bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the temporal trends of diabetes disease burden in China during 1990-2019 from a global perspective
Authors: Liu Jinli , Shen Mingwang , Zhuang Guihua , Zhang Lei
Published: May 2024

Introduction

Diabetes poses a global public health challenge and our understanding of its temporal evolution in China relative to the rest of the world is limited. Our study aims to comprehensively examine the temporal trend of diabetes DALYs in China from a global perspective.

Methods

We analyzed data on diabetes incidence, prevalence, and mortality for individuals aged ≥20 years in China and globally from the Global Burden of Disease (GBD) 2019 study. We assessed trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of diabetes in China and globally by estimating annual percentage changes (EAPCs). We employed decomposition analysis to reveal factors driving the trend of diabetes DALYs in China.

Results

During 1990-2019, the number of diabetes patients increased by 160% from 35.14 million to 91.70 million in China. The ASIR of diabetes increased from 249 per 100,000 to 329 per 100,000 in China, which was lower than the global rate (419 per 100,000 in 2019). The EAPC of diabetes incidence was also lower in China compared to the global rate (1.02% vs. 1.57%). Consistently, the age-standardized prevalence rate of diabetes increased from 4788 per 100,000 to 8170 per 100,000 during 1990-2019 in China, which remained lower than the corresponding global rate (8827 per 100,000 in 2019). Further, the ASMR of diabetes increased from 9 per 100,000 to 15 per 100,000 during 1990-2019 in China, which was lower than the corresponding global rate (30 per 100,000 in 2019). However, EAPC of diabetes mortality in China was much higher than the global level (1.75% vs. 1.07%). Globally, the rising diabetes DALYs was predominantly attributed to population growth (55.2%) and epidemiologic changes (24.6%). In comparison, population growth (48.9%) also played an important role in the increasing diabetes DALYs in China, but aging (43.7%) was second major contributor.

Conclusion

Our findings show that diabetes DALYs in China followed a global increasing trend during 1990-2019. Notably, aging has a very substantial contribution to the increase in diabetes DALYs in China in addition to population growth.
A causal examination of the correlation between hormonal and reproductive factors and low back pain
Authors: Chen Dafu , Zhou Jiaxiang , Lin Chengkai , Li Junhong , Zhu Zhengya , Rao Xuezhi , Wang Jianmin , Li Jianfeng , Chen Hongkun , Wang Fuan , Li Xianlong , Gao Manman , Zhou Zhiyu , Xi Yongming , Li Shufen
Published: May 2024

Background

The relationship between hormonal fluctuations in the reproductive system and the occurrence of low back pain (LBP) has been widely observed. However, the causal impact of specific variables that may be indicative of hormonal and reproductive factors, such as age at menopause (ANM), age at menarche (AAM), length of menstrual cycle (LMC), age at first birth (AFB), age at last live birth (ALB) and age first had sexual intercourse (AFS) on low back pain remains unclear.

Methods

This study employed Bidirectional Mendelian randomization (MR) using publicly available summary statistics from Genome Wide Association Studies (GWAS) and FinnGen Consortium to investigate the causal links between hormonal and reproductive factors on LBP. Various MR methodologies, including inverse-variance weighted (IVW), MR-Egger regression, and weighted median, were utilized. Sensitivity analysis was conducted to ensure the robustness and validity of the findings. Subsequently, Multivariate Mendelian randomization (MVMR) was employed to assess the direct causal impact of reproductive and hormone factors on the risk of LBP.

Results

After implementing the Bonferroni correction and conducting rigorous quality control, the results from MR indicated a noteworthy association between a decreased risk of LBP and AAM (OR=0.784, 95% CI: 0.689-0.891; p=3.53E-04), AFB (OR=0.558, 95% CI: 0.436-0.715; p=8.97E-06), ALB (OR=0.396, 95% CI: 0.226-0.692; p=0.002), and AFS (OR=0.602, 95% CI: 0.518-0.700; p=3.47E-10). Moreover, in the reverse MR analysis, we observed no significant causal effects of LBP on ANM, AAM, LMC and AFS. MVMR analysis demonstrated the continued significance of the causal effect of AFB on LBP after adjusting for BMI.

Conclusion

Our study explored the causal relationship between ANM, AAM, LMC, AFB, AFS, ALB and the prevalence of LBP. We found that early menarche, early age at first birth, early age at last live birth and early age first had sexual intercourse may decrease the risk of LBP. These insights enhance our understanding of LBP risk factors, offering valuable guidance for screening, prevention, and treatment strategies for at-risk women.
Global trends in research on aging associated with periodontitis from 2002 to 2023: a bibliometric analysis
Authors: Liu Xiaomeng , Li Hongjiao
Published: May 2024

Background

Aging has been implicated in many chronic inflammatory diseases, including periodontitis. Periodontitis is an inflammatory disease caused by long-term irritation of the periodontal tissues by the plaque biofilm on the surface of the teeth. However, only a few bibliometric analyses have systematically studied this field to date. This work sought to visualize research hot spots and trends in aging associated with periodontitis from 2002 to 2023 through bibliometric approaches.

Methods

Graphpad prism v8.0.2 was used to analyse and plot annual papers, national publication trends and national publication heat maps. In addition, CtieSpace (6.1.6R (64-bit) Advanced Edition) and VOSviewer (version 1.6.18) were used to analyse these data and visualize the scientific knowledge graph.

Results

The number of documents related to aging associated with periodontitis has steadily increased over 21 years. With six of the top ten institutions in terms of publications coming from the US, the US is a major driver of research in this area. journal of periodontology is the most published journal in the field. Tonetti MS is the most prolific authors and co-cited authors in the field. Journal of Periodontology and Journal of Clinical Periodontology are the most popular journals in the field with the largest literature. Periodontitis, Alzheimer’s disease, and peri-implantitis are current hot topics and trends in the field. Inflammation, biomarkers, oxidative stress cytokines are current research hotspots in this field.

Conclusion

Our research found that global publications regarding research on aging associated with periodontitis increased dramatically and were expected to continue increasing. Inflammation and aging, and the relationship between periodontitis and systemic diseases, are topics worthy of attention.
Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection
Authors: Yang Kangping , Zhang Yihan , Ding Jiatong , Li Zelin , Zhang Hejin , Zou Fang
Published: May 2024

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like β cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D.
Meta-analysis shows that mesenchymal stem cell therapy can be a possible treatment for diabetes
Authors: Habiba Umm E. , Khan Nasar , Greene David Lawrence , Ahmad Khalil , Shamim Sabiha , Umer Amna
Published: May 2024

Objective

This meta-analysis includes the systematic literature review and meta-analysis involving clinical trials to assess the efficacy and safety of mesenchymal stem cell (MSC) transplantation for treating T1DM and T2DM.

Methods

We searched PubMed, ScienceDirect, Web of Science, clinicaltrials.gov, and Cochrane Library for “published” research from their inception until November 2023. Two researchers independently reviewed the studies’ inclusion and exclusion criteria. Our meta-analysis included 13 studies on MSC treatment for diabetes.

Results

The MSC-treated group had a significantly lower HbA1c at the last follow-up compared to the baseline (MD: 0.95, 95% CI: 0.33 to 1.57, P-value: 0.003< 0.05), their insulin requirement was significantly lower (MD: 0.19, 95% CI: 0.07 to 0.31, P-value: 0.002< 0.05), the level of FBG with MSC transplantation significantly dropped compared to baseline (MD: 1.78, 95% CI: -1.02 to 4.58, P-value: 0.212), the FPG level of the MSC-treated group was significantly lower (MD: -0.77, 95% CI: -2.36 to 0.81, P-value: 0.339 > 0.05), and the fasting C-peptide level of the MSC-treated group was slightly high (MD: -0.02, 95% CI: -0.07 to 0.02, P-value: 0.231 > 0.05).

Conclusion

The transplantation of MSCs has been found to positively impact both types of diabetes mellitus without signs of apparent adverse effects.
The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews
Authors: Younis Johnny S. , Taylor Hugh S.
Published: May 2024

Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.
The Blasingame method considering the effect of inter-well interference in a circular homogeneous closed reservoir
Authors: Du Pengfei , Wang Qi , Zhang Jing , Wang Yanwei , Wang Dong , Han Yi , Liu Pengcheng
Published: May 2024

The Blasingame method is a valuable tool for analysing the diminishing production challenge in the presence of variable bottomhole pressure and diverse production conditions. It is essential to highlight that the Blasingame method views the closed reservoir as the outer boundary condition for its model. This paper introduces the concept of the equivalent well control radius and formulates the Blasingame method based on the fluid flow characteristics inherent in twin-well production, taking into account the influence of inter-well interference. This study provides an in-depth analysis of production variations in reservoirs with inter-well interference by examining Blasingame type-curve definitions of the dimensionless parameters. Additionally, it investigates key factors impacting production, including neighbouring wells’ production, distance, and opening time: variations in all three parameters lead to different levels of interference between wells, which manifests itself in the regularised production integral derivative curve with different lengths and heights of convexity. Numerical simulations employing orthogonality are conducted to validate the reliability of this method. The results of these simulations offer theoretical support for the precise evaluation of reservoirs facing similar challenges.
Short-term power load forecasting for integrated energy system based on a residual and attentive LSTM-TCN hybrid network
Authors: Li Hongyi , Li Shenhao , Wu Yuxin , Xiao Yue , Pan Zhichong , Liu Min
Published: May 2024

In the context of Integrated Energy System (IES), accurate short-term power demand forecasting is crucial for ensuring system reliability, optimizing operational efficiency through resource allocation, and supporting effective real-time decision-making in energy management. However, achieving high forecasting accuracy faces significant challenges due to the inherent complexity and stochastic nature of IES’s short-term load profiles, resulting from diverse consumption patterns among end-users and the intricate coupling within the network of interconnected energy sources. To address this issue, a dedicated Short-Term Power Load Forecasting (STPLF) framework for IES is proposed, which relies on a newly developed hybrid deep learning architecture. The framework seamlessly combines Long Short-Term Memory (LSTM) with Temporal Convolutional Network (TCN), enhanced by an attention mechanism module. By merging these methodologies, the network leverages the parallel processing prowess of TCN alongside LSTM’s ability to retain long-range temporal information, thus enabling it to dynamically concentrate on relevant sections of time series data. This synergy leads to improved prediction accuracy and broader applicability. Furthermore, the integration of residual connections within the network structure serves to deepen its learning capabilities and enhance overall performance. Ultimately, results from a real case study of a user-level IES demonstrate that the Mean Absolute Percentage Error (MAPE) of the proposed framework on the test set is 2.35%. This error rate is lower than the averages of traditional methods (3.43%) and uncombined single submodules (2.80%).
Comparative genomic profiling of transport inhibitor Response1/Auxin signaling F-box (TIR1/AFB) genes in eight Pyrus genomes revealed the intraspecies diversity and stress responsiveness patterns
Authors: Yang Sheng , Yu Xiaomei , Gao Xinke , Fatima Kinza , Tahir Ul Qamar Muhammad
Published: May 2024

In the genomics of plants and the phytoecosystem, Pyrus (pear) is among the most nutritious fruits and contains fiber that has great health benefits to humans. It is mostly cultivated in temperate regions and is one of the most cultivated pome fruits globally. Pears are highly subjected to biotic and abiotic stresses that affect their yield. TIR1/AFB proteins act as auxin co-receptors during the signaling of nuclear auxins and play a primary role in development-related regulatory processes and responses to biotic and abiotic stresses. However, this gene family and its members have not been explored in Pyrus genomes, and understanding these genes will help obtain useful insights into stress tolerance and ultimately help maintain a high yield of pears. This study reports a pangenome-wide investigation of TIR1/AFB genes from eight Pyrus genomes: Cuiguan (Pyrus pyrifolia), Shanxi Duli (P. betulifolia), Zhongai 1 [(P. ussuriensis × communis) × spp.], Nijisseiki (P. pyrifolia), Yunhong No.1 (P. pyrifolia), d’Anjou (P. communis), Bartlett v2.0 (P. communis), and Dangshansuli v.1.1 (P. bretschneideri). These genes were randomly distributed on 17 chromosomes in each genome. Based on phylogenetics, the identified TIR1/AFB genes were divided into six groups. Their gene structure and motif pattern showed the intraspecific structural conservation as well as evolutionary patterns of Pyrus TIR1/AFBs. The expansion of this gene family in Pyrus is mainly caused by segmental duplication; however, a few genes showed tandem duplication. Moreover, positive and negative selection pressure equally directed the gene’s duplication process. The GO and PPI analysis showed that Pyrus TIR1/AFB genes are associated with abiotic stress- and development-related signaling pathways. The promoter regions of Pyrus TIR1/AFB genes were enriched in hormone-, light-, development-, and stress-related cis elements. Furthermore, publicly available RNA-seq data analysis showed that DaTIR1/AFBs have varied levels of expression in various tissues and developmental stages, fruit hardening disease conditions, and drought stress conditions. This indicated that DaTIR1/AFB genes might play critical roles in response to biotic and abiotic stresses. The DaTIR1/AFBs have similar protein structures, which show that they are involved in the same function. Hence, this study will broaden our knowledge of the TIR1/AFB gene family in Pyrus, elucidating their contribution to conferring resistance against various environmental stresses, and will also provide valuable insights for future researchers.
LcDel: deletion variation detection based on clustering and long reads
Authors: Yu Yanan , Gao Runtian , Luo Junwei
Published: May 2024

Motivation: Genomic structural variation refers to chromosomal level variations such as genome rearrangement or insertion/deletion, which typically involve larger DNA fragments compared to single nucleotide variations. Deletion is a common type of structural variants in the genome, which may lead to mangy diseases, so the detection of deletions can help to gain insights into the pathogenesis of diseases and provide accurate information for disease diagnosis, treatment, and prevention. Many tools exist for deletion variant detection, but they are still inadequate in some aspects, and most of them ignore the presence of chimeric variants in clustering, resulting in less precise clustering results.

Results: In this paper, we present LcDel, which can detect deletion variation based on clustering and long reads. LcDel first finds the candidate deletion sites and then performs the first clustering step using two clustering methods (sliding window-based and coverage-based, respectively) based on the length of the deletion. After that, LcDel immediately uses the second clustering by hierarchical clustering to determine the location and length of the deletion. LcDel is benchmarked against some other structural variation detection tools on multiple datasets, and the results show that LcDel has better detection performance for deletion. The source code is available in https://github.com/cyq1314woaini/LcDel.
Inhibition of interferon gamma impairs induction of experimental epidermolysis bullosa acquisita
Authors: Gross Natalie , Marketon Jana , Mousavi Sadegh , Kalies Kathrin , Ludwig Ralf J. , Bieber Katja
Published: May 2024

Epidermolysis bullosa acquisita (EBA) is a muco-cutaneous autoimmune disease characterized and caused by autoantibodies targeting type VII collagen (COL7). The treatment of EBA is notoriously difficult, with a median time to remission of 9 months. In preclinical EBA models, we previously discovered that depletion of regulatory T cells (Treg) enhances autoantibody-induced, neutrophil-mediated inflammation and blistering. Increased EBA severity in Treg-depleted mice was accompanied by an increased cutaneous expression of interferon gamma (IFN-γ). The functional relevance of IFN-γ in EBA pathogenesis had been unknown. Given that emapalumab, an anti-IFN-γ antibody, is approved for primary hemophagocytic lymphohistiocytosis patients, we sought to assess the therapeutic potential of IFN-γ inhibition in EBA. Specifically, we evaluated if IFN-γ inhibition has modulatory effects on skin inflammation in a pre-clinical EBA model, based on the transfer of COL7 antibodies into mice. Compared to isotype control antibody, anti-IFN-γ treatment significantly reduced clinical disease manifestation in experimental EBA. Clinical improvement was associated with a reduced dermal infiltrate, especially Ly6G+ neutrophils. On the molecular level, we noted few changes. Apart from reduced CXCL1 serum concentrations, which has been demonstrated to promote skin inflammation in EBA, the expression of cytokines was unaltered in the serum and skin following IFN-γ blockade. This validates IFN-γ as a potential therapeutic target in EBA, and possibly other diseases with a similar pathogenesis, such as bullous pemphigoid and mucous membrane pemphigoid.
Nomogram for predicting post-therapy recurrence in BCLC A/B hepatocellular carcinoma with Child-Pugh B cirrhosis
Authors: Qiao Wenying , Sheng Shugui , Xiong Yiqi , Han Ming , Jin Ronghua , Hu Caixia
Published: May 2024

Introduction

This study conducts a retrospective analysis on patients with BCLC stage A/B hepatocellular carcinoma (HCC) accompanied by Child-Pugh B cirrhosis, who underwent transarterial chemoembolization (TACE) in combination with local ablation therapy. Our goal was to uncover risk factors contributing to post-treatment recurrence and to develop and validate an innovative 1-, 3-, and 5-year recurrence free survival (RFS) nomogram.

Methods

Data from 255 BCLC A/B HCC patients with Child-Pugh B cirrhosis treated at Beijing You’an Hospital (January 2014 - January 2020) were analyzed using random survival forest (RSF), LASSO regression, and multivariate Cox regression to identify independent risk factors for RFS. The prognostic nomogram was then constructed and validated, categorizing patients into low, intermediate, and high-risk groups, with RFS assessed using Kaplan-Meier curves.

Results

The nomogram, integrating the albumin/globulin ratio, gender, tumor number, and size, showcased robust predictive performance. Harrell’s concordance index (C-index) values for the training and validation cohorts were 0.744 (95% CI: 0.703–0.785) and 0.724 (95% CI: 0.644–0.804), respectively. The area under the curve (AUC) values for 1-, 3-, and 5-year RFS in the two cohorts were also promising. Calibration curves highlighted the nomogram’s reliability and decision curve analysis (DCA) confirmed its practical clinical benefits. Through meticulous patient stratification, we also revealed the nomogram’s efficacy in distinguishing varying recurrence risks.

Conclusion

This study advances recurrence prediction in BCLC A/B HCC patients with Child-Pugh B cirrhosis following TACE combined with ablation. The established nomogram accurately predicts 1-, 3-, and 5-year RFS, facilitating timely identification of high-risk populations.
The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy
Authors: Zhang Zhiwei , Zhang Jingzhao , Cai Ming , Huang Xiaorui , Guo Xinyi , Zhu Dengsheng , Guo Tong , Yu Yahong
Published: May 2024

Background

Research of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments.

Methods

The medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn.

Results

Overall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS.

Conclusion

In general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.
Consolidation therapy with autologous stem cell transplantation after remission of induction chemotherapy prolongs the survival of patients with peripheral T-cell lymphoma
Authors: Fulati Wulipan , Ma Jiexian , Wu Min , Qian Wensi , Chen Pingping , Hu Yingwei , Chen Mingyue , Xu Yu , Huang Zilan , Zhang Hongdi , Xie Yanhui , Shen Lin
Published: May 2024

Background

There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL.

Methods

A total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival.

Results

With a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (p<0.003 for OS, p=0.015 for PFS). Subgroup analysis found that patients with high risks benefited more from ASCT. Combination with hemophagocytic lymphohistiocytosis (HLH) (p<0.001), clinical stage more than III (p=0.014), IPI score above 3 (p=0.049), and bone marrow involvement (p=0.010) were the independent prognostic factors significantly associated with worse OS and PFS. Additionally, pegylated liposomal doxorubicin (PLD)–containing chemotherapy regimen could bring a higher overall response rate (ORR) and prolong the survival of patients with PTCL who underwent ASCT.

Conclusion

ASCT may improve the long-term survival of patients with PTCL as consolidation therapy after achieving complete or partial remission of induction treatment, particularly for those with high risks. The chemotherapy regimen containing pegylated liposomal doxorubicin may induce deeper remission than traditional doxorubicin in PTCL. It is crucial to identify the specific groups most likely to benefit from upfront ASCT.
Pharmacodynamic monitoring by residual gene expression of the nuclear factor of activated T cell-regulated genes in lung transplant recipients and its correlation with tacrolimus blood levels
Authors: Boada-Pérez Meritxell , Ruiz de Miguel Victoria , Erro Marta , Ussetti Piedad , Aguilar Myriam , Castejón Raquel , Rosado Silvia , Escobar-Fornieles Roser , Revilla-López Eva , Bravo Carlos , Sáez-Giménez Berta , Zapata-Ortega Marta , Villena-Ortiz Yolanda , Vima-Bofarull Jaume , Monforte Víctor , Gómez-Ollés Susana
Published: May 2024

Introduction

Trough blood levels (C0) of tacrolimus are used to adjust drug dosage, but they do not consistently correlate with clinical outcomes. Measurement of residual gene expression of nuclear factor of activated T cell (NFAT)-regulated genes (NFAT-RGE) has been proposed as a pharmacodynamic biomarker to assess the degree of immunosuppression in certain solid organ transplantations, but little is known regarding lung transplant recipients (LTR). Our primary objective is to correlate tacrolimus blood levels with NFAT-RGE.

Methods

NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were determined in 42 patients at three, six and 12 months post-transplantation.

Results

Tacrolimus C0 did not exhibit a correlation with NFAT-RGE, whereas C1.5 did. Besides, over 20% of measurements indicated high levels of immunosuppression based on the below 30% NFAT-RGE threshold observed in many studies. Among those measurements within the therapeutic range, 19% had an NFAT-RGE<30%.

Conclusion

Consequently, a subset of patients within the tacrolimus therapeutic range may be more susceptible to infection or cancer, potentially benefiting from NFAT-RGE and tacrolimus peak level monitoring to tailor their dosage. Further quantitative risk assessment studies are needed to elucidate the relationship between NFAT-RGE and the risk of infection, cancer, or rejection.
Application of CD38 monoclonal antibody in kidney disease
Authors: Chen Zhiyi , Xu Qianchun , Shou Zhangfei
Published: May 2024

CD38 antigen is a glycoprotein that found on the surface of several immune cells, and this property makes its monoclonal antibodies have the effect of targeted elimination of immune cells. Therefore, the CD38 monoclonal antibody (such as daratumumab, Isatuximab) becomes a new treatment option for membranous nephropathy, lupus nephritis, renal transplantation, and other refractory kidney diseases. This review summarizes the application of CD38 monoclonal antibodies in different kidney diseases and highlights future prospects.
The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment
Authors: Xie Lin-feng , Xie Qi-gui , Gao Wen-ping , Wu Qing-song , Lin Xin-fan , Qiu Zhi-huang , Chen Liang-wan
Published: May 2024

Background

The systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment.

Methods

We conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test.

Results

A total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001).

Conclusion

Preoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.
The role of different nutrients in the prevention and treatment of cardiovascular diseases
Authors: Tu Zhi , Yang Jinfu , Fan Chengming
Published: May 2024

Cardiovascular health is a hot topic around the world, and as the incidence of cardiovascular disease increases each year, people are increasingly focusing on the management of their heart health. Dietary and lifestyle changes as non-pharmacological treatments have been increasingly recognized as important in the prevention of cardiovascular disease and in reducing the risk of cardiovascular accidents. Awareness of different nutrients and their effects on cardiovascular health is important for establishing a good dietary pattern. This review summarizes the effects of the five major nutrients in the daily diet, namely carbohydrates, proteins, dietary fats, vitamins, and minerals, on cardiovascular health, and aims to provide a more comprehensive understanding of the effects of a healthy dietary pattern on cardiovascular health.
Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants
Authors: Ashraf Muhammad Imtiaz , Mengwasser Joerg , Reutzel-Selke Anja , Polenz Dietrich , Führer Kirsten , Lippert Steffen , Tang Peter , Michaelis Edward , Catar Rusan , Pratschke Johann , Witzel Christian , Sauer Igor M. , Tullius Stefan G. , Kern Barbara
Published: May 2024

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation. By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11b-CD11c+), mature (CD11b-CD11c+MHCII+) and active (CD11b-CD11c+CD40+) DCs and cDC2 subset (CD11b+CD11c+ MHCII+) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.
Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma
Authors: Maiorano Brigida Anna , Schinzari Giovanni , Carbone Carmine , Piro Geny , Rossi Ernesto , Di Maio Massimo , Di Giacomo Annamaria , Maiello Evaristo
Published: May 2024

Background

Avelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Cytokines represent circulating mediators of the complex interaction between cancer, the immune system, and inflammation. Inflammation, a hallmark of cancer, can be expressed by circulating factors. In different tumor subtypes, peripheral blood biomarkers, such as circulating cytokines, and systemic inflammatory indexes, have been addressed as potential prognostic factors for immune checkpoint inhibitors. However, their role in mUC still needs to be determined.

Methods

Between February 2021 and April 2023, we prospectively collected plasma cytokines and inflammation indexes in 28 patients with mUC before starting avelumab as first-line maintenance. The primary endpoint was the relationship between baseline cytokines and inflammatory indexes with the clinical benefit (CB), defined as the number of Responders. Secondary endpoints included the correlation of baseline cytokines and inflammatory indexes with progression-free survival (PFS), overall survival (OS), and the number and grade of immune-related adverse events.

Results

High pre-treatment levels of interferon (IFN)-γ and interleukin (IL)-2, and low levels of IL-6, IL-8, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic-inflammation index (SII) were associated with clinical benefit and longer survival. In the multivariate analysis, low IL-8, NLR, and SII levels maintained a positive prognostic value for OS.

Conclusion

Our data suggest that, in mUC patients receiving avelumab, pre-treatment levels of plasma cytokines and inflammatory indexes may serve as potential prognostic biomarkers for response and efficacy. In particular, patients with signs of pre-therapeutic inflammation showed a significantly lower response and survival to avelumab. On the contrary, low systemic inflammation and high levels of cytokines characterized responders and longer survivors.
Impacts of locally managed periodic octopus fishery closures in Comoros and Madagascar: short-term benefits amidst long-term decline
Authors: McCabe Mary K. , Mudge Laura , Randrianjafimanana Tahiry , Rasolofoarivony Nestin , Vessaz Fanny , Rakotonirainy Robertin , Said Faissoil Ahmed , Rakotoarisoa François , Ratoniherison Tsiorisoa , Box Steve , Cox Courtney
Published: May 2024

Octopus fisheries face heightened demand driven by depleted fish stocks and escalating economic value, leading to overextraction of octopus populations and magnifying threats to coastal ecosystems and the livelihoods of fishers who depend on them. Implementation of management strategies such as periodic fishing closures can offer sanctuary for octopus, providing the necessary space and time for the growth and reproduction of this rapidly proliferating species. Despite evidence of positive management outcomes, the role of periodic closures in the long-term sustainability of octopus populations remains uncertain. Here, we examine trends in octopus landings over time and the effects of periodic closures along the Mozambique Channel from Comoros to Madagascar (12°-25°S). Long-term trends in octopus landings varied across three regions: generally stable over a 6-year period in Comoros, increasing over a 4-year period in the Barren Isles and declining over a 17-year period in Atsimo Andrefana, Madagascar. We observed a significant increase in mean catch per unit effort (CPUE, kilograms/fisher-day), and mean total catch (kilograms/day) following periodic closures across villages extracting octopus from closure areas. When evaluating each region independently, we observed this positive effect across Comoros and Atsimo Andrefana, Madagascar while trends in the Barren Isles showed no effect of octopus closures. We applied generalized linear mixed models to examine the influence of 10 covariates on mean daily total catch and CPUE within 7 days and 30 days post-closure. Baseline conditions (quantified by the pre-closure CPUE and daily total catch), closure duration and start month of closure had positive, statistically significant correlations with post-closure CPUE and daily total catch. Additionally, closure duration from 13 to 16 weeks and closure size of approximately 70 hectares were qualitatively associated with net gains in CPUE. Although periodic closures yield positive outcomes for octopus fisheries, the effects may be short-lived, as observed in Atsimo Andrefana, Madagascar, where catch declined over the long-term despite temporary improvements. Our findings underscore a need for a diverse portfolio of management strategies to restore and sustain populations over the long-term.
Application of two-sample Mendelian randomization method to assess the causal relationship between rheumatoid arthritis and osteoporotic fracture
Authors: Zhenyu Cai , Le Chang , Shiyong Zeng , Jinding Lin , Mingzhong Liu , Haifeng Tang , Rongdong Zeng
Published: May 2024

Background

The association between rheumatoid arthritis (RA) and osteoporotic fracture has garnered considerable attention; however, the causal relationships between diseases remain uncertain. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the causal effects of RA on osteoporotic fracture.

Methods

The summary data for RA and osteoporotic fracture were extracted from the genome-wide association studies (GWAS) catalog and the Finn Biobank database. The database provides information about diseased and health control subjects. We searched the database for the following conditions: RA, osteoporosis (OP), and osteoporotic fractures. Entries were published by investigating centers, which had established definitions and diagnostic criteria. We downloaded and processed the data to obtain the single-nucleotide polymorphisms (SNPs) strongly associated with RA, OP, and osteoporotic fracture. RA genetic associations were obtained from the GWAS catalog, including 1961 cases and 454,387 controls. The osteoporosis of the GWAS catalog involved 991 cases and 455,357 controls, and the data of the Finn Biobank involved 8,017 cases and 391,037 controls. Genetic associations for osteoporotic fracture were taken from the Finn Biobank of 1822 cases and 311,210 controls. Independent SNPs that are significantly associated with meeting the criteria of p < 5 × 10–8, r2 < 0.001, and kb = 10,000 were selected for MR analysis. The inverse variance-weighted (IVW) method along with other MR methods was employed for analysis, while sensitivity analyses were conducted to assess reliability and stability.

Results

The results provided strong evidence that RA was causally and positively associated with osteoporosis from the GWAS catalog (OR = 1.16590; 95% CI: 1.04067–1.30619; p = 0.00811) and the Finn Biobank database (OR = 1.07314; 95% CI: 1.03455–1.11317; p = 0.00016). Moreover, a positive causal relationship was detected between RA and osteoporotic fracture (OR = 1.10132; 95% CI: 1.00506–1.20680; p = 0.03863). The results were robust according to sensitivity tests.

Conclusion

This study showed positive causal relationships between RA and osteoporotic fracture. These results should be considered in further studies and public health measures on osteoporosis prevention strategies.
Evaluating sarcopenia prevalence and SARC-F effectiveness in elderly Spanish women with RA: a comparative study of EWGSOP criteria
Authors: Valencia-Muntalà Lidia , Gómez-Vaquero Carmen , Mora Maribel , Berbel-Arcobé Laura , Benavent Diego , Narváez Javier , Juanola Xavier , Nolla Joan M.
Published: May 2024

Introduction

The European Working Group on Sarcopenia in Older People (EWGSOP) has put forward two key proposals for diagnosing sarcopenia: the EWGSOP1 in 2010 and the EWGSOP2 in 2019. These proposals are currently the most widely used guidelines for diagnosing sarcopenia. However, data on the prevalence of sarcopenia in patients with rheumatoid arthritis (RA) based on EWGSOP criteria are limited. This study aimed to: (a) establish the prevalence of sarcopenia in an elderly Spanish cohort of women with RA using both EWGSOP1 and EWGSOP2 criteria; and (b) evaluate the effectiveness of the SARC-F questionnaire in detecting sarcopenia.

Methods

In this observational, cross-sectional study, 67 women aged over 65 years who met the ACR 2010 criteria for RA were consecutively recruited from a tertiary university hospital. Assessments included: (a) demographic and anthropometric data; (b) RA-related variables (disease history, analytical evaluation, activity, disability, quality of life); and (c) sarcopenia-related variables (muscle strength, gait speed, skeletal muscle mass, and SARC-F questionnaire). The prevalence of sarcopenia was determined using both EWGSOP1 and EWGSOP2 criteria. Furthermore, the effectiveness of the SARC-F questionnaire for detecting sarcopenia were calculated.

Results

The prevalence of sarcopenia was 43% according to the EWGSOP1 criteria and 16% according to the EWGSOP2 criteria. Patients diagnosed with sarcopenia based on the latter criteria also met the EWGSOP1's criteria for sarcopenia. Agreement between the two sets of EWGSOP criteria was poor. The SARC-F questionnaire demonstrated an inherently high sensitivity (100%) as well as good specificity (75%) and diagnostic accuracy (79%) in detecting sarcopenia according to EWGSOP2 criteria.

Conclusions

The prevalence rate of sarcopenia among elderly Spanish women with RA varies significantly depending on whether EWGSOP1 or EWGSOP2 criteria are applied. The SARC-F questionnaire is effective for predicting sarcopenia when used in conjunction with the EWGSOP2 criteria, which is currently the most accepted standard in clinical practice.