bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glofitamab as a salvage treatment for B‐cell lymphomas in the real world: A multicenter study in Taiwan
Authors: Hsu Ya‐Ting , Wu Shang‐Ju , Kao Hsiao‐Wen , Hsiao Sheng‐Yen , Liao Chun‐Kai , Chen Tsai‐Yun , Wang Ming‐Chung 
Published: February 2024

AbstractBackgroundGlofitamab is a bispecific antibody with promise for treating relapsed/refractory B‐cell lymphoma according to a phase 1/2 clinical trial. This study examined its real‐world effectiveness.MethodsThis was an investigator‐initiated, multicenter retrospective study including 34 patients who had relapsed/refractory B‐cell lymphomas after at least three prior lines of therapy and received glofitamab monotherapy in a compassionate use program in Taiwan between January 2021 and October 2022.ResultsAt a median follow‐up of 15.9 months, 56% of patients responded to glofitamab and 23% achieved complete remission. Response to the previous line of therapy significantly correlated with response to glofitamab (p = .020). Most responses were durable; only five out of the 19 responders had documented disease recurrence at the data cutoff date. The estimated progression‐free survival (PFS) was 3.2 months, and the estimated 1‐year PFS was 33% for the entire cohort. PFS was better for responders than nonresponders (median PFS, 16.9 vs. 1.8 months; 1‐year PFS, 60% vs. 0%). Forty‐three cytokine release syndrome (CRS) events were observed, three of which were grade 3; all were manageable without glofitamab discontinuation. No immune effector cell–associated neurotoxicity was reported. Among seven hepatitis B virus (HBV) carriers (six had antiviral prophylaxis) and 14 patients with remote HBV (four had antiviral prophylaxis), no HBV reactivation was observed.ConclusionsIn this real‐world cohort, glofitamab exhibited effectiveness comparable to trial results without excessive CRS or new safety issues. With appropriate prophylaxis, glofitamab‐treated patients with chronic or remote HBV infection are unlikely to experience virus reactivation.
Selectivity and Activity of Benzene‐1,2,4‐triol and its Dimers as Antimicrobial Compounds Against Xanthomonas citri subsp. citri
Authors: Cavalca Lúcia B. , Atlason Úlfur Á. , Trofin Alexandru , Ribeiro Camila M. , Pavan Fernando R. , Deuss Peter J. , Scheffers Dirk‐Jan 
Published: February 2024

AbstractCitrus canker, caused by the bacterium Xanthomonas citri subsp. citri, is one of the main threats to citrus fruit production. Several phenolic compounds active against X. citri have been described in recent years. Benzene‐1,2,4‐triol is a bio‐based phenolic compound that has shown high potential as a scaffold for the synthesis of new anti‐X. citri compounds. However, benzene‐1,2,4‐triol is prone to oxidative dimerization. We evaluated the antibacterial activity of benzene‐1,2,4‐triol, its oxidized dimers, and analogous compounds. Benzene‐1,2,4‐triol has a low inhibitory concentration against X. citri (0.05 mM) and is also active against other bacterial species. Spontaneous formation of benzenetriol dimers (e. g. by contact with oxygen in aqueous solution) reduced the antimicrobial activity of benzenetriol solutions. Dimers themselves displayed lower antibacterial activity and where shown to be more stable in solution. Unlike many other phenolic compounds with anti‐X. citri activity, benzene‐1,2,4‐triol does not act by membrane permeabilization, but seems to limit the availability of iron to cells. Benzene‐1,2,4‐triol is widely recognized as toxic – our results indicate that the toxicity of benzene‐1,2,4‐triol is largely due to spontaneously formed dimers. Stabilization of benzene‐1,2,4‐triol will be required to allow the safe use of this compound.
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

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

AbstractBackgroundMutations 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.MethodsWe 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.ResultsOur 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.ConclusionsThese 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

AbstractTemperature 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

AbstractThis 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

AbstractWhen 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

AbstractObjectiveWe 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.DesignSixty‐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.DiscussionFindings 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

AbstractSoursop (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

AbstractBackgroundSeveral 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.MethodsWe 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.ResultsThe 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.ConclusionGenetic 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

AbstractBackgroundInflammatory 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.MethodsOn 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.ResultsThe 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.ConclusionsThis 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.