bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Treatment Patterns and Survival Outcomes of Mantle Cell Lymphoma Patients Managed at Chinese Academic Centers in the Rituximab Era: A Real-World Study
Authors: Wu Meng , Li Yun , Huang Huiqiang , Xu Wei , Wang Yanyan , Huang Haiwen , Zhao Weili , Liu Shuo , Xu Pengpeng , Chen Zhengming , Zhu Jun , Song Yuqin , Ruan Jia , Wu Depei 
Published: January 2022

PurposeThe aim of the study was to delineate the disease characteristics, the initial treatment patterns, and survival in patients with mantle cell lymphoma (MCL) managed in the real world.MethodsData of 518 MCL patients from 5 major Chinese Hematology Centers in the period from 2007 to 2017 were retrospectively analyzed.ResultsThe median age was 58 years. Of the patients, 88.6% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1 and 80.7% had advanced-stage disease. Ki67 expression was &lt;30% in 39.6% of the patients, and 43.2% of patients were categorized into a low-risk group based on the Mantle Cell Lymphoma International Prognostic Index (MIPI) scoring system. Overall, 73.4% of the patients received rituximab as their first-line therapy. The most commonly used chemotherapy was the CHOP-like (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) regimen (45.2%), followed by high-dose cytarabine-containing chemotherapy (31.3%) and bendamustine (3.3%). Of the patients, 13.7% (n = 71) underwent consolidative autologous stem cell transplantation (ASCT), and 19.3% (n = 100) received novel agents containing first-line regimens. With a median follow-up time of 52 months, the 3- and 5-year overall survival (OS) rates were 73.7% and 61.4%, respectively. Age ≤60 years, ECOG PS 0–1, stages I–II, normal lactate dehydrogenase (LDH), absence of bone marrow involvement, Ki67 &lt;30%, and lower-risk IPI/MIPI scores were significantly associated with improved OS (p &lt; 0.05). The inclusion of rituximab improved the 5-year OS, with borderline significance (62.5% vs. 55.2%, p = 0.076). High-dose cytarabine-containing chemotherapy showed significant clinical benefit in 5-year OS (72.1% vs. 55.9%, p = 0.010). Patients with ASCT had better 5-year OS in the younger (≤60 years) age group (87.2% vs. 64.8%, p = 0.002).ConclusionThis large retrospective dataset unequivocally confirmed the survival advantage afforded by cytarabine-containing regimen and ASCT in a first-line setting under real-world management in the rituximab era.
Hedgehog−Gli2 Signaling Promotes Chemoresistance in Ovarian Cancer Cells by Regulating MDR1
Authors: Wang Qian , Wei Xin , Hu Lanyan , Zhuang Lingling , Zhang Hong , Chen Qi 
Published: January 2022

BackgroundCisplatin (DDP) resistance remains a key challenge in improving the clinical outcome of patients with ovarian cancer (OC). Gli2 overexpression can lead to DDP resistance in OC cells, but the specific underlying regulatory mechanism remains unclear. The membrane transporter encoding gene MDR1 positively regulates chemotherapy resistance in various cancer types. We evaluated MDR1 as a potential Gli2 downstream target and the contribution of the Gli2/MDR1 axis in promoting DDP resistance in OC cells.MethodsTo generate drug-resistant SKOV3/DDP cells, SKOV3 cells were grown for six months under continuous induction wherein the DDP concentration was steadily increased. Gli2 expression in OC cells with varying DDP sensitivities was detected using western blot. Cell counting kit-8 assays were used to assess the DDP sensitivity of SKOV3, SKOV3/DDP, A2780, and A2780/DDP cells and reversal of DDP resistance in SKOV3/DDP and A2780/DDP cells. Cell proliferation was analyzed using 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The transcriptional regulation of MDR1 by Gli2 was determined using luciferase reporter assays. Finally, xenograft OC tumors were generated in nude mice, which were then treated with intraperitoneal DDP or phosphate-buffered saline (PBS) injections to investigate if Gli2 affected DDP resistance in OC in vivo.ResultsDDP-resistant SKOV3/DDP and A2780/DDP cells showed higher expression of Gli2 and MDR1 as compared with that in DDP-sensitive OC cells. Gli2 knockdown in SKOV3/DDP cells significantly reduced MDR1 expression, whereas it increased DNA damage, thereby sensitizing OC cells to DDP. Similar results were obtained after targeting Gli2 expression with the Gli-antagonist 61 inhibitor (GANT61) in SKOV3/DDP and A2780/DDP cells. In cells stably overexpressing Gli2, treatment with gradient concentrations of verapamil, an MDR1 inhibitor, significantly inhibited MDR1 expression. Our findings indicate that downregulation of MDR1 expression may reverse OC cell resistance to DDP. Moreover, dual-luciferase reporter gene assays confirmed that MDR1 is a direct downstream target of Gli2, with Gli2 positively regulating MDR1 expression. Finally, subcutaneous xenotransplantation in nude mice demonstrated that Gli2 plays a key role in regulating OC drug resistance.ConclusionsWe identified a mechanism by which Hedgehog-Gli signaling regulates OC chemoresistance by modulating MDR1 expression. Hence, Gli2 and MDR1 are potential biomarkers and therapeutic targets in patients with chemoresistant OC.
Uric Acid Is Elevated in Children With Obesity and Decreases After Weight Loss
Authors: Jørgensen Rasmus Møller , Bøttger Bjarke , Vestergaard Esben Thyssen , Kremke Britta , Bahnsen Rikke Frederiksen , Nielsen Bent Windelborg , Bruun Jens Meldgaard 
Published: January 2022

Introduction: Childhood obesity is an increasing condition associated with continuous obesity into adulthood and development of comorbidities. Adult studies show an association between serum uric acid (SUA) levels and body mass index (BMI). The aim of this retro perspective exploratory study was to investigate SUA in obese children and adolescents and the effects of a subsequent weight reduction.Materials and Methods: One hundred and seventy-one children (age 4–18), with obesity (i.e. BMI-SDS of +2 or higher) were included in a multifactorial lifestyle intervention. The children participating were annually measured for anthropometrics, blood samples and DEXA-scans for up to 3 years. Eighty-nine children were included for follow-up analysis.Results: After a follow-up of 20.7 ± 9.4 months a reduction in BMI-SDS of −0.34 ± 0.53 (p &lt; 0.01) was observed. SUA was found to be positively associated with changes in BMI-SDS. SUA levels decreased in the 65 children who lost weight during the trial, conversely, SUA increased in the 23 children who gained weight during the trial (p &lt; 0.01 between groups).Conclusion: SUA was found to correlate with measures of obesity and for the first time, this intervention demonstrates a positive relationship between SUA and weight reduction in children with obesity.
Pharmacokinetic/Pharmacodynamic Based Breakpoints of Polymyxin B for Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Pathogens
Authors: Bian Xingchen , Liu Xiaofen , Hu Fupin , Feng Meiqing , Chen Yuancheng , Bergen Phillip J. , Li Jian , Li Xin , Guo Yan , Zhang Jing 
Published: January 2022

The latest PK/PD findings have demonstrated negligible efficacy of intravenous polymyxins against pulmonary infections. We investigated pharmacokinetic/pharmacodynamic (PK/PD)-based breakpoints of polymyxin B for bloodstream infections and the rationality of the recent withdrawal of polymyxin susceptibility breakpoints by the CLSI. Polymyxin B pharmacokinetic data were obtained from a phase I clinical trial in healthy Chinese subjects and population pharmacokinetic parameters were employed to determine the exposure of polymyxin B at steady state. MICs of 1,431 recent clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae collected from across China were determined. Monte-Carlo simulations were performed for various dosing regimens (0.42–1.5 mg/kg/12 h via 1 or 2-h infusion). The probability of target attainment, PK/PD breakpoints and cumulative fraction of response were determined for each bacterial species. MIC90 of polymyxin B was 1 mg/L for P. aeruginosa and 0.5 mg/L for A. baumannii and K. pneumoniae. With the recommended polymyxin B dose of 1.5–2.5 mg/kg/day, the PK/PD susceptible breakpoints for P. aeruginosa, A. baumannii and K. pneumoniae were 2, 1 and 1 mg/L respectively for bloodstream infection. For Chinese patients, polymyxin B dosing regimens of 0.75–1.5 mg/kg/12 h for P. aeruginosa and 1–1.5 mg/kg/12 h for A. baumannii and K. pneumoniae were appropriate. Breakpoint determination should consider the antimicrobial PK/PD at infection site and delivery route. The recent withdrawal of polymyxin susceptible breakpoint by CLSI primarily based on poor efficacy against lung infections needs to be reconsidered for bloodstream infections.
Magnesium Isoglycyrrhizinate Ameliorates Concanavalin A-Induced Liver Injury by Inhibiting Autophagy
Authors: Fan Zihao , Li Yuxian , Chen Sisi , Xu Ling , Tian Yuan , Cao Yaling , Pan Zhenzhen , Zhang Xiangying , Chen Yu , Ren Feng 
Published: January 2022

Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury.Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry.Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy.Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.
The Human Dive Reflex During Consecutive Apnoeas in Dry and Immersive Environments: Magnitude and Synchronicity
Authors: Nordine Michael , Schwarz Anton , Bruckstein Renana , Gunga Hanns-Christian , Opatz Oliver 
Published: January 2022

Introduction: The human dive reflex (HDR), an O2 conserving reflex, is characterised by an interplay of central parasympathetic and peripheral sympathetic reactions, which are presumed to operate independently of each other. The HDR is fully activated during apnoea with facial immersion in water and complete immersion in water is thought to increase the magnitude of HDR during consecutive apnoeas. A comparison of HDR activity between consecutive apnoeas in full-body immersion with consecutive apnoeas in dry conditions has not been fully explored. Also, the interplay between parasympathetic and sympathetic reactions involved in the HDR has not been thoroughly analysed.Methods: 11 human volunteers performed 3 consecutive 60 s apnoeas with facial immersion in dry conditions (FIDC) and 3 consecutive apnoeas with facial immersion in full immersion (FIFI). Heart rate (HR), R-R interval (RRI), finger pulse amplitude (FPA), splenic width (SW) and SpO2 were all measured before, during and after apnoeas. A one-way ANOVA using Dunn’s post hoc test was performed to assess HDR activity, and a Pearson’s correlation test was performed to assess HDR synchronisation between physiological parameters during both conditions.Results: Although HDR activity was not significantly different between both conditions, HR and RRI showed progressively greater changes during FIFI compared with FIDC, while SW and FPA changes were relatively equivalent. During FIDC, significant correlations were found between SW &amp; SpO2 and FPA &amp; SpO2. During FIFI, significant correlations were found between RRI &amp; FPA, SW &amp; FPA, HR &amp; SpO2 and FPA &amp; SpO2.Discussion: While there was no significant difference found between HDR activity during FIDC and FIFI, consecutive apnoeas during FIFI triggered a greater magnitude of cardiac activity. Furthermore, significant correlations between RRI and SW with FPA indicate a crosstalk between parasympathetic tone with splenic contraction and increased peripheral sympathetic outflow during FIFI compared to FIDC. In conclusion, HDR activity during consecutive apnoeas does not differ between FIDC and FIFI. There appears to be however a greater level of synchronicity during apnoeas in FIFI compared to FIDC and that this is most likely due to the physiological effects of immersion, which could induce neural recruitment and increased cross talk of HDR pathways.
Association Between Basal Metabolic Rate and All-Cause Mortality in a Prospective Cohort of Southern Chinese Adults
Authors: Han Fengyu , Hu Feng , Wang Tao , Zhou Wei , Zhu Linjuan , Huang Xiao , Bao Huihui , Cheng Xiaoshu 
Published: January 2022

Objective: The aim of this study was to assess the relationship between basal metabolic rate (BMR) and all-cause mortality in southern Chinese adults.Methods: We prospectively examined the relationship between BMR and all-cause mortality in 12,608 Southern Chinese adults with age ≥ 35 years who participated in the National Key R&amp;D Program from 2013–2014 to 2019–2020. Cox proportional hazard models were used to examine the association between BMR and all-cause mortality.Results: A total of 809 deaths (including 478 men and 331 women) occurred during a median follow-up period of 5.60 years. All-cause mortality was higher in elderly individuals than in non-elderly individuals (11.48 vs. 2.04%, P &lt; 0.001) and was higher in male subjects than in female subjects (9.84 vs. 4.56%, P &lt; 0.001). There was a significantly inverse relationship between BMR levels and all-cause mortality in elderly male individuals (adjusted-HR per SD increase: 0.80, 95% CI: 0.70–0.91, P &lt; 0.001). Compared with BMR levels ≤ 1,115 kJ/day, there was lower all-cause mortality in third and highest BMR quartiles in the elderly male subjects (adjusted-HR: 0.71, 95% CI: 0.53–0.95, P = 0.022; adjusted-HR: 0.60, 95% CI: 0.43–0.84, P = 0.003, respectively).Conclusion: An elevated BMR was independently inversely associated with all-cause mortality in elderly male subjects in a southern Chinese population.
Enhancing Meaning in Life and Psychological Well-Being Among a European Cohort of Young Adults via a Gratitude Intervention
Authors: Czyżowska Natalia , Gurba Ewa 
Published: January 2022

Background: Strengthening the sense of meaning in life and psychological well-being brings benefits for mental health. The group particularly vulnerable to mental problems are young adults, therefore the aim of our research was to explore how a gratitude intervention will affect the sense of meaning in life, psychological well-being, general health and perceived stress among them. The research also took into account the issue of expressing gratitude.Method: The study involved 80 young adults (58 women and 22 men) who were randomly assigned to the experimental group that filled out the specially prepared diaries for a week (participants were asked to list three things for which they feel grateful, to whom they are grateful and if and how they expressed their gratitude) or the control group. Participants completed the Meaning in Life Questionnaire (MLQ), the General Health Questionnaire – 28 (GHQ-28), the Perceived Stress Scale (PSS), and the Ryff Scales of Psychological Well-Being (PWBS) twice (before and after intervention).Results: In the experimental group significant increases were observed in three areas of psychological well-being: environmental mastery, relationships with others and purpose in life. The significant decrease was also noted in anxiety/insomnia and depression symptoms as well as in perceived stress. There were no differences in the level of meaning in life. There was a positive relationship between expressing gratitude and meaning in life and psychological well-being.Conclusion: Proposed gratitude intervention has the potential to enhance psychological well-being among young adults, however, it may not be effective in enhancing meaning in life.
Spontaneous Facial Expressions and Micro-expressions Coding: From Brain to Face
Authors: Dong Zizhao , Wang Gang , Lu Shaoyuan , Li Jingting , Yan Wenjing , Wang Su-Jing 
Published: January 2022

Facial expressions are a vital way for humans to show their perceived emotions. It is convenient for detecting and recognizing expressions or micro-expressions by annotating a lot of data in deep learning. However, the study of video-based expressions or micro-expressions requires that coders have professional knowledge and be familiar with action unit (AU) coding, leading to considerable difficulties. This paper aims to alleviate this situation. We deconstruct facial muscle movements from the motor cortex and systematically sort out the relationship among facial muscles, AU, and emotion to make more people understand coding from the basic principles:
We derived the relationship between AU and emotion based on a data-driven analysis of 5,000 images from the RAF-AU database, along with the experience of professional coders.We discussed the complex facial motor cortical network system that generates facial movement properties, detailing the facial nucleus and the motor system associated with facial expressions.The supporting physiological theory for AU labeling of emotions is obtained by adding facial muscle movements patterns.We present the detailed process of emotion labeling and the detection and recognition of AU.Based on the above research, the video's coding of spontaneous expressions and micro-expressions is concluded and prospected.
Knowledge, Attitudes, Risk Perceptions, and Practices of Spanish Adolescents Toward the COVID-19 Pandemic: Validation and Results of the Spanish Version of the Questionnaire
Authors: Aguilar-Latorre Alejandra , Asensio-Martínez Ángela , García-Sanz Olga , Oliván-Blázquez Bárbara 
Published: January 2022

Background: Adolescence is a period with physical, psychological, biological, intellectual, and social changes in which there is usually little perception of risk. COVID-19 has generated constant situations of change and uncertainty worldwide. During the pandemic, the acquisition of preventive behaviors has been relevant. Various studies carried out with adults associate risk perception and the implementation of preventive behaviors with knowledge about the COVID-19 and with age, but there are not many studies with adolescents. Therefore, the objective is to validate, in Spanish, the questionnaire of the knowledge, attitudes, risk perceptions, and practices of adolescents toward the pandemic, and analyze it according to sociodemographic characteristics.Method: This study was a descriptive cross-sectional study, which included adolescents between the ages of 12–18 (n = 354). First, a translation and a back-translation of the questionnaire were performed. The questionnaire was presented in several high schools chosen by convenience sampling and following a non-probabilistic snowball sampling. Reliability and validity analyses were then carried out and the relationships between the different sociodemographic variables (gender, place of residence, level of education, if the person was in a sentimental relationship, and financial aid) were analyzed.Results: The reliability of the questionnaire is acceptable (ordinal alpha = 77%). Knowledge was higher in women, and in those with a higher level of education; and were lower in those who lived in smaller towns, as well as in those who had a member of their family receiving financial aid. In terms of attitudes and risk perceptions, younger adolescents had higher scores, and those who had a member of their family receiving financial aid, lower.Conclusion: The questionnaire is a reliable tool in the Spanish adolescent population. Knowledge was influenced by gender, place of residence, level of education, and financial aid. Attitudes and risk perceptions were influenced by age and financial aid. For practices, no predictors were found. In general, adolescents scored lower on knowledge about COVID-19, but they scored higher on COVID-19 safety practices.
Anxiety and Depression Prevalence and Risk Factors Among Patients With Cardiovascular Diseases in Post-COVID-19 China
Authors: Wu Minglan , Shen Liying , Wang Qiqi , Liu Li , Lu Sen , Jin Jianmei , Dai Zhen , Shu Zheyue 
Published: January 2022

Objective: Data are limited on the psychological disorders of patients with cardiovascular disease during the post-COVID-19 period, although mental health status is associated with morbidity and mortality. We aimed to investigate the prevalence of anxiety and depression and risk factors among patients with cardiovascular disease in the post-pandemic period.Method: A cross-sectional survey was conducted through opportunistic and snowball sampling in southeast China from 10 October to 24 November. Anxiety and depression were assessed on the hospital anxiety and depression scale (HADS).Results: A total of 435 patients with hypertension (48.05%), atrial fibrillation (17.24%), coronary artery disease (14.48%), heart failure (9.89%) and other heart diseases (10.34%) completed the survey. Interestingly, most patients reported monthly income comparable to (90.11%) or even greater than (8.51%) pre-pandemic income. The occurrence of anxiety and depression was 11.72 and 9.20%, respectively. Marital status and treatment interruption during the pandemic were independent risk factors for both anxiety and depression. Moreover, current monthly income and access to telemedicine during the pandemic were independent risk factors for anxiety.Conclusion: Patients with cardiovascular disease may experience anxiety and depression not only because of disease complications but also because of the effects of the pandemic. In facing the global challenge posed by the coronavirus, efforts should be made to improve patients' psychological well-being in the management of populations with cardiovascular disease.