bluuebunny/crossref_metadata_2025_split huggingface dataset:
جائحة كورونا والقيم الإنسانية: دراسة في المجال الفلسفي
Authors: المهدي العبيدي د.محمود محمد 
Published: January 2024

تعد القيم من الإشكاليات المعاصرة بسبب ما تمر به البشرية من نوازل وكوارث من بينها جائحة كورونا، التي جعلت البشرية في موقف حرج، بسبب بعض التصرفات تجاه مقاومة المرض، حيث اختلطت الأمور في ذهنية البشر حول ما يجب فعله وما يجب تركه، بجانب خطاب التهويل والترهيب الإعلامي الذي واكب هذه الجائحة، فجاء هذا البحث لمناقشة الأثر القيمي للوباء العابر للحدود، وهو بمثابة استرشاد توعوي بأهمية المجال الفلسفي في مثل هذه النوازل الكونية، وكيف يعمل هذا المجال على ترسيخ التمسك بالقيم الإنسانية، وتعزيز الأخلاق المهنية، لا سيما في الجانب الطبي، أن الدعوة إلى تثبيت القيم والإشارة إليها في زمن قدس فيه الإنسان الماديات وابتعد عن احترام قيمة المعنويات شيء في غاية الأهمية.
أن عملية توكيد القيم الإنسانية والحث والتبصير بها لمقاومة بعض السلوكيات السلبية التي تمارس في المجال الطبي ستسهم في الحفاظ على القيمة الوجودية للإنسان، أننا نحاول أن نستخلص موقف المجال الفلسفي إزاء هذا العالم المضطرب بالأحداث والثورات العلمية ذات الصلة بقيمة الإنسان، فمسألة الإشارة إلى القيم الإنسانية ذات قيمة في تحديد مسار الأخلاق الطبية أمام التصاعد المستمر والسريع في مجال الطب والبيولوجية، فالتطور الحاصل في هذا المجال العلمي هدّد القيم، وسبّب بعض الاضطرابات حول معرفة مقاييسها، ومستوياتها، ومدى مصداقيتها، ولهذا هناك مشاكل متعلقة بالجانب الأخلاقي الذي يجب علينا الإشارة إليه، والعمل على ضرورة التأكيد على الالتزام بالمبادئ والقيم الإنسانية التي حددتها البشرية عبر مواثيق دينية وقانونية مختلفة.
Les Misérables, roman historique
Authors: EL ARIBI Khadija  Elzenati 
Published: January 2024

Le roman, ou l’œuvre de Victor Hugo, qui n’est pas seulement un chef d’œuvre, on décèle au fur et à mesure qu’on tourne les pages, l’innovation de certains évènements qui ont fait, et font toujours l’histoire.
D’une part, par ses personnages historiques, qu’on peut dire programmés et ancrés fortement dans les mémoires. On y trouve des chapitres qui forment de grandes fresques historiques. Comme en 1817 « Waterloo ».
Le narrateur a raconté une visite à pied sur les vestiges de la défaite napoléonienne. Victor Hugo réfléchit sur les causes de ce désastre napoléonien.
Nous constatons que l’auteur des Misérables a introduit dans son roman, des personnages comme Thénardier, (personnage qui dépouillait les cadavres, et qui est arrivé à sauver de la mort un colonel) alors qu’il racontait dans ce passage funèbre cette défaite de Waterloo.
Les évènements historiques dans ce roman, sont nombreux et divers. Ils relatent la vie mouvementée des personnages, leur misère, leur courage.
Nous remarquerons aussi qu’à cette époque, lors de l’évènement républicain du 5 Juin 1832 , alors que l’on enterrait le général Larque après son échec dans la bataille, une fameuse phrase a été prononcée : « les morts ont raison, et les vivants n’ont pas tort ». L’insurrection de 1832 n’a pas été du tout interprété comme il fallait le dire par
(le soulèvement du peuple).
Hugo situe l'action entre 1815 et 1832 car il a aimé cette époque. Hugo est un homme de la génération romantique. Dans Les Misérables, l'histoire occupe une grande place à travers deux périodes. Ces deux époques ne sont pas choisies au hasard, elles représentent l'une ce que Hugo a aimé dans sa jeunesse, l'autre, des événements qu'il a vécus et qui l'ont sans doute influencé dans le reste de sa vie.
Experimental Medications Made with <i>Сetraria islandica</i> Showing Antiviral Activity against Influenza A Virus
Authors: Makarevich E. V. , Protsenko M. A. , Mazurkov O. Yu. , Filippova E. I. , Mazurkova N. A. 
Published: January 2024

Background. To date, virologists have identified more than 25,000 influenza virus А serotypes, and their number will increase in the future. Therefore, the development of new antiviral drugs will always be relevant.The aim of the study is to obtain and test the chemical composition and antiviral activity of the lichen Cetraria islandica extracts against the influenza A virus.Material and methods. Samples of lichen Cetraria islandica (aqueous and ethanol extracts) were tested for toxic properties and antiviral activity against influenza A virus in MDCK cell culture.Results. Samples of aqueous and ethanol extracts of Cetraria islandica were obtained; their chemical composition was described. In MDCK cell culture, the extracts exhibited antiviral activity against human influenza virus А/H3N2 and avian influenza virus А/H5N1. When studying the mechanism of action of Cetraria islandica extracts, it was noted that Cetraria islandica samples possess pronounced antiviral properties against avian influenza A/chicken/Kurgan/05/2005 (H5N1) and human influenza A/Aichi/2/68 (H3N2) at the stage of their adsorption and reproduction.Conclusions. Samples of Cetraria islandica have antiviral activity at the stage of adsorption and reproduction of influenza A virus in MDCK cell culture. The ethanol extract shows a higher antiviral efficacy compared to the aqueous extract.
Bilateral bidirectional superior cavopulmonary shunt is more beneficial in medium and long term clinical outcomes than unilateral shunt
Authors: XU Yao-qiang , LIU Ying-long , LÜ Xiao-dong , LI Yong-qing , YU Cun-tao 
Published: January 2024

Background
The present study was aimed to compare the effects of bilateral and unilateral bidirectional superior cavopulmonary shunt (b-BDG and u-BDG) on pulmonary artery growth and clinical outcomes.

Methods
The 51 subjects enrolled in this study were divided into two groups: those receiving b-BDG (n=21) and those receiving u-BDG (n=30). Clinical records were reviewed retrospectively at a mean of 43.3 months after BDG procedures. Chi square and t-tests were performed to analyze the data.

Results
Left and right pulmonary artery diameters increased 27%-37% in both groups. The pulmonary artery index increased 37.2% after b-BDG and 27.0% after u-BDG. b-BDG patients experienced a significant decrease in mean hemoglobin concentration and hematocrit value, and a correlated change in postoperative diameter of left pulmonary artery (LPA) and pulmonary artery index (y=0.2719, x=-1.8278; R=0.564, P=0.008). The change ratio of hemoglobin and postoperative LPA were also correlated in b-BDG patients (y= -0.0522x + 0.3539; R=-0.479, P=0.028). Only one b-BDG patient versus twelve u-BDG patients needed total cavopulmonary connections 31.8 months after BDG surgery (P=0.0074). Moreover, only one (4.8%) b-BDG patient but eight u-BDG patients (26.7%) developed pulmonary arteriovenous malformations.

Conclusions
b-BDG increases bilateral pulmonary blood flow and promotes growth of bilateral pulmonary arteries, with preferable physiological outcomes to u-BDG. Results may imply that subsequent Fontan repair may not always be needed.
Using intramyocardial electrograms combined with other noninvasive methods for monitoring acute rejection following human heart transplantation
Authors: JIA Yi-xin , MENG Xu , SUN Ling-bo , HAN Jie , CHEN Yang-tian 
Published: January 2024

Background
Acute allograft rejection in heart transplantation remains as one of the major complications. Obligatory graft surveillance is still achieved with the invasive and expensive endomyocardial biopsy (EMB). Our study aimed to study the use of intramyocardial electrograms combined with other noninvasive methods for the monitoring of acute rejection after human heart transplantation.

Methods
Permanent pacemakers were implanted in 58 patients undergoing heart transplantations. Intramyocardial electrograms (IMEG) were recorded periodically and the results were compared with those from EMBs. The R wave amplitude of the IMEG was used as the index value, the average R wave amplitude at the third week following transplantation was considered as the baseline, and a reduction of >20% compared with the baseline was regarded as a positive result. EMB was performed in cases of positive IMEG results and also at other times. Other noninvasive methods were used to help the diagnosis. Acute rejection (AR) was defined as International Society of Heart-Lung Transplantation grade IIIA or higher.

Results
We obtained 1231 IMEG records and 127 EMBs. Of the total 127 EMBs, 53 were positive, in which there were 42 IMEG positive results and 11 negative, while in the rest 74 negative EMBs, there were 9 IMEG positive results and 65 negative. The sensitivity of IMEG for the diagnosis of AR was 79.2%, and the specificity was 87.8%. The positive predictive value was 82.4% and the negative predictive value was 85.5%. Of the total of 1231 IMEG records, 51 were positive and 1180 were negative. Excluding 11 proved by EMB to be false negative, if the other 1169 were considered as no evidence of rejection, through the other noninvasive methods, AR diagnosed by this noninvasive monitoring strategy, the sensitivity was 79.2%, and the specificity was 99.2%. The positive predictive value was 82.4% and the negative predictive value was 99.1%.

Conclusions
IMEG can be used as a noninvasive method for monitoring AR following heart transplantation. It is a continuous, safe and inexpensive method, and could reduce the need for EMB combined with other noninvasive methods, without reducing the detection of rejection.
The regulating role of mutant IκBα in expression of TIMP-2 and MMP-9 in human glioblastoma multiform
Authors: HU Yu-hua , YU Li-Jie , SHAO En-de , WU Jian-liang , JI Jian-wen 
Published: January 2024

Background
Our previous studies demonstrated that mutant IκBα (IκBαM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IκBαM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IκBαM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM.

Methods
We established the following four GBM cell lines stably expressing IκBαM by plasmid construction, gene transfection and screening for IκBαM protein expression: mutant IκBα-transfected cells (G36δ-M), wild-type IκBα-transfected cells (G36δ-W), empty plasmid transfected cells (G36δ-P) and untransfected cells (G36δ). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods.

Results
The results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36δ-M group at both the RNA and protein levels compared with the G36δ-W group, G36δ-P group and G36δ group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36δ-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups.

Conclusions
Our findings indicate that IκBαM inhibits the activation of NF-κB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IκBαM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.
Overexpression or knock-down of runt-related transcription factor 1 affects BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo in mice
Authors: YANG Li-jun , YU Wei-dong , DU Jun-bao , CHAO Shuang , CHEN Min-xia , ZHAO He-hua , GUO Jing-zhu 
Published: January 2024

Background
Runt-related transcription factor 1 (Runx1) plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runx1 will induce leukemia and how the change of Runx1 expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runx1 in BaF3 cells alone would induce leukemogenesis. And we also wanted to know if abnormal expression of Runx1 in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runx1 in BaF3 cells would induce leukemogenesis.

Methods
Plasmids containing full-length Runx1 cDNA were transduced into BaF3 cells and BaF3-P185wt cells (BCR-ABL transformed BaF3 cells) by electroporation. Plasmids containing a short hairpin RNA of Runx1 were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runx1 expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runx1 on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-EGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes.

Results

In vitro analysis revealed that overexpression of Runx1 in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runx1 could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe splenomegaly and hepatomegaly. No splenomegaly or hepatomegaly was detected in mice transplanted with MSCV-BaF3-Runx1 cells or MSCV-BaF3-shRNA cells. Both the mice of MSCV-BaF3-Runx1 group and MSCV-BaF3-shRNA group were healthy with no sign of leukemia for up to three months.

Conclusions
Overexpression or knock-down of Runx1 gene in BaF3 cells alone could not induce leukemogenesis. However, in BaF3-P185wt cells, alteration of Runx1 expression could affect BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo.
Vascular endothelial growth factor up-regulates the expression of intracellular adhesion molecule-1 in retinal endothelial cells via reactive oxygen species, but not nitric oxide
Authors: ZHANG Xiao-ling , WEN Liang , CHEN Yan-jiong , ZHU Yi 
Published: January 2024

Background
The vascular endothelial growth factor (VEGF) is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 (ICAM-1) is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells (ECs) is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs.

Methods
Bovine retinal ECs (BRECs) were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF (100 ng/ml) and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase (eNOS) were detected using Western blotting. Griess reaction was used to detect nitric oxide (NO).

Results
Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C (PKC) altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase (PI3K) or reactive oxygen species (ROS) significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased.

Conclusion
ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.
Mitochondrial DNA 4977-bp deletion correlated with reactive oxygen species production and manganese superoxide dismutase expression in gastric tumor cells
Authors: WANG Juan , LÜ You-yong 
Published: January 2024

Background
Mitochondrial DNA 4977-bp deletion (ΔmtDNA4977) was reported in many human neoplasia. However, its biological significance remains to be evaluated and the molecular mechanism needs to be investigated. In this study, we analyzed the frequency of ΔmtDNA4977 in gastric cancer (GC) cell lines and tissues, as well as reactive oxygen species (ROS) contents and manganese superoxide dismutase (MnSOD) expression levels in GC cell lines to explore its biological significance and molecular mechanism.

Methods
Semi-quantitative PCR and real-time PCR were used to detect the incidence of ΔmtDNA4977 in 13 GC cell lines and 272 human gastric tissues (108 GC specimens and the respective adjacent normal tissues, and 56 normal gastric mucosa from non-cancer patients). We further identified intracellular ROS production by flow cytometry and MnSOD expression by semi-quantitative reverse transcription-PCR (RT-PCR) and Western blotting. Statistical analyses were carried out using the Logistic regression analysis and Kaplan-Meier method.

Results
Based on our earlier study, we optimized the PCR amplification condition by reducing the cycle number. In this study, we systematically documented the high incidence of ΔmtDNA4977 in GC cell lines (10/13, 76.9%), GC tissues (86/108, 79.6%), matched normal tissues (73/108, 67.6%), and normal gastric mucosa of non-cancer patients (29/56, 51.8%). A significantly higher incidence of mutated ΔmtDNA4977 was observed in GC tissues with respect to the adjacent normal tissues (79.6% vs 67.6%, P=0.045), and they were both higher than that in normal controls (P <0.05). Most importantly, we linked the ΔmtDNA4977 mutations with the expression level of MnSOD and ROS contents. The cell lines containing lower expression level of MnSOD was found to have generally higher frequent ΔmtDNA4977 and more ROS.

Conclusion
The decreased anti-oxidative ability, which leads to increased ROS contents, is correlated with the mtDNA damage during gastric carcinogenesis.

Chin Med J 2009;122(4):431–436
Predictors and clinical significance of the positive cone margin in cervical intraepithelial neoplasia III patients
Authors: SUN Xiao-guang , MA Shui-qing , ZHANG Jin-xia , WU Ming 
Published: January 2024

Background
Conization is being widely accepted for diagnosis and treatment of cervical intraepithelial neoplasia (CIN). There is controversy as to which factors are most predictive of a positive cone margin and the clinical significance of it. We conducted this study to identify the predictive factors and to evaluate the clinical significance of a positive cone margin in CIN III patients.

Methods
A retrospective review was conducted of 207 patients who had undergone conization due to CIN III from January 2003 to December 2005 at Peking Union Medical College Hospital. Of these, 67 had a subsequent hysterectomy. Univariate and multivariate analysis were utilized to define the predictive factors for a positive cone margin, and to compare the pathologic results of conization with subsequent hysterectomy.

Results
One hundred and fifty-one (72.9%) were margin free of CIN I or worse, 37 (17.9%) had CIN lesions close to the margin and 19 (9.2%) had margin involvement. Atotal of 56 cases (27.1%) had positive cone margins (defined as the presence of CIN at or close to the edge of a cone specimen). Univariate analysis showed that the parity, cytological grade, multi-quadrants of CIN III by punch biopsy, gland involvement, as well as the depth of conization were significant factors correlated with a positive cone margin (P <0.05). However the age, gravidity, grade of dysplasia in punch biopsy, as well as the cone methods were not significantly correlated (P >0.05). Multivariate analysis revealed that the cytological grade (OR=1.92), depth of conization (OR=2.03), parity (OR=3.02) and multi-quadrants of CIN III (OR=4.60) were significant predictors with increased risk for positive margin. The frequency of residual CIN I or worse in hysterectomy specimens was found to be 55.6% (20/36) in patients who were margin free, 71.4% (15/21) in patients with CIN occurring close to margin, and 80.0% (8/10) in patients with margin involvement. The frequency of residual CIN III or worse was found to be 13.9% (5/36), 23.8% (5/21) and 50.0% (5/10) respectively in different groups.

Conclusions
Cytological grade, depth of conization, parity and multi-quadrants of CIN III in punch biopsy were significant factors with increased risk in predicting a positive cone margin. Margin status of conization did not mean the presence or absence of CIN, but rather the varied frequency of residual CIN in specimens of subsequent hysterectomy. In view of this fact, it is suggested that the margin status of conization be a valuable surrogate marker for clinical management of CIN III.
Issues on the selection of non-inferiority margin in clinical trials
Authors: HOU Yan , WU Xiao-yan , LI Kang 
Published: January 2024

Objective
The determination of non-inferiority margin is an important and confusing issue which directly influences the acceptability of a new medication. We reviewed the published literature, International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guidelines and Committee for Proprietary Medicinal Products (CPMP) papers on the selection of non-inferiority margin and the corresponding statistical tests in clinical trials, in order to provide practical recommendations and suggestions for establishing reference criteria for the non-inferiority margin in China.

Data sources
The literature on the selection of a non-inferiority margin and statistical tests was mainly extracted from relevant English articles on non-inferior clinical trials published from 1990 to 2007. The starting point (1990) was chosen due to lack of such papers published prior to 1990. This literature was searched via PubMed, Medline and Chinese Knowledge Information (CNKI). ICH guidelines and CPMP papers were downloaded from their official websites. The keywords “clinical trial”, “non-inferiority” and “non-inferiority margin” were used.

Study selection
Forty-three original articles and critical reviews, ICH E10 guideline and CPMP papers were selected.

Results
The non-inferiority testing with treatment difference and ratio are commonly used, where the non-inferiority margin is determined with and without historical data. Traditionally, this margin is treated as a fixed value, while developed methods take the variation into account in the determination of this margin, on which the test depends is more convincing. The mixed margin consisting of a margin based on treatment difference and a margin based on treatment ratio can exactly control the type I error at the desirable level and obtain a better power. In this review, we also provide some recommendations and suggestions for the selection of the non-inferiority margin in the western countries and China.

Conclusions
Besides the magnitude and variability of the standard control and placebo effects, the determination of the margin depends on other factors, such as, the safety profiles of the two comparative therapies, method of administration and product cost. Hence the margin should be made specifically for a certain case. Reference criteria for different medications should be given to avoid the arbitrary conclusion.