bluuebunny/crossref_metadata_2025 huggingface dataset:
Ranscriptome Analysis Reveals the Molecular Mechanism of Yiqi Rougan Decoction in Reducing CCl4-induced Liver Fibrosis in Rats
Authors: Xiong Yu , Hu Jinyuan , Xuan Chen , Tian Jiayu , Tan Kaiyue , Chen Zhiwei , Luo Yan , Du Xuqin , Cheng Junxiong , Zhang Lanyue , Cao Wenfu
Published: October 2021

BackgroundLiver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its molecular mechanism. MethodsWe used low-, medium-, and high-dose YQRG to treat CCl4-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot, and real-time quantitative PCR. ResultsThe results showed that YQRG effectively alleviated CCl4-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these finding subsequently verified experimentally. Conclusion﻿These findings showed that YQRG improved CCl4-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.
Rate of Recovery and Symptomatic Efficacy of a Polyherbal AYUSH Formulation in the Treatment of SARS CoV-2 disease: A Single-arm trial
Authors: Kanchibhotla Divya , Harsora Prateek , Subramanian Saumya , reddy Ravi , Venkatesh Hari
Published: October 2021

Background: The COVID-19 pandemic, caused by the human coronavirus SARS CoV-2, has led to millions of deaths across the globe. Not only is the SARS CoV-2 virus highly infectious, it also mutates very easily. This creates additional challenges for development of robust therapeutic solutions. Along with modern system of healthcare, there is a definite need for exploring natural plant based antiviral compounds directed against the SARS CoV-2 virus. Objective: The present observational study investigates the efficacy of an Ayurvedic polyherbal formulation of 19 ingredients, NOQ19, in the management of COVID-19. Methodology: A single arm, single centric, open label study design was adopted for this feasibility study. 161 RT-PCR positive COVID-19 patients were enrolled. The enrolled participants were provided the Ayurvedic intervention, 2 tablets of NOQ19, thrice daily along with the standard of care treatment. Follow up COVID-19 RT- PCR tests were conducted on Day 5, Day 10 and Day 14, or until the patient turned negative. The time required for testing negative on the RT-PCR test or becoming asymptomatic was noted. Results: A subjective analysis demonstrated that 74% of patients turned RT-PCR negative within 5 days of taking NOQ19. Additionally, 98% of the subjects turned RT-PCR Negative on Day 10 after taking NOQ19 in addition to the standard of care treatment of Vitamin C , Zinc and antipyretic (as necessary). None of the participants reported any adverse or side effects to the medication.Conclusion: NOQ19 Ayurvedic polyherbal formulation can be an effective and safe option for the symptomatic management of COVID-19.
Association between Resting-state EEG oscillation and psychometric properties in perimenopausal women
Authors: Hwang Ren-Jen , Hsu Hsiu-Chin , Chen Hsin-Ju , Lee Yu -Sheun , Chuang Yueh-O
Published: October 2021

Background: The perimenopausal period is associated with higher risk for various mood disorders. Resting-state EEG (rsEEG) brain oscillatory activity has been associated with various neuropsychological disorders and behaviors but has not been assessed in perimenopausal women. Aim: This study aimed to evaluate quantitative relationships between psychometric properties and rsEEG rhythms (δ, θ, α, and γ powers) in perimenopausal women. Methods: A cross-sectional correlational descriptive study was conducted to quantitatively analyze the correlations among rsEEG low to high band activity (δ, θ, α, and γ powers) and psychometric properties for 14 perimenopausal women. Participants completed a psychological inventory comprised of a State Anxiety Inventory (SAI), Depression Inventory (DI), Behavioral Inhibition Scale (BIS), and short-form UPPS Impulsive Behavior Scale (IS) before EEG recording. Results: Results showed that impulsivity was positively related to the β power, symmetrical at most channels (frontal, temporal, central, parietal, and occipital regions; p <.05), but did not relate to the δ, θ, α, and γ powers. The brainwave low to high bands, δ, θ, α, β, and γ power, were not associated with DI, SAI, or BIS scores. Conclusions: This study’s findings suggest that significantly enhanced resting-state beta activity is a trait marker of impulsivity in perimenopausal women. This finding has potential implications for preclinical or clinical evaluation of perimenopausal women.
Bayesian Updating and Sequential Testing: Overcoming Inferential Limitations of Screening Tests
Authors: Balayla Jacques
Published: October 2021

Background: Bayes’ Theorem confers inherent limitations on the accuracy of screening tests as a function of disease prevalence. Herein, we establish a mathematical model to determine whether sequential testing with a single test overcomes the aforementioned Bayesian lim- itations and thus improves the reliability of screening tests. Methods: We use Bayes’ Theorem to derive the positive predictive value equation, and apply the Bayesian updating method to obtain the equation for the positive predictive value (PPV) following repeated testing. We likewise derive the equation which determines the number of iterations of a positive test needed to obtain a desired positive pre- dictive value, represented graphically by the tablecloth function. Results: For a given PPV ρ approaching k, the number of positive test iterations given a prevalence φ needed is: [see equation], where ni = number of testing iterations necessary to achieve ρ, the desired positive predictive value, ln = the natural logarithm, a = sensitivity, b = specificity, φ = disease prevalence/pre-test probability and k = constant. Conclusions: Based on the aforementioned derivation, we provide reference tables for the number of test iterations needed to obtain a ρ(φ) of 50, 75, 95 and 99% as a function of various levels of sensitivity, specificity and disease prevalence/pre-test probability. Clinical vali- dation of these concepts needs to be obtained prior to its widespread application.
The interplay among MAP3K1 and SOX2 regulated metastasis by MAPK signaling pathway through interaction with KLF4 in triple-negative breast cancer
Authors: Zheng Lixiang , Zheng Xilei , Ren Xiaoying , Hunag Ping , Wang Ke , Yu Zhipeng , Zeng Meifang , Liu Tingting , Zhou Lu
Published: October 2021

BackgroundTumor metastasis with poor prognosis is still the leading cause of deaths among triple-negative breast caner (TNBC) patients. Therefore, understanding the underlying molecular mechanisms of TNBC metastasis and identifying the molecules contributing to the process are of great importance.It would be provided targets for the prevention and treatment of recurrence and metastasis of TNBC. MethodsThe expression level of MAP3K1 and its up-or downstream genes,SOX2 and KLF4 were detected using Western blotting assay. Cell migration and proliferation were measure by xCELLigence Real-Time Cell Analyzer (RTCA). Protein interaction was used for co-immunorecipitation. ResultCompared with metastasis (Met) in TBNC model, the expression of MAP3K1,KLF4,ERK1/2, C-jun and werelower, while SOX2, Ras,Rafand c-Fos were higher in non-metastasis (non-Met) samples. In MAP3K1 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were increased. The expression level of KLF4 was lower than SOX2 reduced or minimal interaction of both. In SOX2 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were decreased, while the expression of KLF4 and MAP3K1 were higher, the interaction of MAP3K1 and KLF4 was inhibited. ConclusionsIt is demonstrated for the very first time that SOX2 and MAP3K1 are playing an important rolesin TNBC cell metastasis by regulating MAPK signaling pathway by interacting with KLF4 .
Exploring Alterations in Sensory Pathways in Migraine
Authors: Meylakh Noemi , Henderson Luke A.
Published: October 2021

BackgroundMigraine is a neurological disorder characterized by intense, debilitating headaches, often coupled with nausea, vomiting and sensitivity to light and sound. Whilst changes in sensory processes during a migraine attack have been well-described, there is growing evidence that even between migraine attacks, sensory abilities are disrupted in migraine. Brain imaging studies have investigated altered coupling between areas of the descending pain modulatory pathway but coupling between somatosensory processing regions between migraine attacks has not been properly studied. The aim of this study was to determine if ongoing functional connectivity between visual, auditory, olfactory, gustatory and somatosensory cortices are altered during the interictal phase of migraine. MethodsTo explore the neural mechanisms underpinning interictal changes in sensory processing, we used functional magnetic resonance imaging to compare resting brain activity patterns and connectivity in migraineurs between migraine attacks (n= 32) and in healthy controls (n=71). Significant differences between groups were determined using two-sample random effects procedures (p<0.05, corrected for multiple comparisons, minimum cluster size 10 contiguous voxels, age and gender included as nuisance variables). ResultsIn the migraine group, increases in infra-slow oscillatory activity were detected in the right primary visual cortex (V1), secondary visual cortex (V2) and third visual complex (V3), and left V3. In addition, resting connectivity analysis revealed that migraineurs displayed significantly enhanced connectivity between V1 and V2 with other sensory cortices including the auditory, gustatory, motor and somatosensory cortices. ConclusionsThese data provide evidence for a dysfunctional sensory network in pain-free migraine patients which may be underlying altered sensory processing between migraine attacks.
A new regime that “FIRE”s fusion plasmas for long sustained and high performance reactor conditions
Authors: Na Yong-Su , Han Hyunsun , Park Sangjin , Kang Jisung , Lee Young-Ho , Jung Jinil , Cha Minsoo , Choi Gyungjin , Choi Minjun , Gwak Jinwoo , Hahm Taik Soo , Hahn Sang Hee , Jang Juhyeok , Lee Kwan Chul , Kim Boseong , Kim Junghee , Kim SangKyeun , Kim Woong Chae , Ko Jinseok , Ko Wonha , Lee Chanyoung , Lee Jaehyun , Lee Jekil , Lee Jungpyo , Lee Kyu-Dong , Park Jong-Kyu , Park Young-Seok , Seo Jaemin , Sung Choongki , Yang SeongMoo , Yoon Siwoo
Published: October 2021

We report a discovery of a fusion plasma regime suitable for commercial fusion reactor where the ion temperature was sustained above 100 million degree about 20 s for the first time. Nuclear fusion as a promising technology for replacing carbon-dependent energy sources has currently many issues to be resolved to enable its large-scale use as a sustainable energy source. State-of-the-art fusion reactors cannot yet achieve the high levels of fusion performance, high temperature, and absence of instabilities required for steady-state operation for a long period of time on the order of hundreds of seconds. This is a pressing challenge within the field, as the development of methods that would enable such capabilities is essential for the successful construction of commercial fusion reactor. Here, a new plasma confinement regime called fast ion roled enhancement (FIRE) mode is presented. This mode is realized at Korea Superconducting Tokamak Advanced Research (KSTAR) and subsequently characterized to show that it meets most of the requirements for fusion reactor commercialization. Through a comparison to other well-known plasma confinement regimes, the favourable properties of FIRE mode are further elucidated and concluded that the novelty lies in the high fraction of fast ions, which acts to stabilize turbulence and achieve steady-state operation for up to 20 s by self-organization. We propose this mode as a promising path towards commercial fusion reactors.
Association between triglyceride–glucose index and nonalcoholic fatty liver disease in type 2 diabetes mellitus
Authors: li wei , Wang Yan , He Feng , Liu Zhuo , Zhang Yuqi , Li Tianfang , Liu Shengyun , Chen En
Published: October 2021

Background
Lipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride–glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population.
Methods
A total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD.
Results
Logistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03–5.27; P < 0.001) for NAFLD in the highest TyG quartile after adjustment for known confounders (Model 4). According to receiver operating characteristic (ROC) curve analysis, the optimal cut-off point of the TyG index for the risk of NAFLD was 9.3 with an area under the ROC curve of 0.683 (95% CI 0.658–0.707), a sensitivity of 60.6%, and a specificity of 65.8%. In stratified analysis, an elevated TyG index is significantly associated with NAFLD in younger patients (<65 years; OR, 2.35; 95% CI, 1.83–3.02; P < 0.001), females (OR, 2.69; 95% CI, 1.67–4.32; P < 0.001), patients with BMI < 25 kg/m2 (OR, 2.80; 95% CI, 2.01–3.91; P < 0.0001), and with lower high-density lipoprotein cholesterol (<1 mmol/L; OR, 2.76; 95% CI, 1.98–3.83; P < 0.001).
Conclusion
The TyG index is remarkably associated with NAFLD and shows superior discriminative ability for NAFLD risk compared with other lipid and glycemic parameters in the T2DM population.
Radiomics Analysis Based on CT’s greater-omental caking for Predicting Pathological Grading of Pseudomyxoma Peritonei
Authors: Zhou Nan , Dou Ruixue , Zhai Xichao , Fang Jingyang , Wang Jiajun , Ma Ruiqing , Xu Jingxu , cui Bin , Lei Liang
Published: October 2021

Purpose: The objective of this study was to predict the preoperative pathological grading and survival period of Pseudomyxoma peritonei (PMP) by establishing models, including a radiomics model with greater mental caking as the imaging observation index, a clinical model including clinical indexes, and a combination model of these two.Methods: A total of 88 PMP patients were selected. Clinical data of patients, including age, sex, preoperative serum tumor markers [CEA, CA125, and CA199], survival time, and preoperative computed tomography (CT) images were analyzed. Three models (clinical model, radiomics model and joint model) were used to predict PMP pathological grading. The models’ diagnostic efficiency was compared and analyzed by building the receiver operating characteristic (ROC) curve. Simultaneously, the impact of PMP’s different pathological grades was evaluated.Results: The results showed that the radiomics model based on the CT’s greater omental caking, an area under the ROC curve ([AUC] = 0.878), and the combined model (AUC = 0.899) had diagnostic power n for determining PMP pathological grade.Conclusion: The imaging radiomics model based on CT greater omental caking can be used to predict PMP pathological grade, which is important in the treatment selection method and prognosis assessment.
RiboPlotR: a Visualization Tool for Periodic Ribo-seq Reads
Authors: Wu Hsin-Yen Larry , Hsu Polly Yingshan
Published: October 2021

Background: Ribo-seq has revolutionized the study of genome-wide mRNA translation. High-quality Ribo-seq data display strong 3-nucleotide (nt) periodicity, which corresponds to translating ribosomes deciphering three nts at a time. While 3-nt periodicity has been widely used to study novel translation events such as upstream ORFs in 5’ untranslated regions and small ORFs in presumed non-coding RNAs, tools that allow the visualization of these events remain underdeveloped.Results: RiboPlotR is a visualization package written in R that presents both RNA-seq coverage and Ribo-seq reads in genomic coordinates for all annotated transcript isoforms of a gene. Specifically, for individual isoform models, RiboPlotR plots Ribo-seq data related to splice junctions and presents the reads for all three reading frames in three different colors. Moreover, RiboPlotR shows Ribo-seq reads in upstream ORFs, 5' and 3' untranslated regions and introns, which is critical for observing new translation events and identifying potential regulatory mechanisms.Conclusions: RiboPlotR is freely available (https://github.com/hsinyenwu/RiboPlotR and https://sourceforge.net/projects/riboplotr/) and allows the visualization of translated features identified in Ribo-seq data.
Data Driven Identification of Plasma Metabolite Clusters and Metabolites of Interest for Potential Detection of Early Stage Non-Small Cell Lung Cancer Cases Versus Cancer-Free Controls
Authors: Kim Julian Oliver , Balshaw Robert , Trevena Connel , Banerji Shantanu , Murphy Leigh , Dawe David , Tan Lawrence , Srinat Sadeesh , Buduhan Gordon , Kidane Biniam , Qing Gefei , Domaratzki Michael , Aliani Michel
Published: October 2021

Objectives: Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven, assessment of plasma from early-stage non-small cell lung cancer (ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify classes of metabolites for further targeted metabolomics biomarker development. Materials and Methods: Plasma from 250 ES-NSCLC cases and 250 CFCs underwent Ultra High-Performance Liquid Chromatography/Quadrupole Time-Of-Flight Mass Spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in ≥80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. Results: 1,900 UHPLC-QTOF-MS assessments identified 1,667 and 2,032 endogenous metabolites in the ESI positive and ESI negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5’-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol.Conclusions: Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop non-invasive metabolomics-based detection of early-stage NSCLC.
Alterations in the Composition of the Gut Microbiota in Celiac Disease, Non-Coeliac Gluten Sensitivity and Irritable Bowel Syndrome
Authors: Naseri Kaveh , Shahrbaf Mohammad Amin , Olfatifar Meysam , Yadegar Abbas , Soheilian-Khorzoghi Mona , Dabiri Hossein , Nejad Mohammad Rostami , Sadeghi Amir , Zali Mohammad Reza
Published: October 2021

Background and aims: Some chronic intestinal disorders, including irritable bowel syndrome (IBS), coeliac disease (CD), and non-coeliac gluten sensitivity (NCGS), can make some changes to the gut microbiota composition and cause dysbiosis. This study aimed to determine the gut microbiota alterations in CD, NCGS, and IBS patients among the Iranian population compared to healthy controls.Materials and Methods: In this prospective study, 72 patients, including 15 healthy controls (HC), 30 IBS, 12 NCGS, and 15 CD patients were included. IBS, CD, and NCGS were diagnosed based on the Rome IV diagnostic criteria, Modified Marsh classification, and gluten challenge test. Stool samples were collected from patients, and after DNA extraction, quantitative real-time PCR (qPCR) was performed for assessing the relative abundance of Firmicutes, Bacteroidetes, Bifidobacterium spp., and Lactobacillus spp. Results: Firmicutes and Lactobacillus spp. were the most and the least abundant phylum in all samples, respectively. In CD patients, Firmicutes phylum was the most significant relative abundance. Bacteroidetes phylum had a significant relative abundance in CD (P<0.01) and NCGS (P<0.05) patients. The relative abundance of Bifidobacterium spp. was statistically lower in CD (P<0.05) and IBS patients (P<0.001) compared to the HCs. The Firmicutes to Bacteroidetes ratio was statistically significant in NCGS and CD patients compared to the HCs (P = 0.05).Conclusion: Chronic intestinal diseases, including IBS, CD, and NCGS, can alter the gut microbiota composition.
Light Intensity: the Role Player in Cucumber Response to Cold Stress
Authors: Ashrestaghi Tahereh , Aliniaeifard Sasan , Shomali Aida , Azizinia Shiva , Koohpalekani Jahangir Abbasi , Moosavi-Nezhad Moein
Published: October 2021

Low temperatures are an important limitation for geographic distributions of warm-season crops like cucumber (Cucumis sativus L.). Tolerance to low temperatures varies among different plant species and genotypes when changes in normal environmental cues occur. To cope with low temperature, biochemical and biophysical events should be coordinated to form a physiological response. We examined how light intensity influences the effects of low temperature on photosynthesis machinery and some biochemical traits. We used chlorophyll fluorescence imaging and polyphasic fluorescence transient (OJIP) to analyze cold stress (4 ºC) damage to photosynthetic electron transport chain (ETC) under different Photosynthetic Photon Flux Densities (PPFDs; 0, 300 and 600 μmol m-2 s-1), in four accessions of cucumber. The results showed that, the negative effects of cold stress are PPFD-dependent. The adverse effect of cold stress on ETC was more pronounced in plants exposed to 600 μmol m-2 s-1 compared to the control and dark-exposed plants; indicated by disturbance in ETC and higher energy dissipation. Moreover, biochemical traits including H2O2 content, ascorbate peroxidase activity and electrolyte leakage, and water-soluble carbohydrate was increased under low temperature by increase in PPFD, while chlorophyll and carotenoid contents decreased under low temperature by PPFD elevation. Low temperature induced H2O2 accumulation via suppressing APX activity in a PPFD-dependent manner. In conclusion, high PPFDs exacerbate the adverse effects of low temperature on the cucumber seedlings.
Preventive Treatment With CGRP Monoclonal Antibodies Restores Brain Stem Habituation Deficits and Excitability to Painful Stimuli in Migraineurs: Results From a Prospective Case-control Study
Authors: Thiele Anne , Klehr Lara , Strauß Sebastian , Angermaier Anselm , Schminke Ulf , Kronenbuerger Martin , Nägel Steffen , Fleischmann Robert
Published: October 2021

Background & ObjectivesCalcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraineurs. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and might thus possess disease modifying potential. This study addresses this question by investigating the nociceptive blink reflex (NBR), which is closely tied to central disease activity, before and after treatment with CGRP antibodies.MethodsWe enrolled 22 episodic migraineurs (21 female, 46.2 ± 13.8 years of age) and 22 age-/gender-matched controls. Patients received assessments of the NBR (R2 component, 10 trials, 6 stimuli/trial) before (V0) and three months (V3) after treatment with CGRP antibodies started, controls were assessed once. The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) of the stimulated/non-stimulated side (_s/_ns) following repeated supraorbital stimulation provide a direct readout of brainstem excitability and habituation as key mechanisms in migraine.ResultsAll patients showed a substantial reduction of headache days/month (V0: 12.4±3.3, V3: 6.6 ± 4.9). R2a_s (Fglobal=5.86, p<0.001; block 1: R2a_s: -28%, p<0.001) and R2a_ns (Fglobal=8.22, p<0.001, block 1: R2a_ns: -22%, p=0.003) were significantly decreased, and R2h_ns was significantly enhanced (Fglobal=3.07, p<0.001; block 6: R2h_ns: r=-1.36, p=0.007) from V0 to V3. The global test for changes of R2h_s was non-significant (Fglobal=1.46, p=0.095). Changes of R2h significantly correlated with improvement of headache frequency (R2h_s, r=0.56, p=0.010; R2h_ns: r=0.45, p=0.045). None of the NBR parameters assessed at baseline predicted treatment response.DiscussionWe provide evidence that three months of treatment with CGRP antibodies restores brain stem responses to painful stimuli and thus might be considered disease modifying. The nociceptive blink reflex may provide a biomarker to monitor central disease activity. Future studies should evaluate the blink reflex as a clinical biomarker to predict treatment response at baseline and to establish the risk of relapse after treatment discontinuation.Trial registrationThis trial was prospectively registered at clinicaltrials.gov (ID: NCT04019496, date of registration: July 15, 2019).
Clomiphene Citrate Priming Increases Sensitivity During Ovarian Stimulation in Poor Ovarian Responders Undergoing In Vitro Fertilization Treatment: A Retrospective Cohort Study
Authors: Liu Shan , Liu Xinyu , Li Huanhuan , Liu Minghui , Lv Yasu , Li Yuan
Published: October 2021

Background: Since ovarian stimulation was introduced as an assisted reproductive technology, poor ovarian response (POR) management has challenged clinicians. Guidance on optimally managing patients with poor response and/or low sensitivity to ovarian stimulation is still lacking. We aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. Methods: This single-center retrospective cohort study included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. Results: Total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter in the study group. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300-1.933, P = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were directly associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients stimulated by the CC priming antagonist protocol were administered less gonadotropin (1,739.09 ± 719.39 vs. 3,114.77 ± 1,171.23, P < 0.001) at a lower gonadotropin dosage per follicle (637.36 ± 373.05 vs. 1286.26 ± 976.66, P < 0.001) and for a shorter duration (6.58 ± 2.23 vs. 9.80 ± 1.90, P < 0.001). Conclusions: The CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.
Pulmonary Involvement in Neonatal Lupus from Clinical Diagnoses to Autopsy Findings: A Case Report
Authors: Wu Fan , Ying Li , Hanzhen Xiong , Lili Lin , Weiliang Huang
Published: October 2021

Background: Neonatal lupus erythematosus (NLE) is an uncommon immunemediated disease caused by the transplacental passage of maternal autoantibodies. In this paper, we described a case of a newborn with NLE involving lung damage from clinical diagnoses to autopsy findings. Case presentation: The mother had no history of immune system disease; however, the test for antinuclear antibodies was positive. A boy was delivered spontaneously at 36+2 weeks’ gestation without asphyxia (birth weight: 1.21 kg, length: 38 cm, head circumference: 26 cm). Soon after birth, intermittent shortness of breath occurred, followed by cyanosis and severe hypoxemia. Blood tests suggested that the infant was positive for anti-nuclear antibodies. Although multiple respiratory support methods were used, death could not be avoided and occurred at 6.5 days due to cardiopulmonary failure. The results of the autopsy revealed diffuse interstitial inflammation and interstitial fibrosis in both lungs, manifesting as telangiectasia, hyperemia, alveolar cavity dilatation and fusion, and obvious interstitial widening with chronic inflammatory cell infiltration. The newborn was finally diagnosed with nonspecific interstitial pneumonia with fibrosis caused by congenital systemic lupus erythematosus. Conclusions: Pulmonary involvement with NLE is a diagnostic challenge at present. Close attention should be given to newborns whose mothers have systemic lupus erythematosus.
Shallow and Deep Feature Fusion for Digital Audio Tampering Detection
Authors: Zeng Chunyan , Yang Yao , Wang Zhifeng , Kong Shuai , Feng Shixiong , Zhao Nan
Published: October 2021

Digital Audio tampering detection can be applied to verify the authenticity of digital audio. However, the current methods are mostly based on visual comparison analysis of the continuity of electronic network frequency (ENF) of digital audio with a standard ENF database. It is usually tricky to obtain the ENF database, and the feature expression of the visualization method is weak, which leads to low detection accuracy. In order to solve this problem, this paper proposed an audio tampering detection method based on the fusion of shallow and deep features. Firstly, the band-pass filtering process is performed on the audio signal to obtain the ENF components, and then the discrete Fourier transform and Hilbert transform are applied to obtain the phase and instantaneous frequency of the ENF components. Secondly, the shallow features are extracted by performing framing and fitting operations on the estimated phase and instantaneous frequency. Then, the designed convolutional neural network is used to obtain deep features, and the attention mechanism is applied to fuse shallow features and deep features. Finally, after dimensionality reduction through the fully connected layer, the Softmax layer is used for classification to detect the tampering audio. The method achieves 97.03% accuracy on three classic databases, which are Carioca 1, Carioca 2, and New Spanish. In addition, we have achieved an accuracy of 88.31% on the newly constructed database GAUDI-DI. Experimental results show that the proposed method is superior to the state-of-the-art method.
Feature Stability and Setup Minimization for EEG-EMG-Enabled Monitoring Systems
Authors: Cisotto Giulia , Capuzzo Martina , Guglielmi Anna Valeria , Zanella Andrea
Published: October 2021

Delivering healthcare at home emerged as a key advancement to reduce healthcare costs and infection risks, as during the SARS-Cov2 pandemic. In particular, in motor training applications, wearable and portable devices can be employed for movements recognition and monitoring of the associated brain signals. In this context, it is essential to minimize the monitoring setup and the amount of data to collect, process, and share. In this paper, we address this challenge for a monitoring system that includes high-dimensional EEG and EMG data for hand movements classification. We fuse EEG and EMG into the magnitude squared coherence (MSC) signal, from which we extracted features using different algorithms (one from the authors) to solve binary classification problems. Finally, we propose a mapping-and-aggregating strategy to increase the interpretability of the machine learning results. The proposed approach provides very low mis-classification errors ( < 0. 1 ), with very few and stable MSC features ( < 10% of the initial set of available features). Furthermore, we identified a common pattern across algorithms and classification problems, i.e., the activation of the centro-parietal brain areas and arm ’s muscles in 8 ÷ 80 Hz, in line with previous literature. Thus, this study represents a step forward to the minimization of a reliable EEG-EMG setup to enable precise motor training at home.
Multifarious Biomarker Approach Elucidate Stocking Density Mediated Stress, Modulates Growth Attributes in Cage Reared Rohu, Labeo Rohita (Hamilton)
Authors: Swain Himanshu Sekhar , Das Basanta Kumar , Upadhyay Aurobinda , Ramteke Mitesh Hiradas , Kumar Vikas , Meena Dharmendra Kumar , Sarkar Uttam Kumar , Chadha Narinder Kumar , Rawat Kiran Dube
Published: October 2021

The present study was conducted for 240 days to evaluate the effects of stocking density based on growth attributes, digestive enzymes, muscular composition, biochemical and physiological responses of Labeo rohita fingerlings in tropical inland open water cages. L. rohita (30.35±1.08 g) were randomly distributed into three treatments, namely low stocking density, LSD (10 m− 3), medium stocking density, MSD (20 m− 3) and high stocking density, HSD (30 m− 3) in triplicates. Fish were fed twice daily with CIFRI CAGEGROW® floating feed (crude protein-28%, crude fat-4%). Fish growth and feed efficiency was higher (P<0.05) in LSD, however MSD registered higher yield. Amylase and protease activity reduced whereas lipase activity increased with increasing stocking density. Muscle crude protein and crude fat formed inverse correlation. The fillet quality deteriorated at higher stocking densities based on Muscle pH, drip loss and frozen leakage rate. The stress biomarkers level (glucose, cortisol, superoxide dismutase and catalase) increased in serum under crowding condition. Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum was significantly increased in HSD. Serum protein level decreased with increase in stocking densities. Body ionic imbalance (Na+, Cl− and K+) observed under crowding stress. Based on growth attributes and multiple biomarker responses, L. rohita @ 10 m− 3 found to be optimum density for inland open water cage culture.
RETRACTED: Current Challenges Lack of the legality of Nurse Prescribing in Intensive Care Units: A Qualitative Study
Authors: Naderi Azam , Abbaszadeh Abbas , Jalali Rostam , Pazokian Marzieh , Rohani Camelia
Published: October 2021

The authors have requested that this preprint be removed from Research Square.
Macroeconomic, Political, And Institutional Determinants of Private Investment In Ethiopia: A Dynamic Analysis
Authors: Mekonnen Hulunayen Yizengew , Mogess Yohannes Kefale
Published: October 2021

This article investigates the macroeconomic, political, and institutional determinants of private investment in Ethiopia based on a time series data from 1985 to 2018. We apply ARDL approach to Co-integration to investigate the long-run and short run outcomes. The result reveals that real GDP has positive significant effect on private investment growth in both long run and short run while public investment has a crowding-out effect in short run but crowding-in effect in the long run. Real interest rate has a significant negative effect on private investment growth in long run unlike its short run effect. Hence, we recommend more effort has to be excreted to increase the market-size and real income of the people to promote private investment. Secondly, public investment in infrastructures is crucial to attract private investors though public investment in sectors that compete directly with the private sector retard private investment growth. Thirdly, given the negative significant effect of real effective exchange rate on private investment, devaluation is not a long-lasting solution to promote private investment unless the marshal-learner condition is satisfied. Fourthly, the government has to ensure consistent management strategies to minimize corruption, violent uprisings, and bureaucratic inefficiencies to build up confidence of private investors.
AVL9 Promotes Colorectal Carcinoma Cell Migration via Regulating EGFR Expression
Authors: Wu Qiong , Chen JingDe , Zhou Zhuqing
Published: October 2021

Background: Despite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it’s biological function and mechanism in CRC remain unclear.Aim: To investigate the biological role and mechanism of AVL9 in colorectal carcinoma.Results: AVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration.Conclusion: These findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, implying a potential biomarker for CRC early diagnosis.
Mortality and Its Associated Factors of Bowel Obstruction after Surgical Treatment Among Adult Patients at Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia 2021 (Retrospective Cross-Sectional Study)
Authors: Simachew Addisu , Haile Dessalegn , Tesfaye Bekele , Kebede Tiringo , Nahusenay Hiowt , Shimkaw Atirsaw , Endawok Migbaru , kefale fasil
Published: October 2021

Background: - Bowel obstruction is a mechanical or functional obstruction of bowel that prevents the normal movements of products of digestions. Even if Treatment outcome of bowel obstruction varies from area to area, time to time, and also increasing age is significant factor of treatment outcomes of bowel obstruction. Outcome of bowel obstruction and associated factors on adults have been poorly explored in the previous Ethiopian study particularly in the study area. Objective: To assess prevalence and its associated factors of mortality after surgical treatment of bowel obstruction among adult patients at Debre Markos comprehensive specialized hospital, Northwest Ethiopia 2021 Methodology: - Institution based Cross sectional study design was used. A total 517 study participates was included by using consecutive sampling techniques from 23/02/2017 to 23/02/2021 at Debre Markos Comprehensive specialized Hospital. Data was collected from patient registration books and medical records available in the hospital by using checklists. Then data were entered to Epi data version 4.1 and exported to SPSS version 25 for analysis. A binary logistic regression model was fitted to identify factors associated with treatment outcome of bowel obstruction. P value less than 0.05 considered as significant in multivariable analysis Result: Among patients treated for bowel obstruction 70(13.5%) was died. Old age (>=55) ((AOR=3.70; 95% CI [1.02,3.39, p=0.046], Gangrenous large bowel (AOR 5.58; 95%CI [2.33, 3.36), p=0.0001].. prolonged hospital stay(AOR= 2.42; 95%CI [1.10, 5.55, p=0.043]). late presentation (AOR=2.84; 95% CI [1.33, 6.04]), comorbidity (AOR=3.79; 95%CI [(1.75, 8.21), p=0.001]), WBC(AOR=3.53 ;95% CI [(1.61, 7.70), P=0.002]). Low hemoglobin (AOR=3.50, 95%CI [(1, 62, 7.60), P=0.001]) was independent predicator of mortality.Conclusion: Mortality after surgical treatment of bowel obstruction were high and having gangrenous bowel, low hemoglobin level, late presentation, post-operative complications, leukocytosis and comorbidity was independent predicator of unfavorable outcomes. Give special care for patients treated with low hemoglobin, late presentation, having complications and leucocytosis. Create awareness to the public on advantage of early presentation to hospital.
Monitoring Cardiopulmonary Resuscitation Quality in Emergency Department: A National Survey in China on Current Knowledge, Attitudes, and Practices
Authors: Zheng Kang , Du Lanfang , Cao Yu , Niu Zhendong , Song Zhenju , Liu Zhi , Liu Xiaowei , Xiang Xudong , Zhou Qidi , Xiong Hui , Chen Fengying , Zhang Guoqiang , Ma Qingbian
Published: October 2021

Background: To investigate current knowledge, attitudes, and practices for CPR quality control among emergency physicians in Chinese tertiary hospitals.Methods: Anonymous questionnaires were distributed to physicians in 75 tertiary hospitals in China between January and July 2018.Results: A total of 1405 respondents answered survey without obvious logical errors. Only 54.4% knew all criteria of high-quality CPR. The main problems during CPR were related to chest compression: low quality due to fatigue (67.3%), inappropriate depth (57.3%) and rate (54.1%). 91.0% respondents considered CPR quality monitoring should be used, 72.4% knew objective method for monitoring, and 63.2% always/often monitored CPR quality during actual resuscitation. The utilization rate of recommended monitoring methods was reported as follow, ETCO2 was 42.7%, audio-visual feedback devices was10.1%, coronary perfusion pressure was 17.9%, and invasive arterial pressure was 31.1%. 96.3% respondents considered it was necessary to participate in regular CPR retraining, but 21.4% did not receive any retraining. The ideal retraining interval was considered to be 3 to 6 months, but actual interval was 6 to 12 months. CPR feedback devices were always/often used in training was reported by 49.7% of respondents.Conclusion: Chinese emergency physicians were very concerned about CPR quality, but they did not fully understand the high-quality criteria and impact on prognosis. CPR quality monitoring was not routine procedure during actual resuscitation. The methods recommended in guidelines were rarely used in practice. Many physicians have not received retraining or have received retraining at long intervals. Feedback devices were not commonly used in training.
STAT3 Suppresses The AMPKα-ULK1-Dependent Induction of Autophagy In Glioblastoma Cells
Authors: Bhattacharya Sujoy , Yin Jinggang , Yang Chuan He , Wang Yinan , Sims Michelle , Pfeffer Lawrence M. , Chaum Edward
Published: October 2021

Despite advances in molecular characterization, glioblastoma (GBM) remains the most lethal type of brain tumor with high mortality rates in both pediatric and adult patients. The signal transducer and activator of transcription 3 (STAT3), is an important oncogenic driver of GBM. Although STAT3 reportedly plays a role in autophagy of some cells, its role in cancer cell autophagy remains unclear. In this study, we found STAT3 phosphorylation on Y705 and S727 residues, acetylation on K685, and tri-methylation on K180 was constitutive in GBM cell lines. Tyrosine phosphorylation of STAT3 in MT330 GBM cells suppresses autophagy, whereas knockout (KO) of STAT3 increases ULK1 gene expression, increases TSC2-AMPKa-ULK1 signaling and Prom1/CD133 expression, decreases p62 gene expression and accumulation, and increases lysosomal Cathepsin D processing, leading to the stimulation of autophagic flux. Rescue of STAT3-KO cells by the enforced expression of wild-type (WT) STAT3 reverses these pathways and inhibits autophagic flux. Conversely, expression of Y705F-STAT3 and S727A-STAT3 mutants in STAT3-KO cells did not suppress autophagy. Inhibition of ULK1 activity (by MRT68921) or its expression (by siRNA) in STAT3-KO cells inhibits autophagy flux and sensitizes cells to apoptosis. Taken together, our findings suggest that both STAT3 serine and tyrosine phosphorylation play critical roles in STAT3-dependent autophagy in GBM and the potential of targeting this pathway to treat GBM.
How Young is a 300-Year-Old Wetland? The Case of the Pantanal Marimbus, Chapada Diamantina, Brazil
Authors: Lima Geraldo Marcelo , Macário Kita , Costa Alexandre , Alves Eduardo , Filho Joaquim , Poggio Carolina
Published: October 2021

The Chapada Diamantina, in Northeastern Brazil, is one of the few places where one can find drylands with a backswamp containing hundreds of dead deciduous trees in the floodplain. During the 18th century, the region was globally important due to the exploration of mineral resources. The death of these trees was caused by mining activities that silted the main river, leading to the impoundment of the tributary river, and resulting in a wetland known as Pantanal Marimbus, having as indicators: (i) backswamp morphological feature that remains permanently flooded in the axis of the fluvial course, and (ii) alluvial fans concentrated in one footslope area where mining activities at the Chapada Diamantina were also concentrated. The hydrological and sedimentological behavior was investigated to multi-methods. By analysing four different samples from the bark and core of the same tree, we obtained calibrated radiocarbon dates within the 18th century. For no robust dendrochronology could be performed, a simple sequence model was built, revealing a high probability that the tree lived until approximately 1700 AD. 14C-AMS measured pioneering possible to evaluate the 300-years-old wetlands juvenile evolutionary state.