bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis Of The Effect Of Leverage On Company Value (Study PT case. Gajah Tunggal Tbk 2019-2022)
Authors: Wijaya S. , Masniah A.
Published: December 2024

Company PT. Gajah Tunggal Tbk is the largest tire in Asia especially in Asia southeast . Founded in 1971 and in 1990 officially has offices at the Jakarta Stock Exchange and the Surabaya Stock Exchange . This company located in Jakarta and has factory in town attack and tangerang For support activity the production . objective study This This is For analyze the effect of leverage on mark company PT. Gajah Tunggal Tbk 2020-2022 . Method writing this paper using Grand Theory where to be base the theory are Leverage and Company Value. Grand Theory is something that becomes base birth theory Where theory the Still nature macro or wide Then formulated at the next level . In this paper using quantitative data Where data sources used is secondary data that comes from from report PT finance . Gajah Tunggal Tbk . 2019-2022 . Based on Measurable Leverage serving with Debt to Assets Ratios and Company Value are measured with using the Price to Book Value (PBV) of The years 2019 – 2022 show that PT. Gajah Tunggal Tbk has Debt to Assets The ratio (DAR) is in the GOOD CATEGORY based on category Cashmere (2016) in Fitria (2022). However  Debt to Asset value The ratio (DAR) is still ≥ 0.5 according to moneyduck.com.id (2022) including . This matter show that part big asset company financed by debt . Whereas mark company PT. Gajah Tunggal Tbk is calculated through Price to Book Value (PBV) is in the UNDERVALUED CATEGORY .
The Influence of Accounting Information System Implementation on Financial Performance at PT Bank Pembangunan Daerah Jawa Timur, Tbk
Authors: Dewi N. D. , Malinda O.
Published: December 2024

The financial performance of a company is crucial in providing information to investors. A company's performance can be assessed from its financial statements, which serve as a benchmark to determine how the company achieves the results it has aimed for. As an evolving organization, the company is expected to carry out its activities in line with the vision, mission, and objectives established by management. The purpose of this study is to examine the impact of the implementation of the Accounting Information System on financial performance at PT Bank Pembangunan Daerah Jawa Timur, Tbk. The research method used in this study is qualitative, supported by textual explanations and images to provide a deeper understanding of the scholarly work. According to the research findings, it can be concluded that the implementation of the accounting information system has a significant effect on the financial performance at PT Bank Pembangunan Daerah Jawa Timur. This study indicates that proper and effective implementation of the accounting information system can improve a company's financial performance, which can then be understood by stakeholders.
Non-flow-through static (closed chamber) method for sampling of greenhouse gases in crop production systems
Authors: Mazengo Tumaini Erasto Robert , Zhong Xiuli , Liu Xiaoying , Mwema Mwema Felix , Gill Rubina
Published: December 2024

Methods and procedures for measuring greenhouse gases vary in different aspects, which could dictate most of the decisions. Even within the same context of measurements, there are different techniques and procedures. This study presents a harmonized approach so that results from different studies are easily compared, and methods can be reproduced. The relevant literature on sampling has been discussed and used to establish consistency. The applied knowledge acquired during the two related field experiments, 2017-2018 and 2018-2019, has also been used to leverage the procedures. It was observed that the non-flow-through steady-state (closed or static chamber) method is the widely used method in the field for greenhouse gas measurements. Its chronological sampling’s main steps are anchor installation, upper part chamber placement, temperature recording, gas sample withdrawal, injecting the sample into the vial, flushing the syringe with air twice, upper chamber part removal from the anchor, and placement on the plot border beside the respective anchors. These leveraged procedures can ensure consistency in acquiring data for reliable results to help make informed decisions about greenhouse gas reductions.
Efficacy and safety of pegylated liposomal doxorubicin and epirubicin as neoadjuvant chemotherapy for breast cancer
Authors: Shen Yuanyuan , Hua Qingling , Dong Menghao , Jin Wei , Hu Xueyang , Gu Kangsheng
Published: December 2024

Aim

This study aims to compare the efficiencies and toxicities of pegylated liposomal doxorubicin (PLD) based and epirubicin based chemotherapeutic regimens as neoadjuvant chemotherapy (NAC) for early breast cancer.

Patients and methods

We retrospectively analyzed 391 patients with stage II-III breast cancer who received NAC in multiple centers. The efficiencies and toxicities of PLD and epirubicin based NAC regimens were compared by using both propensity-score matched (PSM) and unmatched data. The status of relevant gene loci was detected through next-generation sequencing (NGS) technology and the correlation between mutations of genes and serious adverse events (AEs) was preliminarily analyzed.

Results

A total of 391 patients were included in this study. Among them, 235 patients received PLD based NAC (PLD group), and the other 156 patients were administrated with EPI based NAC (EPI group). The pathological complete response (pCR) rate of patients in PLD group was significantly higher than EPI group (before PSM:32.3% vs. 23.1%; after PSM:42.5% vs. 24.7%). Most severe AEs of patients in EPI group were more than PLD group (before PSM: 1.3%–37.8% vs. 0%–10.6%; after PSM: 1.4%–37.0% vs. 0%–9.6%). Mutation rates of 7 gene (MTHFR, DPYD, NQO1, ERCC1, UGT1A1, TYMS and TP53) of patients with severe AEs were significantly higher compared with patients with slight AEs (grade 1/2) or without AEs.

Conclusion

PLD based chemotherapeutic regimen is a viable option for NAC of breast cancer. Epirubicin should be avoided for patients with mutations of some specific genes considering the potential severe AEs.
Efficacy of natural NF-κB inhibitors in the treatment of fibrosarcoma: an in vitro model study
Authors: Radzka Justyna , Gizak Agnieszka , Drąg-Zalesińska Małgorzata , Haczkiewicz-Leśniak Katarzyna , Kulus Michał , Szewczyk Anna , Szlasa Wojciech , Podhorska-Okołów Marzenna , Kulbacka Julita
Published: December 2024

Introduction

NF-κB plays a pivotal role in the progression of cancers, including myosarcomas such as fibrosarcoma. Plants possess considerable potential for the provision of chemotherapeutic effects against cancer. The present study assessed, among others, the cytotoxicity, migration capacity and DNA damage induced by several natural compounds (berberine, curcumin, biochanin A, cucurbitacin E (CurE) and phenethyl caffeic acid (CAPE)) in cancer cells (WEHI-164) and normal muscle cells (L6).

Methods

IC50 parameter was determined for all substances after 24-hour incubation. Molecular docking studies were performed to assess compound binding to cytoskeletal proteins. Neutral comet assay and immunocytochemical analysis were used to assess the intensity of apoptosis, and transmission electron microscopy was employed to validate these results at the ultrastructural level.

Results and Discussion

The results showed that the tested compounds had a significantly increased cytotoxic effect on cancer cells compared to normal cells. Furthermore, molecular docking studies indicated that CAPE, biochanin A, and CurE could inhibit actin polymerization, suggesting their potential role in disrupting the cytoskeleton of cancer cells. Increased expression of caspase-3 and PARP-1 in WEHI-164 cells after treatment indicated the induction of apoptosis. Transmission electron microscopy confirmed the presence of cellular stress and vacuolation in cells treated with these compounds, with more pronounced effects observed in cancer cells compared to normal cells. The results indicate that natural NF-κB inhibitors may be capable of selectively targeting cancer cells, reducing their viability and inducing apoptosis while sparing normal cells. This selectivity is of great importance for the development of safer anticancer therapies. The results of this research support the hypothesis that these natural compounds may be effective anticancer agents, particularly in the treatment of fibrosarcoma. Further, in vivo studies and clinical trials are required to gain a full understanding of their mechanisms of action and potential synergies with existing chemotherapeutic agents.
Zebrafish as a model system for studying reproductive diseases
Authors: Zha Wenwen , Hu Weitao , Ge Chenkai , Chen Jianjun , Cao Zigang
Published: December 2024

Reproductive system diseases have become a major health challenge facing humans, so extensive investigations are needed to understand their complex pathogenesis and summarize effective treatments. In the study of reproductive diseases, mice are the most commonly used animal model. However, the cost and time required to establish mouse animal models are high. The existing zebrafish model can solve this problem well. Zebrafish is an animal model with great application prospects and has lots of advantages, including high degree of genetic conservation with humans, short reproductive cycle, transparent embryos, and rapid growth, providing unique opportunities for high-throughput drug screening and identification of potential treatments. Researchers have successfully used chemical induction, physical damage, gene editing technology, etc., to induce reproductive system damage in zebrafish to study the biological processes related to its reproductive diseases. Therefore, in this review, the main models and related advantages of zebrafish in reproductive diseases are summarized, the pathological mechanisms of zebrafish as a reproductive disease model are clarified, and new perspectives and valuable insights are provided for the treatment of human reproductive diseases. The literature and data cited in the review are all from PubMed, covering important research results on zebrafish reproductive diseases in the past 10 years.
PLK1 inhibition impairs erythroid differentiation
Authors: Jia Peijun , Li Yan , Duan Lulu , Zhang Jingxin , Xu Yuanlin , Zhang Huan , Wang Chenghui , Gong Yaqian , Zhang Ying , Zhao Longzhen , Huang Yumin , Zhang Shijie
Published: December 2024

Polo-like kinase 1 (PLK1), a key regulator of the G2/M phase in mitosis, is frequently overexpressed in numerous tumors. Although PLK1 inhibitors have emerged as promising therapeutic agents for cancer, their use has been linked to significant anemia in a subset of patients, yet the underlying mechanisms remain poorly understood. In this study, we utilized an in vitro human umbilical cord blood-derived CD34+ cell-based erythroid differentiation system, alongside a murine model, to investigate the impact of PLK1 inhibitors on erythropoiesis. Our results indicate that PLK1 inhibitors, specifically GSK461364 and BI6727, significantly suppress the proliferation of erythroid cells, resulting in G2/M phase cell cycle arrest, increased apoptosis in erythroid cells, and the formation of abnormally nucleated late-stage erythroblasts. In vivo, administration of PLK1 inhibitors in mice induced severe anemia, as evidenced by a marked reduction in red blood cells and hemoglobin levels. More specifically, PLK1 inhibition impaired the differentiation and erythroid commitment of hematopoietic stem cells in the bone marrow, resulting in abnormal accumulation of BFU-E cells and reduced proliferation and differentiation of CFU-E, and a decrease in the number of terminal erythrocytes. Mechanistically, PLK1 inhibitors primarily induce apoptosis in erythroid cells by reducing Mitochondrial membrane potential and arresting the cell cycle at the G2/M phase. Overall, our findings underscore the critical role of PLK1 in erythropoiesis and shed light on the mechanisms underlying PLK1 inhibitor-induced anemia, providing essential guidance for developing strategies to prevent and manage anemia in clinical applications of PLK1-targeted therapies.
VRAC channel inhibition as a novel strategy for the treatment of ischemia-reperfusion injury
Authors: Gao Yuhan , Li Lu , Zhang Yuejun , Chu Yanlong , Han Guang
Published: December 2024

Ischemia-reperfusion injury is a serious clinical pathology involving multiple organs such as the heart and brain. The injury results from oxidative stress, inflammatory response and cell death triggered by restoring tissue blood flow after ischemia, leading to severe cell and tissue damage. In recent years, the volume-regulated anion channel (VRAC) has gained attention as an important membrane protein complex. VRAC plays a dual role in ischemia-reperfusion injury: on the one hand, activated VRAC promotes the release of intracellular chloride and glutamate, exacerbating cellular swelling and excitotoxicity, and on the other hand, the regulatory effect of VRAC may also provide protection to cardiomyocytes. This article reviews the pathophysiological mechanisms of ischemia-reperfusion injury, existing therapeutic strategies and their limitations, focuses on the molecular structure of VRAC, its activation mechanism, and its role in ischemia-reperfusion injury, and concludes with a discussion of the potential of targeted inhibition of VRAC as an emerging therapeutic strategy and the challenges it faces. A deeper understanding of the role of VRAC in ischemia-reperfusion injury is expected to provide new therapeutic ideas to improve patient prognosis.
A non-linear association of low-density lipoprotein cholesterol with all-cause and cardiovascular mortality among patients with hypertension
Authors: Liang Guoliang , Zhang Wenhao , Gu Xinxin , Zhang Qiong , Liu Ankang , Qing Xinran , Ma Jiangwei
Published: December 2024

Background

Although a few studies have examined the correlation between low-density lipoprotein cholesterol (LDL-C) and mortality, no study has explored these associations in hypertensive populations. This study aims to investigate the relationship between low-density lipoprotein cholesterol and cardiovascular and all-cause mortality in adults with hypertension.

Methods

Hypertensive participants aged ≥18 years from the National Health and Nutrition Examination Survey 1999–2018 with blood lipid testing data and complete follow-up data until 31 December 2019 were enrolled in the analysis. Univariate and multivariate Cox regression were conducted for the calculation of hazard ratios and 95% confidence intervals. A restricted cubic spline curve was performed to visually represent the relationship between LDL-C and mortality. Kaplan–Meier survival analysis and stratification analysis were also carried out.

Results

We finally analysed a cohort of 9,635 participants (49.6% male, mean age of 59.4 years). After a median follow-up of 98 months, there were 2,283 (23.7%) instances of all-cause fatalities, with 758 (7.9%) cases attributed to cardiovascular disease. Multivariate Cox regression analysis showed that lower levels of LDL-C were associated with a higher risk of all-cause and cardiovascular mortality; the LDL-C group’s lowest level (<2.198 mmol/L) still showed a 19.6% increased risk of all-cause mortality (p = 0.0068) in the model that was completely adjusted. Both all-cause mortality and cardiovascular mortality showed a non-linear association with LDL-C concentration in restricted cubic spline regression analysis.

Conclusions

In individuals with hypertension, LDL-C was linked to cardiovascular and all-cause mortality. It was further demonstrated that this relationship was non-linear.
Association of frailty with cardiovascular and all-cause mortality in community-dwelling older adults: insights from the Chinese longitudinal healthy longevity survey
Authors: Gao Hui , Ma Qiaoli , Li Jiahai , Zhang Qinghui
Published: December 2024

Background

Previous studies suggest that frailty increases the risk of mortality, but the risk of cardiovascular disease (CVD) and all-cause mortality in Chinese community-dwelling older adults remains understudied. Our aim was to explore the effect of frailty on cardiovascular and all-cause mortality in older adults based on a large-scale prospective survey of community-dwelling older adults in China.

Methods

We utilized the 2014–2018 cohort of the Chinese Longitudinal Healthy Longevity Survey and constructed a frailty index (FI) to assess frailty status. Propensity score matching was used to equalize the baseline characteristics of participants to strengthen the reliability of the findings. Hazard ratios and 95% confidence intervals (CIs) were estimated using multivariate Cox models, adjusting for potential confounders, to assess the association between frailty and cardiovascular and all-cause mortality. The relationship between frailty and cardiovascular mortality was further explored using a competing risk model considering death as a competing event. The dose–response relationships between them were estimated using restricted cubic spline models.

Results

The results of the multivariate Cox model found that the frailty group had a higher risk of CVD mortality (1.94, 95% CI: 1.43–2.63) and all-cause mortality (1.87, 95% CI: 1.63–2.14) in compared with the non-frailty group. The multivariate competing risks model suggested a higher risk of CVD mortality in the frailty group (1.94, 95% CI: 1.48–2.53). The analysis found no non-linear relationship between FI and the risk of CVD mortality but a non-linear dose–response relationship with the risk of all-cause mortality.

Conclusions

Frail older adults demonstrated a stronger risk of CVD and all-cause mortality. Reversing frailty in older adults is therefore expected to reduce the risk of death in older adults.
Artificial intelligence in dentistry and dental biomaterials
Authors: Rokaya Dinesh , Jaghsi Ahmad Al , Jagtap Rohan , Srimaneepong Viritpon
Published: December 2024

Artificial intelligence (AI) technology is being used in various fields and its use is increasingly expanding in dentistry. The key aspects of AI include machine learning (ML), deep learning (DL), and neural networks (NNs). The aim of this review is to present an overview of AI, its various aspects, and its application in biomedicine, dentistry, and dental biomaterials focusing on restorative dentistry and prosthodontics. AI-based systems can be a complementary tool in diagnosis and treatment planning, result prediction, and patient-centered care. AI software can be used to detect restorations, prosthetic crowns, periodontal bone loss, and root canal segmentation from the periapical radiographs. The integration of AI, digital imaging, and 3D printing can provide more precise, durable, and patient-oriented outcomes. AI can be also used for the automatic segmentation of panoramic radiographs showing normal anatomy of the oral and maxillofacial area. Recent advancement in AI in medical and dental sciences includes multimodal deep learning fusion, speech data detection, and neuromorphic computing. Hence, AI has helped dentists in diagnosis, planning, and aid in providing high-quality dental treatments in less time.
Adaptability evaluation of the FIRST model in Hobq Desert, northern China
Authors: Zheng Xinqian , Yang Fan , Wang Jingshu , Xu Lishuai , Abudukade Silalan , Ma Mingjie , Sun Yingwei
Published: December 2024

Obtaining high temporal and spatial resolution spectral data is the key to revealing the influencing factors, effects, and mechanisms of land-atmosphere interactions in deserts. This study, we used MODIS and Sentinel-2 data as data sources to calculate daily reflectance and Normalized Difference Vegetation Index (NDVI) data with a spatial resolution of 10 m, based on the Spatiotemporal Fusion Incorporating Spectral Autocorrelation (FIRST) model, across different climatic zones in the Hobq Desert, northern China, in March. Then, we evaluated the adaptability of the FIRST model in the Hobq Desert based on spatial and textural characteristics, as well as spatial-temporal distribution characteristics, using qualitative analysis, quantitative analysis, and geographic detectors. The results show that the correlation coefficients of First fused data and Sentinel-2 data in red, green, blue, near-infrared bands, and NDVI were 0.574 (p < 0.01), 0.448 (p < 0.01), 0.485 (p < 0.01), 0.573 (p < 0.01), and 0.625 (p < 0.01), and the scatter points were evenly distributed on both sides of y = x. Meanwhile, FIRST NDVI and Sentinel-2 NDVI maintained consistency in spatial texture and hue changes, with similar value ranges. The daily scale coefficient of variation (CV) of FIRST NDVI in different desert types were less than that of MODIS NDVI. Among them, the variability of FIRST NDVI in fixed dunes was significantly smaller than that of MODIS NDVI, with the former’s CV being 0.034 smaller than the latter’s. Besides, it was found that there were significant differences in First NDVI among different desert types based on risk detection, while MODIS NDVI showed insignificant differences between fixed dunes and semi-fixed dunes. This suggests that First model integrated effectively various types of remote sensing data and had strong applicability in the eastern part of Hobq Desert, which could distinguish between fixed dunes and semi-fixed dunes, providing a more accurate monitoring tool for environmental zoning management in desert areas.
Classification and prediction of rock mass drillability for a tunnel boring machine based on operational data mining
Authors: Sun Mingshe , Chen Song , He Huafei , Wang Wenzheng , Song Kezhi , Lin Xuebing
Published: December 2024

Currently, the accurate prediction of tunnel boring machine (TBM) performance remains a considerable challenge due to the complex interactions between the TBM and rock mass. In this study, the research work is based on part of a metro tunnel project that covers 2,083.94 m. The Gaussian mixture model (GMM) and K-nearest neighbor algorithm (KNN) are used to classify and predict the rock mass drillability in the TBM excavation process. Drillability indexes are introduced to cluster and classify the rock mass, including the penetration (P), field penetration index (FPI), torque penetration index (TPI), and specific energy (SE). Statistical characteristics of the drillability indexes were analyzed, and it was found that their distributions did not conform to the normal distribution, with large variation coefficients. Clustering analysis was then conducted on the TPI and FPI within the training group using the Gaussian mixture model, and six drillability categories of rock mass were classified. Subsequently, the mapping relationship between the cutterhead speed, advance speed, total advance force, and cutterhead torque in the training group and the drillability of rock mass was established based on the KNN classification model. It was revealed that when the K-value is set to 4, the model has high macro-F1, macro-P, and macro-R. Validated by the testing group data, this method has been proven to be feasible and effective. The research results indicate that this method can effectively classify and predict the drillability of tunneling surrounding rock mass in shield construction, particularly when the rock mass at the shield face is uniform and homogeneous. This provides a theoretical basis and technical support for safe and efficient shield tunneling.
Environmental education during the COVID-19 pandemic: lessons from Ontario, Canada
Authors: Millward Andrew A. , Borisenoka Inga , Bhagat Nickesh , LeBreton Gregory T. O.
Published: December 2024

This study investigates the integration of place-based environmental education (PBEE) during emergency remote education (ERE) and in-person teaching, considering the implications of COVID-19. The objectives include (a) to understand if and how teachers used PBEE as a pedagogical learning tool during ERE, (b) to identify PBEE adaptations for implementation in an online context, and (c) to explore opportunities and barriers to PBEE during ERE. Ontario (Canada) educators’ perspectives were obtained through an online survey and focus groups. Using non-parametric statistical analyses, perspectives concerning opportunities and challenges to integrating and delivering PBEE in lessons were identified. Additional focus included educators’ views on student receptivity and knowledge retention. Findings indicate educators’ appreciation for PBEE as a pedagogical approach, yet delivery challenges arise from systemic barriers causing inconsistency in PBEE delivery. Obstacles include curriculum demands, institutional disinvestment, grade-level constraints, and limited training. Despite challenges, educators showcase innovation and commitment to PBEE during ERE, emphasizing its enduring value. The study underscores educators’ resourcefulness in adapting PBEE methods and the potential for renewed significance of outdoor education amidst the pandemic’s influence on students’ connection to nature.
The role of multimodality imaging in diabetic cardiomyopathy: a brief review
Authors: Adel Fadi W. , Chen Horng H.
Published: December 2024

Diabetic cardiomyopathy (DMCM), defined as left ventricular dysfunction in the setting of diabetes mellitus without hypertension, coronary artery disease or valvular heart disease, is a well-recognized entity whose prevalence is certainly predicted to increase alongside the rising incidence and prevalence of diabetes mellitus. The pathophysiology of DMCM stems from hyperglycemia and insulin resistance, resulting in oxidative stress, inflammation, cardiomyocyte death, and fibrosis. These perturbations lead to left ventricular hypertrophy with associated impaired relaxation early in the course of the disease, and eventually culminating in combined systolic and diastolic heart failure. Echocardiography, cardiac nuclear imaging, and cardiac magnetic resonance imaging are crucial in the diagnosis and management of the structural and functional changes associated with DMCM. There appears to be a U-shaped relationship between glycemic control and mortality. Exogenous insulin therapy, while crucial, has been identified as an independent risk factor for worsening cardiovascular outcomes. On the other hand, Glucagon-like Peptide-1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors appear to potentially offer glycemic control and cardiovascular protection. In this review, we briefly discuss the pathophysiology, staging, role of multimodality imaging, and therapeutics in DMCM.
Triglyceride-glucose index as a mediator of body mass index and cardiovascular disease in middle-aged and older Chinese adults: a nationally representative longitudinal cohort study
Authors: Gan Ying-Yuan , Zhai Lu , Liao Qian , Huo Rong-Rui
Published: December 2024

Background

Body mass index (BMI) consistently correlates with the triglyceride-glucose (TyG) index, a marker of insulin resistance, which in turn is linked to heightened cardiovascular disease (CVD) risk. Thus, insulin resistance could potentially mediate the association between BMI and CVD risk. However, few studies have explored this mechanism in the general population.

Methods

We used data from the China Health and Retirement Longitudinal Study, which is an ongoing prospective cohort study. It initially enrolled 7233 middle-aged and older Chinese adults who were free of heart disease and stroke at baseline. The exposure variable was BMI. Incident CVD, defined as self-reported physician-diagnosed heart disease and stroke combined, served as the main outcome.

Results

Of the 7 233 participants (mean [SD] age, 58.93 [9.33] years), 3 415 (47.2%) were men. During the 7 years of follow-up, 1 411 incident CVD cases were identified. Both BMI and TyG index were associated with CVD risk (HR per 1-SD increase: BMI, 1.23; 95% CI, 1.17–1.29; TyG, 1.13; 95% CI, 1.07–1.19). The 4-way decomposition analysis show that, overweight increased CVD risk by 28% (HR [total association], 1.28; 95% CI, 1.14–1.45), with 18.1% (95% CI, 2.2%–34.0%) mediated by TyG index (HR [pure indirect association], 1.05; 95% CI, 1.02–1.09); while obesity increased CVD risk by 91% (HR [total association], 1.91; 95% CI, 1.63–2.23), with 9.5% (95% CI, 2.2%–16.7%) mediated by TyG index (HR [pure indirect association], 1.09; 95% CI, 1.03–1.15). No evidence suggested TyG index modified BMI’s association with incident CVD.

Conclusions

The study revealed that the TyG index was associated to CVD risk and acted as a small partial mediator in the relationship between BMI and CVD among middle-aged and older Chinese adults. Consequently, solely addressing insulin resistance might not significantly mitigate the impact of body weight on CVD. Thus, exploring alternative pathways and potential mediators of CVD risk becomes imperative.
Targeted deletion of the pancreatic β-cell oxytocin receptor and its effects on metabolic regulation and β-cell health
Authors: Mendez Armando J. , Szeto Angela , Boulina Maria , Westwright Jesica , Rahman Hafsha , Abushamma Sarah , Schneider Riley , McCabe Philip M.
Published: December 2024

The neuropeptide oxytocin (OXT) and its receptor (OXTR) have been shown to play an important role in glucose metabolism, and pancreatic islets express this ligand and receptor. In the current study, OXTR expression was identified in α-, β-, and δ-cells of the pancreatic islet by in situ RNA hybridization, and OXT protein expression was observed only in β-cells. In order to examine the contribution of islet OXT/OXTR in glycemic control and islet β-cell heath, we developed a β-cell specific OXTR knock-out (β-KO) mouse. In isolated islets from control mice, OXT enhanced glucose stimulated secretion of insulin, but this response was abolished in the β-KO mice. In vivo, supraphysiological doses of OXT reduced blood glucose levels in hyperglycemic Control mice and during a glucose tolerance test. Once again, this response was abolished in the β-KO mice, suggesting that β-cell OXTR may play a role in glycemic regulation. Despite these findings, β-cell deletion of OXTR had no effect on fasting glucose, fasting insulin or glucose tolerance in mice fed a low fat- or high fat-diet for 23 weeks. The low fat or high fat diets did not alter β-cell mass by immundetection or a measure of apoptosis, however, β-KO mice on a high fat diet did exhibit increased β-cell proliferation. In mice treated with the cytotoxic agent, streptozotocin, deletion of OXTR resulted in greater hyperglycemia in β-KO mice relative control mice, suggesting that β-cell OXTR may provide some cytoprotection. In conclusion, the present study provides mixed support for a role of the β-cell OXTR in glycemic regulation. On one hand, in vitro experiments and in vivo pharmacologic experiments provided evidence that under hyperglycemia, OXTR activation can potentiate insulin secretion and glucose suppression. On the other hand, β-KO followed by chronic dietary manipulation had no effect on whole body glucose regulation in vivo. In terms of β-cell health, our data suggests a role of the OXTR in β-cell proliferation and cytoprotection following metabolic or cytotoxic challenge.
Prevalence and risk factors for type 2 diabetes mellitus in women with gestational diabetes mellitus: a systematic review and meta-analysis
Authors: Chen Kaiqi , Tang Lichao , Wang Xinwei , Li Yunhua , Zhang Xijian , Cui Shikui , Chen Wei , Jin Zhao , Zhu Danping
Published: December 2024

Introduction

This study aims to explore the risk factors in the progression of gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM).

Material and methods

Relevant studies were comprehensively searched from PubMed, Web of Science, Cochrane Library, and Embase up to March 12. Data extraction was performed. Differences in risk factors were presented as odds ratios (OR) and corresponding 95% confidence intervals (CI). The quality of the included studies was assessed through the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality scale.

Results

This meta-analysis encompassed 46 studies involving a total of 196,494 patients. The factors most strongly associated with the risk of developing T2DM following GDM were the use of progestin-only contraceptives (odds ratio [OR]: 2.12, 95% confidence interval [CI] = 1.00–4.45, P = 0.049), recurrence of GDM (OR: 2.63, 95% CI = 1.88–3.69, P < 0.001), insulin use during pregnancy (OR: 4.35, 95% CI = 3.17–5.96, P < 0.001), pre-pregnancy body mass index (BMI) (OR: 2.97, 95% CI = 2.16–4.07, P < 0.001), BMI after delivery (OR: 4.17, 95% CI = 2.58–6.74, P < 0.001), macrosomia (OR: 3.30, 95% CI = 1.45–7.49, P = 0.04), hypertension (OR: 5.19, 95% CI = 1.31–20.51, P = 0.019), and HbA1c levels (OR: 3.32, 95% CI = 1.81–6.11, P < 0.001). Additionally, age (OR: 1.71, 95% CI = 1.23–2.38, P = 0.001), family history of diabetes (OR: 1.47, 95% CI = 1.27–1.70, P < 0.001), BMI during pregnancy (OR: 1.06, 95% CI = 1.00–1.12, P = 0.056), fasting blood glucose (FBG) (OR: 1.58, 95% CI = 1.36–1.84, P < 0.001), 1-hour oral glucose tolerance test (OGTT) (OR: 1.38, 95% CI = 1.02–1.87, P = 0.037), and 2-hour OGTT (OR: 1.54, 95% CI = 1.28–1.58, P < 0.001) were identified as moderate-risk factors for the development of T2DM.

Conclusion

The systematic review and meta-analysis identified several moderate- to high-risk factors associated with the progression of T2DM in individuals with a history of GDM. These risk factors include the use of progestin-only contraceptives, pre-pregnancy BMI, BMI after delivery, macrosomia, hypertension, persistently elevated levels of HbA1c, fasting blood glucose (FBG), 1-hour and 2-hour oral glucose tolerance tests (OGTT), age, and family history of diabetes. Our findings serve as evidence for the early prevention and clinical intervention of the progression from GDM to T2DM and offer valuable insights to guide healthcare professionals in formulating customized management and treatment strategies for female patients with diverse forms of GDM.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024545200.
The value of air conditioning
Authors: Phelan P. E. , Phelan B. E. , Sharma A.
Published: December 2024

The advent of global climate change and rising incomes, particularly in some developing countries such as Egypt, means that the use of air conditioning is poised for a dramatic increase over the next few decades. Although this anticipated increase appears inevitable, it is often associated with a negative connotation because of the increased energy demands and greenhouse gas emissions associated with expanded air conditioning use. Yet, the benefits of air conditioning are not often described in existing literature in conjunction with its associated negative externalities. For example, higher productivity in commercial buildings, and positive health benefits in all manner of buildings (residential, commercial, and industrial) could potentially offset the greater energy consumption and related disadvantages. A levelized cost of cooling (LCOC) analysis is presented to quantify under what circumstances building air conditioning provides benefits that exceed its costs, and vice versa. The LCOC is calculated for the application of air conditioning to a small office building located in either Phoenix, Arizona, United States, or in Cairo, Egypt. The electrical energy required for cooling is calculated with EnergyPlus software. The results indicate that the benefits of air conditioning far outweigh its disadvantages for the Phoenix location, largely because of the productivity benefits derived from maintaining the interior temperature at a comfortable setting. The results for Egypt are more nuanced, but still indicate the overall benefits of air conditioning in an office environment.
Case Report and literature review: Delayed diagnosis of ARCL1B due to a newly reported homozygous mutation c.464A>C p. (Tyr155Ser) in the EFEMP2 gene
Authors: Ouyang Lixue , Yang Fan , Duan Hongyu , Wang Chuan
Published: December 2024

Background

Autosomal recessive cutis laxa type 1B (ARCL1B) is an extremely rare disease characterized by severe systemic connective tissue abnormalities, including cutis laxa, aneurysm and fragility of blood vessels, birth fractures and emphysema. The severity of this disease ranges from perinatal death to manifestations compatible with survival. To date, no cases have been reported in the Chinese population. Due to its rarity, the disease is susceptible to misdiagnosis or missed diagnosis by clinicians. By presenting this case and reviewing the relevant literature, the aim is to enhance clinicians’ awareness and vigilance in diagnosing this disease.

Case presentation

We report a 7-month-old Chinese male infant who initially presented with severe respiratory infection, respiratory failure, and heart failure, and was misdiagnosed with Takayasu arteritis. Despite treatment, his condition did not improve. Due to the features of vascular malformations, developmental delay, and early onset of the disease, whole exome sequencing (WES) was performed, results revealed a homozygous mutation c.464A>C in exon 5 on the EFEMP2 gene p. (Tyr155Ser) that had never been reported before. Molecular protein prediction results suggest that this mutation site exhibits a high probability of pathogenicity. Combining the clinical manifestations, the results of cardiac color ultrasound and cardiac great vessels angiography, and the WES results, the patient was finally diagnosed with ARCL1B. Given the absence of established guidelines for the clinical manifestation, treatment, follow-up, and prognosis of ARCL1B, we searched the literatures of pubmed and web of science from inception to February 2024 to provide an essential reference for physicians to deepen the understanding of ARCL1B.

Conclusion

The EFEMP2 gene mutation identified in this patient has not been previously reported, expanding the mutation spectrum of the gene. This is the first documented case of this disease in the Chinese population. The diagnostic and therapeutic journey of this patient, along with the accompanying literature review, provides valuable insights. It highlights the importance of clinicians maintaining a high level of vigilance when encountering cases involving younger patients with multiple pulmonary artery aneurysms, as they may indicate the presence of this rare disease.
Viral infection, APOBEC3 dysregulation, and cancer
Authors: Lehle Jake , Soleimanpour Mohadeseh , Mokhtari Samira , Ebrahimi Diako
Published: December 2024

Viral infection plays a significant role in the development and progression of many cancers. Certain viruses, such as Human Papillomavirus (HPV), Epstein-Barr Virus (EBV), and Hepatitis B and C viruses (HBV, HCV), are well-known for their oncogenic potential. These viruses can dysregulate specific molecular and cellular processes through complex interactions with host cellular mechanisms. One such interaction involves a family of DNA mutators known as APOBEC3 (Apolipoprotein B mRNA Editing Catalytic Polypeptide-like 3). The primary function of these cytidine deaminases is to provide protection against viral infections by inducing viral mutagenesis. However, induction and dysregulation of A3 enzymes, driven by viral infection, can inadvertently lead to cellular DNA tumorigenesis. This review focuses on the current knowledge regarding the interplay between viral infection, A3 dysregulation, and cancer, highlighting the molecular mechanisms underlying this relationship.
Integration of gene expression and DNA methylation data using MLA-GNN for liver cancer biomarker mining
Authors: Lu Chun-Yu , Liu Zi , Arif Muhammad , Alam Tanvir , Qiu Wang-Ren
Published: December 2024

The early symptoms of hepatocellular carcinoma patients are often subtle and easily overlooked. By the time patients exhibit noticeable symptoms, the disease has typically progressed to middle or late stages, missing optimal treatment opportunities. Therefore, discovering biomarkers is essential for elucidating their functions for the early diagnosis and prevention. In practical research, challenges such as high-dimensional features, low sample size, and the complexity of gene interactions impact the reliability of biomarker discovery and disease diagnosis when using single-omics approaches. To address these challenges, we thus propose, Multi-level attention graph neural network (MLA-GNN) model for analyzing integrated multi-omics data related to liver cancer. The proposed protocol are using feature selection strategy by removing the noise and redundant information from gene expression and DNA methylation data. Additionally, it employs the Cartesian product method to integrate multi-omics datasets. The study also analyzes gene interactions using WGCNA and identifies potential genes through the MLA-GNN model, offering innovative approaches to resolve these issues. Furthermore, this paper identifies FOXL2 as a promising liver cancer marker through gene ontology and survival analysis. Validation using box plots showed that the expression of the gene FOXL2 was higher in patients with hepatocellular carcinoma than in normal individuals. The drug sensitivity correlation and molecular docking results of FOXL2 with the liver cancer-targeting agent lenvatinib emphasized its potential role in hepatocellular carcinoma treatment and highlighted the importance of FOXL2 in hepatocellular carcinoma treatment.
Characterization of a novel AEL allele harboring a c.28 + 5G>A mutation on the ABO*A2.01 background: a study utilizing PacBio third-generation sequencing and functional assays
Authors: Shao Lin-Nan , Song Wen-Qian , Zhou Lu , Pan Ling-Zi , Duan Ying , Xiao Nan , Zhou Shi-Hang , Liang Xiao-Hua
Published: December 2024

Background

Mutations in the ABO gene, including base insertions, deletions, substitutions, and splicing errors, can result in blood group subgroups associated with the quantity and quality of blood group antigens. Here, we employed third-generation PacBio sequencing to uncover a novel AEL allele arising from an intron splice site mutation, which altered the expected A2 phenotype to manifest as an Ael phenotype. The study aimed to characterize the molecular mechanism underlying this phenotypic switch

Methods

A 53-year-old healthy male blood donor with an atypical agglutination pattern was investigated. PacBio sequencing was used to sequence the entire ABO gene of the proband. In silico analysis predicted aberrant splicing, which was experimentally verified using a minigene splicing assay.

Results

Based on serological characteristics, the proband was determined to have an Ael phenotype. Sequencing revealed heterozygosity for ABO*O.01.02 and a novel ABO*A2.01-like allele with an additional c.28 + 5G>A mutation in intron 1. In silico predictions also indicated that this mutation is likely to cause aberrant splicing. Minigene analysis suggested that this mutation disrupted the 5’-end canonical donor splice site in intron 1, activated a cryptic donor site, and resulted in a 167 bp insertion, producing a truncated glycosyltransferase (p.Lys11Glufs*66). Meanwhile, a small amount of the wild type transcript was also generated through normal splicing, contributing to the Ael phenotype.

Conclusion

A novel AEL allele was identified in a Chinese male blood donor on the ABO*A2.01 background, characterized by the c.28 + 5G>A variant. This study provides insights into the molecular basis of blood group antigen variation.
Geny: a genotyping tool for allelic decomposition of killer cell immunoglobulin-like receptor genes
Authors: Zhou Qinghui , Ghezelji Mazyar , Hari Ananth , Ford Michael K. B. , Holley Connor , Sahinalp S. Cenk , Numanagić Ibrahim
Published: December 2024

Introduction

Accurate genotyping of Killer cell Immunoglobulin-like Receptor (KIR) genes plays a pivotal role in enhancing our understanding of innate immune responses, disease correlations, and the advancement of personalized medicine. However, due to the high variability of the KIR region and high level of sequence similarity among different KIR genes, the generic genotyping workflows are unable to accurately infer copy numbers and complete genotypes of individual KIR genes from next-generation sequencing data. Thus, specialized genotyping tools are needed to genotype this complex region.

Methods

Here, we introduce Geny, a new computational tool for precise genotyping of KIR genes. Geny utilizes available KIR allele databases and proposes a novel combination of expectation-maximization filtering schemes and integer linear programming-based combinatorial optimization models to resolve ambiguous reads, provide accurate copy number estimation, and estimate the correct allele of each copy of genes within the KIR region.

Results & Discussion

We evaluated Geny on a large set of simulated short-read datasets covering the known validated KIR region assemblies and a set of Illumina short-read samples sequenced from 40 validated samples from the Human Pangenome Reference Consortium collection and showed that it outperforms the existing state-of-the-art KIR genotyping tools in terms of accuracy, precision, and recall. We envision Geny becoming a valuable resource for understanding immune system response and consequently advancing the field of patient-centric medicine.
Immune-related thyroid dysfunction as a positive prognostic factor for patients with lung cancer in China: a real-world retrospective study
Authors: Guo Ge , Jing Zihan , Dou Wenrui , Wang Guiqin , Dang JunJie , Li Yajie , Wang Ruqiong , Zhang Huan , Sun Jing , Shang Lihua
Published: December 2024

Introduction

The relationship between immune-related thyroid dysfunction (irTD) and survival rates in cancer patients remains unclear. Furthermore, the impact of variations in immunotherapy line numbers and pathological types among lung cancer patients on this relationship has not been fully elucidated. This study aims to evaluate the potential of irTD as a prognostic marker for immunotherapy in Chinese patients with lung cancer.

Methods

A retrospective analysis was conducted on data collected from patients with locally advanced or metastatic lung cancer who received immune checkpoint inhibitor treatment at the Harbin Medical University Cancer Hospital. The study period spanned from December 1, 2016, to November 30, 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while the objective response rate served as the secondary endpoint.

Results

Among the 361 patients in this study, 42.7% developed irTD. Significant differences were observed between the groups with and without irTD regarding inflammatory indices, thyroid-stimulating hormone levels, and thyroid autoantibody positivity (P < 0.05). Patients with irTD demonstrated longer OS (32.5 vs. 22 months, HR: 0.65, 95% CI: 0.49-0.88; P = 0.005). For NSCLC patients, OS was significantly prolonged in those with irTD (40.8 vs. 27.2 months, HR: 0.68, 95% CI: 0.48-0.96; P = 0.028). Similarly, SCLC patients who developed irTD exhibited longer OS (27.9 vs. 13.8 months, HR: 0.51, 95% CI: 0.29-0.90; P = 0.022). Notably, irTD was observed exclusively in patients receiving immunotherapy in the second or later lines, showing a significant association with extended OS (40.8 vs. 19.4 months, HR: 0.56, 95% CI: 0.35-0.88; P = 0.012), while the presence of irTD during first-line immunotherapy did not confer a benefit to patients (32.4 vs 24.5 months, HR: 0.74, 95% CI: 0.50-1.10; P = 0.134). The effects of different irTD types, severities, or clinical symptoms on PFS and OS did not differ significantly (P > 0.05).

Conclusion

irTD demonstrates potential as a predictive marker for long-term survival benefits in Chinese patients with lung cancer. However, our exploratory analysis indicates that this association was exclusively observed in individuals receiving immunotherapy as a second-line or subsequent treatment.