bluuebunny/crossref_metadata_2025 huggingface dataset:
DEAD‐Box Helicase 17 exacerbates non‐alcoholic steatohepatitis via transcriptional repression of cyp2c29, inducing hepatic lipid metabolism disorder and eliciting the activation of M1 macrophages
Authors: Ning Deng , Jin Jie , Fang Yuanyuan , Du Pengcheng , Yuan Chaoyi , Chen Jin , Huang Qibo , Cheng Kun , Mo Jie , Xu Lei , Guo Hui , Yang Mia Jiming , Chen Xiaoping , Liang Huifang , Zhang Bixiang , Zhang Wanguang
Published: February 2024

Objective

Our study was to elucidate the role of RNA helicase DEAD‐Box Helicase 17 (DDX17) in NAFLD and to explore its underlying mechanisms.

Methods

We created hepatocyte‐specific Ddx17‐deficient mice aim to investigate the impact of Ddx17 on NAFLD induced by a high‐fat diet (HFD) as well as methionine and choline‐deficient l‐amino acid diet (MCD) in adult male mice. RNA‐seq and lipidomic analyses were conducted to depict the metabolic landscape, and CUT&Tag combined with chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted.

Results

In this work, we observed a notable increase in DDX17 expression in the livers of patients with NASH and in murine models of NASH induced by HFD or MCD. After introducing lentiviruses into hepatocyte L02 for DDX17 knockdown or overexpression, we found that lipid accumulation induced by palmitic acid/oleic acid (PAOA) in L02 cells was noticeably weakened by DDX17 knockdown but augmented by DDX17 overexpression. Furthermore, hepatocyte‐specific DDX17 knockout significantly alleviated hepatic steatosis, inflammatory response and fibrosis in mice after the administration of MCD and HFD. Mechanistically, our analysis of RNA‐seq and CUT&Tag results combined with ChIP and luciferase reporter assays indicated that DDX17 transcriptionally represses Cyp2c29 gene expression by cooperating with CCCTC binding factor (CTCF) and DEAD‐Box Helicase 5 (DDX5). Using absolute quantitative lipidomics analysis, we identified a hepatocyte‐specific DDX17 deficiency that decreased lipid accumulation and altered lipid composition in the livers of mice after MCD administration. Based on the RNA‐seq analysis, our findings suggest that DDX17 could potentially have an impact on the modulation of lipid metabolism and the activation of M1 macrophages in murine NASH models.

Conclusion

These results imply that DDX17 is involved in NASH development by promoting lipid accumulation in hepatocytes, inducing the activation of M1 macrophages, subsequent inflammatory responses and fibrosis through the transcriptional repression of Cyp2c29 in mice. Therefore, DDX17 holds promise as a potential drug target for the treatment of NASH.
Pan‐cancer analyses of bromodomain containing 9 as a novel therapeutic target reveals its diagnostic, prognostic potential and biological mechanism in human tumours
Authors: Chen Yu , Gao Zitong , Mohd‐Ibrahim Isam , Yang Hua , Wu Lang , Fu Yuanyuan , Deng Youping
Published: February 2024

Background

Mutations in one or more genes responsible for encoding subunits within the SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin‐remodelling complexes are found in approximately 25% of cancer patients. Bromodomain containing 9 (BRD9) is a more recently identified protein coding gene, which can encode SWI/SNF chromatin‐remodelling complexes subunits. Although initial evaluations of the potential of BRD9‐based targeted therapy have been explored in the clinical application of a small number of cancer types, more detailed study of the diagnostic and prognostic potential, as well as the detailed biological mechanism of BRD9 remains unreported.

Methods

We used various bioinformatics tools to generate a comprehensive, pan‐cancer analyses of BRD9 expression in multiple disease types described in The Cancer Genome Atlas (TCGA). Experimental validation was conducted in tissue microarrays and cell lines derived from lung and colon cancers.

Results

Our study revealed that BRD9 exhibited elevated expression in a wide range of tumours. Analysis of survival data and DNA methylation for BRD9 indicated distinct conclusions for multiple tumours. mRNA splicing and molecular binding were involved in the functional mechanism of BRD9. BRD9 may affect cancer progression through different phosphorylation sites or N6‐methyladenosine site modifications. BRD9 could potentially serve as a novel biomarker for diagnosing different cancer types, especially could accurately forecast the prognosis of melanoma patients receiving anti‐programmed cell death 1 immunotherapy. BRD9 has the potential to serve as a therapeutic target, when pairing with etoposide in patients with melanoma. The BRD9/SMARCD1 axis exhibited promising discriminative performance in forecasting the prognosis of patients afflicted with liver hepatocellular carcinoma (LIHC) and mesothelioma. Additionally, this axis appears to potentially influence the immune response in LIHC by regulating the programmed death‐ligand 1 immune checkpoint. For experimental validation, high expression levels of BRD9 were observed in tumour tissue samples from both lung and colon cancer patients. Knocking down BRD9 led to the inhibition of lung and colon cancer development, likely via the Wnt/β‐catenin signalling pathway.

Conclusions

These pan‐cancer study revealed the diagnostic and prognostic potential, along with the biological mechanism of BRD9 as a novel therapeutic target in human tumours.
Growing‐season climate as an explanation of spatial variations in temperature sensitivity of green‐up on Tibetan Plateau
Authors: Yang Zhiyong , Jiang Nan , Huang Yan , Shen Miaogen , Zhu Wenquan , Fu Yongshuo , Tang Yanhong , Janssens Ivan
Published: February 2024

Temperature sensitivity (TS) of the green‐up date (GUD) of plants is crucial for the prediction of grassland phenology that is important for animal husbandry and pasture management. Spatial variations in the TS are known to reflect interannual temperature variability and/or accumulated precipitation preceding the GUD (pre‐GUD). However, whether spatial TS variations are related to the interaction between pre‐GUD temperature variability and precipitation, which is a potential indicator of frost risk, remains unclear. Furthermore, because the interaction between interannual temperature variability and accumulated precipitation following the GUD (post‐GUD) can exert selection pressure on the plant life cycle, it may also be involved in shaping the spatial TS pattern. Using long‐term ground observations of GUD on the Tibetan Plateau, we show that TS is more negative (greater GUD advance per unit temperature increase) in areas with more pre‐GUD precipitation and low pre‐GUD interannual temperature variability, but less negative in areas with more pre‐GUD precipitation and high pre‐GUD interannual temperature variability. This result is likely because more pre‐GUD precipitation facilitates sprout and leaf development under stable temperature conditions, whereas it increases frost risk when the temperature variability is high. In contrast, TS magnitude decreases with increases in post‐GUD precipitation in areas where post‐GUD interannual temperature variability is low, but increases with post‐GUD precipitation in areas where post‐GUD interannual temperature variability is high. We speculate that because hydrothermal demands for leaf growth from the onset of green‐up to maturity are more easily fulfilled when interannual temperature variability is lower and precipitation is higher, green‐up need not be sensitive to pre‐GUD temperature. In contrast, high post‐GUD precipitation likely aggravates low‐temperature constraints on leaf growth when temperature variability is high, resulting in greater TS to maximize growing season length. These results suggest that spatial TS variations on the Tibetan Plateau are likely associated with adaptations of leaf‐out phenology to background pre‐GUD climatic conditions together with selection pressure from post‐GUD conditions.
Seismic resilience mechanism of self‐centering dual‐limb thin‐walled rocking piers with replaceable energy dissipation beams
Authors: Guo Jin , Guo Boyu , Nie Liwei , Pan Haiyang , Sun Ruojin , Zhao Weigang
Published: February 2024

This paper presents an innovative self‐centering dual‐limb thin‐walled rocking pier with replaceable energy dissipation beams (DLTW‐REDB), combining self‐centering hybrid system concepts with DLTW bridge piers. It addresses the issue of DLTW piers being prone to damage in the longitudinal direction during strong earthquakes, enabling rapid post‐earthquake recovery. The study focuses on the following aspects: (1) A 1:5 scale quasistatic reversed cyclic test was conducted to assess the seismic performance of the system. The results demonstrated that the hybrid system exhibited a characteristic “flag‐shaped” hysteretic response, similar to traditional rocking bridge piers. It exhibited excellent energy dissipation and self‐centering capability. Moreover, plastic damage primarily occurred in the replaceable energy dissipation beam, which could be easily replaced within 2 h while restoring the original structural behavior. (2) The self‐centering mechanism of the system was analyzed based on principles of structural mechanics, explicitly deriving the hysteresis, and residual deformation expressions. A quantitative index, the self‐centering coefficient (λ), was established to measure the self‐centering capability. (3) Numerical models were employed to analyze the sensitivity of parameters such as the prestressed reinforcement ratio, initial tension in prestressing tendons, and yield force of the energy dissipation beam. The results suggested that raising the initial tension enhanced the bearing force and reduced the residual displacement. However, raising the yield force improved the bearing capacity and energy dissipation capability, while residual displacement increased. Therefore, it is recommended to set the self‐centering coefficient at approximately 1.0 to achieve a trade‐off between effective energy dissipation capacity and acceptable residual deformation.
An integrated simulation method for large‐scale earthquake‐induced falling debris in building groups
Authors: Xu Zhen , Zhu Yian , Gu Donglian , Zhou Quan
Published: February 2024

When building groups are subjected to earthquakes, the potential hazard of exterior falling debris poses a significant risk of causing severe injuries and fatalities. In this study, an integrated simulation method of the large‐scale earthquake‐induced exterior falling debris for building groups is proposed, which includes modeling, calculation, and visualization. Firstly, a modeling algorithm is established for falling debris models of building groups. This algorithm employs the Octree algorithm to support the transformation of the three‐dimensional (3D) building surface model into falling debris models. Subsequently, the generated falling debris models are aggregated using a density clustering algorithm, and their motion is efficiently calculated based on the physics engine and time history analysis. Finally, a cooperative visualization algorithm is developed to effectively present a 3D scene that incorporates both structural displacement and the motion of falling debris in building groups. The actual distribution of exterior falling debris during the earthquake in Turkey validates the proposed simulation method, which is then integrally applied to the Beijing central business district. This integrated simulation method has the capability to provide a large‐scale 3D scene of falling debris for the virtual safety drills of earthquake evacuation and rescue within urban building groups.
A randomised controlled feasibility trial of intermittent theta burst stimulation with an open longer‐term follow‐up for young people with persistent anorexia nervosa (RaISE): Study protocol
Authors: Hemmings Amelia , Gallop Lucy , İnce Başak , Cutinha Darren , Kan Carol , Simic Mima , Zadeh Ewa , Malvisi Isabella , McKenzie Katie , Zocek Lucy , Sharpe Helen , O’Daly Owen , Campbell Iain C. , Schmidt Ulrike
Published: February 2024

Objective

We present the protocol of a feasibility randomised controlled trial (RCT) of intermittent theta burst stimulation (iTBS) for young people with anorexia nervosa (AN). Effective first‐line psychological therapies exist for young people with AN, but little is known about how to treat those who do not respond. Non‐invasive neuromodulation, such as iTBS, could address unmet treatment needs by targeting neurocircuitry associated with the development and/or maintenance of AN.

Design

Sixty‐six young people (aged 13–30 years) with persistent AN will be randomly allocated to receive 20 sessions of real or sham iTBS over the left dorsolateral prefrontal cortex in addition to their usual treatment. Outcomes will be measured at baseline, post‐treatment (1‐month post‐randomisation) and 4‐months post‐randomisation (when unblinding will occur). Additional open follow‐ups will be conducted at 12‐ and 24‐months post‐randomisation. The primary feasibility outcome is the proportion of participants retained in the study at 4‐months. Secondary outcomes include AN symptomatology, other psychopathology, quality of life, service utilisation, neurocognitive processes, and neuroimaging measures.

Discussion

Findings will inform the development of a future large‐scale RCT. They will also provide exploratory data on treatment efficacy, and neural and neurocognitive predictors and correlates of treatment response to iTBS in AN.
Assessment of the changes in product characteristics, total ascorbic acid, total flavonoid content, total polyphenol content and antioxidant activity of dried soursop fruit tea (Annona muricata L.) during product storage
Authors: Do Yen Vy , Le Quynh Nhu Thi , Nghia Nguyen Huu , Vu Ngoc Duc , Tran Nhi Thi Yen , Bay N. T. , Tran Thi Tuu , Bach Long Giang , Dao Tan Phat
Published: February 2024

Soursop (Annona muricata L.) fruit tea is a health‐beneficial product that promotes economic development and addresses the issue of excessive agricultural waste. Prolonging the shelf‐life of soursop fruit tea has been of scientific interest currently. This study evaluated the effects of three types of packaging materials of soursop fruit tea (e.g., paper, paper‐combined Polyetylen (PE), and aluminum‐combined PE) and different storage temperatures (5, 15, 30, and 45°C) on various product characteristics, total polyphenol content (TPC), total flavonoid content (TFC), total ascorbic acid (TAA), and 2,2‐diphenyl‐1‐picryl hydrazyl (DPPH)/2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) free radical scavenging capacity during 4 weeks of storage. The results revealed that the sample stored in aluminum‐combined PE packaging at 30°C retained most of the product's characteristics and nutritional values. This was evidenced by the moisture content of 2.49%, TAA of 3.9 ± 1.4 mg/100 g dry weight, TPC of 12.89 ± 0.47 mgGAE/g, TFC of 0.54 ± 0.004 mgQE/g, DPPH scavenging activity of 4.06 ± 0.02 mgAA/g, and ABTS scavenging activity of 13.34 ± 0.32 mgAA/g. Additionally, the microbiological quality of the sample met the standard of TCVN 9740:2013. Overall, the study highlights the importance of packaging materials and storage temperatures to maintain the nutritional quality of soursop fruit tea. It provides valuable insights into the suitable storage conditions for preserving the quality and health‐promoting effects of this product.
Causal inference between serum bilirubin levels and juvenile idiopathic arthritis‐associated uveitis: A bidirectional Mendelian randomization study
Authors: Zhang Jun , Zhou Peng , Hu Shuqiong , Cai Shiya , He Tao
Published: February 2024

Background

Several observational studies have suggested an association between low serum bilirubin levels and Behçet's disease uveitis. However, the causal inference between bilirubin level and juvenile idiopathic arthritis‐associated uveitis (JIAU) remains ambiguous. We investigated the potential causal relationship between serum bilirubin levels and JIAU using a bidirectional two‐sample Mendelian randomization (MR) framework.

Methods

We systemically integrated summary‐level data from published large‐scale genome‐wide association studies on bilirubin level and JIAU in a Caucasian British population. To determine the causal effect of bilirubin level on JIAU, we constructed strong instrumental variables using 47 and 80 single‐nucleotide polymorphisms (SNPs) specific to direct bilirubin and total bilirubin levels, respectively. For reverse causal inference, seven SNPs associated with JIAU were included in our study. Multiple complementary methods were further performed to evaluate the robustness of MR estimates.

Results

The inverse‐variance weighted estimate did not show any significant causal associations of genetically predicted serum direct or total bilirubin level with the risk of JIAU (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 0.750–1.359, p = 0.947; OR: 0.867, 95% CI: 0.688–1.093; p = 0.227, respectively). MR–Egger and weighted median methods also obtained similar associations. Additionally, the results of reverse MR analyses using JIAU as exposure showed no associations of genetically predicted risk of JIAU with serum bilirubin levels (p > 0.05). In sensitivity analysis, the causal estimate between serum bilirubin levels and JIAU did not differ when SNPs associated with possible confounders were omitted.

Conclusion

Genetic evidence from our bidirectional analysis did not support a causal association between serum bilirubin levels and JIAU risk in the Caucasian British population. Future large‐scale studies should be conducted to validate these findings and explore any causal effects on the disease process.
MiR‐9‐enriched mesenchymal stem cells derived exosomes prevent cystitis‐induced bladder pain via suppressing TLR4/NLRP3 pathway in interstitial cystitis mice
Authors: Cui Xiangrong , Bi Xingyu , Zhang Xiuping , Zhang Zhiping , Yan Qin , Wang Yanni , Huang Xia , Wu Xueqing , Jing Xuan , Wang Hongwei
Published: February 2024

Background

Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles （EVs） derived from miR‐9‐edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation.

Methods

On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC‐EVs enriched with miR‐9 in the treatment of bladder pain of IC/BPS.

Results

The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis‐induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR‐9‐enreched MSCs derived exosomes were effective in the treatment of cystitis‐induced pelvic/bladder nociception by inhibiting TLR4/NF‑κb/NLRP3 signal pathway in central nervous system of IC/BPS mice.

Conclusions

This study demonstrated that miR‐9‐enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis‐induced bladder pain by inhibiting TLR4/NF‑κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis‐induced bladder pain.
Knockdown of liver cancer cell‐secreted exosomal PSMA5 controls macrophage polarization to restrain cancer progression by blocking JAK2/STAT3 signaling
Authors: Xie Shujie , Li Xiang , Yan Jia , Yu Hua , Chen Shuhuai , Chen Kana
Published: February 2024

Introduction

Tumor‐associated macrophages, a major component of the tumor microenvironment, undergo polarization into M2 macrophages (M2), and thereby exert an immunosuppressive effect to induce cancer metastasis. This study strives to uncover a molecular mechanism underlying this event in hepatocellular carcinoma (HCC).

Methods

Proteasome subunit alpha 5 (PSMA5) expression in liver hepatocellular carcinoma (LIHC) tissues and its association with LIHC patients were predicted using StarBase. PSMA5 level in human HCC cells was manipulated via transfection. Exosomes were isolated from HCC cells, and internalized into macrophages which were cocultured with HCC cells. Exosome internalization was observed after fluorescence labeling. HCC cell migration and invasion were evaluated by wound healing and Transwell assays. Xenograft assay was performed to investigate the role of PSMA5 in in vitro tumorigenesis. M2 polarization was assessed by enzyme‐linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry. PSMA5 expression in exosomes and Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) activation in macrophages and tumors were detected by Western blot analysis.

Results

High PSMA5 expression was observed in LIHC tissues and associated with compromised survival of LIHC patients. PSMA5 knockdown inhibited HCC cell migration and invasion. PSMA5 knockdown in HCC cells downregulated PSMA5 level in exosomes from these HCC cells. HCC cell‐isolated exosomes were successfully internalized into macrophages, and facilitated M2 polarization and JAK2/STAT3 pathway activation. HCC cell‐secreted exosomal PSMA5 knockdown inhibited the exosome‐induced effect on macrophages, and attenuated the promotion induced by exosome‐treated macrophages on HCC cell migration/invasion and tumorigenesis along with in vivo M2 polarization and JAK2/STAT3 pathway activation.

Conclusion

HCC cell‐secreted exosomal PSMA5 knockdown hinders M2 polarization to suppress cancer progression by restraining JAK2/STAT3 signaling.
Effects of myeloperoxidase on inflammatory responses with hypoxia in Citrobacter rodentium‐infectious mice
Authors: Gao Xiang , Zhang Yu , Zhu Qinfang , Han Ying , Jia Ruhan , Zhang Wei
Published: February 2024

Purpose

Myeloperoxidase (MPO) has been identified as a mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the role of MPO in these phenomena remains unclear.

Methods

By building the MPO‐/‐ mice, we evaluated relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo haematoxylin‐eosin staining and assess the degree of pathological damage. ELISA assays were performed to quantify the serum levels of TNF‐α, IFN‐γ, IL‐6, and IL‐1β inflammatory cytokines. PCR, WB, and IF assays were conducted to determine the expression of chemokines MCP1, MIP2, and KC in the colon and spleen.

Results

The C. rodentium infection and hypoxia caused weight loss, intestinal colitis, and splenic inflammatory cells active proliferation in wild‐type mice. MPO deficiency alleviated this phenomenon. MPO‐/‐ mice also displayed a significant decline in bacteria clearing ability. The level of TNF‐α in the serum and spleen was both lower in MPO‐/‐ hypoxia C. rodentium‐infected mice than that in wild‐type mice. The chemokines expression levels of MIP2, KC, and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (p < .05), while in hypoxia, the factors in the spleen and colon were decreased (p < .05). MPO deficiency was found to lower the levels of these chemokines compared with wild‐type mice.

Conclusion

MPO plays an important role of the inflammatory responses in infectious enteritis and hypoxia in mice, and the loss of MPO may greatly reduce the body's inflammatory responses to fight diseases.
Sirtuin2 suppresses the polarization of regulatory T cells toward T helper 17 cells through repressing the expression of signal transducer and activator of transcription 3 in a mouse colitis model
Authors: Ge Liuqing , Xu Min , Huang Meifang , Liu Shaoping , Zhou Zhidai , Xia Ziqin , Zhao Qiu , Zhou Feng
Published: February 2024

Introduction

Regulatory T cells (Tregs) play an important role in inflammatory bowel diseases (IBDs) through modulating intestinal inflammation. However, the factors affecting Treg function and plasticity during IBD progression are not thoroughly disclosed. The current study aims to reveal new molecular mechanisms affecting Treg plasticity.

Methods

A mouse strain, in which tdTomato and enhanced green fluorescent protein were under the control of the Foxp3 promoter and Il17a promoter, was established and subjected to colitis induction with dextran sulfate sodium. The existence of Tregs and IL‐17‐expressing Tregs (i.e., Treg/T helper 17 [Th17] cells) were observed and sorted from the spleen, mesenteric lymph nodes, and lamina propria by flow cytometry, followed by measuring Sirtuin2 (Sirt2) expression using quantitative reverse transcription polymerase chain reaction and Immunoblotting. Lentivirus‐induced Sirt2 silencing was applied to determine the impact of Sirt2 on Treg polarization to Treg/Th17 cells and even Th17 cells. The effect of Sirt2 on Stat3 was analyzed by flow cytometry and immunoblotting.

Results

Sirt2 was highly expressed in lamina propria Tregs and it moderately suppressed Foxp3 expression as well as the immunosuppressive function of Tregs. Surprisingly, lentivirus‐mediated Sirt2 silencing promoted the generation of Treg/Th17 cells out of Tregs. Sirt2 silencing also enhanced the generation of Th17 cells out of Tregs under the Th17 induction condition. Furthermore, Sirt2 inhibited Th17 induction by suppressing the protein level of the signal transducer and activator of transcription 3.

Conclusion

Sirt2 suppresses Treg function but also inhibits Treg polarization toward Treg/Th17 cells and Th17 cells. The ultimate effect of Sirt2 on colitis might depend on the balance among Tregs, Treg/Th17 cells, and Th17 cells.
Self‐monitoring and public posting improve competitive youth cyclists' training performance
Authors: Ayvazo Shiri , Naveh Mey‐Elle
Published: January 2024

This study investigated the effects of self‐monitoring and public posting on the cycling performance of competitive youth cyclists. We measured three primary dependent variables: performance volume, intensity precision, and performance‐duration deviation. In addition, we evaluated self‐monitoring accuracy and social validity. The participants were three males aged 14–16 years. We used an ABAB design to evaluate an intervention package that consisted primarily of self‐monitoring and public posting. Athletes self‐monitored their performance after training using an online summative Google Form. The coach publicly posted performance‐based rankings on the social media application WhatsApp. Results indicate that the intervention package positively improved all performance measures across all athletes. Social‐validity measures were also favorable.
CEO turnover after product‐harm crises
Authors: Paik Daniel Gyung , Meng Bo , Lee Brandon Byunghwan , Nguyen Nhat Q.
Published: February 2024

Product‐harm crises are discrete events in which product failures expose consumers to safety hazards. Firms facing such crises must legally recall their products to protect consumers from further harm. In this study, we examine the effects of product‐harm crises and their recall strategies on CEO turnover. We find that firms are more likely to replace their CEOs after issuing product recalls, especially for recalls that are proactive and that offer extensive corrective actions. We further find that firms with poor performance and with limited financial flexibility are more likely to dismiss their CEOs after product recalls. Our study contributes to the disciplines of accounting, finance, and management by documenting product‐harm crises are a strong predictor of CEO dismissal, that is, incremental to other measures of firm performance for U.S. companies.
The importance of cybersecurity disclosures in customer relationships
Authors: Nelson Aaron , Wang Shensi
Published: February 2024

The escalating use of digital technologies has spotlighted the crucial role of cybersecurity in safeguarding sensitive information within companies. This study explores the relationship between a firm's major customers and its cybersecurity awareness. Drawing on SEC‐mandated disclosures, we employ four proxies to measure changes in customer‐supplier relationships. Our findings reveal that customers increase their purchases from suppliers whose cybersecurity awareness scores improve. Additionally, we examine the interplay between customers and suppliers more susceptible to nonpublic adverse news, particularly during cyber events. The study emphasizes the importance of cybersecurity disclosure for regulators, supply chain partners, and corporate management. It also contributes to the literature on factors influencing the duration of customer‐supplier relationships and underscores the significance of supplier characteristics. “Understanding and disclosing cybersecurity risks are” paramount in an increasingly digital business landscape.
RACK1 promotes the occurrence and progression of cervical carcinoma
Authors: Yang Dandan , Lu Xiaojuan , Zhang Xuegang , Zhang Xiaojuan , Zhu Lixia , Liu Qin
Published: February 2024

Background

RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression.

Methods

The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis in vivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells in vitro.

Results

We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over‐expression prolonged the G0/G1 phase by up‐regulating the expression of cyclinD1, down‐regulating p21 and p27 probably by modulating the phosphorylation of AKT.

Conclusions

Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.
The role of the complement system in disc degeneration and Modic changes
Authors: Heggli Irina , Teixeira Graciosa Q. , Iatridis James C. , Neidlinger‐Wilke Cornelia , Dudli Stefan
Published: February 2024

Disc degeneration and vertebral endplate bone marrow lesions called Modic changes are prevalent spinal pathologies found in chronic low back pain patients. Their pathomechanisms are complex and not fully understood. Recent studies have revealed that complement system proteins and interactors are dysregulated in disc degeneration and Modic changes. The complement system is part of the innate immune system and plays a critical role in tissue homeostasis. However, its dysregulation has also been associated with various pathological conditions such as rheumatoid arthritis and osteoarthritis. Here, we review the evidence for the involvement of the complement system in intervertebral disc degeneration and Modic changes. We found that only a handful of studies reported on complement factors in Modic changes and disc degeneration. Therefore, the level of evidence for the involvement of the complement system is currently low. Nevertheless, the complement system is tightly intertwined with processes known to occur during disc degeneration and Modic changes, such as increased cell death, autoantibody production, bacterial defense processes, neutrophil activation, and osteoclast formation, indicating a contribution of the complement system to these spinal pathologies. Based on these mechanisms, we propose a model how the complement system could contribute to the vicious cycle of tissue damage and chronic inflammation in disc degeneration and Modic changes. With this review, we aim to highlight a currently understudied but potentially important inflammatory pathomechanism of disc degeneration and Modic changes that may be a novel therapeutic target.
Development of physiologically‐informed computational coronary artery plaques for use in virtual imaging trials
Authors: Sauer Thomas J. , Buckler Andrew J. , Abadi Ehsan , Daubert Melissa , Douglas Pamela S. , Samei Ehsan , Segars William P.
Published: February 2024

Background

As a leading cause of death, worldwide, cardiovascular disease is of great clinical importance. Among cardiovascular diseases, coronary artery disease (CAD) is a key contributor, and it is the attributed cause of death for 10% of all deaths annually. The prevalence of CAD is commensurate with the rise in new medical imaging technologies intended to aid in its diagnosis and treatment. The necessary clinical trials required to validate and optimize these technologies require a large cohort of carefully controlled patients, considerable time to complete, and can be prohibitively expensive. A safer, faster, less expensive alternative is using virtual imaging trials (VITs), utilizing virtual patients or phantoms combined with accurate computer models of imaging devices.

Purpose

In this work, we develop realistic, physiologically‐informed models for coronary plaques for application in cardiac imaging VITs.

Methods

Histology images of plaques at micron‐level resolution were used to train a deep convolutional generative adversarial network (DC‐GAN) to create a library of anatomically variable plaque models with clinical anatomical realism. The stability of each plaque was evaluated by finite element analysis (FEA) in which plaque components and vessels were meshed as volumes, modeled as specialized tissues, and subjected to the range of normal coronary blood pressures. To demonstrate the utility of the plaque models, we combined them with the whole‐body XCAT computational phantom to perform initial simulations comparing standard energy‐integrating detector (EID) CT with photon‐counting detector (PCD) CT.

Results

Our results show the network is capable of generating realistic, anatomically variable plaques. Our simulation results provide an initial demonstration of the utility of the generated plaque models as targets to compare different imaging devices.

Conclusions

Vast, realistic, and variable CAD pathologies can be generated to incorporate into computational phantoms for VITs. There they can serve as a known truth from which to optimize and evaluate cardiac imaging technologies quantitatively.
Wenn Eltern forschen wollen
Authors: Tietze Alexandra
Published: January 2024

Ulla Gerling‐Driessen und ihr Mann arbeiten beide in der Forschung. Ohne verständnisvolle Vorgesetzte wäre das kaum denkbar. Ein Einblick aus Deutschland und den USA.
Nachruf: Egon Fanghänel (1935 – 2023)
Authors: Hartmann Horst , Hennig Horst , Kießling Renate , Taube Rudolf
Published: January 2024

Auf vielen Feldern aktiv: GDCh‐Ehrenmitglied Egon Fanghänel war Wissenschaftler, Hochschullehrer, Lehrbuchautor und Wissenschaftsorganisator.
Gründerkolumne: Was ist ein Founding Angel und wie kann er unterstützen?
Authors: Festel Gunter
Published: January 2024

Was ist ein Founding Angel und wie kann er unterstützen?
Thermal conductive nylon 6 composites using hybrid fillers to construct a three‐dimensional thermal conductive network
Authors: Li Qian , Rao Ranyi , Hong Xiansheng , Hu Hanwen , Li Yu , Gong Ziyu , Zheng Yuying
Published: February 2024

The rapid progress in miniaturization and integration of semiconductor power devices has made heat dissipation a critical concern in the development of high‐performance semiconductor devices, thereby increasing the demands for the heat transfer efficiency of polymer composites. To address this issue, an efficient three‐dimensional (3D) heat conduction network structure is constructed in the polymer matrix by leveraging the mutual reaction of amino and epoxy groups on the surface of the filler treated by coupling during the melt mixing process, this approach leads to an enhancement in the thermal conductivity of the composites. First, the inert surfaces of graphene nanosheets (EX‐G) and carbon fibers (CF) are coated with polydopamine (PDA) to form active sites. Subsequently, the graphene (EX‐G), alumina (Al2O3), and carbon fiber (CF) are treated with an amine coupling agent (KH550) and epoxy coupling agent (KH560), respectively. Notably, at a filler content of 25 wt%, the thermal conductivity (TC) of the composites increases by approximately 282% compared to pure nylon 6. This research contributes novel insights into the field of thermally conductive polymer composites.

Highlights

The surface of the EX‐G and CF covered by PDA generates active sites.

Fillers reduce the interface thermal resistance through chemical bonds.

Fillers surface reaction builds a 3D thermal conductive network.

3D network structure can significantly improve the TC of composites.

Only 25 wt% of hybrid fillers in a 282% increased TC of composites.
In‐situ experimental study on the hydrolysis and pyrolysis processes of polylactic acid
Authors: Zhao Xia , Zheng Zhi , Chen Jiangzhi , Sun Jianhui , Xiong Mengjun , Hou Xue , Mei Shenghua
Published: February 2024

In order to better understand the hydrolysis and pyrolysis process of polylactic acid (PLA), we carried out in‐situ experiments by observing the decomposition process of PLA at high temperature (up to 285°C) in both aqueous and anhydrous environments through fused silica capillary reactor (FSCR) combined with Raman spectroscopy analysis. By analyzing the strength change of characteristic peaks of PLA with increasing temperature, it was found that the initial melting temperature of PLA, in both the hydrolysis and pyrolysis processes, is around 170°C. Based on infrared spectroscopy analysis, it was found that the products of PLA pyrolysis are CO2, CH3CHCO, and CH3CHO, indicating that the pyrolysis process of PLA results from a free radical reaction. By comparing the Raman peak area ratios at different peak positions at different temperatures, it was found that the hydrolysis process of PLA mainly involves breaking the COC and CCO bonds of PLA, producing lactic acid, ethanol, CO2, and H2O. The hydrolysis reaction rate of PLA increases with the increase of temperature and exhibits a slow‐fast‐slow S‐shaped trend. The kinetic process of hydrolysis of PLA was well described using the Logistic model. The activation energy for the hydrolysis (Q) of PLA is 18.1 kcal∙mol−1 in the temperature range of 250–285°C. The results of this study provide important insights and crucial parameters for the production and application of PLA.
Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives
Authors: Chen Yuan , Tan Xiyue , Zhang Wenwen , Li Yubing , Deng Xinyu , Zeng Jinhao , Huang Lihua , Ma Xiao
Published: February 2024

Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer‐related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy‐related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy‐modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β‐catenin, Beclin‐1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double‐edged sword in HCC management.
Experimental Schistosoma haematobium pulmonary hypertension
Authors: Kassa Biruk , Fonseca‐Balladares Dara C. , Kumar Rahul , Lee Michael H. , Mickael Claudia , Sanders Linda , Nolan Kevin , Graham Brian B.
Published: February 2024

Whether all Schistosoma species cause pulmonary hypertension (PH) is unclear. Experimentally exposing mice to Schistosoma haematobium eggs caused PH, which was less severe than that induced by S. mansoni exposure. These findings align with the relatively uncommon reports of pulmonary arterial hypertension associated with S. haematobium.
Cytological diagnosis of exercise‐induced pulmonary haemorrhage: Comparison of tracheal wash and bronchoalveolar lavage in standardbred racehorses
Authors: Barbazanges Pauline , Richard Eric A. , Lemonnier Louise C. , Wouters Clovis P. , Toquet Marie‐Pierre , Couroucé Anne
Published: January 2024

Background

Cytology of airway samples is sensitive for diagnosis of exercise‐induced pulmonary haemorrhage (EIPH), but the association between tracheal wash (TW) and bronchoalveolar lavage fluid (BALF) is unknown. The objective of this study was to determine whether diagnosis of EIPH, using haemosiderophages/macrophages (H/M) ratio, differs when based on TW or BALF.

Methods

A prospective cross‐sectional study was conducted on 102 standardbred horses in training. TW and BALF were collected concomitantly from all horses at rest (at least 24 hours after their last training or race), and their H/M ratios were calculated. Spearman's correlation, Cohen's kappa and Gwet's coefficient tests were performed to evaluate the association between TW and BALF samples.

Results

With BALF, 21 horses met the cytological inclusion criteria for an EIPH diagnosis from individual and/or pooled samples. With TW, 20 horses had occasional (H/M < 10%) haemosiderophages, and nine, one and three horses had small (10%–25%), moderate (25%–50%) and large (>50%) proportions, respectively. Poor correlations and inconsistent concordances between TW and BALF were found for H/M ratio.

Limitations

Limitations include the use of a single staining method and the absence of a total haemosiderin score.

Conclusion

No association between TW and BALF was found for the cytological diagnosis of EIPH. Based on H/M ratio, BALF remains the sample type of choice for cytological diagnosis of EIPH.
An insight into vitamin E and lipid nutrition of the plains‐wanderer Pedionomus torquatus
Authors: Jarman Angela K. , Shaw Michelle E. , Liu Sonia Y. , Grueber Catherine E.
Published: January 2024

Vitamin E, as α‐tocopherol, is an essential antioxidant protecting the body from free radicals. The vitamin E requirement of managed wildlife species is known to be greater than their wild counterparts, predominantly due to higher dietary lipid content and potentially stressful environments. The plains‐wanderer (Pedionomus torquatus, Family Pedionomidae [monotypical]) is a critically endangered, superficially quail‐like bird that is the focus of an ongoing captive breeding programme in Australia. It is estimated that plains‐wanderers have a high vitamin E requirement (compared with domestic poultry species) to offset a high lipid diet and their naturally flighty temperament. This study therefore aims to gain a greater understanding of the nutritional status and vitamin E requirements of plains‐wanderers in managed environments. Total lipid and α‐tocopherol intake were quantified for 26 zoo‐managed plains‐wanderers over a series of diet intake trials in addition to measurement of plasma α‐tocopherol and cholesterol concentrations. Plains‐wanderers that consumed higher portions of dietary fat had significantly lower circulating α‐tocopherol concentrations than birds that consumed lower total dietary fat (p < .001). Additionally, plasma cholesterol concentrations of managed plains‐wanderers were found to be significantly greater than all other bird species reviewed, irrespective of Family or feeding type. We also present the first published data quantifying the nutritional makeup of stomach contents of a wild plains‐wanderer for use as a potential guide for diet formulation. This study forms a vital foundational insight into the nutritional management of plains‐wanderers, but further research is required to understand their dietary habits and cholesterol metabolism.
Development Resilience as the Scope of Social Protection
Authors: Rahman Andaleeb , Pingali Prabhu
Published: February 2024

Social protection policies have traditionally provided band-aid policy responses to daily risks and vulnerabilities. In this chapter, we argue that the overall welfare objective of social protection policies should be to promote and build resilience. Historical experience of social welfare policies suggests that as countries develop and reduce poverty, social policy become more encompassing creating a virtuous cycle of progress where those ‘falling through the cracks’ are given social protection by the state. The focus, form, and scope of social protection therefore evolves along the path of structural transformation. As developing countries build their social protection strategies, plenty can be learnt from the experience of more advanced nations, but also innovations are required to adapt welfare policies to newer challenges such as deindustrialization, rising informalization of the economy, and the changing nature of work.
Einarbeitung in der Intensiv- und Notfallmedizin in Deutschland
Authors: Naendrup Jan-Hendrik , Hertrich Anna Carola , Briegel Janika , Reifarth Eyleen , Hoffmann Julian , Mucha Anuschka , König Victoria , Weber Theresa
Published: February 2024

Hintergrund

Die Therapie akut lebensbedrohlicher Krankheitsverläufe in der Intensiv- und Notfallmedizin verlangt nach einer fundierten Aus- und Weiterbildung, wobei der Einarbeitung eine Schlüsselrolle zufällt.

Fragestellung

Wie sind die Struktur und Qualität der ärztlichen und pflegerischen Einarbeitung auf Intensivstationen und in Notaufnahmen in Deutschland?

Methodik

Mithilfe einer Befragungssoftware wurde ein deutschsprachiger Online-Fragebogen mit 40 Fragen zur genannten Thematik zur anonymisierten Datenerhebung entworfen. Die Verbreitung erfolgte über die Website der Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin (DGIIN) und über Social-Media-Kanäle.

Ergebnisse

103 Pflegefachpersonen und 125 Ärzt:innen nahmen an der Befragung teil. Die Berufserfahrung der Pflegefachpersonen lag bei durchschnittlich 8,5 ± 5,1 Jahren, die der Ärzt:innen bei 3,0 ± 3,1 Jahren. Die Teilnehmenden arbeiteten schwerpunktmäßig auf Intensivstationen (59 %) oder in Notaufnahmen (22 %). Die Einarbeitung der Pflegefachpersonen dauerte durchschnittlich 45 ± 27 Tage, die der Ärzt:innen 13 ± 13 Tage. Nur 20 % der Einarbeitung erfolgten losgelöst von der klinischen Routineversorgung als Seminar oder Praxistraining. 47 % der Teilnehmenden gaben an, dass sie die avisierte Einarbeitungszeit nicht vollständig absolvieren konnten. Nur 49 % wurden rechtskonform in die Geräte ihres Arbeitsbereichs eingewiesen. Nach der Einarbeitung gaben 35 % an, sich sicher oder eher sicher im Umgang mit planbaren Tätigkeiten zu fühlen, bei akuten Notfällen waren es 15 %.

Diskussion

Die Einarbeitung in der Intensiv- und Notfallmedizin ist vielerorts inadäquat und birgt sowohl Sicherheits- als auch Haftungsrisiken. Es bedarf neuer Konzepte, um die Einarbeitung klinikübergreifend zu verbessern.