bluuebunny/crossref_metadata_2025_split huggingface dataset:
DLG2 Impairs dsDNA Break Repair and Maintains Genome Integrity in Neuroblastoma
Authors: Keane Simon , de Weerd Hendrik A. , Ejeskär Katarina 
Published: June 2021

Abstract
Background: In primary neuroblastoma, deletions on chromosome 11q are known to result in an increase in the total number of chromosomal breaks. Microhomology mediated-end joining (MMEJ) is an error-prone pathway for DNA double-strand break repair that is often upregulated in cancer. DLG2, a candidate tumor suppressor gene on chromosome 11q, has previously been implicated in DNA repair.Methods: We evaluated an association between MMEJ gene expression and neuroblastoma patient outcome, risk categorization, and 11q status using publicly available microarray data from independent neuroblastoma patient datasets. Functional studies were conducted using comet assay and H2AX phosphorylation in neuroblastoma cell lines and in the fruit fly with UVC-induced DNA breaks. Results: We show that the MMEJ genes PARP1 and FEN1 are over expressed in neuroblastoma and restoration of DLG2 impairs their gene and protein expression. When exposed to UVC radiation, cells with DLG2 over expression show less DNA fragmentation and induce apoptosis in a p53 S46 dependent manner. We could also confirm that DLG2 expression results in CHK1 phosphorylation consistent with previous reports of G2/M maintenance. Conclusions: Taken together, we show that DLG2 expression increases p53 mediated apoptosis in response to genotoxicity, by maintaining S317 CHK1 phosphorylation and reducing the DNA replication machinery.
Dynamic of a Two-strain COVID-19 Model with Vaccination
Authors: Tchoumi Stéphane yanick , Rwezaura Herieth , Tchuenche Jean Michel 
Published: June 2021

Abstract

COVID-19 is a respiratory illness caused by an RNA virus prone to mutations. In December 2020, variants with different characteristics that could affect transmissibility and death emerged around the world. To address this new dynamic of the disease, we formulate and analyze a mathematical model of a two-strain COVID-19 transmission dynamics with strain 1 vaccination. The model is theoretically analyzed and sufficient conditions for the stability of its equilibria are derived. In addition to the disease-free and endemic equilibria, the model also has single-strain 1 and strain 2 endemic equilibria. Using the center manifold theory, it is shown that the model does not exhibit the phenomenon of backward bifurcation, and global stability of the model equilibria when the basic reproduction number R 0 is either less or greater than unity as the case maybe are proved using various approaches. Simulations to support the model theoretical results are provided. We calculate the basic reproductive number for both strains R_1 and R_2 independently. Results indicate that - both strains will persist when both R 1 > 1 and R 2 > 1 - Stain 2 could establish itself as the dominant strain if R 1 < 1 and R 2 > 1, or when R 2 is at least two times R 1 . However, with the current knowledge of the epidemiology of the COVID-19 pandemic and the availability of treatment and an effective vaccine against strain 1, eventually, strain 2 will likely be eradicated in the population if the threshold parameter R 2 is controlled to remain below unity.
Cognitive Improvement is Correlated with Increased Dynamic Functional Connectivity of Default Mode Network by Personalized rTMS in Alzheimer's Disease
Authors: Wei Lili , Wang Jintao , Zhang Yingchun , Xu Luoyi , Yang Kehua , Lv Xinghui , Zhu Zhenwei , Gong Qian , Hu Weiming , Li Xia , Qian Mincai , Shen Yuedi , Chen Wei 
Published: June 2021

Abstract
Background

Repetitive transcranial magnetic stimulation (rTMS) is thought to be a promising therapeutic approach for Alzheimer's disease patients.
Methods

In the present report, a double-blind, randomized, sham-controlled rTMS trial was conducted in mild-to-moderate Alzheimer's disease patients. High-frequency rTMS was delivered to a subject-specific left lateral parietal region that demonstrated highest functional connectivity with the hippocampus using resting-state fMRI. The Mini Mental State Examination (MMSE) and Philadelphia Verbal Learning Test (PVLT) were used to evaluate patients’ cognitive functions.
Results

Patients receiving active rTMS treatment (n = 31) showed a significant increase in the MMSE, PVLT-Immediate recall, and PVLT-Short Delay recall scores after two weeks of rTMS treatment, whereas patients who received sham rTMS (n = 27) did not show significant changes in these measures. Dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) in the active-rTMS group showed a significant increase after two weeks of rTMS treatment, and no significant changes were found in the sham-rTMS group. There was a significantly positive correlation between changes of the MMSE and changes of the dFC magnitude of DMN in the active-rTMS group, but not the sham-rTMS group.
Conclusions

Our findings are novel in demonstrating the feasibility and effectiveness of the fMRI-guided rTMS treatment in Alzheimer's disease patients, and DMN might play a vital role in therapeutic effectiveness of rTMS in Alzheimer’s disease.
Trial registration:
China National Medical Research Platform (http://114.255.48.20/login, No:MR-33-20-004217), retrospectively registered 2020-12-23.
Generalization of Higuchi’s Fractal Dimension for Multifractal Analysis of Time Series with Limited Length
Authors: Carrizalez-Velazquez Carlos , Donner Reik , Guzmán-Vargas Lev 
Published: June 2021

Abstract
We introduce a generalization of Higuchi’s estimator of the fractal dimension as a new way to characterize the multifractal spectrum of univariate time series. The resulting multifractal Higuchi dimension anal ysis (MF-HDA) method considers the order-q moments of the partition function provided by the length of the time series graph at different levels of subsampling. The results obtained for different types of stochastic processes as well as real-world examples of word length series from fictional texts demonstrate that MF-HDA provides a reliable estimate of the multifractal spectrum already for moderate time series lengths. Practical advantages as well as disadvantages of the new approach as compared to other state-of-the-art methods of multifractal analysis are discussed, highlighting the particular potentials of MF-HDA to distinguish mono from multifractal dynamics based on relatively short time series.
Sensitive Ratiometric Probing of Tamsulosin Hydrochloride Based On Dual-Emission Fluorescent In Biological Fluids Utilizing Amine-Carbon Quantum Dots And Rhodamine B
Authors: Mousavi Aida , Zare-Dorabei Rouholah , Mosavi Seyed Hossein 
Published: June 2021

Abstract
In this work, amine-carbon quantum dots (CQDs)/rhodamine B (RhB) ratiometric fluorescent (RF) sensor was employed for effective and selective determination of tamsulosin hydrochloride (TMS) based on a dual-emission fluorescence system. Although the function of amine-CQDs is to transfer the specific interaction between TMS and sensor into detectable fluorescence (FL) signals, RhB as a reference unit has been employed to omit internal and external effects. The FL signal was quenched by adding the TMS at 442nm; nevertheless, it did not change at 569nm. The material characterization and investigation of the sensing mechanism were done by UV-Vis, fluorimetry, EDS, TEM, FT-IR, and zeta potential analyses. The optimization of pH, the volumetric ratio of CQDs to RhB, and interaction time parameters were carried out by the one-variable-at-a-time (OVAT) method. The quantitative analysis of the concentration of TMS for this RF sensor in a linear range of 0.446-7.083 μg mL-1 was obtained (R2=0.9969, n=3) under optimum conditions. The limit of detection and quantitation values were estimated to be 0.033 μg mL-1 and 0.109 μg mL-1, respectively. Repeatability of intra-day and inter-day were less than one percent. This inexpensive RF probe was well applied to determine TMS in biological fluids, and acceptable achievements were obtained.
Protective Effects and Mechanisms of Babao Dan Capsules on ANIT-Induced Intrahepatic Cholestasis Liver Disease in Mice
Authors: Mao Hua , Liu Guowei , Huang Liyun , Xie Shiyi , Lu Min , Liu Chuan 
Published: June 2021

Abstract
Background

Babao Dan(BBD), as a traditional Chinese medicine, is widely used in a variety of diseases, especially chronic liver diseases. The aim of this study is to observe the effects and possible mechanisms of Babao Dan(BBD) Capsules on α-Naphthyl isothiocyanate (ANIT) - induced intrahepatic cholestasis liver disease in mice.
Methods

Fifteen mice were randomly divided into three groups: control group, model group, and treatment group, with five in each group. Except for the mice in the control group, the mice in the other two groups were gavaged with a 1% α-Naphthyl isothiocyanate (ANIT) olive oil solution, and cholestasis models were established at a dose of 100 mg/Kg. Meanwhile, at the same time point, the control group was gavaged with the same amount of olive oil. After modeling, the control group, the model group and the treatment group were gavaged with the same amount of saline, saline and BBD saline suspension once daily for 10 days, respectively. On the 10th day, we took the blood preparation and liver samples, then we detected serum levels of liver function indexes(TBA, TBil, DBil, ALT, AST, ALP, GGT), liver fibrosis indexes(HA, LN, PC-Ⅲ, C-Ⅳ). Hepatic pathological examinations were observed by hematoxylin and eosin staining(HE), Masson staining and picric acid-Sirius red staining. The protein expression of TGF-β1 and Smad3 were detected by immunohistochemistry. The level of mRNA expression of TGF-β1 and Smad3 were detected by RT-PCR.
Results

Compared with the control group, serum levels of liver function indexes(TBA, TBil, DBil, ALT, AST, ALP, GGT) and liver fibrosis indexes(HA, LN, PC-Ⅲ, C-Ⅳ) in the model group were significantly increased (P < 0.01).Similarly, compared with control group, in the model group, HE staining showed that hepatocyte swelling, hepatocellular necrosis and destroyed hepatic lobular structure; Masson staining showed that a large amount of blue collagen fibers deposited in the liver tissue, forming fibrous septa and pseudolobule; Picric acid-Sirius red staining showed that type Ⅰ collagen and type Ⅲ collagen in liver tissue increased significantly, the total area of collagen increased significantly. The protein expression of TGF-β1 and Smad3 were significantly up-regulated; the mRNA expression of TGF-β1 and Smad3 was significantly up-regulated. Compared with the model group, the above indexes in treatment group were significantly decreased(P < 0.01).
Conclusions

Babao Dan(BBD) has significant therapeutical effects on intrahepatic cholestasis liver disease by inhibiting TGF-β/Smad signaling pathway.
Time Interval After Various Types of Gastrectomy Until Metachronous Multiple Gastric Cancer: Analysis of Data From A Nationwide Japanese Survey
Authors: Kumagai Koshi , Lee Sang-Woong , Ohira Masaichi , Aizawa Masaki , Kamiya Satoshi , Takahata Takaomi , Toda Makoto , Cho Haruhiko , Takahashi Masazumi , Kubota Takeshi , Kinami Shinichi , Kosaka Takeo 
Published: June 2021

Abstract
Background
The time interval between initial partial gastrectomy and diagnosis of cancer in the remnant stomach reportedly differs according to the reconstruction procedure used in the initial gastrectomy. However, factors correlated with the time interval from the initial surgery for gastric cancer to the detection of metachronous multiple gastric cancer (MMGC) remain unclear. This study was performed to evaluate the association between the type of initial gastrectomy or reconstruction procedure and the time interval from initial gastrectomy to detection of MMGC as well as the association between the type of initial gastrectomy and the procedure performed for MMGC.
Methods
A questionnaire survey on remnant stomach cancer was conducted by the Japanese Society for Gastro-Surgical Pathophysiology in 2018. Participating facilities were asked to indicate the number of patients who underwent surgery for MMGC between 2003 and 2017, in accordance with the time interval from the initial gastrectomy until treatment for MMGC by type of initial gastrectomy or reconstruction procedure. The number of patients who underwent each treatment procedure (completion total gastrectomy or partial gastrectomy) was also collected.
Results
Analyses were performed using data from 45 facilities. Gastrectomy for MMGC was performed in 1,234 patients during the period. Billroth-II and Roux-en Y accounted for 22.3% (103/462) and 1.3% (6/462), respectively, of patients who underwent surgery for MMGC ≥ 10 years from initial DG, while these patients accounted for 8.0% (23/286) and 21.7% (65/286), respectively, of patients who underwent surgery for MMGC within 5 years after initial DG. Likewise, the proportion of each reconstruction procedure differed by the time interval from initial proximal gastrectomy to treatment for MMGC. In terms of the treatments performed for MMGC, the proportion of patients who underwent partial gastrectomy increased in accordance with the size of the remnant stomach after the initial gastrectomy.
Conclusions
The types of gastrectomy or reconstruction procedures for initial gastrectomy differed significantly by time interval between the initial gastrectomy and treatment for MMGC, and their time trends were assumed to be a major cause of the differences. The proportion of patients who underwent completion total gastrectomy deceased as the size of the remnant stomach increased.
Safety and Efficacy of Autologous Non-Hematopoietic Enriched Stem Cell Nebulization in Covid-19 Patients. A Randomized Clinical Trial, Abu Dhabi 2020.
Authors: Carmenate Yendry Ventura , Alkaabi Fatima Mohammed , Aleman Yandy Marx Castillo , Valverde Carlos Agustin Villegas , Ahmed Yasmine Maher , Sanna Pierdanilo , Almarzooqi Ayesha Abdulla , Abdelrazik Abeer , Zambrano Gina Marcela Torres , Mateo Maura Wade , Saliba David Quesada , Hadi Loubna Abdel , Hernandez Antonio Alfonso Bencomo , Jimenez Rene Antonio Rivero 
Published: June 2021

Abstract
Background: The novel SARS-Cov-2 has caused the COVID-19 pandemic. Currently, with insufficient worldwide vaccination rates, the identification of treatment solutions to reduce the impact of the virus is urgently needed. Method: An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the “SENTAD-COVID Study” was conducted by the Abu Dhabi Stem Cells Center under conditional exceptional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4 to July 31, 2020, using an autologous peripheral blood nonhematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital, whichever occurred first. Results: The study included a total of 139 randomized COVID-19 patients with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events occurred in 43 (62.32%) patients receiving PB-NHESC-C vs. 44 (62.86%) in the control group, and most adverse events were related to the disease. After the first nine days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR=0.84; 95% CI, 0.56-1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR=0.69; 95% CI, 0.56-0.88). Conclusions: Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. Trial registration: ClinicalTrials.gov. NCT04473170. Registered 16 July 2020. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04473170.
Analysis of Outcomes of Endovascular Embolisation: A Cross-Sectional Multicenter Study on 46 Visceral Artery Pseudoaneurysms
Authors: Omar Mohammad Koriem Mahmoud , Othman Moustafa H. M. , Morgan Robert A. , Abdallah Abdelkarem Hasan , Seif Hany M. A. , Zidan Mohamed , Khairallah Mahmoud K. A. , El-Aleem Reham Abd 
Published: June 2021

Abstract
Purpose
Visceral artery aneurysms are subdivided into true aneurysms and pseudoaneurysms. Visceral artery pseudoaneurysms (VAPAs) are uncommon in clinical practice but may have serious clinical outcomes up to death. Endovascular management is a safe effective alternative option to traditional surgical procedures. This study assesses the outcome of different embolic materials and techniques used in the endovascular management of visceral artery pseudoaneurysms.
Materials and methods
This is a multicentric prospective analysis of endovascular embolisation of 46 VAPAs with a mean pseudoaneurysm size of 13 ± 11.35 mm. Management using coils only was done in 28/46 patients (60.87%), NBCA glue only in 16/46 patients (34.78%), combined coils and NBCA glue in 1/46 patient (2.17%), and Amplatzer plugs only in 1 patient (2.17%). The management techniques were sac packing in 9/46 patients (19.57%), inflow occlusion in 28/46 patients (60.87%) and trapping in 9/46 patients (19.57%).
Results
The overall clinical success rate was 93.48%, the overall perioperative complication rate was 15.22% and 30-day mortality was zero. For the coil subgroup (n = 28), the clinical success was 92.86%, while the subgroup of NBCA glue (n = 16) showed clinical success of 93.75%. There was no significant statistical difference between clinical success among coil, and NBCA glue subgroups (P > 0.05). The technical success rate was 100%. Effectiveness of the procedures during the follow-up was 97.83%. Target lesion re-intervention rate was 2.17%.
Conclusion
Transarterial embolisation can provide high technical and clinical success rates with low perioperative complication and re-intervention rates, as well as satisfactory procedure effectiveness in the management of VAPAs.
Dynamic change of COVID-19 seroprevalence among asymptomatic office workers in Tokyo from May through Dec 2020 during the second waves of COVID-19.
Authors: Hibino Sawako , Hayashida Kazutaka , Ahn Andrew C , Hayashida Yasutaka 
Published: June 2021

Abstract
Background COVID-19 deaths per capita in Japan have been low compared to Western Countries despite the absence of the lockdown. It is still unclear either the less spreading of the virus or, the less progression to the severe illness. Therefore, it is crucial to determine the seropositivity rates (SPR) in the general population. We determined SPR in healthy office workers in Tokyo with validation of results by comparing two test results from the same individual a month apart.Method Healthy office workers for a Japanese company in Tokyo were determined seropositivity against COVID19 weekly from May 26 to August 25, 2020, by a rapid COVID19 IgM/IgG test kit using fingertip blood. SPR was calculated by pooled data from each two-week window. For each participant, tests were offered twice, separated by a month, to provide self-reference to validate the results. The seropositive individuals were offered a follow-up test on Dec 8th or 15th, 2020, when the third wave loomed in Tokyo, to determine the persistence of the seropositivity.Results 615 volunteers (mean + SD 40.8 + 10.0; 45.7 % female) from 11 discrete locations received at least one test. 350 individuals completed two tests a month apart. The comparison showed that 93.2 % showed reasonable status changes and no instances with physiologically unexpected changes (e.g., IgG (+) turns IgM(+) in a month). Seroprevalence increased from 5.8 % to 46.8 %, paralleling the rise of the cases in Tokyo. Among 152 seropositive participants, 74 participants underwent the follow-up test in Dec 2020. 40.5 % turned seronegative in four months (mean ± S.D. 120 ± 17 days).Conclusion COVID-19 infection may have spread widely in Tokyo despite the low fatality. Given the temporal correlation between the rise in seropositivity and the peak out of COVID-19 cases without a lockdown, temporary herd immunity might be achieved. However, the relatively short-lived antibodies among the asymptomatic individuals may explain why the herd immunity strategy has not succeeded, and COVID-19 resurgence happens every several months. Moreover, sequential testing for serological response against COVID-19 is useful for understanding the dynamics of COVID-19 infection at the population level.
The Expression Discrepancy and Characteristics of Long Non-Coding RNAs in Peripheral Blood Leukocytes From Amyotrophic Lateral Sclerosis Patients
Authors: Yu Yujiao , Pang Dejiang , Li Chunyu , Gu Xiaojing , Chen Yongping , Ou Ruwei , Wei Qianqian , Shang Huifang 
Published: June 2021

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is known to be a progressive neurodegenerative disease that affects upper and lower motor neurons. Less than 10% of ALS patients are defined as familial ALS, more than 90% are sporadic ALS (SALS). According to the genomic information described in existing databases, up to 98% of the human genome consists of non-coding sequences. And of these, nearly 40% of long non-coding RNAs (lncRNAs) are specifically expressed in the brain. Hence, we believe the discrepancy of lncRNAs expression plays a key role in neurodegenerative diseases. It is demanded to search for potential lncRNA biomarkers of SALS and find their involvement in related disease mechanisms.
Methods
We screened 30 lncRNAs with altered expression from peripheral blood leukocytes of SALS patients by microarray and validated 13 of them in leukocytes of SALS, Parkinson's disease (PD) patients and healthy controls (HC). The statistical evaluation of expression was performed by the two-tailed Mann-Whitney U test for means between groups. We followed the bioinformatics to perform a functional enrichment analysis of co-expressed mRNAs, transcription factors and lncRNAs for functional prediction. Co-expressed mRNAs of lncRNAs were identified by calculating Pearson Correlation.
Results
We identified lnc-DYRYK2-7:1, lnc-ABCA12-3:1 and lnc-POTEM-4:7 show decreased expression in SALS patients, whereas in PD patients they show increased expression or no change. In addition, expression of lnc-CNTN4-2:1 and lnc-NR3C2-8:1 were decreased in both SALS and PD patients. We found that XIST was only reduced in male patients with SALS and PD, and not in female patients with SALS but was elevated in PD by gender grouping. Furthermore, we performed GO term enrichment and KEGG pathway analysis for lncRNAs showing differential expression in microarray. We discovered that a significant proportion of differential expressed lncRNAs were associated with various signaling pathways and transcription factors which are consistent with other clinical findings.
Conclusion
Our study enriches the analysis of lncRNA transcriptome sequencing for ALS and PD to date. We validated 3 lncRNA transcripts with specific expression differences only in SALS patients and investigated the bioinformatics information of lncRNAs for subsequent functional studies related to neurodegenerative diseases.