bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome-wide N6-methyladenosine (m6A) methylation in watermelon under CGMMV infection
Authors: He Yanjun , Li Lili , Yao Yixiu , Li Yulin , Zhang Huiqing , Fan Min 
Published: November 2021

Abstract
Background
Cucumber green mottle mosaic virus (CGMMV) causes substantial global losses in cucurbit crops, especially watermelon. N6-methyladenosine (m6A) methylation in RNA is one of the most important post-transcriptional modification mechanisms in eukaryotes. It has been shown to have important regulatory functions in some model plants, but there has been no research regarding m6A modifications in watermelon.

Results
We measured the global m6A level in resistant watermelon after CGMMV infection using a colorimetric method. And the results found that the global m6A level significantly decreased in resistant watermelon after CGMMV infection. Specifically, m6A libraries were constructed for the resistant watermelon leaves collected 48 h after CGMMV infection and the whole-genome m6A-seq were carried out. Numerous m6A modified peaks were identified from CGMMV-infected and control (uninfected) samples. The modification distributions and motifs of these m6A peaks were highly conserved in watermelon transcripts but the modification was more abundant than in other reported crop plants. In early response to CGMMV infection, 422 differentially methylated genes (DMGs) were identified, most of which were hypomethylated, and probably associated with the increased expression of watermelon m6A demethylase gene ClALKBH4B. Gene Ontology (GO) analysis indicated quite a few DMGs were involved in RNA biology and stress responsive pathways. Combined with RNA-seq analysis, there was generally a negative correlation between m6A RNA methylation and transcript level in the watermelon transcriptome. Both the m6A methylation and transcript levels of 59 modified genes significantly changed in response to CGMMV infection and some were involved in plant immunity.

Conclusions
Our study represents the first comprehensive characterization of m6A patterns in the watermelon transcriptome and helps to clarify the roles and regulatory mechanisms of m6A modification in watermelon in early responses to CGMMV.
Right stellate ganglion block improves learning and memory dysfunction and hippocampal injury in rats with sleep deprivation
Authors: Dai Dongsheng , Zheng Biqiong , Yu Zenggui , Lin Shizhu , Tang Yijie , Chen Mengnan , Ke Peng , Zheng Chengjie , Chen Yanqing , Wu Xiaodan 
Published: November 2021

Abstract
Background
Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats.

Methods
Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels.

Results
Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1β and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased.

Conclusions
The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation.
Effect of fasting blood glucose on risk of new‐onset hypertension in rural Chinese population: a 15-year follow-up cohort
Authors: Liu Jing , Cheng Nan N. , Zhou Zi Y. , Zhang Yue , Yang Jie , Liu Li S. , Song Yun , Huang Xiao , Tang Gen F. , Wang Bin Y. , Qin Xian H. , Xu Xi P. , Kong Xiang Q. 
Published: November 2021

AbstractBackgroundThe purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors.MethodsWe conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25–64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings.Results393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1–Q3: < 5.74 mmol/L; clinical cut points: < 5.6 mmol/L), higher baseline fasting blood glucose levels (Q4: ≥ 5.74 mmol/L; clinical cut points: ≥ 5.6 mmol/L and < 7.0 mmol/L) increased the risk of new-onset hypertension significantly [(OR: 1.54, 95% CI 1.19–1.98, P < 0.001); (OR: 1.38, 95% CI 1.09–1.75, P = 0.008)] in women. Additionally, a stronger significant association was found in women with elevated fasting blood glucose on risk of new-onset of hypertension with higher total cholesterol (≥ 5.2 mmol/L) [(OR: 2.76; 95% CI: (1.54, 4.96), P < 0.001)]. However, no association was found between fasting blood glucose and risk of new-onset hypertension in men.ConclusionsHigh fasting blood glucose may be significantly associated with risk of new-onset hypertension in Chinese women, especially in women with higher total cholesterol. Further randomized studies are needed to confirm our findings.
Cardiogenic shock with highly complicated course after influenza A virus infection treated with vva-ECMO and Impella CP (ECMELLA): a case report
Authors: Ebert Daniel , Mungard Nils , Mensch Alexander , Homeister Lorenz , Willsch Jan , Ibe Richard , Baust Henning , Stiller Markus , Rebelo Artur , Ukkat Joerg , Rigopoulos Angelos G. , Weber Elke , Bucher Michael , Noutsias Michel 
Published: November 2021

Abstract
Background
The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial.

Case presentation
A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission.

Conclusions
This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.
The relationship between arterial stiffness index and coronary heart disease and its severity
Authors: Gao Longjian , Lu Dasheng , Xia Guangwei , Zhang Hao 
Published: November 2021

Abstract
Background
Arterial stiffness index (ASI) is closely related to coronary atherosclerosis. This study aims to explore whether ASI can predict coronary heart disease (CHD) and its severity.

Methods
In this study, a total of 726 patients with suspected CHD were recruited. Based on coronary angiography results, the subjects were assigned into three groups: the control group (without obvious coronary artery disease), single-vessel disease group, and multi-vessel disease group (the number of vessels diseased ≥ 2). At the same time, according to the results of angiography, myocardial enzyme spectrum, electrocardiogram, color Doppler echocardiography and clinical manifestations, these patients were divided into four groups: the control group, stable angina (SA) Group, unstable angina (UA) group, and acute myocardial infarction (AMI) group. We have compared whether there were differences in ASI and related baseline data between groups. Receiver operating curve (ROC) analysis was conducted to determine whether ASI could predict CHD and evaluate the severity.

Results
ASI was positively correlated with the number of diseased branches of coronary artery. The value of ASI was increased as the number of the diseased branches increased. The ASI value in the SA group was significantly higher compared with the control group. Furthermore, the ASI value in the UA and AMI groups was remarkably increased compared with the control and SA groups. The results of ROC analysis indicated that the sensitivity and specificity of ASI was 71.0% and 85.4% in diagnosing CHD, respectively. While ASI was used in predicting the severity of CHD, the sensitivity was 72.1% and specificity 57.9%.

Conclusion
ASI is of great value in the diagnosis of coronary heart disease and the prediction of its severity.
Risk prediction of biomarkers for early multiple organ dysfunction in critically ill patients
Authors: Ishikawa Shigeto , Teshima Yuto , Otsubo Hiroki , Shimazui Takashi , Nakada Taka-aki , Takasu Osamu , Matsuda Kenichi , Sasaki Junichi , Nabeta Masakazu , Moriguchi Takeshi , Shibusawa Takayuki , Mayumi Toshihiko , Oda Shigeto 
Published: November 2021

Abstract
Background
Shock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA).

Methods
This was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels.

Results
Of 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651–0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711–852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771–0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799–0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC.

Conclusions
The addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction.
Visualizing adverse events in clinical trials using correspondence analysis with R-package visae
Authors: Diniz Márcio A. , Gresham Gillian , Kim Sungjin , Luu Michael , Henry N. Lynn , Tighiouart Mourad , Yothers Greg , Ganz Patricia A. , Rogatko André 
Published: November 2021

Abstract
Background
Graphical displays and data visualization are essential components of statistical analysis that can lead to improved understanding of clinical trial adverse event (AE) data. Correspondence analysis (CA) has been introduced decades ago as a multivariate technique that can communicate AE contingency tables using two-dimensional plots, while quantifying the loss of information as other dimension reduction techniques such as principal components and factor analysis.

Methods
We propose the application of stacked CA using contribution biplots as a tool to explore differences in AE data among treatments in clinical trials. We defined five levels of refinement for the analysis based on data derived from the Common Terminology Criteria for Adverse Events (CTCAE) grades, domains, terms and their combinations. In addition, we developed a Shiny app built in an R-package, visae, publicly available on Comprehensive R Archive Network (CRAN), to interactively investigate CA configurations based on the contribution to the explained variance and relative frequency of AEs. Data from two randomized controlled trials (RCT) were used to illustrate the proposed methods: NSABP R-04, a neoadjuvant rectal 2 × 2 factorial trial comparing radiation therapy with either capecitabine (Cape) or 5-fluorouracil (5-FU) alone with or without oxaliplatin (Oxa), and NSABP B-35, a double-blind RCT comparing tamoxifen to anastrozole in postmenopausal women with hormone-positive ductal carcinoma in situ.

Results
In the R04 trial (n = 1308), CA biplots displayed the discrepancies between single agent treatments and their combinations with Oxa at all levels of AE classes, such that these discrepancies were responsible for the largest portion of the explained variability among treatments. In addition, an interaction effect when adding Oxa to Cape/5-FU was identified when the distance between Cape+Oxa and 5-FU + Oxa was observed to be larger than the distance between 5-FU and Cape, with Cape+Oxa and 5-FU + Oxa in different quadrants of the CA biplots. In the B35 trial (n = 3009), CA biplots showed different patterns for non-adherent Anastrozole and Tamoxifen compared with their adherent counterparts.

Conclusion
CA with contribution biplot is an effective tool that can be used to summarize AE data in a two-dimensional display while minimizing the loss of information and interpretation.
Clinical outcomes of surgical resection versus radiofrequency ablation in very-early‐stage hepatocellular carcinoma: a propensity score matching analysis
Authors: Li Yuan-Chen , Chen Ping-Hung , Yeh Jen-Hao , Hsiao Pojen , Lo Gin-Ho , Tan TaoQian , Cheng Pin-Nan , Lin Hung-Yu , Chen Yaw-Sen , Hsieh Kun-Chou , Hsieh Pei-Min , Lin Chih-Wen 
Published: November 2021

Abstract
Background
The detection rate of Barcelona Clinic Liver Cancer (BCLC) very-early-stage hepatocellular carcinoma (HCC) is increasing because of advances in surveillance and improved imaging technologies for high-risk populations. Surgical resection (SR) and radiofrequency ablation (RFA) are both first‐line treatments for very-early-stage HCC, but the differences in clinical outcomes between patients treated with SR and RFA remain unclear. This study investigated the prognosis of SR and RFA for very-early‐stage HCC patients with long‐term follow‐up.

Methods
This study was retrospectively collected data on the clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) of 188 very-early-stage HCC patients (≤ 2 cm single HCC). OS and DFS were analyzed using the Kaplan–Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.

Results
Of the 188 HCC patients, 103 received SR and 85 received RFA. The median follow‐up time was 56 months. The SR group had significantly higher OS than the RFA group (10-year cumulative OS: 55.2% and 31.3% in the SR and RFA groups, respectively). No statistically significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 45.9% and 32.6% in the SR and RFA groups, respectively). After PSM, the OS in the SR group remained significantly higher than that in the RFA group (10-year cumulative OS: 54.7% and 42.2% in the SR and RFA groups, respectively). No significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 43.0% and 35.4% in the SR and RFA groups, respectively). Furthermore, in the multivariate Cox regression analysis, treatment type (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.31–0.95; P = 0.032) and total bilirubin (HR: 1.92; 95% CI: 1.09–3.41; P = 0.025) were highly associated with OS. In addition, age (HR: 2.14, 95% CI: 1.36–3.36; P = 0.001) and cirrhosis (HR: 1.79; 95% CI: 1.11–2.89; P = 0.018) were strongly associated with DFS.

Conclusion
For patients with very-early-stage HCC, SR was associated with significantly higher OS rates than RFA. However, no significant difference was observed in DFS between the SR and RFA groups.
Role of health extension workers in the relationship between vector control interventions and malaria in Ethiopia
Authors: Aliye Mohammed , Hong Tao 
Published: November 2021

Abstract
Background
Despite a tremendous decline in the burden of malaria through public health interventions, it is yet remains a critical parasitic health problem in Ethiopia. Insecticide-treated nets and indoor residual spray are considered as the most effective preventive interventions against malaria. This study intended to determine the role of health extension workers in influencing the relationship between vector control strategies and malaria prevalence in Ethiopia.

Methods
The study adopted a descriptive study based on panel data collected from 10 regions of Ethiopia from 2010 to 2018. The data collected were analyzed using STATA version 13.0. Structural equation modelling was used to assess the mediating effect of health extension workers in the relationship. Further, the random effect model was employed to investigate the direct relationship among the study variables.

Results
We observed a strong mediating role of health extension workers to the relationship between strategic interventions and malaria prevalence, where the direct path is (β = 0.64, p < 0.05), and the indirect path (β = 0.72, p < 0.001) and (β = 0.98, p < 0.001) confirming the mediation condition to appear. Our analysis revealed that, insecticide-treated nets and indoor residual spray significantly impacts the malaria prevalence (β = 0.20, p < 0.05) and (β = 0.70, p < 0.001) respectively. Further, our analysis suggests that the cumulative effect of indoor residual spray and insecticide-treated mosquito nets have helped better avert malaria prevalence (β = 81.3%, P < 0.05). Moreover, the finding demonstrates the incremental rate of 30.2%, which is the indirect effect of the research [(β = 0.813) - (β1 = 0.511)].

Conclusion
The findings are potentially useful for the health sector in charge of infectious disease prevention and control, particularly in developing countries explaining how these group provided support to reduce malaria ensuring the provision of proper health message about the program.
Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy
Authors: Bendala Estrada Alejandro David , Calderón Parra Jorge , Fernández Carracedo Eduardo , Muiño Míguez Antonio , Ramos Martínez Antonio , Muñez Rubio Elena , Rubio-Rivas Manuel , Agudo Paloma , Arnalich Fernández Francisco , Estrada Perez Vicente , Taboada Martínez María Luisa , Crestelo Vieitez Anxela , Pesqueira Fontan Paula Maria , Bustamante Marta , Freire Santiago J. , Oriol-Bermúdez Isabel , Artero Arturo , Olalla Sierra Julián , Areses Manrique María , Carrasco-Sánchez H. Francisco Javier , Vento Vanessa Carolina , García García Gema María , Cubero-Morais Pablo , Casas-Rojo José-Manuel , Núñez-Cortés Jesús Millán 
Published: November 2021

AbstractBackgroundSince December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection.MethodsThis work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality.ResultsOf 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21–1.62;p < .001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64–0.76;p < .001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often.ConclusionsBacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment.