bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting early endodontic treatment failure following primary root canal treatment
Authors: Jang Young-Eun , Kim Yemi , Kim Sin-Young , Kim Bom Sahn 
Published: March 2024

Abstract
Background
Understanding when and why endodontic treatments fail could help clinicians make prognoses and thus improve treatment outcomes. This study was aimed to assess potential predictors of early endodontic treatment failure. We explored factors contributing to the failure of initial root canal treatment were explored, with a specific emphasis on evaluating the influence of the time elapsed since the initial treatment.

Methods
This retrospective cohort study enrolled 1262 patients who sought endodontic treatment at our department and 175 patients were included for analysis. Potential causes of endodontic treatment failure were investigated, such as inadequate obturation quality, inadequate coronal status, the presence of additional untreated canals, anatomical complexity, instrument separation, iatrogenic perforation, cracks, and endodontic-periodontal lesions. The patients were divided into “short-term” and “long-term” groups depending on the time that had passed since the initial treatment (i.e., < 5 and > 10 years, respectively). The causes of failure in the short-term and long-term group were analyzed and compared using logistic regression analyses. Subgroup analysis was performed according to the number of years since the initial treatment in the short-term group to further investigate the association between the time and cause of failure (i.e., < 1, 2, 3, and 4 years, respectively).

Results
Untreated additional canals were present in 21.7% of all cases, and in 36.9 and 6.4% of cases in the short-term and long-term groups, respectively. Multivariable analysis showed that the presence of untreated additional canals was significantly associated with short-term compared to long-term failure. Untreated additional canals were also associated with endodontic failure within 1, 2, 3, and 4 years.

Conclusions
The presence of untreated additional canals was a predictor of endodontic failure within 5 years following initial root canal treatment. To optimize long-term prognosis, it is important to detect and treat all root canals during the initial treatment.
Implementation difficulties and solutions for a smart-clothes assisted home nursing care program for older adults with dementia or recovering from hip fracture
Authors: Lin Chung-Chih , Yang Ching-Tzu , Su Pei-Ling , Hsu Jung-Ling , Shyu Yea-Ing L. , Hsu Wen-Chuin 
Published: March 2024

Abstract
Background
Wearable devices have the advantage of always being with individuals, enabling easy detection of their movements. Smart clothing can provide feedback to family caregivers of older adults with disabilities who require in-home care.

Methods
This study describes the process of setting up a smart technology-assisted (STA) home-nursing care program, the difficulties encountered, and strategies applied to improve the program. The STA program utilized a smart-vest, designed specifically for older persons with dementia or recovering from hip-fracture surgery. The smart-vest facilitated nurses’ and family caregivers’ detection of a care receiver’s movements via a remote-monitoring system. Movements included getting up at night, time spent in the bathroom, duration of daytime immobility, leaving the house, and daily activity. Twelve caregivers of older adults and their care receiver participated; care receivers included persons recovering from hip fracture (n = 5) and persons living with dementia (n = 7). Data about installation of the individual STA in-home systems, monitoring, and technical difficulties encountered were obtained from researchers’ reports. Qualitative data about the caregivers’ and care receivers’ use of the system were obtained from homecare nurses’ reports, which were explored with thematic analysis.

Results
Compiled reports from the research team identified three areas of difficulty with the system: incompatibility with the home environment, which caused extra hours of manpower and added to the cost of set-up and maintenance; interruptions in data transmissions, due to system malfunctions; and inaccuracies in data transmissions, due to sensors on the smart-vest. These difficulties contributed to frustration experienced by caregivers and care receivers.

Conclusions
The difficulties encountered impeded implementation of the STA home nursing care. Each of these difficulties had their own unique problems and strategies to resolve them. Our findings can provide a reference for future implementation of similar smart-home systems, which could facilitate ease-of-use for family caregivers.
Differentiation is accompanied by a progressive loss in transcriptional memory
Authors: Fourneaux Camille , Racine Laëtitia , Koering Catherine , Dussurgey Sébastien , Vallin Elodie , Moussy Alice , Parmentier Romuald , Brunard Fanny , Stockholm Daniel , Modolo Laurent , Picard Franck , Gandrillon Olivier , Paldi Andras , Gonin-Giraud Sandrine 
Published: March 2024

AbstractBackgroundCell differentiation requires the integration of two opposite processes, a stabilizing cellular memory, especially at the transcriptional scale, and a burst of gene expression variability which follows the differentiation induction. Therefore, the actual capacity of a cell to undergo phenotypic change during a differentiation process relies upon a modification in this balance which favors change-inducing gene expression variability. However, there are no experimental data providing insight on how fast the transcriptomes of identical cells would diverge on the scale of the very first two cell divisions during the differentiation process.ResultsIn order to quantitatively address this question, we developed different experimental methods to recover the transcriptomes of related cells, after one and two divisions, while preserving the information about their lineage at the scale of a single cell division. We analyzed the transcriptomes of related cells from two differentiation biological systems (human CD34+ cells and T2EC chicken primary erythrocytic progenitors) using two different single-cell transcriptomics technologies (scRT-qPCR and scRNA-seq).ConclusionsWe identified that the gene transcription profiles of differentiating sister cells are more similar to each other than to those of non-related cells of the same type, sharing the same environment and undergoing similar biological processes. More importantly, we observed greater discrepancies between differentiating sister cells than between self-renewing sister cells. Furthermore, a progressive increase in this divergence from first generation to second generation was observed when comparing differentiating cousin cells to self renewing cousin cells. Our results are in favor of a gradual erasure of transcriptional memory during the differentiation process.
Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway
Authors: Wang Heng , Tian Qinqin , Zhang Ruijing , Du Qiujing , Hu Jie , Gao Tingting , Gao Siqi , Fan Keyi , Cheng Xing , Yan Sheng , Zheng Guoping , Dong Honglin 
Published: March 2024

Abstract
Background
Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood.

Methods
This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions.

Results
(1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression.

Conclusions
Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.
Primary care providers’ preferences for pay-for-performance programs: a discrete choice experiment study in Shandong China
Authors: Zhang Wencai , Li Yanping , Yuan BeiBei , Zhu Dawei 
Published: March 2024

Abstract
Background
Pay-for-performance (P4P) schemes are commonly used to incentivize primary healthcare (PHC) providers to improve the quality of care they deliver. However, the effectiveness of P4P schemes can vary depending on their design. In this study, we aimed to investigate the preferences of PHC providers for participating in P4P programs in a city in Shandong province, China.

Method
We conducted a discrete choice experiment (DCE) with 882 PHC providers, using six attributes: type of incentive, whom to incentivize, frequency of incentive, size of incentive, the domain of performance measurement, and release of performance results. Mixed logit models and latent class models were used for the statistical analyses.

Results
Our results showed that PHC providers had a strong negative preference for fines compared to bonuses (− 1.91; 95%CI − 2.13 to − 1.69) and for annual incentive payments compared to monthly (− 1.37; 95%CI − 1.59 to − 1.14). Providers also showed negative preferences for incentive size of 60% of monthly income, group incentives, and non-release of performance results. On the other hand, an incentive size of 20% of monthly income and including quality of care in performance measures were preferred. We identified four distinct classes of providers with different preferences for P4P schemes. Class 2 and Class 3 valued most of the attributes differently, while Class 1 and Class 4 had a relatively small influence from most attributes.

Conclusion
P4P schemes that offer bonuses rather than fines, monthly rather than annual payments, incentive size of 20% of monthly income, paid to individuals, including quality of care in performance measures, and release of performance results are likely to be more effective in improving PHC performance. Our findings also highlight the importance of considering preference heterogeneity when designing P4P schemes.
Research progress of the chemokine/chemokine receptor axes in the oncobiology of multiple myeloma (MM)
Authors: Du Jun , Lin Zheng , Fu Xue-Hang , Gu Xiao-Ran , Lu Guang , Hou Jian 
Published: March 2024

Abstract
Background
The incidence of multiple myeloma (MM), a type of blood cancer affecting monoclonal plasma cells, is rising. Although new drugs and therapies have improved patient outcomes, MM remains incurable. Recent studies have highlighted the crucial role of the chemokine network in MM’s pathological mechanism. Gaining a better understanding of this network and creating an overview of chemokines in MM could aid in identifying potential biomarkers and developing new therapeutic strategies and targets.

Purpose
To summarize the complicated role of chemokines in MM, discuss their potential as biomarkers, and introduce several treatments based on chemokines.

Methods
Pubmed, Web of Science, ICTRP, and Clinical Trials were searched for articles and research related to chemokines. Publications published within the last 5 years are selected.

Results
Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Other chemokines, including CXCL4, CCL19, and CXCL10, may aid in recruiting immune cells, increasing their cytotoxicity against cancer cells, and inducing apoptosis of malignant cells.

Conclusion
Utilizing anti-tumor chemokines or blocking pro-tumor chemokines may provide new therapeutic strategies for managing MM. Inspired by developed CXCR4 antagonists, including plerixafor, ulocuplumab, and motixafortide, more small molecular antagonists or antibodies for pro-tumor chemokine ligands and their receptors can be developed and used in clinical practice. Along with inhibiting pro-tumor chemokines, studies suggest combining chemokines with chimeric antigen receptor (CAR)-T therapy is promising and efficient.
The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling
Authors: Li Tianye , Niu Mengke , Zhou Jianwei , Wu Kongming , Yi Ming 
Published: March 2024

AbstractThe programmed cell death 1 (PD-1) signaling pathway, a key player in immune checkpoint regulation, has become a focal point in cancer immunotherapy. In the context of cancer, upregulated PD-L1 on tumor cells can result in T cell exhaustion and immune evasion, fostering tumor progression. The advent of PD-1/PD-L1 inhibitor has demonstrated clinical success by unleashing T cells from exhaustion. Nevertheless, challenges such as resistance and adverse effects have spurred the exploration of innovative strategies, with bispecific antibodies (BsAbs) emerging as a promising frontier. BsAbs offer a multifaceted approach to cancer immunotherapy by simultaneously targeting PD-L1 and other immune regulatory molecules. We focus on recent advancements in PD-1/PD-L1 therapy with a particular emphasis on the development and potential of BsAbs, especially in the context of solid tumors. Various BsAb products targeting PD-1 signaling are discussed, highlighting their unique mechanisms of action and therapeutic potential. Noteworthy examples include anti-TGFβ × PD-L1, anti-CD47 × PD-L1, anti-VEGF × PD-L1, anti-4-1BB × PD-L1, anti-LAG-3 × PD-L1, and anti-PD-1 × CTLA-4 BsAbs. Besides, we summarize ongoing clinical studies evaluating the efficacy and safety of these innovative BsAb agents. By unraveling the intricacies of the tumor microenvironment and harnessing the synergistic effects of anti-PD-1/PD-L1 BsAbs, there exists the potential to elevate the precision and efficacy of cancer immunotherapy, ultimately enabling the development of personalized treatment strategies tailored to individual patient profiles.
Predicting long-term progression of Alzheimer’s disease using a multimodal deep learning model incorporating interaction effects
Authors: Wang Yifan , Gao Ruitian , Wei Ting , Johnston Luke , Yuan Xin , Zhang Yue , Yu Zhangsheng ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2024

Abstract
Background
Identifying individuals with mild cognitive impairment (MCI) at risk of progressing to Alzheimer’s disease (AD) provides a unique opportunity for early interventions. Therefore, accurate and long-term prediction of the conversion from MCI to AD is desired but, to date, remains challenging. Here, we developed an interpretable deep learning model featuring a novel design that incorporates interaction effects and multimodality to improve the prediction accuracy and horizon for MCI-to-AD progression.

Methods
This multi-center, multi-cohort retrospective study collected structural magnetic resonance imaging (sMRI), clinical assessments, and genetic polymorphism data of 252 patients with MCI at baseline from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Our deep learning model was cross-validated on the ADNI-1 and ADNI-2/GO cohorts and further generalized in the ongoing ADNI-3 cohort. We evaluated the model performance using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 score.

Results
On the cross-validation set, our model achieved superior results for predicting MCI conversion within 4 years (AUC, 0.962; accuracy, 92.92%; sensitivity, 88.89%; specificity, 95.33%) compared to all existing studies. In the independent test, our model exhibited consistent performance with an AUC of 0.939 and an accuracy of 92.86%. Integrating interaction effects and multimodal data into the model significantly increased prediction accuracy by 4.76% (P = 0.01) and 4.29% (P = 0.03), respectively. Furthermore, our model demonstrated robustness to inter-center and inter-scanner variability, while generating interpretable predictions by quantifying the contribution of multimodal biomarkers.

Conclusions
The proposed deep learning model presents a novel perspective by combining interaction effects and multimodality, leading to more accurate and longer-term predictions of AD progression, which promises to improve pre-dementia patient care.
Shifting the paradigm: engaging multicellular networks for cancer therapy
Authors: Hu Joyce , Ascierto Paolo , Cesano Alessandra , Herrmann Volker , Marincola Francesco M. 
Published: March 2024

AbstractMost anti-cancer modalities are designed to directly kill cancer cells deploying mechanisms of action (MOAs) centered on the presence of a precise target on cancer cells. The efficacy of these approaches is limited because the rapidly evolving genetics of neoplasia swiftly circumvents the MOA generating therapy-resistant cancer cell clones. Other modalities engage endogenous anti-cancer mechanisms by activating the multi-cellular network (MCN) surrounding neoplastic cells in the tumor microenvironment (TME). These modalities hold a better chance of success because they activate numerous types of immune effector cells that deploy distinct cytotoxic MOAs. This in turn decreases the chance of developing treatment-resistance. Engagement of the MCN can be attained through activation of immune effector cells that in turn kill cancer cells or when direct cancer killing is complemented by the production of proinflammatory factors that secondarily recruit and activate immune effector cells. For instance, adoptive cell therapy (ACT) supplements cancer cell killing with the release of homeostatic and pro-inflammatory cytokines by the immune cells and damage associated molecular patterns (DAMPs) by dying cancer cells. The latter phenomenon, referred to as immunogenic cell death (ICD), results in an exponential escalation of anti-cancer MOAs at the tumor site. Other approaches can also induce exponential cancer killing by engaging the MCN of the TME through the release of DAMPs and additional pro-inflammatory factors by dying cancer cells. In this commentary, we will review the basic principles that support emerging paradigms likely to significantly improve the efficacy of anti-cancer therapy.
Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics
Authors: Chen Shuming , Huang Weidi , Wan Qiaoqian , Tang Zichun , Li Xie , Zeng Fang , Zheng Shuyan , Li Zhuo , Liu Xiao 
Published: March 2024

Abstract
Background
Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment.

Methods
To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved.

Results
Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group.

Conclusions
AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.