bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nomogram For Predicting HCC Patients’ Overall Survival Based On Double Hub Genes and Other Clinical Risk Factors.
Authors: Chen Jianfei , Liu Zhong-liang , Su Song , Fan Jun , Tan Shun-de , Li Bo , Yang Xiao-li 
Published: November 2021

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the series malignant aggressive disease which shows elusive biological behavior and terrible prognosis. It is inadequate for the single evaluation system such as tumor-node-metastasis (TNM) staging system to predict the overall survival (OS) in HCC patients. Here, we conducted this study to identify prognosis-related genes, so as to form a reliable prognostic assessment model.Results: From three datasets in the GEO database, we identified two hub genes cytoskeleton associated protein 2 (CKAP2) and forkhead box M1 (FOXM1) among 348 differentially expressed genes (DGEs) that were differentially expressed between HCC and normal samples. The function analysis of those DEGs are enriched in cell division process (e.g., mitotic nuclear division, nuclear chromosome segregation) and metabolic process (e.g., organic acid catabolic process). Then, we established a two-gene model, that extremely distinguished the population at risk of liver cancer to high-risk and low-risk and was even viable in the TNM stage i-ii and iii-iv, vascular invasion and non-invasion subgroups (all P<0.05). Next, a nomogram was set out combined with the two hub genes and clinical risk factors, and the predictive power of the nomogram performed more outstanding than the gene expression or clinical parameters alone.Conclusions: Our two-gene-based evaluation system effectively filtered out the high-risk HCC patients, and could potentially be used for clinical decision-making and individualized management of particular HCC patients.
MPP2 Interacts With SK2 Rescue The Excitability of Glutamatergic Neurons in The BLA and Facilitate The Extinction of Conditioned Fear in Mice
Authors: Peng Xiao-Han , Chen Pan-Pan , Zhang Yang , Wu Ke , Ji Ningning , Gao Jing-hua , Zhang Yong-mei , Xu Tie , Hua Rong , Wang Hui 
Published: November 2021

Abstract
Posttraumatic stress disorder (PTSD) and other anxiety disorders stem from dysregulated fear memory in which the basolateral amygdala (BLA) plays an integral role. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergic neurons. However, definitive evidence for the involvement of the SK2 channel in the BLA in fear extinction is lacking. Here, we discovered that fear conditioning decreased the levers of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levers of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane palmitoylated protein 2 (MPP2). Collectively, our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of fear memory. These findings expand our understanding of the neurobiological mechanism of PTSD and provide a new direction for PTSD treatment.
Debt for nature swaps – which nature, how much and who pays?
Authors: Nedophil Christoph , Yue Mengdi , Hughes Alice 
Published: November 2021

Abstract
Financially viable means to conserve biodiversity are urgently needed. We analyze how debt-for-nature swaps could conserve currently unprotected biodiversity priority-areas for six biomes in 67 countries under the debt service suspension initiative related to COVID19. Using novel methods and data, we find that the 67 countries hold over 22% of global priority-areas, yet 82.96% is unprotected. For 35 of the 67 countries, swapping 0.1% of public debt could conserve 100% of unprotected priority-areas. By swapping 5.09% of these countries’ total public debt (USD26.5 billion) in a pooled swap, 100% of priority-areas could be protected across the countries. Management costs could partly be covered through re-routed interest payments within the countries, with further annual funding of USD0.5-3.5 billion required. One-Sentence Summary: We develop a framework for efficient application of debt-for-nature swaps to maximize biodiversity conservation.
Identification KCNE4 and DNASE1L3 for Prognostic Utility in Colorectal Cancer: A Bioinformatics Analysis
Authors: Liu Deming , Xiang Xue , Chen Yaqiong , Jiao Yajun , Wang Liuli , Wang Yongfeng , Ma Haizhong , Ma Shixun , Cai Hui , Guo Tiankang 
Published: November 2021

Abstract
Objective: Immunotherapy has improved the prognosis of cancer patients who did not benefit from conventional treatment and decreased mortality, which has become an effective treatment for multiple carcinomas in their advanced stages. Patients with colorectal cancer (CRC) were mostly in the state of mismatch repair-proficient or microsatellite stability, with limited benefit in immunotherapy. Hence, immunotherapy strategies for CRC still need to be explored continuously. Methods: Based on comprehensive analysis of the immune infiltration associated genes in the Cancer Genome Atlas (TCGA) database and differential genes for the progression and metastasis of CRC in the Gene Expression Omnibus (GEO) database, as well as validation analysis on several online databases, we obtained two genes (KCNE4 and DNASE1L3) as novel immune-related molecules for CRC. Results: High expression of KCNE4 and DNASE1L3 were significantly correlated with CRC progression and prognosis, and were strongly associated with the infiltration of different types of macrophages in the CRC tumor microenvironment. In addition, we analysed the guidance value of KCNE4 and DNASE1L3 in anti-PD-1 therapy using data from the IMvigor210 group, and predicted the significant value of KCNE4 and DNASE1L3 in CRC immunotherapy by analyzing the correlation of KCNE4 and DNASE1L3 with the expression of CRC immune checkpoint markers. Conclusions: We hypothesized that DNASE1L3 and KCNE4 would be potential prognostic biomarkers and predictors of immunotherapy in CRC. Our results may serve as an indication of survival prognosis and provide a new assessment indicator for the choice of immunotherapy for CRC patients.
Neonatal Mortality is Modulated by Gestational Age, Birthweight and Fetal Heart Rate Abnormalities in the Low Resource Setting in Tanzania – a Five Year Review 2015-2019
Authors: Shayo Aisa , Mlay Pendo , Ahn Emily , Kidanto Hussein , Espiritu Michael , Perlman Jeffrey M. 
Published: November 2021

Abstract
Background

Neonatal mortality (NM) remains a significant problem in low resource settings. Birth asphyxia (BA) and prematurity contribute significantly to NM. The study objectives were to determine first, the overall NM as well as yearly neonatal mortality rate from 2015 to 2019. Second, the impact of decreasing GA (<37 weeks) and BW (<2500 grams) on NM. Third, the contribution of intrapartum and delivery room (DR) factors and in particular fetal heart rate abnormalities (FHRT) on NM <7 days.
Methods

Retrospective cohort study. Labor and delivery room data were obtained from 2015 to 2019 and included BW, GA, fetal heart rate (FHRT) abnormalities, bag mask ventilation (BMV) during resuscitation, initial temperature, antenatal steroids use. Outcome was binary i.e. either death < 7 days or survival. Analysis included t tests, odds ratios (OR) and multiple logistic regression
Results

The overall neonatal mortality rate was 18/1000 livebirths over the five years. NM was significantly higher for newborns <37 versus ≥37 weeks, OR 10.5 (p<0.0001) and BW <2500 versus ≥2500g OR 9.9 (p<0.0001). For infants <1000g / <28 weeks, the neonatal mortality rate was ~ 588/1000 livebirths. Variables associated with NM included BW - odds of death decreased by 0.55 for every 500g increase in weight, by 0.89 for every week increase in GA, NM increased 6.8-fold with BMV, 2.6-fold with abnormal FHRT, 2.2 fold with no antenatal corticosteroid (ACS), 2.6-fold with moderate hypothermia (all <0.0001).
Conclusion

NM rates was predominantly modulated by decreasing BW and GA, with smaller/ less mature newborns 10-fold more likely to die. NM in term newborns is strongly associated with FHRT abnormalities and when coupled with respiratory depression suggests BA. In smaller newborns, lack of ACS and moderate hypothermia were additional contributing factors. A composite perinatal approach is essential to achieve a sustained reduction in NM.
Factors Influencing Intention to Use Intrauterine Device Among Family Planning Clients in Southwestern Ethiopia
Authors: Amenu Demisew , Wakjira Tekle , Kebede Alemi , Asefa Zerihun , Tadele Afework 
Published: November 2021

Abstract
Background: Intrauterine devices are the second most widely used modern family planning methods in the world. In Ethiopia, only 2% of married women use intrauterine device. Therefore, the aim of this study is to determine factors associated with the intention to use the intrauterine device in southwest, Ethiopia.Methods: A facility-based cross-sectional design was employed to collect data from 784 women using a structured questionnaire. Data were collected from October-November,2020. Data were managed using Kobo Collect v1.25.1 and Stata version 16.0 was used for analysis. A multivariable logistic regression was employed.Results: The prevalence of intention to use intrauterine device in this study was 30%. Having an intrauterine devices information (AOR=2.28(1.63-3.20)), being highest wealth status 1.76 (AOR=1.76(1.07-2.95)), and being able to read and write (AOR = 3.60; 95% CI: 1.59-7.89) were found to be significant factors influencing women’s intention to use an intrauterine device. The most common reasons for not having an intention to use were fear of side effects, lack of knowledge, and husband disapproval.Conclusion: An intention to use an intrauterine device was low. Public health interventions should provide an information focusing on the cited resaons reaching all the community in need, and give priority for women who unable read and write, and lowest wealth status. Further interventional studies were recommended to determine effective interventions to increase women’s intention to use intrauterine device.
The Effects of PCSK9 and Apolipoprotein E Functional Gene Variations On Hypercholesterolemia and Clinical Phenotype in Restenosis Patients After Percutaneous Coronary Angioplasty
Authors: Ozkara Gulcin , Javadova Zahra , Aslan Ezgi , Ceviz A.Begum , Candan Gonca , Ser Ozgur Selim , Kilicarslan Onur , Kucukhuseyin Ozlem , Bostan Cem , Yildiz Ahmet , Ozturk Oguz , Aydogan Hulya Yilmaz 
Published: November 2021

Abstract
Background: In-stent-restenosis is a case restricting the benefits of percutaneous-transluminal coronary angioplasty (PTCA). PCSK9 controls LDLR levels, and variations in PCSK9, ApoE and ApoER genes may affect the development of restenosis. The aim of this study was to assess the effects of genetic variants on restenosis risk after PTCA.Methods and Results: The study groups include 109 CAD-patients with restenosis (S-CAD) and 82 CAD-patients without restenosis (open-stent,OS-CAD). SNPs were analyzed by RT- PCR. PCSK9 levels were detected via ELISA method. The distributions of ApoE Epsilon, APOER (rs5174), PCSK9 rs2182833 and rs11206510 polymorphisms were found similar between study groups while the frequency of the PCSK9 E670G G allele in S-CAD group was found significantly higher than OS-CAD patients (p= 0.015). No difference was found between study groups in terms of the serum levels of PCSK9. LDL-C was found lower and HDL-C was found higher in OS-CAD group comparing with S-CAD group (p=0.042, p=0.008, respectively). Frequencies of Type 2 DM and hyperlipidemia were also found higher in S-CAD group than OS-CAD group (p=0.007, p=0.001, respectively) while EF% was found lower in S-CAD group than OS-CAD group (p=0.007).Conclusions: Our findings indicate that although ApoE Epsilon, APOER (rs5174), PCSK9 rs2182833, rs11206510 and E670G polymorphisms has no effect on serum PCSK9 levels, PCSK9-rs505151G-allele and hyperlipidemia may be risk factors in the development of restenosis.
An Integrative Pan-Cancer Analysis Revealing ETS1 as an Oncogenic Immune Protein in Tumor Microenvironment
Authors: Wu zixuan , Huang Xuyan , Cai Min-jie , Huang Peidong 
Published: November 2021

Abstract
BackgroundPrevious research revealed that ETS Proto-Oncogene 1, Transcription Factor (ETS1) might be useful in cancer immunotherapy. However, the processes underlying its therapeutic potential have yet to be thoroughly investigated. The goal of this work was to look into the association between ETS1 expression and immunity and depict its prognostic landscape in pan-cancer. MethodsThe TCGA provides raw data on 33 different types of cancer. GEO gave GSE67501, GSE78220, and IMvigor210. In addition, we looked at ETS1's genetic changes, expression patterns, and survival studies. The researchers investigated the links between ETS1 and the TME and its linkage to immunological processes/elements and the major histocompatibility complex better to understand the importance of ETS1 in cancer immunotherapy. Meanwhile, three distinct immunotherapeutic cohorts were employed to study the relationship between ETS1 and immunotherapeutic response. Finally, PPI analysis and functional gene enrichment were performed using GSEA. ResultsETS1 expression was shown to be higher in tumor tissue on average. Elevated ETS1 expression has been connected to a worse clinical outcome in patients with OS. ETS1 has been linked to immune cell infiltration, immunological modulators, and immunotherapeutic markers. Furthermore, increased ETS1 expression has been connected to immune-related pathways. However, there was no statistically significant link found between ETS1 and immunotherapeutic response. ConclusionsETS1 might be a biomarker for immune infiltration and poor cancer prognosis. It is possible that treatment targets should be researched further.
Oral Allergy Syndrome Caused by Japanese Radish: A Case Report
Authors: Uesugi Atsushi , Tsushima Fumihiko , Miyamoto Youji , Harada Hiroyuki 
Published: November 2021

Abstract
Background:Oral allergy syndrome (OAS) is a type of food allergy that manifests as hypersensitivity symptoms of the oropharyngeal mucosa on ingestion of specific foods with oral findings resembling herpetic gingivostomatitis. Symptoms can also appear in parts other than the oral cavity. There are a few reports of OAS caused by consuming radishes in the literature.Case presentation:A 31-year-old male presented to our department with stomatitis and pharyngeal pain. The patient did not have a history of allergy, and herpetic gingivostomatitis was suspected. He was admitted to the emergency room of our hospital after complaining of oral and epigastric pain a few days later. On admission, symptoms noted were similar to those when he first visited our department. After detailed history taking, he reported consuming raw Japanese radish frequently, which gave rise to his symptoms. Radish was strongly suspected as the causative allergen. The skin prick test result was positive, confirming the diagnosis of OAS.Conclusions:OAS can be diagnosed easily once the food causing symptoms is identified. However, guiding the diagnosis can be challenging if the patient is unaware of food allergies. Upon encountering widespread erosion in the oral cavity, it is essential to consider OAS as the possible cause.
Developing Evaluation Criteria for Competency-Based Curriculum in Medical Colleges
Authors: Lee So Young , Lee Seung-Hee , Shin Jwa-Seop , Kim Jooah , Yoon Hyun Bae 
Published: November 2021

Abstract
Background
The present study was conducted to examine the operation status of the Competency-Based Curriculum (CBC), which has become the main curriculum in the medical schools in Korea, and prepare valid evaluation criteria consented by experts to make improvements. The evaluation criteria were derived based on a model built by combining the Context, Input, Process and Product (CIPP) evaluation model and the Kirkpatrick evaluation model, which are representative educational evaluation models.

Methods
Firstly, literature survey was performed and a semi-structured interview was conducted with 5 experts to develop a draft of the evaluation criteria. To verify the validity of the draft of the developed evaluation criteria, two surveys based on the modified Delphi methodology were conducted with a panel consisting of 20 experts.

Results
Based on the literature survey and the expert interview, a draft of the evaluation criteria was derived, including 5 evaluation areas, 18 evaluation items and 58 evaluation indicators. Two Delphi surveys were conducted to validate the evaluation criteria. The evaluation criteria that showed a relatively low content validity ratio (CVR) were corrected and complemented by reflecting the experts’ opinions to finally derive 5 evaluation areas, 16 evaluation items and 51 evaluation indicators.

Conclusions
The significance of the present study is that an evaluation model and its evaluation criteria suitable for the curriculums of the medical schools in Korea were developed with the consensus of the experts. The preparation of valid evaluation criteria will open up the possibility of improving the evaluation in medical schools, contributing to the improvement of the educational quality and the continued quality improvement of medical education.
WITHDRAWN: Use of a Novel Multi-View Image-Based Motion Analysis System in the Field of Sports
Authors: Lee Nam-Gi , Ahn Jung-Hoon , Lim Woo-Taek 
Published: November 2021

Abstract
Background: Sports-related injuries are the most common in the lower extremities among physical regions, and overall injury rates were higher among males and persons aged 5–24 years. To evaluate impaired functional performance in sports training facilities and sports, a marker-less motion analysis system that can measure joint kinematics in bright indoor and outdoor environments is required. Objective: To establish the concurrent and angle-trajectory validity and intra-trial reliability of a novel multi-view image-based motion analysis system with marker-less during lower extremity tasks in healthy young men.Methods: Ten healthy young men participated voluntarily in this study. The hip and knee joint angles were collected using a multi-view image-based motion analysis system (marker-less) and a Vicon motion capture system (with markers) during the lower extremity tasks. Intraclass correlation coefficient (ICC) analyses were used to identify the concurrent and angle-trajectory validity and intra-trial reliability of the multi-view image-based motion analysis system.Results: In the concurrent validity, the correlation analysis revealed that the ICC3, k values on the hip and knee flexions during knee bending in sitting, standing, and squat movements were 0.747 to 0.936 between the two systems. In particular, the angle-trajectory validity was very high (ICC3, 1 = 0.859–0.998), indicating a high agreement between the two systems. The intra-trial reliability of each system was excellent (ICC3, 1 = 0.773–0.974), reflecting high reproducibility. Conclusion: We suggest that this novel marker-less motion analysis system is highly accurate and reliable for measuring joint kinematics of the lower extremities during the rehabilitation process and monitoring the sports performance of athletes in sports training facilities.
Difference and Linkage in Climate Change Modes from East and Central Asia at Multi-Time Scales
Authors: Peng Simin , Li Yu 
Published: November 2021

Abstract
Previous studies argued that climate change modes from East and Central Asia (EA and CA) are out of phase at multi-time scales. However, in recent years, dry/wet changes in CA which contradict traditional views have provoked further discussion. The synchronization of rain and heat periods is a common climate phenomenon in most regions of East and Central Asia. In this paper, we selected EA and CA to carry out a comprehensive study of modern observations, paleoclimate records, and model simulations at multi-time scales. EOF analysis results of modern grid precipitation and self-calibrating Palmer Drought Severity Index (scPDSI) demonstrate the synchronization of rain and heat periods in EA and the east of CA at the short-term timescale. Meanwhile, paleoclimate records indicate parallel dry/wet changes in EA and the east of CA since the Last Glacial Maximum (LGM), also reflecting the synchronization of rain and heat periods at long-term timescales triggered by the insolation. The climate mechanism of difference and linkage in climate change modes from EA and CA, under the framework of the synchronization of rain and heat periods, is analyzed by PMIP3 simulations between the LGM and Mid-Holocene (MH). Overall, we suggest that, in addition to the regional differences caused by different circulation systems (the westerlies and Asian summer monsoon), climate change modes in EA and CA universally have inter-regional connections affected by the synchronization of rain and heat periods at multi-time scales.
Willingness and Uptake of the COVID-19 Testing and Vaccination in Urban China: An Online Cross-Sectional Survey at Early 2021
Authors: Song Suhang , Zang Shujie , Gong Liubing , Xu Cuilin , Lin Leesa , Francis Mark R. , Hou Zhiyuan 
Published: November 2021

Abstract
Background: Regular testing and vaccination are effective measures to mitigate the ongoing COVID-19 pandemic. Few studies have focused on COVID-19 testing and vaccination uptake may change as the pandemic continues. This study aims to examine willingness and uptake of COVID-19 testing and vaccination during a low-risk period of the COVID-19 pandemic in urban China.Methods: A cross-sectional online survey was conducted among 2244 adults in urban China. Descriptive analyses were performed to compare the respondents’ willingness and uptake of COVID-19 testing and vaccination. Multivariate logistic regressions were fitted to investigate the factors associated with willingness and uptake of the two measures.Findings: In early 2021, 52.45% of the respondents had received or scheduled a COVID-19 test at least once, and a majority (95.63%) were willing to receive testing. 63.28% of the respondents had received/scheduled or were willing to receive a COVID-19 vaccine. Willingness and uptake of COVID-19 testing were not associated with socio-demographic characteristics, except for occupation. Being of older age, migrants, having higher educational attainment and secure employment were associated with a higher uptake of COVID-19 vaccination among the surveyed respondents, while willingness to vaccinate was consistent across socio-demographic characteristics among those who had not been vaccinated. Interpretation: Chinese adults expressed almost universal willingness of COVID-19 testing and relatively low willingness of COVID-19 vaccination at the low-risk period of the COVID-19 pandemic, independent from their socio-demographic characteristics. Maintaining willingness of COVID-19 vaccination are key especially when the pandemic evolved into a low-risk period.