bluuebunny/crossref_metadata_2025 huggingface dataset:
A TEORIA DAS AÇÕES MENTAIS E APRENDIZAGEM MATEMÁTICA DE ESTUDANTES COM DEFICIÊNCIA INTELECTUAL: UMA REVISÃO SISTEMÁTICA DE LITERATURA
Authors: De Abrêu Corrêa Gisély , Reis Thiengo Edmar , Veiga Ferreira de Souza Maria Alice
Published: August 2023

Este artigo apresenta uma revisão sistemática de literatura que buscou identificar pesquisas que utilizaram a Teoria da Formação Planejada das Ações Mentais e dos Conceitos, do médico e psicólogo soviético Piotr Yakovlevich Galperin, para promover a aprendizagem matemática na Educação Básica em escola regular, classificar quais dessas pesquisas direcionaram-se à aprendizagem matemática de estudantes com deficiência intelectual e discutir quais aspectos da teoria em questão contribuíram para a aprendizagem matemática desses estudantes. A teoria é fundamentada na perspectiva de aprendizagem e desenvolvimento da psicologia histórico-cultural e considera a motivação fundamental para a apropriação de conceitos. A formação das ações mentais inicia-se com a elaboração da base orientadora da nova ação, seguida da formação do seu aspecto material. O aspecto linguístico da ação indica uma das etapas da formação de conceitos, até chegar à ação como um ato mental. Para atender à finalidade desta revisão, elaborou-se um protocolo de busca em bases de dados utilizadas com mais frequência em pesquisas no campo educacional, com critérios de inclusão e exclusão definidos para abarcar os trabalhos que contemplassem os objetivos definidos. As produções selecionadas reconheceram contribuições da teoria de Galperin para a aprendizagem matemática de estudantes com deficiência intelectual: a teoria ofereceu mais direção ao ensino, possibilitou o avanço dos estudantes em relação aos conceitos matemáticos na fase das ações materiais voltadas à fase da linguagem externa. Além disso, a motivação, considerada primordial pela teoria, gerou engajamento dos alunos durante a pesquisa. A revisão constatou um crescente número de pesquisas relacionando a teoria das ações mentais com aprendizagem matemática, mas as investigações ainda são reduzidas referentes aos estudantes com deficiência intelectual matriculados na educação básica em escola regular, o que pode indicar novas investigações no campo da Educação Matemática Inclusiva utilizando a teoria de Galperin.
Recent advances in lipid nanovesicles for targeted treatment of spinal cord injury
Authors: Lu Di , Wu Jiu-Ping , Yang Qi-Wei , Wang Hua-Yi , Yang Jun-Jie , Zhang Gang-Gang , Wang Chen , Yang Yan-Lian , Zhu Ling , Sun Xin-Zhi
Published: August 2023

The effective regeneration and functional restoration of damaged spinal cord tissue have been a long-standing concern in regenerative medicine. Treatment of spinal cord injury (SCI) is challenging due to the obstruction of the blood-spinal cord barrier (BSCB), the lack of targeting of drugs, and the complex pathophysiology of injury sites. Lipid nanovesicles, including cell-derived nanovesicles and synthetic lipid nanovesicles, are highly biocompatible and can penetrate BSCB, and are therefore effective delivery systems for targeted treatment of SCI. We summarize the progress of lipid nanovesicles for the targeted treatment of SCI, discuss their advantages and challenges, and provide a perspective on the application of lipid nanovesicles for SCI treatment. Although most of the lipid nanovesicle-based therapy of SCI is still in preclinical studies, this low immunogenicity, low toxicity, and highly engineerable nanovesicles will hold great promise for future spinal cord injury treatments.
Investigation of PESTEL factors driving change in capital project organizations
Authors: Bou Hatoum Makram , Nassereddine Hala , Musick Sean , El-Jazzar Mahmoud
Published: August 2023

In a volatile, uncertain, complex, and ambiguous environment, organizational change has been a central concern for capital project organizations, that continue to suffer from poor project performance in a growing industry. As such, capital project organizations must understand the changing environment and the factors driving change within their organizations to remain successful in a changing environment and adapt to change. To help the capital projects industry achieve successful organizational change efforts, this paper aims to 1) identify the external factors that are pushing capital project organizations to change and 2) investigate whether these factors impact organizations differently. To achieve the desired objective, a total of 22 PESTEL (political, economic, social, technological, environmental, and legal) factors were identified and validated with a group of 14 subject matter experts and defined via the context of literature. Then, the factors were evaluated via an online survey to understand whether they impact organizations differently based on their age maturity (including contemporary, transitional, and legacy organizations) and type of work (including owners, contractors, and service providers). Findings from this study can provide capital project practitioners and researchers with valuable insights needed to understand the external factors shaping change within the industry.
Genome instability-derived genes as a novel prognostic signature for lung adenocarcinoma
Authors: Zhang Xu , Lam Tak-Wah , Ting Hing-Fung
Published: August 2023

Background: An increasing number of patients are being diagnosed with lung adenocarcinoma, but there remains limited progress in enhancing prognostic outcomes and improving survival rates for these patients. Genome instability is considered a contributing factor, as it enables other hallmarks of cancer to acquire functional capabilities, thus allowing cancer cells to survive, proliferate, and disseminate. Despite the importance of genome instability in cancer development, few studies have explored the prognostic signature associated with genome instability for lung adenocarcinoma.

Methods: In the study, we randomly divided 397 lung adenocarcinoma patients from The Cancer Genome Atlas database into a training group (n = 199) and a testing group (n = 198). By calculating the cumulative counts of genomic alterations for each patient in the training group, we distinguished the top 25% and bottom 25% of patients. We then compared their gene expressions to identify genome instability-related genes. Next, we used univariate and multivariate Cox regression analyses to identify the prognostic signature. We also performed the Kaplan–Meier survival analysis and the log-rank test to evaluate the performance of the identified prognostic signature. The performance of the signature was further validated in the testing group, in The Cancer Genome Atlas dataset, and in external datasets. We also conducted a time-dependent receiver operating characteristic analysis to compare our signature with established prognostic signatures to demonstrate its potential clinical value.

Results: We identified GULPsig, which includes IGF2BP1, IGF2BP3, SMC1B, CLDN6, and LY6K, as a prognostic signature for lung adenocarcinoma patients from 42 genome instability-related genes. Based on the risk score of the risk model with GULPsig, we successfully stratified the patients into high- and low-risk groups according to the results of the Kaplan–Meier survival analysis and the log-rank test. We further validated the performance of GULPsig as an independent prognostic signature and observed that it outperformed established prognostic signatures.

Conclusion: We provided new insights to explore the clinical application of genome instability and identified GULPsig as a potential prognostic signature for lung adenocarcinoma patients.
Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model
Authors: Horánszky Alex , Shashikadze Bachuki , Elkhateib Radwa , Lombardo Salvo Danilo , Lamberto Federica , Zana Melinda , Menche Jörg , Fröhlich Thomas , Dinnyés András
Published: August 2023

Bisphenol A (BPA) exposure is associated with a plethora of neurodevelopmental abnormalities and brain disorders. Previous studies have demonstrated BPA-induced perturbations to critical neural stem cell (NSC) characteristics, such as proliferation and differentiation, although the underlying molecular mechanisms remain under debate. The present study evaluated the effects of a repeated-dose exposure of environmentally relevant BPA concentrations during the in vitro 3D neural induction of human induced pluripotent stem cells (hiPSCs), emulating a chronic exposure scenario. Firstly, we demonstrated that our model is suitable for NSC differentiation during the early stages of embryonic brain development. Our morphological image analysis showed that BPA exposure at 0.01, 0.1 and 1 µM decreased the average spheroid size by day 21 (D21) of the neural induction, while no effect on cell viability was detected. No alteration to the rate of the neural induction was observed based on the expression of key neural lineage and neuroectodermal transcripts. Quantitative proteomics at D21 revealed several differentially abundant proteins across all BPA-treated groups with important functions in NSC proliferation and maintenance (e.g., FABP7, GPC4, GAP43, Wnt-8B, TPPP3). Additionally, a network analysis demonstrated alterations to the glycolytic pathway, potentially implicating BPA-induced changes to glycolytic signalling in NSC proliferation impairments, as well as the pathophysiology of brain disorders including intellectual disability, autism spectrum disorders, and amyotrophic lateral sclerosis (ALS). This study enhances the current understanding of BPA-related NSC aberrations based mostly on acute, often high dose exposures of rodent in vivo and in vitro models and human GWAS data in a novel human 3D cell-based model with real-life scenario relevant prolonged and low-level exposures, offering further mechanistic insights into the ramifications of BPA exposure on the developing human brain and consequently, later life neurological disorders.
Clinical characteristics of respiratory tract infection caused by Klebsiella pneumoniae in immunocompromised patients: a retrospective cohort study
Authors: Liu Yahui , Huang Lin , Cai Jing , Zhu Haixing , Li Junjie , Yu Youchao , Xu Yumin , Shi Guochao , Feng Yun
Published: August 2023

Purpose

With advancements in medical technology and the growth of an aging society, the number of immunocompromised patients has increased progressively. Klebsiella pneumoniae (K. pneumoniae) is one of the most common opportunistic pathogens, causing a severe disease burden. We aimed to further clarify the differences in respiratory tract K. pneumoniae infections between immunocompromised and immunocompetent populations.

Methods

We retrospectively compared cases of respiratory tract K. pneumoniae infection in immunocompromised and immunocompetent patients admitted to Ruijin Hospital in Shanghai between January 2019 and August 2020 to clarify the differences between the two groups.

Results

We enrolled 400 immunocompromised patients and 386 immunocompetent patients. Compared to the immunocompetent group, immunocompromised patients were more likely to develop bacteremia and shock and to require mechanical ventilation support during hospitalization. Immunocompromised patients also had a greater probability of polymicrobial infection and a higher rate of antibacterial resistance to carbapenem, which resulted in a higher intensive care unit admission rate, 30-day case fatality rate (CFR), and 6-month CFR. Multivariate analysis indicated that immunocompromised patients with respiratory diseases (odds ratio [OR], 2.189; 95% confidence interval [CI], 1.103-4.344; P = 0.025) and cardiovascular diseases (OR, 2.008; 95% CI, 1.055-3.822; P = 0.034), using mechanical ventilation (OR, 3.982; 95% CI, 2.053-7.722; P = 0.000), or infected with multidrug-resistant K. pneumoniae (OR, 3.870; 95%, 1.577-9.498; P = 0.003) were more likely to have a higher 30-day CFR.

Conclusion

The disease burden of K. pneumoniae infection in immunocompromised patients is high. Immunocompromised patients who presented with respiratory diseases and cardiovascular diseases, used mechanical ventilation, or were infected with multidrug-resistant K. pneumoniae experienced a higher 30-day mortality rate.
A complicated infection by cutaneous Nocardia wallacei and pulmonary Mycobacterium abscessus in a Chinese immunocompetent patient: a case report
Authors: Qin Ling , Wang Sidan , Zheng Zhifen , Zhang Wenqian , Qu Qiang , Li Jun , Tan Yurong , Cao Liming
Published: August 2023

Nocardiosis is an infectious disease caused by Nocardia that primarily affects immunocompromised hosts. Mycobacterium abscessus is a common opportunistic pathogen that causes disease in humans, including pulmonary and extrapulmonary infection. Nocardia spp. infection is uncommon, and infection with Nocardia wallacei and Mycobacterium abscessus is even rarer. A 59-year-old immunocompetent woman with risk factors for environmental exposure developed nocardiosis and presented to the hospital with a cough, shortness of breath, hemoptysis, and a back abscess. An enhanced computed tomography (CT) of the chest revealed partial destruction of the right lung, as well as consolidation of the right upper lobe. Rare pathogens N. wallacei and Mycobacterium abscessus were detected by metagenomic next-generation sequencing (mNGS) from abscess on the back and lung puncture tissue, respectively. She was treated with a combination of antibiotics and was finally discharged with a good prognosis. In this case, we present a patient who was successfully diagnosed with N. wallacei and Mycobacterium abscessus infection using mNGS. This importance of using mNGS in pathogen detection and the effective use of antibiotics in treating patients with long-term rare infections is highlighted in this report.
Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in isolated mouse ventricular myocytes
Authors: Tarnowski Daniel , Feder Anna-Lena , Trum Maximilian , Kreitmeier Klaus-Georg , Stengel Laura , Maier Lars S. , Sag Can Martin
Published: August 2023

Background

The Bruton tyrosine kinase (BTK) inhibitor Ibrutinib is associated with a higher incidence of cardiotoxic side effects including heart failure (HF).

Objectives

Ibrutinib is capable of inhibiting PI3K/Akt signaling in neonatal rat ventricular cardiomyocytes when stimulated with insulin-like growth factor 1 (IGF-1). We therefore hypothesized that Ibrutinib might disrupt IGF-1-mediated activation of intracellular Ca handling in adult mouse cardiomyocytes by inhibiting PI3K/Akt signaling.

Methods

Isolated ventricular myocytes (C57BL6/J) were exposed to IGF-1 at 10 nmol/L in the presence or absence of Ibrutinib (1 µmol/L) or Acalabrutinib (10 µmol/L; cell culture for 24 ± 2 h). Intracellular Ca handling was measured by epifluorescence (Fura-2 AM) and confocal microscopy (Fluo-4 AM). Ruptured-patch whole-cell voltage-clamp was used to measure ICa. Levels of key cardiac Ca handling proteins were investigated by immunoblots.

Results

IGF-1 significantly increased Ca transient amplitudes by ∼83% as compared to vehicle treated control cells. This was associated with unaffected diastolic Ca, enhanced SR Ca loading and increased ICa. Co-treatment with Ibrutinib attenuated both the IGF-1-mediated increase in SR Ca content and in ICa. IGF-1 treated cardiomyocytes had significantly increased levels of pS473Akt/Akt and SERCA2a expression as compared to cells concomitantly treated with IGF-1 and Ibrutinib. SR Ca release (as assessed by Ca spark frequency) was unaffected by either treatment. In order to test for potential off-target effects, second generation BTK inhibitor Acalabrutinib with greater BTK selectivity and lower cardiovascular toxicity was tested for IGF1-mediated activation of intracellular Ca handling. Acalabrutinib induced similar effects on Ca handling in IGF-1 treated cultured myocytes as Ibrutinib in regard to decreased Ca transient amplitude and slowed Ca transient decay, hence implying a functional class effect of BTK inhibitors in cardiac myocytes.

Conclusions

Inhibition of BTK by Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in adult ventricular mouse myocytes in the face of disrupted Akt signaling and absent SERCA2a upregulation.
Concomitant valve surgery is associated with worse outcomes in surgical treatments of post-infarction ventricular aneurysm
Authors: Liu Yuqi , Cai Ziwen , Xu Li , Zheng Yidan , Chen Ming , Dong Nianguo , Chen Si
Published: August 2023

Objective

To evaluate the impact of concomitant valve surgery on the prognosis of patients who experienced coronary artery bypass graft (CABG) with/without ventricular reconstruction for the ventricular aneurysm.

Methods

In our department, 354 patients underwent CABG with/without ventricular reconstruction for a ventricular aneurysm from July 23rd, 2000 to December 23rd, 2022. A total of 77 patients received concomitant valve surgery, 37 of whom underwent replacement, and 40 of whom underwent repair. The baseline characteristics, prognostic, and follow-up information were statically analyzed. Univariate and multivariate Cox regression analyses were applied to identify the risk factors of long-term outcomes.

Results

Compared with patients who did not undergo valvular surgery, patients who experienced concomitant valve surgical treatments had a significantly lower survival rate (p = 0.00022) and a longer total mechanical ventilation time. Subgroup analysis indicated that the options of repair or replacement exhibited no statistically significant difference in postoperative mortality (p = 0.44) and prognosis. The multivariate Cox regression analysis suggested that the pre-operative cholesterol level (HR = 1.68), postoperative IABP (HR = 6.29), NYHA level (HR = 2.84), and pre-operative triglyceride level (HR = 1.09) were independent and significant predictors for overall all-cause mortality after surgery.

Conclusion

Concomitant valve surgery was considerably related to a higher risk of postoperative mortality in patients with post-infarction ventricle aneurysms who underwent surgical treatments. No significant difference in the prognosis outcomes was observed between the operating methods of repair or replacement valve surgery.
Synthetic biomedical data generation in support of In Silico Clinical Trials
Authors: Simalatsar Alena
Published: August 2023

Living in the era of Big Data, one may advocate that the additional synthetic generation of data is redundant. However, to be able to truly say whether it is valid or not, one needs to focus more on the meaning and quality of data than on the quantity. In some domains, such as biomedical and translational sciences, data privacy still holds a higher importance than data sharing. This by default limits access to valuable research data. Intensive discussion, agreements, and conventions among different medical research players, as well as effective techniques and regulations for data anonymization, already made a big step toward simplification of data sharing. However, the situation with the availability of data about rare diseases or outcomes of novel treatments still requires costly and risky clinical trials and, thus, would greatly benefit from smart data generation. Clinical trials and tests on animals initiate a cyclic procedure that may involve multiple redesigns and retesting, which typically takes two or three years for medical devices and up to eight years for novel medicines, and costs between 10 and 20 million euros. The US Food and Drug Administration (FDA) acknowledges that for many novel devices, practical limitations require alternative approaches, such as computer modeling and engineering tests, to conduct large, randomized studies. In this article, we give an overview of global initiatives advocating for computer simulations in support of the 3R principles (Replacement, Reduction, and Refinement) in humane experimentation. We also present several research works that have developed methodologies of smart and comprehensive generation of synthetic biomedical data, such as virtual cohorts of patients, in support of In Silico Clinical Trials (ISCT) and discuss their common ground.
Metabolic and molecular effects of dietary extra virgin olive oil in blood and placenta of women with GDM
Authors: Gomez Ribot Dalmiro , Diaz Esteban , Fazio María Victoria , Gómez Hebe Lorena , Careaga Valeria , Maier Marta , Macchi Silvia Beatriz , Gresta Carlos Alberto , Capobianco Evangelina , Jawerbaum Alicia
Published: August 2023

Gestational diabetes mellitus (GDM) increases the risks of maternal, placental, and neonatal complications. Previously, we found that a diet enriched in extra virgin olive oil (EVOO) prevents increased maternal triglyceridemia and placental proinflammatory markers in a cohort of GDM patients. The aim of this work was to evaluate maternal circulating markers of insulin resistance, placental collagen, glycogen and lipid levels, and placental levels of proteins, mRNAs, and a microRNA involved in the endocytic pathway in the same cohort of control women and women with GDM who received or did not receive a diet enriched in EVOO (36 g/day) from weeks 24 to 28 of pregnancy until term.

Results

At term, the TG/HDL cholesterol ratio, fatty acid binding protein 4 circulating levels, and maternal BMI were increased in the GDM patients, alterations prevented by the maternal diet enriched in EVOO. Although there were no changes in placental lipid levels and lipid profile, GDM placentas were thicker than controls and showed increased glycogen and collagen content, alterations prevented by the EVOO enriched diet. GDM placentas showed increases in megalin levels, in the expression of several genes involved in the endocytic pathway, and in miR-199, which targets these genes, alterations prevented by the maternal diet enriched in EVOO.

Conclusions

We identified novel beneficial effects of an EVOO-enriched diet in GDM women, a diet capable of regulating maternal insulin resistance, the structure and metabolism of the placenta, and the placental endocytic pathway, suggesting effects that may be beneficial for fetal development.
A comparative study of human and zebrafish glucocorticoid receptor activities of natural and pharmaceutical steroids
Authors: Toso Anna , Boulahtouf Abdelhay , Escande Aurélie , Garoche Clémentine , Balaguer Patrick
Published: August 2023

Introduction

The action of environmental steroids on the human glucocorticoid receptor (hGR) has been pointed out with the risk to impair physiological immune and metabolic processes regulated by this nuclear receptor. However, there is still a lack of mechanistic information regarding their ability to interact with GR in aquatic species.

Methods

To investigate ligand activation differences between hGR and zebrafish GR (zfGR), we tested several natural and synthetic steroids using reporter cell lines expressing hGR or zfGR.

Results and discussion

Almost all the glucocorticoids tested (dexamethasone, cortisol, bimedrazol, medrol, cortivazol and fluticasone) are agonists of the two receptors with similar potencies. The dissociated glucocorticoids, RU24782 and RU24858 are agonists of both zfGR and hGR but with a better potency for the latter. On the other hand, the synthetic glucocorticoid forbimenol and the mineralocorticoid aldosterone are agonist on hGR but antagonist on zfGR. The other steroids tested, androgens and progestins, are all antagonists of both GRs with equal or lower potency on zfGR than on hGR. Surprisingly, the lower efficacy and potency on zfGR of aldosterone, forbimenol and the dissociated glucocorticoids is not related to their affinity for the receptors which would suggest that it could be related to less efficacious recruitment of coactivators by zfGR compared to hGR.
Household structure is independently associated with malaria risk in rural Sussundenga, Mozambique
Authors: Searle Kelly M. , Earland Dominique , Francisco Albino , Muhiro Valy , Novela Anisío , Ferrão João
Published: August 2023

Introduction

Mozambique has the fourth highest malaria cases and malaria mortality globally. Locally, malaria incidence increases from low in the southern region to high in the central and northern regions. Manica Province in central Mozambique has the fourth highest prevalence of malaria out of the 11 provinces, and the highest in the central region of the country. In this area where coverage of interventions has been limited, household level risk factors can be important for understanding the natural history of infection, as well as the implementation of current and future interventions. There has been indication that the relationship between household structure and malaria risk is actually a mediating one between the true relationship between household income and education and Plasmodium falciparum infection. The objective of this study was to determine and quantify these complex relationships.

Methods

We conducted a community-based cross-sectional study in Sussundenga village. Sussundenga is a rural village, located in Sussundenga District, Manica Province, Mozambique. We enrolled 303 participants from 83 randomly selected households. We collected information on demographics, household construction, and administered a P. falciparum rapid diagnostic test (RDT). We constructed several generalized estimating equations logistic regression models to determine the independent effects of housing construction on malaria risk. We also constructed models separate from generalized estimating equations logistic mediation models to determine the proportion of effects mediated by household construction material in the relationship between head of household occupation and education and malaria risk.

Results

The overall malaria prevalence among the study population by RDT was 30.8%. In the multivariable model adjusting for all individual and household factors as potential confounders, rudimentary roof structure was the only household structural variable that was statistically significantly associated with increased malaria risk [OR 2.41 (1.03–5.63)]. We found no evidence that household structure mediated the relationship between head of household education or employment and malaria risk in our study population.

Discussion

Household structure was a significant risk factor for malaria infection in our study population. These findings are consistent with malaria being a disease of poverty and an area that could be targeted for future interventions that could have long-term impacts.
Phenotypic plasticity in an egg parasitoid affects olfactory response to odors from the plant–host complex
Authors: Chierici Elena , Sabbatini-Peverieri Giuseppino , Roversi Pio Federico , Rondoni Gabriele , Conti Eric
Published: August 2023

Female egg parasitoids must optimize their ability to find a suitable host for reproduction in a limited foraging time. Odorant cues associated with the plant–host complex play an essential role in guiding females toward the host. However, parasitoid response is not always identical within the same genotype, and it could be influenced by the environment. This phenotypic plasticity affects parasitoid behavior and morphology and is directly linked to rearing conditions. Yet, how plasticity influences olfactory responses of egg parasitoids toward plant–host odors is largely unexplored. Trissolcus japonicus (Ashmead) (Hymenoptera: Scelionidae) is an effective biocontrol agent of the invasive brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae). Laboratory no-choice and choice tests showed T. japonicus potential to develop in eggs of non-target Pentatomidae. In Y-tube olfactometer we evaluated the olfactory responses of T. japonicus reared on different hosts toward plant–host derived volatiles associated with H. halys and two other stink bug species. Parasitoids reared on the main host H. halys positively responded only to odors from V. faba–H. halys complex. When reared on alternative hosts, T. japonicus was smaller and did not exhibit attraction to any stimuli, although egg load was only partially affected. Host-induced phenotypic plasticity should be considered when evaluating parasitoids for classical biological control.
Spatiotemporal evolution and driving factors of urban green technology innovation efficiency in the Chengdu-Chongqing Economic Circle of China
Authors: Deng Shicheng , Wu Yuming
Published: August 2023

Introduction

Green technology innovation efficiency (GTIE) growth is an essential route to protect the urban ecological environment in the Chengdu-Chongqing Economic Circle (CCEC). However, the measurement and spatial driving factors of GTIE are still puzzled.

Methods

This study constructs an urban GTIE indicator system including inputs, desired outputs, and undesired outputs, and evaluates urban GTIE in the CCEC using the super-efficiency slacks-based measure (S-SBM). Then, the exploratory spatial data analysis (ESDA) method is applied to analyze the geographical distribution and spatial correlation characteristics of urban GTIE, and a spatial econometric model is used to analyze the influencing factors of urban GTIE from the perspective of spatial spillover.

Results

The results suggest that: (1) From 2006 to 2020, the urban GTIE of CCEC has obviously increased, and its spatial distribution has a prominent unbalanced feature. (2) The urban GTIE of CCEC mainly presents a significant spatial positive correlation, mainly manifested in the "high-efficiency type" and "low-efficiency type" regional agglomeration patterns, and the spatial "core-edge" structure centering on Chengdu and Chongqing tends to be stable. (3) Economic development (ED), government support (GS), and environmental regulation (ER) can promote the urban GTIE. The negative spillover effects of external opening (EO) and ER are significant, and they have negative effects on the GTIE of neighboring cities. (4) Spatial heterogeneity analysis shows that the driving factors of urban GTIE with different efficiency levels are significantly different, and the spatial spillover effect of the driving factors of GTIE is more significant in high-efficiency cities.

Discussion

The urban GTIE in the CCEC is showing a growth trend, but it needs to narrow the gap in GTIE between cities. Firstly, cities can improve the GTIE by improving ED, strengthening GS, and enhancing ER. Secondly, cities need to pay attention to the negative spatial spillover effects of ER and EO in the process of improving the GTIE. Finally, cities with different efficiency types need to develop differentiated green innovation development strategies based on their own conditions.
Deformation triggers and stability evolution of landslide from multiple observations
Authors: Yang Beibei , Liu Zhongqiang , Lacasse Suzanne , Wang Luqi , Xiao Ting
Published: August 2023

External causes like changes in reservoir level and intense rainfall can cause reservoir landslides. Exploring the factors that govern landslide deformation and analyzing its stability evolution is essential in mitigating the associated risks. The Sanzhouxi landslide, which has experienced ongoing movements and has been implemented a professional monitoring system, is chosen for analysis in this paper. A combination of geological survey and analysis of monitoring data is utilized to explore landslide deformation characteristics. A data mining method, grey relation analysis (GRA), is subsequently performed to determine the causes of landslide deformation. Furthermore, the stability of the Sanzhouxi landslide in response to reservoir level fluctuation and rainfall for each day over an entire year is assessed using the Morgenstern-Price (MP) approach in 2D GeoStudio software. Such a process illustrates clearly how the landslide stability alters with external triggers changing. The findings reveal that the landslide deforms variably in spatial and temporal. The reservoir level rising contributes to landslide deformation primarily, while rainfall has a secondary impact. The factor of safety (FS) of the Sanzhouxi landslide drops from 1.17 to 1.07 during high reservoir water level periods and remain the same or increase in other periods except for some transitory moments while decreasing only by about 2% under the effect of rainfall. The daily FS results validate the dominant influence of reservoir level fluctuation on the stability of the landslide. The comprehensive understanding of landslide movement based on deformation characteristics, triggering factor identification, and daily stability validation, contributes to realizing nearly real-time prediction and evaluating the risk due to slope movements in similar geological settings worldwide.
Analysis of plant expression profiles revealed that aphid attack triggered dynamic defense responses in sorghum plant
Authors: Huang Yinghua , Huang Jian
Published: August 2023

Sorghum [Sorghum bicolor (L.) Moench] is one of the most important cereal crops grown worldwide but is often attacked by greenbug (aphid). In response to aphid attack, host plant initiates a large transcriptional reorganization, leading to activation of the host defense genes in aphid-attacked plants. In this study, our objective was to analyze defensive responses of sorghum against aphid and identify aphid resistance genes in sorghum. For the experiments, seedlings developed from an aphid resistant germplasm line (PI 550607) were divided into two groups, then, one group was infested with greenbug ((Schizaphis graminum Rondani) and the other group was used as control (un-infested). In addition, seedlings of sorghum cultivar Tx 7000, a susceptible genotype, prepared under the same conditions, were used as a genetic control. Those plant samples were used to develop transcriptional profiles using the microarray method, from which 26.1% of the 1,761 cDNA sequences spotted on the microarray showed altered expression between two treatments at 4 days after infestation. Sequence annotation and molecular analysis revealed that many differentially expressed genes (DEGs) were related to direct host defense or signal transduction pathways, which regulate host defense. In addition to common responsive genes, unique transcripts were identified in response to greenbug infestation specifically. Later, a similar transcriptional profiling was conducted using the RNA-seq method, resulted in the identification of 2,856 DEGs in the resistant line with a comparison between infested and non-infested at 4 days and 4,354 DEGs in the resistant genotype compared to the susceptible genotype at 4 days. Based on the comparative analysis, the data of RNA-seq provided a support for the results from the microarray study as it was noticed that many of the DEGs are common in both platforms. Analysis of the two differential expression profiles indicate that aphid triggered dynamic defense responses in sorghum plants and sorghum plant defense against aphid is a complex process involving both general defense systems and specific resistance mechanisms. Finally, the results of the study provide new insights into the mechanisms underlying host plant defense against aphids and will help us design better strategies for effectively controlling aphid pest.
Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM
Authors: Su Zhenguo , Lu Huihui , Wu Yan , Li Zejun , Duan Lian
Published: August 2023

Introduction: Lung cancer is one of the most frequent neoplasms worldwide with approximately 2.2 million new cases and 1.8 million deaths each year. The expression levels of programmed death ligand-1 (PDL1) demonstrate a complex association with lung cancer. Neuroblastoma is a high-risk malignant tumor and is mainly involved in childhood patients. Identification of new biomarkers for these two diseases can significantly promote their diagnosis and therapy. However, in vivo experiments to discover potential biomarkers are costly and laborious. Consequently, artificial intelligence technologies, especially machine learning methods, provide a powerful avenue to find new biomarkers for various diseases.

Methods: We developed a machine learning-based method named LDAenDL to detect potential long noncoding RNA (lncRNA) biomarkers for lung cancer and neuroblastoma using an ensemble of a deep neural network and LightGBM. LDAenDL first computes the Gaussian kernel similarity and functional similarity of lncRNAs and the Gaussian kernel similarity and semantic similarity of diseases to obtain their similar networks. Next, LDAenDL combines a graph convolutional network, graph attention network, and convolutional neural network to learn the biological features of the lncRNAs and diseases based on their similarity networks. Third, these features are concatenated and fed to an ensemble model composed of a deep neural network and LightGBM to find new lncRNA–disease associations (LDAs). Finally, the proposed LDAenDL method is applied to identify possible lncRNA biomarkers associated with lung cancer and neuroblastoma.

Results: The experimental results show that LDAenDL computed the best AUCs of 0.8701, 107 0.8953, and 0.9110 under cross-validation on lncRNAs, diseases, and lncRNA‐disease pairs on Dataset 1, respectively, and 0.9490, 0.9157, and 0.9708 on Dataset 2, respectively. Furthermore, AUPRs of 0.8903, 0.9061, and 0.9166 under three cross‐validations were obtained on Dataset 1, and 0.9582, 0.9122, and 0.9743 on Dataset 2. The results demonstrate that LDAenDL significantly outperformed the other four classical LDA prediction methods (i.e., SDLDA, LDNFSGB, IPCAF, and LDASR). Case studies demonstrate that CCDC26 and IFNG-AS1 may be new biomarkers of lung cancer, SNHG3 may associate with PDL1 for lung cancer, and HOTAIR and BDNF-AS may be potential biomarkers of neuroblastoma.

Conclusion: We hope that the proposed LDAenDL method can help the development of targeted therapies for these two diseases.
Upregulated CD8+ MAIT cell differentiation and KLRD1 gene expression after inactivated SARS-CoV-2 vaccination identified by single-cell sequencing
Authors: Dou Xiaowen , Peng Mian , Jiang Ruiwei , Li Weiqin , Zhang Xiuming
Published: August 2023

Background

The primary strategy for reducing the incidence of COVID-19 is SARS-CoV-2 vaccination. Few studies have explored T cell subset differentiation and gene expressions induced by SARS-CoV-2 vaccines. Our study aimed to analyze T cell dynamics and transcriptome gene expression after inoculation with an inactivated SARS-CoV-2 vaccine by using single-cell sequencing.

Methods

Single-cell sequencing was performed after peripheral blood mononuclear cells were extracted from three participants at four time points during the inactivated SARS-CoV-2 vaccination process. After library preparation, raw read data analysis, quality control, dimension reduction and clustering, single-cell T cell receptor (TCR) sequencing, TCR V(D)J sequencing, cell differentiation trajectory inference, differentially expressed genes, and pathway enrichment were analyzed to explore the characteristics and mechanisms of postvaccination immunodynamics.

Results

Inactivated SARS-CoV-2 vaccination promoted T cell proliferation, TCR clone amplification, and TCR diversity. The proliferation and differentiation of CD8+ mucosal-associated invariant T (MAIT) cells were significantly upregulated, as were KLRD1 gene expression and the two pathways of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay, and translational initiation.

Conclusion

Upregulation of CD8+ MAIT cell differentiation and KLRD1 expression after inactivated SARS-CoV-2 vaccination was demonstrated by single-cell sequencing. We conclude that the inactivated SARS-CoV-2 vaccine elicits adaptive T cell immunity to enhance early immunity and rapid response to the targeted virus.
Activated mast cells in periprosthetic joint infection-associated tissue
Authors: Fisher Cody R. , Patel Robin
Published: August 2023

Background

Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty surgery. Increased densities of activated mast cells have been predicted to be present in PJI compared to non-infectious arthroplasty failure based on analysis of transcriptomic data, but their presence in PJI-associated periprosthetic tissues has not been visually confirmed.

Objective

This preliminary study investigated the presence and activation status of mast cells in periprosthetic tissues associated with PJI.

Methods

Periprosthetic tissues from five PJI cases and three arthroplasty failures due to instability and one due to stiffness were immunohistochemically stained using tryptase and microscopically evaluated to enumerate mast cells and evaluate overall activation status within tissue samples. Mast cell activation was evidenced by the release of tryptase into the extracellular space surrounding mast cells.

Results

Mast cells were found in all samples, with average cellular densities of 22 and 26 cells/mm2 tissue in PJI and uninfected samples, respectively (p, 0.6610). Apparent mast cell activation and degranulation was readily observed throughout each of the five PJI samples studied, but not in any of the uninfected samples studied.

Conclusion

While preliminary, these findings provide evidence for a role of mast cells in the immune response in PJI. Additional investigation of the role of mast cells during arthroplasty failure is warranted, providing a better understanding of underlying biology and informing potential diagnostic and treatment targets.
Molecular techniques drive cutting edge advancements in management of cutaneous T cell lymphoma
Authors: Lefebvre Mitchell N. , Borcherding Nicholas , Reis Ryan J. , Mou Eric , Liu Vincent , Jabbari Ali
Published: August 2023

Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping via sequencing to detect CTCL earlier in the disease course and single-cell RNA sequencing to identify gene expression patterns that commonly drive CTCL pathogenesis. Experience with these techniques has afforded novel insights which may translate into enhanced diagnostic and therapeutic approaches for CTCL.
Single-cell RNA sequencing reveals distinct chondrocyte states in femoral cartilage under weight-bearing load in Rheumatoid arthritis
Authors: Yan Mingyue , Sun Zewen , Wang Junjie , Zhao Haibo , Yu Tengbo , Zhang Yingze , Wang Tianrui
Published: August 2023

Introduction

Rheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the disease. Chondrocytes are the main functional component of articular cartilage, which is relevant to disease progression. Mechanical loading affects the structure and function of articular cartilage and chondrocytes, but the effect of weight bearing on chondrocytes in rheumatoid arthritis is still unclear.

Methods

In this paper, single-cell RNA sequencing (scRNA-seq) was performed on collected cartilage from the weight-bearing region (Fb group) and non-weight-bearing region (Fnb group) of the femur, and the differences between the Fb and Fnb groups were analyzed by cell type annotation, pseudotime analysis, enrichment analysis, cell interactions, single-cell regulatory network inference and clustering (SCENIC) for each cell type.

Results

A total of 87,542 cells were analyzed and divided into 9 clusters. Six chondrocyte subpopulations were finally identified by cellular annotation, and two new chondrocyte subtypes were annotated as immune-associated chondrocytes. The presence of each chondrocyte subpopulation and its distribution were verified using immunohistochemical staining (IHC). In this study, the atlas of femoral cartilage in knee rheumatoid arthritis and 2 new immune-related chondrocytes were validated using scRNA-seq and IHC, and chondrocytes in the weight-bearing and non-weight-bearing regions of the femur were compared. There might be a process of macrophage polarization transition in MCs in response to mechanical loading, as in macrophages.

Conclusion

Two new immune-associated chondrocytes were identified. MCs have contrasting functions in different regions, which might provide insight into the role of immune and mechanical loading on chondrocytes in the development of knee rheumatoid osteoarthritis.
Growth performance, digestive capacity and intestinal health of juvenile spotted seabass (Lateolabrax maculatus) fed dietary laminarin supplement
Authors: Qin Huihui , Long Zhongying , Ma Jianrong , Kong Lumin , Lin Hao , Zhou Sishun , Lin Yi , Huang Zhangfan , Liu Longhui , Li Zhongbao
Published: August 2023

Laminarin has antioxidant and immunomodulatory properties and favorably impacts gut microbial composition, providing a potential solution for the treatment of intestinal diseases in fish. The aim of this study was to investigate the effects of laminarin on the growth and intestinal health of juvenile spotted seabass, Lateolabrax maculatus. A total of 450 juveniles (initial body weight: 7.14 ± 0.10 g) were randomly divided into 6 groups with 3 replicates per group and 25 fish per replicate. Six diets were prepared with laminarin supplementation at doses of 0% (Control), 0.4% (P0.4), 0.8% (P0.8), 1.2% (P1.2), 1.6% (P1.6), and 2% (P2). Each group was fed the corresponding diet for 8 weeks. The results indicated that dietary laminarin supplementation of 0.4-1.6% enhanced the specific growth rate (SGR), weight gain rate (WGR), and feed conversion ratio (FCR) of juvenile spotted seabass, and the difference was significant in the P0.8 group (P<0.05). Significantly higher intestinal amylase activity was measured in P0.8 compared with the control group. Trypsin activity was significantly increased in P0.4 and P0.8 groups in contrast to the control (P<0.05). Lipase activity was significantly increased in P0.4, P0.8, P1.6, and P2 groups in contrast to the control (P<0.05). Total antioxidant capacity was significantly increased in the P0.8, P1.2, and P1.6 groups compared to the control group (P<0.05). The P0.8 group exhibited significant increases in reduced glutathione, alkaline phosphatase, and lysozyme levels (P<0.05), whereas the concentrations of diamine oxidase and D-lactate were significantly decreased (P<0.05). Furthermore, intestinal villus height, villus width, and crypt depth were significantly increased in P0.8 and P2 groups (P<0.05), and muscular thickness was significantly increased in the P1.2 group (P<0.05). Intestinal microbial analysis revealed that the alpha diversity of the laminarin supplemented groups was significantly higher than that of the control group. Moreover, the abundance of intestinal beneficial bacteria Lactobacillus and Klebsiella in P0.4 and P0.8 groups was significantly increased (P<0.05), indicating that laminarin altered the composition of intestinal flora and the abundance of dominant bacteria, with a low dose being more conducive to the formation of beneficial bacteria. In conclusion, dietary laminarin supplementation can improve the growth performance and intestinal function of juvenile spotted seabass. Based on the regression analyses of weight gain rate and specific growth rate, the optimal supplemental level of laminarin was estimated to be 0.97% and 0.98%, respectively.