bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Novel Model of Soil Legacy P Assessment for Calcareous and Acidic Soils
Authors: Yu Wenjia , Li Guohua , Hartmann Tobias Edward , Xu Minggang , Yang Xueyun , Li Haigang , Zhang Junling , Shen Jianbo
Published: January 2021

Phosphate (P) rock is a finite natural resource, and its use for P fertilizer production has resulted in its rapid depletion worldwide. In order to reduce the use of natural P resources, reducing the input of P into agricultural systems is necessary. The assessment of legacy P in soil is an option to maintain crop yield with low P fertilizer input. Many models have been tested to assess the contribution of legacy soil P to crop uptake. However, these models face a common challenge as conceptual soil P pools in models cannot be accurately initiated and evaluated using measured soil P indexes. In this study, a novel legacy P assessment (LePA) model was developed according to empirical equations about crop P uptake, soil Olsen-P, and total P from two long-term fertilizer experiments in typical calcareous and acidic soils in China. We used the DPPS (dynamic phosphorus pool simulator) model as a contrast model to estimate the simulation accuracy of the new LePA model. The calibration and validation datasets for both models were set-up by collecting data from two long-term fertilizer experiments in typical calcareous and acidic soils in China. The results showed that the LePA model simulated crop P uptake similar to the DPPS model in calcareous soil. While the DPPS model failed to depict crop P uptake under low pH conditions, the LePA model worked well after modification when limited crop growth caused by acidic conditions was considered. Moreover, the LePA model can also predict changes in soil TP and Olsen-P with P fertilizer application, which are new functions compared with the DPPS model. Based on a scenario analysis generated by the LePA model, P fertilizer application could be reduced by 52% in Yangling and 46% in Qiyang compared with the conventional application rate during this period to maintain the current yields if soil legacy P can be utilized efficiently. The LePA model is a useful tool for guiding soil P management from the field to country scales.
Effects of Wood Hydraulic Properties on Water Use and Productivity of Tropical Rainforest Trees
Authors: Kotowska Martyna M. , Link Roman M. , Röll Alexander , Hertel Dietrich , Hölscher Dirk , Waite Pierre-André , Moser Gerald , Tjoa Aiyen , Leuschner Christoph , Schuldt Bernhard
Published: January 2021

The efficiency of the water transport system in trees sets physical limits to their productivity and water use. Although the coordination of carbon assimilation and hydraulic functions has long been documented, the mutual inter-relationships between wood anatomy, water use and productivity have not yet been jointly addressed in comprehensive field studies. Based on observational data from 99 Indonesian rainforest tree species from 37 families across 22 plots, we analyzed how wood anatomy and sap flux density relate to tree size and wood density, and tested their combined influence on aboveground biomass increment (ABI) and daily water use (DWU). Results from pairwise correlations were compared to the outcome of a structural equation model (SEM). Across species, we found a strong positive correlation between ABI and DWU. Wood hydraulic anatomy was more closely related to these indicators of plant performance than wood density. According to the SEM, the common effect of average tree size and sap flux density on the average stem increment and water use of a species was sufficient to fully explain the observed correlation between these variables. Notably, after controlling for average size, only a relatively small indirect effect of wood properties on stem increment and water use remained that was mediated by sap flux density, which was significantly higher for species with lighter and hydraulically more efficient wood. We conclude that wood hydraulic traits are mechanistically linked to water use and productivity via their influence on sap flow, but large parts of these commonly observed positive relationships can be attributed to confounding size effects.
Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester
Authors: Xu Danping , Zhu Yiyang , Li Lanfang , Xu Yingping , Yan Weihua , Dai Meizhen , Gan Linghong
Published: January 2021

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.
Gnas Inactivation Alters Subcutaneous Tissues in Progression to Heterotopic Ossification
Authors: Brewer Niambi , Fong John T. , Zhang Deyu , Ramaswamy Girish , Shore Eileen M.
Published: January 2021

Heterotopic ossification (HO), the formation of bone outside of the skeleton, occurs in response to severe trauma and in rare genetic diseases such as progressive osseous heteroplasia (POH). In POH, which is caused by inactivation of GNAS, a gene that encodes the alpha stimulatory subunit of G proteins (Gsα), HO typically initiates within subcutaneous soft tissues before progressing to deeper connective tissues. To mimic POH, we used conditional Gnas-null mice which form HO in subcutaneous tissues upon Gnas inactivation. In response to Gnas inactivation, we determined that prior to detection of heterotopic bone, dermal adipose tissue changed dramatically, with progressively decreased adipose tissue volume and increased density of extracellular matrix over time. Upon depletion of the adipose tissue, heterotopic bone progressively formed in those locations. To investigate the potential relevance of the tissue microenvironment for HO formation, we implanted Gnas-null or control mesenchymal progenitor cells into Gnas-null or control host subcutaneous tissues. We found that mutant cells in a Gnas-null tissue environment induced a robust HO response while little/no HO was detected in control hosts. Additionally, a Gnas-null tissue environment appeared to support the recruitment of control cells to heterotopic bone, although control cell implants were associated with less HO formation compared to mutant cells. Our data support that Gnas inactivation alters the tissue microenvironment to influence mutant and wild-type progenitor cells to contribute to HO formation.
Global Transcriptome and Weighted Gene Co-expression Network Analyses of Growth-Stage-Specific Drought Stress Responses in Maize
Authors: Liu Songtao , Zenda Tinashe , Dong Anyi , Yang Yatong , Wang Nan , Duan Huijun
Published: January 2021

Drought is the major abiotic stress threatening maize (Zea mays L.) production globally. Despite recent scientific headway in deciphering maize drought stress responses, the overall picture of key genes, pathways, and co-expression networks regulating maize drought tolerance is still fragmented. Therefore, deciphering the molecular basis of maize drought tolerance remains pertinent. Here, through a comprehensive comparative leaf transcriptome analysis of drought-tolerant hybrid ND476 plants subjected to water-sufficient and water-deficit treatment conditions at flared (V12), tasseling (VT), the prophase of grain filling (R2), and the anaphase of grain filling (R4) crop growth stages, we report growth-stage-specific molecular mechanisms regulating maize drought stress responses. Based on the transcriptome analysis, a total of 3,451 differentially expressed genes (DEGs) were identified from the four experimental comparisons, with 2,403, 650, 397, and 313 DEGs observed at the V12, VT, R1, and R4 stages, respectively. Subsequently, 3,451 DEGs were divided into 12 modules by weighted gene co-expression network analysis (WGCNA), comprising 277 hub genes. Interestingly, the co-expressed genes that clustered into similar modules exhibited diverse expression tendencies and got annotated to different GO terms at different stages. MapMan analysis revealed that DEGs related to stress signal transduction, detoxification, transcription factor regulation, hormone signaling, and secondary metabolites biosynthesis were universal across the four growth stages. However, DEGs associated with photosynthesis and amino acid metabolism; protein degradation; transport; and RNA transcriptional regulation were uniquely enriched at the V12, VT, R2, and R4 stages, respectively. Our results affirmed that maize drought stress adaptation is a growth-stage-specific response process, and aid in clarifying the fundamental growth-stage-specific mechanisms regulating drought stress responses in maize. Moreover, genes and metabolic pathways identified here can serve as valuable genetic resources or selection targets for further functional validation experiments.
Epigenetic Regulation of Kupffer Cell Function in Health and Disease
Authors: Bennett Hunter , Troutman Ty D. , Sakai Mashito , Glass Christopher K.
Published: January 2021

Kupffer cells, the resident macrophages of the liver, comprise the largest pool of tissue macrophages in the body. Within the liver sinusoids Kupffer cells perform functions common across many tissue macrophages including response to tissue damage and antigen presentation. They also engage in specialized activities including iron scavenging and the uptake of opsonized particles from the portal blood. Here, we review recent studies of the epigenetic pathways that establish Kupffer cell identity and function. We describe a model by which liver-environment specific signals induce lineage determining transcription factors necessary for differentiation of Kupffer cells from bone-marrow derived monocytes. We conclude by discussing how these lineage determining transcription factors (LDTFs) drive Kupffer cell behavior during both homeostasis and disease, with particular focus on the relevance of Kupffer cell LDTF pathways in the setting of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.
Predicting Non-Alcoholic Fatty Liver Disease Progression and Immune Deregulations by Specific Gene Expression Patterns
Authors: Zeng Fanhong , Zhang Yue , Han Xu , Zeng Min , Gao Yi , Weng Jun
Published: January 2021

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide with rising rates in parallel to obesity, type 2 diabetes, and metabolic syndrome. NAFLD includes pathologies ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis and cirrhosis (NASH), which may eventually develop into hepatocellular carcinoma (HCC). Mechanically, lipids accumulation and insulin resistance act as the first hit, inflammation and fibrosis serve as the second hit. Currently, the diagnosis of NAFLD mainly depends on pathology examination and medical imaging, whereas proper gene signature classifiers are necessary for the evaluation of disease status. Here, we developed three signature classifiers to distinguish different NAFLD disease states (NAFL and NASH). Moreover, we found that B cells, DCs, and MAIT cells are key deregulated immune cells in NAFLD, which are associated with NAFLD and NAFLD-HCC progression. Meanwhile, AKR1B10 and SPP1 are closely related to the above three immune cell infiltrations and immunosuppressive cytokines expressions in NAFLD and NAFLD-HCC. Subsequently, we screened out AKR1B10 and SPP1 sensitive molecules TGX-221, which may provide a possible therapy for NAFLD and NAFLD-HCC.
Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases
Authors: Serra Pau , Santamaria Pere
Published: January 2021

The development of autoimmunity results from a breakdown of immunoregulation and involves cellularly complex immune responses against broad repertoires of epitope specificities. As a result, selective targeting of specific effector autoreactive T- or B-cells is not a realistic therapeutic option for most autoimmune diseases. Induction of autoantigen-specific regulatory T-cells capable of effecting bystander (dominant), yet tissue-specific, immunoregulation has thus emerged as a preferred therapeutic alternative. We have shown that peptide-major histocompatibility complex (pMHC)-based nanomedicines can re-program cognate autoantigen-experienced T-cells into disease-suppressing regulatory T-cells, which in turn elicit the formation of complex regulatory cell networks capable of comprehensively suppressing organ-specific autoimmunity without impairing normal immunity. Here, we summarize the various pMHC-based nanomedicines and disease models tested to date, the engineering principles underpinning the pharmacodynamic and therapeutic potency of these compounds, and the underlying mechanisms of action.
Self-Nucleic Acid Sensing: A Novel Crucial Pathway Involved in Obesity-Mediated Metaflammation and Metabolic Syndrome
Authors: Ferriere Amandine , Santa Pauline , Garreau Anne , Bandopadhyay Purbita , Blanco Patrick , Ganguly Dipyaman , Sisirak Vanja
Published: January 2021

Obesity and overweight are a global health problem affecting almost one third of the world population. There are multiple complications associated with obesity including metabolic syndrome that commonly lead to development of type II diabetes and non-alcoholic fatty liver disease. The development of metabolic syndrome and severe complications associated with obesity is attributed to the chronic low-grade inflammation that occurs in metabolic tissues such as the liver and the white adipose tissue. In recent years, nucleic acids (mostly DNA), which accumulate systemically in obese individuals, were shown to aberrantly activate innate immune responses and thus to contribute to metabolic tissue inflammation. This minireview will focus on (i) the main sources and forms of nucleic acids that accumulate during obesity, (ii) the sensing pathways required for their detection, and (iii) the key cellular players involved in this process. Fully elucidating the role of nucleic acids in the induction of inflammation induced by obesity would promote the identification of new and long-awaited therapeutic approaches to limit obesity-mediated complications.
Design and Synthesis of Single-Actuator Walking Robots via Coupling of Linkages
Authors: Zhang Yang , Arakelian Vigen
Published: January 2021

This paper deals with the development of single actuator walking robots designed by coupling of two mechanisms. The advantages of such robots are the simplicity of the design and its control system. In this paper, three various design concepts are carried out via coupling of two units which are four-bar linkages, slider-crank mechanisms, and a cam mechanism and a pantograph linkage. The geometrical syntheses of these mechanisms have been analyzed, and based on them, analytical and numerical methods have been adopted to ensure the reproduction of given trajectory similar to the human walking gait. Three single-actuator robots have been designed based on these mechanisms where two of them can be easily reconfigured to reproduce gaits with different lengths or even tilted gaits which make the robot able to climb stairs. All suggested design concepts have been validated through CAD simulations carried out via ADAMS software.
68Ga-DOTATOC PET/CT-Based Radiomic Analysis and PRRT Outcome: A Preliminary Evaluation Based on an Exploratory Radiomic Analysis on Two Patients
Authors: Liberini Virginia , Rampado Osvaldo , Gallio Elena , De Santi Bruno , Ceci Francesco , Dionisi Beatrice , Thuillier Philippe , Ciuffreda Libero , Piovesan Alessandro , Fioroni Federica , Versari Annibale , Molinari Filippo , Deandreis Désirée
Published: January 2021

Aim: This work aims to evaluate whether the radiomic features extracted by 68Ga-DOTATOC-PET/CT of two patients are associated with the response to peptide receptor radionuclide therapy (PRRT) in patients affected by neuroendocrine tumor (NET).

Methods: This is a pilot report in two NET patients who experienced a discordant response to PRRT (responder vs. non-responder) according to RECIST1.1. The patients presented with liver metastasis from the rectum and pancreas G3-NET, respectively. Whole-body total-lesion somatostatin receptor-expression (TLSREwb-50) and somatostatin receptor-expressing tumor volume (SRETV wb-50) were obtained in pre- and post-PRRT PET/CT. Radiomic analysis was performed, extracting 38 radiomic features (RFs) from the patients' lesions. The Mann–Whitney test was used to compare RFs in the responder patient vs. the non-responder patient. Pearson correlation and principal component analysis (PCA) were used to evaluate the correlation and independence of the different RFs.

Results: TLSREwb-50 and SRETVwb-50 modifications correlate with RECIST1.1 response. A total of 28 RFs extracted on pre-therapy PET/CT showed significant differences between the two patients in the Mann–Whitney test (p < 0.05). A total of seven second-order features, with poor correlation with SUVmax and PET volume, were identified by the Pearson correlation matrix. Finally, the first two PCA principal components explain 83.8% of total variance.

Conclusion: TLSREwb-50 and SRETVwb-50 are parameters that might be used to predict and to assess the PET response to PRRT. RFs might have a role in defining inter-patient heterogeneity and in the prediction of therapy response. It is important to implement future studies with larger and more homogeneous patient populations to confirm the efficacy of these biomarkers.
Purification of Crude Fructo-Oligosaccharide Preparations Using Probiotic Bacteria for the Selective Fermentation of Monosaccharide Byproducts
Authors: Fan Rong , Burghardt Jan Philipp , Huang Jinqing , Xiong Tao , Czermak Peter
Published: January 2021

Probiotics are microbes that promote health when consumed in sufficient amounts. They are present in many fermented foods or can be provided directly as supplements. Probiotics utilize non-digestible prebiotic oligosaccharides for growth in the intestinal tract, contributing to a healthy microbiome. The oligosaccharides favored by probiotics are species-dependent, as shown by the selective utilization of substrates in mixed sugar solutions such as crude fructo-oligosaccharides (FOS). Enzymatically produced crude FOS preparations contain abundant monosaccharide byproducts, residual sucrose, and FOS varying in chain length. Here we investigated the metabolic profiles of four probiotic bacteria during the batch fermentation of crude FOS under controlled conditions. We found that Bacillus subtilis rapidly utilized most of the monosaccharides but little sucrose or FOS. We therefore tested the feasibility of a microbial fed-batch fermentation process for the purification of FOS from crude preparations, which increased the purity of FOS from 59.2 to 82.5% with a final concentration of 140 g·l−1. We also tested cell immobilization in alginate beads as a means to remove monosaccharides from crude FOS. This encapsulation concept establishes the basis for new synbiotic formulations that combine probiotic microbes and prebiotic oligosaccharides.
Plant-Soil-Microbiota Combination for the Removal of Total Petroleum Hydrocarbons (TPH): An In-Field Experiment
Authors: Zuzolo Daniela , Guarino Carmine , Tartaglia Maria , Sciarrillo Rosaria
Published: January 2021

The contamination of soil with total petroleum hydrocarbons (TPH) may result in dramatic consequences and needs great attention, as soil rehabilitation would need more effort from a sustainability perspective. However, there is still no known general method since the remediation technology is strictly site-specific. Adaptive biological system dynamics can play a key role in understanding and addressing the potential of situ-specific biological combinations for soil pollutants removal. The potential worst-case of TPH contamination reflects soil affected by heavy industrial activities, such as oil refineries. Therefore, the experimental trial was conducted on a 2,000 m2 area from a contaminated site located in northern Italy. We evaluated the remediation potential over time (270 days) assessing (i) the phytoremediation efficiency of two species of Poaceae (Festuca arundinacea Schreb. and Dactylis glomerata L.) and two species of Fabaceae (Medicago sativa L. and Lotus corniculatus L.) and (ii) the role of the indigenous bacteria flora and endo-mycorrhizae consortium addition in plant growth promotion. We also induced resistance to contamination stress in a field experiment. Thirty-three indigenous bacteria selected from the contaminated soils showed marked plant growth promotion. Moreover, functional metagenomics confirmed the metabolic capability of hydrocarbon-degrading microorganisms living in the polluted soil. Our data showed that soil enzymatic activities increased with hydrocarbon degradation rate after 60 days. Both Poaceae and Fabaceae resulted in remarkable remediation potential. Stress markers and antioxidant activity indicated that the selected plant species generally need some time to adapt to TPH stress. In conclusion, our evaluation implied both the rhizosphere effects and functional features of the plant and suggested that plants should (i) have marked tolerance to specific contaminants, (ii) be characterized by an extensive root system, and (iii) be susceptible to arbuscular mycorrhizal fungi (AMF) infection.
Futuristic Non-antibiotic Therapies to Combat Antibiotic Resistance: A Review
Authors: Kumar Manoj , Sarma Devojit Kumar , Shubham Swasti , Kumawat Manoj , Verma Vinod , Nina Praveen Balabaskaran , JP Devraj , Kumar Santosh , Singh Birbal , Tiwari Rajnarayan R.
Published: January 2021

The looming problem of resistance to antibiotics in microorganisms is a global health concern. The drug-resistant microorganisms originating from anthropogenic sources and commercial livestock farming have posed serious environmental and health challenges. Antibiotic-resistant genes constituting the environmental “resistome” get transferred to human and veterinary pathogens. Hence, deciphering the origin, mechanism and extreme of transfer of these genetic factors into pathogens is extremely important to develop not only the therapeutic interventions to curtail the infections, but also the strategies to avert the menace of microbial drug-resistance. Clinicians, researchers and policymakers should jointly come up to develop the strategies to prevent superfluous exposure of pathogens to antibiotics in non-clinical settings. This article highlights the present scenario of increasing antimicrobial-resistance in pathogenic bacteria and the clinical importance of unconventional or non-antibiotic therapies to thwart the infectious pathogenic microorganisms.
Microsurgery vs. Gamma Knife Radiosurgery for the Treatment of Brainstem Cavernous Malformations: A Systematic Review and Meta-Analysis
Authors: Gao Xiangyu , Yue Kangyi , Sun Jidong , Cao Yuan , Zhao Boyan , Zhang Haofuzi , Dai Shuhui , Zhang Lei , Luo Peng , Jiang Xiaofan
Published: January 2021

Background: Brainstem cavernous malformations (BSCMs) are a subset of cerebral cavernous malformations with precarious locations and potentially devastating clinical courses. The effects and outcomes of treating BSCMs by microsurgery or gamma knife radiosurgery (GKRS) vary across studies.

Methods: We searched the Medline, Web of Science, The Cochrane Library, PubMed, and China Biology Medicine disc databases for original articles published in peer-reviewed journals of cohort studies reporting on 20 or more patients of any age with BSCMs with at least 80% completeness of follow-up.

Results: We included 43 cohorts involving 2,492 patients. Both microsurgery (RR = 0.04, 95% CI 0.01–0.16, P < 0.01) and GKRS (RR = 0.11, 95% CI 0.08–0.16, P < 0.01) demonstrated great efficacy in reducing the rehemorrhage rate after treatment for BSCMs. The incidence rates of composite outcomes were 19.8 (95% CI 16.8–22.8) and 15.7 (95% CI 11.7–19.6) after neurosurgery and radiosurgery, respectively. In addition, we found statistically significant differences in the median numbers of patients between neurosurgical and radiosurgical cohorts in terms of symptomatic intracranial hemorrhage (ICH; neurosurgical cohorts: median 0, range 0–33; radiosurgical cohorts: median 4, range 1–14; P < 0.05) and persistent focal neurological deficit (FND; neurosurgical cohorts: median 5, range 0–140; radiosurgical cohorts: median 1, range 0–3; P < 0.05).

Conclusions: The reported effects of treating BSCMs by microsurgery or GKRS are favorable for reducing recurrent hemorrhage from BSCMs. Patients in the neurosurgery cohort had a lower incidence of symptomatic ICH, while patients in the radiosurgical cohort had a lower incidence of persistent FND.
SPARC Knockdown Reduces Glutamate-Induced HT22 Hippocampal Nerve Cell Damage by Regulating Autophagy
Authors: Chen Shuang , Zou Qin , Guo Qiang , Chen Yongmin , Kuang Xi , Zhang Yukang , Liu Yan , Wu Wengang , Li Ge , Tu Linzhi , Tong Jingyi , Li Songrong , Ma Lin , Li Qifu
Published: January 2021

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein involved in the extracellular matrix and interactions between cells during neural development of the central nervous system (CNS). Oxidative glutamate toxicity is involved in CNS diseases, including epilepsy, Alzheimer’s disease, and ischemic stroke. However, the molecular mechanism of nerve injury is not fully understood in CNS diseases. Herein, the glutamate-induced nerve damage model was used to explore the molecular mechanisms affecting nerve damage. The levels of SPARC and autophagy were increased in glutamate-induced HT22 hippocampal nerve injury. In summary, the current study confirmed that SPARC regulates autophagy in HT22 hippocampal nerve cells, and its knockdown reduces the glutamate-induced HT22 hippocampal nerve injury by inhibiting autophagy. These findings suggested that SPARC plays a crucial role in nerve injury of CNS diseases.
The Subventricular Zone, a Hideout for Adult and Pediatric High-Grade Glioma Stem Cells
Authors: Lombard Arnaud , Digregorio Marina , Delcamp Clément , Rogister Bernard , Piette Caroline , Coppieters Natacha
Published: January 2021

Both in adult and children, high-grade gliomas (WHO grades III and IV) account for a high proportion of death due to cancer. This poor prognosis is a direct consequence of tumor recurrences occurring within few months despite a multimodal therapy consisting of a surgical resection followed by chemotherapy and radiotherapy. There is increasing evidence that glioma stem cells (GSCs) contribute to tumor recurrences. In fact, GSCs can migrate out of the tumor mass and reach the subventricular zone (SVZ), a neurogenic niche persisting after birth. Once nested in the SVZ, GSCs can escape a surgical intervention and resist to treatments. The present review will define GSCs and describe their similarities with neural stem cells, residents of the SVZ. The architectural organization of the SVZ will be described both for humans and rodents. The migratory routes taken by GSCs to reach the SVZ and the signaling pathways involved in their migration will also be described hereafter. In addition, we will debate the advantages of the microenvironment provided by the SVZ for GSCs and how this could contribute to tumor recurrences. Finally, we will discuss the clinical relevance of the SVZ in adult GBM and pediatric HGG and the therapeutic advantages of targeting that neurogenic region in both clinical situations.
Review on Mechanical Support and Cell-Based Therapies for the Prevention and Recovery of the Failed Fontan-Kreutzer Circulation
Authors: Ferrari Margaret R. , Di Maria Michael V. , Jacot Jeffrey G.
Published: January 2021

Though the current staged surgical strategy for palliation of single ventricle heart disease, culminating in a Fontan circulation, has increased short-term survival, mounting evidence has shown that the single ventricle, especially a morphologic right ventricle (RV), is inadequate for long-term circulatory support. In addition to high rates of ventricular failure, high central venous pressures (CVP) lead to liver fibrosis or cirrhosis, lymphatic dysfunction, kidney failure, and other comorbidities. In this review, we discuss the complications seen with Fontan physiology, including causes of ventricular and multi-organ failure. We then evaluate the clinical use, results, and limitations of long-term mechanical assist devices intended to reduce RV work and high CVP, as well as biological therapies for failed Fontan circulations. Finally, we discuss experimental tissue engineering solutions designed to prevent Fontan circulation failure and evaluate knowledge gaps and needed technology development to realize a more robust single ventricle therapy.
Effects of Hematopoietic Cell Transplantation on the Pulmonary Immune Response to Infection
Authors: Zinter Matt S. , Hume Janet R.
Published: January 2021

Pulmonary infections are common in hematopoietic cell transplant (HCT) patients of all ages and are associated with high levels of morbidity and mortality. Bacterial, viral, fungal, and parasitic pathogens are all represented as causes of infection. The lung mounts a complex immune response to infection and this response is significantly affected by the pre-HCT conditioning regimen, graft characteristics, and ongoing immunomodulatory therapy. We review the published literature, including animal models as well as human data, to describe what is known about the pulmonary immune response to infection in HCT recipients. Studies have focused on the pulmonary immune response to Aspergillus fumigatus, gram-positive and gram-negative bacteria, and viruses, and show a range of defects associated with both the innate and adaptive immune responses after HCT. There are still many open areas for research, to delineate novel therapeutic targets for pulmonary infections as well as to explore linkages to non-infectious inflammatory lung conditions.
A Systematic Review of the European Rapid Alert System for Food and Feed: Tendencies in Illegal Food Supplements for Weight Loss
Authors: Koncz Dorottya , Tóth Barbara , Roza Orsolya , Csupor Dezső
Published: January 2021

Background: Slimming products represent a dynamically growing group of food supplements worldwide. The efficacy of safely usable natural ingredients is usually below consumers’ expectations. Certain manufacturers add unauthorized or prohibited ingredients to weight loss supplements in order to increase their efficacy. Hence, many of these products are adulterated and may pose a risk to the consumers’ health.

Aims: The aim of our work was to give an overview on natural ingredients used in slimming products, to summarize the frequently used synthetic adulterants and also to assess the trends of adulterated and illegal food supplements in the European Union based on the warnings of the Rapid Alert System for Food and Feed (RASFF) in the time period of 1988–2019.

Methods: Reports between 1988–2019 were extracted from the RASFF portal on January 1, 2020. Each entry was individually reviewed.

Results: 2,559 records of food supplements with quality problems were identified in the RASFF, several of which [319 (12,5%)] were marketed to facilitate weight loss. 202 (63,3%) contained unapproved, synthetic drug ingredients. The major adulterant (113 of 319, 35.4%) was DNP (2,4-dinitrophenol), whereas sibutramine was the second most frequent adulterant agent (69 products, 21,6%) between 1988 and 2019.

Conclusion: The number of approved medicines for the indication of weight loss is relatively low and their efficacy (and also that of the natural ingredients) is limited. Therefore, a significant number of weight loss supplements is adulterated to satisfy patients’ expectations. Hence, these products may cause serious adverse effects in sensitive patients.
Role of Cardiac A2A Receptors Under Normal and Pathophysiological Conditions
Authors: Boknik P. , Eskandar J. , Hofmann B. , Zimmermann N. , Neumann J. , Gergs U.
Published: January 2021

This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A2A-AR in cells in the living heart, as well as the known interactions of A2A-AR with membrane-bound receptors, will be addressed. The possible role that the receptors play in some relevant cardiac pathologies, such as persistent or transient ischemia, hypoxia, sepsis, hypertension, cardiac hypertrophy, and arrhythmias, will be reviewed. Moreover, the cardiac utility of A2A-AR as therapeutic targets for agonistic and antagonistic drugs will be discussed. Gaps in our knowledge about the cardiac function of A2A-AR and future research needs will be identified and formulated.
The Structure of the Barley Husk Influences Its Resistance to Mechanical Stress
Authors: Grant Kathryn R. , Brennan Maree , Hoad Stephen P.
Published: January 2021

This paper explores the links between genotype, plant development, plant structure and plant material properties. The barley husk has two organs, the lemma and the palea, which protect the grain. When the husk is exposed to mechanical stress, such as during harvesting, it can be damaged or detached. This is known asgrain skinning, which is detrimental to grain quality and has a significant economic impact on industry. This study focused on the lemma, the husk organ which is most susceptible to grain skinning. This study tested three hypotheses: (1) genotype and plant development determine lemma structure, (2) lemma structure influences the material properties of the lemma, and (3) the material properties of the lemma determine grain skinning risk. The effect of genotype was investigated by using plant material from four malting barley varieties: two with a high risk of grain skinning, two with a low risk. Plant material was assessed at two stages of plant development (anthesis, GS 65; grain filling, GS 77). Structure was assessed using light microscopy to measure three physiological features: thickness, vasculature and cell area. Material properties were approximated using a controlled impact assay and by analyzing fragmentation behavior. Genotype had a significant effect on lemma structure and material properties from anthesis. This indicates that differences between genotypes were established during floral development. The lemma was significantly thinner in high risk genotypes, compared to low risk genotypes. Consequently, in high risk genotypes, the lemma was significantly more likely to fragment. This indicates a relationship between reduced lemma thickness and increased fragmentation. Traditionally, a thin husk has been considered beneficial for malting quality, due to an association with malt extract. However, this study finds a thin lemma is less resistant to mechanical stress. This may explain the differences in grain skinning risk in the genotypes studied.
Commercial Video Games in School Teaching: Two Mixed Methods Case Studies on Students’ Reflection Processes
Authors: Rüth Marco , Kaspar Kai
Published: January 2021

Commercial video games are popular entertainment media and part of students’ media reality. While commercial video games’ main purpose is not learning, they nonetheless could and should serve as objects of reflection in formal educational settings. Teachers could guide student learning and reflection as well as motivate students with commercial video games, but more evidence from formal educational settings is required. We conducted two mixed methods case studies to investigate students’ reflection processes using commercial video games in regular formal high school teaching. In a double lesson, 29 students of a 10th-grade biology course (Study 1) and 17 students of a 12th-grade advanced course on history (Study 2) played and discussed a commercial video game related to the current curricular topic. We examined the reflection processes of students in terms of their reactions to the teachers’ game-related statements and questions. Regarding teachers’ statements, students discussed several topics related to game enjoyment and the games’ representation of topic-related content. Regarding teachers’ questions, students discussed multiple goals in each game, how the games represented topic-related content, and how the games could be appropriate for learning. In Study 2, students additionally discussed emotions, stereotypes, violence, and the narrative related to the digital history game. We found that the discussions provided students opportunities to reflect on their game experiences and the current curricular topic as well as to practice media criticism. We further provide quantitative results on students’ perceived topic knowledge, on several facets of their learning motivation, and on their acceptance of video games. Overall, our findings illustrate the educational value of using commercial video games as objects of reflection.
Effect of Social Support on the Psychological Adjustment of Chinese Left-Behind Rural Children: A Moderated Mediation Model
Authors: Fan Zhiyu , Fan Xinghua
Published: January 2021

There are tens of millions of children left behind by one or both rural-to-urban migrant parents (left-behind children, LBC) in rural China. Compared to non-left-behind children (NLBC), LBC are disadvantaged in psychological adjustment. Research has shown social support can help LBC grow up healthily, but the plausible mechanisms linking support to adjustment remain unclear. The present study investigated the mediating role of basic psychological need satisfaction (BPNS) in the above relationship, as well as whether the predictive pathways of support on adjustment and BPNS were moderated by resilience in a sample of 692 LBC and 264 NLBC. Structural equation modeling indicated social support positively predicted LBC’s psychological adjustment, which was completely mediated by BPNS. In addition, the mediating effect was weaker for LBC with higher levels of resilience, which indicated resilience was a necessary asset for LBC’s growth amid the adversity of low social support.
Catechol-O-Methyltransferase Gene Val158Met Polymorphism Moderates the Effect of Social Exclusion and Inclusion on Aggression in Men: Findings From a Mixed Experimental Design
Authors: Wang Meiping , Chen Pian , Li Hang , Kemp Andrew Haddon , Zhang Wenxin
Published: January 2021

Accumulating research has identified the interactive effects of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and environmental factors on aggression. However, available evidence was mainly based upon correlational design, which yields mixed findings concerning who (Val vs. Met carriers) are more affected by environmental conditions and has been challenged for the low power of analyses on gene–environment interaction. Drawing on a mixed design, we scrutinized how COMT Val158Met polymorphism (between-group variable) impacts on aggression, assessed by hostility, aggressive motivation, and aggressive behavior, under different social conditions (exclusion vs. inclusion, within-group variable) in a sample of 70 Chinese male undergraduate students. We found that both Val/Val homozygote and Met alleles carriers showed differences in the feelings of hostility and aggressive motivation under conditions of exclusion versus inclusion, but these differences were more pronounced for Met allele carriers. These findings implied that COMT Val158Met polymorphism did not respond to environmental stimuli in an all-or-none way and shed light on the importance of examining the gene–environment interaction using a mixed design.
A Study on the Psychological Wound of COVID-19 in University Students
Authors: Padrón Isabel , Fraga Isabel , Vieitez Lucía , Montes Carlos , Romero Estrella
Published: January 2021

An increasing number of studies have addressed the psychological impact of the COVID-19 crisis on the general population. Nevertheless, far less is known about the impact on specific populations such as university students, whose psychological vulnerability has been shown in previous research. This study sought to examine different indicators of mental health in university students during the Spanish lockdown; we also analyzed the main sources of stress perceived by students in relation to the COVID-19 crisis, and the coping strategies adopted when faced with the situation. Data was collected from 932 students (704 women) through a web-based platform. Measures of anxiety (i.e., GAD-7), depression (PHQ-9), irritability, and self-perceived change in mental health were administered, as well as ad hoc measures of stressors and coping strategies. Results indicated that students experienced considerable psychological problems during the confinement, with higher rates of emotional difficulties in women and undergraduate students than in men and postgraduates, respectively. Psychological distress was mainly related to several specific domains of stressors, as perceived by the participants: academic future, task overload, worsening of interpersonal conflicts, and restrictions in pleasant social contact; and far less related to the spread of the disease and its consequences for physical health. As regards coping strategies, both reframing skills and daily routines were shown to be the most effective. A path-analysis model integrating stressors, coping, and mental health revealed that coping strategies partially mediated the effect of stressors on psychological health. In general, results suggest that students’ psychological health was substantially affected by the COVID-19 situation and that the academic and relational changes were the most notable sources of stress. This study reinforces the need to monitor and promote mental health in university students to boost resilience in times of crisis. Our results on effective coping strategies may inform preventive programs aimed at helping students to deal with challenges like the COVID-19 pandemic.
New Methods for Assessing Rapid Changes in Suicide Risk
Authors: Ballard Elizabeth D. , Gilbert Jessica R. , Wusinich Christina , Zarate Carlos A.
Published: January 2021

Rapid-acting interventions for the suicide crisis have the potential to transform treatment. In addition, recent innovations in suicide research methods may similarly expand our understanding of the psychological and neurobiological correlates of suicidal thoughts and behaviors. This review discusses the limitations and challenges associated with current methods of suicide risk assessment and presents new techniques currently being developed to measure rapid changes in suicidal thoughts and behavior. These novel assessment strategies include ecological momentary assessment, digital phenotyping, cognitive and implicit bias metrics, and neuroimaging paradigms and analysis methodologies to identify neural circuits associated with suicide risk. This review is intended to both describe the current state of our ability to assess rapid changes in suicide risk as well as to explore future directions for clinical, neurobiological, and computational markers research in suicide-focused clinical trials.
Autism Rating Scale: A New Tool for Characterizing the Schizophrenia Phenotype
Authors: Palumbo Davide , Stanghellini Giovanni , Mucci Armida , Ballerini Massimo , Giordano Giulia Maria , Lysaker Paul H. , Galderisi Silvana
Published: January 2021

Social dysfunctions (SD) are frequently observed in subjects with schizophrenia. Some of these dysfunctions are also observed in other neuropsychiatric disorders such as autism spectrum disorders (ASD), major depression, bipolar disorder, or Alzheimer disease. Recently, a characterization of a specific type of SD in schizophrenia has been proposed, with the concept of dis-sociality, which form the core aspect of “Schizophrenic Autism” (SA). The present study aimed to explore the presence in people with schizophrenia of SA, independent of other autistic traits, which can be often found in schizophrenia and other neurodevelopmental disorders. We used a structured interview—the Autism Rating Scale (ARS), an instrument devised to detect and measure SA. Fifty-one outpatients affected by schizophrenia (26 remitted, SCZ-r) and 28 affected by bipolar disorder type 1, with psychotic features, in the euthymic phase (BD-e) were recruited. Before assessing the specificity for schizophrenia of SA, we tested the internal consistency, the convergent and divergent validity of the ARS in the schizophrenia sample. Specificity was assessed by examining potential differences in ARS scores between SCZ-r and BD-e subjects. ARS showed good internal consistency, as well as convergent and divergent validity. ARS items were more frequently of moderate severity in SCZ-r than in BD-e subjects. This scale can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, and opens up the possibility of identifying a different type of SD in schizophrenia, independent of autistic traits and negative symptoms, which might benefit from different treatments.
Geographical and Epidemiological Characteristics of 3,487 Confirmed Cases With COVID-19 Among Healthcare Workers in China
Authors: Feng Maohui , Li Zhixiao , Xiong Jun , Xu Weiguo , Xiang Boqi
Published: January 2021

As the first area to report the outbreak, China used to be the front line of the battle against the novel coronavirus SARS-CoV-2. The present descriptive analysis of 3,487 COVID-19-confirmed cases with health workers reported through April 30, 2020 offers important new information to the international community on the epidemic in China. These data showed that Chinese measures including the high-grade protective gear used, mask wearing, and social distancing, are effective in reducing transmission in hospitals.