bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Bioinformatic Analysis of DNA Methylation and Immune Infiltration in Endometrial Cancer
Authors: dai fangfang , Deng Zhimin , Tan Wei , Yuan Mengqin , Yang Dongyong , Liu Shiyi , Zheng Yajing , Hu Min , Cheng Yanxiang 
Published: August 2021

Abstract
Background: Endometrial cancer greatly threatens the health of female. Emerging evidences demonstrated that the DNA methylation and immune infiltration involve in the occurrence and development of endometrial cancer. However, the mechanism and prognosis biomarker of endometrial cancer is unclear. In this study, we attempt to assess the DNA methylation and immune infiltration via bioinformatic analysis. Methods: The latest RNA-Seq, DNA methylation data and clinical data of endometrial cancer were download from the UCSC Xena dataset. The methylated driven genes were selected out, and then the risk score was obtained using the “MethylMix” and “corrplot” package. The correction of methylated genes and prognosis values, and the expression of above driven genes were identified by via survminer package and beeswarm package, respectively. Finally, the role of VTCN1 gene in immune infiltration was analyzed via CIBERSORT package. Results: In this study, 179 up-regulated genes, and 311 down-regulated genes are identified, which are related to the extracellular matrix organization, cell-cell junction, and cell adhesion molecular binding. Above them, 13 methylated driven genes were selected out. Meanwhile, it’s obvious that the expression of PGR and VTCN1 are lower in tumor group than that of in normal group. Conversely, VTCN1 gene expresses the opposite. high methylation & low expression of PGR and GYPC are positive correction with the prognosis, while the VTCN1 has the inverse relationship with the prognosis of endometrial cancer. More importantly, the hypomethylation of VTCN1 promoter leads to its high expression, which can cause tumor development by inhibiting CD8+T cell infiltration. Conclusions: In total, our study firstly reveals the mechanism of endometrial cancer combining DNA methylation and immune cell infiltration via integrated bioinformatic analysis. Besides, we found the pivotal prognosis biomarker for this disease. Our study may provide the potential targets for the diagnosis and prognosis of endometrial cancer.
Self-assembled Epitaxial Ferroelectric Oxide Nano-spring with Super-scalability
Authors: Dong Guohua , Hu Yue , Guo Changqing , Wu Haijun , Liu Haixia , Peng Ruobo , Xian Dan , Mao Qi , Dong Yongqi , Zhao Yanan , Peng Bin , Wang Zhiguang , Hu Zhongqiang , Zhang Junwei , Wang Xueyun , Hong Jiawang , Luo Zhenlin , Ren Wei , Ye Zuo-Guang , Jiang Zhuangde , Zhou Ziyao , Huang Houbing , Peng Yong , Liu Ming 
Published: August 2021

Abstract
Oxide nano-springs have attracted many research interests because of their anti-corrosion, high-temperature tolerance, oxidation resistance, and enhanced-mechanic-response from unique helix structures, enabling various nano-manipulators, nano-motors, nano-switches, sensors, and energy harvesters. However, preparing oxide nano-springs is a challenge for their intrinsic nature of lacking elasticity. Here, we developed an approach for preparing self-assembled, epitaxial, ferroelectric nano-springs with built-in strain due to the lattice mismatch in freestanding La0.7Sr0.3MnO3/BaTiO3 (LSMO/BTO) bilayer heterostructures. We find that these LSMO/BTO nano-springs can be extensively pulled or pushed up to their geometry limits back and forth without breaking, exhibiting super-scalability with full recovery capability. The phase-field simulations reveal that the excellent scalability originates from the continuous ferroelastic domain structures, resulting from twisting under co-existing axial and shear strains. In addition, the oxide hetero-structural springs exhibit strong resilience due to the limited plastic deformation nature and the built-in strain between the bilayers. This discovery provides an alternative way for preparing and operating functional oxide nano-springs that can be applied to various technologies.
The Use of Medical Cannabis in Pediatric Palliative Care: A Case Series
Authors: Divisic Antuan , Avagnina Irene , De Tommasi Valentina , Santini Anna , Brogelli Laura , Giacomelli Luca , Benini Franca 
Published: August 2021

Abstract
Background: Medical cannabis may be a useful tool for the management of treatment-resistant epilepsy and chronic pain, which affect many patients who are in PPC; however, little evidence is available in this setting. Case presentation: We aimed to describe a clinical experience, in a setting where high-level evidence may not be obtained. We report our clinical experience in a pediatric palliative care department in Italy. Caregivers reported changes in intensity and frequency of pain and epilepsy events. Six patients received a titrated plant extract of cannabis sativa for 1 year. Only mild and transient adverse events occurred. All patients experienced seizures during the pre-treatment observation period, and obtained a reduction in seizure frequency, although with variable extent while receiving cannabis. In addition, a benefit on pain was observed, based on the caregiver’s evaluation, and a reduction of analgesic use. Conclusion: Our experience suggests that a titrated plant extract preparation of medical cannabis may be useful to control treatment-resistant pain and epilepsy in PPC patients.
Analysis of the COVID-19 Pandemic: Lessons for a Contextualized and Effective Response to Public Health Emergencies
Authors: Assefa Yibeltal , Gilks Charles F , Reid Simon , de Pas Remco van , Gete Dereje Gedle , Damme Wim Van 
Published: August 2021

Abstract
Background: The pandemic of Coronavirus Disease 2019 (COVID-19) is a timely reminder of the nature and impact of Public Health Emergencies of International Concern. As of 27 May 2021, there were over 169 million cases and over 3.5 million deaths notified since the start of the pandemic. The COVID-19 pandemic takes variable shapes and forms in different regions and countries of the world. The objective of this study is to analyse the COVID-19 pandemic so that lessons can be learned towards an effective public health emergency response. Methods: We conducted a mixed-methods study to understand the heterogeneity of the COVID-19 pandemic. Correlation analysis and scatter plot were employed for the quantitative data. We used Spearman’s correlation analysis. Thematic analysis was conducted on the qualitative data to explain the findings from the quantitative data.Results: We have found that regions and countries with high human development index are most affected by COVID-19 due to international connectedness and mobility of their population related to trade and tourism, and their vulnerability related to older populations and higher rates of non-communicable diseases. The pattern of the pandemic is also variable among high- and middle-income countries due to differences in the governance of the pandemic, fragmentation of health systems, and socio-economic inequities. Conclusion: The aspiration towards a healthier and safer society requires that countries develop and implement a coherent and context-specific national strategy, improve governance of public health emergencies, build the capacity of their (public) health systems, minimize fragmentation, and tackle upstream structural issues, including socio-economic inequities. This is possible through a primary health care approach, which ensures provision of universal and equitable promotive, preventive and curative services, through whole-of-government and whole-of-society approaches.
Viral and Immunological Characteristics of COVID-19 Vaccine Breakthrough Infections
Authors: Arashiro Takeshi , Kanno Takayuki , Miyamoto Sho , Saito Shinji , Moriyama Saya , Sekizuka Tsuyoshi , Kanou Kazuhiko , Stucky Ashley , Iida Shun , Ainai Akira , Katano Harutaka , Kageyama Tsutomu , Hanaoka Nozomu , Saito Masumichi , Fujimoto Tsuguto , Kawana-Tachikawa Ai , Matano Tetsuro , Kobayashi Yusuke , Arima Yuzo , Ota Masayuki , Kasamatsu Ayu , Oba Kunihiro , Nakamura-Uchiyama Fukumi , Shimizu Hidefumi , Saito Tomoya , Takeshita Nozomi , Ohnishi Makoto , Wakita Takaji , Suzuki Motoi , Kuroda Makoto , Takahashi Yoshimasa , Suzuki Tadaki 
Published: August 2021

Abstract
Since little is known about viral and host characteristics of breakthrough infections after COVID-19 vaccination, a nationwide investigation of breakthrough cases was initiated in Japan. 130 cases (90%+ received mRNA vaccines) were reported with respiratory specimens in 117 cases and sera in 68 cases. A subset of cases shed infectious virus regardless of symptom presence or viral lineages. Viral lineages for breakthrough infections matched both temporally and spatially with the circulating lineages in Japan with no novel mutations in spike receptor binding domain that may have escaped from vaccine-induced immunity were found. Anti-spike/neutralizing antibodies of breakthrough infections in the acute phase owing to vaccine-induced immunity were significantly higher than those from unvaccinated convalescent individuals but were comparable to vaccinated uninfected individuals, and followed by boosting in the convalescent phase. Symptomatic cases had low anti-spike/neutralizing antibodies in the acute phase with robust boosting in the convalescent phase, suggesting the presence of serological correlate for symptom development in COVID-19 vaccine breakthrough infections.
A blood marker for Parkinson’s Disease: Neuronal exosome-derived α-synuclein
Authors: Kluge Annika , Bunk Josina , Schaeffer Eva , Drobny Alice , Xiang Wei , Knacke Henrike , Bub Simon , Lückstädt Wiebke , Arnold Philipp , Lucius Ralph , Berg Daniela , Zunke Friederike 
Published: August 2021

Abstract
To date, no reliable clinically applicable biomarker has been established for Parkinson’s disease (PD). Our results indicate that a long hoped blood test for Parkinson’s disease may be realized. We here assess the potential of pathological α-synuclein originating from neuron-derived exosomes from blood plasma as a possible biomarker. Following the isolation of neuron-derived exosomes from plasma of PD patients and non-PD individuals immunoblot analyses were performed to detect exosomal α-synuclein. Under native conditions significantly increased signals of disease-associated α-synuclein forms in neuron-derived exosomes were measured in all individuals with PD and clearly distinguished PD samples from controls. By performing a protein misfolding cyclic amplification assay these aggregates could be amplified and seeding could be demonstrated. Moreover, the aggregates exhibited β-sheet-rich structures and showed a fibrillary appearance. Our study demonstrates that the detection of pathological α-synuclein conformers from neuron-derived exosomes from plasma samples has the potential of a promising blood-biomarker of PD.
Propaganda and Education Can Improve the Quality of Life of Patients With Urologic Cancer Before Surgery
Authors: Li Yajian , Huang Guanghua , Du Yanhua , Chen Xueer , Cheng Wenjuan , Wen Jiajie , Shi Hongzhe , Xing Nianzeng 
Published: August 2021

Abstract
Background: Distributing propaganda materials is a way of doctor-patient communication. Our study aims to demonstrate its influence on patients' quality of life with newly diagnosed urologic cancer before surgery.Methods: Patients with urologic cancer were retrospectively enrolled from April 2020 to March 2021 in the Cancer Hospital of Chinese Academy of Medical Sciences. The propaganda materials were written and published by our center and distributed after admission. The quality of life was assessed by EORTC QLQ-C30 version 3.0 on the day of admission and after patients read the materials.Results: A total of 180 patients were included. Most of them were male and with renal cancer. Sleep disturbance (p=0.002), appetite loss (p=0.013), fatigue (p=0.002) and physical function (p=0.006) showed statistically significant improvement after the intervention. In subgroup analysis, the changes of sleep disturbance, fatigue and physical function remained significant among patients with renal cancer. Several items remained significant among younger patients(≤57 years old).Conclusions: Distributing proper propaganda materials could exert significant impacts among patients with urologic cancer. Patients with renal cancer and younger patients might be more likely to benefit from that.
Age-dependent Oral Manifestations of Neurofibromatosis Type 1: A Case-control Study
Authors: Thota Eshwar , Veeravalli John Jim’s , Manchala Sai Krishna , Lakkepuram Bhargavi Priya , Kodapanen Jayasurya , Wang Li-Tzu , Ma Kevin Sheng-Kai 
Published: August 2021

Abstract
Introduction: Craniofacial manifestations of neurofibromatosis type 1 (NF1) are considered as a result of tumor compression. We sought to determine age-dependent salivary changes, carious, and periodontal complications in NF1 patients without tumors in the oral cavity.Objective and methods: Eleven NF1 patients without tumors in the oral cavity and 29 matched controls without NF1 were enrolled in this case-control study. Demographic information, medical history, and data of intraoral examinations, including the Decayed, Missing, and Filled Teeth (DMFT) scores and Russel’s periodontal index (PI), were recorded. The functional salivary analysis was performed for sialometry, salivary pH values, and amylase activity. Ingenuity Systems Pathway Analysis (IPA) was conducted to identify mutually activated pathways for NF1-associated oral complications.Results: NF1 patients were associated with periodontitis (OR=1.40, 95% CI=1.06-1.73, P = 0.04), gingivitis (OR=1.55, 95% CI=1.09-2.01, P = 0.0002), and decreased salivary flow rate (OR=1.40, 95% CI=1.05-1.76, P = 0.005). Periodontal destruction, salivary changes, and dental caries in NF1 patients were age dependent. Subgroup analyses based on age stratification suggested that salivary flow rates and salivary amylase activity were significantly lower among NF1 patients aged over 20 years and that salivary pH values, PI and DMFT scores were higher among NF1- controls aged over 20. All oral complications were not significantly presented among NF1 patients aged below 20. IPA analyses suggested that cellular mechanisms underlying NF1-associated oral complications involved chronic inflammatory pathways as well as fibrosis signalling pathway.Conclusion: NF1 patients without tumors in the oral cavity presented with a higher prevalence of age-dependent oral complications, including periodontal destruction and salivary gland dysfunction, which were associated with chronic inflammatory pathogenesis.
The Role of pSOFA Score Combined with C-Reactive Protein and Procalcitonin in the Prognostic Evaluation of Children with Sepsis: A Single-Center Cross-Sectional Study
Authors: Zhou Bin , Huang Yuge , Zhong Mianling , Zeng Cizheng , Wu Jiayuan 
Published: August 2021

Abstract
Background: The pediatric sequential organ dysfunction（pSOFA）score, C-reactive protein（CRP）and procalcitonin（PCT）play an important role in the prognosis assessment of children with sepsis. This study explores the value of their combined application, so as to provide a more comprehensive diagnosis method for the early diagnosis and prognosis evaluation of pediatric sepsis.Methods: A retrospective cross-sectional study method was used to collect and analyze the clinical data of 289 children who were hospitalized and diagnosed with sepsis in the Pediatric Intensive Care Unit (PICU) of the Affiliated Hospital of Guangdong Medical University from August 2018 to August 2019. The 28-day survival outcome was divided into survival group and death group. Compare the differences in various physiological and laboratory data of the two groups of children within the first 24 hours after admission to PICU; Use binary logistic regression to analyze high-risk factors that affect the prognosis of children with sepsis; The receiver operating characteristic curve (ROC) was drawn, and the area under the ROC curve (AUC) was used to evaluate the role of pSOFA score combined with CRP and PCT in the early diagnosis and prognosis evaluation of children with sepsis.Results: A total of 289 children were included in the study, 254 cases (87.9%) in the survival group and 35 cases (12.1%) in the death group; There were statistically significant differences between the two groups of children in age, whether to continuously pump vasoactive drugs, mechanical ventilation time, Glasgow coma score, gastrointestinal function, and serum PCT concentration (all P<0.05);Binary logistic regression showed that: pSOFA score and continuous intravenous pumping of vasoactive drugs are high-risk factors for poor prognosis in children with sepsis (P<0.05);The AUC of CRP and PCT in predicting the death of children with sepsis were 0.547 (95%CI: 0.488-0.606), 0.667 (95%CI: 0.609-0.721); and pSOFA+CRP, pSOFA+PCT and pSOFA scores The AUC for predicting the death of children with sepsis was 0.947 (95%CI: 0.914-0.970), and the difference was not statistically significant (P>0.05);Conclusions: The pSOFA score is of high value for the prognostic evaluation of children with sepsis; but the pSOFA score combined with CRP and PCT can not improve the prognostic evaluation ability of children with sepsis.
The Time to Initiate Trophic Feeding and Its Predictors Among Preterm Neonate Admitted to Neonatal Intensive Care Unit, Multicenter Study, Northwest Ethiopia, 2020.
Authors: Adimasu Daniel , Tafere Yilikal , Eshetie Teodros , Endalew Bekalu , Abebaw Ermias , Adimasu Mekonen 
Published: August 2021

Abstract
Background: Trophic feeding is a small volume, hypo-caloric feeding, gut priming or minimal enteral feeding acclimate the immature gut of enteral fasting preterm neonates. Delayed starting of trophic feeding had resulted in short and long-term physical and neurological sequels. The current study aimed to assess time to initiate trophic feeding and its predictors among preterm neonates admitted in the neonatal intensive care unit of Debre Markos, Felege Hiwot, and Tibebe Ghion comprehensive specialized hospitals.Methods: An institutional-based prospective follow-up study was conducted among 210 neonates. The data were collected with interview and chart review, entered into Epi data 3.1 and exported to Stata 14.1 for analysis. Multivariable Cox regression models were fitted to identify predictors of time to initiate trophic feeding. Result: A total of 210 neonates were followed for 10136 person-hours of risk time and 191 (90.95%) of neonates were started trophic feeding. The overall incidence of starting trophic feeding was 2 per 100 (95% CI: 2, 2.2) person-hours observations. The median survival time was 42 hours (95% CI: 36, 48). APGAR- score at first minute <7 (AHR: 0.6, 95% CI: 0.44, 0.82), gestational age of <34 weeks (AHR: 0.69, 95% CI: 0.5, 0.94), presence of respiratory distress syndrome (AHR: 0.5, 95% CI: 0.36, 0.68), presence of hemodynamic instability (AHR: 0.37, 95% CI: 0.24, 0.57), presence of perinatal asphyxia (AHR: 0.63, 95% CI: 0.44, 0.89), cesarean section delivery (AHR: 0.63, 95% CI: 0.44, 89) and being delivered within the study hospitals (AHR: 0.54, 95% CI: 0.39, 0.74) were found to be statistically significant predictors of time to initiate trophic feeding.Conclusion: There was a significant delay to initiate trophic feeding in the studied hospitals. Gestational age of below 34 weeks, APGAR-score of less than seven, out-born delivery, cesarean delivery, presence of respiratory distress syndrome; perinatal asphyxia, and hemodynamic instability were predictors of delay in starting of trophic feeding. Standardized feeding guideline has to be implemented to overcome delays in enteral feeding initiation.
N6-methyladenosine-mediated CELF2 Regulates CD44 Alternative Splicing Affecting Tumorigenesis via ERAD Pathway in Pancreatic Cancer
Authors: Lai Shihui , Wang Yan , Li Ting , Dong Yihong , Lin Yihao , Wang Liang , Zhang Xiang , Weng Shangeng , Lin Chengjie 
Published: August 2021

Abstract
Background: Alternative splicing (AS) of genes has been found to affect gene stability, and its abnormal regulation can lead to tumorigenesis. CELF2 is a vital splicing factor to participate in mRNA alternative splicing. Its downregulation has been confirmed to promote the occurrence and development of pancreatic cancer (PC). However, the regulatory role and mechanisms in PC has not been elucidated.Methods: 80 patients diagnosed with PC were included in this study. The relationhip between CELF2 expression and clinicopathological characteristics was analyed. RNA immunoprecipitation qRT-PCR and RNA pull-down experiments were performed to confirm the potential mechanisms of CELF2 abnormal expression in PC. AS model of PC was established by TCGA database. Functional experiments in vitro and in vivo were conduced to reveal the effects of CELF2 or CD44 on PC cells proliferation, migration and invasion. Transcriptomic analysis was conducted to reveal the mechanism of CELF2-mediated CD44 AS in PC. Results: CELF2 was downregulated in PC tissues, which affected tumor TNM stage and tumor size, and low expression of CELF2 indicated a poor prognosis of PC. In vivo and in vitro experiments showed that abnormal expression of CELF2 affected the stemness, apoptosis, and proliferation of PC cells. Furthmore, we also found that CELF2 was targeted by ALKBH5 for m6A modification, leading to CELF2 degradation by YTHDF2. Bioinformatic analysis of AS model based on the TCGA database indicated that CELF2 could target CD44 to form different spliceosomes, thereby affecting the biological behavior of PC cells. The conversion of CD44s to CD44V is the key to tumorigenesis. Transcriptomic analysis was conducted to reveal the mechanism of CELF2-mediated CD44 AS in PC. We found that CELF2-mediated splicing of CD44 led to changes in the level of endoplasmic reticulum stress, further regulating the endoplasmic reticulum-associated degradation (ERAD) signaling pathway, thereby affecting apoptosis and cell stemness. In addition, ERAD signaling pathway inhibitor, EerI, could effectively reverse the effect of CD44 on tumors. Conclusions: This study indicates that CELF2 promotes AS of CD44, affecting the ERAD pathway and enhence the biological behavior of PC cells. CELF2 is expected to be a new target for targeted-drug development
Understanding the Dynamics of SARS-CoV-2 Variants of Concern in Ontario, Canada: A Case Study
Authors: Layton Anita , Sadria Mehrshad 
Published: August 2021

Abstract
A year after the initial wild-type Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) strains began their devastation of the world, they were supplanted by new variants of concern (VOC). In Ontario, Canada, the wild type was overtaken first by the Alpha/B1.1.17 variant, and then by the Delta/B.1.617 variant. The principal objective of the present study is to develop and apply a much expanded Susceptible-Infection-Recovered-type model to better understand the spread of multiple VOC, and assess the effectiveness of vaccination and non-pharmaceutical interventions (NPI). The model represents competition among VOC, and reveals their mutual inhibitory effects. By separately tracking asymptomatic and symptomatic infections, model simulations identify a significant role of vaccine breakthrough in the spread of Delta. Furthermore, the severity of a Delta outbreak depends not only on the NPI and vaccination rate but also on the vaccine types. Alarmingly, despite Ontario’s existing NPI and relatively successful vaccine rollout, a future, more dangerous VOC could potentially infect a significant fraction of the province’s population and overwhelm the health care system. To stop that VOC, the province may need the simultaneous and rapid deployment of a third booster vaccine and stringent NPI.