bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crocin enhances the sensitivity to paclitaxel in human breast cancer cells by reducing BIRC5 expression
Authors: Jia Yunhao , Yang Han , Yu Jinsong , Li Zhong , Jia Guangwei , Ding Bo 
Published: January 2024

AbstractPaclitaxel (PTX) is one of the first‐line chemotherapeutic agents for treating breast cancer. However, PTX resistance remains a major hurdle in breast cancer therapy. Crocin, the main chemical constituent of saffron, shows anti‐cancer activity against various types of cancer. However, the effect of crocin on the resistance of PTX in breast cancer is still unknown. CCK‐8 and TUNEL assays were employed to detect cell viability and apoptosis, respectively. The targets of crocin were predicted using HERB database and the targets associated with breast cancer were acquired using GEPIA database. The Venn diagram was utilized to identify the common targets between crocin and breast cancer. Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) expression was detected by qRT‐PCR and western blot analysis. The correlation between BIRC5 expression and survival was analyzed by Kaplan–Meier plotter and PrognoScan databases. Our data suggested that crocin aggravated PTX‐induced decrease of viability and increase of apoptosis in MCF‐7 and MCF‐7/PTX cells. BIRC5 was identified as the target of crocin against breast cancer. Crocin inhibited BIRC5 expression in MCF‐7 and MCF‐7/PTX cells. BIRC5 is overexpressed in breast cancer tissues, as well as PTX‐sensitive and PTX‐resistant breast cancer cells. BIRC5 expression is related to the poor survival of patients with breast cancer. Depletion of BIRC5 strengthened PTX‐induced viability reduction and promotion of apoptosis in MCF‐7 and MCF‐7/PTX cells. Moreover, BIRC5 overexpression reversed the inhibitory effect of crocin on PTX resistance in breast cancer cells. In conclusion, crocin enhanced the sensitivity of PTX in breast cancer cells partially through inhibiting BIRC5 expression.
Advancing the implementation of take‐home naloxone by community pharmacists: Testing the role of COM‐B
Authors: Moullin Joanna C. , Staniland Lexy , Uren Hannah , Nielsen Suzanne , Lenton Simon 
Published: January 2024

AbstractIntroductionOpioid‐related overdose fatalities are rising despite the increased accessibility of take‐home naloxone (THN). Targeted implementation strategies are needed to improve the distribution of naloxone. This study investigates the effectiveness of a short video targeting pharmacists that addresses implementation barriers.MethodsA pre‐post, mixed methods design was adopted to examine the effect of a brief behaviour change intervention (an educational video informed by the capability, opportunity, motivation affecting behaviour (COM‐B) model), on factors affecting pharmacists’ implementation of THN in Western Australia. Paired samples t‐tests for were used to investigate intentions, knowledge, skill, confidence, feasibility, appropriateness, acceptability, attitudes, anticipated patient reactions, social support and implementation climate. Structural equation modelling examined the associations between constructs and to test the proposed mediation of motivation on capability and opportunity affecting intentions to discuss and provide THN.ResultsWe analysed data from 102 participants. At follow‐up and after all participants had viewed the video, participants had significantly improved intentions, skill, confidence, anticipated reactions, social support and perceptions that THN implementation was feasible, appropriate and acceptable. No significant differences were seen for attitudes, knowledge or implementation climate. The proposed mediation effect of motivation on the associations between opportunity and intentions and capability and intentions was not supported.Discussion and ConclusionsA short video directly targeting identified implementation barriers has the ability to improve key influences in the provision of THN. Dissemination of information to community pharmacists is a challenge. Implementation strategies addressing knowledge and targeting other levels of influence on intentions and behaviour are required.
Safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of Exendin‐4‐IgG4‐Fc in healthy subjects: A phase 1, single‐centre, randomized, double‐blind, dose escalation study
Authors: Chen Gui‐Ling , Liu Yang , Gao Xue‐Feng , Wu Kai‐Qi , Yang Yun‐Kai , Chen Yong , Peng Cong‐Gao , Jin Ting‐Han , Huang Yu‐Bao , Zhang Yao‐Wen , Su Jing , Jiang Qi , Guo Tong , Zhao Jie , Peng Xiang‐Nan , Peng Jing‐Yu , Li Si‐Xiu , Sun Yong‐Li , Zhang Hong‐Mei , Fu Yan‐Li , Luo Dan , Ma Yaru , Shen Zhen‐Wei , Zhang Yun‐Tao , Shou Zhang‐Fei 
Published: January 2024

AbstractAimNovel long‐acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin‐4‐IgG4‐Fc (E4F4) is a long‐acting glucagon‐like peptide‐1 receptor agonist. This first‐in‐human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects.MethodsThis single‐centre, randomized, double‐blind, placebo‐controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level.ResultsE4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose‐dependent relationship between frequency, severity or causality of treatment‐emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45‐14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose‐dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose‐response relationship in the 1.8‐10.35 mg dose range, with an increased response at the higher doses.ConclusionE4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5‐10.35 mg once every 2 weeks.
International comovements of public debt
Authors: Isomitdinov Hasan , Arčabić Vladimir , Lee Junsoo , Yun Youngjin , Payne James E. 
Published: January 2024

AbstractThis study presents evidence of global and regional comovements in public debt and examines their trends and features. We employ a Bayesian dynamic factor model with time‐varying parameters based on the debt‐to‐GDP ratio of 115 countries. We find the global factor accounts for 38 percent of the total variation in the debt ratio worldwide, but its share decreases over time. Countries with more financial openness and a greater share of external public debt are more exposed to global/regional comovements. The assertion that international financial integration encourages higher government borrowing applies primarily to high‐income countries and it does not hold globally.
Exam evaluation in prosthodontics across preclinical and clinical years from students' perspective: A cross‐sectional study
Authors: Alamoush Rasha A. , Sartawi Samiha , Salim Nesreen A. , Sawair Faleh , Haider Julfikar , Jamani Kifah 
Published: January 2024

AbstractIntroductionThe purpose of this study was to explore the students' perceptions and performance in prosthodontics theory exam.MethodsA cross‐sectional descriptive study was conducted on 560 (80.82%) students of different levels (third, fourth and fifth years) to explore their opinions and performance with regard to a number of issues on a prosthodontics theory exam (exam evaluation, exam preparation, exam material, exam timing). Demographic data were also collected. Descriptive statistics were generated and Chi‐square test, independent samplet‐test, ANOVA test and Pearson's correlation coefficient were used to examine the associations between different variables. The significance level was set atp < .05.ResultsStudents' responses regarding exam evaluation was influenced by their gender, study level, high‐school Grade Point Average (GPA) and undergraduate cumulative GPA. Perceived exam difficulty was significantly affected by gender (p = .03) and study level (p < .001), and negatively correlated to both high‐school GPA (p < .001) and university GPA (p = .03). The vast majority (88.2%) depended on lecture hand‐outs and lecture notes for study. Exam material and preparation were not significantly affected by any of the demographic variables with most respondents (76.8%) thinking that the lectures blended with prosthodontics laboratories/clinics would improve their understanding of the exam material. The suggested best time to conduct the exam was early afternoon (31.6%). Student performance was significantly affected by the study level (p < .001) and cumulative GPA (p < .001) with significant positive correlation between the high‐school GPA and the mark in the exam (r = .29,p < .001) and by the amount of time students spent for exam preparation (p < .001). Those students who reported using textbooks to prepare for the exam got significantly higher marks (66.1 ± 8.7) compared to the students who did not (62.8 ± 9.7) (p = .03).ConclusionsCourse level, GPA and gender were identified as the most influential factors in different aspects of exam evaluation and students' performance. Regular study and use of textbooks were demonstrated to improve academic performance. Additional orientation and guidance relating to the exam (especially for third year students) would be welcomed, as would alternate teaching methods such as small group discussions or study groups.
Expected Classification Accuracy for Categorical Growth Models
Authors: Murphy Daniel , Quesen Sarah , Brunetti Matthew , Love Quintin 
Published: January 2024

AbstractCategorical growth models describe examinee growth in terms of performance‐level category transitions, which implies that some percentage of examinees will be misclassified. This paper introduces a new procedure for estimating the classification accuracy of categorical growth models, based on Rudner's classification accuracy index for item response theory–based assessments. Results of a simulation study are presented to provide evidence for the accuracy and validity of the approach. Also, an empirical example is presented to demonstrate the approach using data from the Indiana Student Performance Readiness and Observation of Understanding Tool growth model, which classifies examinees into growth categories used by the Office of Special Education Programs to monitor the progress of preschool children who receive special education services.
Large analysis of genetic manipulations reveals an inverse correlation between initial alcohol resistance and rapid tolerance phenotypes
Authors: Chvilicek Maggie M. , Seguin Alexandra , Lathen Daniel R. , Titos Iris , Cummins‐Beebee Pearl N. , Pabon Miguel A. , Miščević Maša , Nickel Emily , Merrill Collin B. , Rodan Aylin R. , Rothenfluh Adrian 
Published: January 2024

AbstractTolerance occurs when, following an initial experience with a substance, more of the substance is required subsequently to induce identical behavioral effects. Tolerance is not well‐understood, and numerous researchers have turned to model organisms, particularly Drosophila melanogaster, to unravel its mechanisms. Flies have high translational relevance for human alcohol responses, and there is substantial overlap in disease‐causing genes between flies and humans, including those associated with Alcohol Use Disorder. Numerous Drosophila tolerance mutants have been described; however, approaches used to identify and characterize these mutants have varied across time and labs and have mostly disregarded any impact of initial resistance/sensitivity to ethanol on subsequent tolerance development. Here, we analyzed our own, as well as data published by other labs to uncover an inverse correlation between initial ethanol resistance and tolerance phenotypes. This inverse correlation suggests that initial resistance phenotypes can explain many ‘perceived’ tolerance phenotypes, thus classifying such mutants as ‘secondary’ tolerance mutants. Additionally, we show that tolerance should be measured as a relative increase in time to sedation between an initial and second exposure rather than an absolute change in time to sedation. Finally, based on our analysis, we provide a method for using a linear regression equation to assess the residuals of potential tolerance mutants. These residuals provide predictive insight into the likelihood of a mutant being a ‘primary’ tolerance mutant, where a tolerance phenotype is not solely a consequence of initial resistance, and we offer a framework for understanding the relationship between initial resistance and tolerance.
Regulation of headache response and transcriptomic network by the trigeminal ganglion clock
Authors: Han Chorong , Lim Ji Ye , Koike Nobuya , Kim Sun Young , Ono Kaori , Tran Celia K. , Mangutov Elizaveta , Kim Eunju , Zhang Yanping , Li Lingyong , Pradhan Amynah A. , Yagita Kazuhiro , Chen Zheng , Yoo Seung‐Hee , Burish Mark J. 
Published: January 2024

AbstractObjectiveTo characterize the circadian features of the trigeminal ganglion in a mouse model of headache.BackgroundSeveral headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood.MethodsWe examined trigeminal ganglion ex vivo and single‐cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross‐referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy.ResultsThe trigeminal ganglion demonstrates strong circadian rhythms in both ex vivo and single‐cell cultures, with core circadian proteins found in both neuronal and non‐neuronal cells. Using our novel behavioral model, we showed that nitroglycerin‐treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1/2 double knockout mice. Furthermore, RNA‐sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock‐regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia.ConclusionOur study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology.Plain Language SummarySeveral headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24‐hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.
Deep‐learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy
Authors: Huang Chung‐Yen , Chang Ruey‐Feng , Lin Chih‐Yung , Hsieh Min‐Shu , Liao Po‐Chun , Wang Yu‐Jui , Kao Yu‐Chien , Porta Lorenzo , Lin Pin‐Yu , Lee Chien‐Chang , Lee Yi‐Hsuan 
Published: January 2024

AimsRisk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low‐risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high‐risk lesions. We aimed to develop a machine‐learning algorithm based on whole‐slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision.Methods and ResultsPatients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI‐RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide‐ and patient‐level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high‐grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81).ConclusionThis study demonstrated that deep‐learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.
Species status and phylogenetic relationships of the enigmatic Negros Fruit Dove (Ptilinopus arcanus)
Authors: Nash John A. , Harrington Richard C. , Zyskowski Kristof , Near Thomas J. , Prum Richard O. 
Published: January 2024

The Negros Fruit Dove Ptilinopus arcanus is an enigmatic bird known only from a single specimen collected on Negros Island, Philippines, in 1953. We extracted and sequenced ultra‐conserved elements from historical toe‐pad samples of the type specimen of P. arcanus and 27 other species of ptilinopine doves to investigate the species status and phylogenetic relationships of this taxon. We establish that P. arcanus represents a valid species, resolve its phylogenetic position at the base of the radiation of ‘core’ Ptilinopus fruit doves, and estimate that P. arcanus diverged from its most recent common ancestor several million years before Negros Island emerged from the seafloor. We also perform an ancestral range reconstruction to evaluate the effect of different altitudinal preferences on the putative historical range of this species, and we discuss how these findings can inform future efforts to relocate and potentially conserve this species.
Characterization of the MT‐2 Treg‐like cell line in the presence and absence of forkhead box P3 (FOXP3)
Authors: McCullough Morgan J , Tune Miriya K , Cabrera Johnny Castillo , Torres‐Castillo Jose , He Minghong , Feng Yongqiang , Doerschuk Claire M , Dang Hong , Beltran Adriana S , Hagan Robert S , Mock Jason R 
Published: January 2024

AbstractCD4+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT‐2 cells, an immortalized Treg‐like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)‐mediated knockdown of FOXP3 in MT‐2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT‐2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT‐2 cells and that FOXP3's potential downstream targets include a wide range of transcripts that participate in the cell cycle, promote growth and contribute to inflammatory processes, but do not wholly simulate previously reported human primary Treg transcriptional changes in the absence of FOXP3. We also demonstrate that FOXP3 regulates cell cycling and proliferation, expression of molecules crucial to Treg function and MT‐2 cell–suppressive activities. Thus, MT‐2 cells offer opportunities to address regulatory T‐cell functions in vitro.
Seasonal variation in risk and return trade‐off
Authors: Lee Deok‐Hyeon , Min Byoung‐Kyu 
Published: January 2024

AbstractExisting studies show that firms with large macroeconomic risk do not earn higher returns, incompatible with the theoretical predictions of standard economic models. Using a broad set of macro‐related factors, we find the January seasonality of the macroeconomic risk–return relation. Firms with high macro risk deliver higher returns than firms with low risk in January, that is, the positive risk–return trade‐off holds. Conversely, the negative risk–return relation is observed in non‐January months. The seasonal variation in the macro risk–return relation cannot be explained by existing January effects, including the tax‐loss selling, window dressing, and pronounced gambling preference around New Year.
Tax avoidance and debt maturity in SMEs
Authors: Sánchez‐Ballesta Juan Pedro , Yagüe José 
Published: January 2024

AbstractWe investigate how tax avoidance affects the maturity structure of debt in firms where tax avoidance costs are presumably low, namely SMEs. Previous research has shown that creditors of listed tax‐avoiding companies impose shorter maturities to more frequently reassess the tax avoidance risks in debt contracts. Using a sample of 110,690 firm‐year observations of Spanish SMEs over the period 2007–2020, we examine the relationship between tax avoidance and debt maturity and the channels driving this relationship. We find that tax‐avoiding SMEs show a longer debt maturity. This effect is stronger for SMEs with higher profitability, lower earnings management incentives, and higher reliability of financial reporting. We also find that tax avoidance reduces leverage and short‐term debt, increases future cash flows, and decreases future cash flow volatility. Overall, these findings suggest that, unlike large firms, SMEs use cash tax savings to reduce leverage and short‐term debt in their financial structure and that tax avoidance is positively valued by their lenders.