoma. Our results will facilitate understanding of the melanoma tumor microenvironment and provide a new immune therapy strategy.
Biological Soil Crust Bacterial Communities Vary Along Climatic and Shrub Cover Gradients Within a Sagebrush Steppe Ecosystem
Authors: You Yaqi , Aho Ken , Lohse Kathleen A. , Schwabedissen Stacy G. , Ledbetter Rhesa N. , Magnuson Timothy S.
Published: May 2021

Numerous studies have examined bacterial communities in biological soil crusts (BSCs) associated with warm arid to semiarid ecosystems. Few, however, have examined bacterial communities in BSCs associated with cold steppe ecosystems, which often span a wide range of climate conditions and are sensitive to trends predicted by relevant climate models. Here, we utilized Illumina sequencing to examine BSC bacterial communities with respect to climatic gradients (elevation), land management practices (grazing vs. non-grazing), and shrub/intershrub patches in a cold sagebrush steppe ecosystem in southwestern Idaho, United States. Particular attention was paid to shifts in bacterial community structure and composition. BSC bacterial communities, including keystone N-fixing taxa, shifted dramatically with both elevation and shrub-canopy microclimates within elevational zones. BSC cover and BSC cyanobacteria abundance were much higher at lower elevation (warmer and drier) sites and in intershrub areas. Shrub-understory BSCs were significantly associated with several non-cyanobacteria diazotrophic genera, including Mesorhizobium and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium. High elevation (wetter and colder) sites had distinct, highly diverse, but low-cover BSC communities that were significantly indicated by non-cyanobacterial diazotrophic taxa including families in the order Rhizobiales and the family Frankiaceae. Abiotic soil characteristics, especially pH and ammonium, varied with both elevation and shrub/intershrub level, and were strongly associated with BSC community composition. Functional inference using the PICRUSt pipeline identified shifts in putative N-fixing taxa with respect to both the elevational gradient and the presence/absence of shrub canopy cover. These results add to current understanding of biocrust microbial ecology in cold steppe, serving as a baseline for future mechanistic research.
Biogeography and Ecology of Magnaporthales: A Case Study
Authors: Feng Jia-Wei , Liu Wei-Ting , Chen Jia-Jie , Zhang Chu-Long
Published: May 2021

The order Magnaporthales belongs to Sordariomycetes, Ascomycota. Magnaporthales includes five families, namely Ceratosphaeriaceae, Pseudohalonectriaceae, Ophioceraceae, Pyriculariaceae, and Magnaporthaceae. Most Magnaporthales members are found in Poaceae plants and other monocotyledonous herbaceous plants ubiquitously as plant pathogens or endophytic fungi, and some members are found in decaying wood or dead grass as saprophytic fungi. Therefore, studying the biogeography and ecology of Magnaporthales is of great significance. Here, we described the biodiversity of endophytic Magnaporthales fungi from Poaceae at three latitudes in China and conducted a meta-analysis of the geography and ecology of Magnaporthales worldwide. We found that Magnaporthales is a dominant order in the endophytic fungi of Poaceae. More than half of the endophytic Magnaporthales fungi have a taxonomically uncertain placement. Notably, few endophytic fungi are grouped in the clusters with known saprophytic or pathogenic Magnaporthales fungi, indicating that they may have saprophytic and parasitic differentiation in nutritional modes and lifestyles. The meta-analysis revealed that most species of Magnaporthales have characteristic geographical, host, and tissue specificity. The geographical distribution of the three most studied genera, namelyGaeumannomyces,Magnaporthiopsis, andPyricularia, in Magnaporthales may depend on the distribution of their hosts. Therefore, studies on the endophytic fungal Magnaporthales from monocotyledonous plants, including Poaceae, in middle and low latitudes will deepen our understanding of the biogeography and ecology of Magnaporthales.
Long-Term Administration of Triterpenoids From Ganoderma lucidum Mitigates Age-Associated Brain Physiological Decline via Regulating Sphingolipid Metabolism and Enhancing Autophagy in Mice
Authors: Zeng Miao , Qi Longkai , Guo Yinrui , Zhu Xiangxiang , Tang Xiaocui , Yong Tianqiao , Xie Yizhen , Wu Qingping , Zhang Mei , Chen Diling
Published: May 2021

With the advent of the aging society, how to grow old healthily has become an important issue for the whole of society. Effective intervention strategies for healthy aging are most desired, due to the complexity and diversity of genetic information, it is a pressing concern to find a single drug or treatment to improve longevity. In this study, long-term administration of triterpenoids of Ganoderma lucidum (TGL) can mitigate brain physiological decline in normal aging mice. In addition, the age-associated pathological features, including cataract formation, hair loss, and skin relaxation, brown adipose tissue accumulation, the β-galactosidase staining degree of kidney, the iron death of spleen, and liver functions exhibit improvement. We used the APP/PS1 mice and 3 × Tg-AD mice model of Alzheimer’s Disease (AD) to further verify the improvement of brain function by TGL and found that Ganoderic acid A might be the effective constituent of TGL for anti-aging of the brain in the 3 × Tg-AD mice. A potential mechanism of action may involve the regulation of sphingolipid metabolism, prolonging of telomere length, and enhance autophagy, which allows for the removal of pathological metabolites.
Machine Learning for the Diagnosis of Parkinson's Disease: A Review of Literature
Authors: Mei Jie , Desrosiers Christian , Frasnelli Johannes
Published: May 2021

Diagnosis of Parkinson's disease (PD) is commonly based on medical observations and assessment of clinical signs, including the characterization of a variety of motor symptoms. However, traditional diagnostic approaches may suffer from subjectivity as they rely on the evaluation of movements that are sometimes subtle to human eyes and therefore difficult to classify, leading to possible misclassification. In the meantime, early non-motor symptoms of PD may be mild and can be caused by many other conditions. Therefore, these symptoms are often overlooked, making diagnosis of PD at an early stage challenging. To address these difficulties and to refine the diagnosis and assessment procedures of PD, machine learning methods have been implemented for the classification of PD and healthy controls or patients with similar clinical presentations (e.g., movement disorders or other Parkinsonian syndromes). To provide a comprehensive overview of data modalities and machine learning methods that have been used in the diagnosis and differential diagnosis of PD, in this study, we conducted a literature review of studies published until February 14, 2020, using the PubMed and IEEE Xplore databases. A total of 209 studies were included, extracted for relevant information and presented in this review, with an investigation of their aims, sources of data, types of data, machine learning methods and associated outcomes. These studies demonstrate a high potential for adaptation of machine learning methods and novel biomarkers in clinical decision making, leading to increasingly systematic, informed diagnosis of PD.
Intracranial Atherosclerotic Burden and Cerebral Parenchymal Changes at 7T MRI in Patients With Transient Ischemic Attack or Ischemic Stroke
Authors: Lindenholz Arjen , de Bresser Jeroen , van der Kolk Anja G. , van der Worp H. Bart , Witkamp Theodoor D. , Hendrikse Jeroen , van der Schaaf Irene C.
Published: May 2021

The relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; www.trialregister.nl), 7T MRI was used to investigate if a higher vessel wall lesion burden is associated with more cerebral parenchymal changes in patients with ischemic stroke or transient ischemic attack (TIA). MR images of 82 patients were assessed for the number of vessel wall lesions of the large intracranial arteries and for cerebral parenchymal changes, including the presence and number of cortical, small subcortical, and deep gray matter infarcts; lacunes of presumed vascular origin; cortical microinfarcts; and periventricular and deep white matter hyperintensities (WMHs). Regression analyses showed that a higher vessel wall lesion burden was associated with the presence of small subcortical infarcts, lacunes of presumed vascular origin, and deep gray matter infarcts (relative risk 1.18; 95% CI, 1.03–1.35) and presence of moderate-to-severe periventricular WMHs (1.21; 95% CI, 1.03–1.42), which are all manifestations of small vessel disease (SVD). The burden of enhancing vessel wall lesions was associated with the number of cortical microinfarcts only (1.48; 95% CI, 1.04–2.11). These results suggest an interrelationship between large vessel wall lesion burden and cerebral parenchymal manifestations often linked to SVD or, alternatively, that vascular changes occur in both large and small intracranial arteries simultaneously.
SMA Identified: Clinical and Molecular Findings From a Sponsored Testing Program for Spinal Muscular Atrophy in More Than 2,000 Individuals
Authors: Bowen B. Monica , Truty Rebecca , Aradhya Swaroop , Bristow Sara L. , Johnson Britt A. , Morales Ana , Tan Christopher A. , Westbrook M. Jody , Winder Thomas L. , Chavez Juan C.
Published: May 2021

Background: Spinal muscular atrophy (SMA) linked to chromosome 5q is an inherited progressive neuromuscular disorder with a narrow therapeutic window for optimal treatment. Although genetic testing provides a definitive molecular diagnosis that can facilitate access to effective treatments, limited awareness and other barriers may prohibit widespread testing. In this study, the clinical and molecular findings of SMA Identified—a no-charge sponsored next-generation sequencing (NGS)-based genetic testing program for SMA diagnosis—are reported.

Methods: Between March 2018 and March 2020, unrelated individuals who had a confirmed or suspected SMA diagnosis or had a family history of SMA were eligible. All individuals underwent diagnostic genetic testing for SMA at clinician discretion. In total, 2,459 individuals were tested and included in this analysis. An NGS-based approach interrogated sequence and copy number of SMN1 and SMN2. Variants were confirmed by multiplex ligation-dependent probe amplification sequencing. Individuals were categorized according to genetic test results: diagnostic (two pathogenic SMN1 variants), nearly diagnostic (SMN1 exon-7 deletion with a variant of uncertain significance [VUS] in SMN1 or SMN2), indeterminate VUS (one VUS in SMN1 or SMN2), carrier (heterozygous SMN1 deletion only), or negative (no pathogenic variants or VUS in SMN1 or SMN2). Diagnostic yield was calculated. Genetic test results were analyzed based on clinician-reported clinical features and genetic modifiers (SMN2 copy number and SMN2 c.859G>C).

Results: In total, 2,459 unrelated individuals (mean age 24.3 ± 23.0 years) underwent diagnostic testing. The diagnostic yield for diagnostic plus nearly diagnostic results was 31.3% (n = 771/2,459). Age of onset and clinical presentation varied considerably for individuals and was dependent on SMN2 copy number. Homozygous deletions represented the most common genetic etiology (96.2%), with sequence variants also observed in probands with clinical diagnoses of SMA.

Conclusions: Using a high-yield panel test in a no-charge sponsored program early in the diagnostic odyssey may open the door for medical interventions in a substantial number of individuals with SMA. These findings have potential implications for clinical management of probands and their families.
GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients
Authors: Buijink Arthur W. G. , Prent Naomi , Puts Nicolaas A. , Schrantee Anouk , Potters Wouter V. , van Rootselaar Anne-Fleur
Published: May 2021

Background: Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered in patients responsive to either anticonvulsants or β-adrenergic blockers.

Methods: In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using 1H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls.

Results: There were no group differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. There was no correlation with tremor severity.

Discussion: Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.
Treatment for the Benign Childhood Epilepsy With Centrotemporal Spikes: A Monocentric Study
Authors: Kessi Miriam , Yan Fangling , Pan Langui , Chen Baiyu , Olatoutou Eleonore , Li Dong , He Fang , Rugambwa Tibera , Yang Lifen , Peng Jing , Yin Fei
Published: May 2021

Background and Purpose: To date, there is no specific treatment guideline for the benign childhood epilepsy with centrotemporal spikes (BECTS). Several countries recommend levetiracetam, carbamazepine, sodium valproate, oxcarbazepine, and lamotrigine as first-line drugs. Nevertheless, some of these drugs are associated with cognitive decline. Available studies that investigated the efficacy of levetiracetam and sodium valproate on BECTS involved small sample sizes. This study aimed to evaluate the efficacy of levetiracetam and sodium valproate on cognition, and to investigate the prognostic factors for BECTS as whole.

Methods: Clinical data and treatment status of all patients with BECTS at Xiangya Hospital, Central South University followed from 2008 to 2013 were analyzed retrospectively. Since electrical status epilepticus in sleep (ESES) has been confirmed to play a role in cognitive deterioration, in order to evaluate the response to drugs and their cognitive effects, we created two groups of patients according to the levels of spike wave index (SWI): group 1; 0–50% SWI and group 2; >50% SWI at the last follow up.

Results: A total of 195 cases were enrolled: 49.7% received monotherapies, 24.1% duotherapies and 27.2% polytherapies. Medications included; levetiracetam plus other drug (s) (75.9%), levetiracetam alone (32.8%), sodium valproate plus other drug (s) (31.3%), and sodium valproate alone (5.1%). After 2 years of treatment and follow up, 71% of the cases had a good seizure outcome, 15.9% had an improvement of SWI, and 91.7% had a normal DQ/IQ. Sodium valproate combined with levetiracetam, and sodium valproate alone correlated with good improvement of SWI, whereas, focal spikes were linked with poor improvement. For both groups (group 1 and group 2): monotherapy, levetiracetam alone, and a normal DQ/IQ at seizure onset correlated with good cognitive outcomes, in contrast, polytherapy, sodium valproate plus other drug (s), levetiracetam plus sodium valproate, an initial SWI of ≥85%, and multifocal spikes were linked to cognitive deterioration.

Conclusions: Monotherapy, particularly levetiracetam seems to be a good first-line therapy which can help in normalizing the electroencephalograph and preventing cognitive decline. Polytherapy, mostly the administration of sodium valproate seems to relate with poor cognition, therefore, it is recommended to avoid it.
Characterization of Plasma Cell-Free DNA Integrity Using Droplet-Based Digital PCR: Toward the Development of Circulating Tumor DNA-Dedicated Assays
Authors: Poulet Geoffroy , Garlan Fanny , Garrigou Sonia , Zonta Eleonora , Benhaim Leonor , Carrillon Marie-Jennifer , Didelot Audrey , Le Corre Delphine , Mulot Claire , Nizard Philippe , Ginot Frederic , Boutonnet-Rodat Audrey , Blons Helene , Bachet Jean-Baptiste , Taïeb Julien , Zaanan Aziz , Geromel Vanna , Pellegrina Laurence , Laurent-Puig Pierre , Wang-Renault Shu-Fang , Taly Valerie
Published: May 2021

Background: Cellular-cell free-DNA (ccfDNA) is being explored as a diagnostic and prognostic tool for various diseases including cancer. Beyond the evaluation of the ccfDNA mutational status, its fragmentation has been investigated as a potential cancer biomarker in several studies. However, probably due to a lack of standardized procedures dedicated to preanalytical and analytical processing of plasma samples, contradictory results have been published.

Methods: ddPCR assays allowing the detection of KRAS wild-type and mutated sequences (KRAS p.G12V, pG12D, and pG13D) were designed to target different fragments sizes. Once validated on fragmented and non-fragmented DNA extracted from cancer cell lines, these assays were used to investigate the influence of the extraction methods on the non-mutated and mutated ccfDNA integrity reflected by the DNA integrity index (DII). The DII was then analyzed in two prospective cohorts of metastatic colorectal cancer patients (RASANC study n = 34; PLACOL study n = 12) and healthy subjects (n = 49).

Results and Discussion: Our results demonstrate that ccfDNA is highly fragmented in mCRC patients compared with healthy individuals. These results strongly suggest that the characterization of ccfDNA integrity hold great promise toward the development of a universal biomarker for the follow-up of mCRC patients. Furthermore, they support the importance of standardization of sample handling and processing in such analysis.
Osthole Ameliorates Estrogen Deficiency-Induced Cognitive Impairment in Female Mice
Authors: Adu-Nti Frank , Gao Xu , Wu Jia-Min , Li Jing , Iqbal Javed , Ahmad Riaz , Ma Xin-Ming
Published: May 2021

Loss of endogenous estrogen and dysregulation of the estrogen receptor signaling pathways are associated with an increase in risk for cognitive deficit and depression in women after menopause. Estrogen therapy for menopause increases the risk of breast and ovarian cancers, and stroke. Therefore, it is critical to find an alternate treatment for menopausal women. Osthole (OST), a coumarin, has been reported to have neuroprotective effects. This study examined whether OST improves ovariectomy (OVX)-induced cognitive impairment, and alleviates anxiety- and depression-like behaviors induced by OVX in mice. Adult female C57BL/6J mice were ovariectomized and then treated with OST at a dose of 30 mg/kg for 14 days. At the end of the treatment period, behavioral tests were used to evaluate spatial learning and memory, recognition memory, anxiety- and depression-like behaviors. A cohort of the mice were sacrificed after 14 days of OST treatment and their hippocampi were collected for measurement of the proteins of interest using western blot. OVX-induced alteration in the levels of proteins was accompanied by cognitive deficit, anxiety- and depression-like behaviors. OST treatment improved cognitive deficit, alleviated anxiety- and depression-like behaviors induced by OVX, and reversed OVX-induced alterations in the levels of synaptic proteins and ERα, BDNF, TrKB, p-CREB, p-Akt and Rac1 in the hippocampus. Therefore, reversal of OVX-induced decrease in the levels of hippocampal proteins by OST might contribute to the effects of OST on improving cognitive deficit and alleviating anxiety- and depression-like behaviors induced by OVX.
Clinical Insights Into Novel Immune Checkpoint Inhibitors
Authors: Lee Jii Bum , Ha Sang-Jun , Kim Hye Ryun
Published: May 2021

The success of immune checkpoint inhibitors (ICIs), notably anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as inhibitors of CTLA-4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1), has revolutionized treatment options for solid tumors. However, the lack of response to treatment, in terms of de novo or acquired resistance, and immune related adverse events (IRAE) remain as hurdles. One mechanisms to overcome the limitations of ICIs is to target other immune checkpoints associated with tumor microenvironment. Immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B7 homolog 3 protein (B7-H3), inducible T cell costimulatory (ICOS), and B and T lymphocyte attenuator (BTLA) are feasible and promising options for treating solid tumors, and clinical trials are currently under active investigation. This review aims to summarize the clinical aspects of the immune checkpoints and introduce novel agents targeting these checkpoints.
Student Self-Efficacy and Aptitude to Participate in Relation to Perceived Functioning and Achievement in Students in Secondary School With and Without Disabilities
Authors: Bertills Karin , Granlund Mats , Augustine Lilly
Published: May 2021

School-based Physical Education (PE) is important, especially to students with disabilities whose participation in physical activities out of school is limited. The development over time of participation-related constructs in relation to students’ perceived functioning and achievement is explored. Students in mainstream inclusive secondary school self-rated their PE-specific self-efficacy, general school self-efficacy, aptitude to participate in PE, and perceived physical and socio-cognitive functional skills at two timepoints, year 7 and year 9. Results were compared between three groups of students with: disabilities (n = 28), high grades (n = 47), or low grades (n = 30) in PE. Over time, perceived physical skills of students with disabilities became strongly associated with self-efficacy and aptitude to participate. Perceived socio-cognitive skills in the study sample improved and had a positive effect on PE-specific self-efficacy. Efforts should be made to limit the accelerated negative impact of perceived restricted functioning of students with disabilities. Grading criteria need to be developed to comply with standards adapted to fit abilities of students with disabilities. Meaningful learning experiences appear to be created when participation is promoted and capacity beliefs (PE-specific self-efficacy) are boosted. Allocating resources to support the development of students’ socio-cognitive skills seem to have potential for overall positive school outcome.
Depression and Creativity During COVID-19: Psychological Resilience as a Mediator and Deliberate Rumination as a Moderator
Authors: Xu Yanhua , Shao Jinlian , Zeng Wei , Wu Xingrou , Huang Dongtao , Zeng Yuqing , Wu Jiamin
Published: May 2021

Purpose:The pandemic of coronavirus disease 2019 (COVID-19), which has had a significant impact on people’s lives, has apparently increased the incidence of depression. Although the topic of how depression affects creativity is contested, previous research has revealed a significant relationship between the two. The purpose of this study is to further investigate the relationship and the mechanisms that operate between depression and creativity.

Methods:A total of 881 students at an independent college in China completed a questionnaire consisting of the Self-Reported Depression Scale, Runco Ideational Behavior Scale, Psychological Resilience Scale, Deliberate Rumination Scale and demographic information. Among the respondents, 317 (36.0%) were male and 564 (64.0%) were female, all of whom were from the same grade. Correlation analyses were conducted, and then the researchers carried out mediation analysis and developed a moderated mediation model.

Results:The results indicated that (a) depression was positively related to creativity (r= 0.085,p< 0.05); (b) psychological resilience mediated the relationship between depression and creativity; specifically, psychological resilience was negatively related to depression (r= −0.462,p< 0.01), which in turn was positively related to creativity (r= 0.198,p< 0.01); and (c) deliberate rumination moderated the relationship between depression and psychological resilience, showing a significant negative correlation with depression (r= 0.138,p< 0.01), psychological resilience (r= 0.078,p< 0.05), and creativity (r= 0.288,p< 0.05); specifically, higher levels of deliberate rumination strengthened the negative correlation between psychological resilience and depression.

Conclusion:The results suggest that depression is a positive predictor of creativity and may promote creativity to some extent. Further, individuals with greater psychological resilience are more creative than those with less psychological resilience, as it is a question of whether they can and to what extent they can effectively use depression as an emotional resource. Last, an individual’s level of deliberate rumination moderates the mediating process, especially at the stage where depression is associated with psychological resilience. These findings advance understanding of the mechanisms that operate between depression and creativity.
The Moderating Effect of Store Format on the Relationships Between ICT, Innovation and Sustainability in Retailing
Authors: Marín-García Antonio , Gil-Saura Irene , Ruiz-Molina María-Eugenia , Berenguer-Contrí Gloria
Published: May 2021

Innovation and sustainability are postulated as key variables for the future of large commercial distribution. In addition, the development of Information and Communication Technologies (ICT) solutions, and especially those related to Artificial Intelligence (i.e., Just Walk Out, Intelligent Retail Lab) and digitization, are particularly relevant factors in the current pandemic scenario in which retail companies operate. These tools are essential to face the derived changes in commercial relations, especially between companies and consumers. For all these reasons, this work aims to examine the effect of ICT, as a driving factor for innovation and its direct and indirect impact on sustainability in retailing. Furthermore, this study takes into account the eventual differences in these relationships according to the types of store formats. To achieve the aforementioned objective, a theoretical model is proposed that is tested through an empirical study carried out on a sample of 510 consumers of three store formats of grocery retail formats (i.e., hypermarkets, supermarkets and discount stores) in Spain. For the analysis of the data obtained, the partial least squares (PLS) regression technique and the Multigroup Analysis were used. The results obtained confirm the direct and indirect effect of ICT on innovation and sustainability in grocery retailing. In addition, the results indicate that consumers unequally perceive the technological progress of companies. These differences are greater between discount stores versus hypermarkets and supermarkets. The larger the size of the store format, the higher the incidence of ICT in relation to innovation. Therefore, it is vital to take ICT into consideration, where Artificial Intelligence is imperative for the growth and development of sustainable competitive advantages in retail companies.
Assessing the Constraints to the Adoption of Containerized Agriculture in Northern Canada
Authors: Natcher David , Ingram Shawn , Solotki Ray , Burgess Carl , Kulshreshtha Suren , Vold Lindsey
Published: May 2021

Considerable advancements are being made in containerized agricultural systems in the northern Canada. These systems are proving successful at overcoming the environmental constraints associated with cold climate food production and hold great promise for remote communities that suffer from high rates of food insecurity. However, if new technologies are to provide lasting and meaningful change for northern communities, critical attention needs to be directed to the variable and complex constraints that may limit their adoption and scalable success. To evaluate the potential uptake and use of containerized agriculture in northern Canada we employed the Adoption and Diffusion Outcome Prediction Tool. Twenty-two variables were ranked according to their influence on adoption. Six variables were then identified as being most constraining to the adoption of containerized agricultural systems, including upfront costs, expected profits, environmental impacts, complexity of the technology, trialability, and reversibility. We believe this type of pre-assessment is a critical, yet often over-looked step in technology transfer, and a necessary stage in assessing the scaling out potential for new food production technologies. This is particularly important for new food production technologies that demand significant financial investments that are wholly or partially irreversible.
Nieparlamentarny język Sejmu Rzeczypospolitej
w roku 2019
Authors: Taczkowska Kalina Maria
Published: May 2021

This paper discusses the undesired language behaviours of Members of
the Polish Parliament at the end of one and the beginning of the next term of
offi ce in 2019. Based on shorthand notes of Sejm’s sessions, a list of the most
common violations of the offi cial character of the parliamentary language has
been compiled. Various variants of discrediting, labelling, types of violations of
the principles of language ethics and verbal etiquette have been distinguished
in the contents and grouped. Characteristics of the language of contemporary
parliamentary debates and discussions have been identifi ed based on the Sejm
discourse analysis.
Keywords: Sejm of the Republic of Poland – discrediting – parliamentarism –
labelling – public debate
Jak można badać potoczną świadomość językową
Authors: Lustanski Joanna
Published: May 2021

This paper presents the characteristics of the so-called folk linguistic
awareness based on the assumptions of D.R. Preston and the American school
of folk linguistics. This type of awareness is characterised by the following
distinguishing features: explicit availability, degree of accuracy, level of detail,
and ability to control various language variants. These determinants, which can
be exemplifi ed by the substance of the Polish language and the language used
by the Polish community abroad, had not been used in the Polish research on
linguistic awareness before.
Keywords: folk linguistic awareness – folk linguistics – language attitudes –
Polish community in Canada – determinants of awareness
Determination and Evaluation of Bioavailability of Vitamins from Different Multivitamin Supplements Using a Pig Model
Authors: Yang Pan , Wang Huakai , Li Longxian , Zhang Nan , Ma Yongxi
Published: May 2021

This study was performed to evaluate the plasma vitamin kinetic behavior following oral vitamin supplement administration in pigs, and to determine the bioavailability of vitamins. A total of 36 pigs (fitted with jugular catheters) with an average body weight of 25 ± 2.24 kg were divided into three treatment groups: (1) placebo, (2) non-microencapsulated multivitamins supplement, or (3) lipid matrix microencapsulated multivitamins supplement. The blood samples were obtained starting pre-meal until 72 h post-meal for plasma vitamin analysis. Pharmacokinetic parameters were modeled with a non-compartmental method. The AUC (Area under the curve) from the time of dosing to the time of the last observation, Cmax (Maximum observed concentration), and MRT (Mean residence time) of α-tocopherol from oral non-microencapsulated supplement were significantly lower than oral microencapsulated supplement (p < 0.01). The average relative bioavailability of vitamin A (VA) and vitamin E (VE) from microencapsulated supplement was greater than that from non-microencapsulated supplement, but relative bioavailability of vitamin K3 (VK3) and water-soluble vitamins from microencapsulated supplement was lower than non-microencapsulated supplement. The AUC and Cmax of menadione, thiamine, and riboflavin from microencapsulated supplement were significantly lower than these parameters from oral non-microencapsulated supplement. Lipid matrix microencapsulation was able to delay absorption and improved the bioavailability of VE, whereas there were limited effects of microencapsulation on vitamin D (VD), VK3, and water-soluble vitamins.
Antimicrobial Residues in Food from Animal Origin—A Review of the Literature Focusing on Products Collected in Stores and Markets Worldwide
Authors: Treiber Fritz Michael , Beranek-Knauer Heide
Published: May 2021

The extensive use of antibiotics leads to antibiotic residues in frequently consumed foods. Generally, the main use of antibiotics in animals is to treat and prevent diseases and growth promotion. However, the residues and their breakdown products have several side effects on the human body and, in a broader sense, on the environment. In relation to the human body, the frequency of mutations is increased, the bone marrow is damaged (chloramphenicol), and the reproductive organs of humans are affected. Carcinogenic effects have been found with antibiotics such as sulfamethazine, oxytetracycline, and furazolidone. We summarized data from 73 scientific studies reporting antimicrobial residues in animal products that were freely available for sale. The studies were published in English starting from 1999 till 2021 and identified through the Pubmed search engine. The aims were to find out which antibiotics, legal or illegal, could be found in animal foods worldwide. Which are stable to get into the food chain and exceed the maximum residue limits (MRL) regarding the EU guidelines as a comparison. Reducing antimicrobial residues in food from animal origin and, in addition to this, fighting the tremendous growth and spread of antimicrobial resistance will undoubtedly be one of the most difficult food safety challenges in the coming years.
Involvement of a Multidrug Efflux Pump and Alterations in Cell Surface Structure in the Synergistic Antifungal Activity of Nagilactone E and Anethole against Budding Yeast Saccharomyces cerevisiae
Authors: Ueda Yuki , Tahara Yuhei O. , Miyata Makoto , Ogita Akira , Yamaguchi Yoshihiro , Tanaka Toshio , Fujita Ken-ichi
Published: May 2021

Nagilactone E, an antifungal agent derived from the root bark of Podocarpus nagi, inhibits 1,3-β glucan synthesis; however, its inhibitory activity is weak. Anethole, the principal component of anise oil, enhances the antifungal activity of nagilactone E. We aimed to determine the combinatorial effect and underlying mechanisms of action of nagilactone E and anethole against the budding yeast Saccharomyces cerevisiae. Analyses using gene-deficient strains showed that the multidrug efflux pump PDR5 is associated with nagilactone E resistance; its transcription was gradually restricted in cells treated with the drug combination for a prolonged duration but not in nagilactone-E-treated cells. Green-fluorescent-protein-tagged Pdr5p was intensively expressed and localized on the plasma membrane of nagilactone-E-treated cells but not in drug-combination-treated cells. Quick-freeze deep-etch electron microscopy revealed the smoothening of intertwined fiber structures on the cell surface of drug-combination-treated cells and spheroplasts, indicating a decline in cell wall components and loss of cell wall strength. Anethole enhanced the antifungal activity of nagilactone E by enabling its retention within cells, thereby accelerating cell wall damage. The combination of nagilactone E and anethole can be employed in clinical settings as an antifungal, as well as a food preservative to restrict food spoilage.
The Mitochondria-to-Cytosol H2O2 Gradient Is Caused by Peroxiredoxin-Dependent Cytosolic Scavenging
Authors: de Cubas Laura , Pak Valeriy V. , Belousov Vsevolod V. , Ayté José , Hidalgo Elena
Published: May 2021

Fluorescent protein-based reporters used to measure intracellular H2O2 were developed to overcome the limitations of small permeable dyes. The two major families of genetically encoded redox reporters are the reduction-oxidation sensitive green fluorescent protein (roGFP)-based proteins fused to peroxiredoxins and HyPer and derivatives. We have used the most sensitive probes of each family, roGFP2-Tpx1.C169S and HyPer7, to monitor steady-state and fluctuating levels of peroxides in fission yeast. While both are able to monitor the nanomolar fluctuations of intracellular H2O2, the former is two-five times more sensitive than HyPer7, and roGFP2-Tpx1.C169S is partially oxidized in the cytosol of wild-type cells while HyPer7 is fully reduced. We have successfully expressed HyPer7 in the mitochondrial matrix, and it is ~40% oxidized, suggesting higher steady-state levels of peroxides, in the low micromolar range, than in the cytosol. Cytosolic HyPer7 can detect negligible H2O2 in the cytosol from mitochondrial origin unless the main H2O2 scavenger, the cytosolic peroxiredoxin Tpx1, is absent, while mitochondrial HyPer7 is oxidized to the same extent in wild-type and ∆tpx1 cells. We conclude that there is a bidirectional flux of H2O2 across the matrix and the cytosol, but Tpx1 rapidly and efficiently scavenges mitochondrial-generated peroxides and stops their steady-state cytosolic levels rising.