bluuebunny/crossref_metadata_2025 huggingface dataset:
Tiers 1 and 2 of a German MTSS: impact of a multiple baseline study on elementary school students with disruptive behavior
Authors: Nitz Jannik , Hagen Tobias , Krull Johanna , Verbeck Leonie , Eiben Katrin , Hanisch Charlotte , Hennemann Thomas
Published: June 2023

Introduction

The prevalence of disruptive behavior is increasing worldwide, affecting the learning process and classroom climate, teacher–student relationships, and peer interactions. Disruptive behavior in childhood can have detrimental effects on a child’s long-term growth and may predict similar behavior in adolescence and adulthood. Thus, it is not only contemporary education and school research that are concerned with addressing the issues of teacher workload reduction and improvement of students’ learning environment, but it is also a socially relevant issue. The Multi-tiered Systems of Supports (MTSS) effectively mitigates some of these challenges in the education system and is recognized as a successful framework.

Methods

Therefore, this single-case study examined the first two tiers of an MTSS developed in Germany (Multimo) to determine the impact of its implementation on 32 students with disruptive behavior. The first hypothesis propose that the implementation of Tier 1 can effectively decrease disruptive behavior among all students and the second one that assigning students to Tier 2 can provide an additional reduction in disruptive behavior. Data analysis included multilevel analyses with piecewise-multilevel models and the overlap index, the Nonoverlap of All Pairs, based on teachers’ direct behavior rating. All analyses focused exclusively on the outcome variable of disruptive behavior, which was estimated based on teachers’ daily behavior ratings.

Results

The results of the study showed a significant reduction of disruptive behavior in elementary school students at Tier 1. Disruptive behavior decreased at Tier 2 as well but did not show a significant change compared with Tier 1.

Discussion

The study concludes that in the context of an MTSS, the Good Behavior Game and Daily Behavior Report Card can be used together.
The comparison of three different molecular imaging methods in localization and grading of insulinoma
Authors: Chang Lina , Bi Xinyu , Li Shuo , Tong Qi , Gu Yian , He Zonghao , Li Yansheng , Chen Qiusong , Cui Jingqiu , Yu Haonan , He Qing , Liu Ming
Published: June 2023

Aims

This cross-sectional study compared the value of molecular imaging (Exendin-4 positron emission tomography/computed tomography [PET/CT], 68Ga-DOTATATE PET/CT, 18F- fluorodeoxyglucose [FDG] PET/CT) in insulinoma localization by stratified tumor size and grading, and explored the correlation of the related the maximum standardized uptake value (SUVmax) with insulinoma grading, Ki-67, maximum tumor diameter, and glucose metabolism.

Methods

In 28 insulinoma patients, the sensitivity of three types of PET/CT for localizing insulinoma was calculated according to tumor size and grade. We compared the SUVmax for different insulinoma grades and analyzed the correlation of SUVmax with Ki-67, maximum tumor diameter, and glucose metabolism indicators.

Results

The study included 12 grade (G) 1 and 16 G2 cases, with maximum tumor diameters ranging from 9 to 40 mm. Without differentiation by size and grade, the sensitivity of Exendin-4 PET/CT to localize insulinoma was 100%, which significantly exceeded that of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT (75% and 57%, respectively). In tumors with a maximum diameter ≤ 20 mm and ≤ 15 mm, the sensitivity of Exendin-4 (both 100%) significantly exceeded that of 68Ga-DOTATATE PET/CT (74% and 64%, respectively) and 18F-FDG PET/CT (54% and 50%, respectively). In G1 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of 18F-FDG PET/CT, but not that of 68Ga-DOTATATE PET/CT, while in G2 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of both other types. However, all three PET/CT types missed a metastatic lymph node in one patient. The 18F-FDG PET/CT SUVmax was significantly lower than that of the other PET/CT types and that of 68Ga-DOTATATE PET/CT was significantly lower in G2 than in G1. 68Ga-DOTATATE PET/CT SUVmax correlated negatively with Ki-67. A receiver operating characteristic (ROC) curve suggested that 68Ga-DOTATATE PET/CT SUVmax > 19.9 could predict G1 tumors.

Conclusion

Exendin-4 PET/CT was superior to 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT for insulinoma localization, particularly small and G2 tumors, but its diagnostic value in small metastatic lymph nodes requires further exploration. 68Ga-DOTATATE PET/CT SUVmax could be used as an adjunct to pathology, and a value > 19.9 could predict G1 tumors. No PET/CT SUVmax could predict tumor maximum diameter and glucose metabolism.
Coordinated control of multiple converters in model-free AC/DC distribution networks based on reinforcement learning
Authors: Zhao Qianyu , Han Zhaoyang , Wang Shouxiang , Dong Yichao , Qian Guangchao
Published: June 2023

Taking into account the challenges of obtaining accurate physical parameters and uncertainties arising from the integration of a large number of sources and loads, this paper proposes a real-time voltage control method for AC/DC distribution networks. The method utilizes model-free generation and coordinated control of multiple converters, and employs a combination of agent modeling and multi-agent soft actor critic (MASAC) techniques for modeling and solving the problem. Firstly, a complex nonlinear mapping relationship between bus power and voltage is established by training an power-voltage model, to address the issue of obtaining physical parameters in AC/DC distribution networks. Next, a Markov decision process is established for the voltage control problem, with multiple intelligent agents distributed to control the active and reactive power at each converter, in response to the uncertainties of photovoltaic (PV) and load variations. Using the MASAC method, a centralized training strategy and decentralized execution policy are implemented to achieve distributed control of the converters, with each converter making optimal decisions based on its local observation state. Finally, the proposed method is verified by numerical simulations, demonstrating its sound effectiveness and generalization ability.
Molecular characterization, adaptive evolution, and expression analysis of the Toll-like receptor gene family in Fenneropenaeus chinensis
Authors: Chen Lulu , Tang Dan , Hua Yuyan , Wang Xinyu , Li Yanxuan , Wang Zhengfei
Published: June 2023

Global warming is a challenge to animal health because of the increased environmental temperature, with subsequent induction of immune suppression and increased susceptibility to disease during summer. The Toll-like receptor (TLR) family is an essential pattern recognition receptor (PRR) that initiates the innate immune response by sensing conserved molecular patterns of pathogens. However, research on the TLR gene family in decapod crustaceans has been conducted sporadically, without systematic naming, and the relationship between pathogen immunity adaptation and adaptive evolution of immune-related genes is unclear. In this study, various TLR gene sequences in decapod crustaceans were collected, and the unified name of Fenneropenaeus chinensis was confirmed using sequence alignment. Structural characteristics and evolutionary analyses of TLR genes in decapod crustaceans were performed, and ten FcTLR genes were identified in F. chinensis. Protein domain analysis revealed that FcTLR proteins contain 4–25 LRR domains used to recognize different pathogens. Selection pressure analysis revealed that TLR1 and TLR9 were subjected to positive selection pressure in decapod crustaceans, which may be related to their resistance to environmental changes. Furthermore, the expression of ten TLR genes was detected in F. chinensis following white spot syndrome virus (WSSV) infection. The results demonstrated that FcTLR1, FcTLR7, and FcTLR9 responded positively, which was also consistent with the results of the protein domain and selection pressure analyses. This study provides new insights into the immune response and adaptive evolution of TLRs in decapod crustaceans to prevent environmental damage, such as pathogens and high temperature.
Exploring the future of GM technology in sustainable local food systems in Colombia
Authors: Cárdenas Pardo Néstor Julián , Rodriguez Robayo Dolly Esperanza , Fernandez Lizarazo John Cristhian , Peña-Quemba Diego Camilo , McGale Erica
Published: June 2023

The security of Earth’s food systems is challenged by shifting regional climates. While agricultural processes are disrupted by climate change, they also play a large role in contributing to destabilizing greenhouse gases. Finding new strategies to increase yields while decreasing agricultural environmental impacts is essential. Tropical agriculture is particularly susceptible to climate change: local, smallholder farming, which provides a majority of the food supply, is high risk and has limited adaptation capacity. Rapid, inexpensive, intuitive solutions are needed, like the implementation of genetically modified (GM) crops. In the Latin American tropics, high awareness and acceptance of GM technologies, opportunities to test GM crops as part of local agricultural educations, and their known economic benefits, support their use. However, this is not all that is needed for the future of GM technologies in these areas: GM implementation must also consider environmental and social sustainability, which can be unique to a locality. Primarily from the perspective of its educators, the potential of a rural Colombian university in driving GM implementation is explored, including the role of this type of university in producing agricultural engineers who can innovate with GM to meet regionally-dependent environmental and cultural needs that could increase their sustainability.
A novel disulfidptosis-associated expression pattern in breast cancer based on machine learning
Authors: Wang Zhitang , Du Xianqiang , Lian Weibin , Chen Jialin , Hong Chengye , Li Liangqiang , Chen Debo
Published: June 2023

Background: Breast cancer (BC), the leading cause of cancer-related deaths among women, remains a serious threat to human health worldwide. The biological function and prognostic value of disulfidptosis as a novel strategy for BC treatment via induction of cell death remain unknown.

Methods: Gene mutations and copy number variations (CNVs) in 10 disulfidptosis genes were evaluated. Differential expression, prognostic, and univariate Cox analyses were then performed for 10 genes, and BC-specific disulfidptosis-related genes (DRGs) were screened. Unsupervised consensus clustering was used to identify different expression clusters. In addition, we screened the differentially expressed genes (DEGs) among different expression clusters and identified hub genes. Moreover, the expression level of DEGs was detected by RT-qPCR in cellular level. Finally, we used the least absolute shrinkage and selection operator (LASSO) regression algorithm to establish a prognostic feature based on DEGs, and verified the accuracy and sensitivity of its prediction through prognostic analysis and subject operating characteristic curve analysis. The correlation of the signature with the tumor immune microenvironment and tumor stemness was analyzed.

Results: Disulfidptosis genes showed significant CNVs. Two clusters were identified based on three DRGs (DNUFS1, LRPPRC, SLC7A11). Cluster A was found to be associated with better survival outcomes(p < 0.05) and higher levels of immune cell infiltration(p < 0.05). A prognostic signature of four disulfidptosis-related DEGs (KIF21A, APOD, ALOX15B, ELOVL2) was developed by LASSO regression analysis. The signature showed a good prediction ability. In addition, the prognostic signature in this study were strongly related to the tumor microenvironment (TME), tumor immune cell infiltration, tumor mutation burden (TMB), tumor stemness, and drug sensitivity.

Conclusion: The prognostic signature we constructed based on disulfidptosis-DEGs is a good predictor of prognosis in patients with BC. This prognostic signature is closely related to TME, and its potential correlation provides clues for further studies.
Gendered impacts of the war in Ukraine: identifying potential, presumed or actual women victims of trafficking at the Italian borders
Authors: Cimino Francesca , Degani Paola
Published: June 2023

According to the United Nations High Commissioner for Refugee (UNHCR) data, approximately 8 million people, mostly women and children, entered and registered in Europe since the beginning of the war on the 24th of February, 2022. It is well-known that human trafficking tends to increase during conflicts and humanitarian crises due to the spread of impunity, destruction of institutions, and breakdown of law. The EU and many international organizations have warned those fleeing Ukraine about the high risk of trafficking and adopted policies to prevent and detect trafficking. The EU anti-trafficking coordinator along with other EU agencies have developed the Common Anti-Trafficking Plan to specifically address this risk and support the potential victims fleeing the war in Ukraine meeting one of the goals set in the 10 Point Action Plan issued by the European Council in March to better coordinate EU actions for people leaving Ukraine. Among other goals, the 10 Point Action Plan aims to improve early identification of the victims of human trafficking as provided by the 2021–2025 Strategy on Combatting Trafficking and the 2011 Anti-trafficking Directive. This paper investigates the actions which the Italian government has put in place to detect and prevent the trafficking of women among the Ukrainians fleeing the war from the beginning of the conflict until September 2022, with a focus on the identification process. More specifically we explored the perceptions of front-line workers and street-level bureaucrats at the Slovenian and Austrian borders, where Ukrainians cross to enter Italy. Through interviews we collected data to shed light on the identification procedures adopted. The need to learn more about the current war in Ukraine corroborates this study. The proposed qualitative analysis has identified three main findings: (1) conflicts create increased opportunities for trafficking that in the case of Ukraine are greater due to the scale of those fleeing; (2) temporary Italian residence permit reveals some criticalities that could lead to greater vulnerability; (3) gaps in the identification process can increase the risks of trafficking, especially in the absence of longer-term assistance programs.
Sjogren’s syndrome related autoimmune encephalopathy presenting as depression and involuntary agitation in a 15-year-old girl: a case report
Authors: Lee Yu-Tung , Wu Chao-Yi , Chou I-Jun , Liu Chun-Hao
Published: June 2023

Introduction

Sjogren’s syndrome is an autoimmune disease that commonly involves exocrinopathy. Although studies have reported psychiatric manifestations resulting from Sjogren’s syndrome, few studies have focused on such manifestations in pediatric patients. Herein, we present a case of an adolescent girl with depression and involuntary self-harm behaviors related to Sjogren’s syndrome with central nervous system involvement.

Case presentation

A 15-year-old girl, with an underlying history of epilepsy, developed depressive symptoms of a year’s duration, accompanied by three seizure episodes and involuntary self-harm behaviors. The self-harm behaviors, which included head banging and arm scratching, were sudden onset, involuntary, and unable to be recalled afterwards. After admission to our ward, the patient was positive for serum antinuclear antibodies and Schirmer’s test. Moreover, 24-hour electroencephalography revealed epileptiform discharges during the mood swing episodes. Positive findings for antinuclear antibodies and anti-SSA antibodies in both serum and cerebrospinal fluid, suggested central nervous system involvement in Sjogren’s syndrome. After rituximab treatment, her mood became euthymic, and her involuntary self-harm behaviors ceased.

Conclusion

Central nervous system involvement leading to psychiatric presentations has rarely been reported in adolescents with Sjogren’s syndrome. When treating adolescent patients with involuntary self-harm behaviors and neurological symptoms, it is crucial to consider autoimmune encephalitis related to Sjogren’s syndrome in the differential diagnosis.
The protective and pathogenic role of Th17 cell plasticity and function in the tumor microenvironment
Authors: Pan Yuanyuan , Yang Wenjing , Tang Bo , Wang Xiaobo , Zhang Qi , Li Weiping , Li Li
Published: June 2023

At the turn of the century, researchers discovered a unique subtype of T helper cells that secretes IL-17 and defined it as Th17. The latest study found that Th17 cells play both positive and negative definitive roles in the regulation of antitumor immune responses. Although the function of Th17 in the tumor microenvironment remains poorly understood, more and more studies have shown that this paradoxical dual role is closely related to the plasticity of Th17 cells in recent decades. Further understanding of the characteristics of Th17 cells in the tumor microenvironment could yield novel and useful therapeutic approaches to treat cancer. In this review, we further present the high plasticity of Th17 cells and the function of Th17-producing IL-17 in tumor immunity.
A model to predict the thermodynamic stability of abiotic methane-hydrogen binary hydrates in a marine serpentinization environment
Authors: Zhu Zhiwei , Cao Yuncheng , Zheng Zihan , Wu Nengyou , Chen Duofu
Published: June 2023

Abiotic methane (CH4) and hydrogen (H2), which are produced during marine serpentinization, provide abundant gas source for hydrate formation on ocean floor. However, previous models of CH4–H2 hydrate formation have generally focused on pure water environments and have not considered the effects of salinity. In this study, the van der Waals–Platteeuw model, which considered the effects of salinity on the chemical potentials of CH4, H2, and H2O, was applied in a marine serpentinization environment. The model uses an empirical formula and the Peng–Robinson equation of state to calculate the Langmuir constants and fugacity values, respectively, of CH4 and H2, and it uses the Pitzer model to calculate the activity coefficients of H2O in the CH4–H2–seawater system. The three-phase equilibrium temperature and pressure predicted by the model for CH4–H2 hydrates in pure water demonstrated good agreement with experimental data. The model was then used to predict the three-phase equilibrium temperature and pressure for CH4–H2 hydrates in a NaCl solutions, for which relevant experimental data are lacking. Thus, this study provides a theoretical basis for gas hydrate research and investigation in areas with marine serpentinization.
Coastal landforms and fetch influence shoreline restoration effectiveness
Authors: Toft Jason D. , Accola Kerry L. , Des Roches Simone , Kobelt Julia N. , Faulkner Hannah S. , Morgan Jason R. , Perla Bianca S. , Metler Maria , Dethier Megan N.
Published: June 2023

Coastal shorelines are a key interface between terrestrial and aquatic ecosystems and are vital for human livelihood. As a result, shorelines have experienced substantial human modifications worldwide. Shoreline “hardening” – the construction of armor including seawalls, bulkheads, or rip-rap – is a common modification that has substantial negative ecological effects. Currently, restoration involving the removal of armor and replacement with “living” shorelines is becoming an established practice. Still, the ecological response to armor removal is oftentimes unpredictable and site-specific. We hypothesized that the confluence of larger-scale geophysical features might strongly influence ecological restoration outcomes at particular locations. To measure the effectiveness of armor removal in the context of broad-scale geophysical features across the Salish Sea, WA, USA, we studied 26 paired restored and natural reference beaches of the same shoretype (feeder bluff, accretion shoreform, or pocket beach), as well as corresponding fetch, sub-basin, and percent of shoreline sediment drift cell armored. Sites were restored for an average of six years. We gauged restoration effectiveness based on levels of five ecological response variables: beach wrack (percent, depth), logs (count, width), sediments (percent sand), vegetation (percent overhanging, count of fallen trees), and insects (density, taxa richness). We found that armor removal often restored these variables to natural levels, but that restoration response was dependent on geophysical features such as shoretype and fetch. Natural beaches did have higher measurements of overhanging vegetation, fallen trees, and insect taxa richness, as these features likely take time to mature at restored beaches. Feeder bluffs had a higher proportion of surface sand and number of fallen trees than other shoretypes, coinciding with the erosion of bluff material, whereas natural pocket beaches within bordering rocky headlands had higher insect densities. Sites with a large fetch had higher input of deposited wrack and logs, whereas sites with a small fetch had higher input from localized terrestrial sources – fallen trees and eroding sand. By incorporating the effectiveness of restoration with landscape features such as shoretype and fetch, we can more effectively plan for future restoration actions and better predict their outcomes.
Identification of key regulatory pathways and genes involved in the dynamic progression of pigmentation in Sinibrama taeniatus
Authors: Yuan Dengyue , Liu Xiaoqin , Wang Siya , Wang Haoyu , Li Junting , Zhao Zhe , Wei Lan , Cheng Linfeng , Teng Ran , Wang Zhijian
Published: June 2023

Intorduction

Coloration is a prominent trait in fish that is closely linked to their market value. Fish exhibit a diverse range of body colors, making them an excellent model for studying molecular mechanisms underlying pigmentation. Although regulatory pathways involved in pigmentation have been extensively studied in model fish such as zebrafish and medaka, the presence of varying chromatophore types across different fish species suggests that fish pigmentation mechanisms are not fixed. Therefore, more studies should be conducted on non-model fish. Sinibrama taeniatus is an endemic fish in the upper Yangtze River that is highly valued for its ornamental and edible properties.

Methods

In this study, we identified three chromatophore types in S. taeniatus and investigated changes in body color, chromatophores, and pigments at different developmental stages. Subsequently, RNA-seq analysis revealed that retinol metabolism, thyroid hormone synthesis, purine metabolism, and pyrimidine metabolism pathway are closely associated with pigmentation.

Results

Weighted gene co-expression network analysis (WGCNA) identified several hub genes, including mitf, wnt 9a, wnt10b, wnt11, adcy5, edn1, adcy8, and rdh8, that may play an important role in pigmentation.

Discussion

Overall, our findings provide valuable insights into the role of genes and pathways in fish pigmentation and offer useful information for body color-based molecular breeding programs in aquaculture.
Photosynthesis and whole-plant carbon balances of warm affinity Halophila nipponica and cold affinity Zostera marina in relation to water temperature rise: implication for future geographic distribution
Authors: Kim Seung Hyeon , Kim Hyegwang , Suonan Zhaxi , Zhang Fei , Lee Kun-Seop
Published: June 2023

Climate change associated sea surface temperature rise could significantly affect the physiology, and consequently geographic distribution of seagrasses. Photosynthetic and respiratory responses of warm affinity Halophila nipponica and cold affinity Zostera marina to a change in water temperature (7–26°C) were investigated to estimate whole-plant carbon balance for prediction of the future geographic distributions of these seagrasses in the northwestern Pacific region. It was hypothesized that H. nipponica and Z. marina showed distinctly different patterns of carbon balance with changes in water temperature. Photosynthetic and respiratory rates of H. nipponica and Z. marina generally increased with increasing water temperature, except for Ic and Ik of H. nipponica and α of Z. marina. H. nipponica showed high Pmax and α values, which could support a greater respiratory demand related to the higher proportion of non-photosynthetic tissues (~67%), compared with Z. marina (~34%). The whole-plant carbon balance of Z. marina remained positive throughout the experiment, although it decreased to nearly zero during the high water-temperature period. H. nipponica exhibited a negative carbon balance during winter and early spring, which corresponded with severely limited growth at water temperatures< 15°C. These results suggest that increases in water temperature, particularly during winter, in relation to continuous climate change, could induce substantial changes in the seagrass ecosystem structure and corresponding changes in coastal ecosystem services in the temperate coastal waters of the northwestern Pacific region. The results of this study will provide valuable information on the effective management and conservation of coastal and estuarine ecosystems under ongoing climate change.
Flow and heat transfer analysis on micropolar fluid through a porous medium between a clear and Al2O3−Cu/H2O in conducting field
Authors: Tanuja T. N. , Kavitha L. , Varma S. V. K. , Khan Umair , Sherif El-Sayed M. , Hassan Ahmed M. , Pop Ioan , Sarada K. , Gill Harjot Singh
Published: June 2023

The current study is focused on the flow of micropolar liquid in a saturated permeable medium sandwiched between clear and hybrid nanofluid filled in an inclined channel, with radiation and dissipation effects. Copper and Aluminium oxide nanoparticles is considered along with base (water) fluid. The solution for velocity, micro rotational velocity, and temperature are determined by applying the regular perturbation technique to the dimensionless version of the governing equations. The heat transport rate at the left y=−1 and right y=2 plate is also calculated, as well as shear stress expressed in terms of skin-friction coefficient and Nusselt number. The result obtained for various physical parameters are analyzed through several graphs and tables. Results reveal that an increase in the material parameter of micropolar fluid, the motion of the fluid flow decreases. The heat transport rate is enhanced and the velocity is degraded by the magnetic parameter. The Hybrid nanofluid temperature is greater when compared to clear and binary hybrid nanofluid. This work establishes the mechanisms for heat transport enhancement on micropolar liquid through a porous medium between a clear and hybrid nanofluid in conducting field.
An intelligent detection method for plasmodium based on self-supervised learning and attention mechanism
Authors: Fu Min , Wu Kai , Li Yuxuan , Luo Linkai , Huang Wei , Zhang Qi
Published: June 2023

Background

Malaria remains a severe life-threatening disease caused by plasmodium parasites. Microscopy is widely used for malaria diagnosis. However, it relies heavily on the skills and experience of inspectors. Due to low-level medical services and the lack of skilled inspectors, misdiagnoses are frequently made in some areas.

Methods

In recent years, many successful applications of CNN models have been reported. Unlike images in the ImageNet, the image of plasmodium only has a tiny defect area with a large amount of information. In addition, the dataset is extremely unbalanced: the number of positive samples is much less than that of negative samples. This paper proposes a classification network by combining attention mechanism and ResNeSt for plasmodium detection and using self-supervised learning to pre-train the network. First, the positive samples were adopted to pre-train the network. Then, attention modules were taken to highlight the feature area. To support current and future research, we also constructed a plasmodium dataset with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malaria and non-Plasmodium. Through self-supervised learning, a large amount of unlabeled data is used to mine the representational features, thus improving the feature extraction capability of the model and achieving higher accuracy, while saving the physician’s labeling time and improving the classification accuracy.

Results

The experiments show that our model exhibits an excellent performance and that the test accuracy, sensitivity, and specificity attain 97.8%, 96.5%, and 98.9%, respectively.

Conclusion

The AI classification method proposed in this paper can effectively assist clinicians in the diagnosis and provide a basis for the automatic detection of malaria parasites in the future.
The influence of COVID-19 on colorectal cancer was investigated using bioinformatics and systems biology techniques
Authors: Song Yujia , Huang Tengda , Pan Hongyuan , Du Ao , Wu Tian , Lan Jiang , Zhou Xinyi , Lv Yue , Xue Shuai , Yuan Kefei
Published: June 2023

Introduction

Coronavirus disease 2019 (COVID-19) is a global pandemic and highly contagious, posing a serious threat to human health. Colorectal cancer (CRC) is a risk factor for COVID-19 infection. Therefore, it is vital to investigate the intrinsic link between these two diseases.

Methods

In this work, bioinformatics and systems biology techniques were used to detect the mutual pathways, molecular biomarkers, and potential drugs between COVID-19 and CRC.

Results

A total of 161 common differentially expressed genes (DEGs) were identified based on the RNA sequencing datasets of the two diseases. Functional analysis was performed using ontology keywords, and pathway analysis was also performed. The common DEGs were further utilized to create a protein-protein interaction (PPI) network and to identify hub genes and key modules. The datasets revealed transcription factors-gene interactions, co-regulatory networks with DEGs-miRNAs of common DEGs, and predicted possible drugs as well. The ten predicted drugs include troglitazone, estradiol, progesterone, calcitriol, genistein, dexamethasone, lucanthone, resveratrol, retinoic acid, phorbol 12-myristate 13-acetate, some of which have been investigated as potential CRC and COVID-19 therapies.

Discussion

By clarifying the relationship between COVID-19 and CRC, we hope to provide novel clues and promising therapeutic drugs to treat these two illnesses.
Identification and characterization of a novel aminoglycoside O-nucleotidyltransferase ANT(6)-If from Paenibacillus thiaminolyticus PATH554
Authors: Lu Junwan , Sha Yuning , Gao Mengdi , Shi Weina , Lin Xi , Li Kewei , Bao Qiyu , Feng Chunlin
Published: June 2023

Background

Paenibacillus thiaminolyticus, a species of genus Paenibacillus of the family Paenibacillaceae, exists widely in environments and habitats in various plants and worms, and occasionally causes human infections. This work aimed to characterize the function of a novel aminoglycoside O-nucleotidyltransferase resistance gene, designated ant(6)-If, from a P. thiaminolyticus strain PATH554.

Methods

Molecular cloning, antimicrobial susceptibility testing, enzyme expression and purification, and kinetic analysis were used to validate the function of the novel gene. Whole-genome sequencing and comparative genomic analysis were performed to investigate the phylogenetic relationship of ANT(6)-If and other aminoglycoside O-nucleotidyltransferases, and the synteny of ant(6)-If related sequences.

Results

The recombinant with the cloned ant(6)-If gene (pMD19-ant(6)-If/DH5α) demonstrated a 128-fold increase of minimum inhibitory concentration level against streptomycin, compared with the control strains (DH5α and pMD19/DH5α). The kinetic parameter kcat/Km of ANT(6)-If for streptomycin was 9.01 × 103 M−1·s−1. Among the function-characterized resistance genes, ANT(6)-If shared the highest amino acid sequence identity of 75.35% with AadK. The ant(6)-If gene was located within a relatively conserved genomic region in the chromosome.

Conclusion

ant(6)-If conferred resistance to streptomycin. The study of a novel resistance gene in an unusual environmental bacterium in this work contributed to elucidating the resistance mechanisms in the microorganisms.
Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination against Acinetobacter baumannii
Authors: Zhu Shixing , Yue Jiali , Wang Xintong , Zhang Jiayuan , Yu Mingming , Zhan Yuanchao , Zhu Yuanqi , Sy Sherwin K. B. , Lv Zhihua
Published: June 2023

Introduction

The emergence of multidrug-resistant (MDR) Acinetobacter baumannii prompts clinicians to consider treating these infections with polymyxin combination.

Methods

Metabolomic analysis was applied to investigate the synergistic effects of polymyxin-B, amikacin and sulbactam combination therapy against MDR A. baumannii harboring OXA-23 and other drug resistant genes. The drug concentrations tested were based on their clinical breakpoints: polymyxin-B (2 mg/L), amikacin (16 mg/L), polymyxin-B/amikacin (2/16 mg/L), and polymyxin-B/amikacin/sulbactam (2/16/4 mg/L).

Results

The triple antibiotic combination significantly disrupted levels of metabolites involved in cell outer membrane structure including fatty acids, glycerophospholipids, nucleotides, amino acids and peptides as early as 15 min after administration. Amikacin and polymyxin-B alone perturbed a large number of metabolites at 15 min and 1 h, respectively, but the changes in metabolites were short-lived lasting for less than 4 h. In contrast, the combination treatment disrupted a large amount of metabolites beyond 4 h. Compared to the double-combination, the addition of sulbactam to polymyxin-B/amikacin combination produce a greater disorder in A. baumannii metabolome that further confer susceptibility of bacteria to the antibiotics.

Conclusion

The metabolomic analysis identified mechanisms responsible for the synergistic activities of polymyxin-B/amikacin/sulbactam against MDR A. baumannii.
Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder
Authors: Yuan Lamei , Yu Xuehui , Xiao Heng , Deng Sheng , Xia Hong , Xu Hongbo , Yang Yan , Deng Hao
Published: June 2023

Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology.
Glutamate spillover drives robust all-or-none dendritic plateau potentials—an in silico investigation using models of striatal projection neurons
Authors: Trpevski Daniel , Khodadadi Zahra , Carannante Ilaria , Hellgren Kotaleski Jeanette
Published: June 2023

Plateau potentials are a critical feature of neuronal excitability, but their all-or-none behavior is not easily captured in modeling. In this study, we investigated models of plateau potentials in multi-compartment neuron models and found that including glutamate spillover provides robust all-or-none behavior. This result arises due to the prolonged duration of extrasynaptic glutamate. When glutamate spillover is not included, the all-or-none behavior is very sensitive to the steepness of the Mg2+ block. These results suggest a potentially significant role of glutamate spillover in plateau potential generation, providing a mechanism for robust all-or-none behavior across a wide range of slopes of the Mg2+ block curve. We also illustrate the importance of the all-or-none plateau potential behavior for nonlinear computation with regard to the nonlinear feature binding problem.
How does the brain age in individuals with multiple sclerosis? A systematic review
Authors: Tokarska Nataliya , Tottenham Isabelle , Baaklini Charbel , Gawryluk Jodie R.
Published: June 2023

Multiple Sclerosis (MS) is a complex neurological disorder that involves demyelination, lesions and atrophy in both white and gray matter. Such changes in the central nervous system are diagnostic in MS and has a strong relationship with both physical and cognitive symptoms. As a result, magnetic resonance imaging (MRI) scans as a metric of brain atrophy have emerged as an important outcome measure in MS studies. Recently, research has begun to focus on the contribution of aging to the structural changes in the brain associated with MS; prompting questions about whether there is an amplifying effect of aging superimposed on MS-related brain atrophy. To examine current evidence of how the brain ages in individuals with MS, a systematic review of the literature was performed. Specific questions were focused on how aging affects gray and white matter structure, whether patterns of brain atrophy differ in younger and older cohorts and if there are structural differences in the brain as a function of sex in aging people with MS. This review considered studies that used MRI to examine the effects of aging in adults with MS. Twenty-one studies met eligibility criteria. Findings across these studies revealed that gray matter atrophy was more pronounced in older adults with MS, particularly in subcortical regions such as the thalamus; that the rates of atrophy were similar but varied by region for younger and older cohorts; and that males may experience more brain atrophy than females. Further studies that use multimodal MRI acquisition methods are needed to capture changes in both males and females over time, particularly in middle to older adulthood.
Uterus infantilis: a novel phenotype associated with AARS2 new genetic variants. A case report
Authors: Kazakova Ekaterina , Téllez-Martínez José Alberto , Flores-Lagunes Leonardo , Sosa-Ortiz Ana Luisa , Carillo-Sánchez Karol , Molina-Garay Carolina , González-Domínguez Carlos Alberto , Jimenez-Olivares Marco , Fernandez-Valverde Francisca , Vargas-Cañas Edwin Steven , Vázquez-Memije Martha Elisa , Garcia-Latorre Ethel Awilda , Martínez-Duncker Iván , Alaez-Verson Carmen
Published: June 2023

Objectives

To report the first Mexican case with two novel AARS2 mutations causing primary ovarian failure, uterus infantilis, and early-onset dementia secondary to leukoencephalopathy.

Methods

Detailed clinical, clinimetric, neuroimaging features, muscle biopsy with biochemical assays of the main oxidative phosphorylation complexes activities, and molecular studies were performed on samples from a Mexican female.

Results

We present a 41-year-old female patient with learning difficulties since childhood and primary amenorrhea who developed severe cognitive, motor, and behavioral impairment in early adulthood. Neuroimaging studies revealed frontal leukoencephalopathy with hypometabolism at the fronto-cerebellar cortex and caudate nucleus. Uterus infantilis was detected on ultrasound study. Clinical exome sequencing identified two novel variants, NM_020745:c.2864G>A (p.W955*) and NM_020745:c.1036C>A (p.P346T, p.P346Wfs*18), in AARS2. Histopathological and biochemical studies on muscle biopsy revealed mitochondrial disorder with cytochrome C oxidase (COX) deficiency.

Conclusions

Several adult-onset cases of leukoencephalopathy and ovarian failure associated with AARS2 variants have been reported. To our best knowledge, none of them showed uterus infantilis. Here we enlarge the genetic and phenotypic spectrum of AARS2-related dementia with leukoencephalopathy and ovarian failure and contribute with detailed clinical, clinometric, neuroimaging, and molecular studies to disease and novel molecular variants characterization.
In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression
Authors: Gutiérrez-Casares José Ramón , Segú-Vergés Cristina , Sabate Chueca Juncal , Pozo-Rubio Tamara , Coma Mireia , Montoto Carmen , Quintero Javier
Published: June 2023

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX’s predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view.
Ultrasonic visualization technique for anatomical and functional analyses of the sciatic nerve in rats
Authors: Xu Xiao-Dong , Lin Lei , Qiu Yu-Bei , Zeng Bang-Wei , Chen Ye , Liu Jun-Le , Ye Cai-Hong , Wang Jia-Li , Liu Pei-Chang , Zhang Liang-Cheng
Published: June 2023

Background and objective

Ultrasound has been widely used in the diagnosis and minimally invasive treatment of peripheral nerve diseases in the clinic, but there is still a lack of feasibility analysis in rodent models of neurological disease. The purpose of this study was to investigate the changes in the cross-sectional area of the sciatic nerve of different genders and body weights and to explore the effectiveness and reliability of an ultrasound-guided block around the sciatic nerve in living rats.

Methods

Using ultrasound imaging anatomy of the sciatic nerve of rats, the cross-sectional area of the sciatic nerve in rats of different genders from 6 to 10 weeks old was calculated, and then analyzed its correlation with body weight. Further analyses were conducted through behavioral and cadaveric studies to evaluate the feasibility of ultrasound-guided perineural injection of the sciatic nerve in rats.

Results

We first reported that the sciatic nerve cross-sectional area of rats was increased with age (F= 89.169,P< 0.001), males had a higher sciatic nerve cross-sectional area than females (F= 60.770,P< 0.001), and there was a positive correlation with body weight (rMale= 0.8976,P< 0.001;rFemale= 0.7733,P< 0.001). Behavioral observation of rats showed that the lower extremity complete block rate was 80% following the administration of drugs around the sciatic nerve under ultrasound guidance and staining with methylene blue occurred in all sciatic nerves and surrounding muscles and fascia using 20 ultrasound-guided injections.

Conclusions

Ultrasound visualization technology can be used as a new auxiliary evaluation and intervention therapy for animal models of peripheral nerve injury, and will provide overwhelming new references for the basic research of neurological diseases.
Association of breakfast styles such as Japanese, Western, and cereals with sleeping habits, eating habits, and lifestyle in preschool and elementary school children
Authors: Kuwahara Mai , Tahara Yu , Nitta Lyie , Furutani Akiko , Mochida Seiko , Makino Naomichi , Nozawa Yuki , Shibata Shigenobu
Published: June 2023

Introduction

In Japan, breakfast styles are categorized into five groups; Japanese breakfast (JB; rice and miso soup), Western breakfast (WB; bread and milk), Japanese-Western breakfast (J-WB; alternative daily serving), cereal breakfast (CB), and breakfast skipping. In our recent studies, breakfast style was highly associated with the daily sleep–wake phase (chronotype), and healthy eating habits. In contrast with other breakfast style consumers, JB-consumers were positively associated with the morning chronotype and healthy eating habits such as a high consumption of a variety of protein sources, vegetables, and dietary fibers, and low consumption of sweetened juices. These previous studies included only adult participants; hence, in the current study, we investigated whether similar observations can be made in children.

Methods

Preschool (aged 3–5 years) and elementary school children (6–8 years) (N = 6,104, 49.87% boys, 50.13% girls, mean body mass index 15.39 ± 0.03 kg/m2 for preschoolers and percentage of overweight −2.73 ± 0.22 for elementary school children) participated in this cross-sectional online survey on lifestyle, including eating and sleep habits, through their mother’s responses.

Results

The results showed that the morning-evening type index values (chronotype indicator, smaller indicates morning type) were negatively correlated with JB intake (−0.05, p < 0.01) and positively correlated with WB (0.03, p < 0.05) and CB intake (0.06, p < 0.01), suggesting that the JB group exhibited the morning chronotype and the WB and CB groups exhibited the evening chronotype. The JB group consumed a variety of protein sources (mean ± SE; days/week) with more frequency (fish 2.95 ± 0.038 p < 0.001, soy 3.55 ± 0.043 p < 0.001, egg 3.82 ± 0.044 p < 0.001) compared with the WB group (fish 2.58 ± 0.033, soy 3.00 ± 0.038, egg 3.49 ± 0.039). On the other hand, the JB group consumed snacks (5.48 ± 0.042 p < 0.001) and sweetened juice (2.50 ± 0.050 p < 0.001) less frequently than the WB group (snacks; 5.80 ± 0.037 and sweetened juice; 2.74 ± 0.049).

Discussion

JB-eating children with a morning chronotype exhibited better sleep and eating habits than WB-eating children with an evening type pattern. The results suggest that JB eating habits may be associated with good eating and sleeping lifestyles, even among preschool and elementary school children.