bluuebunny/crossref_metadata_2025_split huggingface dataset:
GJB2 and GJB6 gene transcripts in the human cochlea: A study using RNAscope, confocal, and super-resolution structured illumination microscopy
Authors: Liu Wei , Rask-Andersen Helge 
Published: September 2022

BackgroundGap junction (GJ) proteins, connexin26 and 30, are highly prevalent in the human cochlea (HC), where they are involved in transcellular signaling, metabolic supply, and fluid homeostasis. Their genes, GJB2 and GJB6, are both located at the DFNB1 locus on chromosome 13q12. Mutations in GJB2 may cause mild to profound non-syndromic deafness. Here, we analyzed for the first time the various expressions of GJB2 and GJB6 gene transcripts in the different cell networks in the HC using the RNAscope technique.Materials and methodsArchival paraformaldehyde-fixed sections of surgically obtained HC were used to label single mRNA oligonucleotides using the sensitive multiplex RNAscope® technique with fluorescent-tagged probes. Positive and negative controls also included the localization of ATP1A1, ATP1A2, and KCNJ10 gene transcripts in order to validate the specificity of labeling.ResultsConfocal and super-resolution structured illumination microscopy (SR-SIM) detected single gene transcripts as brightly stained puncta. The GJB2 and GJB6 gene transcripts were distributed in the epithelial and connective tissue systems in all three cochlear turns. The largest number of GJB2 and GJB6 gene transcripts was in the outer sulcus, spiral ligament, and stria vascularis (SV). Oligonucleotides were present in the supporting cells of the organ of Corti (OC), spiral limbus fibrocytes, and the floor of the scala vestibuli. Multiplex gene data suggest that cells in the cochlear lateral wall contain either GJB2 or GJB6 gene transcripts or both. The GJB6, but not GJB2, gene transcripts were found in the intermediate cells but none were found in the marginal cells. There were no GJB2 or GJB6 gene transcripts found in the hair cells and only a few in the spiral ganglion cells.ConclusionBoth GJB2 and GJB6 mRNA gene transcripts were localized in cells in the adult HC using RNAscope®in situ hybridization (ISH) and high resolution microscopy. Generally, GJB6 dominated over GJB2, except in the basal cells. Results suggest that cells may contain either GJB2 or GJB6 gene transcripts or both. This may be consistent with specialized GJ plaques having separate channel permeability and gating properties. A reduction in the number of GJB2 gene transcripts was found in the basal turn. Such information may be useful for future gene therapy.
The impaired distribution of adenosine deaminase isoenzymes in multiple sclerosis plasma and cerebrospinal fluid
Authors: Kutryb-Zajac Barbara , Kawecka Ada , Caratis Fionä , Urbanowicz Krzysztof , Braczko Alicja , Furihata Tomomi , Karaszewski Bartosz , Smolenski Ryszard T. , Rutkowska Aleksandra 
Published: September 2022

BackgroundAdenosine deaminase (ADA) via two isoenzymes, ADA1 and ADA2, regulates intra- and extracellular adenosine concentrations by converting it to inosine. In the central nervous system (CNS), adenosine modulates the processes of neuroinflammation and demyelination that together play a critical role in the pathophysiology of multiple sclerosis (MS). Except for their catalytic activities, ADA isoenzymes display extra-enzymatic properties acting as an adhesion molecule or a growth factor.AimsThis study aimed to explore the distribution and activity of ADA1 and ADA2 in the plasma and the CSF of MS patients as well as in the human brain microvascular endothelial cells (HBMEC), human brain vascular pericytes and human astrocytes.Methods and resultsThe enzyme assay following reverse phase-high performance liquid chromatography (HPLC) analysis was used to detect the ADA1 and ADA2 activities and revealed an increased ratio of ADA1 to ADA2 in both the plasma and the CSF of MS patients. Plasma ADA1 activity was significantly induced in MS, while ADA2 was decreased in the CSF, but significance was not reached. The brain astrocytes, pericytes and endothelial cells revealed on their surface the activity of ADA1, with its basal level being five times higher in the endothelial cells than in the astrocytes or the pericytes. In turn, ADA2 activity was only observed in pericytes and endothelial cells. Stimulation of the cells with pro-inflammatory cytokines TNFα/IL17 for 18 h decreased intracellular nucleotide levels measured by HPLC only in pericytes. The treatment with TNFα/IL17 did not modulate cell-surface ATP and AMP hydrolysis nor adenosine deamination in pericytes or astrocytes. Whereas in endothelial cells it downregulated AMP hydrolysis and ADA2 activity and upregulated the ADA1, which reflects the ADA isoenzyme pattern observed here in the CSF of MS patients.ConclusionIn this study, we determined the impaired distribution of both ADA isoenzymes in the plasma and the CSF of patients with MS. The increased ADA1 to ADA2 ratio in the CSF and plasma may translate to unfavorable phenotype that triggers ADA1-mediated pro-inflammatory mechanisms and decreases ADA2-dependent neuroprotective and growth-promoting effects in MS.
Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as novel diagnostic biomarkers for lung adenocarcinoma
Authors: You Jianbin , Yang Guoliu , Wu Yi , Lu Xuan , Huang Shuyu , Chen Qianshun , Huang Chen , Chen Falin , Xu Xunyu , Chen Liangyuan 
Published: September 2022

ObjectiveTRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are recognized as novel and potential types of non-coding RNAs (ncRNAs), and several tRF/tiRNA signatures are closely associated with tumor diagnosis. This study aimed to analyze the expression profiles of plasma tRFs/tiRNAs and to clarify their diagnostic value in lung adenocarcinoma (LUAD).MethodsThe differential expression profiles of plasma tRFs/tiRNAs in patients with four patients with early LUAD, four patients with advanced LUAD, and four healthy controls were analyzed using high-throughput sequencing technology. Then, plasma tRFs/tiRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR), and their diagnostic efficiency was appraised by receiver operating characteristic curve analysis. The correlation of candidate plasma tRFs/tiRNAs with clinicopathological features was also analyzed. Finally, bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs/tiRNAs.ResultsThe sequencing results revealed that tRFs/tiRNAs from plasma samples in patients with LUAD were differently expressed, supporting the necessity of exploring their potential as biomarkers. The validation results of qRT-PCR demonstrated that the expression level of tRF-1:29-Pro-AGG-1-M6 was downregulated in LUAD, while that of tRF-55:76-Tyr-GTA-1-M2 was upregulated, which was consistent with the sequencing data. The areas under the receiver operating characteristic curve of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 were 0.882 and 0.896, respectively, which have significant values in the diagnosis of LUAD. The expressions of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 in LUAD were obviously correlated with various clinicopathological features such as tumor–node–metastasis stage, node stage, and the expression levels of carcinoembryonic antigen. In addition, their expression was significantly altered from before to after tumor resection in LUAD patients. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses further indicated that tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 are widely distributed and apparently enriched in several tumor-related signaling pathways.ConclusionsPlasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 may be promising components in the development of highly sensitive and non-invasive biomarkers for LUAD diagnosis.
Risk factors of oesophageal cancer at health facilities in Addis Ababa, Ethiopia: Unmatched case control study
Authors: Dessalegn Berhe , Enqueselassie Fikre , Kaba Mirgissa , Assefa Mathewos , Addissie Adamu 
Published: September 2022

BackgroundOesophageal carcinoma is one of the most common cancers in Ethiopia. Its occurrences vary among regional states of the country. The identification of local risk factors of oesophageal cancer will make it simple to design a focused intervention. On local risk factors, there is, however, a shortage of empirical evidence. Therefore, the aim of study was to identify local risk factors.MethodsAn unmatched case control study design was employed. From February 2019 to August 2020, 338 histologically confirmed cases and 338 controls were recruited consecutively from six health facilities in Addis Ababa, Ethiopia’s capital city. To collect data from the cases and the controls, face to face interviews were conducted. Epi-info version 7 was used to enter and cleaned data, and SPSS version 23 was used to analyze it. The odds ratio was calculated based on hierarchal model multivariable logistic regression, and statistically significance was declared at p-value of &lt;0.05.ResultsThe mean (SD) age of the cases and the controls was 54.3 ± 12.5 years old and 40.2 ± 13.7 years old, respectively. The odds of oesophageal cancer was significantly higher among older ages (OR =11.0, 95% CI [6.60, 20.91]), rural residents (OR = 4.2, 95% CI [1.04, 16.80]), and those who had history of smoking (OR =1.3, 95% CI [1.12, 1.60]), khat chewing (OR = 4.0, 95% CI [2.50, 6.60]), raw meat consumers (OR = 2.6, 95% CI [1.75, 3.90]). Increasing monthly income (OR = 0.2, CI 95% [0.09, 0.49]) and a habit of eating fruits or vegetables (OR = 0.49, 95% CI [0.32, 0.76]) were associated with lower risks.ConclusionsTobacco smoking, khat chewing, age, residency, and red raw meat consumption were discovered to be positive predictors of oesophageal cancer, whereas fruit or vegetable consumption and higher monthly income were discovered to be inversely associated. It is advised to avoid the use of khat and tobacco, as well as to avail fruits and vegetables in dish.
Case report: A case of acquired von Willebrand syndrome as onset clinical presentation of systemic lupus erythematosus manifested as epistaxis and pulmonary hemorrhage
Authors: Wang Songmi , Hu Qun , Chen Yaxian , Hu Xiufen , Tang Ning , Zhang Ai , Liu Aiguo 
Published: September 2022

BackgroundAcquired von Willebrand syndrome (AVWS) is a less common bleeding disorder, primarily manifested as mild to moderate mucocutaneous bleeding and laboratory tests are similar to hereditary von Willebrand disease (VWD). AVWS is secondary to other diseases, and systemic lupus erythematosus (SLE) is a relatively rare cause.Case presentationWe report a case of AVWS as onset clinical presentation of SLE manifested as epistaxis and pulmonary hemorrhage. A 13-year-old male child presented to the hospital with a six-month history of recurrent epistaxis and a one-month history of anemia. Routine blood tests demonstrated severe normocytic anemia and normal platelet count. Von Willebrand test revealed a significantly lower level. High-resolution chest computed tomography (CT) showed patchy ground glass opacities consistent with hemorrhagic changes. After ruling out the family history, the patient was diagnosed with AVWS. Additional tests confirmed positive antinuclear and anti-Sm antibodies. The underlying SLE was diagnosed and treated with methylprednisolone with disease recovery.ConclusionWe recommend screening for bleeding disorders in patients with recurrent epistaxis. AVWS should be considered when laboratory findings suggest hereditary von Willebrand disease without a personal or familial history of bleeding. In addition, the underlying disease should be explored.
Hepatoprotective potential of a novel quinazoline derivative in thioacetamide-induced liver toxicity
Authors: Salama Suzy , Kue Chin Siang , Mohamad Haryanti , Omer Fatima , Ibrahim Mohamed Yousif , Abdulla Mahmood , Ali Hapipah , Mariod Abdalbasit , Jayash Soher Nagi 
Published: September 2022

Purpose: The compound quinazoline Q-Br, 3-(5-bromo-2-hydroxybenzylideneamino)-2-(5-bromo-2 hydroxyphenyl) 2,3-dihydroquinazoline-4(1H)-one (Q-Br) was evaluated for its antioxidant capacity and potential hepatoprotectivity against sub-chronic liver toxicity induced by thioacetamide in rats.Materials and Methods: Rats were assigned into five groups; healthy (normal) and cirrhosis control groups were given 5% Tween 20 orally, the reference control group was given a Silymarin dose of 50 mg/kg, and low-dose Q-Br and high-dose Q-Br groups were given a daily dose of 25 mg/kg and 50 mg/g Q-Br, respectively. Liver status was detected via fluorescence imaging with intravenous injection of indocyanine green (ICG) and a plasma ICG clearance test. Liver malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were also tested. The degree of fibrosis was determined histologically by hematoxylin and eosin and Masson’s Trichrome staining. The immunohistochemistry of liver tissue inhibitor of metalloproteinase (TIMP-1), matrix metalloproteinase (MMP-2), and alpha-smooth muscle actin (α-SMA) was performed.Results: Q-Br recorded mild antioxidant capacity, dose-dependent improvement in the liver status, and inhibition of oxidative stress compared to cirrhosis control. Histopathology notified a remarkable reduction in the degree of fibrosis. Immunohistochemistry revealed an obvious low expression of MMP-2 and α-SMA along with a higher expression of TIMP-1 in Q-Br- and Silymarin-treated livers.Conclusion: Q-Br treatment altered the course of toxicity induced by thioacetamide suggesting significant hepatoprotective potential of Q-Br treatment.
Relationships between care burden, resilience, and depressive symptoms among the main family caregivers of stroke patients: A cross-sectional study
Authors: Fang Linlin , Dong Mengyuan , Fang Wenbo , Zheng Jin 
Published: September 2022

ObjectivesThis study aims to explore the potential mediating role of resilience between care burden and depressive symptoms in family caregivers of stroke patients.MethodsA cross-sectional study was conducted with a convenience sample involving 245 main family caregivers of stroke patients recruited from the neurology department of a Tertiary A hospital in China. Mediation analyses were conducted using the PROCESS macro (Model 4) for SPSS, applying the Bootstrap analysis with 5,000 samples and a 95% confidence interval.ResultsThe results showed that with constant hemiplegia side, Barthel Index, education level, monthly income, care time per day, and living with patients in regression equations, the resilience partially mediated the correlation of care burden and depressive symptoms with a mediation effect ratio of 26.32%.ConclusionsResilience plays a mediating role in the correlation between care burden and depressive symptoms.ImpactThe findings indicated a protective effect of resilience in alleviating the negative influences of care burden on depressive symptoms, suggesting that resilience-training intervention may be developed to mitigate depressive symptoms of the main family caregivers of stroke patients.
An evaluation method for product design solutions for healthy aging companionship
Authors: Hu Shan , Jia Qi , Dong Linlin , Han Jialin , Guo Min , Guo Weiqi 
Published: September 2022

BackgroundWith the development trend of healthy aging and intelligent integration, escort products have become a new means of healthy aging. Healthy old-age care pays attention to the convenience and informatization of life. To meet the needs, designers often design multiple accompanying product solutions, and it is very important to use reasonable evaluation methods to decide on the optimal solution.PurposesA new comprehensive evaluation method is proposed to reduce the subjectivity and one-sidedness of the selection process of intelligent escort product design solutions, and to make the decision more objective and reasonable. Such decisions can enhance the experience and naturalness of the elderly using intelligent products.MethodsFirst, a large number of user interviews were analyzed using the grounded theory, gradually refine through theoretical coding, and abstracted with the design scheme evaluation index. Second, the idea of game-theoretic weighting is used to optimize a linear combination of subjective and objective weights to determine the final weights of each evaluation indicator. Finally, the evaluation and selection are completed based on the solution ranking determined by the approximate ideal solution ranking method (TOPSIS). It is applied for the selection of the elderly escort robot design, and the usability test is conducted using the PSSUQ to verify the selection results.ResultsA new comprehensive evaluation method can better complete the preferential selection of product design solutions for healthy aging escorts, and reduce the subjectivity and one-sidedness of the evaluation.ConclusionThis method compensates for the reliance on personal experience in the selection of options, and improve the subjectivity of the evaluation index determination process and the deviation of index weighting. Improving the objectivity and scientificity of decision-making reduces the blindness of design and production. It also provides a theoretical reference for the research scholars of healthy aging companion products.
Changes of factors associated with vaccine hesitancy in Chinese residents: A qualitative study
Authors: Long Sigui , Wu Jingying , Wang Shile , Zhao Yaqi , Wang Jianli , Zhao Shuangyu , Niu Qing , Jin Hui 
Published: September 2022

IntroductionThere is an urgent need to address vaccine hesitancy to achieve booster vaccination. This study aimed to reveal the factors associated with vaccine hesitancy (including COVID-19 vaccine) among Chinese residents, address modifications of the factors since the previous year, and propose vaccination rate improvement measures.Materials and methodsThis qualitative return visit study was performed between January and mid-February 2022, following the last interview conducted between February and March 2021. According to an outline designed in advance, 60 Chinese residents from 12 provinces participated in semi-structured interviews.ResultsVaccine safety was the biggest concern raised by respondents, followed by self-immunity and vaccine effectiveness, eliciting concern since the interview last year. Notably, online media accounted for a more significant portion of suggestion sources than before, and fear of pain was a novel factor affecting vaccine hesitancy. Moreover, unlike other areas, those from provinces with a per capita gross domestic product of 3–5 (RMB 10,000) reported less concern about vaccine price and effectiveness. They tended to seek advice via online media less and were greatly influenced by vaccination policies.ConclusionsInfluential factors of vaccine hesitancy among Chinese residents are changing dynamically. Monitoring these trends is essential for public health measures and higher vaccination levels.
Mobile phone addiction and depressive symptoms among Chinese University students: The mediating role of sleep disturbances and the moderating role of gender
Authors: Liu Meng , Lu Chuntian 
Published: September 2022

BackgroundWith the continuous updating of mobile phone functions, the phenomenon of mobile phone addiction among University students is becoming more and more serious. It is important to identify the potential risk factors for mobile phone addiction. The aim of the study was to examine whether there is a relationship between mobile phone addiction and depression symptoms in University students, and to investigate whether sleep disturbances play a mediating role between mobile phone addiction and depression symptoms, as well as the moderating role of gender.MethodsA cross-sectional study, carried out between September to December 2021, recruited 973 students (478 males) from seven comprehensive universities in western China. The Mobile Phone Addiction Index (MPAI), the Patient Health Questionnaire-9 (PHQ9), and the Pittsburgh Sleep Quality Index (PSQI) were used to complete measures of mobile phone addiction, depressive symptoms, and sleep disturbances. For statistical analyses, descriptive statistics, correlation, regression, mediation and moderated mediation analyses were used. Furthermore, we tested the mediation model and moderated mediation model using the SPSS macro PROCESS.ResultsIn this study, it was found that there were positive correlations between mobile phone addiction and depressive symptoms among Chinese University students. Mediation analyses revealed that this relationship was partially mediated by sleep disturbances, but the mediating role was not moderated by gender.ConclusionSleep disturbances have a partial mediating role in the relationship between mobile phone addiction and depressive symptoms. Our results highlight the critical role of prevention and early identification of mobile phone addiction among University students, especially those with sleep disturbances.
Training student volunteers as community resource navigators to address patients' social needs: A curriculum toolkit
Authors: Gautam Diwas , Sandhu Sahil , Kutzer Kate , Blanchard Lillian , Xu Jacqueline , Sotelo Munoz Veronica , Dennis Erika , Drake Connor , Crowder Carolyn , Eisenson Howard , Prvu Bettger Janet 
Published: September 2022

IntroductionFew resources are available to train students to provide patients assistance for obtaining needed community-based services. This toolkit outlines a curriculum to train student volunteers to become “community resource navigators” to serve patients via telephone at partner health sites.MethodsUniversity students co-designed the Help Desk navigator program and training for volunteer navigators as part of an academic-community partnership with a local Federally Qualified Health Center (FQHC). The multi-modal curricula consisted of five components: didactic instruction on social determinants of health and program logistics, mock patient calls and documentation, observation of experienced navigator interaction with patients, supervised calls with real patients, and homework assignments. In 2020, training materials were adapted for virtual delivery due to the COVID-19 pandemic. Trainees completed a survey after completion to provide qualitative feedback on the training and preparedness.ResultsThe training was offered for the first cohort of 11 student volunteer navigators in 2019, revised and then offered for 13 undergraduate and nursing students over 6 weeks in 2020. In the training evaluation, trainees described the new knowledge and skills gained from the training, the long-term benefits toward their educational and professional career goals, and helpful interactive delivery of the training. Trainees also highlighted areas for improvement, including more time learning about community resources and practicing challenging patient conversations.ConclusionsOur peer-to-peer, multi-modal training prepares student volunteers to become community resource navigators. Student, eager for meaningful clinical experiences, are an untapped resource that can help patients with their social needs.