bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the combination of the triglyceride-glucose index and obesity indicators estimate the risk of cardiovascular disease
Authors: Zhu Xiaoqing , Xu Weihao , Song Tingting , Wang Xinyan , Wang Qingsong , Li Jun , Liu Xixi , Hao Benchuan , Chen Tao , Guo Jun 
Published: June 2024

Abstract
Background
Cardiovascular disease (CVD) is closely associated with the triglyceride glucose (TyG) index and its related indicators, particularly its combination with obesity indices. However, there is limited research on the relationship between changes in TyG-related indices and CVD, as most studies have focused on baseline TyG-related indices.

Methods
The data for this prospective cohort study were obtained from the China Health and Retirement Longitudinal Study. The exposures were changes in TyG-related indices and cumulative TyG-related indices from 2012 to 2015. The K-means algorithm was used to classify changes in each TyG-related index into four classes (Class 1 to Class 4). Multivariate logistic regressions were used to evaluate the associations between the changes in TyG-related indices and the incidence of CVD.

Results
In total, 3243 participants were included in this study, of whom 1761 (54.4%) were female, with a mean age of 57.62 years at baseline. Over a 5-year follow-up, 637 (19.6%) participants developed CVD. Fully adjusted logistic regression analyses revealed significant positive associations between changes in TyG-related indices, cumulative TyG-related indices and the incidence of CVD. Among these changes in TyG-related indices, changes in TyG-waist circumference (WC) showed the strongest association with incident CVD. Compared to the participants in Class 1 of changes in TyG-WC, the odds ratio (OR) for participants in Class 2 was 1.41 (95% confidence interval (CI) 1.08–1.84), the OR for participants in Class 3 was 1.54 (95% CI 1.15–2.07), and the OR for participants in Class 4 was 1.94 (95% CI 1.34–2.80). Moreover, cumulative TyG-WC exhibited the strongest association with incident CVD among cumulative TyG-related indices. Compared to the participants in Quartile 1 of cumulative TyG-WC, the OR for participants in Quartile 2 was 1.33 (95% CI 1.00–1.76), the OR for participants in Quartile 3 was 1.46 (95% CI 1.09–1.96), and the OR for participants in Quartile 4 was 1.79 (95% CI 1.30–2.47).

Conclusions
Changes in TyG-related indices are independently associated with the risk of CVD. Changes in TyG-WC are expected to become more effective indicators for identifying individuals at a heightened risk of CVD.
Elevated SLC1A5 associated with poor prognosis and therapeutic resistance to transarterial chemoembolization in hepatocellular carcinoma
Authors: Zhang Guixiong , Xiao Yitai , Tan Jizhou , Liu Hang , Fan Wenzhe , Li Jiaping 
Published: June 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is a common malignant tumor, and glutamine is vital for tumor cells. The role of glutamine transporter SLC1A5 in tumor progression and transarterial chemoembolization (TACE) efficacy is under study. This research seeks to determine the impact of SLC1A5 expression on the prognosis and TACE efficacy of HCC and elucidate its mechanisms.

Methods
SLC1A5 expression in HCC, correlation with patient outcomes, and response to TACE were studied in an open access liver cancer dataset and confirmed in our cohort. Additionally, the correlation between SLC1A5 expression and hypoxia, angiogenesis and immune infiltration was analyzed and verified by immunohistochemistry, immunofluorescence and transcriptome sequencing. Liver cancer cell lines with SLC1A5 expression knockdown or overexpression were constructed, and cell proliferation, colony formation, apoptosis, migration and drug sensitivity as well as in vivo xenograft tumor were measured. A gene set enrichment analysis was conducted to determine the signaling pathway influenced by SLC1A5, and a western blot analysis was performed to detect protein expression alterations.

Results
SLC1A5 expression was higher in HCC tissue and associated with poor survival and TACE resistance. Hypoxia could stimulate the upregulation of glutamine transport, angiogenesis and SLC1A5 expression. The SLC1A5 expression was positively correlated with hypoxia and angiogenesis-related genes, immune checkpoint pathways, macrophage, Tregs, and other immunosuppressive cells infiltration. Knockdown of SLC1A5 decreased proliferation, colony formation, and migration, but increased apoptosis and increased sensitivity to chemotherapy drugs. Downregulation of SLC1A5 resulted in a decrease in Vimentin and N-cadherin expression, yet an increase in E-cadherin expression. Upregulation of SLC1A5 increased Vimentin and N-cadherin expression, while decreasing E-cadherin. Overexpression of β-catenin in SLC1A5-knockdown HCC cell lines could augment Vimentin and N-cadherin expression, suppress E-cadherin expression, and increase the migration and drug resistance.

Conclusions
Elevated SLC1A5 was linked to TACE resistance and survival shortening in HCC patients. SLC1A5 was positively correlated with hypoxia, angiogenesis, and immunosuppression. SLC1A5 may mediate HCC cell migration and drug resistance via Epithelial-mesenchymal transition (EMT) pathway.
The tumour microenvironment, treatment resistance and recurrence in glioblastoma
Authors: White Jasmine , White Madeleine P. J. , Wickremesekera Agadha , Peng Lifeng , Gray Clint 
Published: June 2024

AbstractThe adaptability of glioblastoma (GBM) cells, encouraged by complex interactions with the tumour microenvironment (TME), currently renders GBM an incurable cancer. Despite intensive research, with many clinical trials, GBM patients rely on standard treatments including surgery followed by radiation and chemotherapy, which have been observed to induce a more aggressive phenotype in recurrent tumours. This failure to improve treatments is undoubtedly a result of insufficient models which fail to incorporate components of the human brain TME. Research has increasingly uncovered mechanisms of tumour-TME interactions that correlate to worsened patient prognoses, including tumour-associated astrocyte mitochondrial transfer, neuronal circuit remodelling and immunosuppression. This tumour hijacked TME is highly implicated in driving therapy resistance, with further alterations within the TME and tumour resulting from therapy exposure inducing increased tumour growth and invasion. Recent developments improving organoid models, including aspects of the TME, are paving an exciting future for the research and drug development for GBM, with the hopes of improving patient survival growing closer. This review focuses on GBMs interactions with the TME and their effect on tumour pathology and treatment efficiency, with a look at challenges GBM models face in sufficiently recapitulating this complex and highly adaptive cancer.
CAPN2 promotes apalutamide resistance in metastatic hormone-sensitive prostate cancer by activating protective autophagy
Authors: Qi Zihao , Bai Xiaojie , Wu Linjie , Zhang Peng , Guo Zhongqiang , Yu Ying 
Published: June 2024

AbstractApalutamide, a novel endocrine therapy agent, has been shown to significantly improve the prognosis of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, resistance to apalutamide has also been reported, and the underlying mechanism for this response has yet to be clearly elucidated. First, this study established apalutamide-resistant prostate cancer (PCa) cells, and confirmed that apalutamide activated the release of calcium ions (Ca2+) and endoplasmic reticulum stress (ERS) to enhance autophagy. Second, RNA sequencing, western blotting, and immunohistochemistry revealed significantly decreased Calpain 2 (CAPN2) expression in the apalutamide-resistant PCa cells and tissues. Furthermore, immunofluorescence and transmission electron microscopy (TEM) showed that CAPN2 promoted apalutamide resistance by activating protective autophagy. CAPN2 promoted autophagy by reducing Forkhead Box O1 (FOXO1) degradation while increasing nuclear translocation via nucleoplasmic protein isolation and immunofluorescence. In addition, FOXO1 promoted protective autophagy through the transcriptional regulation of autophagy-related gene 5 (ATG5). Furthermore, a dual-fluorescence assay confirmed that transcription factor 3 (ATF3) stimulation promoted CAPN2-mediated autophagy activation via transcriptional regulation. In summary, CAPN2 activated protective autophagy by inhibiting FOXO1 degradation and promoting its nuclear translocation via transcriptional ATG5 regulation. ATF3 activation and transcriptional CAPN2 regulation jointly promoted this bioeffect. Thus, our findings have not only revealed the mechanism underlying apalutamide resistance, but also provided a promising new target for the treatment of metastatic PCa.
Deficiency of SDHC promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer
Authors: Ding Zhuoyu , Wei Yiyi , Dai Jingping , Pan Chaomin , Yang Li , Li Qingyuan , Zhang Yue , Yan Qun , Wu Changjie , Li Aimin , Lan Zhixian , Liu Side , Wang Xinke 
Published: June 2024

Abstract
Background
Several studies have demonstrated a strong correlation between impaired Succinate dehydrogenase (SDH) function and the advancement of tumors. As a subunit of SDH, succinate dehydrogenase complex subunit C (SDHC) has been revealed to play tumor suppressive roles in several cancers, while its specific role in colorectal cancer (CRC) still needs further investigation.

Methods
Online database were utilized to investigate the expression of SDHC in colorectal cancer and to assess its correlation with patient prognosis. Cell metastasis was assessed using transwell and wound healing assays, while tumor metastasis was studied in a nude mice model in vivo. Drug screening and RNA sequencing were carried out to reveal the tumor suppressor mechanism of SDHC. Triglycerides, neutral lipids and fatty acid oxidation were measured using the Triglyceride Assay Kit, BODIPY 493/503 and Colorimetric Fatty Acid Oxidation Rate Assay Kit, respectively. The expression levels of enzymes involved in fatty acid metabolism and the PI3K/AKT signaling pathway were determined by quantitative real-time PCR and western blot.

Results
Downregulation of SDHC was found to be closely associated with a poor prognosis in CRC. SDHC knockdown promoted CRC metastasis both in vitro and in vivo. Through drug screening and Gene set enrichment analysis, it was discovered that SDHC downregulation was positively associated with the fatty acid metabolism pathways significantly. The effects of SDHC silencing on metastasis were reversed when fatty acid synthesis was blocked. Subsequent experiments revealed that SDHC silencing activated the PI3K/AKT signaling axis, leading to lipid accumulation by upregulating the expression of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) and reduction of fatty acid oxidation rate by suppressing the expression of acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1A (CPT1A).

Conclusions
SDHC deficiency could potentially enhance CRC metastasis by modulating the PI3K/AKT pathways and reprogramming lipid metabolism.
Factor of time in dendritic cell (DC) maturation: short-term activation of DCs significantly improves type 1 cytokine production and T cell responses
Authors: Poženel Primož , Zajc Kaja , Švajger Urban 
Published: June 2024

AbstractDendritic cells (DCs) have been intensively studied in correlation to tumor immunology and for the development DC-based cancer vaccines. Here, we present the significance of the temporal aspect of DC maturation for the most essential subsequent timepoint, namely at interaction with responding T cells or after CD40-Ligand restimulation. Mostly, DC maturation is still being achieved by activation processes which lasts 24 h to 48 h. We hypothesized this amount of time is excessive from a biological standpoint and could be the underlying cause for functional exhaustion. Indeed, shorter maturation periods resulted in extensive capacity of monocyte-derived DCs to produce inflammatory cytokines after re-stimulation with CD40-Ligand. This effect was most evident for the primary type 1 polarizing cytokine, IL-12p70. This capacity reached peak at 6 h and dropped sharply with longer exposure to initial maturation stimuli (up to 48 h). The 6 h maturation protocol reflected superiority in subsequent functionality tests. Namely, DCs displayed twice the allostimulatory capacity of 24 h- and 48 h-matured DCs. Similarly, type 1 T cell response measured by IFN-γ production was 3-fold higher when CD4+ T cells had been stimulated with shortly matured DC and over 8-fold greater in case of CD8+ T cells, compared to longer matured DCs. The extent of melanoma-specific CD8+ cytotoxic T cell induction was also greater in case of 6 h DC maturation. The major limitation of the study is that it lacks in vivo evidence, which we aim to examine in the future. Our findings show an unexpectedly significant impact of temporal exposure to activation signals for subsequent DC functionality, which we believe can be readily integrated into existing knowledge on in vitro/ex vivo DC manipulation for various uses. We also believe this has important implications for DC vaccine design for future clinical trials.
Low clinical impact of HIV drug resistance mutations in oral pre-exposure prophylaxis: a systematic review and meta-analysis
Authors: Rachman Brian Eka , Khairunisa Siti Qamariyah , Wungu Citrawati Dyah Kencono , Asmarawati Tri Pudy , Rusli Musofa , Bramantono  , Arfijanto M. Vitanata , Hadi Usman , Kameoka Masanori , Nasronudin  
Published: June 2024

Abstract
Introduction
Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM.

Methods
We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061.

Results
A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65–9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23–3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55–9.40) and 7.47% (95% CI 3.80–12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI −0.20 to 2.18, I2 = 0%; p = 0.10).

Discussion
Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21).

Conclusions
Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use.
PROSPERO Number: CRD42022356061.
Automated, IMU-based spine angle estimation and IMU location identification for telerehabilitation
Authors: Pan Huiming , Wang Hong , Li Dongxuan , Zhu Kezhe , Gao Yuxiang , Yin Ruiqing , Shull Peter B. 
Published: June 2024

Abstract
Background
Telerehabilitation is a promising avenue for improving patient outcomes and expanding accessibility. However, there is currently no spine-related assessment for telerehabilitation that covers multiple exercises.

Methods
We propose a wearable system with two inertial measurement units (IMUs) to identify IMU locations and estimate spine angles for ten commonly prescribed spinal degeneration rehabilitation exercises (supine chin tuck head lift rotation, dead bug unilateral isometric hold, pilates saw, catcow full spine, wall angel, quadruped neck flexion/extension, adductor open book, side plank hip dip, bird dog hip spinal flexion, and windmill single leg). Twelve healthy subjects performed these spine-related exercises, and wearable IMU data were collected for spine angle estimation and IMU location identification.

Results
Results demonstrated average mean absolute spinal angle estimation errors of 2.59$$^\circ$$

∘

and average classification accuracy of 92.97%. The proposed system effectively identified IMU locations and assessed spine-related rehabilitation exercises while demonstrating robustness to individual differences and exercise variations.

Conclusion
This inexpensive, convenient, and user-friendly approach to spine degeneration rehabilitation could potentially be implemented at home or provide remote assessment, offering a promising avenue to enhance patient outcomes and improve accessibility for spine-related rehabilitation.
Trial registration: No. E2021013P in Shanghai Jiao Tong University.
Health information management systems and practices in conflict-affected settings: the case of northwest Syria
Authors: Ladadwa Reem , Hariri Mahmoud , Alatras Muhammed Mansur , Elferruh Yasir , Ramadan Abdulhakim , Dowah Mahmoud , Bawaneh Yahya Mohammad , Aljerk Wassel , Patel Preeti , Ekzayez Abdulkarim , El Achi Nassim 
Published: June 2024

Abstract
Background
In conflict settings, as it is the case in Syria, it is crucial to enhance health information management to facilitate an effective and sustainable approach to strengthening health systems in such contexts. In this study, we aim to provide a baseline understanding of the present state of health information management in Northwest Syria (NWS) to better plan for strengthening the health information system of the area that is transitioning to an early-recovery stage.

Methods
A combination of questionnaires and subsequent interviews was used for data collection. Purposive sampling was used to select twenty-one respondents directly involved in managing and directing different domains of health information in the NWS who worked with local NGOs, INGOs, UN-agencies, or part of the Health Working Group. A scoring system for each public health domain was constructed based on the number and quality of the available datasets for these domains, which were established by Checci and others.

Results & conclusions
Reliable and aggregate health information in the NWS is limited, despite some improvements made over the past decade. The conflict restricted and challenged efforts to establish a concentrated and harmonized HIS in the NWS, which led to a lack of leadership, poor coordination, and duplication of key activities. Although the UN established the EWARN and HeRAMS as common data collection systems in the NWS, they are directed toward advocacy and managed by external experts with little participation or access from local stakeholders to these datasets.

Recommendations
There is a need for participatory approaches and the empowerment of local actors and local NGOs, cooperation between local and international stakeholders to increase access to data, and a central domain for planning, organization, and harmonizing the process. To enhance the humanitarian health response in Syria and other crisis areas, it is imperative to invest in data collection and utilisation, mHealth and eHealth technologies, capacity building, and robust technical and autonomous leadership.
Revisiting superiority and stability metrics of cultivar performances using genomic data: derivations of new estimators
Authors: Carvalho Humberto Fanelli , Rio Simon , García-Abadillo Julian , Isidro y Sánchez Julio 
Published: June 2024

AbstractThe selection of highly productive genotypes with stable performance across environments is a major challenge of plant breeding programs due to genotype-by-environment (GE) interactions. Over the years, different metrics have been proposed that aim at characterizing the superiority and/or stability of genotype performance across environments. However, these metrics are traditionally estimated using phenotypic values only and are not well suited to an unbalanced design in which genotypes are not observed in all environments. The objective of this research was to propose and evaluate new estimators of the following GE metrics: Ecovalence, Environmental Variance, Finlay–Wilkinson regression coefficient, and Lin–Binns superiority measure. Drawing from a multi-environment genomic prediction model, we derived the best linear unbiased prediction for each GE metric. These derivations included both a squared expectation and a variance term. To assess the effectiveness of our new estimators, we conducted simulations that varied in traits and environment parameters. In our results, new estimators consistently outperformed traditional phenotype-based estimators in terms of accuracy. By incorporating a variance term into our new estimators, in addition to the squared expectation term, we were able to improve the precision of our estimates, particularly for Ecovalence in situations where heritability was low and/or sparseness was high. All methods are implemented in a new R-package: GEmetrics. These genomic-based estimators enable estimating GE metrics in unbalanced designs and predicting GE metrics for new genotypes, which should help improve the selection efficiency of high-performance and stable genotypes across environments.
POLR1D silencing suppresses lung cancer cells proliferation and migration via inhibition of PI3K-Akt pathway
Authors: Yuan Zhize , Wang Yichao , Yang Yong , Qin Xiong 
Published: June 2024

Abstract
Aim
The most common type of cancer that leads to death worldwide is lung cancer. Despite significant surgery and chemotherapy improvements, lung cancer patient’s survival rate is still poor. The RNA polymerase I subunit D (POLR1D) gene can induce various cancers. A current study reported that POLR1D plays a vital role in cancer prognosis. However, its biological function in the development of lung cancer remains unclear.

Methods
Reverse transcription PCR (RT-PCR) measured the relative POLR1D protein expression level in lung cancer cell lines. Lung cancer cell proliferation, migration, and invasion were analyzed by performing cell counting kit-8 (CCK-8), and transwell. The phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling pathway-related protein expressions were examined by Western blotting assay.

Results
POLR1D protein expression was elevated in lung cancer. Lung cancer cell loss-of-function tests showed that POLR1D silencing could attenuate cell viability both in SK-MES-1 and in H2170 cells. Furthermore, silencing POLR1D inhibited SK-MES-1 and H2170 cells proliferation, migration, and invasion. Moreover, SK-MES-1 and H2170 cells’ migration and invasion capacity were potentially suppressed by the knockdown of POLR1D. The progression of multiple cancers has been implicated in the PI3K/AKT pathway. Here, we observed that POLR1D silencing suppressed lung cancer progression by inhibition of the PI3K-Akt pathway.

Conclusions
The study speculated that POLR1D might provide a new potential therapeutic possibility for treating lung cancer patients via targeting PI3K/AKT.