bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualizing an convergence of three mitochondrial molecule mRNAs for DRP1/MFN2/UCP4 on soma of cerebellar Purkinje cells by RNAscope
Authors: Liu Hui , Luo Tingting , Wu Feifei , Guo Baolin , Zhang Kunlong , Li Shujiao , Li Xiaodong , Wang Ruiqing , Chen Jinghao , Wang Lu , Yang Yanling , Wang Ya-Yun 
Published: September 2021

Abstract
We know little about how mitochondrial dynamic are regulated in the Purkinje cells. To explore it, we first set up a transgenic mice in which Purkinje cells expressed tdTomato in the cerebellum of Gad2-cre;ZsGreen-tdTomatofl/fl mice. Secondly Double stainings verified tdTomato cells were Calbinin (CB)-positive Purkinje cells, but not colocalized either with astrocyte marker GFAP or with microglia marker Iba1. Thirdly, application of RNAscope in situ hybridization with the identification of mRNAs of mitochondrial fusion (Mfn2), calcium transporter (Mcu and Nclx) and uncoupling proteins (Ucp2 and Ucp4) were used onto Purkinje cells for specific spatial analysis. The RNAscope assay used a semi‑quantitative H scoring guideline to evaluate the staining results. The number of bins ranges from 0–4 according to the ACD scoring system. Moreover, ACD scoring system was used to calculate the overall H scores of Dendritic Weighted Formula (DWF) and Soma Weighted Formula (SWF). Our data for the first time demonstrated that Mfn2 mRNAs expression was evident in Prukinje cells with the H scores of DWF and SWF as 60 and 139, respectively. And few Ucp4 mRNAs expression was present in dendritic shafts of Prukinje cells with the H scores of DWF and SWF as 14 and 103, respectively. It should be noted that Mcu mRNAs, Nclx mRNAs, as well as Ucp2 mRNAs expression were only scattered on both soma and dendrites in Prukinje cells with the low H scores of DWF and SWF. Double RNAscope profiling of mitochondrial molecules showed The data showed Mfn1 mRNAs are present only in the soma of the Purkinje cells, instead of processes. Double RNAscope showed almost none of dots of Drp1 mRNAs was co-localized with dots of Mcu mRNAs, as well as almost none of dots of Ucp2 mRNAs was co-localized with dots of Mfn2 mRNAs. All of these results show the mitochondrial Drp1/Mfn2/UCP4 convergence on the Purkinje cells. Finally, a major focus of present research will be to develop new and more specific molecules that tune the activity of the Purkinje cells activate or inactivate and to address diseases for which such druglike molecules may open therapeutic windows for Purkinje cells-related manipulation in the clinic. The molecular identification of drug targets, mechanism of action, and structural basis of their activity will crucially enable preclinical development.
The Changes of Cancer Patients’ Perception, Attitude and Clinical Practice in Complementary and Alternative Medicine during COVID-19: A multicenter before-after cross-sectional study
Authors: Wang Yichao , Yang Geliang , Gu Zhan , Wang Chengyan , Zhang Huiqing , Xu Ling 
Published: September 2021

Abstract
Background

With the rapid spread of COVID-19 worldwide, the clinical practice in cancer treatment of complementary and alternative medicine (CAM) becomes significantly different. This study was designed to explore the changes of China’s cancer patients’ perception, attitude and clinical practice in CAM after the pandemic of COVID-19.
Methods

A multicenter before-after cross-sectional study was conducted, including 448 cancer patients by a survey.
Results

For perception, half of the cancer patients (51.2%) reported they had received adequate information in CAM cancer treatment and had a great expectation in medical appointment pattern (40.2%). For attitudes, most of the cancer patients (79.4%) had full of confidence in CAM cancer treatment and showed a strong desire to learn more about CAM (70.2%). Nearly half of the cancer patients (44.0%) presented their oncology clinics had been greatly affected by COVID-19, however, most (82.8%) refused to the online medical service pattern. For clinical practice, Chinese herbal medicine was widely used before (89.5%) / after (90.3%) the epidemic of COVID-19 and the main purpose of receiving CAM therapy was to improve immune system (71.8%). The frequency of patients’ visiting the clinic decreased significantly (P < 0.001), and most (90.0%) didn’t change their follow-up pattern. The majority of the cancer patients (83.3%) were identified as CAM users and the only predictive factor was national health insurance in the multivariable logistic regression model.
Conclusion

China’s cancer patients show more interest and confidence in treating cancer by CAM, and the new medical pattern such as medical appointment, has been gradually accepted during the COVID-19 pandemic. However, the cancer patients’ perception in CAM and online medical service pattern still need to be improved.
Long-term Survival of Patients With Unoperated Single Ventricle Heart Defect: Four Case Reports and Literature Review
Authors: Zhao Shengnan , Guo Jiantao , Sun Zhixia , Cui Tingting 
Published: September 2021

Abstract
Background: A single ventricle heart defect is a rare complex congenital cardiac malformation. It is rare for patients with single ventricle to spontaneously survive long-term to adulthood. No literature was retrieved that summarized the ultrasonographic features of patients with single ventricle who survived for a long time without surgery.Case presentation: Four patients in this study were diagnosed with single ventricle heart defects during childhood, but received no surgical intervention. All four patients had good outcomes. We summarize the ultrasound findings of these patients.Conclusion: We summarize the factors that contribute to the long-term survival of single ventricle patients without surgical intervention, and discuss the diagnosis and treatment of single ventricle to improve the survival rate of patients.
Impact of Prolonged Face Mask Wearing On Tear Break-Up Time and Dry Eye Symptoms in Health Care Professionals
Authors: Baris Mine Esen , Yilmaz Suzan Guven , Palamar Melis 
Published: September 2021

Abstract
Purpose

To evaluate the impact of prolonged surgical face mask wearing on dry eye symptoms and tear film break-up time (T-BUT) in health care professionals.
Materials and Methods

A total of 33 health care professionals were included in this cross sectional, prospective study. T-BUT measurements were performed twice for all participants in the morning (8 am) and in the afternoon (5 pm) in addition to a complete ophthalmological examination. The subjects also filled-in the ocular surface disease index (OSDI) questionnaire twice, before and after wearing the face mask, on the same day.
Results

Sixty six eyes of 33 participants (17 female and 16 male) were evaluated. The mean age was 33.6 ± 7.55 (24–48) years and mean total duration with mask on between the two evaluations was 514 ± 12.5 (495–526) minutes. The mean T-BUT was 9.3 ± 1.0 (3–16) seconds at 8 am and 8.3 ± 1.5 (3–14) seconds at 5 pm (p = 0.01). The mean OSDI score was 20.1 ± 8.3 (0-68.75) at 8 am and 27.4 ± 10.4 (0-81.25) at 5 pm (p < 0.01).
Conclusion

Use of a surgical mask for the entire work day was seen to worsen T-BUT and dry eye symptoms in healthy individuals. Ophthalmologists should be aware of possible worsening of condition in patients with dry eye with the prolonged use of face masks and consider modifications if necessary.
Global Burden of Cataract and Its Association With Socioeconomic Development Status, 1990-2019
Authors: Han Xiaotong , Zou Minjie , Liu Zhenzhen , Sun Yi , Young Charlotte Aimee , Zheng Danying , Jin Guangming 
Published: September 2021

Abstract
Background: Cataract is the leading cause of blindness globally and more people will be at risk for this common cause of vision loss in the coming years.To estimate the disease burden of cataract and evaluate contributions of various risk factors to cataract-associated disability-adjusted life years (DALYs).Methods: Prevalence of visual impairment due to cataract and disability-adjusted life years of cataract were extracted from the Global Burden of Disease (GBD) study 2019 to explore time trends and annual changes. Regional and country-level socioeconomic indexes were acquired from open databases, and stepwise multiple linear regression was used to evaluate associations between age-standardized rate of DALYs of cataract and potential predictors.Results: Global Prevalence rate of visual impairment due to cataract rose by 58.45% from 791.4 per 100,000 population (95%CI: 705.2 to 890.0 per 100,000 population) to 1253.9 per 100,000 population 95%CI: 1103.3 to 1417.7 per 100,000 population) in 2019 and DALYs rate of cataract rose by 32.18% from 65.3 per 100,000 population (95%CI: 46.4 to 88.2 per 100,000 population) in 1990 to 86.3 per 100,000 population (95%CI: 61.5 to 116.4 per 100,000 population) in 2019.Stepwise multiple linear regression model showed that higher refractive error prevalence (β=0.036, 95% CI: 0.022, 0.050, P<0.001), lower number of physicians per 10,000 population (β=-0.959, 95% CI: -1.685, -0.233, P=0.010) and lower level of HDI (β=-134.93, 95% CI: -209.84, -60.02, P=0.001) were associated with higher disease burden of cataract.Conclusions: Substantial increases in the prevalence of visual impairment and DALYs of cataract were observed from 1990 to 2019. Successful global initiatives targeting improving cataract surgical rate and quality, especially in regions with lower socioeconomic status, is a prerequisite to combating this growing burden of cataract in the aging society.
Epithelial-Mesenchymal Transformation Related Genomic Analysis Reveals Prognostic And Immunogenic Significance In Colorectal Cancer
Authors: Yin Yangyang , Liu Ying , Pan Yun , Yu Tianyu , Liu Bin , Deng Xianyu , Ma Bingwei , Yang Muqing , Li Jiyu 
Published: September 2021

Abstract
Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Epithelial-mesenchymal transition (EMT) has been viewed to play a vital role in immune regulation and treatment response shaping. EMT is associated with an invasive or metastatic phenotype in CRC and is also related to patient prognosis and treatment responsiveness. We aimed to explore an EMT gene panel with potential application in patient classification and precise treatment and assist clinicians to generate individualized immunotherapeutic strategies for CRC patients.Methods: TCGA, GEO, STRING, TRRUST, TragetScan, miRTarBase, miRDB, cBioPortal, StarBase databases were utilized in this study.Results: In this study, EMT factors were screened in three different ways(EMT factors, EMT-related pathways, EMT genotyping genes).And the prognosis-related modules were screened by the WGCNA method. Then, Cox single factor regression analysis was performed on the module hub gene, combined with multivariate Cox regression, the prognosis model was established, and the risk score of each sample was calculated. Then the samples were divided into high-risk samples and low-risk samples according to the risk score, and the differences in immune cell infiltration, mutation, CNV, clinical characteristics between high-risk and low-risk samples were compared. The risk model can effectively predict the prognosis of samples, which is verified by two external data, and it can also effectively predict the prognosis of CRC samples in the other two digestive tract cancers (liver cancer and gastric cancer) and has a good indication for the effect of chemotherapy treatment response and immunotherapy. Conclusion: The prognosis model can effectively predict the prognosis of samples and may be an effective tool for treatment guidance in CRC patients.
Dynein Light Chain LC8 Alleviates Nonalcoholic Steatohepatitis By Regulating Nuclear Factor κB Through Interference With IκBα Phosphorylation
Authors: Lee Gong-Rak , Lee Hye In , Kim Narae , Lee Jiae , Kwon Minjeong , Kang Ye Hee , Song Hyeong Ju , Yeo Chang-Yeol , Jeong Woojin 
Published: September 2021

Abstract
Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation and chronic inflammation in the liver. Although dynein light chain of 8 kDa (LC8) was identified previously as an inhibitor of nuclear factor kappa B (NF-κB), a key regulator of inflammation, its role in NASH remains unknown. In this study, we investigated whether LC8 can alleviate NASH using a mouse model of methionine and choline-deficient (MCD) diet–induced NASH and examined the underlying mechanism. LC8 transgenic (Tg) mice showed lower hepatic steatosis and less progression of NASH, including inflammation, oxidative stress, and hepatic fibrosis, compared to wild-type (WT) mice after consuming an MCD diet. The hepatic expression of lipogenic genes was lower, while that of lipolytic and mitochondrial genes was greater in LC8 Tg mice than WT mice, which might be associated with resistance of LC8 Tg mice to hepatic steatosis. Consumption of an MCD diet enhanced IκBα phosphorylation and subsequent p65 liberation from IκBα and nuclear translocation, resulting in induction of NF-κB targets, including pro-inflammatory cytokines and chemokines. However, these effects of MCD diet were reduced by LC8 overexpression. Taken together, these results suggest that LC8 alleviates MCD diet–induced NASH by inhibiting NF-κB through binding to IκBα to interfere with IκBα phosphorylation.
Can Tracking Mobility be used as a Public Health Tool Against COVID-19 Following the Expiration of Stay-at-Home Mandates?
Authors: Her Peter Hyunwuk , Saeed Sahar , Tram Khai Hoan , Bhatnagar Sahir 
Published: September 2021

Abstract
Considering the emergence of SARS-CoV-2 variants and low vaccine access and uptake, minimizing human interactions remains an effective strategy to mitigate the spread of SARS-CoV-2. Using a functional principal component analysis, we created a multidimensional mobility index (MI) using six metrics compiled by SafeGraph from all counties in Illinois, Ohio, Michigan and Indiana between January 1st to December 8, 2020. Changes in mobility were defined as a time-updated 7-day rolling average. Associations between our MI and COVID-19 cases were estimated using a quasi-Poisson hierarchical generalized additive model adjusted for population density and the COVID-19 community vulnerability index. Individual mobility metrics varied significantly by counties and by calendar time. More than 50% of the variability in the data was explained by the first principal component by each state, indicating good dimension reduction. While an individual metric of mobility was not associated with surges of COVID-19, our MI was independently associated with COVID-19 cases in all four states given varying time-lags. Following the expiration of stay-at-home orders, a single metric of mobility was not sensitive enough to capture the complexity of human interactions. Monitoring mobility can be an important public health tool, however, it should be modelled as a multidimensional construct.
Breast Cancer and Smell: Hints from Epigenetic and Functional Alteration of the Olfaction
Authors: Fessahaye Ghimja , Khalid Reem S , Mohamed Kamal-Hamad , Alsidiq Mohammad O.E , Khalid Amna , Mohamed Hiba S. , Ibrahim Muntaser E. 
Published: September 2021

Abstract
Purpose: Olfactory receptors are G protein coupled surface receptors (GPCRs) of which their ectopic expression is currently of mounting interest to the development and metastasis of malignancies. These genes having a direct contact with the environment may probably be stimulated by various factors which can bring about methylation aberrations, including DNA hypo and hyper-methylation. Here we gather clues from epigenetic and phenotypic data in order to further our understanding of the potential association of the olfaction with oncogenesis.Methods: Whole methylome dataset of breast cancer series generated by Illumina Infinium Human Methylation 450 Bead Chip was interrogated for differentially methylated genes and further subject to network analysis using various search tools. Analysis of putative phenotypic trait in olfaction function was performed using smell detection and smell identification tests and data was analyzed using Mann-Whitney test.Results: Sixty-eight differentially methylated ORs were enriched mainly on chromosomes 1q23, and 11p15, specifically 1q44 (P value 6.867e-20). Amongst the disease signatures of these hypomethylation events was breast cancer itself (P value 0.004437). Network analysis suggests the interaction of differentially hypo and hyper methylated olfactory receptor genes might be pivotal in stimulating several important biological pathways including circadian genes and pathways potentially associated with metastasis. Phenotypic smell test shows a generalized impairment of smell capability in breast cancer patients as compared to controls (Mann-Whitney Test P=0.0001), an effect that is independent of chemotherapyConclusions: The olfaction appears as a crucial element in carcinogenesis, evident by both phenotypic and genotypic (epigenetic) data in a well characterized breast cancer subset.
Bariatric Surgery in Super-Superobese Patients Maintains Metabolic Improvement Beyond The Failure in Expected Weight Loss.
Authors: Susmallian Sergio , Raziel Asnat , Babis Irena , Barnea Royi 
Published: September 2021

Abstract
Background
Extreme obesity leads to increased health risks and perioperative complications. The results of bariatric surgery in patients with super-super obesity (SSO) are presented in this study.
Methods
From April 2008 to August 2019, 60 patients with SSO underwent bariatric surgery. Their weight loss and surgical outcome were analyzed. The mean follow-up time was 7.2 years.
Results
At baseline, the mean age was 41.5 years old, the mean BMI was 63.8 kg/m2, 80% of the patients suffered from co-morbidities, and 23.33% were revisional surgeries. Weight loss continued for up to two years after surgery. The percentage of EBW lost at two years was 62.27%, from two to five years: 61.48%, from five to 10 years: 36.82% and after ten years it was 31.89%, the differences in weight change over the time is significative (P<.001). The mean BMI at last visit (Mean 7.2 years) was 45.1 kg/m2 and 48.33% of the patients failed to lose at least 50% of EBW. Patients with fatty liver, diabetes, sleep apnea and hyperlipidemia had a remission or improvement in more than 70% of the cases. There were 5% perioperative complications, one perioperative death (1.67%) and other patient died in a motor vehicle accident, overall mortality 3.33%.
Conclusion
In the long term, almost half of the patients failed to lose 50% of their EBW. However, the metabolic effects of bariatric surgery were maintained during the follow-up time with a high remission of comorbidities. Revisional bariatric surgery increased the risk of mortality.
Applying the Workload Indicators of Staffing Needs Method in Nursing Health Workforce Planning: Evidences from Four Hospitals in Vietnam
Authors: Thu Nguyen Thi Hoai , Hung Phung Thanh , Bui My Anh 
Published: September 2021

Abstract
Background: Vietnam has encountered difficulties in ensuring an adequate and equitable distribution of health workforce. The traditional staffing norms stated in the Circular 08/TT-BYT issued in 2007 based solely on population or institutional size and do not adequately take into consideration the variations of need such as population density, mortality and morbidity patterns. To address this problem, more rigorous approaches are needed to determine the number of personnel in health facilities. One such approach is Workload Indicators of Staffing Need (WISN) developed by the World Health Organization (WHO), a facility-based workforce planning method that assists managers in defining the responsibilities of different workforce categories and improving the appropriateness and efficiency of a staff mix. Methods: This study applied the WISN approach and was employed in 22 clinical departments at four hospitals in Vietnam between 2015 and 2018. 22 targeted group discussions involving nurses were conducted. Hospital personnel records have been retrieved. The data were analyzed according to WISN instructions. Results: Of the 22 departments, there was a shortage of 1 to 2 nurses in 10 departments, with WISN ratios ranging between 0.88 and 0.95. Only 01 clinical colleges at Can Tho Hospital lacked 05 nurses, facing a high workload with a WISN ratio of 0.78. Administrative time represented 20-40% of the total work time of a nurse. In comparison, nurses at Can Tho Hospital spent time on administration from 24 onwards. 5% to 41.7% of their working time while nurses at Thanh Hoa Hospital spent 21% to 33%. Conclusion: The application of the WISN enabled health managers to analyze the workload of nurses, calculate staffing needs, and thus effectively contribute to the workforce planning process. It is expected that the results of this research will encourage the use of the WISN tool in other hospitals and health facilities across the health system. At provincial and national levels, this study provides important evidence to help policy makers develop guidelines for personnel norms for health facilities in the context of limited resources, while the existing regulation is no longer appropriate.
Astrocytes donate mitochondria to increase glioblastoma tumorigenicity
Authors: Lathia Justin , Watson Dionysios , Bayik Defne , Williford Sarah , Lauko Adam , Zhou Yadi , Deshpande Gauravi , Seder Juliana , Mears Jason , Cheng Feixiong , Hjelmeland Anita 
Published: September 2021

Abstract
Glioblastoma (GBM), the most common primary brain cancer in adults1, is characterized by numerous cell-intrinsic/extrinsic interactions that drive tumorigenesis. In addition to cell-surface and secreted protein/extracellular vesicle interactions2,3, treatment resistance of GBM is augmented by the formation of cytoplasmic interconnections and junctions among tumor cells4. These cytoplasmic bridges among tumor cells enable exchange of cellular metabolites as well as mitochondria4, which can play a key role in metabolic function and cellular programming in GBM5,6. However, the contribution of the tumor microenvironment to mitochondrial transfer, as well as the downstream impact of mitochondrial transfer on GBM remains poorly characterized. Here we identified horizontal mitochondrial transfer from the tumor microenvironment as a mechanism that enhances tumorigenesis in glioblastoma. We found that this transfer occurs primarily from brain-resident cells, including astrocytes, and can be appreciated in vitro and in vivo through intercellular connections between GBM cells and non-malignant host cells. The acquisition of astrocyte mitochondria drives an overall enhancement of mitochondrial membrane potential and metabolic capacity, while increasing glioblastoma cell self-renewal and tumor-initiating capacity. Collectively, our findings demonstrate that astrocyte mitochondrial transfer augments the tumorigenic capacity of glioblastoma cells and reveals a previously unknown cell-cell communication mechanism that drives tumor growth. We anticipate our findings will open new research directions to decipher the molecular events linking mitochondria acquisition from non-malignant cells to increased tumorigenicity of recipient GBM cells. This line of research will lead to new therapeutic opportunities targeting this understudied phenomenon and its sequelae in GBM.