bluuebunny/crossref_metadata_2025_split huggingface dataset:
The projections of global and regional rheumatic heart disease burden from 2020 to 2030
Authors: Hu Yingying , Tong Zijia , Huang Xuewei , Qin Juan-Juan , Lin Lijin , Lei Fang , Wang Wenxin , Liu Weifang , Sun Tao , Cai Jingjing , She Zhi-Gang , Li Hongliang 
Published: October 2022

BackgroundRheumatic heart disease (RHD) remains the leading cause of preventable death and disability in children and young adults, killing an estimated 320,000 individuals worldwide yearly.Materials and methodsWe utilized the Bayesian age-period cohort (BAPC) model to project the change in disease burden from 2020 to 2030 using the data from the Global Burden of Disease (GBD) Study 2019. Then we described the projected epidemiological characteristics of RHD by region, sex, and age.ResultsThe global age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) of RHD increased from 1990 to 2019, and ASPR will increase to 559.88 per 100,000 population by 2030. The global age-standardized mortality rate (ASMR) of RHD will continue declining, while the projected death cases will increase. Furthermore, ASPR and cases of RHD-associated HF will continue rising, and there will be 2,922,840 heart failure (HF) cases in 2030 globally. Female subjects will still be the dominant population compared to male subjects, and the ASPR of RHD and the ASPR of RHD-associated HF in female subjects will continue to increase from 2020 to 2030. Young people will have the highest ASPR of RHD among all age groups globally, while the elderly will bear a greater death and HF burden.ConclusionIn the following decade, the RHD burden will remain severe. There are large variations in the trend of RHD burden by region, sex, and age. Targeted and effective strategies are needed for the management of RHD, particularly in female subjects and young people in developing regions.
Plasma brain injury markers are associated with volume status but not muscle health in heart failure patients
Authors: Lahiri Shouri , Mastali Mitra , Van Eyk Jennifer E. , Hitzeman Tara C. , Bresee Catherine , Raedschelders Koen , Lyden Patrick D. , Gottlieb Roberta A. , Fang James C. , Shaw Robin M. , Hong Ting Ting 
Published: October 2022

Background: Neurofilament light chain protein (NfL) and tau are plasma biomarkers of neuronal injury which can be elevated in patients with neurodegenerative diseases. N-terminal pro-brain natriuretic peptide (NT-proBNP) is an established marker of volume status in patients with heart failure (HF) and plasma cBIN1 score (CS) is an emerging biomarker of cardiac muscle health. It is not known if, in HF patients, there is a correlation between cardiac markers and brain injury markers.Methods: We studied ambulatory HF patients with either preserved and reduced ejection fraction (N = 50 with 25 HFrEF and 25 HFpEF) and age and sex matched healthy controls (N = 50). Plasma NT-proBNP and CS were determined using commercial kits. A bead-based ELISA assay was used to quantify femtomolar concentrations of plasma neuronal markers NfL and total tau.Results: Plasma levels of NT-proBNP and CS in heart failure patients were significantly higher than those from healthy controls. In both patients with HFrEF and HFpEF, we found independent and direct correlations between the volume status marker NT-proBNP, but not the cardiomyocyte origin muscle health marker CS, with NfL (r = 0.461, p = 0.0007) and tau (r = 0.333, p = 0.0183).Conclusion: In patients with HF with or without preserved ejection fraction, plasma levels of NfL and tau correlate with volume status rather than muscle health, indicating volume overload-associated neuronal injury.
Integration analysis identifies the role of metallothionein in the progression from hepatic steatosis to steatohepatitis
Authors: Li Xiaoya , Zhong Shaoping , Sun Yifan , Huang Xinmei , Li Yue , Wang Lihong , Wu Yueyue , Yang Min , Yuan Hai-Xin , Liu Jun , Zang Shufei 
Published: October 2022

BackgroundNon-alcoholic fatty liver disease (NAFLD), a metabolic disorder that develops from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), has become an epidemic of chronic liver dysfunction worldwide. However, mechanisms that govern the transition from NAFL to NASH have not been fully elucidated.MethodsGene expression profile data of NAFLD liver tissues were obtained from Gene Expression Omnibus (GEO), including three microarray datasets with 60 NAFL and 44 NASH patients. Integrative differentially expressed genes (DEGs) between NAFL and NASH patients were identified using robust rank aggregation (RRA) analysis. Hub genes were identified combined with gene ontology functional annotation and protein–protein interaction network construction and validated using a sequencing dataset. Huh-7 cells with palmitate-induced lipid overload and NAFLD-diet mouse model of different stages were used to verify our findings.ResultsRRA analysis determined 70 robust DEGs between NAFL and NASH. The most robustly upregulated genes were SPP1, AKR1B10, CHST9, and ANXA2, while the most robustly downregulated DEGs were SNORD94, SCARNA10, SNORA20, and MT1M. Cellular response to zinc ion (GO: 0071294) ranked first in GO analysis of downregulated genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that mineral absorption (hsa04978) was significantly enriched. The involvement of the metallothionein pathway was further validated by the decrease of Mt1 expression during NAFL to NASH progression in NAFLD mice and the protection from lipotoxicity in liver cells by overexpressing MT1M.ConclusionsOur integrated analysis identified novel gene signatures and provided comprehensive molecular mechanisms underlying the transition from NAFL to NASH. Metallothionein might be a potential intervention target for NAFLD progression.
Complexity of daily precipitation and its change in China during 1961–2015 based on approximate entropy
Authors: Zhao Shanshan , Mei Ying , Jiang Yundi , Wan Shiquan , He Wenping 
Published: October 2022

Approximate entropy (ApEn) can measure the regularity and complexity of a nonlinear system. We find that the results of ApEn are relatively stable when the sample size of a time series exceeds 100, which indicates that the estimation results of the ApEn algorithm are robust to small sample data. In this study, the complexity of the daily precipitation records in China from 1961 to 2015 was first analyzed by using ApEn, and then we further investigated the spatial and temporal variability of the dynamical characteristics of precipitation. The results show that the ApEn values of daily precipitation in China during 1961–2015 present the following characteristics: larger in southern and eastern China and smaller in northern and western China. In addition, ApEn in Northwest China and the Tibetan Plateau has been increasing since 1961. However, since the 1970s, ApEn in the south of the middle and lower reaches of the Yangtze River shows a gradual decrease. The temporal instances of abrupt ApEn changes in daily precipitation occur from region to region. The number of stations with an abrupt ApEn shift has a statistically significant increase since 1984 at a significant level of α = 0.01, which means the complexity characteristic of daily precipitation in China has been more prone to abrupt shifts since 1984 than in the previous period.
Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma
Authors: Li Hujun , Zhao Lina , Sun Zengtian , Yao Yue , Li Li , Wang Jiaojiao , Hua Tian , Ji Shengwei , Wang Shiyuan , Cheng Hai , Shi Ming , Li Zhenyu , Zeng Lingyu , Wu Qingyun , Qiao Jianlin , Chen Chong , Zheng Junnian , Cao Jiang , Xu Kailin 
Published: October 2022

Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (P=0.011; P=0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, P=0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; P=0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.Clinical trial registrationThis trial was registered on 1 May 2017 at http://www.chictr.org.cn as ChiCTR-OIC-17011272.
Assessment and validation of the TREAT-B score to assess the treatment eligibility of patients with chronic hepatitis B virus infection
Authors: Thanapirom Kessarin , Suksawatamnuay Sirinporn , Thaimai Panarat , Treeprasertsuk Sombat , Komolmit Piyawat , Tangkijvanich Pisit 
Published: October 2022

Background and aimsAccess to Hepatitis B virus (HBV) DNA testing to determine treatment eligibility is limited in low-income countries. Therefore, this study aimed to assess and validate the TREAT-B score proposed as the treatment threshold in an Asian cohort in determining the HBV treatment eligibility.MethodsA retrospective analysis was conducted on consecutive patients with treatment-naïve chronic HBV mono-infection who visited the liver clinic at Chulalongkorn University Hospital, Bangkok, Thailand, from 2016 to 2020. The 2018 American Association for the Study of Liver Diseases guideline was the reference standard.ResultsOverall, 825 patients with chronic HBV infection were enrolled, comprising 409 (50.4%) males, with a median age of 50 (38–58) years. Of these, 216 (26.2%), 565 (68.5%), and 377 (45.7%) were eligible for treatment based on the AASLD, TREAT-B score, and simplified WHO criteria, respectively. The area under the receiver operating characteristics curve (AUROC) of the TREAT-B ≥ 2 was better than the simplified WHO criteria (0.69 vs. 0.62, p = 0.006) for selecting patients eligible for antiviral therapy. The sensitivity and specificity of the TREAT-B ≥ 2 were 96.3% and 41.4%, respectively. Applying the TREAT-B ≥ 3 improved the specificity (89.0%) and AUROC (0.80, 95% CI 0.76–0.84, but reduced the sensitivity (70.8%) for selecting eligible patients for HBV therapy.ConclusionsIn resource-constrained countries where HBV DNA is unavailable, the TREAT-B score is an alternative criteria for indicating treatment eligibility. The TREAT-B score of ≥3 is highly accurate and may minimize the number of patients unnecessarily treated in Asian HBV patients.
Decision making under uncertainty in the diagnosis and management of Alzheimer's Disease in primary care: A study protocol applying concepts from neuroeconomics
Authors: Saposnik Gustavo , Ismail Zahinoor , Rivard Anne-Marie , Knifton Debbie , Bromfield Gillian , Terzaghi Maria , Montoya Alonso , Menard Marie-Chantal 
Published: October 2022

BackgroundThe current management of patients with Dementia, primarily with Alzheimer's Disease (AD) is rapidly evolving. However, limited information is available about the current gaps and decision-making in primary care.ObjectivesTo evaluate factors associated with gaps, risk preferences regarding diagnostic and therapeutic choices in the management of patients with AD by primary care physicians (PCP) from across Canada.MethodsWe propose a non-interventional, cross-sectional pilot study involving 120 primary care physicians referred from the College of Family Physicians of Canada to assess diagnostic and therapeutic decisions in the management of ten simulated AD-related case-scenarios commonly encountered in clinical practice. We initially describe the current landscape and gaps regarding diagnostic and therapeutic challenges in the management of patients with AD in primary care. Then, we provide concepts from behavioral economics and neuroeconomics applied to medical decision-making. Specifically, we include standardized tests to measure risk aversion, physicians' reactions to uncertainty, and questions related to risk preferences in different domains. Finally, we summarize the protocol to be implemented to address our goals. The primary study outcome is the proportion of participants that elect to defer initial investigations to the specialist and the associated factors. Secondary outcomes include the proportion of PCP willing to order cerebral spinal fluid studies, PET scans, or initiate treatment according to the simulated case-scenarios. The study will be conducted in English and French.ConclusionsThe study findings will contribute a better understanding of relevant factors associated with diagnostic and therapeutic decisions of PCP in the management of AD, identifying participant's preferences and evaluating the role of behavioral aspects such tolerance to uncertainty, aversion to ambiguity, and therapeutic inertia.
Bibliometric analysis of research on Alzheimer’s disease and non-coding RNAs: Opportunities and challenges
Authors: Fei Xinxing , Wang Shiqi , Li Jiyang , Zeng Qiu , Gao Yaqian , Hu Yue 
Published: October 2022

BackgroundNon-coding RNAs (ncRNA) are a kind of RNA that does not encode protein, which play an important role in Alzheimer’s disease (AD). However, there is a lack of bibliometric analysis and visualization analysis of the research related to AD and ncRNAs.Materials and methodsLiterature related to AD and ncRNAs in the last decade were searched through the Web of Science Core Collection (WOSCC). The relevant information from all the searched articles was collected. The bibliometric visualization website, CiteSpace, and VOSviewer were used for visualization analysis of countries/regions, institutions, authors, and keywords.ResultsIn total, 1,613 kinds of literature were published in the field. Literature in this field were published in 494 journals. The Journal of Alzheimer’s Disease was the most popular journal. China, Louisiana State University System, and Lukiw WJ were the countries/regions, institutions, and authors with the highest scientific productivity, respectively. The research hotspots in this field focused on the role and mechanism of ncRNAs, especially microRNAs, in AD. The level of research was mainly based on basic research, focusing on animal and cellular levels, and related to proteomics. “Circular RNAs,” “regulation of neuroinflammation,” and “tau protein” were the future research directions.ConclusionTaken together, the field of AD and ncRNAs is developing well. The research hotspots and frontiers in this field can provide a reference for researchers to choose their research direction.
Impact of respiratory motion on lung dose during total marrow irradiation
Authors: Kavak Ayse Gulbin , Surucu Murat , Ahn Kang-Hyun , Pearson Erik , Aydogan Bulent 
Published: October 2022

We evaluated the impact of respiratory motion on the lung dose during linac-based intensity-modulated total marrow irradiation (IMTMI) using two different approaches: (1) measurement of doses within the lungs of an anthropomorphic phantom using thermoluminescent detectors (TLDs) and (2) treatment delivery measurements using ArcCHECK where gamma passing rates (GPRs) and the mean lung doses were calculated and compared with and without motion. In the first approach, respiratory motions were simulated using a programmable motion platform by using typical published peak-to-peak motion amplitudes of 5, 8, and 12 mm in the craniocaudal (CC) direction, denoted here as M1, M2, and M3, respectively, with 2 mm in both anteroposterior (AP) and lateral (LAT) directions. TLDs were placed in five selected locations in the lungs of a RANDO phantom. Average TLD measurements obtained with motion were normalized to those obtained with static phantom delivery. The mean dose ratios were 1.01 (0.98–1.03), 1.04 (1.01–1.09), and 1.08 (1.04–1.12) for respiratory motions M1, M2, and M3, respectively. To determine the impact of directional respiratory motion, we repeated the experiment with 5-, 8-, and 12-mm motion in the CC direction only. The differences in average TLD doses were less than 1% when compared with the M1, M2, and M3 motions indicating a minimal impact from CC motion on lung dose during IMTMI. In the second experimental approach, we evaluated extreme respiratory motion 15 mm excursion in only the CC direction. We placed an ArcCHECK device on a commercial motion platform and delivered the clinical IMTMI plans of five patients. We compared, with and without motion, the dose volume histograms (DVHs) and mean lung dose calculated with the ArcCHECK-3DVH tool as well as GPR with 3%, 5%, and 10% dose agreements and a 3-mm constant distance to agreement (DTA). GPR differed by 11.1 ± 2.1%, 3.8 ± 1.5%, and 0.1 ± 0.2% with dose agreement criteria of 3%, 5%, and 10%, respectively. This indicates that respiratory motion impacts dose distribution in small and isolated parts of the lungs. More importantly, the impact of respiratory motion on the mean lung dose, a critical indicator for toxicity in IMTMI, was not statistically significant (p &gt; 0.05) based on the Student’s t-test. We conclude that most patients treated with IMTMI will have negligible dose uncertainty due to respiratory motion. This is particularly reassuring as lung toxicity is the main concern for future IMTMI dose escalation studies.
Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation
Authors: Iacob Speranta , Iacob Razvan , Manea Ioana , Uta Mihaela , Chiosa Andrei , Dumbrava Mona , Becheanu Gabriel , Stoica Luminita , Popa Codruta , Brasoveanu Vlad , Hrehoret Doina , Gheorghe Cristian , Gheorghe Liana , Dima Simona , Popescu Irinel 
Published: October 2022

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis.
Effects of trunk posture on cardiovascular and autonomic nervous systems: A pilot study
Authors: Wang Hao , Gao Xiaolin , Shi Yongjin , Wu Dongzhe , Li Chuangtao , Wang Wendi 
Published: October 2022

Objective: Although regular and moderate physical activity has been shown to improve the cardiovascular and autonomic nervous systems, little has been done to study the effects of postural changes in the movement on the heart and autonomic nervous system. To uncover changes in cardiac function and autonomic nerves induced by different underlying posture transitions and explore which trunk postures lead to chronic sympathetic activation. Therefore, this study investigated the effects of trunk posture on the cardiovascular and autonomic nervous systems.Methods: Twelve male subjects (age 24.7 ± 1.3) underwent this study. The non-invasive cardiac output NICOM monitoring equipment and the FIRSTBEAT system are used to dynamically monitor seven trunk postures in the sitting position simultaneously (neutral position, posterior extension, forward flexion, left lateral flexion, right lateral flexion, left rotation, right rotation). Each posture was maintained for 3 min, and the interval between each movement was 3 min to ensure that each index returned to the baseline level. Repeated analysis of variance test was used to compare and analyze the differences in human cardiac function, heart rate variability index, and respiratory rate under different postures.Results: Compared with the related indicators of cardiac output in a neutral trunk position: the cardiac index (CI) was significantly reduced in forwarding flexion and left rotation (3.48 ± 0.34 vs. 3.21 ± 0.50; 3.48 ± 0.34 vs. 3.21 ± 0.46, Δ L/(min/m2)) (p = 0.016, p = 0.013), cardiac output decreased significantly (6.49 ± 0.78 vs. 5.93 ± 0.90; 6.49 ± 0.78 vs. 6.00 ± 0.96, Δ L/min) (p = 0.006, p = 0.014), the stroke volume (stroke volume)decreased significantly (87.90 ± 15.10 vs. 81.04 ± 16.35; 87.90 ± 15.10 vs. 79.24 ± 16.83, Δ ml/beat) (p = 0.017, p = 0.0003); heart rate increased significantly in posterior extension (75.08 ± 10.43 vs. 78.42 ± 10.18, Δ beat/min) (p = 0.001); left rotation stroke volume index (SVI) decreased significantly (47.28 ± 7.97 vs. 46.14 ± 8.06, Δ ml/m2) (p = 0.0003); in the analysis of HRV-related indicators, compared with the neutral trunk position, the LF/HF of the posterior extension was significantly increased (1.90 ± 1.38 vs. 3.00 ± 1.17, p = 0.037), and the LF/HF of the forward flexion was significantly increased (1.90 ± 1.38 vs. 2.85 ± 1.41, p = 0.041), and the frequency-domain index LF/HF of right rotation was significantly increased (1.90 ± 1.38 vs. 4.06 ± 2.19, p = 0.008). There was no significant difference in respiratory rate (p &gt; 0.05).Conclusion: A neutral trunk is the best resting position, and deviations from a neutral trunk position can affect the cardiovascular and autonomic nervous systems, resulting in decreased stroke volume, increased heart rate, and relative activation of sympathetic tone.