bluuebunny/crossref_metadata_2025 huggingface dataset:
Social support as a mediator between anxiety and quality of sleep among Chinese parents of special children
Authors: Xu Junda , Tang Jiliang
Published: February 2023

Objective

The psychological problems among Chinese parents of special children (mental retardation, limb disorder, hearing impairment, autism, cerebral palsy and other types) should be paid more attention. The aim of this study was to investigate the association between anxiety, social support, coping style and sleep quality among Chinese parents of special children during the early COVID-19 epidemic, so as to provide more help for the mental health of parents of special children scientifically and effectively.

Method

A total of 305 Chinese parents of special children were invited to accomplish four questionnaires. Anxiety was measured by the Self-Rating Anxiety Scale, social support was evaluated by the Perceived Social Support Scale, sleep quality was assessed by the Pittsburgh Sleep Quality Index, and coping style was measured by the Simplified Coping Style Questionnaire.

Results

This study revealed that anxiety was positively correlated with sleep quality (p < 0.01) and negatively correlated with social support (p < 0.01) and coping style (p < 0.01). Sleep quality was negatively correlated with social support (p < 0.01), but not significantly correlated with coping style (p > 0.05). Social support was positively correlated with coping style (p < 0.01). The study confirmed that social support had a partial mediating effect on the relationship between anxiety and sleep quality.

Conclusion

The anxiety of parents of special children not only directly affects sleep quality, but also indirectly affects sleep quality through social support. Social support can alleviate the impact of anxiety on sleep quality through the mediating role.
Monitoring mood state to improve performance in soccer players: A brief review
Authors: Selmi Okba , Ouergui Ibrahim , Muscella Antonella , Levitt Danielle E. , Suzuki Katsuhiko , Bouassida Anissa
Published: February 2023

Introduction

Psychological aspects of sport are key in maintaining athlete motivation and make a difference in competitive outcomes. Adjustments to training may be necessary according to athletes’ emotional state. Therefore, it is important to assess and quantify mood states throughout the season in team sports, including among soccer players. The Profile of Mood States (POMS) is a widely used questionnaire that assesses emotional states characterized by positive or negative feelings and can be administered repeatedly to assess changes in mood state. This review aims to assess and summarize the current literature on mood state variation in soccer players with a specific focus on training loads, training modalities, and competitive performance.

Methods

A literature search was systematically conducted and resulted in 156 records. After removing duplicates, items with irrelevant titles and abstracts were screened out, and full texts were then screened for relevance and compared with inclusion and exclusion criteria. The remaining 37 articles were included in the final qualitative synthesis.

Results

POMS scores were related to variability in training load, intensity of the training period, modality of training exercises, competitive performance and time of day in soccer players. Common recommendations include monitoring the mood state of soccer players during training sessions, matches, and throughout training periods to detect early signs of psychological disturbance and aid in optimizing high-level training performance.

Conclusion

The POMS allows for monitoring of players’ psychological state, providing coaches with data to aid in adjusting acute program variables according to players’ psychological states and improve performance. Results offer practical support for the use of a simple POMS measurement as part of an overall program to monitor the players’ psychological states. Results also highlight how training choices (i.e., load and exercise modality) and competitive performance are related to mood states (i.e., tension, anger, confusion, depression, fatigue, and vigor).
Entrepreneurial role models and college students’ entrepreneurial calling: A moderated mediation model
Authors: Jin Dongmei , Liu Xiaomeng , Zhang Fuqin , Wen Zhiyi
Published: February 2023

Introduction

College entrepreneurship education should not only cultivate a group of college students who have strong willingness to start a business immediately after graduation, but also pay attention to future entrepreneurship success of college students. Correspondingly, in addition to attaching importance to improving college students’ entrepreneurial intention, college entrepreneurship education should pay attention to improving college students’ entrepreneurial calling. At present, there is insufficient research on the association between entrepreneurial role models and entrepreneurial calling. We aim to study the mechanism and boundary condition of the association between entrepreneurial role models and entrepreneurial calling.

Methods

A longitudinal survey was distributed among 519 students from 16 colleges and universities in China. In the survey, the college students answered questions on entrepreneurial role models, entrepreneurial calling, entrepreneurial perceived behavioral control and entrepreneurial hands-on practice. Hierarchical regression was conducted, testing the association between entrepreneurial role models and entrepreneurial calling of college students, mediated by entrepreneurial perceived behavioral control and moderated by entrepreneurial hands-on practice.

Results

Therefore, based on the social learning theory, the theory of planned behavior and the entrepreneurial event model, and by hierarchical regression of the data, this study confirmed that entrepreneurial role models were positively associated with college students’ entrepreneurial calling by partially mediating with entrepreneurial perceived behavioral control. Moreover, Entrepreneurial hands-on practice positively moderated not only the relationship between entrepreneurial perceived behavioral control and entrepreneurial calling, but also the mediating association of entrepreneurial perceived behavioral control between entrepreneurial role models and entrepreneurial calling.

Discussion

This study not only enriches the theoretical research on entrepreneurial calling and entrepreneurial role models, but also provides valuable educational enlightenment for colleges and universities to improve the students’ entrepreneurial calling.
The relationship between coping and distress among faculty members and students during COVID-19 pandemic lockdown: The moderating effect of gender
Authors: Hamid Abdalla A. R. M. , Miskry Abdullah Seif Abdullah Al , Darweesh Abdel Hameed M.
Published: February 2023

Objectives

Previous research has documented significant associations between the COVID-19 pandemic lockdown, various mental health problems, and coping strategies. However, literature on the moderating role of gender on the relationship between distress and coping strategies during COVID-19 is almost nonexistent. Hence, the main objective of this study was two folds. To examine gender differences in distress and coping strategies, and to test the moderating effect of gender on the relationship between distress and coping among university faculty members and students during the COVID-19 pandemic.

Method

A cross-sectional web-based study design was used to collect data from the participants. A sample of 649 participants (68.9% university students and 31.1% faculty members) was selected. The General Health Questionnaire (GHQ-12) and the Coping Inventory for Stressful Situations (CISS) were used to collect data from the participants. The survey was sent out during the COVID-19 lockdown from May 12th to June 30th, 2020.

Results

The results showed significant gender differences in distress and the three coping strategies. Women consistently scored higher on distress (p < 0.01), task-focused (p < 0.05), emotion-focused (p < 0.001), and avoidance coping (p < 0.01) compared to men. Gender moderated the relationship between emotion-focused coping and distress (p < 0.001) but not the relationship between distress and task-focused or avoidance coping.

Conclusion

Increased emotion-focused coping is associated with decreased distress among women while the use of emotion-focused coping by men predicted more distress. Workshops and programs focused on providing skills and techniques on how to cope with stressful situations induced by the COVID-19 pandemic are recommended.
Bibliometric study on clinical research of osteoporosis in adolescents
Authors: Li Dingshuang , Ou Jingxi , Zeng Yang , Hou Lei , Yuan Yu , Luo Zhiyuan
Published: February 2023

Objective

Focusing on the theme of “osteoporosis-related research in adolescents,” a systematic visualization of the developmental lineage, current research status, hot spots, and trends of adolescent osteoporosis was conducted to provide a reference for subsequent related research, clinical diagnosis, and treatment.

Method

The Web of Science core database was used as the data source to retrieve the relevant literature and the bibliometrics method. An online bibliometric platform, CiteSpace, and VOSviewer software were used to conduct co-occurrence analysis on the authors, scientific research institutions, national cooperation, keywords, and funding sources to draw the relevant knowledge map.

Result

A total of 1,199 publications from the Web of Science core database were included in this study. The number of published adolescent osteoporosis (AOP) studies has shown an upward trend over the past 29 years, with the United States being the major contributor to the field with the highest number of publications (291, 24.3%) and the highest number of citations (12,186). The international collaboration map shows that the United States is the country most focused on international collaborative exchanges, with the closest collaboration between the United States and Canada. The most influential research institutions and authors are Children's Hospital and Rauch F. the United States is the primary funding source for this research area. Research hotspots were mainly focused on “bone density,” “osteoporosis,” and “children.”

Conclusion

These knowledge maps review the research hotpots in adolescent osteoporosis research over time, analyze and summarize the research process over the past 29 years, and predict future research directions.
Social norms and couples' division of labor
Authors: He Shuya , Noussair Charles N.
Published: February 2023

The COVID pandemic, which forced children to attend school remotely, compelled many couples to choose one partner to stay home to care for the children. The available evidence indicates that it is more common for women to stop working in such situations than men. In this paper, we conduct an experiment to investigate, in a controlled manner, couples' behaviors in deciding who continues to work and who quits. The design allows us to investigate the relationship between the quitting decision and social norms regarding gender roles, as well as the role of peer pressure in the decision. Participants in the experiment are real-life couples recruited for the study. Other subjects drawn from the same population serve as controls. The experimental design involves both parties undertaking a real effort task for payment. At a certain point in the session, one member of the couple must stop and the other must continue the task and earn income for the couple. We find that the couples are more likely to choose the boyfriend to continue the real-effort task for money and the girlfriend to quit the task. Framing the decision as choosing whom to “quit” working rather than whom to “continue” working has a small effect on decisions. Whether choices are revealed to their peers or not does not influence the outcome. An ancillary experiment reveals that choosing husbands to work and wives to quit the labor force is considered as the norm.

JEL classification

C91, D13, J16, J22, J71.
Little Memory Editors Living Inside Your Brain
Authors: Zheng Jie , Chen Gordon , Kreiman Gabriel , Rutishauser Ueli
Published: February 2023

We interact with the world continuously. However, memories of our experiences are stored as individual events. For example, when we go on a road trip, we do not remember what happens second by second. Instead, we remember only a few special moments or events from a trip, such as dancing around the campfire. Our brains constantly extract memorable events while we interact with the world, and we organize those events based on their relevance. This process is like grouping road trip photos under different folders on the computer, so we can efficiently and accurately retrieve those memories in the future. How does the brain create these memorable events? In this article, you will learn about two groups of neurons inside the brain that help achieve this remarkable feat. You will also learn about how the activation of these neurons shapes the formation and retrieval of memories.
Relationships between surrogate measures of mechanical and psychophysiological load, patellar tendon adaptations, and neuromuscular performance in NCAA division I men's volleyball athletes
Authors: Guthrie Brian M. , King Erica L. , Patwardhan Shriniwas , Wei Qi , Sikdar Siddhartha , Chitnis Parag V. , Jones Margaret T.
Published: February 2023

Introduction

Patellar tendon adaptations occur in response to mechanical load. Appropriate loading is necessary to elicit positive adaptations with increased risk of injury and decreased performance likely if loading exceeds the capacity of the tendon. The aim of the current study was to examine intra-individual associations between workloads and patellar tendon properties and neuromuscular performance in collegiate volleyball athletes.

Methods

National Collegiate Athletics Association Division I men's volleyball athletes (n = 16, age: 20.33 ± 1.15 years, height: 193.50 ± 6.50 cm, body mass: 84.32 ± 7.99 kg, bodyfat%: 13.18 ± 4.72%) competing across 9 weeks of in-season competition participated. Daily measurements of external workloads (i.e., jump count) and internal workloads [i.e., session rating of perceived exertion (sRPE)] were recorded. Weekly measurements included neuromuscular performance assessments (i.e., countermovement jump, drop jump), and ultrasound images of the patellar tendon to evaluate structural adaptations. Repeated measures correlations (r-rm) assessed intra-individual associations among performance and patellar tendon metrics.

Results

Workload measures exhibited significant negative small to moderate (r-rm =−0.26–0.31) associations with neuromuscular performance, negative (r-rm = −0.21–0.30), and positive (r-rm = 0.20–0.32) small to moderate associations with patellar tendon properties.

Discussion

Monitoring change in tendon composition and performance adaptations alongside workloads may inform evidence-based frameworks toward managing and reducing the risk of the development of patellar tendinopathy in collegiate men's volleyball athletes.
Diagnosis and treatment of isolated rib Langerhans cell histiocytosis in an adult: A case report
Authors: Guo Yaxin , Huang QiFeng
Published: February 2023

Langerhans cell histiocytosis (LCH) was first proposed in 1987 to define the disorder characterized by the proliferation of abnormal Langerhans cells. It is more likely to occur in children younger than 15 years of age. Single-site and single-system LCH of rib is rare in adults. We present a rare case of isolated rib LCH in a 61-year-old male patient and expound the diagnosis and treatment of the disease. A 61-year-old male patient who presented with a 15-day history of dull pain in the left chest was admitted to our hospital. PET/CT image showed obvious osteolytic bone destruction and abnormal fluorodeoxy-glucose (FDG) uptake (maximum standardized uptake value: 14.5) in the right fifth rib with local soft tissue mass formation. The patient was eventually confirmed the diagnosis of LCH by immunohistochemistry stain and treated with rib surgery. A thorough review of the literature regarding diagnosis and treatment of LCH is presented in this study.
Simulated gastric hydrolysis and developmental toxicity of dimethyltin bis(2-ethylhexylthioglycolate) in rats
Authors: Kirf Dominik , Costlow Richard , Nasshan Hans , Frenkel Peter , Mondimore Donna
Published: February 2023

Dimethyltin dichloride is used as the putative toxophore for dimethyltin bis-alkylthio esters in a read-across approach. Recent chemical and toxicological investigations challenges this read across as data on dioctyltin bis(2-ethylhexyl thioglycolate) and dibutyltin bis(2-ethylhexyl thioglycolate) showed the dialkyltin thioglycolates do not generate dialkyltin dichloride. Results obtained by 119Sn-NMR spectroscopy demonstrated that dimethyltin bis(2-ethylhexyl thioglycolate), the smallest commercially manufactured dialkyltin thioester molecule of this kind, hydrolyzed to dimethyltin chloro-(2-ethylhexyl) thioglycolate under simulated gastric conditions. These studies did not detect dimethyltin dichloride. Dimethyltin bis(2-ethylhexyl thioglycolate) was administered orally to timed-pregnant Wistar-Han rats in an Arachis oil vehicle at 5, 10, and 25 mg/kg/day [Gestation Day 6 (GD6) through GD20] with no maternal deaths observed. At 25 mg/kg/day treatment statistically significant reductions occurred in feed consumption (−9%), maternal body weight (−2.4%) and adjusted maternal weight gain (−68%). There were no adverse gestational findings. Maternal thymus weight was significantly reduced in rats at 25 mg/kg in the absence of changes in hormone levels of T3, T4 or TSH. There were no effects on fetal growth, no dose-dependent pattern of external, visceral, or skeletal malformations and no toxicologically relevant increase in anatomical variations at any dose group. Based on the obtained experimental data it is concluded that dimethyltin bis(2-ethylhexyl thioglycolate) forms dimethyltin chloro-(2-ethylhexyl thioglycolate), not dimethyltin dichloride, in the stomach environment at pH 1.2, and dimethyltin bis(2-ethylhexyl thioglycolate) was not teratogenic nor fetotoxic in rats. The maternal NOAEL was 10 mg/kg/day, and the developmental NOAEL was 25 mg/kg/day, the high dose. The maternal LOAEL was 25 mg/kg/day based on decreased food consumption, lower adjusted mean body weight gain and reduced maternal thymus weight.
Representing National Culture on the Dance Stage: A Chapter from the History of Hungarian Ballet between the Two World Wars
Authors: Kavecsánszki Máté
Published: February 2023

In the case of a mixture of dance languages, especially in dance productions that are the result of a conscious creative process, the interpretation of the symbolic content and message of the dance language elements becomes important. It is in this context that the dance art endeavours of the 19th and 20th centuries in Hungary can be examined, which aimed at staging folk dance culture on the one hand, and at developing a modern language of dance art by using folk dance culture as a source of inspiration on the other. The underlying motivations behind these dance art endeavours could be different, as they could be born in the spirit of modernism or traditionalism, or they could be the manifestation of political-social artistic aspirations, or the two different motivations could overlap. Taking these aspects into account, my study seeks to answer the question of why and how the need for a stage work to function as a national representation of Hungarianness emerged in the history of Hungarian ballet.
Evaluation of Individuals with Non-Syndromic Global Developmental Delay and Intellectual Disability
Authors: AlMutiri Rowim , Malta Maisa , Shevell Michael I. , Srour Myriam
Published: February 2023

Global Developmental Delay (GDD) and Intellectual Disability (ID) are two of the most common presentations encountered by physicians taking care of children. GDD/ID is classified into non-syndromic GDD/ID, where GDD/ID is the sole evident clinical feature, or syndromic GDD/ID, where there are additional clinical features or co-morbidities present. Careful evaluation of children with GDD and ID, starting with detailed history followed by a thorough examination, remain the cornerstone for etiologic diagnosis. However, when initial history and examination fail to identify a probable underlying etiology, further genetic testing is warranted. In recent years, genetic testing has been shown to be the single most important diagnostic modality for clinicians evaluating children with non-syndromic GDD/ID. In this review, we discuss different genetic testing currently available, review common underlying copy-number variants and molecular pathways, explore the recent evidence and recommendations for genetic evaluation and discuss an approach to the diagnosis and management of children with non-syndromic GDD and ID.
Detection of DoH Traffic Tunnels Using Deep Learning for Encrypted Traffic Classification
Authors: Alzighaibi Ahmad Reda
Published: February 2023

Currently, the primary concerns on the Internet are security and privacy, particularly in encrypted communications to prevent snooping and modification of Domain Name System (DNS) data by hackers who may attack using the HTTP protocol to gain illegal access to the information. DNS over HTTPS (DoH) is the new protocol that has made remarkable progress in encrypting Domain Name System traffic to prevent modifying DNS traffic and spying. To alleviate these challenges, this study explored the detection of DoH traffic tunnels of encrypted traffic, with the aim to determine the gained information through the use of HTTP. To implement the proposed work, state-of-the-art machine learning algorithms were used including Random Forest (RF), Gaussian Naive Bayes (GNB), Logistic Regression (LR), k-Nearest Neighbor (KNN), the Support Vector Classifier (SVC), Linear Discriminant Analysis (LDA), Decision Tree (DT), Adaboost, Gradient Boost (SGD), and LSTM neural networks. Moreover, ensemble models consisting of multiple base classifiers were utilized to carry out a series of experiments and conduct a comparative study. The CIRA-CIC-DoHBrw2020 dataset was used for experimentation. The experimental findings showed that the detection accuracy of the stacking model for binary classification was 99.99%. In the multiclass classification, the gradient boosting model scored maximum values of 90.71%, 90.71%, 90.87%, and 91.18% in Accuracy, Recall, Precision, and AUC. Moreover, the micro average ROC curve for the LSTM model scored 98%.
Thoracoabdominal Aortic Replacement Together with Curative Oncological Surgery in Retroperitoneal and Spinal Tumours
Authors: Lutz Brigitta M. , Schaser Klaus-Dieter , Weitz Jurgen , Kirchberg Johanna , Fritzsche Hagen , Disch Alexander C. , Busch Albert , Wolk Steffen , Reeps Christian
Published: February 2023

Malignancies with an extended encasement or infiltration of the aorta were previously considered inoperable. This series demonstrates replacement and subsequent resection of the thoracoabdominal aorta and its large branches as an adjunct to curative radical retroperitoneal and spinal tumor resection. Five consecutive patients were enrolled between 2016 and 2020, suffering from cancer of unknown primary, pleomorphic carcinoma, chordoma, rhabdoid sarcoma, and endometrial cancer metastasis. Wide surgical resection was the only curative option for these patients. For vascular replacement, extracorporeal membrane oxygenation (ECMO) was used as a partial left-heart bypass. The early technical success rate was 100% for vascular procedures and all patients underwent complete radical tumour resection with negative margins. All patients required surgical revision (liquor leak, n = 2; hematoma, n = 3; bypass revision, n = 1; bleeding, n = 1; biliary leak, n = 1). During follow-up (average 47 months, range 22–70) primary patency rates of aortic reconstructions and arterial bypasses were 100%; no patient suffered from recurrent malignant disease. Thoracoabdominal aortic replacement with rerouting of visceral and renal vessels is feasible in oncologic patients. In highly selected young patients, major vascular surgery can push the limits of oncologic surgery further, allowing a curative approach even in extensive retroperitoneal and spinal malignancies.
Does Testosterone Salvage PDE5i Non-Responders? A Scoping Review
Authors: Pignanelli Mike , Stern Noah , Brock Gerald
Published: February 2023

Erectile physiology, in order to function normally, requires the complex coordination of endocrine, neurocognitive, neuromuscular and vascular mechanisms. Testosterone (T) influences male sexuality as well as penile erections at multiple levels, including a direct influence on the nitric oxide synthase (NOS)/cGMP/phosphodiesterase 5 pathway in the penis. However, the precise role of testosterone replacement (TRT) to “salvage” men with mixed ED failing phosphdiesterase-5 inhibitors (PDE5i) remains unclear. We conducted a scoping review identifying the rationale for TRT in ED failing PDE5i, and we critically discuss clinical trials that have examined TRT in the setting of PDE5i use. Overall, TRT replacement appears to be well tolerated and may enhance the response to PDE5i and quality of life, particularly for men with mixed ED, and particularly among men with very low levels of testosterone. However, most of the available literature examines concurrent TRT alone or simultaneous TRT + PDE5i usage, without necessarily selecting for PDE5i failure cases. The present studies are limited to heterogenous studies with small sample sizes, without an exact predominant etiologic factor causing ED. Furthermore, studies showing the most benefit are non-placebo-controlled trials; however, the correction of more profound hypogonadism may lead to an improved response to PDE5i. Stronger conclusions would require properly selected patient populations and larger placebo-controlled RCTs.
Fatty Acid Sensing in the Gastrointestinal Tract of Rainbow Trout: Different to Mammalian Model?
Authors: Calo Jessica , Comesaña Sara , Alonso-Gómez Ángel , Soengas José , Blanco Ayelén
Published: February 2023

It is well established in mammals that the gastrointestinal tract (GIT) senses the luminal presence of nutrients and responds to such information by releasing signaling molecules that ultimately regulate feeding. However, gut nutrient sensing mechanisms are poorly known in fish. This research characterized fatty acid (FA) sensing mechanisms in the GIT of a fish species with great interest in aquaculture: the rainbow trout (Oncorhynchus mykiss). Main results showed that: (i) the trout GIT has mRNAs encoding numerous key FA transporters characterized in mammals (FA transporter CD36 -FAT/CD36-, FA transport protein 4 -FATP4-, and monocarboxylate transporter isoform-1 -MCT-1-) and receptors (several free FA receptor -Ffar- isoforms, and G protein-coupled receptors 84 and 119 -Gpr84 and Gpr119-), and (ii) intragastrically-administered FAs differing in their length and degree of unsaturation (i.e., medium-chain (octanoate), long-chain (oleate), long-chain polyunsaturated (α-linolenate), and short-chain (butyrate) FAs) exert a differential modulation of the gastrointestinal abundance of mRNAs encoding the identified transporters and receptors and intracellular signaling elements, as well as gastrointestinal appetite-regulatory hormone mRNAs and proteins. Together, results from this study offer the first set of evidence supporting the existence of FA sensing mechanisms n the fish GIT. Additionally, we detected several differences in FA sensing mechanisms of rainbow trout vs. mammals, which may suggest evolutionary divergence between fish and mammals.
Chitosan Nanoparticles as Oral Drug Carriers
Authors: Guadarrama-Escobar Omar Rodrigo , Serrano-Castañeda Pablo , Anguiano-Almazán Ericka , Vázquez-Durán Alma , Peña-Juárez Ma. Concepción , Vera-Graziano Ricardo , Morales-Florido Miriam Isabel , Rodriguez-Perez Betsabe , Rodriguez-Cruz Isabel Marlen , Miranda-Calderón Jorge Esteban , Escobar-Chávez José Juan
Published: February 2023

The use of nanoparticles as drug delivery systems has increased in importance in the last decades. Despite the disadvantages of difficulty swallowing, gastric irritation, low solubility, and poor bioavailability, oral administration stands out as the most widely used route for therapeutic treatments, though it may not always be the most effective route. The effect of the first hepatic pass is one of the primary challenges that drugs must overcome to carry out their therapeutic effect. For these reasons, controlled-release systems based on nanoparticles synthesized from biodegradable natural polymers have been reported to be very efficient in enhancing oral delivery in multiple studies. Chitosan has been shown to have an extensive variability of properties and roles in the pharmaceutical and health fields; of its most important properties are the ability to encapsulate and transport drugs within the body and enhance the drug interaction with the target cells, which improves the efficacy of the encapsulated drugs. The physicochemical properties of chitosan give it the ability to form nanoparticles through multiple mechanisms, which will be addressed in this article. The present review article focuses on highlighting the applications of chitosan nanoparticles for oral drug delivery.
The Epidermal Keratinocyte as a Therapeutic Target for Management of Diabetic Wounds
Authors: Fang Wei-Cheng , Lan Cheng-Che E.
Published: February 2023

Diabetes mellitus (DM) is an important cause of chronic wounds and non-traumatic amputation. The prevalence and number of cases of diabetic mellitus are increasing worldwide. Keratinocytes, the outermost layer of the epidermis, play an important role in wound healing. A high glucose environment may disrupt the physiologic functions of keratinocytes, resulting in prolonged inflammation, impaired proliferation, and the migration of keratinocytes and impaired angiogenesis. This review provides an overview of keratinocyte dysfunctions in a high glucose environment. Effective and safe therapeutic approaches for promoting diabetic wound healing can be developed if molecular mechanisms responsible for keratinocyte dysfunction in high glucose environments are elucidated.
NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate
Authors: Ribeiro Vanessa , Martins Susana G. , Lopes Ana Sofia , Thorsteinsdóttir Sólveig , Zilhão Rita , Carlos Ana Rita
Published: February 2023

NFIX, a member of the nuclear factor I (NFI) family of transcription factors, is known to be involved in muscle and central nervous system embryonic development. However, its expression in adults is limited. Similar to other developmental transcription factors, NFIX has been found to be altered in tumors, often promoting pro-tumorigenic functions, such as leading to proliferation, differentiation, and migration. However, some studies suggest that NFIX can also have a tumor suppressor role, indicating a complex and cancer-type dependent role of NFIX. This complexity may be linked to the multiple processes at play in regulating NFIX, which include transcriptional, post-transcriptional, and post-translational processes. Moreover, other features of NFIX, including its ability to interact with different NFI members to form homodimers or heterodimers, therefore allowing the transcription of different target genes, and its ability to sense oxidative stress, can also modulate its function. In this review, we examine different aspects of NFIX regulation, first in development and then in cancer, highlighting the important role of NFIX in oxidative stress and cell fate regulation in tumors. Moreover, we propose different mechanisms through which oxidative stress regulates NFIX transcription and function, underlining NFIX as a key factor for tumorigenesis.
The Novel RXR Agonist MSU-42011 Differentially Regulates Gene Expression in Mammary Tumors of MMTV-Neu Mice
Authors: Reich Lyndsey A. , Leal Ana S. , Ellsworth Edmund , Liby Karen T.
Published: February 2023

Retinoid X receptor (RXR) agonists, which activate the RXR nuclear receptor, are effective in multiple preclinical cancer models for both treatment and prevention. While RXR is the direct target of these compounds, the downstream changes in gene expression differ between compounds. RNA sequencing was used to elucidate the effects of the novel RXRα agonist MSU-42011 on the transcriptome in mammary tumors of HER2+ mouse mammary tumor virus (MMTV)-Neu mice. For comparison, mammary tumors treated with the FDA approved RXR agonist bexarotene were also analyzed. Each treatment differentially regulated cancer-relevant gene categories, including focal adhesion, extracellular matrix, and immune pathways. The most prominent genes altered by RXR agonists positively correlate with survival in breast cancer patients. While MSU-42011 and bexarotene act on many common pathways, these experiments highlight the differences in gene expression between these two RXR agonists. MSU-42011 targets immune regulatory and biosynthetic pathways, while bexarotene acts on several proteoglycan and matrix metalloproteinase pathways. Exploration of these differential effects on gene transcription may lead to an increased understanding of the complex biology behind RXR agonists and how the activities of this diverse class of compounds can be utilized to treat cancer.
Analysis of the Localization of Schizosaccharomyces pombe Glucan Synthases in the Presence of the Antifungal Agent Caspofungin
Authors: San-Quirico Esther , Curto M. Ángeles , Gómez-Delgado Laura , Moreno M. Belén , Pérez Pilar , Ribas Juan Carlos , Cortés Juan Carlos G.
Published: February 2023

In recent years, invasive fungal infections have emerged as a common source of infections in immunosuppressed patients. All fungal cells are surrounded by a cell wall that is essential for cell integrity and survival. It prevents cell death and lysis resulting from high internal turgor pressure. Since the cell wall is not present in animal cells, it is an ideal target for selective invasive fungal infection treatments. The antifungal family known as echinocandins, which specifically inhibit the synthesis of the cell wall β(13)glucan, has been established as an alternative treatment for mycoses. To explore the mechanism of action of these antifungals, we analyzed the cell morphology and glucan synthases localization in Schizosaccharomyces pombe cells during the initial times of growth in the presence of the echinocandin drug caspofungin. S. pombe are rod-shaped cells that grow at the poles and divide by a central division septum. The cell wall and septum are formed by different glucans, which are synthesized by four essential glucan synthases: Bgs1, Bgs3, Bgs4, and Ags1. Thus, S. pombe is not only a perfect model for studying the synthesis of the fungal β(1-3)glucan, but also it is ideal for examining the mechanisms of action and resistance of cell wall antifungals. Herein, we examined the cells in a drug susceptibility test in the presence of either lethal or sublethal concentrations of caspofungin, finding that exposure to the drug for long periods at high concentrations (>10 µg/mL) induced cell growth arrest and the formation of rounded, swollen, and dead cells, whereas low concentrations (<10 µg/mL) permitted cell growth with a mild effect on cell morphology. Interestingly, short-term treatments with either high or low concentrations of the drug induced effects contrary to those observed in the susceptibility tests. Thus, low drug concentrations induced a cell death phenotype that was not observed at high drug concentrations, which caused transient fungistatic cell growth arrest. After 3 h, high concentrations of the drug caused the following: (i) a decrease in the GFP-Bgs1 fluorescence level; (ii) altered locations of Bgs3, Bgs4, and Ags1; and (iii) a simultaneous accumulation of cells with calcofluor-stained incomplete septa, which at longer times resulted in septation uncoupling from plasma membrane ingression. The incomplete septa revealed with calcofluor were found to be complete when observed via the membrane-associated GFP-Bgs or Ags1-GFP. Finally, we found that the accumulation of incomplete septa depended on Pmk1, the last kinase of the cell wall integrity pathway.
Using Optogenetics to Model Cellular Effects of Alzheimer’s Disease
Authors: Tiwari Prabhat , Tolwinski Nicholas S.
Published: February 2023

Across the world a dementia case is diagnosed every three seconds. Alzheimer’s disease (AD) causes 50–60% of these cases. The most prominent theory for AD correlates the deposition of amyloid beta (Aβ) with the onset of dementia. Whether Aβ is causative remains unclear due to findings such as the recently approved drug Aducanumab showing effective clearance of Aβ, but not improving cognition. New approaches for understanding Aβ function, are therefore necessary. Here we discuss the application of optogenetic techniques to gain insight into AD. Optogenetics, or genetically encoded, light-dependent on/off switches, provides precise spatiotemporal control to regulate cellular dynamics. This precise control over protein expression and oligomerization or aggregation could provide a better understanding of the etiology of AD.
Aberrations of DNA Repair Pathways in Prostate Cancer—The State of the Art
Authors: Boussios Stergios , Sheriff Matin
Published: February 2023

Prostate cancer (PC) is the second most commonly diagnosed cancer in males worldwide and the fifth most common cause of cancer-related death in men [...]
Identification of Novel Core Genes Involved in Malignant Transformation of Inflamed Colon Tissue Using a Computational Biology Approach and Verification in Murine Models
Authors: Markov Andrey V. , Savin Innokenty A. , Zenkova Marina A. , Sen’kova Aleksandra V.
Published: February 2023

Inflammatory bowel disease (IBD) is a complex and multifactorial systemic disorder of the gastrointestinal tract and is strongly associated with the development of colorectal cancer. Despite extensive studies of IBD pathogenesis, the molecular mechanism of colitis-driven tumorigenesis is not yet fully understood. In the current animal-based study, we report a comprehensive bioinformatics analysis of multiple transcriptomics datasets from the colon tissue of mice with acute colitis and colitis-associated cancer (CAC). We performed intersection of differentially expressed genes (DEGs), their functional annotation, reconstruction, and topology analysis of gene association networks, which, when combined with the text mining approach, revealed that a set of key overexpressed genes involved in the regulation of colitis (C3, Tyrobp, Mmp3, Mmp9, Timp1) and CAC (Timp1, Adam8, Mmp7, Mmp13) occupied hub positions within explored colitis- and CAC-related regulomes. Further validation of obtained data in murine models of dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS-stimulated CAC fully confirmed the association of revealed hub genes with inflammatory and malignant lesions of colon tissue and demonstrated that genes encoding matrix metalloproteinases (acute colitis: Mmp3, Mmp9; CAC: Mmp7, Mmp13) can be used as a novel prognostic signature for colorectal neoplasia in IBD. Finally, using publicly available transcriptomics data, translational bridge interconnecting of listed colitis/CAC-associated core genes with the pathogenesis of ulcerative colitis, Crohn’s disease, and colorectal cancer in humans was identified. Taken together, a set of key genes playing a core function in colon inflammation and CAC was revealed, which can serve both as promising molecular markers and therapeutic targets to control IBD and IBD-associated colorectal neoplasia.
TCF-1 Is Required for CD4 T Cell Persistence Functions during AlloImmunity
Authors: Mammadli Mahinbanu , Suo Liye , Sen Jyoti Misra , Karimi Mobin
Published: February 2023

The transcription factor T cell factor-1 (TCF-1) is encoded by Tcf7 and plays a significant role in regulating immune responses to cancer and pathogens. TCF-1 plays a central role in CD4 T cell development; however, the biological function of TCF-1 on mature peripheral CD4 T cell-mediated alloimmunity is currently unknown. This report reveals that TCF-1 is critical for mature CD4 T cell stemness and their persistence functions. Our data show that mature CD4 T cells from TCF-1 cKO mice did not cause graft versus host disease (GvHD) during allogeneic CD4 T cell transplantation, and donor CD4 T cells did not cause GvHD damage to target organs. For the first time, we showed that TCF-1 regulates CD4 T cell stemness by regulating CD28 expression, which is required for CD4 stemness. Our data showed that TCF-1 regulates CD4 effector and central memory formation. For the first time, we provide evidence that TCF-1 differentially regulates key chemokine and cytokine receptors critical for CD4 T cell migration and inflammation during alloimmunity. Our transcriptomic data uncovered that TCF-1 regulates critical pathways during normal state and alloimmunity. Knowledge acquired from these discoveries will enable us to develop a target-specific approach for treating CD4 T cell-mediated diseases.
Can Modification with Urethane Derivatives or the Addition of an Anti-Hydrolysis Agent Influence the Hydrolytic Stability of Resin Dental Composite?
Authors: Szczesio-Wlodarczyk Agata , Barszczewska-Rybarek Izabela M. , Chrószcz-Porębska Marta W. , Kopacz Karolina , Sokolowski Jerzy , Bociong Kinga
Published: February 2023

Due to the questionable durability of dental restorations, there is a need to increase the lifetime of composite restoration. The present study used diethylene glycol monomethacrylate/4,4′-methylenebis(cyclohexyl isocyanate) (DEGMMA/CHMDI), diethylene glycol monomethacrylate/isophorone diisocyanate (DEGMMA/IPDI) monomers, and bis(2,6-diisopropylphenyl)carbodiimide (CHINOX SA-1) as modifiers of a polymer matrix (40 wt% urethane dimethacrylate (UDMA), 40 wt% bisphenol A ethoxylateddimethacrylate (bis-EMA), and 20 wt% triethyleneglycol dimethacrylate (TEGDMA)). Flexural strength (FS), diametral tensile strength (DTS), hardness (HV), sorption, and solubility were determined. To assess hydrolytic stability, the materials were tested before and after two aging methods (I-7500 cycles, 5 °C and 55 °C, water and 7 days, 60 °C, 0.1 M NaOH; II-5 days, 55 °C, water and 7 days, 60 °C, 0.1 M NaOH). The aging protocol resulted in no noticeable change (median values were the same as or higher than the control value) or a decrease in the DTS value from 4 to 28%, and a decrease in the FS value by 2 to 14%. The hardness values after aging were more than 60% lower than those of the controls. The used additives did not improve the initial (control) properties of the composite material. The addition of CHINOX SA-1 improved the hydrolytic stability of composites based on UDMA/bis-EMA/TEGDMA monomers, which could potentially extend the service life of the modified material. Extended studies are needed to confirm the possible use of CHINOX SA-1 as an antihydrolysis agent in dental composites.
A Nucleus Accumbens Tac1 Neural Circuit Regulates Avoidance Responses to Aversive Stimuli
Authors: He Zi-Xuan , Xi Ke , Liu Kai-Jie , Yue Mei-Hui , Wang Yao , Yin Yue-Yue , Liu Lin , He Xiao-Xiao , Yu Hua-Li , Xing Zhen-Kai , Zhu Xiao-Juan
Published: February 2023

Neural circuits that control aversion are essential for motivational regulation and survival in animals. The nucleus accumbens (NAc) plays an important role in predicting aversive events and translating motivations into actions. However, the NAc circuits that mediate aversive behaviors remain elusive. Here, we report that tachykinin precursor 1 (Tac1) neurons in the NAc medial shell regulate avoidance responses to aversive stimuli. We show that NAcTac1 neurons project to the lateral hypothalamic area (LH) and that the NAcTac1→LH pathway contributes to avoidance responses. Moreover, the medial prefrontal cortex (mPFC) sends excitatory inputs to the NAc, and this circuit is involved in the regulation of avoidance responses to aversive stimuli. Overall, our study reveals a discrete NAc Tac1 circuit that senses aversive stimuli and drives avoidance behaviors.
Increased EGFRvIII Epitope Accessibility after Tyrosine Kinase Inhibitor Treatment of Glioblastoma Cells Creates More Opportunities for Immunotherapy
Authors: Tręda Cezary , Włodarczyk Aneta , Pacholczyk Marcin , Rutkowska Adrianna , Stoczyńska-Fidelus Ewelina , Kierasińska Amelia , Rieske Piotr
Published: February 2023

The number of glioblastoma (GB) cases is increasing every year, and the currently available therapies remain ineffective. A prospective antigen for GB therapy is EGFRvIII, an EGFR deletion mutant containing a unique epitope that is recognized by the L8A4 antibody used in CAR-T (chimeric antigen receptor T cell) therapy. In this study, we observed that the concomitant use of L8A4 with particular tyrosine kinase inhibitors (TKIs) does not impede the interaction between L8A4 and EGFRvIII; moreover, in this case, the stabilization of formed dimers results in increased epitope display. Unlike in wild-type EGFR, a free cysteine at position 16 (C16) is exposed in the extracellular structure of EGFRvIII monomers, leading to covalent dimer formation in the region of L8A4–EGFRvIII mutual interaction. Following in silico analysis of cysteines possibly involved in covalent homodimerization, we prepared constructs containing cysteine–serine substitutions of EGFRvIII in adjacent regions. We found that the extracellular part of EGFRvIII possesses plasticity in the formation of disulfide bridges within EGFRvIII monomers and dimers due to the engagement of cysteines other than C16. Our results suggest that the EGFRvIII-specific L8A4 antibody recognizes both EGFRvIII monomers and covalent dimers, regardless of the cysteine bridging structure. To summarize, immunotherapy based on the L8A4 antibody, including CAR-T combined with TKIs, can potentially increase the chances of success in anti-GB therapy.
Chitooligosaccharides Derivatives Protect ARPE-19 Cells against Acrolein-Induced Oxidative Injury
Authors: Yang Cheng , Yang Rongrong , Gu Ming , Hao Jiejie , Wang Shixin , Li Chunxia
Published: February 2023

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS–5) and its N-acetylated derivative (N–5) showed the best protective activity. Pretreatment with COS–5 or N–5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N–5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.