bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the impact of long‐term storage on the quality and integrity of biological specimens in a reproductive biobank
Authors: Wang Zhao , Zhang Changming , Zhang Xin , Bian Yuehong , Cao Yongzhi 
Published: June 2024

AbstractBiobanks hold a pivotal role in facilitating translational and clinical research endeavors. However, the effects of prolonged storage on frozen blood samples analytes are not well defined yet. The aim of this study was to investigate the long‐term stability of the quality of DNA, RNA, and endocrine markers within blood samples amassed from the biobank over the past 11 years. The results show that the overall quality and integrity of DNA remained not significantly influenced. However, RNA integrity and purity displayed substantial deterioration as storage duration increased, to ensure high‐quality RNA for downstream analyses, advised to prioritize using blood samples stored within 3 years. Furthermore, the study examined the influence of storage time on endocrine markers. Through repeated measures ANOVA and linear regression analyses, it was evident that storage duration significantly influenced the levels of endocrine markers. This insight aids researchers in selecting appropriate markers for their investigations and augments the precision and dependability of results when dealing with long‐term stored samples.
Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab‐paclitaxel plus gemcitabine as second or later‐line treatment
Authors: Giordano Guido , Milella Michele , Landriscina Matteo , Bergamo Francesca , Tirino Giuseppe , Santaniello Antonio , Zaniboni Alberto , Vasile Enrico , De Vita Ferdinando , Re Giovanni Lo , Vaccaro Vanja , Giommoni Elisa , Natale Donato , Conca Raffaele , Santini Daniele , Maiorino Luigi , Sanna Gianni , Ricci Vincenzo , Iop Aldo , Montesarchio Vincenzo , Procaccio Letizia , Noventa Silvia , Bianco Roberto , Febbraro Antonio , Lonardi Sara , Tortora Giampaolo , Sperduti Isabella , Melisi Davide 
Published: June 2024

AbstractBackgroundPancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions.MethodsThe study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice.ResultsAG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS.ConclusionsThis study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy.
Prevalence of neurotrophic tropomyosin receptor kinase (NTRK) fusion gene positivity in patients with solid tumors in Japan
Authors: Nakata Eiji , Osone Tatsunori , Ogawa Toru , Taguchi Tomoyuki , Hattori Kana , Kohsaka Shinji 
Published: June 2024

AbstractBackgroundMembers of the neurotrophic tropomyosin receptor kinase (NTRK) gene family, NTRK1, NTRK2, and NTRK3 encode TRK receptor tyrosine kinases. Intra‐ or inter‐chromosomal gene rearrangements produce NTRK gene fusions encoding fusion proteins which are oncogenic drivers in various solid tumors.MethodsThis study investigated the prevalence of NTRK fusion genes and identified fusion partners in Japanese patients with solid tumors recorded in the Center for Cancer Genomics and Advanced Therapeutics database of comprehensive genomic profiling test.ResultsIn the analysis population (n = 46,621), NTRK fusion genes were detected in 91 patients (0.20%). The rate was higher in pediatric cases (<18 years; 1.69%) than in adults (0.16%). NTRK gene fusions were identified in 21 different solid tumor types involving 38 different partner genes including 22 (57.9%) previously unreported NTRK gene fusions. The highest frequency of NTRK gene fusions was head and neck cancer (1.31%) and thyroid cancer (1.31%), followed by soft tissue sarcoma (STS; 0.91%). A total of 97 NTRK fusion gene partners were analyzed involving mainly NTRK1 (49.5%) or NTRK3 (44.2%) gene fusions. The only fusion gene detected in head and neck cancer was ETV6::NTRK3 (n = 22); in STS, ETV6::NTRK3 (n = 7) and LMNA::NTRK1 (n = 5) were common. Statistically significant mutual exclusivity of NTRK fusions with alterations was confirmed in TP53, KRAS, and APC. NTRK gene fusion was detected from 11 STS cases: seven unclassified sarcoma, three sarcoma NOS, and one Ewing sarcoma.ConclusionsNTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.
Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large‐scale multicenter study
Authors: Wang Yong‐Shuai , Wang Wei , Zhang Shen‐Yu , Cai Wei , Song Rui‐Peng , Mei Tao , Wang Wei , Zhang Feng , Qi Fei‐Yu , Zhang Sai , Liu Yan , Li Hao‐Ran , Ji Peng , Gao Miao , Song Hua‐Chuan , Yao Huan‐Zhang , Meng Fan‐Zheng , Lu Zheng , Wang Ji‐Zhou , Liu Lian‐Xin 
Published: June 2024

AbstractBackgroundTo date, carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients.MethodsA total of 1121 patients from the Liver Cancer Clin‐Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular‐cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness.ResultsROC curves obtained by combining CA50, CA19‐9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856–0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841–0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853–0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818–0.927, 94.2%, and 64.6%) in the validation cohort.ConclusionThe model combining CA50, CA19‐9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.
The establishment of kidney cancer organoid line in drug testing
Authors: Tse Ryan Tsz‐Hei , Wong Christine Yim‐Ping , Ding Xiaofan , Cheng Carol Ka‐Lo , Chow Chit , Chan Ronald Cheong‐Kin , Ng Joshua Hoi‐Yan , Tang Victor Wai‐Lun , Chiu Peter Ka‐Fung , Teoh Jeremy Yuen‐Chun , Wong Nathalie , To Ka‐Fai , Ng Chi‐Fai 
Published: June 2024

AbstractIntroductionKidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC.ObjectiveRecently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC.Materials and MethodsPatients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes.ResultsOur results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents.ConclusionOur RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices.
Escalated‐dose radiotherapy for unresected locally advanced pancreatic cancer: Patterns of care and survival in the United States
Authors: Shi Christopher , De Brian , Tran Cao Hop S. , Liu Suyu , Florez Marcus A. , Kouzy Ramez , Grippin Adam J. , Katz Matthew H. G. , Tzeng Ching‐Wei D. , Ikoma Naruhiko , Kim Michael P. , Lee Sunyoung , Willis Jason , Noticewala Sonal S. , Minsky Bruce D. , Smith Grace L. , Holliday Emma B. , Taniguchi Cullen M. , Koong Albert C. , Das Prajnan , Ludmir Ethan B. , Koay Eugene J. 
Published: June 2024

AbstractIntroductionWith locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated‐dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes.MethodsWe searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas‐directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional‐dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively.ResultsAmong the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas‐directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p < 0.001) and treatment between 2016 and 2019 (aOR 2.54, p < 0.001) were associated with greater receipt of EDR, whereas use of chemotherapy (aOR 0.60, p < 0.001) was associated with less receipt. Median OS estimates for EDR and CDR were 14.5 months and 13.0 months (p < 0.0001), respectively. For radiation therapy subset patients with available survival data (n = 13,579), multivariable Cox regression correlated EDR (adjusted hazard ratio 0.85, 95% confidence interval 0.80–0.91; p < 0.001) with longer OS versus CDR.Discussion and ConclusionsUtilization of EDR has increased since 2016, but overall utilization of RT for LAPC has remained at less than one in five patients for almost two decades. These real‐world results additionally provide an estimate of effect size of EDR for future prospective trials.
The relationship between lifelong learning and professional development activities in a Portuguese sample
Authors: Coelho Rodrigo Ponces , Pires António Pazo , Neimeyer Greg , Vaz Alexandre , Neto David , Sousa Daniel 
Published: June 2024

AbstractObjectiveA dispositional commitment to lifelong learning (LL) is an important aspect of continuing professional development for practicing psychotherapists. Equally important is the dedication of psychotherapists to engaging in professional development activities to foster growth and maintain competence. However, there are limited available data on the range of practices and factors influencing psychotherapists' commitment to these activities. The primary objective of this study was to examine whether a higher commitment to LL would significantly predict greater participation in a range of different professional development activities.MethodA sample of 166 Portuguese psychotherapists completed an online survey on professional development. The survey included two key measures: the Jefferson Scale of Psychotherapist Lifelong Learning and a list of professional development activities based on the Retrospective Analysis of Psychotherapists' Involvement in Deliberate Practice. Exploratory factorial analysis was conducted to determine an alternative and suitable grouping for the list of activities, and structural equation modelling was utilised to assess the relationship between the commitment to LL and engagement in these activities.FindingsResults provided valuable insight into the diverse levels of participation among therapists across five categories of activities: (1) supervision and case discussion; (2) recording‐related activities; (3) reading and focussed learning; (4) reflecting; and (5) workshops supporting ongoing professional competence. Findings indicated that a stronger commitment to LL significantly predicted increased dedication to reading, focussed learning activities and attendance to training workshops. The implications and limitations of the study are discussed concerning their practical application for professional psychologists, counsellors and psychotherapists.
Antioxidant Mechanism, Spectroscopic and Pharmacological Properties of Four Flavonoids: DFT, Docking and Molecular Dynamics
Authors: Lai Wu‐Ji , Lu Jia‐Hao , Chen Wen‐hao , Jiang Li‐he , Shen Li‐Qun 
Published: June 2024

AbstractMyricetin (1), Quercetin (2), Kaempferol (3) and Kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them were investigated in detail. The lowest hydroxyl dissociation enthalpies of 1, 2, 3 and 4 were calculated by DFT, respectively. The hydroxyl dissociation enthalpies of the four flavonoids at the O2 site are the highest. By analyzing the intramolecular hydrogen bonds and HOMO‐LUMO orbitals of the four flavonoids, the reasons for their divergence of hydroxyl dissociation enthalpies and antioxidant mechanisms were further investigated. The UV–vis and IR spectra of four flavonoids were compared. The interactions about electrostatic attraction, p–π conjugation and hydrogen bond combined the flavonoid with the target protein closely. The root mean square deviation of peroxisome proliferator‐activated receptor γ combined with 1, 2 and 3 increased, while that of PPARγ combined with 4 decreased.
Protective Effect of a Isothiazolinone Derivative on Acute Lung Injury by Regulating PI3K‐AKT Signaling Pathway
Authors: Li Hua , Guo Jie , Zhang Gaiyue , Zhou Jing , Wang Qiang 
Published: June 2024

AbstractAcute lung injury (ALI) is a prevalent organ injury in sepsis, characterized by an inflammatory reactive disorder. Both the incidence and mortality rates of ALI have been steadily increasing. Isothiazolinone derivatives have displayed anti‐inflammatory activity and have shown effectiveness in treating pneumonia. The objective of the study is to assess the effects and mechanisms of the isothiazolinone derivative 4‐benzoyl‐2‐butyl‐5‐(ethylsulfinyl)isothiazol‐3(2H)‐one (C6) on sepsis‐induced ALI.The analysis of biological function and signal pathway enrichment demonstrated that C6 primarily exhibited anti‐inflammatory effects. Administration of different doses of C6 through intraperitoneal injection significantly improved the survival rate, body temperature, and body mass of mice with ALI induced by cecal ligation and puncture (CLP). Additionally, it mitigated lung tissue injury, pulmonary edema, lung permeability, inflammatory cell infiltration, apoptosis, and the expression of inflammatory cytokines. Network targeting analysis and experimental validation in mouse leukemia cells of monocyte macrophage (RAW264.7) cells and CLP‐induced ALI mice revealed that the anti‐inflammatory effect of C6 was mediated by the inhibition of the phosphatidylinositol 3 kinase ‐protein kinase B (PI3K‐AKT) signaling pathway.The research suggest that C6 has protective effects against ALI by inhibiting the PI3K‐AKT signaling pathway. This information could be valuable in developing potential treatments for ALI.
GenusBerberis: A Comprehensive and Updated Review on Ethnobotanical Uses, Phytochemistry and Pharmacological Activities
Authors: Fatima Hashmi Samar , Saleem Hammad , Khurshid Umair , Khursheed Anjum , Tauquir Alam Md , Imran Mohd , Abida  , Nayeem Naira , Shoaib Ali Gill Muhammad 
Published: June 2024

AbstractGenusBerberisis an excellent choice for research due to its history in traditional medicine, diverse pharmacological properties, and it has potential for drug discovery. This review presents information on the ethnobotany, pharmacological activities, and many phytochemicals identified fromBerberisspecies. It examines the existing literature on the genusBerberis, drawn from online databases, including PubMed, Web of Science, Science Direct, Elsevier, and Google Scholar, etc encompassing the data from 1960 to 2023. This review focuses on the structural details of reported phytochemicals ofBerberisspecies and pharmacological actions. Different extraction techniques were evaluated for extracts preparation. According to literature review, phytochemical analysis exhibited the presence of alkaloids, flavonoids, and phenolic compounds. A major bioactive alkaloid, berberine exhibits its main role in treatment of many gastric, infectious, and chronic disorders. This literature indicates thatBerberisgenus exhibits a variety of biological activities, i.e anti‐inflammatory, cytotoxic, hepatoprotective, antimicrobial, antidiabetic and antioxidant activities and utilization of these effects in the treatment and management of various diseases, like diabetes, microbial infections, inflammation, liver disorders, and cancer. However, conventional medicines, validation of traditional uses, and in‐depth phytochemical analysis are areas of research in genusBerberis.
Exploring New 5‐Nitroimidazole Derivatives As Potent Acetylcholinesterase and Butyrylcholinesterase Enzyme Inhibitors
Authors: Gursoy Sule , Satici Doruk , Kuzu Burak , Turkmenoglu Burcin , Dilek Esra , Algul Oztekin 
Published: June 2024

AbstractDiscovering new compounds capable of inhibiting physiologically and metabolically significant drug targets or enzymes is of paramount importance in biological chemistry. With this aim, new 5‐nitroimidazole derivatives (1–4) were designed and synthesized, and their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were discovered using acetyl (butyryl) thiocholine and Ellman's reagents for spectrophotometric assay. The inhibitory profiles of the synthesized compounds were assessed by comparing their IC50 and Ki values. Results demonstrate significant inhibitory activity of all synthesized compounds against both AChE and BuChE compared to the reference compound, donepezil. Notably, compound 4 exhibited dual inhibition of these enzymes, showing the highest activity against Electrophorus electricus AChE (EeAChE) with a Ki value of 0.024±0.009 nM and against equine BuChE (eqBuChE) with a Ki value of 0.087±0.017 nM. Furthermore, molecular modeling was conducted to study the interaction modes of the most potent compound (4) and donepezil in the active site of their related enzymes’ crystal structures (PDB ID: 4EY7 and 4BDS, respectively). Additionally, drug‐likeness, ADME, and toxicity profiles of the compounds and metronidazole were predicted. The above results indicated that the dual inhibition of these enzymes is considered as a promising strategy for the treatment of neurological disorder especially Alzheimer's disease.
Discovery of Sesquiterpene Lactones with Cytotoxicity from the Herb of Youngia japonica
Authors: Ye Xian‐Sheng , Lin Kuan , Tao Xiao‐Qing , Shang Jin‐Ting , Gui Yu‐Ran , Zhu Shu‐Xiu , Zhou Le , Xia Yi‐Yuan , Liu Wei , Sun Bin‐Lian , Chen Hai‐Feng , Shu Xi‐Ji 
Published: June 2024

AbstractIn the process of searching for anti‐breast cancer agents, five sesquiterpene lactones (1‐5), including two previously undescribed ones, yjaponica B‐C (1‐2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60 μM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl‐2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti‐breast cancer agent.