bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Assessment of the Contributions of Climate Change and Human Activities to Vegetation Variation in the Qinling Mountains
Authors: Cheng Dandong , Qi Guizeng , Song Jinxi , Zhang Yixuan , Bai Hongying , Gao Xiangyu
Published: December 2021

Quantitative assessment of the contributions of climate change and human activities to vegetation change is important for ecosystem planning and management. To reveal spatial differences in the driving mechanisms of vegetation change in the Qinling Mountains, the changing patterns of the normalized difference vegetation index (NDVI) in the Qinling Mountains during 2000–2019 were investigated through trend analysis and multiple regression residuals analysis. The relative contributions of climate change and human activities on vegetation NDVI change were also quantified. The NDVI shows a significant increasing trend (0.23/10a) from 2000 to 2019 in the Qinling Mountains. The percentage of areas with increasing and decreasing trends in NDVI is 87.96% and 12.04% of the study area, respectively. The vegetation change in the Qinling Mountains is caused by a combination of climate change and human activities. The Tongguan Shiquan line is a clear dividing line in the spatial distribution of drivers of vegetation change. Regarding the vegetation improvement, the contribution of climate change and human activities to NDVI increase is 51.75% and 48.25%, respectively. In the degraded vegetation area, the contributions of climate change and human activities to the decrease in NDVI were 22.11% and 77.89%, respectively. Thus, vegetation degradation is mainly caused by human activities. The implementation of policies, such as returning farmland to forest and grass, has an important role in vegetation protection. It is suggested that further attention should be paid to the role of human activities in vegetation degradation when formulating corresponding vegetation protection measures and policies.
DI (Differentiated Instruction) Does Matter! The Effects of DI on Secondary School Students’ Well-Being, Social Inclusion and Academic Self-Concept
Authors: Pozas Marcela , Letzel Verena , Lindner Katharina-Theresa , Schwab Susanne
Published: December 2021

In consideration of the substantial increase in students’ learning demands, teachers are urged to address student heterogeneity in their daily teaching practice by means of differentiated instruction (DI). The practice of DI, as a vehicle to achieve inclusive education, not only aims to support all students’ academic learning but also foster their social and emotional development. However, current research in the field of DI has mostly been limited to an examination of its effects on students’ achievement outcomes. Consequently, the potential impact of DI on students’ socio-emotional outcomes has, till now, received very little attention. In order to address this gap in the research, the current researchers seek to investigate the effects of DI on school students’ well-being, social inclusion and academic self-concept. Survey participants in this study included 379 students from 23 inclusive and regular classes in secondary schools in Austria. Following multilevel analyses, the results have indicated that students’ rating of their teachers’ DI practice is positively associated with their school well-being, social inclusion and academic self-concept. However, a t-test for dependent samples demonstrated that students perceive their teachers’ DI practice to be infrequent. Implications of the results along with further lines of research are also presented in this paper.
Isolating and Characterizing Phosphorus Solubilizing Bacteria From Rhizospheres of Native Plants Grown in Calcareous Soils
Authors: Li Krystal S. , Zeghbroeck J. Van , Liu Qingchun , Zhang Shouan
Published: December 2021

Many soils including urban soils have high legacy soil phosphorus (P) due to repeated applications of P fertilizers, but a large portion legacy soil P is fixed by calcium in the calcareous soils. Phosphorus solubilizing bacteria (PSB) have the ability to transfer fixed (non-labile) soil P into bioavailable P. The aim of this study was to isolate P solubilizing bacteria from the rhizospheres of four local native plants [broomsedge bluestem (Andropogon virginicus), giant sword ferns (Nephrolepis biserrata), sawgrass (Cladium jamaicense), and sea ox-eye daisy (Borrichia frutescens)] grown in low bioavailable P calcareous soils and to determine their ability to solubilize P. A total of 44 strains of PSB were isolated with 15 of them being identified by sequencing the 16S rRNA genes as Bacillus flexus, Beijerinckia fluminensis, Enterobacter ludwigii, Enterobacter sp., and Pantoea cypripedii. After a 7-day incubation, these strains reduced pH to <4.27 and increased water-soluble P up to 588 mg L−1. Enterobacter ludwigii showed superior P solubilizing ability amount PSB isolated. Therefore, the isolated strains from the local native environment have the potential to thrive in local calcareous soils and possess strong ability to transform non-labile P into bioavailable forms for plants to uptake.
Diagnostic Value of Immune-Related Genes in Kawasaki Disease
Authors: Liu Dong , Song Meixuan , Jing Fengchuan , Liu Bin , Yi Qijian
Published: December 2021

Kawasaki disease (KD) is a systemic vasculitis that predominantly damages medium- and small-sized vessels, and mainly causes coronary artery lesions (CALs). The diagnostic criterion of KD mainly depends on clinical features, so children could be easily misdiagnosed and could suffer from CALs. Through analysis, a total of 14 immune-related DEGs were obtained, of which IL1B, ADM, PDGFC, and TGFA were identified as diagnostic markers of KD. Compared with the non-KD group, KD patients contained a higher proportion of naive B cells, activated memory CD4 T cells, gamma delta T cells, and neutrophils, while the proportions of memory B cells, CD8 T cells, activated memory CD4 T cells, and activated NK cells were relatively lower. In conclusion, immune-related genes can be used as diagnostic markers of KD, and the difference in immune cells between KD and non-KD might provide new insight into understanding the pathogenesis of KD.
Phasor Histone FLIM-FRET Microscopy Maps Nuclear-Wide Nanoscale Chromatin Architecture With Respect to Genetically Induced DNA Double-Strand Breaks
Authors: Lou Jieqiong , Solano Ashleigh , Liang Zhen , Hinde Elizabeth
Published: December 2021

A DNA double-strand break (DSB) takes place in the context of chromatin, and there is increasing evidence for chromatin structure to play a functional role in DSB signaling and repair. Thus, there is an emerging need for quantitative microscopy methods that can directly measure chromatin network architecture and detect changes in this structural framework upon DSB induction within an intact nucleus. To address this demand, here we present the phasor approach to fluorescence lifetime imaging microscopy (FLIM) of Förster resonance energy transfer (FRET) between fluorescently labeled histones in the DSB inducible via AsiSI cell system (DIvA), which has sufficient spatial resolution to map nuclear-wide chromatin compaction at the level of nucleosome proximity with respect to multiple site-specific DSBs. We also demonstrate that when phasor histone FLIM-FRET is coupled with immunofluorescence, this technology has the unique advantage of enabling exploration of any heterogeneity that exists in chromatin structure at the spatially distinct and genetically induced DSBs.
Transcription-Replication Collisions and Chromosome Fragility
Authors: Wu Wei , He Jing Na , Lan Mengjiao , Zhang Pumin , Chu Wai Kit
Published: December 2021

Accurate replication of the entire genome is critical for cell division and propagation. Certain regions in the genome, such as fragile sites (common fragile sites, rare fragile sites, early replicating fragile sites), rDNA and telomeres, are intrinsically difficult to replicate, especially in the presence of replication stress caused by, for example, oncogene activation during tumor development. Therefore, these regions are particularly prone to deletions and chromosome rearrangements during tumorigenesis, rendering chromosome fragility. Although, the mechanism underlying their “difficult-to-replicate” nature and genomic instability is still not fully understood, accumulating evidence suggests transcription might be a major source of endogenous replication stress (RS) leading to chromosome fragility. Here, we provide an updated overview of how transcription affects chromosome fragility. Furthermore, we will use the well characterized common fragile sites (CFSs) as a model to discuss pathways involved in offsetting transcription-induced RS at these loci with a focus on the recently discovered atypical DNA synthesis repair pathway Mitotic DNA Synthesis (MiDAS).
IL-15Rα-Independent IL-15 Signaling in Non-NK Cell-Derived IFNγ Driven Control of Listeria monocytogenes
Authors: Nandi Madhuparna , Moyo Mitterrand Muamba , Orkhis Sakina , Mobulakani Jeanne Masunga Faida , Limoges Marc-André , Rexhepi Fjolla , Mayhue Marian , Cayarga Anny Armas , Marrero Gisela Cofino , Ilangumaran Subburaj , Menendez Alfredo , Ramanathan Sheela
Published: December 2021

Interleukin-15, produced by hematopoietic and parenchymal cells, maintains immune cell homeostasis and facilitates activation of lymphoid and myeloid cell subsets. IL-15 interacts with the ligand-binding receptor chain IL-15Rα during biosynthesis, and the IL-15:IL-15Rα complex is trans-presented to responder cells that express the IL-2/15Rβγccomplex to initiate signaling. IL-15-deficient and IL-15Rα-deficient mice display similar alterations in immune cell subsets. Thus, the trimeric IL-15Rαβγccomplex is considered the functional IL-15 receptor. However, studies on the pathogenic role of IL-15 in inflammatory and autoimmune diseases indicate that IL-15 can signal independently of IL-15Rαviathe IL-15Rβγcdimer. Here, we compared the ability of mice lacking IL-15 (no signaling) or IL-15Rα (partial/distinct signaling) to controlListeria monocytogenesinfection. We show that IL-15-deficient mice succumb to infection whereas IL-15Rα-deficient mice clear the pathogen as efficiently as wildtype mice. IL-15-deficient macrophages did not show any defect in bacterial uptake or iNOS expressionin vitro.In vivo, IL-15 deficiency impaired the accumulation of inflammatory monocytes in infected spleens without affecting chemokine and pro-inflammatory cytokine production. The inability of IL-15-deficient mice to clearL. monocytogenesresults from impaired early IFNγ production, which was not affected in IL-15Rα-deficient mice. Administration of IFNγ partially enabled IL-15-deficient mice to control the infection. Bone marrow chimeras revealed that IL-15 needed for early bacterial control can originate from both hematopoietic and non-hematopoietic cells. Overall, our findings indicate that IL-15-dependent IL-15Rα-independent signalingviathe IL-15Rβγcdimeric complex is necessary and sufficient for the induction of IFNγ from sources other than NK/NKT cells to control bacterial pathogens.
Evidence of Antitumor and Antimetastatic Potential of Induced Pluripotent Stem Cell-Based Vaccines in Cancer Immunotherapy
Authors: Kishi Masae , Asgarova Afag , Desterke Christophe , Chaker Diana , Artus Jérôme , Turhan Ali G. , Bennaceur-Griscelli Annelise , Griscelli Frank
Published: December 2021

Cancer is maintained by the activity of a rare population of self-renewing “cancer stem cells” (CSCs), which are resistant to conventional therapies. CSCs over-express several proteins shared with induced pluripotent stem cells (iPSCs). We show here that allogenic or autologous murine iPSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a highly aggressive triple-negative breast cancer, as a relevant cancer stemness model. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumoral effect was correlated with the generation of CD4+, CD8+ T cells, and CD44+ CD62L- CCR7low CD127low T-effector memory cells, and the reduction of CD4+ CD25+FoxP3+ Tregs, Arg1+ CD11b+ Gr1+, and Arg1+ and CD11b+ Ly6+ myeloid-derived suppressor cell populations within the tumor. The anti-tumoral effect was associated with a reduction in metastatic dissemination and an improvement in the survival rate. These results demonstrate for the first time the clinical relevance of using an off-the-shelf allogeneic iPSC-based vaccine combined with an HDACi as a novel pan-cancer anti-cancer immunotherapy strategy against aggressive tumors harboring stemness features with high metastatic potential.
The Effect of Conservative Oxygen Therapy in Reducing Mortality in Critical Care Patients: A Meta-Analysis and Trial Sequential Analysis
Authors: Ni Yue-Nan , Wang Ting , Liang Bin-Miao , Liang Zong-An
Published: December 2021

Background: Conservative oxygen therapy can prevent both hypoxemia and hyperoxemia, but the effect on the prognosis of patients admitted to the intensive care unit (ICU) remains controversial.

Methods: All controlled studies comparing conservative oxygen therapy and conventional oxygen therapy in adult patients admitted to the ICU were searched. The primary outcome was mortality, and the secondary outcomes were length of ICU stay (ICU LOS), length of hospital stay (hospital LOS), length of mechanical ventilation (MV) hours, new organ failure during ICU stay, and new infections during ICU stay.

Results: Nine trials with a total of 5,759 patients were pooled in our final studies. Compared with conventional oxygen therapy, conservative oxygen therapy did not reduce overall mortality (Z = 0.31, p = 0.75) or ICU LOS (Z = 0.17, p = 0.86), with firm evidence from trial sequential analysis, or hospital LOS (Z = 1.98, p = 0.05) or new infections during the ICU stay (Z = 1.45, p = 0.15). However, conservative oxygen therapy was associated with a shorter MV time (Z = 5.05, p < 0.00001), reduction of new organ failure during the ICU stay (Z = 2.15, p = 0.03) and lower risk of renal replacement therapy (RRT) (Z = 2.18, p = 0.03).

Conclusion: Conservative oxygen therapy did not reduce mortality but did decrease MV time, new organ failure and risk of RRT in critically ill patients.

Systematic Review Registration: identifier [CRD42020171055].
A Machine Learning Approach for the Prediction of Traumatic Brain Injury Induced Coagulopathy
Authors: Yang Fan , Peng Chi , Peng Liwei , Wang Jian , Li Yuejun , Li Weixin
Published: December 2021

Background: Traumatic brain injury-induced coagulopathy (TBI-IC), is a disease with poor prognosis and increased mortality rate.

Objectives: Our study aimed to identify predictors as well as develop machine learning (ML) models to predict the risk of coagulopathy in this population.

Methods: ML models were developed and validated based on two public databases named Medical Information Mart for Intensive Care (MIMIC)-IV and the eICU Collaborative Research Database (eICU-CRD). Candidate predictors, including demographics, family history, comorbidities, vital signs, laboratory findings, injury type, therapy strategy and scoring system were included. Models were compared on area under the curve (AUC), accuracy, sensitivity, specificity, positive and negative predictive values, and decision curve analysis (DCA) curve.

Results: Of 999 patients in MIMIC-IV included in the final cohort, a total of 493 (49.35%) patients developed coagulopathy following TBI. Recursive feature elimination (RFE) selected 15 variables, including international normalized ratio (INR), prothrombin time (PT), sepsis related organ failure assessment (SOFA), activated partial thromboplastin time (APTT), platelet (PLT), hematocrit (HCT), red blood cell (RBC), hemoglobin (HGB), blood urea nitrogen (BUN), red blood cell volume distribution width (RDW), creatinine (CRE), congestive heart failure, myocardial infarction, sodium, and blood transfusion. The external validation in eICU-CRD demonstrated that adapting boosting (Ada) model had the highest AUC of 0.924 (95% CI: 0.902–0.943). Furthermore, in the DCA curve, the Ada model and the extreme Gradient Boosting (XGB) model had relatively higher net benefits (ie, the correct classification of coagulopathy considering a trade-off between false- negatives and false-positives)—over other models across a range of threshold probability values.

Conclusions: The ML models, as indicated by our study, can be used to predict the incidence of TBI-IC in the intensive care unit (ICU).
Genomic Characterization of Clinical Listeria monocytogenes Isolates in Beijing, China
Authors: Zhang Xiaoai , Liu Yuzhu , Zhang Penghang , Niu Yanlin , Chen Qian , Ma Xiaochen
Published: December 2021

Listeria monocytogenes is a foodborne human pathogen that affects public health worldwide. Whole-genome sequencing (WGS) can classify L. monocytogenes isolates and identify virulence islands and resistance genes potentially influencing infectivity. Herein, WGS was used to assess 151 L. monocytogenes isolates from 120 cases of clinical infection in Beijing, China, between 2014 and 2018. Most isolates were either serogroup 1/2a,3a or serogroup 1/2b,3b,7, with 25 multilocus sequence typing (MLST) types (STs) represented, of which ST8, ST87, and ST5 were the most common. Core-genome MLST (cgMLST) grouped the 151 isolates into 116 cgMLST types. The discriminatory power of cgMLST was greater than other subtypes, revealing that isolates from the same patient were highly related (only differing at one allele). Eighty-six isolates formed 30 complexes with ≤ 7 cgMLST alleles between neighboring isolates, suggesting possible outbreaks. Compared with isolates in the United States, ST8, ST121, ST619, ST87, and ST155 isolates were grouped into unified clades. All 151 isolates were positive for common virulence-associated loci, and 26 lineage I isolates harbored the pathogenicity island 3 (LIPI-3) locus, while 42 lineage I isolates harbored the complete LIPI-4 locus. Eleven ST619 isolates had both LIPI-3 and LIPI-4. Among the 151 isolates, 13 were resistant to at least one antibiotic, and no multidrug-resistant isolates were identified. Resistance phenotypes correlated with genotypes, apart from two meropenem resistance isolates. The findings provided insight into the nature of L. monocytogenes strains currently causing clinical disease in Beijing, and WGS analysis indicated possible outbreaks.
Longitudinal Sampling Reveals Persistence of and Genetic Diversity in Extended-Spectrum Cephalosporin-Resistant Escherichia coli From Norwegian Broiler Production
Authors: Mo Solveig Sølverød , Norström Madelaine , Slettemeås Jannice Schau , Urdahl Anne Margrete , Telke Amar Anandrao , Sunde Marianne
Published: December 2021

There are knowledge gaps concerning dynamics of extended-spectrum cephalosporin (ESC)-resistant Escherichia coli and their plasmids in broiler production and the persistence of strains on broiler farms. Thus, we aimed at characterising ESC-resistant Escherichia coli collected from all flocks reared on 10 different farms during a six-months sampling period. All isolates (n = 43) were subjected to whole-genome sequencing, and a subset of isolates (n = 7) were also sequenced using oxford nanopore technology and subsequent hybrid assembly in order to do in-depth characterisation of the ESC resistance plasmids. The 43 isolates belonged to 11 different sequence types, and three different ESC resistance gene/plasmid combinations were present, namely, IncK2/blaCMY-2 (n = 29), IncI1/blaCMY-2 (n = 6) and IncI1/blaCTX-M-1 (n = 8). ESC-resistant E. coli of different STs and with different ESC resistance gene/plasmid combinations could be present on the same farm, while a single ST and ESC resistance gene/plasmid displaying zero or few SNP differences were present on other farms. In-depth characterisation of IncK2/blaCMY-2 plasmids revealed that at least two distinct variants circulate in the broiler production. These plasmids showed close homology to previously published plasmids from other countries. Our longitudinal study show that ESC-resistant E. coli belong to a multitude of different STs and that different ESC resistance genes and plasmids occur. However, there is also indication of persistence of both ESC-resistant E. coli strains and IncK2/blaCMY-2 plasmids on farms. Further studies are warranted to determine the dynamics of strains, plasmids and ESC resistance genes within single broiler flocks.
Beneficial Effects of a Short Course of Physical Prehabilitation on Neurophysiological Functioning and Neurovascular Biomarkers in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Trubnikova Olga A. , Tarasova Irina V. , Moskin Evgeniy G. , Kupriyanova Darya S. , Argunova Yuliya A. , Pomeshkina Svetlana A. , Gruzdeva Olga V. , Barbarash Olga L.
Published: December 2021

This study aimed to evaluate the effects of a short course of physical prehabilitation on neurophysiological functioning and markers of the neurovascular unit in patients undergoing coronary artery bypass grafting (CABG). We performed a prospective randomized study involving 97 male CABG patients aged 45–70 years, 47 of whom underwent a 5–7-day preoperative course of aerobic physical training (PhT). Both groups of patients were comparable with respect to baseline clinical and anamnestic characteristics. An extended neuropsychological and electroencephalographic (EEG) study was performed before surgery and at 7–10 days after CABG. Markers of the neurovascular unit [S100β, neuron-specific enolase (NSE), and brain-derived neurotrophic factor (BDNF)] were examined as metabolic correlations of early postoperative cognitive dysfunction (POCD) at three time points: before surgery, within the first 24 h after surgery, and 7–10 days after CABG. POCD developed in 58% of patients who underwent preoperative PhT, and in 79.5% of patients who did not undergo training, 7–10 days after CABG. Patients without prehabilitation demonstrated a higher percentage of theta1 power increase in the relative change values as compared to the PhT patients (p = 0.015). The short preoperative course of PhT was associated with low plasma S100β concentration, but high BDNF levels in the postoperative period. Patients who underwent a short preoperative course of PhT had better cognitive and electrical cortical activity indicators. Markers of the neurovascular unit indicated lower perioperative brain injury after CABG in those who underwent training. A short course of PhT before CABG can decrease the brain’s susceptibility to ischemia and reduce the severity of cognitive impairments in cardiac surgery patients. Electrical brain activity indicators and neurovascular markers, such as S100β and BDNF, can be informative for the effectiveness of cardiac rehabilitation programs.
The Role of Beta-Endorphin in Cocaine-Induced Conditioned Place Preference, Its Extinction, and Reinstatement in Male and Female Mice
Authors: Singh Prableen K. , Lutfy Kabirullah
Published: December 2021

Endogenous opioids have been implicated in cocaine reward. However, the role of each opioid peptide in this regard is unknown. Notably, the role of each peptide in extinction and reinstatement is not fully characterized. Thus, we assessed whether cocaine-induced conditioned place preference (CPP) and its extinction and reinstatement would be altered in the absence of beta-endorphin. We also examined if sex-related differences would exist in these processes. Male and female mice lacking beta-endorphin and their respective controls were tested for baseline place preference on day 1. On day 2, mice were treated with saline/cocaine (15 mg/kg) and confined to the vehicle- or drug-paired chamber for 30 min, respectively. In the afternoon, mice were treated with the alternate treatment and confined to the opposite chamber. Mice were then tested for CPP on day 3. Mice then received additional conditioning on this day as well as on day 4. Mice were then tested for CPP on day 5. Mice then received extinction training on day 9. On day 10, mice were tested for extinction and then reinstatement of CPP following a priming dose of cocaine (7.5 mg/kg). Male and female mice lacking beta-endorphin did not exhibit CPP following single conditioning with cocaine. On the other hand, only male mice lacking beta-endorphin failed to show CPP after repeated conditioning. Nonetheless, reinstatement of CPP was blunted in both male and female mice lacking beta-endorphin compared to controls. The present results suggest that beta-endorphin plays a functional role in cocaine-induced CPP and its reinstatement, and sex-related differences exist in the regulatory action of beta-endorphin on the acquisition but not reinstatement of cocaine CPP.
Adapting Highly-Dynamic Compliant Movements to Changing Environments: A Benchmark Comparison of Reflex- vs. CPG-Based Control Strategies
Authors: Schmidt Annika , Feldotto Benedikt , Gumpert Thomas , Seidel Daniel , Albu-Schäffer Alin , Stratmann Philipp
Published: December 2021

To control highly-dynamic compliant motions such as running or hopping, vertebrates rely on reflexes and Central Pattern Generators (CPGs) as core strategies. However, decoding how much each strategy contributes to the control and how they are adjusted under different conditions is still a major challenge. To help solve this question, the present paper provides a comprehensive comparison of reflexes, CPGs and a commonly used combination of the two applied to a biomimetic robot. It leverages recent findings indicating that in mammals both control principles act within a low-dimensional control submanifold. This substantially reduces the search space of parameters and enables the quantifiable comparison of the different control strategies. The chosen metrics are motion stability and energy efficiency, both key aspects for the evolution of the central nervous system. We find that neither for stability nor energy efficiency it is favorable to apply the state-of-the-art approach of a continuously feedback-adapted CPG. In both aspects, a pure reflex is more effective, but the pure CPG allows easy signal alteration when needed. Additionally, the hardware experiments clearly show that the shape of a control signal has a strong influence on energy efficiency, while previous research usually only focused on frequency alignment. Both findings suggest that currently used methods to combine the advantages of reflexes and CPGs can be improved. In future research, possible combinations of the control strategies should be reconsidered, specifically including the modulation of the control signal's shape. For this endeavor, the presented setup provides a valuable benchmark framework to enable the quantitative comparison of different bioinspired control principles.
Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency
Authors: Lotz-Havla Amelie S. , Weiß Katharina , Schiergens Katharina , Regenauer-Vandewiele Stephanie , Parhofer Klaus G. , Christmann Tara , Böhm Luise , Havla Joachim , Maier Esther M.
Published: December 2021

In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume (p = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced (p = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control (p = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies.
Impact of Intrapartum Antibiotic Prophylaxis on Offspring Microbiota
Authors: Prescott S. , Dreisbach C. , Baumgartel K. , Koerner R. , Gyamfi A. , Canellas M. , St. Fleur A. , Henderson W. A. , Trinchieri G.
Published: December 2021

Infants are born into a world filled with microbes and must adapt without undue immune response while exploiting the microbiota's ability to produce otherwise unavailable nutrients. The process by which humans and microbes establish this relationship has only recently begun to be studied with the aid of genomic methods. Nearly half of all pregnant women receive antibiotics during gestation to prevent maternal and neonatal infection. Though this has been largely successful in reducing early-onset sepsis, we have yet to understand the long-term consequences of antibiotic administration during gestation to developing infants. Studies involving antibiotic use in infants suggest that dysbiosis during this period is associated with increased obesity, allergy, autoimmunity, and chronic diseases in adulthood, however, research around the limited doses of intravenous antibiotics used for intrapartum prophylaxis is limited. In this mini review, we focused on the state of the science regarding the effects of intrapartum antibiotic prophylaxis on the newborn microbial colonization process. Although, the literature indicates that there is wide variety in the specific bacteria that colonize infants from birth, limited parenteral antibiotic administration prior to delivery consistently affects the microbiota of infants by decreasing bacteria in the phylum Bacteroidetes and increasing bacteria in the phylum Proteobacteria, thus altering the normal pattern of colonization that infants experience. Delivery by cesarean section and formula feeding magnify and prolong this effect. Our mini review shows that the impact of intravenous antibiotic administration during gestation has on early colonization, growth, or immune programming in the developing offspring has not been well studied in human or animal models.
Gross Motor Coordination: We Have a Problem! A Study With the Körperkoordinations Test für Kinder in Youth (6–13 Years)
Authors: Giuriato Matteo , Biino Valentina , Bellafiore Marianna , Battaglia Giuseppe , Palma Antonio , Baldari Carlo , Guidetti Laura , Gallotta Maria Chiara , Schena Federico , Lanza Massimo
Published: December 2021

The main goal of our cross-sectional research was to determine the current values of gross motor coordination (GMC) of Italian boys and girls between 6 and 13 years of age. Secondary goals were to study gender differences, and the four subtests trend with ages. Results were compared with the references proposed by KTK authors and with similar searches. Anthropometric measurements and KTK data from 2,206 schoolchildren (girls: n = 1,050; boys: n = 1,156) were collected. The KTK raw score (RS) increased with the age of the subjects (r = 0.678; p < 0.001). In 11–13-year-old subjects, the increase in results is less than in younger subjects. RS showed differences by gender (F = 5.899; p = 0.015) and age (F = 269.193; p < 0.001) without interaction gender × age. Motor quotient (MQ) tended to decrease with age (r = −0.148; p < 0.001); it showed differences by gender (F = 79.228; p < 0.001), age (F = 14.217; p < 0.001), and an interaction gender × age (F = 2.249; p < 0.05). Boys showed better performance than did girls in the raw scores of three of four subtests (JS: F = 24.529; MS: F = 9.052; HH: F = 11.105). Girls show better performances than did boys in the WB (F = 14.52). Differences between genders make us believe it appropriate to maintain a differentiated standardization. RS increased with age, and it seems reasonable, therefore, to maintain a GMC age-based normalization. On the contrary, MQ tended to decrease. All this makes us speculate that today's young people accumulate less significant motor experiences over the years compared to those achieved by their peers in the 1970s. Italian data were lower than German references and Belgian results but slightly higher than the Brazilian ones. The comparison among these four searches confirmed a worrying downward trend in GMC and its characterization by geographical and sociocultural areas. Updated parameters of the KTK can provide helpful references to improve policies to support physical activity, sport, and physical education in youth.
Astragalus mongholicus Bunge Water Extract Exhibits Anti-inflammatory Effects in Human Neutrophils and Alleviates Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice
Authors: Cheng Wei-Jen , Chiang Chih-Chao , Lin Cheng-Yu , Chen Yu-Li , Leu Yann-Lii , Sie Jia-Yu , Chen Wen-Ling , Hsu Chung-Yuan , Kuo Jong-Jen , Hwang Tsong-Long
Published: December 2021

Neutrophils are the primary immune cells in innate immunity, which are related to various inflammatory diseases. Astragalus mongholicus Bunge is a Chinese medicinal herb used to treat various oxidative stress-related inflammatory diseases. However, there are limited studies that elucidate the effects of Astragalus mongholicus Bunge in human neutrophils. In this study, we used isolated human neutrophils activated by various stimulants to investigate the anti-inflammatory effects of Astragalus mongholicus Bunge water extract (AWE). Cell-free assays were used to examine free radicals scavenging capabilities on superoxide anion, reactive oxygen species (ROS), and nitrogen-centered radicals. Imiquimod (IMQ) induced psoriasis-like skin inflammation mouse model was used for investigating anti-psoriatic effects. We found that AWE inhibited superoxide anion production, ROS generation, and elastase release in human neutrophils, which exhibiting a direct anti-neutrophil effect. Moreover, AWE exerted a ROS scavenging ability in the 2,2’-Azobis (2-amidinopropane) dihydrochloride assay, but not superoxide anion in the xanthine/xanthine oxidase assay, suggesting that AWE exhibited anti-oxidation and anti-inflammatory capabilities by both scavenging ROS and by directly inhibiting neutrophil activation. AWE also reduced CD11b expression and adhesion to endothelial cells in activated human neutrophils. Meanwhile, in mice with psoriasis-like skin inflammation, administration of topical AWE reduced both the affected area and the severity index score. It inhibited neutrophil infiltration, myeloperoxidase release, ROS-induced damage, and skin proliferation. In summary, AWE exhibited direct anti-inflammatory effects by inhibiting neutrophil activation and anti-psoriatic effects in mice with IMQ-induced psoriasis-like skin inflammation. Therefore, AWE could potentially be a pharmaceutical Chinese herbal medicine to inhibit neutrophilic inflammation for anti-psoriasis.
Sigma-1 Receptor is a Pharmacological Target to Promote Neuroprotection in the SOD1G93A ALS Mice
Authors: Gaja-Capdevila Núria , Hernández Neus , Navarro Xavier , Herrando-Grabulosa Mireia
Published: December 2021

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the death of motoneurons (MNs) with a poor prognosis. There is no available cure, thus, novel therapeutic targets are urgently needed. Sigma-1 receptor (Sig-1R) has been reported as a target to treat experimental models of degenerative diseases and, importantly, mutations in the Sig-1R gene cause several types of motoneuron disease (MND). In this study we compared the potential therapeutic effect of three Sig-1R ligands, the agonists PRE-084 and SA4503 and the antagonist BD1063, in the SOD1G93A mouse model of ALS. Pharmacological administration was from 8 to 16 weeks of age, and the neuromuscular function and disease progression were evaluated using nerve conduction and rotarod tests. At the end of follow up (16 weeks), samples were harvested for histological and molecular analyses. The results showed that PRE-084, as well as BD1063 treatment was able to preserve neuromuscular function of the hindlimbs and increased the number of surviving MNs in the treated female SOD1G93A mice. SA4503 tended to improve motor function and preserved neuromuscular junctions (NMJ), but did not improve MN survival. Western blot analyses revealed that the autophagic flux and the endoplasmic reticulum stress, two pathways implicated in the physiopathology of ALS, were not modified with Sig-1R treatments in SOD1G93A mice. In conclusion, Sig-1R ligands are promising tools for ALS treatment, although more research is needed to ascertain their mechanisms of action.
Assessment of Drug Proarrhythmicity Using Artificial Neural Networks With in silico Deterministic Model Outputs
Authors: Yoo Yedam , Marcellinus Aroli , Jeong Da Un , Kim Ki-Suk , Lim Ki Moo
Published: December 2021

As part of the Comprehensive in vitro Proarrhythmia Assay initiative, methodologies for predicting the occurrence of drug-induced torsade de pointes via computer simulations have been developed and verified recently. However, their predictive performance still requires improvement. Herein, we propose an artificial neural networks (ANN) model that uses nine multiple input features, considering the action potential morphology, calcium transient morphology, and charge features to further improve the performance of drug toxicity evaluation. The voltage clamp experimental data for 28 drugs were augmented to 2,000 data entries using an uncertainty quantification technique. By applying these data to the modified O’Hara Rudy in silico model, nine features (dVm/dtmax, APresting, APD90, APD50, Caresting, CaD90, CaD50, qNet, and qInward) were calculated. These nine features were used as inputs to an ANN model to classify drug toxicity into high-risk, intermediate-risk, and low-risk groups. The model was trained with data from 12 drugs and tested using the data of the remaining 16 drugs. The proposed ANN model demonstrated an AUC of 0.92 in the high-risk group, 0.83 in the intermediate-risk group, and 0.98 in the low-risk group. This was higher than the classification performance of the method proposed in previous studies.
Polyamine Putrescine Regulates Oxidative Stress and Autophagy of Hemocytes Induced by Lipopolysaccharides in Pearl Oyster Pinctada fucata martensii
Authors: Cao Yanfei , Jiao Yu , Zhan Shuzhi , Liang Xueru , Li Zhixin , Chen Jiayi , Xiong Xinwei , Gu Zefeng , Du Xiaodong , Zheng Zhe
Published: December 2021

The polyamine putrescine (Put) is a ubiquitous small cationic amine. It plays an essential role in controlling the innate immune response. However, little is known about its function in mollusks. In this study, the Put content was observed to increase in the serum of pearl oyster Pinctada fucata martensii after 6 and 24 h of lipopolysaccharide (LPS) stimulation. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) increased, and nitric oxide synthase was downregulated in the Put group (i.e., combined treatment with Put and LPS) compared with that in the LPS group (i.e., combined treatment with phosphate-buffered saline and LPS). Furthermore, activities of alkaline phosphatase and acid phosphatase were inhibited after 6 h of LPS stimulation. The expression levels of the nuclear factor kappa B, IκB kinase, Janus kinase, and signal transducer and activator of transcription proteins genes were all significantly suppressed at 12 and 24 h in the Put group. Pseudomonas aeruginosa and Bacillus subtilis grew better after being incubated with the serum from the Put group than that from the LPS group. Additionally, the Put treatment remarkably inhibited the autophagy of hemocytes mediated by the AMP-activated protein kinase-mammalian target of rapamycin-Beclin-1 pathway. This study demonstrated that Put can effectively inhibit the inflammatory response induced by LPS in pearl oysters. These results provide useful information for further exploration of the immunoregulatory functions of polyamines in bivalves and contribute to the development of immunosuppressive agents.
Effects of Light on Secondary Metabolite Biosynthesis in Medicinal Plants
Authors: Zhang Shuncang , Zhang Lei , Zou Haiyan , Qiu Lin , Zheng Yuwei , Yang Dongfeng , Wang Youping
Published: December 2021

Secondary metabolites (SMs) found in medicinal plants are one of main sources of drugs, cosmetics, and health products. With the increase in demand for these bioactive compounds, improving the content and yield of SMs in medicinal plants has become increasingly important. The content and distribution of SMs in medicinal plants are closely related to environmental factors, especially light. In recent years, artificial light sources have been used in controlled environments for the production and conservation of medicinal germplasm. Therefore, it is essential to elucidate how light affects the accumulation of SMs in different plant species. Here, we systematically summarize recent advances in our understanding of the regulatory roles of light quality, light intensity, and photoperiod in the biosynthesis of three main types of SMs (polyphenols, alkaloids, and terpenoids), and the underlying mechanisms. This article provides a detailed overview of the role of light signaling pathways in SM biosynthesis, which will further promote the application of artificial light sources in medicinal plant production.
Diseases Detection of Occlusion and Overlapping Tomato Leaves Based on Deep Learning
Authors: Wang Xuewei , Liu Jun , Liu Guoxu
Published: December 2021

Background: In view of the existence of light shadow, branches occlusion, and leaves overlapping conditions in the real natural environment, problems such as slow detection speed, low detection accuracy, high missed detection rate, and poor robustness in plant diseases and pests detection technology arise.

Results: Based on YOLOv3-tiny network architecture, to reduce layer-by-layer loss of information during network transmission, and to learn from the idea of inverse-residual block, this study proposes a YOLOv3-tiny-IRB algorithm to optimize its feature extraction network, improve the gradient disappearance phenomenon during network deepening, avoid feature information loss, and realize network multilayer feature multiplexing and fusion. The network is trained by the methods of expanding datasets and multiscale strategies to obtain the optimal weight model.

Conclusion: The experimental results show that when the method is tested on the self-built tomato diseases and pests dataset, and while ensuring the detection speed (206 frame rate per second), the mean Average precision (mAP) under three conditions: (a) deep separation, (b) debris occlusion, and (c) leaves overlapping are 98.3, 92.1, and 90.2%, respectively. Compared with the current mainstream object detection methods, the proposed method improves the detection accuracy of tomato diseases and pests under conditions of occlusion and overlapping in real natural environment.
Cerebellar Functional Lateralization From the Perspective of Clinical Neuropsychology
Authors: Starowicz-Filip Anna , Prochwicz Katarzyna , Kłosowska Joanna , Chrobak Adrian Andrzej , Myszka Aneta , Bętkowska-Korpała Barbara , Kwinta Borys
Published: December 2021

Objective: The cerebellar functional laterality, with its right hemisphere predominantly involved in verbal performance and the left one engaged in visuospatial processes, has strong empirical support. However, the clinical observation and single research results show that the damage to the right cerebellar hemisphere may cause extralinguistic and more global cognitive decline. The aim of our research was to assess the pattern of cognitive functioning, depending on the cerebellar lesion side, with particular emphasis on the damage to the right cerebellar hemisphere.

Method: The study sample consisted of 31 patients with focal cerebellar lesions and 31 controls, free of organic brain damage. The Addenbrooke’s Cognitive Examination ACE III and the Trail Making Test TMT were used to assess patients’ cognitive functioning.

Results: Left-sided cerebellar lesion patients scored lower than controls in attention and visuospatial domain, but not in language, fluency, and memory functions. Participants with right-sided cerebellar lesion demonstrated a general deficit of cognitive functioning, with impairments not only in language and verbal fluency subscales but also in all ACE III domains, including memory, attention, and visuospatial functions. The TMT results proved that cerebellar damage is associated with executive function impairment, regardless of the lesion side.

Conclusion: The cognitive profiles of patients with cerebellum lesions differ with regard to the lesion side. Left-sided cerebellar lesions are associated with selective visuospatial and attention impairments, whereas the right-sided ones may result in a more global cognitive decline, which is likely secondary to language deficiencies, associated with this lateral cerebellar injury.
Preschoolers' Empathy Profiles and Their Social Adjustment
Authors: Simon Poline , Nader-Grosbois Nathalie
Published: December 2021

Preschoolers face new challenges in their social life: the development of social and emotional abilities in order to have positive relationships with peers and adults. Empathy, the ability to share and understand the emotions of others, contributes to this socio-emotional adjustment. This exploratory study examines mothers and fathers' perceptions of their child's empathy and individual factors, such as age, gender, and personality, which are related to cognitive and affective empathy in 63 typically developing preschoolers. Links between children's individual characteristics (empathy and personality) and their social adjustment on the one hand and risk of developing internalized vs. externalized behaviors on the other were also investigated. Parents completed four questionnaires about their child's empathy, personality, and social (mal)adjustment. The results showed that mothers and fathers perceived their children's cognitive and affective empathy, attention to others' feelings, and social actions (such as helping), in the same way, except for emotion contagion. Gender differences appeared specifically for some components of empathy: girls were said to pay more attention to others' emotions while boys had better cognitive empathy. Moreover, children's empathy as perceived by mothers or fathers was positively linked with their age, and with personality factors (extraversion, emotional stability, agreeableness, and openness to experience). Cognitive empathy and personality were found to be partly related to higher social skills and lower externalized and internalized behaviors. The results nuanced specific links between cognitive and affective empathy and social adjustment as well as behavior problems at preschool age. These results may have some implications for future research and prevention in childhood.