bluuebunny/crossref_metadata_2025 huggingface dataset:
Interprofessional Collaboration in Fall Prevention: Insights from a Qualitative Study
Authors: Baumann Isabel , Wieber Frank , Volken Thomas , Rüesch Peter , Glässel Andrea
Published: August 2022

(1) Background and objective: to explore the experiences of Swiss health care providers involved in a community fall prevention pilot project on barriers and facilitations in interprofessional cooperation between 2016 and 2017 in three regions of Switzerland. (2) Methods: semi-structured interviews with health care providers assessed their perspective on the evaluation of jointly developed tools for reporting fall risk, continuous training of the health care providers, sensitizing media campaigns, and others. (3) Results: One of the project’s strengths is the interprofessional continuous trainings. These trainings allowed the health care providers to extend their network of health care providers, which contributed to an improvement of fall prevention. Challenges of the project were that the standardization of the interprofessional collaboration required additional efforts. These efforts are time consuming and, for some categories of health care providers, not remunerated by the Swiss health care system. (4) Conclusions: On a micro and meso level, the results of the present study indicate that the involved health care providers strongly support interprofessional collaboration in fall prevention. However, time and financial constraints challenge the implementation. On a macro level, potential ways to strengthen interprofessional collaboration are a core element in fall prevention.
Association of Polymorphism CHRNA5 and CHRNA3 Gene in People Addicted to Nicotine
Authors: Chmielowiec Krzysztof , Chmielowiec Jolanta , Strońska-Pluta Aleksandra , Trybek Grzegorz , Śmiarowska Małgorzata , Suchanecka Aleksandra , Woźniak Grzegorz , Jaroń Aleksandra , Grzywacz Anna
Published: August 2022

Smoking is a chronic and relapsing addictive trait that harms public health. Among the many identified genetic variants of nicotine dependence, the variants in the CHRNA5/A3/B4 gene cluster on chromosome 15 that encode the α5, α3, and β4 subunits have recently received a lot of attention. Importantly, variants in this gene cluster have been associated with nicotine addiction. Among the many significant variants in this cluster, the polymorphism SNP rs16969968 seems to be the most interesting factor in nicotine addiction. This polymorphism causes an amino acid change from aspartate to asparagine at position 398 of the α5 nicotinic receptor protein sequence. Our study aimed to analyze three polymorphic variants: the rs16969968 located in the CHRNA5 gene, the rs578776 and rs1051730 located in the CHRNA3 gene in nicotine-addicted subjects, and in controls. Our study encompasses an association analysis of genotypes and haplotypes. A group of 401 volunteers was recruited for the study and divided into two groups: the study group consisted of addicted smokers and a control group of 200 unrelated non-smokers who were not dependent on any substance and healthy. A statistically significant difference was observed in the frequency of genotypes of the rs1051730 polymorphism of the CHRNA3 gene (χ2 = 6.704 p = 0.035). The T/T genotype was statistically significantly more frequent in the group of nicotine-dependent subjects. The haplotypes rs16969968, rs578776, and rs1051730 were distinguished, of which the G-T-T and G-C-T haplotypes were present only in the study group. With differences in frequencies, statistical significance was noted—for the G-T-T haplotype p = 0.01284 and the G-C-T haplotype p = 0.00775. The research stated that novel haplotypes G-T-T and G-C-T, though with very low-frequency variants in CHRNA3, were associated with nicotine addiction.
Implementing and Delivering Youth Mental Health Services: Approaches Taken by the Australian Primary Health Network ‘Lead Sites’
Authors: Oostermeijer Sanne , Williamson Michelle , Nicholas Angela , Machlin Anna , Bassilios Bridget
Published: August 2022

Aim: This paper aims to report on effective approaches for, and early impacts of, implementing and delivering services for youth with, or at risk of, severe mental illness commissioned by 10 Primary Health Network (PHN) Lead Sites (reform leaders) in Australia. Methods: The following qualitative data sources were analyzed using a thematic approach: focus group consultations with 68 Lead Site staff and 70 external stakeholders from Lead Site regions; and observational data from one Lead Site meeting with a focus on services for youth with, or at risk of, severe mental illness and one national symposium that was attended by Lead Site staff and service providers. Results: The Lead Site staff described common effective strategies for implementing and delivering youth enhanced services as follows: building on existing youth services, establishing effective linkages with other local youth enhanced services, and providing complementary clinical and non-clinical services. Early impacts of youth enhanced services that were described by Lead Site staff and external stakeholders included: improved service quality and access, positive effects on consumers and/or carers (e.g., reduced symptomology), and sector-wide impacts such as improved service integration. Staff members from two Lead Sites also mentioned negative impacts (e.g., uncertainty of continued funding). Suggestions for future improvements by Lead Site staff and external stakeholders included: involving young people in service design and planning, improving service access, addressing clinical workforce shortages, improving data collection and usage, and establishing greater service integration. Conclusions: These findings highlight the necessity for collaborative and localized responses as well as service models that combine clinical and non-clinical care to address the needs of young people with, or at risk of, severe mental illness. Early impacts that were reported by stakeholders indicated that PHN-commissioned youth-enhanced services had positive impacts for consumers, carers, and the wider service sector.
Validation of the Computerized Cognitive Assessment Test: NNCT
Authors: Oliva Itxasne , Losa Joan
Published: August 2022

Population aging brings with it cognitive impairment. One of the challenges of the coming years is the early and accessible detection of cognitive impairment. Therefore, this study aims to validate a neuropsychological screening test, self-administered and in software format, called NAIHA Neuro Cognitive Test (NNCT), designed for elderly people with and without cognitive impairment. This test aims to digitize cognitive assessments to add greater accessibility than classic tests, as well as to present results in real time and reduce costs. To this end, a comparison is made with tests such as MMSE, Clock Drawing Test (CDT) and CAMCOG. For this purpose, the following statistical analyses were performed: correlations, ROC curves, and three ANOVAs. The NNCT test evaluates seven cognitive areas and shows a significant and positive correlation with other tests, at total and subareas levels. Scores are established for the detection of both mild cognitive impairment and dementia, presenting optimal sensitivity and specificity. It is concluded that the NNCT test is a valid method of detection of cognitive impairment.
A Comprehensive Hydrothermal Co-Liquefaction of Diverse Biowastes for Energy-Dense Biocrude Production: Synergistic and Antagonistic Effects
Authors: Zhang Guanyu , Wang Kejie , Liu Quan , Han Lujia , Zhang Xuesong
Published: August 2022

Hydrothermal co-liquefaction (co-HTL) is a promising technology to valorize binary or even ternary biowastes into bioenergy. However, the complex biochemical compositions and unclear synergistic effect prevent the development of this technology. Thus, this study explored a comprehensive co-HTL of representative biowastes to investigate the synergistic and antagonistic effects. An apparent synergistic effect on biocrude yield was observed when sewage sludge was co-liquefied with cow manure or wheat straw. Further, the co-HTL of sewage sludge-cow manure was investigated in a detailed manner. The highest yield (21.84 wt%) of biocrude, with a positive synergistic effect (11.37%), the highest energy recovery (47.48%), and a moderate biocrude HHV (34.31 MJ/kg) were achieved from co-HTL at 350 °C for 30 min. Hydrochar and gas products were also characterized to unravel the reaction pathways. Accordingly, this work indicates that sewage sludge co-liquefied with other biowastes can serve as a multi-purpose solution for biowaste treatment and bioenergy production.
Financial Reasons for Working beyond the Statutory Retirement Age: Risk Factors and Associations with Health in Late Life
Authors: Burkhalter Denise , Wagner Aylin , Feer Sonja , Wieber Frank , Ihle Andreas , Baumann Isabel
Published: August 2022

Despite an increasing trend of working life prolongation, little is known about the risk factors for financial reasons for working beyond the statutory retirement age (SRA), and how these reasons relate to health. The present study examined (1) the determinants of working beyond the SRA, (2) the workers’ self-reported reasons for working beyond the SRA, and (3) the association between these reasons and health in late life. Cross-sectional data of 1241 individuals from the Swiss survey “Vivre/Leben/Vivere” were analyzed. The results showed that people with a low level of education and with a low income have an 80% higher risk of working beyond the SRA for financial reasons than for other reasons (p < 0.001). Moreover, self-rated health was not significantly associated with working beyond the SRA for financial reasons but was significantly associated with education and income (p < 0.01). In conclusion, while previous studies have already identified financial difficulties as one important reason for working beyond the SRA, the present study indicated the socioeconomic factors that are crucial for increasing the risk for working beyond the SRA. Thus, our results help to guide the adaptation of social policies for better maintaining and promoting the health of particularly vulnerable older workers.
The Moderator Role of Interpersonal Emotion Regulation on the Associations between Commitment, Intimacy, and Couple Satisfaction
Authors: Jitaru Mihaela , Turliuc Maria Nicoleta
Published: August 2022

Couple satisfaction is seen as very important by all those in a romantic relationship; however, there are no recipes for it. Using a dyadic approach, we investigate how commitment and intimacy influence couple satisfaction and the moderator role of interpersonal emotion regulation (affect-improving and -worsening strategies). To achieve the scope of the study, we collected data from 131 couples, which were later analyzed using the actor–partner interdependence model with moderation (APIMoM). The results showed that the actor-effect of both commitment and intimacy on couple satisfaction is significant. We found mixed results for the partner-effect of the two variables. Both partners’ strategies moderated the association between commitment and couple satisfaction. Women’s use of affect-worsening strategies moderated the link between men’s intimacy and women’s couple satisfaction. The impact of the interactions of commitment or intimacy with interpersonal affect-improving and -worsening strategies on couple satisfaction is discussed further, as well as the implications and importance of the results.
Differences in Oral Lesions Associated with Tobacco Smoking, E-Cigarette Use and COVID-19 Infection among Adolescents and Young People in Nigeria
Authors: Alade Omolola , Folayan Morenike Oluwatoyin , Adeniyi Abiola , Adeyemo Yewande Isabella , Oyapero Afolabi , Olatosi Olubukola Olamide , Nzomiwu Chioma , Popoola Bamidele Olubukola , Eigbobo Joycelyn , Oziegbe Elizabeth , Oyedele Titus , El Tantawi Maha , Sabbagh Heba Jafar
Published: August 2022

COVID-19 infection is associated with oral lesions which may be exacerbated by tobacco smoking or e-cigarette use. This study assessed the oral lesions associated with the use of e-cigarettes, tobacco smoking, and COVID-19 among adolescents and young people in Nigeria. A national survey recruited 11–23-year-old participants from the 36 States of Nigeria and the Federal Capital Territory, Abuja. Data were collected using Survey Monkey®. Binary logistic regression analysis was conducted. Statistical significance was set at p-value less than 0.05. There were 2870 participants, of which 386 (13.4%) were tobacco smokers, 167 (5.8%) e-cigarette users, and 401 (14.0%) were both e-cigarette and tobacco users; and 344 (12.0%) had ever tested positive to COVID-19. Adolescents and young people who smoked tobacco had more than twice the odds of reporting gingival inflammation, oral ulcers, dry mouth, and changes in taste than those who did not smoke. Those who used e-cigarettes had 1.5 times higher odds of reporting oral lesions. Respondents who had COVID-19 infection had higher odds of reporting gingival inflammation and lower odds of reporting dry mouth than those who did not have COVID-19 infection. These findings were significant, and may help clinicians to screen for tobacco use and COVID-19 among adolescents and young people in Nigeria.
Effectiveness of Exercise in Patients with Overweight or Obesity Suffering from Knee Osteoarthritis: A Systematic Review and Meta-Analysis
Authors: Jurado-Castro Jose Manuel , Muñoz-López Mariano , Ledesma Agustín Sánchez-Toledo , Ranchal-Sanchez Antonio
Published: August 2022

Objectives: The main purpose of this study was to review the evidence about the effectiveness of exercise in patients with overweight or obesity suffering from knee osteoarthritis. Methods: Randomized clinical trials (RCTs) published between January 2002 and May 2022 were included. Results: A total of 64 articles were identified, of which six met the criteria for meta-analysis. The pain scale score was higher in the control group (mean difference 0.95; confidence interval 0.42–1.47; p < 0.001; I2 = 44%). The physical function scale (lower scores indicate lower levels of symptoms or physical disability) presented a higher score in the control group (mean difference 3.74; confidence interval 0.85–6.53; p < 0.05; I2 = 56%). Moreover, the intervention group achieved a greater distance (meters) walking in a 6 min interval (mean difference 38.18; confidence interval 20.01–56.35; p < 0.001; I2 = 0%). Conclusions: Exercise interventions seem effective in improving quality of life in people with overweight or obesity suffering from knee osteoarthritis, reducing pain and improving physical function.
Mitochondria in Mycobacterium Infection: From the Immune System to Mitochondrial Haplogroups
Authors: Souza Felipe Gouvea de , Cavalcante Giovanna C.
Published: August 2022

In humans, mitochondria play key roles in the regulation of cellular functions, such as the regulation of the innate immune response and are targets of several pathogenic viruses and bacteria. Mycobacteria are intracellular pathogens that infect cells important to the immune system of organisms and target mitochondria to meet their energy demands. In this review, we discuss the main mechanisms by which mitochondria regulate the innate immune response of humans to mycobacterial infection, especially those that cause tuberculosis and leprosy. Notably, the importance of mitochondrial haplogroups and ancestry studies for mycobacterial diseases is also discussed.
Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs
Authors: Chu Xiangyu , Yang Yinmo , Tian Xiaodong
Published: August 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC.
Rational Design of Lipase ROL to Increase Its Thermostability for Production of Structured Tags
Authors: Chow Jeng Yeong , Nguyen Giang Kien Truc
Published: August 2022

1,3-regiospecific lipases are important enzymes that are heavily utilized in the food industries to produce structured triacylglycerols (TAGs). The Rhizopus oryzae lipase (ROL) has recently gained interest because this enzyme possesses high selectivity and catalytic efficiency. However, its low thermostability limits its use towards reactions that work at lower temperature. Most importantly, the enzyme cannot be used for the production of 1,3-dioleoyl-2-palmitoylglycerol (OPO) and 1,3-stearoyl-2-oleoyl-glycerol (SOS) due to the high melting points of the substrates used for the reaction. Despite various engineering efforts used to improve the thermostability of ROL, the enzyme is unable to function at temperatures above 60 °C. Here, we describe the rational design of ROL to identify variants that can retain their activity at temperatures higher than 60 °C. After two rounds of mutagenesis and screening, we were able to identify a mutant ROL_10x that can retain most of its activity at 70 °C. We further demonstrated that this mutant is useful for the synthesis of SOS while minimal product formation was observed with ROL_WT. Our engineered enzyme provides a promising solution for the industrial synthesis of structured lipids at high temperature.
Advances of Epigenetic Biomarkers and Epigenome Editing for Early Diagnosis in Breast Cancer
Authors: Sarvari Pourya , Sarvari Pouya , Ramírez-Díaz Ivonne , Mahjoubi Frouzandeh , Rubio Karla
Published: August 2022

Epigenetic modifications are known to regulate cell phenotype during cancer progression, including breast cancer. Unlike genetic alterations, changes in the epigenome are reversible, thus potentially reversed by epi-drugs. Breast cancer, the most common cause of cancer death worldwide in women, encompasses multiple histopathological and molecular subtypes. Several lines of evidence demonstrated distortion of the epigenetic landscape in breast cancer. Interestingly, mammary cells isolated from breast cancer patients and cultured ex vivo maintained the tumorigenic phenotype and exhibited aberrant epigenetic modifications. Recent studies indicated that the therapeutic efficiency for breast cancer regimens has increased over time, resulting in reduced mortality. Future medical treatment for breast cancer patients, however, will likely depend upon a better understanding of epigenetic modifications. The present review aims to outline different epigenetic mechanisms including DNA methylation, histone modifications, and ncRNAs with their impact on breast cancer, as well as to discuss studies highlighting the central role of epigenetic mechanisms in breast cancer pathogenesis. We propose new research areas that may facilitate locus-specific epigenome editing as breast cancer therapeutics.
LjAMT2;2 Promotes Ammonium Nitrogen Transport during Arbuscular Mycorrhizal Fungi Symbiosis in Lotus japonicus
Authors: Wang Yanping , Zhou Wenqing , Wu Jiandong , Xie Kailing , Li Xiaoyu
Published: August 2022

Arbuscular mycorrhizal fungi (AMF) are important symbiotic microorganisms in soil that engage in symbiotic relationships with legumes, resulting in mycorrhizal symbiosis. Establishment of strong symbiotic relationships between AMF and legumes promotes the absorption of nitrogen by plants. Ammonium nitrogen can be directly utilised by plants following ammonium transport, but there are few reports on ammonium transporters (AMTs) promoting ammonium nitrogen transport during AM symbiosis. Lotus japonicus is a typical legume model plant that hosts AMF. In this study, we analysed the characteristics of the Lotus japonicus ammonium transporter LjAMT2;2, and found that it is a typical ammonium transporter with mycorrhizal-induced and ammonium nitrogen transport-related cis-acting elements in its promoter region. LjAMT2;2 facilitated ammonium transfer in yeast mutant supplement experiments. In the presence of different nitrogen concentrations, the LjAMT2;2 gene was significantly upregulated following inoculation with AMF, and induced by low nitrogen. Overexpression of LjAMT2;2 increased the absorption of ammonium nitrogen, resulting in doubling of nitrogen content in leaves and roots, thus alleviating nitrogen stress and promoting plant growth.
An Introduction to Spiral Steroids
Authors: Chasalow Fred
Published: August 2022

In addition to classical steroids, which have cholesterol as a precursor, there are steroids with 7-dehydrocholesterol as a precursor. This review describes the identification of these steroids, their biosynthesis, and some aspects of their function. There are three classes of these compounds, distinguished by the number of their carbon atoms, 23, 24, and 25. Each class has a spiral steroid and is a phosphodiester. Up until these investigations, no spiral steroids or steroid phosphodiesters were known. There are at least 13 compounds, of which six have been purified to near homogeneity; each one has been characterized by its mass and proposed composition, and they function by regulating the NaK-ATPase. Based on the tissues in which they have been detected, each class of compound seems to regulate a different isoform of the NaK-ATPase. This is an important site of endocrine regulation.
Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients
Authors: Ryu Woo Kyung , Oh Sekyung , Lim Jun Hyeok , Lee Seung Jae , Shin Hyun-Tae , Ryu Jeong-Seon
Published: August 2022

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.
Biomimetic Keratin-Coated Gold Nanoparticles for Photo-Thermal Therapy in a 3D Bioprinted Glioblastoma Tumor Model
Authors: Chirivì Maila , Bearzi Claudia , Rosa Paolo , Miglietta Selenia , Petronella Francesca , De Falco Elena , Calogero Antonella , Pani Roberto , Petrozza Vincenzo , Perotto Giovanni , Rizzi Roberto , De Sio Luciano
Published: August 2022

Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of innovative therapies to be studied without sacrificing animals, while providing helpful information and details. We report on the powerful combination of 3D bioprinting (3DB) and photo-thermal therapy (PTT) applications. To this end, we realize a 3DB construct consisting of glioblastoma U87-MG cells in a 3D geometry, incorporating biomimetic keratin-coated gold nanoparticles (Ker-AuNPs) as a photo-thermal agent. The resulting plasmonic 3DB structures exhibit a homogeneous cell distribution throughout the entire volume while promoting the localization of Ker-AuNPs within the cells. A 3D immunofluorescence assay and transmission electron microscopy (TEM) confirm the uniform distribution of fluorescent-labeled Ker-AuNPs in the volume and their capability to enter the cells. Laser-assisted (λ = 532 nm) PTT experiments demonstrate the extraordinary ability of Ker-AuNPs to generate heating, producing the highest temperature rise of about 16 °C in less than 2 min.
Immobilized Sulfuric Acid on Silica Gel as Highly Efficient and Heterogeneous Catalyst for the One-Pot Synthesis of Novel α-Acyloxycarboxamides in Aqueous Media
Authors: Salami Sodeeq Aderotimi , Manyeruke Meloddy , Siwe-Noundou Xavier , Krause Rui Werner Maçedo
Published: August 2022

The application of immobilized sulfuric acid on silica gel (H2SO4-SiO2) as an efficient and easily reusable solid catalyst was explored in the synthesis of novel α-acyloxycarboxamide derivatives via a Passerini reaction of benzoic acid, aldehyde/ketone, and isocyanides. The Passerini adducts were obtained in high to excellent yields within 10 min in aqueous media under catalytic conditions. The key advantages of the process include a short reaction time, high yields, the catalyst’s low cost, and the catalyst’s reusability.
Altered Expression of TMEM43 Causes Abnormal Cardiac Structure and Function in Zebrafish
Authors: Zink Miriam , Seewald Anne , Rohrbach Mareike , Brodehl Andreas , Liedtke Daniel , Williams Tatjana , Childs Sarah J. , Gerull Brenda
Published: August 2022

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease caused by heterozygous missense mutations within the gene encoding for the nuclear envelope protein transmembrane protein 43 (TMEM43). The disease is characterized by myocyte loss and fibro-fatty replacement, leading to life-threatening ventricular arrhythmias and sudden cardiac death. However, the role of TMEM43 in the pathogenesis of ACM remains poorly understood. In this study, we generated cardiomyocyte-restricted transgenic zebrafish lines that overexpress eGFP-linked full-length human wild-type (WT) TMEM43 and two genetic variants (c.1073C>T, p.S358L; c.332C>T, p.P111L) using the Tol2-system. Overexpression of WT and p.P111L-mutant TMEM43 was associated with transcriptional activation of the mTOR pathway and ribosome biogenesis, and resulted in enlarged hearts with cardiomyocyte hypertrophy. Intriguingly, mutant p.S358L TMEM43 was found to be unstable and partially redistributed into the cytoplasm in embryonic and adult hearts. Moreover, both TMEM43 variants displayed cardiac morphological defects at juvenile stages and ultrastructural changes within the myocardium, accompanied by dysregulated gene expression profiles in adulthood. Finally, CRISPR/Cas9 mutants demonstrated an age-dependent cardiac phenotype characterized by heart enlargement in adulthood. In conclusion, our findings suggest ultrastructural remodeling and transcriptomic alterations underlying the development of structural and functional cardiac defects in TMEM43-associated cardiomyopathy.
The Neuroprotective Effects of Exosomes Derived from TSG101-Overexpressing Human Neural Stem Cells in a Stroke Model
Authors: Yoon Eun-Jung , Choi Yunseo , Kim Tae Myoung , Choi Ehn-Kyoung , Kim Yun-Bae , Park Dongsun
Published: August 2022

Although tissue-type plasminogen activator was approved by the FDA for early reperfusion of occluded vessels, there is a need for an effective neuroprotective drug for stroke patients. In this study, we established tumor susceptibility gene (TSG)101-overexpressing human neural stem cells (F3.TSG) and investigated whether they showed enhanced secretion of exosomes and whether treatment with exosomes during reperfusion alleviated ischemia-reperfusion-mediated brain damage. F3.TSG cells secreted higher amounts of exosomes than the parental F3 cells. In N2A cells subjected to oxygen–glucose deprivation (OGD), treatment with exosomes or coculture with F3.TSG cells significantly attenuated lactate dehydrogenase release, the mRNA expression of proinflammatory factors, and the protein expression of DNA-damage-related proteins. In a middle cerebral artery occlusion (MCAO) rat model, treatment with exosomes, F3 cells, or F3.TSG cells after 2 h of occlusion followed by reperfusion reduced the infarction volume and suppressed inflammatory cytokines, DNA-damage-related proteins, and glial fibrillary acidic protein, and upregulated several neurotrophic factors. Thus, TSG101-overexpressing neural stem cells showed enhanced exosome secretion; exosome treatment protected against MCAO-induced brain damage via anti-inflammatory activities, DNA damage pathway inhibition, and growth/trophic factor induction. Therefore, exosomes and F3.TSG cells can affect neuroprotection and functional recovery in acute stroke patients.
Hierarchy of Bioapatites
Authors: Kuczumow Andrzej , Gorzelak Mieczysław , Kosiński Jakub , Lasota Agnieszka , Blicharski Tomasz , Gągała Jacek , Nowak Jakub , Jarzębski Maciej , Jabłoński Mirosław
Published: August 2022

Apatites are one of the most intensively studied materials for possible biomedical applications. New perspectives of possible application of apatites correspond with the development of nanomaterials and nanocompounds. Here, an effort to systematize different kinds of human bioapatites forming bones, dentin, and enamel was undertaken. The precursors of bioapatites and hydroxyapatite were also considered. The rigorous consideration of compositions and stoichiometry of bioapatites allowed us to establish an order in their mutual sequence. The chemical reactions describing potential transformations of biomaterials from octacalcium phosphate into hydroxyapatite via all intermediate stages were postulated. Regardless of whether the reactions occur in reality, all apatite biomaterials behave as if they participate in them. To conserve the charge, additional free charges were introduced, with an assumed meaning to be joined with the defects. The distribution of defects was coupled with the values of crystallographic parameters “a” and “c”. The energetic balances of bioapatite transformations were calculated. The apatite biomaterials are surprisingly regular structures with non-integer stoichiometric coefficients. The results presented here will be helpful for the further design and development of nanomaterials.
miRNA-10a-5p Targeting the BCL6 Gene Regulates Proliferation, Differentiation and Apoptosis of Chicken Myoblasts
Authors: Zhang Genxi , Zhang Xinchao , Zhou Kaizhi , Ling Xuanze , Zhang Jin , Wu Pengfei , Zhang Tao , Xie Kaizhou , Dai Guojun
Published: August 2022

Proliferation, differentiation, and apoptosis are three essential stages in cell development, and miRNAs can achieve extensive regulation of cellular developmental processes by repressing the expression of target genes. According to our previous RNA-seq results, miRNA-10a-5p was differentially expressed at different periods in chicken myoblasts, revealing a possible association with muscle development. In this study, we concluded that miRNA-10a-5p inhibited chicken myoblasts’ proliferation and differentiation and promoted chicken myoblasts’ apoptosis by directly targeting BCL6, a critical transcription factor involved in muscle development and regeneration. Overexpression of BCL6 significantly facilitated myoblasts’ proliferation and differentiation and suppressed myoblasts’ apoptosis. On the contrary, knockdown of BCL6 significantly repressed myoblasts’ proliferation and differentiation and induced myoblasts’ apoptosis. The results above suggest that miRNA-10a-5p plays a potential role in skeletal muscle growth, development and autophagy by targeting the BCL6 gene. We first revealed the functions of miRNA-10a-5p and BCL6 in the proliferation, differentiation, and apoptosis of chicken myoblasts.
Cellular and Molecular Variations in Male and Female Murine Skeletal Muscle after Long-Term Feeding with a High-Fat Diet
Authors: Emerald Bright Starling , Al Jailani Mohammed A. , Ibrahim Marwa F. , Kumar Challagandla Anil , Allouh Mohammed Z.
Published: August 2022

Current information regarding the effects of a high-fat diet (HFD) on skeletal muscle is contradictory. This study aimed to investigate the effects of a long-term HFD on skeletal muscle in male and female mice at the morphological, cellular, and molecular levels. Adult mice of the C57BL/6 strain were fed standard chow or an HFD for 20 weeks. The tibialis anterior muscles were dissected, weighed, and processed for cellular and molecular analyses. Immunocytochemical and morphometric techniques were applied to quantify fiber size, satellite cells (SCs), and myonuclei. Additionally, PCR array and RT-qPCR tests were performed to determine the expression levels of key muscle genes. Muscles from HFD mice showed decreases in weight, SCs, and myonuclei, consistent with the atrophic phenotype. This atrophy was associated with a decrease in the percentage of oxidative fibers within the muscle. These findings were further confirmed by molecular analyses that showed significant reductions in the expression of Pax7, Myh1, and Myh2 genes and increased Mstn gene expression. Male and female mice showed similar trends in response to HFD-induced obesity. These findings indicate that the long-term effects of obesity on skeletal muscle resemble those of age-related sarcopenia.
Vps21 Directs the PI3K-PI(3)P-Atg21-Atg16 Module to Phagophores via Vps8 for Autophagy
Authors: Zhao Lei , You Weiming , Sun Dan , Xu Hui , You Xia , Xu Haiqian , Wu Zulin , Xie Zhiping , Liang Yongheng
Published: August 2022

Phosphatidylinositol 3-phosphate (PI(3)P) serves important functions in endocytosis, phagocytosis, and autophagy. PI(3)P is generated by Vps34 of the class III phosphatidylinositol 3-kinase (PI3K) complex. The Vps34-PI3K complex can be divided into Vps34-PI3K class II (containing Vps38, endosomal) and Vps34-PI3K class I (containing Atg14, autophagosomal). Most PI(3)Ps are associated with endosomal membranes. In yeast, the endosomal localization of Vps34 and PI(3)P is tightly regulated by Vps21-module proteins. At yeast phagophore assembly site (PAS) or mammalian omegasomes, PI(3)P binds to WD-repeat protein interacting with phosphoinositide (WIPI) proteins to further recruit two conjugation systems, Atg5-Atg12·Atg16 and Atg8-PE (LC3-II), to initiate autophagy. However, the spatiotemporal regulation of PI(3)P during autophagy remains obscure. Therefore, in this study, we determined the effect of Vps21 on localization and interactions of Vps8, Vps34, Atg21, Atg8, and Atg16 upon autophagy induction. The results showed that Vps21 was required for successive colocalizations and interactions of Vps8-Vps34 and Vps34-Atg21 on endosomes, and Atg21-Atg8/Atg16 on the PAS. In addition to disrupted localization of the PI3K complex II subunits Vps34 and Vps38 on endosomes, the localization of the PI3K complex I subunits Vps34 and Atg14, as well as Atg21, was partly disrupted from the PAS in vps21∆ cells. The impaired PI3K-PI(3)P-Atg21-Atg16 axis in vps21∆ cells might delay autophagy, which is consistent with the delay of early autophagy when Atg21 was absent. This study provides the first insight into the upstream sequential regulation of the PI3K-PI(3)P-Atg21-Atg16 module by Vps21 in autophagy.
The Role of RNA-Binding Proteins in Hematological Malignancies
Authors: Aguilar-Garrido Pedro , Otero-Sobrino Álvaro , Navarro-Aguadero Miguel Ángel , Velasco-Estévez María , Gallardo Miguel
Published: August 2022

Hematological malignancies comprise a plethora of different neoplasms, such as leukemia, lymphoma, and myeloma, plus a myriad of dysplasia, such as myelodysplastic syndromes or anemias. Despite all the advances in patient care and the development of new therapies, some of these malignancies remain incurable, mainly due to resistance and refractoriness to treatment. Therefore, there is an unmet clinical need to identify new biomarkers and potential therapeutic targets that play a role in treatment resistance and contribute to the poor outcomes of these tumors. RNA-binding proteins (RBPs) are a diverse class of proteins that interact with transcripts and noncoding RNAs and are involved in every step of the post-transcriptional processing of transcripts. Dysregulation of RBPs has been associated with the development of hematological malignancies, making them potential valuable biomarkers and potential therapeutic targets. Although a number of dysregulated RBPs have been identified in hematological malignancies, there is a critical need to understand the biology underlying their contribution to pathology, such as the spatiotemporal context and molecular mechanisms involved. In this review, we emphasize the importance of deciphering the regulatory mechanisms of RBPs to pinpoint novel therapeutic targets that could drive or contribute to hematological malignancy biology.
Investigation of the Associations of Novel Inflammatory Biomarkers—Systemic Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI)—With the Severity of Coronary Artery Disease and Acute Coronary Syndrome Occurrence
Authors: Dziedzic Ewelina A. , Gąsior Jakub S. , Tuzimek Agnieszka , Paleczny Justyna , Junka Adam , Dąbrowski Marek , Jankowski Piotr
Published: August 2022

Atherosclerosis, the underlying cause of coronary artery disease (CAD), has a significant inflammatory component. White blood cell count is an affordable and accessible way to assess the systemic immune response, as it comprises many subgroups with distinct and complex functions. Considering their multidirectional effect on atherosclerosis, new biomarkers integrating various leukocyte subgroups, the Systemic Inflammatory Index (SII) and the Systemic Inflammatory Response Index (SIRI), were recently devised to describe the balance between inflammation and immune reaction. This research aimed to evaluate the relationship of the intensity of inflammation measured by these biomarkers with the severity of CAD assessed with coronary angiography and with the diagnosis of acute coronary syndrome (ACS) or stable CAD in 699 patients. SIRI, but not SII, was associated with the diagnosis, having the highest values for patients with ACS (STEMI), significantly higher than in patients with stable CAD (p < 0.01). The highest SII and SIRI values were observed in patients with three-vessel CAD. SII and SIRI require further in-depth and well-designed research to evaluate their potential in a clinical setting.
Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro
Authors: Hoffmann Anne L. C. , Hauck Stefanie M. , Deeg Cornelia A. , Degroote Roxane L.
Published: August 2022

In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.
A Comparative Study of the ADDIE Instructional Design Model in Distance Education
Authors: Spatioti Adamantia G. , Kazanidis Ioannis , Pange Jenny
Published: August 2022

Distance education is now a reality introducing a “specific methodology of flexible and interactive multiform learning”. Due to its characteristics, different instructional design models apply to distance education as guidelines of the design thinking process pursuing specific learning outcomes. This study refers to the investigation of good teaching practices and approaches in relation to the ADDIE model in distance online environments. The purpose of this paper is to investigate both the effectiveness of the ADDIE model in distance education and its contribution to the online teaching process. Meta-analysis is chosen as the research methodology. Specifically, we export a total of 58 articles referring to the ADDIE model. From these, we find that only 23 articles are appropriate for the meta-analysis. According to the results of this study, we observe that the ADDIE model applies to meet different teaching requirements in all online educational environments. In this study, we observe that good practices of teaching are the multimedia presentation, feedback, variety of interactive exercises or activities, combined learning strategy (individualized and collaborative), and role of educators. Then, an asynchronous approach was preferred in distance education. Finally, the ADDIE model is considered as a valuable source of additional information by providing good teaching practices.
Once-Weekly Semaglutide Use in Patients with Type 2 Diabetes: Results from the SURE Spain Multicentre, Prospective, Observational Study
Authors: Bellido Virginia , Abreu Padín Cristina , Catarig Andrei-Mircea , Clark Alice , Barreto Pittol Sofía , Delgado Elias
Published: August 2022

Type 2 diabetes (T2D) is a complex disease for which an individualised treatment approach is recommended. Once-weekly (OW) semaglutide is a glucagon-like peptide-1 receptor agonist approved for the treatment of insufficiently controlled T2D. The aim of this study was to investigate the use of OW semaglutide in adults with T2D in a real-world context. SURE Spain, from the 10-country SURE programme, was a prospective, multicentre, open-label, observational study, approximately 30 weeks in duration. Adults with T2D and ≥1 documented HbA1c value ≤12 weeks before semaglutide initiation were enrolled. Change in HbA1c from baseline to end of study (EOS) was the primary endpoint, with change in body weight (BW), waist circumference, and patient-reported outcomes as secondary endpoints. Of the 227 patients initiating semaglutide, 196 (86.3%) completed the study on-treatment with semaglutide. The estimated mean changes in HbA1c and body weight between baseline and EOS were −1.3%-points (95% confidence interval (CI) −1.51;−1.18%-points) and −5.7 kg (95% CI −6.36;−4.98 kg). No new safety concerns were identified. Therefore, in routine clinical practice in Spain, OW semaglutide was shown to be associated with statistically significant and clinically relevant reductions in HbA1c and BW in adults with T2D.
Clinical Outcome of Intraoperative Recurrent Laryngeal Nerve Monitoring during Thoracoscopic Esophagectomy and Mediastinal Lymph Node Dissection for Esophageal Cancer
Authors: Huang Chang-Lun , Chen Chun-Min , Hung Wei-Heng , Cheng Ya-Fu , Hong Ruei-Ping , Wang Bing-Yen , Cheng Ching-Yuan
Published: August 2022

Mediastinal lymph dissection in esophagectomy for patients with esophageal cancer is important. The dissection of recurrent laryngeal nerve (RLN) lymph nodes could cause RLN injury, vocal cord palsy, pneumonia, and respiratory failure. This retrospective study aimed to evaluate the effects of intraoperative RLN monitoring in esophagectomy and mediastinal lymph node dissection in preventing RLN injury and vocal cord palsy. This study included 75 patients who underwent minimally invasive esophagectomy and mediastinal lymph node dissection for esophageal cancer with (38 patients) and without (37 patients) IONM at Changhua Christian Hospital from 2015 to 2020. The surgical and clinical outcomes were reviewed. Patients in the IONM group had more advanced clinical T status, shorter operation time (570 vs. 633 min, p = 0.007), and less blood loss (100 mL vs. 150 mL, p = 0.019). The IONM group had significantly less postoperative vocal palsy (10.5% vs. 37.8%, p = 0.006) and pneumonia (13.2% vs. 37.8%, p = 0.014) than that in the non-IONM group. IONM was an independent factor for less postoperative vocal cord palsy that was related to postoperative 2-year survival. This study demonstrated that IONM could reduce the incidence of postoperative vocal cord palsy and pneumonia.
Effectiveness of Early Rehabilitation with Exergaming in Virtual Reality on Gait in Patients after Total Knee Replacement
Authors: Hadamus Anna , Błażkiewicz Michalina , Wydra Kamil T. , Kowalska Aleksandra J. , Łukowicz Małgorzata , Białoszewski Dariusz , Marczyński Wojciech
Published: August 2022

Total knee replacement (TKR) is the treatment of choice for advanced stages of osteoarthritis but it requires good postoperative rehabilitation. This study aimed to assess the effectiveness of exercises using virtual reality to improve gait parameters in patients after TKR. Fifty-nine patients 7–14 days after TKR surgery were divided into a study group (VRG, n = 38) and a control group (CG, n = 21). Both groups underwent the same 4-week rehabilitation protocol. The VRG group had 12 additional nonimmersive virtual reality game sessions on the Virtual Balance Clinic prototype system at 30 min each, focusing on gait and balance improvement. Spatiotemporal, force and foot plantar pressure parameters were collected on an instrumented treadmill during a 30 s walk. The most significant improvement was in the symmetry indices of forefoot force, maximum forefoot force, loading response time, and preswing time (p < 0.05) in both groups. Gait speed increased by 31.25% and 44% in the VRG and CG groups, respectively (p < 0.005). However, the extra exergaming sessions did not significantly improve rehabilitation outcomes. Therefore, additional VR training does not improve gait better than standard rehabilitation alone, but the improvement of gait, especially its symmetry, is significant within the first six weeks after surgery.