bluuebunny/crossref_metadata_2025 huggingface dataset:
Criticality, Connectivity, and Neural Disorder: A Multifaceted Approach to Neural Computation
Authors: Heiney Kristine , Huse Ramstad Ola , Fiskum Vegard , Christiansen Nicholas , Sandvig Axel , Nichele Stefano , Sandvig Ioanna
Published: February 2021

It has been hypothesized that the brain optimizes its capacity for computation by self-organizing to a critical point. The dynamical state of criticality is achieved by striking a balance such that activity can effectively spread through the network without overwhelming it and is commonly identified in neuronal networks by observing the behavior of cascades of network activity termed “neuronal avalanches.” The dynamic activity that occurs in neuronal networks is closely intertwined with how the elements of the network are connected and how they influence each other's functional activity. In this review, we highlight how studying criticality with a broad perspective that integrates concepts from physics, experimental and theoretical neuroscience, and computer science can provide a greater understanding of the mechanisms that drive networks to criticality and how their disruption may manifest in different disorders. First, integrating graph theory into experimental studies on criticality, as is becoming more common in theoretical and modeling studies, would provide insight into the kinds of network structures that support criticality in networks of biological neurons. Furthermore, plasticity mechanisms play a crucial role in shaping these neural structures, both in terms of homeostatic maintenance and learning. Both network structures and plasticity have been studied fairly extensively in theoretical models, but much work remains to bridge the gap between theoretical and experimental findings. Finally, information theoretical approaches can tie in more concrete evidence of a network's computational capabilities. Approaching neural dynamics with all these facets in mind has the potential to provide a greater understanding of what goes wrong in neural disorders. Criticality analysis therefore holds potential to identify disruptions to healthy dynamics, granted that robust methods and approaches are considered.
Neural Underpinnings of Proactive Interference in Working Memory: Evidence From Patients With Unilateral Lesions
Authors: Ries Stephanie K. , Schendel Krista L. , Herron Timothy J. , Dronkers Nina F. , Baldo Juliana V. , Turken And U.
Published: February 2021

Proactive interference in working memory refers to the fact that memory of past experiences can interfere with the ability to hold new information in working memory. The left inferior frontal gyrus (LIFG) has been proposed to play an important role in resolving proactive interference in working memory. However, the role of white matter pathways and other cortical regions has been less investigated. Here we investigated proactive interference in working memory using the Recent Probes Test (RPT) in 15 stroke patients with unilateral chronic lesions in left (n= 7) or right (n= 2) prefrontal cortex (PFC), or left temporal cortex (n= 6). We examined the impact of lesions in both gray and white matter regions on the size of the proactive interference effect. We found that patients with left PFC lesions performed worse overall, but the proactive interference effect in this patient group was comparable to that of patients with right PFC lesions, temporal lobe lesions, and controls. Interestingly, the size of the interference effect was significantly correlated with the degree of damage in the extreme/external capsule and marginally correlated with the degree of damage in the inferior frontal occipital fasciculus (IFOF). These findings suggests that ventral white matter pathways connecting the LIFG to left posterior regions play a role in resolving proactive interference in working memory. This effect was particularly evident in one patient with a very large interference effect (>3 SDs above controls) who had mostly spared LIFG, but virtually absent ventral white matter pathways (i.e., passing through the extreme/external capsules and IFOF). This case study further supports the idea that the role of the LIFG in resolving interference in working memory is dependent on connectivity with posterior regions via ventral white matter pathways.
Tau Pathology and Adult Hippocampal Neurogenesis: What Tau Mouse Models Tell us?
Authors: Houben Sarah , Homa Mégane , Yilmaz Zehra , Leroy Karelle , Brion Jean-Pierre , Ando Kunie
Published: February 2021

Adult hippocampal neurogenesis (AHN) has been widely confirmed in mammalian brains. A growing body of evidence points to the fact that AHN sustains hippocampal-dependent functions such as learning and memory. Impaired AHN has been reported inpost-mortemhuman brain hippocampus of Alzheimer's disease (AD) and is considered to contribute to defects in learning and memory. Neurofibrillary tangles (NFTs) and amyloid plaques are the two key neuropathological hallmarks of AD. NFTs are composed of abnormal tau proteins accumulating in many brain areas during the progression of the disease, including in the hippocampus. The physiological role of tau and impact of tau pathology on AHN is still poorly understood. Modifications in AHN have also been reported in some tau transgenic and tau-deleted mouse models. We present here a brief review of advances in the relationship between development of tau pathology and AHN in AD and what insights have been gained from studies in tau mouse models.
Association Between Inflammatory Potential of the Diet and Ulcerative Colitis: A Case-Control Study
Authors: Khademi Zeinab , Saneei Parvane , Hassanzadeh-Keshteli Ammar , Daghaghzadeh Hamed , Tavakkoli Hamid , Adibi Peyman , Esmaillzadeh Ahmad
Published: February 2021

Background/Aim:Despite the inflammatory nature of inflammatory bowel disease (IBD), limited data are available on the association of inflammatory potential of the diet and risk of ulcerative colitis (UC). We aimed to investigate the association of inflammatory potential of the diet (IPD) score and odds of UC in a case-control study.

Methods:Patients with UC were enrolled from Iranian IBD registry, whose disease was confirmed by a gastroenterologist. Controls were selected randomly from the Study of the Epidemiology of Psycho Alimentary Health and Nutrition (SEPAHAN) study, a large population-based study on more than 8,000 apparently healthy individuals. Dietary intakes of 28 food items obtained from a validated dish-based food frequency questionnaire (FFQ), were used to compute IPD score.

Results:This case-control study was carried out among 109 cases and 218 randomly chosen controls. Mean age of cases and controls was 39.5 ± 10.0 and 41.5 ± 11.8 y, respectively. Totally, 52% of study participants were female and 48% were male. After controlling for age, sex, and body mass index (BMI), we found that the patients with UC were more likely to be in the highest quartile of IPD score compared with controls (OR: 2.83; 95% CI: 1.41–5.69,P-trend < 0.001). This association strengthened after additional adjustment for education, smoking, medical history, and physical activity (OR: 3.48; 95% CI: 1.32–9.10,P-trend = 0.003). When we took dietary habits into account, the association was slightly attenuated (OR: 3.33; 95% CI: 1.20–9.20,P-trend = 0.005).

Conclusions:We found that adherence to a pro-inflammatory diet was positively associated with greater odds of UC. Further studies are required to confirm these findings.
Development and Validation of an Immune-Related Gene-Pair Model of High-Grade Serous Ovarian Cancer After Platinum-Based Chemotherapy
Authors: Lin Jiaxing , Xu Xiao , Sun Dan , Li Tianren
Published: February 2021

Background

High-grade serous ovarian cancer (HGSOC) is a common cause of death from gynecological cancer, with an overall survival rate that has not significantly improved in decades. Reliable bio-markers are needed to identify high-risk HGSOC to assist in the selection and development of treatment options.

Method

The study included ten HGSOC cohorts, which were merged into four separate cohorts including a total of 1,526 samples. We used the relative expression of immune genes to construct the gene-pair matrix, and the least absolute shrinkage and selection operator regression was performed to build the prognosis model using the training set. The prognosis of the model was verified in the training set (363 cases) and three validation sets (of 251, 354, and 558 cases). Finally, the differences in immune cell infiltration and gene enrichment pathways between high and low score groups were identified.

Results

A prognosis model of HGSOC overall survival rate was constructed in the training set, and included data for 35 immune gene-related gene pairs and the regression coefficients. The risk stratification of HGSOC patients was successfully performed using the training set, with a p-value of Kaplan-Meier of < 0.001. A score from this model is an independent prognostic factor of HGSOC, and prognosis was evaluated in different clinical subgroups. This model was also successful for the other three validation sets, and the results of Kaplan-Meier analysis were statistically significant (p < 0.05). The model can also predict patient progression-free survival with HGSOC to reflect tumor growth status. There was a lower infiltration level of M1 macrophages in the high-risk group compared to that in the low-risk group (p < 0.001). Finally, the immune-related pathways were enriched in the low-risk group.

Conclusion

The prognostic model based on immune-related gene pairs developed is a potential prognostic marker for high-grade serous ovarian cancer treated with platinum. The model has robust prognostic ability and wide applicability. More prospective studies will be needed to assess the practical application of this model for precision therapy.
Chromosome-Level Genome Assembly of the American Cranberry (Vaccinium macrocarpon Ait.) and Its Wild Relative Vaccinium microcarpum
Authors: Diaz-Garcia Luis , Garcia-Ortega Luis Fernando , González-Rodríguez Maria , Delaye Luis , Iorizzo Massimo , Zalapa Juan
Published: February 2021

The American cranberry (Vaccinium macrocarpon Ait.) is an iconic North American fruit crop of great cultural and economic importance. Cranberry can be considered a fruit crop model due to its unique fruit nutrient composition, overlapping generations, recent domestication, both sexual and asexual reproduction modes, and the existence of cross-compatible wild species. Development of cranberry molecular resources started very recently; however, further genetic studies are now being limited by the lack of a high-quality genome assembly. Here, we report the first chromosome-scale genome assembly of cranberry, cultivar Stevens, and a draft genome of its close wild relative species Vaccinium microcarpum. More than 92% of the estimated cranberry genome size (492 Mb) was assembled into 12 chromosomes, which enabled gene model prediction and chromosome-level comparative genomics. Our analysis revealed two polyploidization events, the ancient γ-triplication, and a more recent whole genome duplication shared with other members of the Ericaeae, Theaceae and Actinidiaceae families approximately 61 Mya. Furthermore, comparative genomics within the Vaccinium genus suggested cranberry-V. microcarpum divergence occurred 4.5 Mya, following their divergence from blueberry 10.4 Mya, which agrees with morphological differences between these species and previously identified duplication events. Finally, we identified a cluster of subgroup-6 R2R3 MYB transcription factors within a genomic region spanning a large QTL for anthocyanin variation in cranberry fruit. Phylogenetic analysis suggested these genes likely act as anthocyanin biosynthesis regulators in cranberry. Undoubtedly, these new cranberry genomic resources will facilitate the dissection of the genetic mechanisms governing agronomic traits and further breeding efforts at the molecular level.
Molecular Tools for Adapting Viticulture to Climate Change
Authors: Gomès Éric , Maillot Pascale , Duchêne Éric
Published: February 2021

Adaptation of viticulture to climate change includes exploration of new geographical areas, new training systems, new management practices, or new varieties, both for rootstocks and scions. Molecular tools can be defined as molecular approaches used to study DNAs, RNAs, and proteins in all living organisms. We present here the current knowledge about molecular tools and their potential usefulness in three aspects of grapevine adaptation to the ongoing climate change. (i) Molecular tools for understanding grapevine response to environmental stresses. A fine description of the regulation of gene expression is a powerful tool to understand the physiological mechanisms set up by the grapevine to respond to abiotic stress such as high temperatures or drought. The current knowledge on gene expression is continuously evolving with increasing evidence of the role of alternative splicing, small RNAs, long non-coding RNAs, DNA methylation, or chromatin activity. (ii) Genetics and genomics of grapevine stress tolerance. The description of the grapevine genome is more and more precise. The genetic variations among genotypes are now revealed with new technologies with the sequencing of very long DNA molecules. High throughput technologies for DNA sequencing also allow now the genetic characterization at the same time of hundreds of genotypes for thousands of points in the genome, which provides unprecedented datasets for genotype-phenotype associations studies. We review the current knowledge on the genetic determinism of traits for the adaptation to climate change. We focus on quantitative trait loci and molecular markers available for developmental stages, tolerance to water stress/water use efficiency, sugar content, acidity, and secondary metabolism of the berries. (iii) Controlling the genome and its expression to allow breeding of better-adapted genotypes. High-density DNA genotyping can be used to select genotypes with specific interesting alleles but genomic selection is also a powerful method able to take into account the genetic information along the whole genome to predict a phenotype. Modern technologies are also able to generate mutations that are possibly interesting for generating new phenotypes but the most promising one is the direct editing of the genome at a precise location.
Quantitative High-Throughput, Real-Time Bioassay for Plant Pathogen Growth in vivo
Authors: Zhang Chunqiu , Mansfeld Ben N. , Lin Ying-Chen , Grumet Rebecca
Published: February 2021

Effective assessment of pathogen growth can facilitate screening for disease resistance, mapping of resistance loci, testing efficacy of control measures, or elucidation of fundamental host-pathogen interactions. Current methods are often limited by subjective assessments, inability to detect pathogen growth prior to appearance of symptoms, destructive sampling, or limited capacity for replication and quantitative analysis. In this work we sought to develop a real-time, in vivo, high-throughput assay that would allow for quantification of pathogen growth. To establish such a system, we worked with the broad host-range, highly destructive, soil-borne oomycete pathogen, Phytophthora capsici. We used an isolate expressing red fluorescence protein (RFP) to establish a microtiter plate, real-time assay to quantify pathogen growth in live tissue. The system was successfully used to monitor P. capsici growth in planta on cucumber (Cucumis sativus) fruit and pepper (Capsicum annuum) leaf samples in relation to different levels of host susceptibility. These results demonstrate usefulness of the method in different species and tissue types, allowing for highly replicated, quantitative time-course measurements of pathogen growth in vivo. Analyses of pathogen growth during initial stages of infection preceding symptom development show the importance of very early stages of infection in determining disease outcome, and provide insight into points of inhibition of pathogen growth in different resistance systems.
Exploring the Relationship Between Users' Psychological Contracts and Their Knowledge Contribution in Online Health Communities
Authors: Liu Wenlong , Chen Xinting , Lu Xuanyu , Fan Xiucheng
Published: February 2021

The knowledge contribution of members is essential and beneficial to both the business and users of online health communities (OHCs). This study explores and tests the effects of OHC users' psychological contracts on their community identification and knowledge-sharing behavior. A total of 362 valid responses from several well-known OHCs in China are used in the data analysis. The results of the path analysis with structural equation modeling show that users' transactional psychological contracts have a negative effect on their knowledge contribution both directly and indirectly by weakening their community identification. In contrast, users' relational psychological contracts can lead to increased active knowledge contributions both directly and indirectly by enhancing their community identification. Knowledge sharing self-efficacy can strengthen the relationship between relational psychological contracts and knowledge contributions, and the relationship between community identification and knowledge contributions. However, it has no significant impact on the path from transactional psychological contracts to knowledge contribution. The implications and direction of future works are presented on the basis of the results of the empirical analysis.
The Investor Psychology and Stock Market Behavior During the Initial Era of COVID-19: A Study of China, Japan, and the United States
Authors: Naseem Sobia , Mohsin Muhammad , Hui Wang , Liyan Geng , Penglai Kun
Published: February 2021

A highly transmittable and pathogenic viral infection, COVID-19, has dramatically changed the world with a tragically large number of human lives being lost. The epidemic has created psychological resilience and unbearable psychological pressure among patients and health professionals. The objective of this study is to analyze investor psychology and stock market behavior during COVID-19. The psychological behavior of investors, whether positive or negative, toward the stock market can change the picture of the economy. This research explores Shanghai, Nikkei 225, and Dow Jones stock markets from January 20, 2020, to April 27, 2020, by employing principal component analysis. The results showed that investor psychology was negatively related to three selected stock markets under psychological resilience and pandemic pressure. The negative emotions and pessimism urge investors to cease financial investment in the stock market, and consequently, the stock market returns decreased. In a deadly pandemic, the masses were more concerned about their lives and livelihood and less about wealth and leisure. This research contributes to the literature gap of investors’ psychological behavior during a pandemic outbreak. The study suggests that policy-makers should design a plan to fight against COVID-19. The government should manage the health sector’s budget to overcome future crises.
“Soldiers of the System”: Maternity Care in Russia Between Bureaucratic Instructions and the Epidemiological Risks of COVID-19
Authors: Ozhiganova Anna
Published: February 2021

Preventive measures taken by the Russian maternity care system in response to the COVID-19 pandemic are very tough. Supporting persons (doulas and partners) are being completely excluded from the maternity hospitals. Pregnant women and newborns are distributed in different types of hospitals according to their epidemiological status (confirmed, suspected, contact, or “clear”). Severe infection control measures are introduced for women with confirmed or suspected COVID-19: separation from newborns and weeks of hospital quarantine. How do obstetricians and other perinatal specialists perceive these measures? What strategies do they choose and what new practices are being created? The study is based on interviews conducted between March and August 2020 with obstetricians-gynecologists, midwives, perinatal psychologistsdoulas, and women who gave birth during the pandemic and is focused on their subjective interpretations of COVID-related changes in maternal care. My data indicate that this pandemic with its high risks and uncertainties reveals multiple ethical and organizational conflicts among bureaucratic, managerial and professional logics in Russian health care in which mistrust has played an important role.
The Shrinking Resource Base of Pastoralism: Saami Reindeer Husbandry in a Climate of Change
Authors: Tyler Nicholas J. C. , Hanssen-Bauer Inger , Førland Eirik J. , Nellemann Christian
Published: February 2021

The productive performance of large ungulates in extensive pastoral grazing systems is modulated simultaneously by the effects of climate change and human intervention independent of climate change. The latter includes the expansion of private, civil and military activity and infrastructure and the erosion of land rights. We used Saami reindeer husbandry in Norway as a model in which to examine trends in, and to compare the influence of, both effects on a pastoral grazing system. Downscaled projections of mean annual temperature over the principal winter pasture area (Finnmarksvidda) closely matched empirical observations across 34 years to 2018. The area, therefore, is not only warming but seems likely to continue to do so. Warming notwithstanding, 50-year (1969–2018) records of local weather (temperature, precipitation and characteristics of the snowpack) demonstrate considerable annual and decadal variation which also seems likely to continue and alternately to amplify and to counter net warming. Warming, moreover, has both positive and negative effects on ecosystem services that influence reindeer. The effects of climate change on reindeer pastoralism are evidently neither temporally nor spatially uniform, nor indeed is the role of climate change as a driver of change in pastoralism even clear. The effects of human intervention on the system, by contrast, are clear and largely negative. Gradual liberalization of grazing rights from the 18thCentury has been countered by extensive loss of reindeer pasture. Access to ~50% of traditional winter pasture was lost in the 19thCentury owing to the closure of international borders to the passage of herders and their reindeer. Subsequent to this the area of undisturbed pasture within Norway has decreased by 71%. Loss of pasture due to piecemeal development of infrastructure and to administrative encroachment that erodes herders' freedom of action on the land that remains to them, are the principal threats to reindeer husbandry in Norway today. These tangible effects far exceed the putative effects of current climate change on the system. The situation confronting Saami reindeer pastoralism is not unique: loss of pasture and administrative, economic, legal and social constraints bedevil extensive pastoral grazing systems across the globe.
Deltacoronavirus Evolution and Transmission: Current Scenario and Evolutionary Perspectives
Authors: Vlasova Anastasia N. , Kenney Scott P. , Jung Kwonil , Wang Qiuhong , Saif Linda J.
Published: February 2021

Deltacoronavirus (DCoV)–the only coronavirus that can infect multiple species of mammals and birds–was initially identified in several avian and mammalian species, including pigs, in China in 2009–2011. Porcine DCoV has since spread worldwide and is associated with multiple outbreaks of diarrheal disease of variable severity in farmed pigs. In contrast, avian DCoV is being reported in wild birds in different countries without any evidence of disease. The DCoV transboundary nature and the recent discovery of its remarkably broad reactivity with its cellular receptor–aminopeptidase N (APN)–from different species emphasize its epidemiological relevance and necessitate additional research. Further, the ability of porcine DCoV to infect and cause disease in chicks and turkey poults and gnotobiotic calves is suggestive of its increased potential for interspecies transmission or of its avian origin. Whether, porcine DCoVs were initially acquired by one or several mammalian species from birds and whether avian and porcine DCoVs continue co-evolving with frequent spillover events remain to be major unanswered questions. In this review, we will discuss the current information on the prevalence, genetic diversity, and pathogenic potential of porcine and avian DCoVs. We will also analyze the existing evidence of the ongoing interspecies transmission of DCoVs that may provide novel insights into their complex evolution.
Spermatozoa Obtained From Alpaca vas deferens. Effects of Seminal Plasma Added at Post-thawing
Authors: Aisen Eduardo G. , Huanca López Wilfredo , Pérez Durand Manuel G. , Torres Mamani Edita , Villanueva Mori Juan C. , Ousset María J. , Medina Víctor H. , Pérez Guerra Uri H. , Huanca Mamani Teodosio
Published: February 2021

The viscous seminal plasma (SP) is currently a major impediment to the handling of ejaculate and the development of some biotechnologies in South American camelids. The vas deferens-collected spermatozoa of alpacas is a useful technique to avoid this problem. On the other hand, SP contains a large protein component that has been implicated in the function of spermatozoa within the female reproductive tract. In this sense, the low fertility achieved using transcervical insemination with frozen-thawed spermatozoa in alpacas could be improved by adding SP. This study aimed to evaluate the effect of the whole SP on some in vitro parameters of alpaca spermatozoa after the freezing-thawing-process and the fertility after artificial insemination. It would contribute to a better understanding of the interaction between thawed sperm cells and SP. Spermatozoa were obtained by surgically diverted vas deferens. The samples were diluted with a Tris-based extender, packaged in straws, and frozen. At thawing, each straw was divided into two post-thawing conditions: with the addition of 10% of PBS (control) or with 10% SP (treatment). The sperm cells were evaluated using dynamic parameters, sperm cell morphology, and morphometry. Fertility was assessed by an artificial insemination trial. All in vitro parameters were analyzed by ANOVA. A heterogeneity test was scheduled for the fertility trial. After the freezing-thawing process, motility and plasma membrane functionality was improved when SP was added. No differences were found for post-thaw viability between the control and treatment samples. The percentage of normal cells was higher with SP at post-thawing, and a decrease of the presence of bent tailed spermatozoa with a droplet in the SP group was observed. The length of the head spermatozoa was 3.4% higher in the samples with PBS compared to those in which SP was added. Females pregnant at day 25 post-insemination were 0/12 (with SP inside the straw) and 1/10 (without SP inside the straw). In conclusion, the presence of 10% SP at post-thawing improves sperm cells' motility, functionality, and morphology, indicating that it would be beneficial to improve the frozen-thawed alpaca's physiology spermatozoa. More fertility trials must be developed to increase this knowledge.
Inhibition of Mitochondrial Dynamics Preferentially Targets Pancreatic Cancer Cells with Enhanced Tumorigenic and Invasive Potential
Authors: Courtois Sarah , de Luxán-Delgado Beatriz , Penin-Peyta Laure , Royo-García Alba , Parejo-Alonso Beatriz , Jagust Petra , Alcalá Sonia , Rubiolo Juan A. , Sánchez Laura , Sainz Bruno , Heeschen Christopher , Sancho Patricia
Published: February 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, partly due to its intrinsic aggressiveness, metastatic potential, and chemoresistance of the contained cancer stem cells (CSCs). Pancreatic CSCs strongly rely on mitochondrial metabolism to maintain their stemness, therefore representing a putative target for their elimination. Since mitochondrial homeostasis depends on the tightly controlled balance between fusion and fission processes, namely mitochondrial dynamics, we aim to study this mechanism in the context of stemness. In human PDAC tissues, the mitochondrial fission gene DNM1L (DRP1) was overexpressed and positively correlated with the stemness signature. Moreover, we observe that primary human CSCs display smaller mitochondria and a higher DRP1/MFN2 expression ratio, indicating the activation of the mitochondrial fission. Interestingly, treatment with the DRP1 inhibitor mDivi-1 induced dose-dependent apoptosis, especially in CD133+ CSCs, due to the accumulation of dysfunctional mitochondria and the subsequent energy crisis in this subpopulation. Mechanistically, mDivi-1 inhibited stemness-related features, such as self-renewal, tumorigenicity, and invasiveness and chemosensitized the cells to the cytotoxic effects of Gemcitabine. In summary, mitochondrial fission is an essential process for pancreatic CSCs and represents an attractive target for designing novel multimodal treatments that will more efficiently eliminate cells with high tumorigenic potential.
The Identity of PDGFRA D842V-Mutant Gastrointestinal Stromal Tumors (GIST)
Authors: Rizzo Alessandro , Pantaleo Maria Abbondanza , Astolfi Annalisa , Indio Valentina , Nannini Margherita
Published: February 2021

The majority of gastrointestinal stromal tumors (GIST) carry a sensitive primary KIT mutation, but approximately 5% to 10% of cases harbor activating mutations of platelet-derived growth factor receptor (PDGFRA), mainly involving the A-loop encoded by exon 18 (~5%), or more rarely the JM domain, encoded by exon 12 (~1%), or the ATP binding domain encoded by exon 14 (<1%). The most frequent mutation is the substitution at position 842 in the A-loop of an aspartic acid (D) with a valine (V) in exon 18, widely recognized as D842V. This mutation, as well known, provides primary resistance to imatinib and sunitinib. Thus, until few years ago, no active drugs were available for this subtype of GIST. Conversely, recent years have witnessed the development of a new specific inhibitor—avapritinib—that has been studied in in vitro and clinical setting with promising results. In light of this primary resistance to conventional therapies, the biological background of D842V-mutant GIST has been deeply investigated to better understand what features characterize this peculiar subset of GIST, and some promising insights have emerged. Hereinafter, we present a comprehensive overview on the clinical features and the molecular background of this rare subtype of GIST.
New Biomarkers in Cancers
Authors: Novak Daniel , Utikal Jochen
Published: February 2021

In this Special Issue of Cancers, the latest insights on biomarkers in cancers are presented in 33 up-to-the-minute research papers and reviews summing up the tremendous progress in this interesting and important field of research [...]
Noncoding RNAs in the Interplay between Tumor Cells and Cancer-Associated Fibroblasts: Signals to Catch and Targets to Hit
Authors: Tassinari Martina , Gandellini Paolo
Published: February 2021

Cancer development and progression are not solely cell-autonomous and genetically driven processes. Dynamic interaction of cancer cells with the surrounding microenvironment, intended as the chemical/physical conditions as well as the mixture of non-neoplastic cells of the tumor niche, drive epigenetic changes that are pivotal for the acquisition of malignant traits. Cancer-associated fibroblasts (CAF), namely fibroblasts that, corrupted by cancer cells, acquire a myofibroblast-like reactive phenotype, are able to sustain tumor features by the secretion of soluble paracrine signals and the delivery extracellular vesicles. In such diabolic liaison, a major role has been ascribed to noncoding RNAs. Defined as RNAs that are functional though not being translated into proteins, noncoding RNAs predominantly act as regulators of gene expression at both the transcriptional and post-transcriptional levels. In this review, we summarize the current knowledge of microRNAs and long noncoding RNAs that act intracellularly in either CAFs or cancer cells to sustain tumor-stroma interplay. We also report on the major role of extracellular noncoding RNAs that are bidirectionally transferred between either cell type. Upon presenting a comprehensive view of the existing literature, we provide our critical opinion regarding the possible clinical utility of tumor-stroma related noncoding RNAs as therapeutic target/tools or prognostic/predictive biomarkers.
Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response
Authors: Toffoli Elisa C. , Sheikhi Abdolkarim , Höppner Yannick D. , de Kok Pita , Yazdanpanah-Samani Mahsa , Spanholtz Jan , Verheul Henk M. W. , van der Vliet Hans J. , de Gruijl Tanja D.
Published: February 2021

Natural Killer (NK) cells are innate immune cells with the unique ability to recognize and kill virus-infected and cancer cells without prior immune sensitization. Due to their expression of the Fc receptor CD16, effector NK cells can kill tumor cells through antibody-dependent cytotoxicity, making them relevant players in antibody-based cancer therapies. The role of NK cells in other approved and experimental anti-cancer therapies is more elusive. Here, we review the possible role of NK cells in the efficacy of various anti-tumor therapies, including radiotherapy, chemotherapy, and immunotherapy, as well as the impact of these therapies on NK cell function.
Associations between Prenatal Education, Breastfeeding and Autistic-Like Behaviors in Pre-Schoolers
Authors: Chen Jing , Strodl Esben , Huang Li-Hua , Chen Jing-Yi , Liu Xin-Chen , Yang Jian-Hui , Chen Wei-Qing
Published: February 2021

This study aimed to investigate the association between prenatal education and autistic-like behaviors of preschoolers as well as the mediating role of breastfeeding in their associations. A cross-sectional study via a structured questionnaire was conducted with 67,578 preschool children and parents from Longhua District of Shenzhen, China. Hierarchical logistic regression models were performed to explore the associations between maternal participation in prenatal education and autistic-like behaviors in preschoolers, as well as the mediating effect of breastfeeding in the associations. After controlling for potential confounders, logistic regression analysis indicated that maternal participation in prenatal education could significantly increase the prevalence of breastfeeding, and the strength of the association was enhanced with the increase frequency of prenatal education visits (ORs ranging from 1.191 to 1.899). While both maternal participation in prenatal education (ORs ranging from 0.732 to 0.798) and breastfeeding (OR = 0.773) were significantly associated with the lower presence of autistic-like behaviors in preschoolers. The crossover analysis indicated that children with both maternal prenatal education and breastfeeding had the lower risk of presence of autistics-like behaviors (OR = 0.569). Furthermore, mediation analysis illustrated that breastfeeding mediated the association between maternal participation in prenatal education and the presence of autistic-like behaviors in preschoolers, with a mediating effect of approximately 14.3%. Our findings suggest that maternal participation in prenatal education is significantly associated with a decreased risk of autistic-like behaviors in preschool children through increased breastfeeding in the mothers who attended prenatal education.
Defining Conservation Requirements for the Suweon Treefrog (Dryophytes suweonensis) Using Species Distribution Models
Authors: Park Il-Kook , Park Daesik , Borzée Amaël
Published: February 2021

Numerous amphibian species are declining because of habitat loss and fragmentation due to urbanization of landscapes and the construction of roads. This is a mounting threat to species restricted to habitats close to urban areas, such as agricultural wetlands in North East Asia. The Suweon treefrog (Dryophytes suweonensis) falls into the list of species threatened with habitat loss and most populations are under threat of extirpation. Over the last decades, sub-populations have become increasingly disconnected and specifically the density of paved roads has increased around the only site connecting northern and southern Seoul populations. We surveyed this locality in Hojobeol, Siheung, Republic of Korea in 2012, 2015 and 2019 to first confirm the decline in the number of sites where D. suweonensis was present. The second objective was to analyze the habitat characteristics and determine the remaining suitable habitat for D. suweonensis through a species distribution model following the maximum entropy method. Our results show that rice paddy cover and distance from the paved road are the most important factor defining suitable habitat for D. suweonensis. At this locality, uninterrupted rice paddies are a suitable habitat for the species when reaching at least 0.19 km2, with an average distance of 138 ± 93 m2 from the roads. We link the decrease in the number of sites where D. suweonensis is present with the decrease in rice paddy cover, generally replaced by localized infrastructures, greenhouses and habitat fragmentation. Rice paddies should remain connected over a large area for the protection of the remaining populations. In addition, habitat requirements should be integrated in the requisites to designate protected areas.
Long Term Interactions of Native and Invasive Species in a Marine Protected Area Suggest Complex Cascading Effects Challenging Conservation Outcomes
Authors: Dimitriadis Charalampos , Fournari-Konstantinidou Ivoni , Sourbès Laurent , Koutsoubas Drosos , Katsanevakis Stelios
Published: February 2021

Understanding the interactions among invasive species, native species and marine protected areas (MPAs), and the long-term regime shifts in MPAs is receiving increased attention, since biological invasions can alter the structure and functioning of the protected ecosystems and challenge conservation efforts. Here we found evidence of marked modifications in the rocky reef associated biota in a Mediterranean MPA from 2009 to 2019 through visual census surveys, due to the presence of invasive species altering the structure of the ecosystem and triggering complex cascading effects on the long term. Low levels of the populations of native high-level predators were accompanied by the population increase and high performance of both native and invasive fish herbivores. Subsequently the overgrazing and habitat degradation resulted in cascading effects towards the diminishing of the native and invasive invertebrate grazers and omnivorous benthic species. Our study represents a good showcase of how invasive species can coexist or exclude native biota and at the same time regulate or out-compete other established invaders and native species.
Genesis, Evolution, and Genetic Diversity of the Hexaploid, Narrow Endemic Centaurea tentudaica
Authors: Moreyra Lucía D. , Márquez Francisco , Susanna Alfonso , Garcia-Jacas Núria , Vázquez Francisco María , López-Pujol Jordi
Published: February 2021

Within the genus Centaurea L., polyploidy is very common, and it is believed that, as to all angiosperms, it was key in the history of its diversification and evolution. Centaurea tentudaica is a hexaploid from subsect. Chamaecyanus of unknown origin. In this study, we examined the possible autopolyploid or allopolyploid origin using allozymes and sequences of three molecular markers: nuclear-ribosomic region ETS, and low-copy genes AGT1 and PgiC. We also included three species geographically and morphologically close to C. tentudaica: C. amblensis, C. galianoi, and C. ornata. Neighbor-Net and Bayesian analyses show a close relationship between C. amblensis and C. tentudaica and no relationship to any of the other species, which suggest that C. tentudaica is an autopolyploid of C. amblensis. Allozyme banding pattern also supports the autopolyploidy hypothesis and shows high levels of genetic diversity in the polyploid, which could suggest multiple origins by recurrent crosses of tetraploid and diploid cytotypes of C. amblensis. Environmental niche modeling was used to analyze the distribution of the possible parental species during the present, Last Glacial Maximum (LGM), Last Interglacial Period (LIG), and Penultimate Glacial Maximum (PGM) environmental conditions. Supporting the molecular suggestions that C. tentudaica originated from C. amblensis, environmental niche modeling confirms that past distribution of C. amblensis overlapped with the distribution of C. tentudaica.
Classification of Noise Sources for Port Area Noise Mapping
Authors: Fredianelli Luca , Bolognese Matteo , Fidecaro Francesco , Licitra Gaetano
Published: February 2021

Maritime transportation is recognized to have advantages in terms of environmental impact compared to other forms of transportation. However, an increment in traffic volumes will also produce an increase in noise emissions in the surroundings for a greener source, as ports are frequently surrounded by urban areas. When more sources or higher noise emissions are introduced, the noise exposure of citizens increases, and the likelihood of official complaints rises. As a consequence, among the most demanding aspects of port management is effective noise management aimed at a reduction in the exposure of citizens while ensuring the growth of maritime traffic. At the same time, the topic has not been thoroughly studied by the scientific community, mostly because port areas are challenging from a noise management point of view; they are often characterized by a high degree of complexity, both in terms of the number of different noise sources and their interaction with the other main transportation infrastructure. Therefore, an effective methodology of noise modeling of the port area is currently missing. With regard to the INTERREG Maritime Program, the present paper reports a first attempt to define noise mapping guidelines. On the basis of the current state-of-the-art and the authors’ experiences, noise sources inside port areas can be divided into several different categories: road sources, railway sources, ship sources, port sources, and industrial sources. A further subdivision can be achieved according to the working operation mode and position of the sources. This classification simplifies actions of identification of the responsible source from control bodies, in the case that noise limits are exceeded or citizen complaints arise. It also represents a necessary tool to identify the best placing of medium/long-term noise monitoring stations. The results also act as a base for a future definition of specific and targeted procedures for the acoustic characterization of port noise sources.
Application of Unsupervised Anomaly Detection Techniques to Moisture Content Data from Wood Constructions
Authors: García Faura Álvaro , Štepec Dejan , Cankar Matija , Humar Miha
Published: February 2021

Wood is considered one of the most important construction materials, as well as a natural material prone to degradation, with fungi being the main reason for wood failure in a temperate climate. Visual inspection of wood or other approaches for monitoring are time-consuming, and the incipient stages of decay are not always visible. Thus, visual decay detection and such manual monitoring could be replaced by automated real-time monitoring systems. The capabilities of such systems can range from simple monitoring, periodically reporting data, to the automatic detection of anomalous measurements that may happen due to various environmental or technical reasons. In this paper, we explore the application of Unsupervised Anomaly Detection (UAD) techniques to wood Moisture Content (MC) data. Specifically, data were obtained from a wood construction that was monitored for four years using sensors at different positions. Our experimental results prove the validity of these techniques to detect both artificial and real anomalies in MC signals, encouraging further research to enable their deployment in real use cases.
Development of an Algebraic Model of Empirical Parameterization of Near Wakes around a Vehicle
Authors: Kimura Arata , Asami Mitsufumi , Oka Hideyuki , Oka Yasushi
Published: February 2021

In this paper, we describe and evaluate an algebraic model that has been adopted in a diagnostic wind flow model. Our numerical model is based on the Röckle’s wind modelling approach and we intend to reproduce the steady-state flow patterns of recirculation vortices that are generated in the near-wake region behind a vehicle. The evaluation of the practicality of our proposed model is performed by comparing the wind tunnel experiments of the flow around a vehicle conducted by the Loughborough University. We also compare the numerical results of our model with the CFD model. The proposed model reproduces the flow patterns behind a vehicle and it has significant advantages, such as low numerical costs. We expect that further improvements in the algebraic model when considering the vehicle’s shape will improve its practicality for the numerical analysis of flow fields around a vehicle.
High Levels of Genetic Variation in MHC-Linked Microsatellite Markers from Native Chicken Breeds
Authors: Manjula Prabuddha , Kim Minjun , Cho Sunghyun , Seo Dongwon , Lee Jun Heon
Published: February 2021

The major histocompatibility complex (MHC) is a highly polymorphic gene region that regulates cellular communication in all specific immune responses. In this study, we investigated 11 microsatellite (MS) markers in the MHC-B region of chicken populations from four countries: Sri Lanka, Bangladesh, South Korea, and Nigeria. The MS markers were divided into two sets. Set 1 included five novel MS markers, which we assessed using 192 samples from 21 populations. Set 2 included six previously reported markers, which we assessed using 881 samples from 29 populations. The Set 1 MS markers had lower polymorphism (polymorphic information content (PIC) < 0.5) than the Set 2 markers (PIC = 0.4–0.9). In all populations, the LEI0258 marker was the most polymorphic, with a total of 38 alleles (PIC = 0.912, expected heterozygosity (He) = 0.918). Local populations from Sri Lanka, Bangladesh, and Nigeria had higher allele diversity and more haplotypes for Set 2 MS markers than Korean and commercial populations. The Sri Lankan Karuwalagaswewa village population had the highest MHC diversity (mean allele number = 8.17, He = 0.657), whereas the white leghorn population had the lowest (mean allele number = 2.33, He = 0.342). A total of 409 haplotypes (89 shared and 320 unique), with a range of 4 (Rhode Island red) to 46 (Karuwalagaswewa village (TA)), were identified. Among the shared haplotypes, the B21-like haplotype was identified in 15 populations. The genetic relationship observed in a neighbour-joining tree based on the DA distance agreed with the breeding histories and geographic separations. The results indicated high MHC diversity in the local chicken populations. The difference in the allelic pattern among populations presumably reflects the effects of different genotypes, environments, geographic variation, and breeding policies in each country. The selection of MHC allele in domestic poultry can vary due to intensification of poultry production. Preserved MHC diversity in local chicken provides a great opportunity for future studies that address the relationships between MHC polymorphisms and differential immune responses.