bluuebunny/crossref_metadata_2025 huggingface dataset:
An Exploratory Study of a Novel Combined Therapeutic Modality for Obsessive-Compulsive Disorder
Authors: Huang Yueqi , Yang Hangyi , Zhu Cheng , Jiang Xiaoying , Zhu Wenjing , Liang Yan , Ma Lisha , Wang Yunzan , Tang Wenxin
Published: September 2022

Objective: To explore whether a systematic combined therapeutic modality (CTM) could quickly and effectively improve the severity of obsessive–compulsive disorder (OCD) and the insight of OCD patients. Methods: Included in this study were 100 patients with OCD according to the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), for a 2-week short-term treatment. They were assigned to a drug-alone group (n = 57), and a CTM group (n = 43) using drug treatment in combination with cognitive behavioral treatment (CBT) and repetitive transcranial magnetic stimulation (rTMS). The therapeutic outcome was assessed by the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS), Brown Assessment of Beliefs Scale (BABS), 24-item Hamilton Depression Scale (HAMD-24) and Hamilton Anxiety Scale (HAMA) before and after treatment. All data were treated with SPSS25.0 Software. Results: After the 2-week treatment, the success rate in the CTM group was significantly higher than that in the drug-alone group. Y-BOCS overall and factor scores were decreased as compared with those before treatment in both groups. HAMD, HAMA and BABS overall scores were all decreased after treatment in the CTM group. In addition, compared with the drug-alone group, the Y-BOCS overall score and factor score, HAMD overall score and HAMA overall score were all decreased significantly in CTM group, while the Y-BOCS score reduction rate was increased significantly. Insight was improved in eight cases (57.14%) in the CTM group containing 14 cases with poor insight. Multinomial logistic regression analysis showed that CTM was beneficial for the insight improvement of OCD patients (OR = 91.04–139.68); this improvement was more pronounced in patients with low baseline BABS overall scores (OR = 0.07). Conclusion: CTM may be an effective short-term strategy to improve the severity of OCD and insight of OCD patients and, therefore, is worthy of clinical promotion and application.
Rehabilitation of Severe Impairment in Motor Function after Stroke: Suggestions for Harnessing the Potentials of Mirror Neurons and the Mentalizing Systems to Stimulate Recovery
Authors: Abdullahi Auwal , Wong Thomson W. L. , Ng Shamay S. M.
Published: September 2022

Rehabilitation of severe impairment in motor function following stroke is very challenging. This is because one of the driving forces for recovery of motor function is tasks practice, something this category of patients cannot voluntarily perform. However, it has now been shown that tasks practice can equally be carried out cognitively and through observation of another person’s practice, using techniques known as mental practice and tasks observation, respectively. Mental practice and tasks observation are believed to activate networks of neurons in the brain known as mirror neurons and mentalizing systems to induce recovery. The effectiveness of these techniques has, however, limited evidence at the moment. One possible explanation for this could be the nature of the protocols of these techniques, especially as regards to the intensity of practice. This article proposes ways the potentials of the mirror neurons and mentalizing systems can be harnessed to optimize recovery of severe impairment in motor function using mental practice and tasks observation. The article suggests, among other ways, protocols where tasks observation or mirror therapy are carried out first, and are then followed by mental practice, increasing the number of times the tasks are observed or mentalized, observation of significant others performing the tasks and mental practice of very familiar tasks.
Symptoms of Attention Deficit/Hyperactivity Disorder Are Associated with Sub-Optimal and Inconsistent Temporal Decision Making
Authors: Gabrieli-Seri Ortal , Ert Eyal , Pollak Yehuda
Published: September 2022

The link between Attention-Deficit/Hyperactivity Disorder (ADHD) and steeper delay discounting has been established and incorporated into theories of ADHD. This study examines a novel interpretation according to which ADHD is linked to sub-optimal temporal decision-making and suggests inconsistency as a potential underlying mechanism. In two experiments, MTurk workers completed a self-report questionnaire on symptoms of ADHD and a temporal decision making task consisting of choices between smaller–immediate and larger–delayed options. The delayed option was better in some items, whereas the immediate option was better in others. The rate of choices of the delayed option and the consistency of choices were measured. The results of both studies show that high symptoms of ADHD were linked to fewer choices of the delayed option when it was better, but also to more choices of the delayed option when it was not better. In addition, ADHD was linked to higher inconsistency in both conditions. The findings suggest that ADHD is linked to sub-optimal temporal decision-making rather than steeper delay discounting, and provide further support to the phenomenon of inconsistency in ADHD.
Is That “Mr.” or “Ms.” Lemon? An Investigation of Grammatical and Semantic Gender on the Perception of Household Odorants
Authors: White Theresa L. , Cunningham Caitlin M. , Zampini Mary L.
Published: September 2022

Linguistic relativism is the idea that the structure of language influences thought. The present study investigates linguistic relativism by asking whether people who speak a gendered language think of objects in a way that is consistent with the grammatical gender (more masculine or feminine) more than people who speak a language without that linguistic feature. Odorants are unique stimuli for examining this question, because they carry a semantic gender without a biological one, yet gender is thought to be a central dimension of their perception. Canadian participants in the present study (native French or native English speakers) described a set of labeled odorants that varied systematically in grammatical and semantic gender to produce an implicit gender measure and also explicitly rated them for gender. Analysis of the implicit femininity contained in participants’ descriptions showed a tendency for both native French and native English speakers to produce descriptions that were consistent with semantic gender; moreover, there were no effects of grammatical gender on implicit or explicit ratings. These results suggest that in a bilingual culture, French speakers may have been influenced by the anthropomorphism associated with odorants rather than grammatical gender.
Reactivity of the Oxytocinergic and Neuroendocrine System Following the Adult Attachment Projective Picture System in Men of Recent Fatherhood: Results from an Exploratory Pilot Study with a Cross-Sectional Design
Authors: Karabatsiakis Alexander , de Punder Karin , Doyen-Waldecker Cornelia , Ramo-Fernández Laura , Krause Sabrina , Gumpp Anja Maria , Bach Alexandra Maria , Fegert Jörg Michael , Kolassa Iris-Tatjana , Gündel Harald , Ziegenhain Ute , Buchheim Anna
Published: September 2022

The attachment representation (AR) of individuals affects emotional and cognitive information processes and is considered an important modulating factor of neuroendocrine stress responses. The neuropeptide oxytocin is studied as one biomolecular component underpinning this modulation. A validated procedure used in attachment-related research is the Adult Attachment Projective Picture System (AAP). To date, only a limited number of studies investigated oxytocin and neuroendocrine reactivity in the context of an attachment-related stimulus similar to the APP. In this pilot study, N = 26 men of recent fatherhood were exposed to the AAP to classify AR and to investigate salivary changes in oxytocin, cortisol and dehydroepiandrosterone (DHEA) after AAP stimulation. We observed increased oxytocin levels in response to AAP exposure, and this increase was more pronounced in fathers with unresolved/disorganized AR. No significant changes in cortisol and DHEA concentrations were observed in response to AAP administration. Interestingly, differences in basal cortisol levels (before the AAP) also depended on AR classification. Here, the group of men with unresolved/disorganized AR showed higher levels of cortisol compared to fathers with organized AR. To conclude, the finding of increased salivary oxytocin levels in response to the AAP further indicates its validity as an instrument to stimulate the attachment system.
Reading Behaviors through Patterns of Finger-Tracking in Italian Children with Autism Spectrum Disorder
Authors: Marzi Claudia , Narzisi Antonio , Milone Annarita , Masi Gabriele , Pirrelli Vito
Published: September 2022

The paper proposes an ecological and portable protocol for the large-scale collection of reading data in high-functioning autism spectrum disorder (ASD) children based on recording the finger movements of a subject reading a text displayed on a tablet touchscreen. By capitalizing on recent evidence that movements of a finger that points to a scene or text during visual exploration or reading may approximate eye fixations, we focus on recognition of written content and function words, pace of reading, and accuracy in reading comprehension. The analysis showed significant differences between typically developing and ASD children, with the latter group exhibiting greater variation in levels of reading ability, slower developmental pace in reading speed, less accurate comprehension, greater dependency on word length and word frequency, less significant prediction-based processing, as well as a monotonous, steady reading pace with reduced attention to weak punctuation. Finger-tracking patterns provides evidence that ASD readers may fail to integrate single word processing into major syntactic structures and lends support to the hypothesis of an impaired use of contextual information to predict upcoming stimuli, suggesting that difficulties in perception may arise as difficulties in prediction.
On the Applicability of Conventional Seismic Design Methodologies to Hybrid RC-Steel Systems
Authors: Falcão Moreira Rodrigo , Varum Humberto , Castro José Miguel
Published: September 2022

This paper addresses the application of conventional (force-based) seismic design methodologies to hybrid RC-steel systems. The q-factor-based EC8-3 seismic assessment procedure is first reviewed. A case-study application follows, analyzing and discussing the difficulties a practitioner will face when assessing the efficiency of a steel-brace retrofitting system designed within the framework of EC8-1. Afterward, the performance of the obtained retrofitted structure is evaluated using nonlinear analysis. The obtained results are discussed in light of the EC8-3 performance requirements, and conclusions are drawn about the adequacy of the force-based design (FBD) methodology (and associated q-factors) for such situations. The study shows that the process does not ensure the adequate seismic behavior of the retrofitted structures. It thus calls for the development of an effective performance-based design methodology that explicitly considers the interaction between the two structural systems (RC structure and steel braces), namely the influence of the steel braces’ resistance on the deformation capacity of RC members.
An Investigation of Construction Project Efficiency: Perception Gaps and the Interrelationships of Critical Factors
Authors: Milind Mehta Siddhant , Chang Soowon , Oh Heung Jin , Kwon Jin-Hyuk , Kim Sungjin
Published: September 2022

Construction projects are complex as various project entities involve and collaborate with each other. This complexity not only causes issues such as project delays but also makes it difficult to manage projects. Previous research has often used productivity and efficiency interchangeably, but they are not the same. The field of construction efficiency has not been fully studied to understand its entire potential in a practical context. Toward this end, this research aims to support efficient construction project management by exploring the inefficiency factors as well as identifying the perception gaps between different occupations and the interrelationships between the factors. Twenty inefficiency factors were identified through a comprehensive literature review; then, the importance of the factors and the perception gaps among stakeholders were studied by analyzing online survey data using RII (relative importance index), Welch’s t-test, and factor analysis. In addition, interviews with field engineers and managers allowed us to explore cause-and-effect relationships among the factors and determine triggering and critical factors based on their chain reactions. This research found that a major perception gap among project stakeholders was in the factor of unrealistic scheduled dates. The research contributes to project risk management and strategic planning for construction project efficiency.
Conservation of the Beira Railway Station in Mozambique: Lessons from a 20th-Century Heritage Case Study in Africa
Authors: Chaves Estefanía , Ortega Javier , Silva Sandra M. , Lourenço Paulo B.
Published: September 2022

The conservation of built cultural heritage is a fundamental task for modern societies. Specialized expertise is necessary to define a proper strategy to preserve a heritage that is accumulating damage due to the deterioration of materials, repeated loading, and exceptional events. This paper provides part of the work developed for the definition of the Conservation Management Plan of a 20th-century building in Africa. The monumental building, the Beira railway station, is in Mozambique and was considered among the one hundred more important 20th-century Portuguese engineering buildings. The work presented focuses on the analysis of damage, material characterization, and assessment of the comfort conditions of this concrete building—fundamental tasks for the understanding of the current condition of the building and the definition of appropriate remedial actions and maintenance tasks. The work provides a detailed definition of different approaches and techniques that can be implemented for this type of building to obtain reliable information to define measures and actions that are more in line with the reality of the building. Moreover, the work allows for a discussion on the long-term performance of Modern Movement buildings with low maintenance and the success of comfort concepts in local climatic conditions.
Developing a Performance Evaluation Framework for Public Private Partnership Projects
Authors: Ahmad Zeeshan , Mubin Sajjad , Masood Rehan , Ullah Fahim , Khalfan Malik
Published: September 2022

The public–private partnership (PPP) is a potential procurement strategy for delivering complex construction projects. However, implementing PPPs has not been explored extensively in developing countries like Pakistan. A performance framework is developed in this study to evaluate the application of PPP projects based on 10 key performance indicators (KPIS) and 41 performance measures (PMS). This framework was reviewed by experts for coverage and relevance, then validated through two case studies involving road construction. A triangulation approach was adopted to collect the relevant data through multiparty focus group sessions, archives, and site observations, which enhances the reliability of the data. Results showed there is a difference in performance for six KPIS, but similar practices were reported for four KPIS. The developed performance evaluation framework (PEF) for PPP projects is suitable for developing countries transitioning toward adopting this procurement strategy.
Remdesivir Decreases Mortality in COVID-19 Patients with Active Malignancy
Authors: Jaroszewicz Jerzy , Kowalska Justyna , Pawłowska Małgorzata , Rogalska Magdalena , Zarębska-Michaluk Dorota , Rorat Marta , Lorenc Beata , Czupryna Piotr , Sikorska Katarzyna , Piekarska Anna , Dworzańska Anna , Zaleska Izabela , Mazur Włodzimierz , Kozielewicz Dorota , Kłos Krzysztof , Podlasin Regina , Angielski Grzegorz , Oczko-Grzesik Barbara , Figlerowicz Magdalena , Szetela Bartosz , Bolewska Beata , Frańczak-Chmura Paulina , Flisiak Robert , Tomasiewicz Krzysztof
Published: September 2022

Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.
Identification of Biomarkers Associated with Liver Metastasis Progression from Colorectal Cancer Using Exosomal RNA Profiling
Authors: Lee Soohyeon , Park Young Soo , Kim Jwa Hoon , Lim Ah Reum , Hyun Myung Han , Kim Boyeon , Lee Jong Won , Lee Saet Byeol , Kim Yeul Hong
Published: September 2022

This study aimed to identify novel biomarkers for metastatic colorectal cancer progression using exosomal RNA expression profiling. The exosomal RNA expression profiles of 54 patients with mCRC were investigated. Exosomal RNA profiling was performed at the time of relapse immediately before metastasectomy and cancer recurrence or progression after metastasectomy. The up- and down-regulated RNA expression profiles were screened and analyzed using H-cluster, principle component analysis and gene ontology. The tissue expression profile of the liver metastases was compared with the GSE 41258 set using GSEA tools. We identified two distinctive biological process gene sets (IFNA and PCDB families) related to metastatic progression. The interferon-α response gene set was enriched, especially when the tumor volume was ≥1 cm3. CXCL10, CXCL11 and SAMD 9 mRNA were highly expressed in the plasma exosome samples of patients with mCRC to the liver. Furthermore, high expression of CXCL10 but not CXCL11 or SAMD9 was associated with a poor prognosis and shorter progression-free survival. Conclusions: Cancer-derived exosomal CXCL10 may be a novel biomarker for liver metastasis of mCRC and a potential target for the prevention and treatment of mCRC with liver metastasis.
A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility
Authors: Marchena-Perea Erik Michel , Salazar-Hidalgo Milton Eduardo , Gómez-Sanz Alicia , Arranz-Ledo Mónica , Barroso Alicia , Fernández Victoria , Tejera-Pérez Hugo , Pita Guillermo , Núñez-Torres Rocío , Pombo Luz , Morales-Chamorro Rafael , Cano-Cano Juana María , Soriano Maria del Carmen , Garre Pilar , Durán Mercedes , Currás-Freixes María , de la Hoya Miguel , Osorio Ana
Published: September 2022

Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18–4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene.
A Novel Method for Dynamic Molecular Weight Distribution Determination in Organometallic Catalyzed Olefin Polymerizations
Authors: Shiri Masoud , Parvazinia Mahmoud , Yousefi Ali Akbar , Bahri-Laleh Naeimeh , Poater Albert
Published: September 2022

In this study, a mathematical model for the time evolution of molecular weight distribution (MWD) was developed. This temporal model is based on the well-known Ziegler–Natta polymerization mechanism and reaction kinetics by the parametric solving of related differential equations. However, due to the generality of the reactions involved, the model can be extended to the other type of catalysts, such as metallocenes, Phillips, etc. The superiority of this model lies in providing the possibility of a more precise prediction over the active sites and kinetic parameters using a simple mathematical equation, which leads to improved reactor design in large-scale production. The model uses a function to develop a methodology for MWD calculations. In this way, the transient response is limited to the first few minutes of the reaction; however, it is important as it demonstrates the establishment of the final MWD. According to the results, almost for practical conditions with negligible transfer resistances, the time dependency of the MWD has a transient interval, depending on the kinetic constants of polymerization reactions. Increasing the time to infinity results in an increase in MW and a widening in MWD, which confirms the experimental plots well. In short, the main advantage of our proposed model over the previous ones is its ability to predict the MWD even before the completion of the polymerization reaction. The results of the present model match well with those of the well-known Schulz–Flory distribution, which only predicts the final molecular weight distribution, thus confirming that the model is reliable and generalizable.
Synthesis and Catalytic Activity of Organocatalysts Based on Enaminone and Benzenediamine Hydrogen Bond Donors
Authors: Ciber Luka , Požgan Franc , Brodnik Helena , Štefane Bogdan , Svete Jurij , Grošelj Uroš
Published: September 2022

A total of 24 novel organocatalysts based on (S)-quininamine as a chiral tertiary amine and on enaminone or 1,2-benzenediamine as hydrogen bond donors were synthesized. The enaminone-type catalysts were prepared by the transamination of N,N-dimethyl enaminones with (S)-quininamine (9 examples) and the 1,2-benzenediamine-type catalysts were prepared in 3 steps from (S)-quininamine and ortho-fluoronitrobenzene derivatives (15 examples). Their organocatalytic activity was evaluated in the Michael addition of acetylacetone to trans-β-nitrostyrene. Enantioselectivities of up to 72% ee were observed.
Recent Progress in WS2-Based Nanomaterials Employed for Photocatalytic Water Treatment
Authors: Yousef Aseel , Thiehmed Zeineb , Abdul Shakoor Rana , Altahtamouni Talal
Published: September 2022

Water pollution is one of the most serious environmental issues globally due to its harmful consequences on the ecosystem and public health. Various technologies have been developed for water treatment such as photocatalysis, which has recently drawn scientists’ attention. Photocatalytic techniques using semiconductors have shown an efficient removal of various water contaminants during water treatment as well as cost effectivity and low energy consumption. Tungsten disulfide (WS2) is among the promising Transition Metal Dichalcogenides (TMDs) photocatalysts, as it has an exceptional nanostructure and special properties including high surface area and high carrier mobility. It is usually synthesized via hydrothermal technique, chemical vapor deposition (CVD), and liquid-phase exfoliation (LPE) to obtain a wide variety of nanostructures such as nanosheets and nanorods. Most common examples of water pollutants that can be removed efficiently by WS2-based nanomaterials through semiconductor photocatalytic techniques are organic contaminants, pharmaceuticals, heavy metals, and infectious microorganisms. This review summarizes the most recent work on employing WS2-based nanomaterials for different photocatalytic water treatment processes.
Single-Phase θ-Fe3C Derived from Prussian Blue and Its Catalytic Application in Fischer-Tropsch Synthesis
Authors: Zhang Wei , Ma Caiping , Liu Xingwu , Yang Yong , Li Yongwang , Wen Xiaodong
Published: September 2022

Elucidation of the intrinsic catalytic principle of iron carbides remains a substantial challenge in iron-catalyzed Fischer-Tropsch synthesis (FTS), due to possible interference from other Fe-containing species. Here, we propose a facile approach to synthesize single-phase θ-Fe3C via the pyrolysis of a molecularly defined Fe-C complex (Fe4[Fe(CN)6]3), thus affording close examination of its catalytic behavior during FTS. The crystal structure of prepared θ-Fe3C is unambiguously verified by combined XRD and MES measurement, demonstrating its single-phase nature. Strikingly, single-phase θ-Fe3C exhibited excellent selectivity to light olefins (77.8%) in the C2-C4 hydrocarbons with less than 10% CO2 formation in typical FTS conditions. This strategy further succeeds with promotion of Mn, evident for its wide-ranging compatibility for the promising industrial development of catalysts. This work offers a facile approach for oriented preparation of single-phase θ-Fe3C and provides an in-depth understanding of its intrinsic catalytic performance in FTS.
Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota
Authors: Prakash Amog , Nourianpour Milad , Senok Abiola , Atiomo William
Published: September 2022

Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the ‘Human Microbiome Project’ in 2016. We obtained 200 articles by inputting keywords such as ‘gut microbiome’, ‘gut microbiota’, ‘gut dysbiosis’, ‘PCOS’, and ‘endometrial cancer’ into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.
Liquid–Liquid Phase Separation in Cardiovascular Diseases
Authors: Mo Yuanxi , Feng Yuliang , Huang Wei , Tan Ning , Li Xinyi , Jie Minwen , Feng Tong , Jiang Hao , Jiang Lei
Published: September 2022

Liquid–liquid phase separation (LLPS) is a biochemical process in cells that can drive proteins, RNA, and other molecules to concentrate into droplets. These droplets do not have a lipid membrane but rather exist as distinct organelles relative to the surrounding environment, and act as biochemical reaction chambers. In recent years, significant progress has been made in the study of LLPS, especially in the neurodegenerative disease, cancer, and virology fields, but little is known about LLPS in cardiovascular disease (CVD). In this review, we discuss the current understanding of the mechanism and biological functions of LLPS, particularly its roles in regulating CVD.
Nrf2-Mediated Dichotomy in the Vascular System: Mechanistic and Therapeutic Perspective
Authors: Wu Weiwei , Hendrix Andrew , Nair Sharad , Cui Taixing
Published: September 2022

Nuclear factor-erythroid 2-related factor 2 (Nrf2), a transcription factor, controls the expression of more than 1000 genes that can be clustered into different categories with distinct functions ranging from redox balance and metabolism to protein quality control in the cell. The biological consequence of Nrf2 activation can be either protective or detrimental in a context-dependent manner. In the cardiovascular system, most studies have focused on the protective properties of Nrf2, mainly as a key transcription factor of antioxidant defense. However, emerging evidence revealed an unexpected role of Nrf2 in mediating cardiovascular maladaptive remodeling and dysfunction in certain disease settings. Herein we review the role of Nrf2 in cardiovascular diseases with a focus on vascular disease. We discuss the negative effect of Nrf2 on the vasculature as well as the potential underlying mechanisms. We also discuss the clinical relevance of targeting Nrf2 pathways for the treatment of cardiovascular and other diseases.
Brain Endothelial Cells in Contrary to the Aortic Do Not Transport but Degrade Low-Density Lipoproteins via Both LDLR and ALK1
Authors: Kakava Sofia , Schlumpf Eveline , Panteloglou Grigorios , Tellenbach Flavia , von Eckardstein Arnold , Robert Jerome
Published: September 2022

The transport of low-density lipoprotein (LDL) through the endothelium is a key step in the development of atherosclerosis, but it is notorious that phenotypic differences exist between endothelial cells originating from different vascular beds. Endothelial cells forming the blood–brain barrier restrict paracellular and transcellular passage of plasma proteins. Here, we systematically compared brain versus aortic endothelial cells towards their interaction with LDL and the role of proteins known to regulate the uptake of LDL by endothelial cells. Both brain endothelial cells and aortic endothelial cells bind and internalize LDL. However, whereas aortic endothelial cells degrade very small amounts of LDL and transcytose the majority, brain endothelial cells degrade but do not transport LDL. Using RNA interference (siRNA), we found that the LDLR–clathrin pathway leads to LDL degradation in either endothelial cell type. Both loss- and gain-of-function experiments showed that ALK1, which promotes transcellular LDL transport in aortic endothelial cells, also limits LDL degradation in brain endothelial cells. SR-BI and caveolin-1, which promote LDL uptake and transport into aortic endothelial cells, limit neither binding nor association of LDL to brain endothelial cells. Together, these results indicate distinct LDL trafficking by brain microvascular endothelial cells and aortic endothelial cells.
Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity
Authors: Maixner Nitzan , Haim Yulia , Blüher Matthias , Chalifa-Caspi Vered , Veksler-Lublinsky Isana , Makarenkov Nataly , Yoel Uri , Bashan Nava , Liberty Idit F. , Kukeev Ivan , Dukhno Oleg , Levy Dan , Rudich Assaf
Published: September 2022

Objective: Up-regulated expression of transcription-factor E2F1 in human visceral adipose tissue (VAT) characterizes a dysmetabolic obesity sub-phenotype. An E2F1-miRNA network has been described in multiple cancers. Here we investigated whether elevated VAT-E2F1 in obesity is associated with VAT-miRNA alterations similar to, or distinct from, those described in cancer. Furthermore, we assessed if E2F1-associated miRNA changes may contribute to the link between high- VAT-E2F1 and a dysmetabolic obesity phenotype. Methods: We assembled a cohort of patients with obesity and high-VAT-E2F1, matched by age, sex, ±BMI to patients with low-VAT-E2F1, with and without obesity (8 patients/groupX3 groups). We performed Nanostring©-based miRNA profiling of VAT samples from all 24 patients. Candidate E2F1-related miRNAs were validated by qPCR in an independent cohort of patients with extreme obesity, with or without type-2-diabetes (T2DM) (n = 20). Bioinformatic tools and manipulation of E2F1 expression in cells were used to establish the plausibility of the functional VAT-E2F1-miRNA network in obesity. Results: Among n = 798 identified miRNAs, 17 were differentially expressed in relation to E2F1 and not to obesity itself. No evidence for the cancer-related E2F1-miRNA network was identified in human VAT in obesity. In HEK293-cells, overexpression/downregulation of E2F1 correspondingly altered the expression of miRNA-206 and miRNA-210-5p, two miRNAs with reported metabolic functions consistent with those of E2F1. In VAT from both cohorts, the expression of both miRNA-206 and 210-5p intercorrelated, and correlated with the expression of E2F1. In cohort 1 we did not detect significant associations with biochemical parameters. In cohort 2 of patients with extreme obesity, all those with high VAT-E2F1 showed a diabetes-complicated obesity phenotype and higher expression of miRNA-206 and miRNA-210-5p, which also correlated with fasting glucose levels (both miRNAs) and fasting insulin (miRNA-210-5p). Conclusions: Whilst the previously described cancer-related E2F1-miRNA network does not appear to operate in VAT in obesity, miRNAs-206 and 210-5p may link high-E2F1 expression in VAT with diabetes-complicated extreme obesity phenotype.
Nestin Modulates Airway Smooth Muscle Cell Migration by Affecting Spatial Rearrangement of Vimentin Network and Focal Adhesion Assembly
Authors: Wang Ruping , Khan Sakeeb , Liao Guoning , Wu Yidi , Tang Dale D.
Published: September 2022

Airway smooth muscle cell migration plays a role in the progression of airway remodeling, a hallmark of allergic asthma. However, the mechanisms that regulate cell migration are not yet entirely understood. Nestin is a class VI intermediate filament protein that is involved in the proliferation/regeneration of neurons, cancer cells, and skeletal muscle. Its role in cell migration is not fully understood. Here, nestin knockdown (KD) inhibited the migration of human airway smooth muscle cells. Using confocal microscopy and the Imaris software, we found that nestin KD attenuated focal adhesion sizes during cell spreading. Moreover, polo-like kinase 1 (Plk1) and vimentin phosphorylation at Ser-56 have been previously shown to affect focal adhesion assembly. Here, nestin KD reduced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation), vimentin phosphorylation at Ser-56, the contacts of vimentin filaments to paxillin, and the morphology of focal adhesions. Moreover, the expression of vimentin phosphorylation-mimic mutant S56D (aspartic acid substitution at Ser-56) rescued the migration, vimentin reorganization, and focal adhesion size of nestin KD cells. Together, our results suggest that nestin promotes smooth muscle cell migration. Mechanistically, nestin regulates Plk1 phosphorylation, which mediates vimenitn phosphorylation, the connection of vimentin filaments with paxillin, and focal adhesion assembly.
Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway
Authors: Su Kuan-Wei , Lin Hung-Yun , Chiu Hsien-Chung , Shen Shin-Yu , ChangOu Chun A. , Crawford Dana R. , Yang Yu-Chen S. H. , Shih Ya-Jung , Li Zi-Lin , Huang Haw-Ming , Whang-Peng Jaqueline , Ho Yih , Wang Kuan
Published: September 2022

Oral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T4) stimulates cancer cell proliferation via a receptor on integrin αvβ3 of plasma membranes. It also induces the expression of programmed death-ligand 1 (PD-L1) and cell proliferation in cancer cells. Thyroid hormone also activates β-catenin-dependent cell proliferation in cancer cells. However, the relationship between PD-L1 and cancer proliferation is not fully understood. In the current study, we investigated the role of inducible thyroid hormone-induced PD-L1-regulated gene expression and proliferation in oral cancer cells. Thyroxine bound to integrin αvβ3 to induce PD-L1 expressions via activation of ERK1/2 and signal transducer and activator of transcription 3 (STAT3). Inactivated STAT3 inhibited PD-L1 expression and nuclear PD-L1 accumulation. Inhibition of PD-L1 expression reduced β-catenin accumulation. Furthermore, nuclear PD-L1 formed a complex with nuclear proteins such as p300. Suppression PD-L1 expression by shRNA blocked not only expression of PD-L1 and β-catenin but also signal transduction, proliferative gene expressions, and cancer cell growth. In summary, thyroxine via integrin αvβ3 activated ERK1/2 and STAT3 to stimulate the PD-L1-dependent and β-catenin-related growth in oral cancer cells.
Development of a Versatile Strategy for Inkjet-Printed Molecularly Imprinted Polymer Microarrays
Authors: Bokeloh Frank , Gibson Kasia , Haupt Karsten , Ayela Cédric
Published: September 2022

Biochips are composed of arrays of micropatterns enabling the optical detection of target analytes. Inkjet printing, complementary to commercially available micro- and nanospotters, is a contactless and versatile micropatterning method. Surprisingly, the inkjet printing of molecularly imprinted polymers (MIPs), also known as biomimetic synthetic antibodies, has not been demonstrated as yet. In this work, core–shell structures are proposed through the combination of inkjet printing of the core (top-down approach) and controlled radical polymerization (CRP) to decorate the core with a thin film of MIP (bottom-up approach). The resulting biochips show quantitative, specific, and selective detection of antibiotic drug enrofloxacin by means of fluorescence analysis.
Plasmonic Nanosensors and Metasensors Based on New Physical Mechanisms
Authors: Li Qiaoyu , Wu Xiongbin , Zhou Yongjin
Published: September 2022

Plasmonics can bind light to their surface while increasing its intensity. The confinement and enhancement of light allows high–density, independent, subwavelength sensor elements to be constructed in micrometer–sized arrays. Plasmonic nanostructures have been widely used in the sensing field because of their fast, real–time and label–free characteristics. Numerous plasmonic metasensors have been configured for next–generation technologies since the emergence of metamaterials and metasurfaces. Among these applications, the development of high–sensitivity sensors based on new physical mechanisms has received tremendous interest recently. This review focuses on high–sensitivity plasmonic nanosensors and metasensors based on new physical mechanisms, especially based on Fano resonance and the exceptional point (EP). The asymmetric Fano resonance generated by the interference of different resonance modes has a narrower bandwidth, while an EP occurs whenever two resonant modes coalesce both in their resonant frequency and their rate of decay or growth. Both physical mechanisms could tremendously improve the sensitivity of the plasmonic sensors. We summarize the working principles, the latest development status and the development trends of these plasmonic nanosensors and metasensors. It is believed that these new sensing mechanisms can inspire more fruitful scientific research.
Differences in Motor Competence of Chilean Schoolchildren According to Biological and Sociocultural Correlates
Authors: Quintriqueo-Torres Juan , Menares-Quiroz Diego , Aguilar-Farias Nicolas , Salvo-Garrido Sonia , Carcamo-Oyarzun Jaime
Published: September 2022

(1) Background: In this study, we aimed to determine differences in the levels of motor competence according to biological factors (sex, age and weight status) and sociocultural factors (socioeconomic level and belonging to an indigenous people or not) in students of the La Araucanía Region, Chile. (2) Methods: A total of 552 students in 5th and 6th grade were evaluated (49.6% girls; age M = 11.3; SD = 0.8). To assess motor competence (domains of object control and self-movement), the MOBAK 5-6 test was applied. (3) Results: In the object control dimension, significant differences were found according to sex, with the boys performing higher than the girls. According to age, schoolchildren aged 11.0 to 11.9 performed higher than those aged 10.0 to 10.9, and according to socioeconomic status, schoolchildren from schools with a higher socioeconomic status showed a higher motor performance. No significant interaction effects were found between groups. With regard to the self-movement domain, statistically significant differences were only found according to weight status, where students of normal weight presented the highest performance. No significant effects were found between any of the groups. (4) Conclusions: This study shows the importance of considering the biological and sociocultural characteristics in the development of motor competence when interpreting data or planning interventions in different settings.
Managing Autism Spectrum Disorder in the Face of Pandemic Using Internet-Based Parent-Mediated Interventions: A Systematic Review of Randomized Controlled Trials
Authors: Yosep Iyus , Prayogo Stephanie Amabella , Kohar Kelvin , Andrew Hubert , Mardhiyah Ai , Amirah Shakira , Maulana Sidik
Published: September 2022

ASD is a neurodevelopmental disorder that is primarily treated with psychosocial intervention. However, it is costly and requires extensive resources to be effective. This inaccessibility is also further worsened by the ongoing COVID-19 pandemic, making the shift to a digital approach a sensible option. Among the available ASD therapies, parent-mediated interventions (PMIs) have a broad application and lower implementation cost. Hence, this systematic review aims to evaluate the potential that telehealth-based PMI holds and explore its feasibility throughout the COVID-19 pandemic. To build up this study, a systematic search through PubMed, Scopus, ProQuest, Wiley, and Cochrane was performed until 14 January 2021. Using the preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we ultimately included six studies in the review. Each study was evaluated utilizing the Cochrane Risk of Bias (ROB)-2 tool. Generally, parents’ outcomes (knowledge, satisfaction, and compliance) were higher in intervention group (E-learning) compared to control (standard treatment or wait-list). Children also showed some improvements in social skill, communication skill, and intelligence after receiving the treatment. In addition, coaching or therapist sessions were found to be crucial as adjuvant to support parents during the intervention. In conclusion, internet-based parent-mediated interventions are promising and recommended for managing ASD patients, in the face of pandemic. However, more variety in study locations is also needed, particularly in low- and middle-income countries, to tackle the knowledge and clinical application gap. Further research should be conducted with a uniform measurement tool to achieve the same perception and reliable pooled analysis.
Association between Pediatric Adenovirus Infection and Type 1 Diabetes
Authors: Arafa Amany A. , Abdel-Moneim Adel , Khalil Rehab G. , El-Senousy Waled M. , Kamel Mahmoud M. , Kadry Dalia Y. , Allam Gamal , Abdel-Moneim Ahmed S.
Published: September 2022

Background: Viruses are among the inducers of type 1 diabetes (T1D) as they are implicated in the initiation of β-cell destruction. This study aimed to explore the link between adenoviruses’ infection, inflammatory biomarkers, and the development of T1D. Methods: The study population included 80 children with T1D and 40 healthy controls (2–16 years old). The T1D group was further clustered into two groups according to time of T1D diagnosis: a group of children who were diagnosed during the first year of life and a second group who were diagnosed after the first year of life. Adenovirus DNA, anti-adenovirus IgG, cytokines, and lipid profiles were screened in the different groups. The results were statistically assessed using one-way analysis of variance (ANOVA) and LSD t-test. Results: Positive adenovirus PCR was detected in 2.5% and 20% of normal and T1D children, respectively. Moreover, the positive PCR results for adenovirus were found significantly higher in the T1D group, who were diagnosed during the first year of life (33.4%), in comparison to those diagnosed after the first year of life (12%). Anti-adenoviruses IgG was found in 12.5% and 40% of healthy controls and diabetic children, respectively. Seropositive results were found to be higher in newly diagnosed children (46.7%) in comparison to those previously diagnosed with T1D (36%). Body mass index (BMI), IFN-γ, IL-15, adiponectin, lipid profile, and microalbuminuria were significantly increased in T1D adenoviruses-positive children compared to children who were negative for adenoviruses. Conclusions: Adenovirus infection could be among the contributing risk factors and may play a role in the induction of T1D in children.
Sleep Habits in Pairs of Japanese High School Students and Their Mothers in Summer and Autumn
Authors: Mizuno Koh , Okamoto-Mizuno Kazue , Maeda Akiko
Published: September 2022

This study aimed to examine the sleep habits in pairs of Japanese high school students and their mothers in the summer and autumn. Nineteen pairs of high school students and their mothers participated in this study. Wrist actigraphy, subjective sleep evaluations, and bedroom environmental measurements (temperature, humidity, and light) were performed for a duration of one week. The results of a split-plot analysis of variance revealed no significant difference in the actigraphically evaluated time spent in bed (TIB) between the seasons and between the mothers and students. The TIB was approximately 6 h on weekdays, and significantly lengthened to approximately 7 h on weekends (p < 0.05). The average sleep efficiency values recorded were higher than 90%. The mothers showed significantly advanced sleep phases compared to those of the students (p < 0.05). In addition, the waking time on Monday morning was significantly correlated between the mothers and students in the summer and autumn (p < 0.05). A perceived sleep loss “almost every day” or “several times per week” was reported by approximately half of the mothers and students in each season. The students occasionally fell into nocturnal sleep with the room light turned on. These results suggest that sleep hygiene education considering life habit characteristics is required to ensure sufficient sleep time.