bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia‐Reperfusion Injury
Authors: Mu Qingchun , Yao Kai , Syeda Madiha Zahra , Zhang Min , Cheng Qian , Zhang Yufei , Sun Rui , Lu Yuting , Zhang Huamiao , Luo Zhicheng , Huang Hanning , Liu Xiaojing , Luo Chunmei , Zhu Xiulong , Wu Shuyu , Cui Liao , Huang Chunming , Chen Xiaoyuan , Tang Longguang 
Published: April 2023

AbstractIschemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood–brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl‐F‐(D)L‐F‐(D)L‐F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)‐responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation‐related diseases.
Taking the long view: Long‐term couple earnings arrangements across the transition to parenthood
Authors: Steinbring Ruth , Perales Francisco , Baxter Janeen , Lam Jack 
Published: April 2023

AbstractThis paper examines household earnings arrangements and parenthood. Previous research has shown that parenthood is associated with a motherhood wage penalty with women withdrawing from the labour market or reducing their work hours. But few studies have examined within‐couple relative earnings and breadwinning arrangements across the transition to parenthood. We identify three types of households—“female‐breadwinner households” (where women earn more than 60 per cent of the couple's annual labour income); “male‐breadwinner households” (where women earn less than 40 per cent of the joint income); and “equal‐earner households” (where women earn 40 per cent to 60 per cent of the joint income). Using longitudinal data from the Household Income and Labour Dynamics in Australia (HILDA) Survey and fixed effects models, we find a substantial decrease in the percentage of couples in equal‐earner households in the year prior to and after parenthood that is largely replaced by an increase in the percentage in male‐breadwinner households. We observe little return to pre‐parenthood earnings arrangements for equal‐earner and male‐breadwinner households. For female‐breadwinner households, we observe a gradual return to pre‐parenthood arrangements. These results provide evidence that parenthood is a major milestone contributing to gender inequality and highlight the importance of policies for reducing the impact of parenthood on women's earnings.
Opportunities to inform German residents about the possibility of skin cancer screening and to inform stakeholders to take appropriate actions: A qualitative approach
Authors: Steeb Theresa , Wessely Anja , Heppt Markus V. , Erdmann Michael , Klug Stefanie J. , Berking Carola 
Published: April 2023

AbstractBackgroundThe national skin cancer screening (SCS) was introduced in Germany in 2008. However, public awareness and participation rates remain low. There are no campaigns or target group‐specific invitation strategies for SCS yet. Thus, our aim was to derive potential suggestions on how to best inform German residents about the possibility of SCS.MethodsSemi‐structured, individual interviews with male and female German residents aged ≥35 years were conducted in Erlangen (Germany) to explore opportunities on raising awareness of SCS. Interviews were audiotaped, transcribed verbatim, and analyzed using qualitative content analysis.ResultsOverall, 39 persons were interviewed. About 79.5% (31/39) had already undergone at least one SCS. Numerous opportunities to raise awareness of the possibility of SCS were suggested which were categorized into three main topics: the role of public promotion, health‐related caregivers, and health insurance. Similar themes were identified for inviting entitled persons to undergo SCS after 2 years. Furthermore, age‐dependent communication approaches were proposed, that is, younger persons should be approached electronically, while the older generation should be targeted with traditional media like mail.ConclusionsThe results of this project will inform stakeholders to take appropriate actions. The findings may contribute to increase participation rates in SCS and thus lead to earlier detection of skin cancer.
NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer
Authors: Xiong Qunli , Zhou Ying , Zhang Su , Zhang Yaguang , Xu Yongfeng , Yang Yang , Zhou Congya , Zeng Zhu , Han Junhong , Zhu Qing 
Published: April 2023

AbstractBackgroundMembers of the nuclear receptor‐binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf–Hirschhorn syndrome candidate 1‐like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological processes and cancer, knowledge of their expression levels to prognosticate in cancer remains unclear.MethodsWe analyzed the expression patterns for NSD family genes across multiple cancer types and examined their association with clinical features and patient survival profiles. Next, we explored the association between NSD3 expression and described features of the tumor microenvironment (TME) in PAAD, a severe type of pancreatic cancer. In particular, we correlated promoter methylation levels for NSD3 with patient outcomes in PAAD. Finally, we explored the putative oncogenic roles for NSD3 using a series of experiments with pancreatic cancer cells.ResultsWe report that the expression of NSD family members is correlated with clinical prognosis across multiple types of cancers. Also, we demonstrate that NSD3 variants are most prevalent among NSD genes across cancers we analyzed. Notably, when compared with NSD1 and NSD2, we find that NSD3 is prominently expressed, and its expression is significantly linked with clinical outcome in pancreatic cancer. Furthermore, NSD3 is frequently amplified, exhibits low promoter methylation, and is correlated with immune cell infiltration and enhanced proliferation of pancreatic cancer. Finally, we demonstrate that knockdown of NSD3 alters H3K36me2 methylation, downstream gene expression and EGFR/ERK signaling in pancreatic cancer cells.ConclusionsWe find that expression levels, the presence of genetic variants of NSD family genes, as well as their promoter methylation are correlated with clinical outcomes in cancer, including pancreatic cancer. Our in vitro experiments suggest that NSD3 may be relevant to gene expression regulation and growth factor signaling in pancreatic cancer.
Risk stratification and beneficiary selection among elderly nasopharyngeal carcinoma patients from concurrent chemoradiotherapy combined with induction chemotherapy
Authors: He Shuiqing , Wu Yan‐Ling , Gao Yongxiang , He Danjie , Huang Ying 
Published: April 2023

AbstractObjectiveThis study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC).Materials and MethodsA total of 909 elderly non‐metastatic NPC patients treated with cisplatin‐based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well‐matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed.ResultsNomograms of overall survival (OS) (C‐index: 0.64, 95% CI, 0.61–0.89) and disease special survival (DSS) (C‐index: 0.65, 95% CI, 0.62–0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5‐year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5‐year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5‐year OS and DSS rate compared with CCRT (5‐year OS rate, 73.5% versus 51.8%, p = 0.006; 5‐year DSS rate, 81.4% versus 61.3%, p = 0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p = 0.259, 0.186; DSS: p = 0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results.ConclusionCompared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended.
Molecular profiling of colorectal cancer in a genetically admixed Hispanic population
Authors: Montes‐Rodríguez Ingrid M. , Centeno‐Girona Hilmaris , Rivera‐Lynch Camila , Rivera Noridza , Cruz‐Correa Marcia 
Published: April 2023

AbstractBackgorundColorectal cancer (CRC) is among the leading causes of cancer‐related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients.MethodsWe conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next‐generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan‐Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)‐Non‐Hispanic, and GENIE‐Hispanic datasets.ResultsAmong the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE‐Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability‐high (MSI), wild‐type KRAS, wild‐type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients.ConclusionThis is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non‐Hispanic and USH populations.
The Milan system for reporting salivary gland cytopathology—A single‐center study of 2156 cases
Authors: Tochtermann Giulia , Nowack Miriam , Hagen Cristina , Rupp Niels J. , Ikenberg Kristian , Broglie Martina A. , Saro Francesca , Lenggenhager Daniela , Bode Peter K. 
Published: April 2023

AbstractBackgroundFine‐needle aspiration cytology (FNAC) represents an important diagnostic tool for the workup of salivary gland (SG) lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a six‐tiered system for standardizing diagnoses and improvement of communication between pathologists and clinicians, providing risk of malignancy (ROM) rates for every category. The aims of the present study were (i) to validate the use of MSRSGC in a large series of SG FNAC in a tertiary center in Switzerland, (ii) to determine ROM for each category and compare them with data from MSRSGC and similar studies, and (iii) to investigate whether there were relevant differences of non‐diagnostic results between fine‐needle aspirations (FNA) performed by cytopathologists compared to non‐cytopathologists.MethodsThe files of the department of Pathology in the University Hospital Zurich (UHZ) were searched for SG FNAC between 2010 and 2019. The MSRSGC guidelines were applied retrospectively. Furthermore, ROM, risk of neoplasia (RON), sensitivity, and specificity were calculated based on the cases with histopathological follow‐up.ResultsA total of 2156 SG FNAC including 753 cases with histopathological follow‐up were evaluated. Generally, ROM was within the range of values provided by MSRSGC, with some minor deviations. Sensitivity was 94.6%, and specificity was 99.3%.ConclusionsOur study confirms the usefulness of MSRSGC. In addition, it provides a detailed insight into the wide spectrum of SG FNAC. Finally, we showed that the rate of non‐diagnostic FNA was significantly lower in FNAs performed by cytopathologists compared to non‐cytopathologists.
Epidemiological, therapeutic, and survival trends in malignant pleural mesothelioma: A review of the National Cancer Database
Authors: Bou‐Samra Patrick , Chang Austin , Azari Feredun , Kennedy Gregory , Segil Alix , Guo Emily , Marmarelis Melina , Langer Corey , Singhal Sunil 
Published: April 2023

AbstractBackgroundMalignant pleural mesothelioma (MPM) is an aggressive cancer of the cells lining the pleural cavity with a low overall incidence. The National Cancer Database (NCDB) released in August 2022 updated data that reflect the newest trends in MPM.MethodsThe NCDB was queried for patients diagnosed with MPM between 2004 and 2020. Variables collected included demographics, tumor characteristics, and treatment. Student's t‐test and independent‐samples proportions test were used for means analysis. Survival was assessed by the Kaplan–Meier method using SPSS version 28.ResultsA total of 41,074 patients were diagnosed with mesothelioma, with a steady incidence (0.25%) between 2004 and 2017. The mean age of diagnosis was 70 (SD 13). 73.2% of the patients were males, 69% had no comorbidities, and 93.3% were white. More patients were diagnosed at Stage 1 after 2008 (p < 0.001). Since 2010, there has been a significant increase in patients offered treatment with 73.9% receiving some therapy (p < 0.01): 50.5% received chemotherapy, 27.6% surgery, 8.6% radiation, and 5.4% immunotherapy. The median overall survival was 10.3 months from diagnosis [95% CI: 10.2–10.5]. Risk factors associated with 30‐day mortality from surgical intervention included age (OR = 1.02, p < 0.001), male gender (OR = 1.3, p = 0.03), poorly differentiated grade (OR = 2.1, p < 0.001), Stage 4 (OR = 1.4, p = 0014), and epithelioid histology (OR = 0.51, p = 0.03).ConclusionThe current management of MPM is based on stage and histologic subtype. Due to the small numbers of patients at most academic centers, the NCDB provides a robust dataset to draw upon broad data points in treatment discussions with patients.
Distinct circulating cytokine/chemokine profiles correlate with clinical benefit of immune checkpoint inhibitor monotherapy and combination therapy in advanced non‐small cell lung cancer
Authors: Hu Yue , Li Shixun , Xiao He , Xiong Yanli , Lu Xianfeng , Yang Xiao , Luo Wei , Luo Jiamin , Zhang Shiheng , Cheng Yi , Zhang Lei , Dai Xiaoyan , Yang Yuxin , Wang Dong , Li Mengxia 
Published: April 2023

AbstractBackgroundAn ever‐increasing number of efforts are focused on identifying effective biomarkers for immune checkpoint inhibitors (ICIs). Cytokines and chemokines are critical to tumor growth, metastasis, tumor angiogenesis, and the immune response against tumor cells. In the study here, we determined the correlation between circulating cytokines/chemokines and the clinical benefit of ICIs for non‐small cell lung cancer (NSCLC) patients.MethodsPeripheral blood samples were collected before and during treatment (at 12th week). Plasma levels of cytokines/chemokines and specific stress response markers were measured using the Bio‐Plex Pro Human Cytokines Grp I Panel (27‐plex), an APEX1 detection kit, and a human LAP(TGF‐β1) immunoassay kit. A Mann–Whitney U‐test or Wilcoxon signed‐rank test and a Cox proportional hazards model were employed for statistical analysis.ResultsIn the ICI monotherapy cohort, a high level of IL‐6 at pretreatment or an elevation of IL‐6, IL‐8, FGF2, CXCL10, CCR1, PDFGB, TNF, and APEX1 posttreatment was associated with poor progress‐free survival (PFS). A posttreatment elevation (defined herein as change rate) of CXCL10 was also associated with poor overall survival (OS). In the combinational therapy group, a high level of IL‐12, IL‐17A, FGF2, VEGF, and APEX1 at pretreatment and an elevation of CCL2 posttreatment were associated with poor PFS. A high level of IL‐9, FGF2, PDFGB, CCL4, TFGB, and APEX1 at pretreatment and an elevation of IL‐13, CSF2, and CCL2 at posttreatment were associated with poor OS of patients receiving combination therapy.ConclusionsThe study here suggests that circulating cytokines/chemokines are feasible, noninvasive biomarkers for predicting clinical benefit of ICI treatment for NSCLC. Distinct circulating factor profiles were observed in individuals receiving ICI monotherapy or combination therapy.
Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival
Authors: Soares Kevin C. , Jolissaint Joshua S. , McIntyre Sarah M. , Seier Kenneth P. , Gönen Mithat , Sigel Carlie , Nasar Naaz , Cercek Andrea , Harding James J. , Kemeny Nancy E. , Connell Louise C. , Koerkamp Bas Groot , Balachandran Vinod P. , D'Angelica Michael I. , Drebin Jeffrey A. , Kingham T. Peter , Wei Alice C. , Jarnagin William R. 
Published: April 2023

AbstractPurposeThe role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy.Patients and MethodsIn this single‐institution retrospective analysis, patients with biopsy‐proven IHC treated with either curative‐intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver‐limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver‐limited recurrence was analyzed in the resection cohort.ResultsFrom 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver‐only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression‐free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001).ConclusionIn patients with liver‐limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver‐directed therapy.
The impact of curative conversion therapy aimed at a cancer‐free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab
Authors: Shimose Shigeo , Iwamoto Hideki , Shirono Tomotake , Tanaka Masatoshi , Niizeki Takashi , Kajiwara Masahiko , Itano Satoshi , Yano Yoichi , Matsugaki Satoru , Moriyama Etsuko , Noda Yu , Nakano Masahito , Kuromatsu Ryoko , Koga Hironori , Kawaguchi Takumi 
Published: April 2023

AbstractBackground and AimsWe aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer‐ and drug‐free states in patients with unresectable hepatocellular carcinoma (u‐HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy.MethodsThis retrospective study enrolled 156 patients who were Child‐Pugh class A with u‐HCC treated using Atez/Beva. The profile of objective response was investigated using decision‐tree analysis. Progression‐free, recurrence‐free, and overall survival were assessed.ResultsThe progression‐free and overall survival were 6.1 and 18.0 months, respectively. Objective response and disease control rates were 32.0% and 84.0%, respectively. Decision‐tree analysis revealed that neutrophil‐to‐lymphocyte ratio (NLR) <3, modified albumin‐bilirubin grade (m‐ALBI) 1 or 2a, and age < 75 were sequential splitting variables for the objective response, respectively. In the multivariate analysis, NLR <3 and m‐ALBI grade 1 or 2a were identified as predictive factors for objective response. We successfully achieved eligibility for conversion therapy in 17 patients after Atez/Bev therapy significant response. Following conversion therapy, the curative therapy group, including surgical resection or radiofrequency ablation (RFA), had significantly higher recurrence‐free survival than did the transcatheter arterial chemoembolization (TACE) and Atez/Bev discontinuation (surgical resection or RFA; not reached vs. TACE; 5.3 months, p = 0.008, Atez/Bev discontinuation; 3.9 months, p = 0.048, respectively) groups.ConclusionsNLR <3 and m‐ALBI grade 1 or 2a were predictive factors for conversion therapy, leading to cancer‐ and drug‐free states in patients with u‐HCC undergoing Atez/Bev therapy. Moreover, surgery or RFA may be suitable for conversion therapy for cancer‐free status.