bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between beta‐blocker atenolol use and prostate cancer upgrading in active surveillance1
Authors: Zahalka Ali H. , Fram Ethan , Garden Evan , Howard Lauren , Wiggins Emily , Babar Mustufa , Annam Jay , Reagan Allison , Eilender Benjamin , de Hoedt Amanda , Freedland Stephen J. , Tewari Ash , Watts Kara L. 
Published: October 2024

AbstractObjectivesThe objective of this study is to investigate the association between the use of beta‐adrenergic antagonist atenolol and risk of pathologic upgrade in patients on active surveillance, considering growing literature implicating adrenergic innervation with disease progression mediated through beta‐adrenergic signalling.Patients and MethodsMen with low‐risk or favourable intermediate‐risk prostate cancer who were placed on an active surveillance protocol between 2006 and 2020 across three diverse urban hospitals were included. Exposure was duration of atenolol use, and outcome was pathologic grade group upgrading (to GG ≥ 3) on final prostate biopsy. Cox proportional hazard regression models were used to determine the associations between atenolol use and risk of upgrading with time, on a per‐examination basis.ResultsA total of 467 men with initial GG ≤ 2 were included. Postdiagnosis atenolol use was associated with a decreased risk of pathologic upgrade to GG ≥ 3 on final repeat biopsy (HR 0.81, 95% CI 0.39–0.98). Longer duration of postdiagnosis atenolol use (>2 years) and greater cumulative atenolol dose (>730 defined daily doses) were associated with a more pronounced decreased risk of upgrade to GG ≥ 3 (HR 0.41, 95% CI 0.05–0.88, and HR 0.32, 95% CI 0.15–0.99, respectively). Initiation of atenolol use prior to prostate cancer diagnosis had a slightly greater protective effect than drug initiation postdiagnosis (HR 0.79, 95% CI 0.43–0.98, and HR 0.83, 95% CI 0.30–0.99, respectively).ConclusionsBeta‐adrenergic blockade with atenolol use in men on active surveillance is associated with a reduced risk for clinically significant grade group pathologic upgrade.
Selecting Endogenous Promoters for Improving Biosynthesis of Squalene in Schizochytrium sp.
Authors: Nong Fang‐Tong , Zhang Zi‐Xu , Xu Lu‐Wei , Du Fei , Ma Wang , Yang Guang , Sun Xiao‐Man 
Published: October 2024

ABSTRACTSqualene (C30H50) is an acyclic triterpenoid compound renowned for its myriad physiological functions, such as anticancer and antioxidative properties, rendering it invaluable in both the food and pharmaceutical sectors. Due to the natural resource constraints, microbial fermentation has emerged as a prominent trend. Schizochytrium sp., known to harbor the intact mevalonate acid (MVA) pathway, possesses the inherent capability to biosynthesize squalene. However, there is a dearth of reported key genes in both the MVA and the squalene synthesis pathways, along with the associated promoter elements for their modification. This study commenced by cloning and characterizing 13 endogenous promoters derived from transcriptome sequencing data. Subsequently, five promoters exhibiting varying expression intensities were chosen from the aforementioned pool to facilitate the overexpression of the squalene synthase gene squalene synthetase (SQS), pivotal in the MVA pathway. Ultimately, a transformed strain designated as SQS‐3626, exhibiting squalene production 2.8 times greater than that of the wild‐type strain, was identified. Finally, the optimization of nitrogen source concentrations and trace element contents in the fermentation medium was conducted. Following 120 h of fed‐batch fermentation, the accumulated final squalene yield in the transformed strain SQS‐3626 reached 2.2 g/L.
Thermoresponsive and Supramolecular Polymers: Interesting Biomaterials for Drug Delivery
Authors: Darvishi Ahmad , Ansari Mojtaba 
Published: October 2024

ABSTRACTHow to use and deliver drugs to diseased and damaged areas has been one of the main concerns of pharmacologists and doctors for a long time. With the efforts of researchers, the advancement of technology, and the involvement of engineering in the health field, diverse and promising approaches have been studied and used to achieve this goal. A better understanding of biomaterials and the ability of production equipment led researchers to offer new drug delivery systems to the world. In recent decades, responsive polymers (exclusively to temperature and pH) and supramolecular polymers have received much attention due to their unique capabilities. Although this field of research still needs to be scrutinized and studied more, their recognition, examination, and use as drug delivery systems is a start for a promising future. This review study, focusing on temperature‐responsive and supramolecular biomaterials and their application as drug delivery systems, deals with their structure, properties, and role in the noninvasive and effective delivery of medicinal agents.
Development of a Human Recombinant Collagen for Vat Polymerization‐Based Bioprinting
Authors: Schlauch Domenic , Ebbecke Jan Peter , Meyer Johanna , Fleischhammer Tabea Marie , Pirmahboub Hamidreza , Kloke Lutz , Kara Selin , Lavrentieva Antonina , Pepelanova Iliyana 
Published: October 2024

ABSTRACTIn light‐based 3D‐bioprinting, gelatin methacrylate (GelMA) is one of the most widely used materials, as it supports cell attachment, and shows good biocompatibility and degradability in vivo. However, as an animal‐derived material, it also causes safety concerns when used in medical applications. Gelatin is a partial hydrolysate of collagen, containing high amounts of hydroxyproline. This causes the material to form a thermally induced gel at ambient temperatures, a behavior also observed in GelMA. This temperature‐dependent gelation requires precise temperature control during the bioprinting process to prevent the gelation of the material. To avoid safety concerns associated with animal‐derived materials and reduce potential issues caused by thermal gelation, a recombinant human alpha‐1 collagen I fragment was expressed in Komagataella phaffii without hydroxylation. The resulting protein was successfully modified with methacryloyl groups and underwent rapid photopolymerization upon ultraviolet light exposure. The developed material exhibited slightly slower polymerization and lower storage modulus compared to GelMA, while it showed higher stretchability. However, unlike the latter, the material did not undergo physical gelation at ambient temperatures, but only when cooled down to below 10°C, a characteristic that has not been described for comparable materials so far. This gelation was not caused by the formation of triple‐helical structures, as shown by the absence of the characteristic peak at 220 nm in CD spectra. Moreover, the developed recombinant material facilitated cell adherence with high cell viability after crosslinking via light to a 3D structure. Furthermore, desired geometries could be easily printed on a stereolithographic bioprinter.
The efficacy of first and second immunotherapy exposure in patients with recurrent or metastatic cervical cancer
Authors: Ju Mingxiu , Pan Baoyue , Huang Yongwen , Zhou Yun , Chen Jieping , Xiang Huiling , Xu Shije , Chen Siyu , Lan Chunyan , Li Jundong , Zheng Min 
Published: October 2024

AbstractObjectiveImmunotherapy has led to changes in cervical cancer guidelines. Therefore, additional biomarkers to identify the ideal patient who would experience the most benefit may be important.MethodsWe retrospectively collected 208 patients with R/M CC and recorded clinicopathologic information, peripheral blood markers and treatments to analyze the prognostic factors of clinical outcomes. Response rate comparison, univariate, and multivariate analyses were performed to assess the efficacy of different factors.ResultsA total of 43.27% patients achieved objective responses, including 18 with complete response and 72 with partial response. Patients receiving first‐line immunotherapy had much higher objective response rate (ORR) than the remaining patients (53.8% vs. 34.8%, p = 0.006). CRP >3 ECOG ≥1 and recurrence in 6 months predicted shorter progression free survival (PFS). CRP >3, GLU >6.1 independently predicted unfavorable overall survival (OS). Compared with no antiangiogenic therapy, previous antiangiogenic therapy reduced the median OS by nearly 14 months. Immunotherapy rechallenge was still effective after first immunotherapy failure, and combined with dual‐immunotherapy or bevacizumab combined with chemoradiotherapy resulted in a 60.00% or 62.50% ORR, respectively. Patients with squamous cell carcinoma, with stable disease or objective response in the first immunotherapy or without chemotherapy in second immunotherapy had favorable clinical outcome.ConclusionThe baseline CRP levels in serum was an independent factor for PFS and OS of R/M CC patients treated with immunotherapy, and previous antiangiogenic therapy was associated with poor OS. Patients still show response to immunotherapy rechallenge and combined treatment with bevacizumab or candonilimab showed higher response rate than anti‐PD‐1 after immunotherapy failure.
Edodes Cultured Extract Regulates Immune Stress During Puberty and Modulates MicroRNAs Involved in Mammary Gland Development and Breast Cancer Suppression
Authors: Yasavoli‐Sharahi Hamed , Shahbazi Roghayeh , Alsadi Nawal , Robichaud Samuel , Kambli Darshan Babu , Izadpanah Amirhossein , Mohsenifar Zhaleh , Matar Chantal 
Published: October 2024

ABSTRACTBackgroundImmune stressors, such as lipopolysaccharides (LPS), profoundly affect microbiota balance, leading to gut dysbiosis. This imbalance disrupts the metabolic phenotype and structural integrity of the gut, increasing intestinal permeability. During puberty, a critical surge in estrogen levels is crucial for mammary gland development. However, inflammation originating from the gut in this period may interfere with this development, potentially heightening breast cancer risk later. The long‐term effects of pubertal inflammation on mammary development and breast cancer risk are underexplored. Such episodes can dysregulate cytokine levels and microRNA expression, altering mammary cell gene expression, and predisposing them to tumorigenesis.MethodsThis study hypothesizes that prebiotics, specifically Lentinula edodes Cultured Extract (AHCC), can counteract LPS's adverse effects. Using BALB/c mice, an acute LPS dose was administered at puberty, and breast cancer predisposition was assessed at 13 weeks. Cytokine and tumor‐related microRNA levels, tumor development, and cancer stem cells were explored through immunoassays and qRT‐PCR.ResultsResults show that LPS induces lasting effects on cytokine and microRNA expression in mammary glands and tumors. AHCC modulates cytokine expression, including IL‐1β, IL‐17A/F, and IL‐23, and mitigates LPS‐induced IL‐6 in mammary glands. It also regulates microRNA expression linked to tumor progression and suppression, particularly counteracting the upregulation of oncogenic miR‐21, miR‐92, and miR‐155. Although AHCC slightly alters some tumor‐suppressive microRNAs, these changes are modest, highlighting a complex regulatory role that warrants further study.ConclusionThese findings underscore the potential of dietary interventions like AHCC to mitigate pubertal LPS‐induced inflammation on mammary gland development and tumor formation, suggesting a preventive strategy against breast cancer.
Preoperative Serum Glycan Levels Reflect Progression of Patients With Hepatocellular Carcinoma
Authors: Liu Sheng‐Sheng , Ye Lei , Dai Qing‐Qing , Gao Yi , Chen Guang‐Hou , Zhao Hong‐Chuan , Du Wei‐Dong 
Published: October 2024

ABSTRACTBackgroundAbnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge.MethodsA study dynamically comparing levels of fifteen lectin‐specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan–Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression‐free survival (PFS) of the HCC patients.ResultsHCC patients presented significantly higher levels of the lectin‐specific glycans in preoperative serum than disease‐free individuals (p < 0.001 − p = 0.029), except ConA. The glycans in preoperative sera were significantly related to tumor size, pTNM, metastasis, BCLC stage, portal hypertension (PHT), and platelet count (PLT), respectively (p < 0.05). Multivariate logistic analyses indicated that tumor size and pTNM independently impact on glycan‐specific lectins either LTL, UEA‐I, VVL, NPL, WGA, PNA, MAL‐I, SNA, or PHA‐L (p = 0.003 − p = 0.044); BCLC stage and PLT were independent factors influencing the serum glycans recognizable DSA (p = 0.024) and SNA (p = 0.050), respectively. Surgical excision of tumor mass significantly reduced glycan levels in sera. Tumor differentiation, albumin, and ABO type significantly revealed independent influence on glycan‐specific lectins, such as RCA‐I (p = 0.024), VVL (p = 0.024), and Con A (p = 0.026) in the postoperative serum. HCC patients with high levels of VVL‐binding glycans significantly benefited from a longer OS time (p = 0.016, HR: 0.460, 95% CI: 0.237–0.892) and a better PFS time (p = 0.004; HR: 0.435, 95% CI: 0.237–0.799), respectively.ConclusionSerum glycans could reflect surgical outcomes in at‐risk patients and become valuable biomarkers in evaluating the progression of HCC patients.
Mutational Landscape of Gastric Adenocarcinoma of the Fundic Gland Type Revealed by Whole Genome Sequencing
Authors: Wei Hu , Chen Ze Min , Xue Xiu Fen , Xia Xi Li , Yang Gen Hua , Zhai Zhi Yong , Huang Zhao Yu , Zhou Ping , Bao Chong Ju , You Li Juan , Ou Yang Mei Ping , Xia Gui Li , Zeng Zhi Yu , Cui Xiao Bing , Pei Xiao Juan , Gong Wei 
Published: October 2024

ABSTRACTBackgroundGastric adenocarcinoma of the fundic gland type (GA‐FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features.MethodsWe performed whole‐genome sequencing (WGS) in formalin‐fixed paraffin‐embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA‐FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA‐FG disease.ResultsWe characterized the genomic architecture of GA‐FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored “Kataegis.” Distinct genomic alterations between GA‐FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non‐silent alterations of formerly well‐known drivers such as TP53, PIK3CA and KRAS were identified in GA‐FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA‐FG and conventional gastric cancer.ConclusionOur study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA‐FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease.
Unveiling the Clinical Path of Microinvasive Breast Cancer: A Comparative Study With Tis‐T1 Breast Cancer
Authors: Song Ran , Lee Dong‐Eun , Jung So‐Youn , Lee Seeyoun , Kang Han‐Sung , Han Jai Hong , Woo Jaeyeon , Lee Eun‐Gyeong 
Published: October 2024

ABSTRACTPurposeThe prognosis of microinvasive breast cancer (MIBC) is controversial, with a high reported rate of local recurrence (LR). This study aimed to evaluate the characteristics, treatments, and prognosis of patients with MIBC compared to those with carcinoma in situ (CIS) or early invasive cancer.MethodsPatients who diagnosed with CIS or stage I breast cancer were retrospectively enrolled. Using the Kaplan–Meier method, local recurrence‐free survival (LRFS), systemic recurrence‐free survival (SRFS), and cancer‐specific survival (CSS) were compared according to T stage. The prognostic factors associated with LRFS were identified using the Cox proportional hazards model.ResultsAccording to T stage, 517 (21.6%), 200 (8.4%), 207 (8.7%), 363 (15.2%), and 1101 (46.1%) patients had Tis, T1mi, T1a, T1b, and T1c tumors, respectively. The proportion of human epidermal growth factor receptor 2‐positive tumors was significantly higher in patients with MIBC (p < 0.0001). The administered adjuvant treatments also showed differences according to T stage (p < 0.0001). During the 73‐month median follow‐up period, patients with MIBC showed significantly worse LRFS than those with T1a or T1c tumors (p = 0.002). There was no significant difference in SRFS and CSS. In the Cox regression analysis, tumor multiplicity (p = 0.017), Ki‐67 (p = 0.025), cancer subtype (p = 0.034), adjuvant endocrine therapy (p = 0.003), and adjuvant radiation therapy (p < 0.0001) were significant prognostic factors associated with LRFS.ConclusionThe risk of LR was higher in patients with MIBC than in those with small invasive breast cancer. Therefore, if indicated, adjuvant endocrine and radiation therapies should be administered to prevent undertreatment in patients with MIBC.
Chemical enhanced oil recovery from shale‐rich tight carbonate reservoirs using 2‐butoxyethanol as a mutual solvent and diluted seawater
Authors: Nowrouzi Iman , Mohammadi Amir H. , Khaksar Manshad Abbas 
Published: October 2024

AbstractOil production from tight reservoirs due to their very low permeability and high capillary pressure requires complex operations and materials, so that hydraulic fracturing in these reservoirs is recommended before any chemical injection. This operation turns the reservoir into a fractured one that can produce more oil by activating the imbibition mechanism. The interfacial tension (IFT) of oil and water and reservoir rock wettability as key parameters of overproduction from this type of reservoir can affect this mechanism. In this study, the potential of 2‐butoxyethanol as a mutual solvent for enhanced oil recovery (EOR) was investigated with a focus on the oil production under imbibition in this type of reservoir through performing experiments and calculations of IFT, oil swelling, contact angle, and oil production. The analysis of the results shows that the mechanisms of IFT reduction, wettability alteration, and oil swelling, which all directly affect the oil production under imbibition, reached the desired values using 2‐butoxyethanol in the appropriate concentration along with the dilution of seawater. The lowest values for interfacial tension and contact angle at 0.03 M concentration of the solvent and 5000 ppm salinity at 90°C temperature were 1.315 mN/m and 71.57°, respectively. These values are much lower compared to the values obtained by similar additives, while solvents, unlike 2‐butoxyethanol, are effective in much higher volume ratios. The oil swelling increased by about 14% using 2‐butoxyethanol due to its mass transfer between water and oil phases through the interface. Finally, the oil recovery factors of 42% and 59% were achieved under one‐ and multi‐dimensional spontaneous imbibition (ODSI and MDSI), respectively.
Environmental, social, and governance, board gender diversity, and firm efficiency: Evidence from the global mining industry pre‐ and post‐COVID‐19 pandemic
Authors: Lu Wen‐Min , Kuo Kuo‐Cheng , Kweh Qian Long , Ganbaatar Oyunchimeg 
Published: October 2024

AbstractWe examine (i) the impacts of environmental, social, and governance (ESG) on firm efficiency and (ii) how board gender diversity (BGD) moderates these impacts in mining multinational enterprises (MNCs). We first employ a two‐stage network data envelopment analysis (DEA) approach to estimate eco‐efficiency (EE) and profitability efficiency (PE), and a network‐based ranking model to rank the mining MNCs. Second, we utilize multivariate regression analysis on 294 firm‐year observations of 49 global MNCs spanning from 2016 to 2021 to achieve our research objectives. Based on our findings, it appears that mining MNCs have a bigger room for improvement when it comes to their profitability efficiency than their eco‐efficiency. The DEA average efficiency scores for EE and PE stand at around 83% and 50%, respectively. Moreover, our regression results reveal that ESG significantly and positively influences EE but insignificantly affects PE. Environmental pillar score (EPS), social pillar score (SPS), and governance pillar score insignificantly influence EE, whereas EPS and SPS significantly affect PE. In addition, BGD significantly moderates the effect of ESG on EE. BGD significantly moderates only the impact of SPS on PE. Overall, this study emphasizes the significance of focusing on BGD when examining the relationship between ESG and firm efficiency, which thus provides crucial insights for stakeholders in the global mining industry, including investors, policymakers, and researchers.
Genetic Structure of Monochamus alternatus (Hope) in Qinling‐Daba Mountains and Expansion Trend: Implications for Pest Prevention and Management
Authors: Qi Jingyu , Nan Junke , Zhao Xiaogu , Liang Chaoqiong , Fan Jiangbin , He Hong 
Published: October 2024

ABSTRACTPine wilt disease (PWD), caused by Bursaphelenchus xylophilus, severely threatens global pine forests. Monochamus alternatus is the primary vector of B. xylophilus in East Asia. Understanding the population structure and evolutionary forces of vector insects is critical for establishing effective PWD management strategies. The present work explores the genetic structure and phylogenetic relationships of 20 populations of M. alternatus from the Qinling‐Daba Mountains (QDM) in China using the mitochondria DNA dataset, supplemented by ecological niche modeling (ENM). All M. alternatus populations were categorized into three phylogeographic clusters (Clade A, Clade B, and Clade C), with Clade A and Clade B corresponding to the western and eastern QDM, respectively. The results of divergence time estimation concur with environmental changes induced by Quaternary glacial climate oscillations in QDM of China. M. alternatus populations exhibited significant genetic differentiation, with expansion in their population size. Ecological niche modeling (ENM) demonstrated that precipitation and temperature significantly influence the distribution of M. alternatus and the species is anticipated to grow into higher latitude and higher altitude regions in the future. In a nutshell, exploring the genetic structure and evolutionary dynamics of M. alternatus can provide valuable insights into the prevention and occurrence of B. xylophilus. These findings also serve as a reference for research on population differentiation and phylogeography of other species in QDM and adjacent areas.