bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regioselective Difluoroalkylation of 2‐Pyridones with Fluoroalkyl Bromides Enabled by a Nickel(II) Catalyst
Authors: Pradhan Chandini , Khandelwal Disha , Punji Benudhar 
Published: January 2025

AbstractRegioselective C−H difluoroalkylation of diverse 2‐pyridones with ethyl bromodifluoroacetates and bromodifluoroacetamides is accomplished by using a (dppf)NiCl2 catalyst under mild conditions. This efficient protocol could deliver a variety of C‐3 difluoroalkylated pyridones with the tolerance of a range of highly susceptible functionalities, such as −Cl, −Br, −I, −COMe, −CN, −NMe2 and −NO2, including heteroarenes like pyridinyl, furanyl, thiophenyl and carbazolyl moieties. A preliminary mechanistic study suggests the radical pathway for the reaction involving fluoroalkyl radical intermediate.
Comparison of Blocked Versus Mixed Trialing When Teaching Foundational Skills to Early Learners
Authors: McKeown Ciobha A. , Walker Stephen F. , Peters Kerri P. 
Published: January 2025

ABSTRACTWhen teaching discriminations, clinicians may choose to teach one target at a time, repeatedly, until mastery (blocked‐trial instruction), or they may choose to teach multiple targets, interspersed, simultaneously (mixed‐trial instruction). Historically, it was recommended clinicians use mixed‐trial instruction at the onset of teaching as blocked‐trial instruction may produce faulty stimulus control. However, a recent study demonstrated that a modified blocked‐trial instructional arrangement was more efficient than mixed‐trial instruction and block‐size fading was unnecessary to maintain discriminated performance in adults with intellectual and developmental disabilities. The generality of these results to early learners is unknown. This study extended the aforementioned research to early learners diagnosed with autism spectrum disorder. Using an adapted alternating treatment design, we compared the rate of acquisition with both instructional formats across two foundational early learner skills. Comparable learning across both formats for all four early learners was observed.
Predictive Value of Machine Learning Models for Cerebral Edema Risk in Stroke Patients: A Meta‐Analysis
Authors: Deng Qi , Yang Yu , Bai Hongyu , Li Fei , Zhang Wenluo , He Rong , Li Yuming 
Published: January 2025

ABSTRACTIntroductionStroke patients are at high risk of developing cerebral edema, which can have severe consequences. However, there are currently few effective tools for early identification or prediction of this risk. As machine learning (ML) is increasingly used in clinical practice, its effectiveness in predicting cerebral edema risk in stroke patients has been explored. Nonetheless, the lack of systematic evidence on its predictive value challenges the update of simple and user‐friendly risk assessment tools. Therefore, we conducted a systematic review to evaluate the predictive utility of ML for cerebral edema in stroke patients.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane Database up to February 21, 2024. The risk of bias in selected studies was assessed using a bias assessment tool for predictive models. Meta‐analysis synthesized results from validation sets.ResultsWe included 22 studies with 25,096 stroke patients and 25 models, which were constructed using common and interpretable clinical features. In the validation cohort, the models achieved a concordance index (c‐index) of 0.840 (95% CI: 0.810–0.871) for predicting poststroke cerebral edema, with a sensitivity of 0.76 (95% CI: 0.72–0.79) and a specificity of 0.87 (95% CI: 0.83–0.90).ConclusionML models are significant in predicting poststroke cerebral edema, providing clinicians with a powerful prognostic tool. However, radiomics‐based research was not included. We anticipate advancements in radiomics research to enhance the predictive power of ML for poststroke cerebral edema.
Quantitative Assessment of Deep Gray Matter Susceptibility and Correlation With Cognition in Patients With Liver Cirrhosis
Authors: Wu Wenjun , Su Yu , Qin Ziji , Kang Jiamin , Xiang Dongqiao , Liu Dingxi , Zheng Chuansheng , Haacke E. Mark , Wang Lixia 
Published: January 2025

ABSTRACTBackground and ObjectivesAccumulation of metals quantified by quantitative susceptibility mapping (QSM) in deep gray matter (DGM) and their impact on cognition have not been studied in patients with liver cirrhosis. This study aims to use QSM to investigate the association between DGM susceptibility and cognition in cirrhotic patients.MethodsThirty cirrhotic patients and 30 age‐, gender‐, and education‐matched controls were imaged using a multiecho gradient‐echo sequence for QSM analysis in a 3T scanner. The susceptibility values were determined for the caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). All subjects underwent number connection test A (NCT‐A), digit substitution test (DST), and Montreal Cognitive Assessment (MoCA). Comparisons between the two groups and the correlation between the susceptibility values and neuropsychological scores were analyzed.ResultsThe susceptibility values of bilateral CN, TH, and RN were significantly lower in cirrhotic patients. Cirrhotic patients exhibited significantly prolonged NCT‐A time and decreased DST and MoCA scores. The NCT‐A, DST, MoCA, and sub‐domain scores were correlated with susceptibility values of RN, DN, SN, and CN, respectively. The susceptibility value of the left RN was a predictor variable for the DST, MoCA, and visuospatial–executive scores; those of the right CN and left RN were predictor variables for the naming score, and that of the left SN was an independent predictor variable for the language score.ConclusionsAltered susceptibility values of DGM measured by QSM are potential quantitative indicators of cognitive impairment in cirrhotic patients.
The Role of Atrial Fibrillation and Oral Anticoagulation Status in Health‐Related Quality of Life 12 Months After Ischemic Stroke or TIA
Authors: Olma Manuel C. , Steindorf‐Sabath Lena , Tütüncü Serdar , Kunze Claudia , Fiessler Cornelia , Kirchhof Paulus , Dietzel Joanna , Schurig Johannes , Oschmann Patrick , Niehaus Ludwig , Urbanek Christian , Thomalla Götz , Nabavi Darius G. , Röther Joachim , Laufs Ulrich , Veltkamp Roland , Heuschmann Peter U. , Haeusler Karl Georg , Endres Matthias ,   for the MonDAFIS Investigators
Published: January 2025

ABSTRACTAimsAtrial fibrillation (AF) accounts for about 20% of all ischemic strokes worldwide. It is known that AF impairs health‐related quality of life (HRQOL) in the general population, but data on HRQOL in stroke patients with newly diagnosed AF are sparse.MethodsPost hoc analysis of the prospective, investigator‐initiated, multicenter MonDAFIS study (NCT02204267) to analyze whether AF‐related oral anticoagulation (OAC), and/or AF‐symptom severity are associated with HRQOL after ischemic stroke or transient ischemic attack (TIA). HRQOL was measured using the EQ‐5D‐3L‐questionnaire (including EQ‐index/EQ‐VAS) at baseline and after 12 months using multivariable linear mixed models. AF symptom severity was assessed using the European Heart Rhythm Association classification and symptom severity score (EHRA score) categorizing patients with no/mild/severe/disabling AF‐related symptoms.ResultsA first episode of AF was detected in 261/2927 (8.9%) patients within 12 months after the index stroke and 227/2920 (7.8%) patients had AF and were anticoagulated at 12 months. HRQOL (measured by EQ‐index, n = 2495 patients) was higher in AF patients on OAC compared to AF patients without OAC at 12 months after stroke (mean difference: MD: –16.8, 95% CI: 5.6 to 28.0), and similar in AF patients under OAC compared with patients without AF (MD: 2.0, 95% CI: –2.2 to 6.3). AF‐related symptoms were negatively associated with HRQOL (measured by EQ‐index) indicating that stroke patients with AF‐related symptoms had a lower HRQOL compared to asymptomatic AF patients (mild vs. asymptomatic: MD: –9.0, 95% CI: –17.7 to –0.3; severe/disabling vs. asymptomatic: MD: –19.1, 95% CI: –34.7 to –3.4).DiscussionStroke patients with newly diagnosed AF are at risk of lower quality of life at 12 months, depending on OAC status and AF symptom severity.
Optimizing Sustainable Resource Efficiency: A Fuzzy‐Set Qualitative Comparative Analysis of Sustainable Practices in SMEs
Authors: Edu Abeeku S. , Ofosuhene Eunice , Agozie Divine Q. , Gyamfi Bright Akwasi , Asongu Simplice A. 
Published: January 2025

ABSTRACTThis study examines the influence of sustainability practices on resource efficiency in Ghana's small and medium‐sized enterprises (SMEs), utilizing a comprehensive framework that integrates environmental and social dimensions, enabling conditions, innovative practices, and technological advancements. Through a survey of 462 manufacturing SMEs, the research uncovers the complex interrelationships between sustainability practices and their impact on resource efficiency. The findings reveal four distinct sustainability pathways: the first underscores the critical importance of environmental dimensions and enabling conditions without robust social dimensions and innovative practices. The second highlights the significance of environmental and enabling conditions, even when technological innovativeness is limited. The third and fourth pathways emphasize the pivotal role of social dimensions and technological innovation, with innovative practices as supportive elements. Additionally, two typologies emerge, illustrating the integration of environmental and social dimensions with enabling conditions and the synergy between technological innovation, social dimensions, and innovative practices. This research advances the discourse on sustainability within SMEs, emphasizing the necessity for reduced resource consumption, conservation, efficient production, circular economy principles, and waste minimization. The findings suggest that achieving SDG 8.4 by 2030, which targets global resource efficiency, hinges on adopting these sustainable pathways with emphasis on Ghanaian SMEs. This study provides a deeper understanding of sustainability practices among developing economy SMEs, shedding light on the intricate dynamics that enhance resource management. It offers critical insights for policymakers and practitioners seeking to promote sustainability in local SMEs, particularly in Ghana, advocating for a holistic approach that considers the multifaceted nature of sustainability.
Empowering Engineering Students Through Artificial Intelligence (AI): Blended Human–AI Creative Ideation Processes With ChatGPT
Authors: Baltà‐Salvador Rosó , El‐Madafri Ismail , Brasó‐Vives Enric , Peña Marta 
Published: January 2025

ABSTRACTThe integration of artificial intelligence (AI) into education has the potential to revolutionize how students engage in academic activities and tasks. This research empirically analyses the influence of AI on creative ideation within educational settings to validate AI's role in enhancing human creativity since creative tasks, which inherently rely on human intuition, emotion and divergent thinking, may be stifled by systematic AI tools. The study explores whether ChatGPT can aid the creative process or inadvertently limit human creativity with a mixed‐method approach consisting of a randomized controlled experiment with third‐year engineering students in which a total of 728 ideas were obtained, along with a structured survey. The results revealed a predominantly positive perception towards AI‐assisted ideation; nevertheless, concerns were raised about AI's influence on creativity and innovation. While no significant differences in ideation outcomes were observed between the groups that used AI and those that did not, significant differences emerged between students who had prior experience with ChatGPT and those who did not. Qualitative insights provided a nuanced view of student experiences on blended human–AI ideation processes, shedding light on its advantages and disadvantages in educational practices. This research also underscores critical considerations and potential risks associated with the adoption of AI, suggesting that while AI has a place in educational settings, its role should be carefully calibrated to support rather than stifle student creativity and innovation. From the findings, the study provides practical recommendations and best practices regarding the integration of AI tools in education.
Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS
Authors: Koscielniak Ewa , Stegmaier Sabine , Ljungman Gustaf , Kazanowska Bernarda , Niggli Felix , Ladenstein Ruth , Blank Bernd , Hallmen Erika , Vokuhl Christian , Blattmann Claudia , Sparber‐Sauer Monika , Klingebiel Thomas 
Published: January 2025

AbstractBackgroundThe histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established. The objective of this analysis was to evaluate survival outcomes of patients with localized and metastatic aRMS and its association with fusion status and subtype (PAX3/7::FOXO1, FOXO1 break), and clinical prognostic factors.MethodsA total of 470 patients with aRMS ≤21 years of age enrolled in two CWS‐trials and two registries was eligible for the analysis.ResultsThe 5‐year event‐free survival (EFS) and overall survival (OS) rates for all patients with localized vs. metastatic tumors were: 56% and 65% vs. 18% and 22%, respectively. Of the 368 (78%) tumors tested, specific fusion was found in 330 (90%), considered “fusion positive” FP (PAX3::FOXO1 in 280, PAX7::FOXO1 in 49, FOXO1 break in 59 tumors). In patients with localized tumors, univariate analysis revealed that clinical group, tumor invasiveness (T1 vs.T2), regional lymph node involvement (N0 vs. N1) and FOXO1 fusion were significantly associated with EFS and OS, tumor size and PAX variant with OS only. In patients with metastatic aRMS, age, bone/marrow (B/BM) metastases, FOXO1 fusion and PAX variant were associated with EFS and OS, T status with OS only. Multivariate analysis identified PAX3::FOXO1 fusion as an independent adverse prognostic factor for EFS in patients with localized disease and for EFS and OS in patients with metastatic disease, B/BM metastases for EFS.ConclusionPAX3::FOXO1 fusion should replace FOXO1 fusion as an adverse prognostic factor in risk stratification. The prognostic relevance of PAX7::FOXO1‐positive and FOXO1 fusion negative aRMS, along with the clinical factors described in this report, allows further refinement of risk assessment of patients with localized and metastatic aRMS.
Cancer Incidence Among People With a Prior Hospital Record of Depression in Scotland, 1991–2019: A Cohort Study
Authors: Ashcroft Thulani , Fleetwood Kelly , Campbell Christine , Jackson Caroline A. 
Published: January 2025

ABSTRACTObjectiveCurrent evidence on the association between depression and cancer risk is conflicting, with little understanding of how associations vary by time period or sociodemographic factors. We aimed to compare cancer incidence in people with versus without a previous hospital admission record for depression, by sociodemographic factors and over time.MethodsWe conducted a cohort study using national linked data in Scotland from 1991 to 2019. We calculated sex‐stratified age standardised incidence rates for all cancers, lung, female breast, colorectal and prostate cancer, and used quasi‐Poisson regression models to obtain sex‐specific estimates of cancer incidence and relative risks of cancer in those with versus without a prior hospital admission record of depression.ResultsThere were 128,654 people with a hospital record of depression with 12,802 incident cancers and 847,656 cancers among those without depression. Age‐standardised cancer incidence rates were higher in both males and females with versus without depression. Depression was associated with a 20%–30% increased risk of all cancers combined, a difference that did not vary by sex, age or deprivation and persisted over three decades. Depression was associated with higher risks of lung (RR 1.79, 95% CI 1.70–1.88) and colorectal cancer (RR 1.12, 95% CI 1.05–1.19), but not breast or prostate cancer.ConclusionsWe identified an entrenched disparity in cancer incidence by depression status. Further research should identify underlying mechanisms and inform cancer prevention strategies in this vulnerable group. Meanwhile, health care professionals have a key role to play in optimising physical health care for people with depression.
FXYD3 Is Frequently Expressed in Pancreatic Ductal Adenocarcinoma but Does Not Predict Survival
Authors: Rasko Nathalie B. , Nahm Christopher B. , Turchini John , Teh Rachel , Rasmussen Helge , Byeon Sooin , Sahni Sumit , Samra Jaswinder S. , Gill Anthony J. , Mittal Anubhav 
Published: January 2025

ABSTRACTBackgroundFXYD3 is a Na/K‐ATPase modulator which is upregulated in pancreatic ductal adenocarcinoma (PDAC), but its prognostic role is unknown. This study evaluated FXYD3 expression in chemo‐naive patients with surgically‐resected PDAC at a single centre (1993–2014).MethodFXYD3 expression was assessed in tumour specimens using immunohistochemistry.Results145 of 180 PDAC tumour specimens were FXYD3‐immunopositive (80.5%). There was no difference in median overall survival between the FXYD3 negative (27.60 months) and positive groups (25.00 months) (log‐rank p = 0.9718). FXYD3 expression correlated positively with late‐stage disease (OR 3.041, 95% CI 1.190–7.455, p = 0.0175). There was no significant association with T stage, positive lymph nodes, perineural invasion, lymphovascular invasion or histological grade.ConclusionImmunohistochemical FXYD3 expression does not predict survival in chemo‐naive PDAC patients, but is associated with late‐stage disease. The high rate of FXYD3 overexpression warrants therapeutic evaluation.
DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications
Authors: Muletier Romane , Bourgne Céline , Guy Laurent , Dougé Aurore 
Published: January 2025

ABSTRACTBackgroundProstate cancer is a common cancer with a variable prognosis. Its management is currently guided by histological and biological markers such as the Gleason score and PSA. Developments in molecular biology are now making it possible to identify new targets for better classification of prostate cancer. Among emerging biomarker, DNA methylation, an epigenetic process, is increasingly being studied in carcinogenesis. Techniques for analyzing DNA methylation are constantly improving, and digital PCR now allows absolute methylation quantification with high sensitivity. These techniques can be performed on circulating tumor DNA.Materials & MethodsWe conducted a literature review of scientific articles addressing the topic of DNA methylation in prostate cancer.Results & discussionThis review summarizes the different genes whose methylation is involved in carcinogenesis and their clinical implications, both diagnostic and prognostic. Methylation monitoring could also be useful for the prediction of treatment response. However, most studies are retrospective, and prospective studies are needed to validate these data.
Baseline FIB‐4 May Be a Risk Factor of Recurrence After SBRT in Patients With HBV‐Related Small HCC
Authors: Zeng Zhan , Han Yifan , Li Wengang , Chen Hongyu , Lin Ning , Yu Yanyan , Xu Xiaoyuan 
Published: January 2025

ABSTRACTAimsExploring fibrosis index‐4 (FIB‐4)'s predictive value for HBV‐related hepatocellular carcinoma (HCC) in assessing recurrence following stereotactic body radiation therapy (SBRT) in patients with HBV‐related HCC.MethodsHBV‐related HCC patients who underwent SBRT were retrospectively enrolled from March 2012 to March 2020. Patients were divided into recurrence and non‐recurrence groups based on the HCC recurrence situation. Baseline data were collected from all patients before treatment and at 3 and 6 months after treatment, and FIB‐4 was calculated at the corresponding time points. Risk factors were selected using Cox regression. The FIB‐4 was stratified for survival analysis.ResultsOne hundred and fifty‐two patients were included. With a mean age of 53.5 years old, 94.1% of them had liver cirrhosis. The median recurrence‐free survival (RFS) time for recurrent patients was 17.5 months. The tumor response rate of SBRT was 94.8%. HCC recurrence rates at 12, 24, 36, 48, and 60 months were 19.7% (30/152), 38.2% (58/152), 48.0% (73/152), 52.0% (79/152), and 53.3% (81/152), respectively. Cox regression showed that baseline FIB‐4 (95% CI: 1.030 ~ 1.144, p = 0.002) and 3 tumor nodules (95% CI: 3.727 ~ 260.663, p = 0.002) are risk factors for HCC recurrence. Patients with a baseline FIB‐4 > 6.55 were at a higher risk of HCC recurrence than those with a baseline FIB‐4 < 6.55 (p < 0.001).ConclusionBaseline FIB‐4 is a risk factor for recurrence after SBRT in patients with HBV‐related HCC, and the predictive threshold for FIB‐4 is higher in patients with cirrhosis. For patients who received radiotherapy, postoperative FIB‐4 levels are elevated.
Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series
Authors: Wirta Erkki‐Ville , Elomaa Hanna , Mecklin Jukka‐Pekka , Seppälä Toni T. , Hyöty Marja , Böhm Jan , Ahtiainen Maarit , Väyrynen Juha P. 
Published: January 2025

ABSTRACTBackgroundImmune checkpoint inhibition therapies have provided remarkable results in numerous metastatic cancers, including mismatch repair–deficient (dMMR) colorectal cancer (CRC). To evaluate the potential for PD‐1 blockade therapy in a large population‐based cohort, we analyzed the tumor microenvironment and reviewed the clinical data and actualized treatment of all dMMR CRCs in Central Finland province between 2000 and 2015.Material and MethodsOf 1343 CRC patients, 171 dMMR tumors were identified through immunohistochemical screening. Histological tumor parameters were evaluated from hematoxylin‐ and eosin‐stained whole‐slide samples. CD3 and CD8 immunohistochemistry were analyzed to calculate T‐cell densities in the tumor center and invasive margin, and G‐cross function values to estimate cancer cell–T‐cell co‐localization. Multiplex immunohistochemistry was used to identify CD68+PD‐L1+ and CD3+PD‐1+ immune cells and PD‐L1 expression on tumor cells.ResultsA total of 35 (20%) patients with dMMR tumors were diagnosed as having a metastatic disease. Twelve patients (34%) were fit enough to be offered oncological treatments at the onset of non‐curable metastatic disease. High proportions of necrosis and stroma were common in metastatic tumors and were associated with worse survival. Crohn's‐like reaction, T‐cell proximity score, and CD68+/PD‐L1+ on the tumor center and invasive margin were independent prognostic immune factors.ConclusionAs dMMR CRC patients are generally older, with often significant comorbidities, only a limited portion of patients with metastatic dMMR tumors ended up in oncological treatments. Many of the metastatic tumors presented features that may impair response to PD‐1 blockade therapy.