bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor‐mutated non‐small‐cell lung cancer patients with brain metastases
Authors: Liang Shimeng , Liu Xiaoqin , Liu Jia , Na Feifei , Lai Jialu , Du Leiya , Gong Youling , Zhu Jiang , Huang Meijuan , Zhou Xiaojuan , Xu Yong , Zhou Lin 
Published: April 2023

AbstractBackgroundFor epidermal growth factor receptor (EGFR)‐mutated non‐small‐cell lung cancer (NSCLC) patients with limited brain metastases (BMs), who eventually receive both tyrosine kinase inhibitors (TKIs) treatment and brain radiotherapy, the optimal timing of radiotherapy is not clear. The present retrospective analysis aimed to partly solve this problem.MethodsIn total 84 EGFR‐mutated NSCLC patients with limited BMs, who received both TKI treatment and brain hypofractionated stereotactic radiotherapy (HSRT), were enrolled. Patients were divided into three groups based on whether the HSRT was administrated 2 weeks before or after the beginning of TKI treatment (upfront HSRT), when intracranial lesions stabilized after TKI treatment (consolidative HSRT), or when the intracranial disease progressed after TKI treatment (salvage HSRT). The clinical efficacy and toxicities were evaluated.ResultsThe median intracranial progression‐free survival (iPFS) and overall PFS calculated from the initiation of HSRT (iPFS1 and PFS1) of all patients were 17.5 and 13.1 months, respectively. The median iPFS and PFS calculated from the initiation of TKI treatment (iPFS2 and PFS2) of all patients were 24.1 and 18.4 months, respectively. Compared to consolidative and salvage HSRT, upfront HSRT improved iPFS1 (not reached vs. 17.5 months vs. 11.0 months,p < 0.001) and PFS1 (18.4 months vs. 9.1 months vs. 7.9 months,p < 0.001), and reduced the initial intracranial failure rate (12.5% vs. 48.1% vs. 56%,p < 0.001). However, there were no significant differences between the three groups for iPFS2, PFS2, and overall survival. Hepatic metastases and diagnosis‐specific Graded Prognostic Assessment (ds‐GPA) at 2–3 were poor prognostic factors.ConclusionFor patients who receive both TKI treatment and brain HSRT, the timing of HSRT does not seem to influence the eventual therapeutic effect. Further validation in prospective clinical studies is needed.
Evaluating whether KRAS/BRAF mutation status, anaemia and obstruction are associated with recurrence and mortality in non‐metastatic colorectal cancer
Authors: Juszczyk Karolina , Afzal Mohamed Zaafer , Ganguly Timothy , Kelly Thu‐Lan , Zeelie Robyn , Murphy Elizabeth Mary Ann 
Published: April 2023

AbstractBackgroundKRAS and BRAF testing is currently recommended in metastatic colorectal cancer. There is evidence that KRAS and BRAF mutation status may act as a prognostic biomarker in patients with non‐metastatic colorectal cancer. Data is limited on whether KRAS and BRAF mutation status impacts recurrence and mortality in patients with non‐metastatic colorectal cancer.MethodsA retrospective cohort study was conducted in a tertiary hospital examining outcomes in patients who had KRAS and BRAF testing for colorectal cancer in 2017. Primary outcomes were all‐cause mortality and recurrence. Multivariable analysis for both outcomes, used cause specific Cox proportional hazards models with KRAS/BRAF status as exposure. For time to recurrence, a sensitivity analysis was performed with a weighted Fine‐Grey model with death as a competing risk.ResultsKRAS mutation status was not associated with all‐cause mortality (average Hazard Ratio (aHR) = 0.78, 95% CI 0.28–2.21) or recurrence (aHR = 0.96, 95% CI 0.32–2.86). BRAF mutation status was not associated with time to all‐cause mortality (aHR = 3.06, 95% CI 0.79–11.8) or recurrence (aHR = 0.94, 95% CI 0.13–6.57). Increased risk of recurrence was significantly associated with large bowel obstruction (aHR = 2.73, 95% CI 1.16–6.45) and anaemia (aHR = 3.39, 95% CI 1.06–10.8) at time of surgery.ConclusionThis study did not demonstrate an association between KRAS and BRAF mutations and all‐cause mortality or recurrence. A significantly increased risk of cancer recurrence was found in patients with large bowel obstruction and in patients with anaemia at time of surgery. Anaemia should be promptly investigated and corrected prior to colorectal cancer surgery.
Saikosaponin A alleviates glycolysis of breast cancer cells through repression of Akt/STAT3 pathway
Authors: Zhang Yan , Dai Kun , Xu Dedong , Fan Hua , Ji Nannan , Wang Di , Zhao Yunlu , Liu Rui 
Published: April 2023

AbstractSaikosaponin A (SSA) has been revealed to have anti‐breast cancer (BC) effect. However, the association between SSA and BC glycolysis is obscure. We want to probe the function and mechanism of SSA on BC glycolysis. Kaplan–Meier plotter revealed the relationship between STAT3 and the survival curve of BC. The protein kinase B (Akt)/signal transducer and activator of transcription 3 (STAT3) pathway and the viability in cells treated with or without 0, 5, 10, and 15 μM SSA were assessed by Western blot and cell counting kit‐8. The biological behaviors, lactate, and ATP contents, glucose uptake, and Akt/STAT3 pathway‐related markers in BC cells treated with colivelin or SSA were evaluated using cell function experiments, kit, and Western blot. Then, the impacts of colivelin and SSA on BC cells were tested again. The overexpressions of p‐STAT3 and p‐Akt in BC cells were weakened by 5, 10, and 15 μM SSA. Colivelin boosted the BC cell viability and proliferation and impeded apoptosis, while SSA did the opposite. Meanwhile, colivelin intensified lactate and ATP contents, glucose uptake, and Akt/STAT3 pathway‐related markers level in BC cells, while SSA was the opposite. The modulation of SSA on the biological behavior, lactate and ATP productions, glucose uptake, and Akt/STAT3 pathway was rescued by colivelin. Our research unveiled new insights into SSA as a valuable candidate therapeutic agent for weakening glycolysis, and protruded the Akt/STAT3 pathway as a latent molecular target for SSA and glycolysis modulation.
Effects of radioactive iodine on clonal hematopoiesis in patients with thyroid cancer: A prospective study
Authors: Boucai Laura , Ptashkin Ryan N. , Levine Ross L. , Fagin James A. 
Published: April 2023

AbstractObjectiveExposure to therapeutic radioactive iodine (RAI) is associated with an increased relative risk of myeloid malignancies. Clonal hematopoiesis (CH) is a precursor state that can be detected in blood of healthy individuals decades before overt development of leukemia. We prospective studied the effects of RAI on CH.DesignProspective cohort study.Patients and MeasurementsWe examined the effect of RAI on CH in 20 patients exposed to RAI for thyroid carcinoma and 20 age‐matched unexposed controls. CH status was determined at baseline, 6, 12, 18 and 24 months. We also examined the effect of CH on structural progression of disease.ResultsNo CH mutations were observed in the patient population that were not present at baseline. Using a variant allelic fraction (VAF) of 2% to define CH, 6/20 older patients (55−80 years old) had CH compared to 2/20 younger patients (20−40 years old) (p = 0.11). Six patients exposed to RAI had CH compared to two patients not exposed to RAI (30% vs. 10%, p = 0.11). There was no significant difference in CH VAF increase in patients treated with RAI compared to untreated age‐matched controls (3.8% vs. 1.2%, p = 0.2). CH was significantly associated with somatic BRAFV600E mutations and with worse progression‐free survival in the overall cohort as well as among BRAFV600E‐mutant tumors.ConclusionsThere was no increase in CH in patients treated with RAI over a 2‐year follow‐up period. Larger studies with longer follow‐up periods are needed to investigate the association between RAI and clonal dynamics. The presence of CH is associated with worse structural progression in both BRAFV600E‐mutant and wild‐type thyroid cancers.
Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta‐analysis
Authors: Wei Naili , Liu Haoxin , Ye Wenrui , Xu Shengliang , Lu Changhao , Dai Anxiang , Hou Ting , Zeng Xin , Wu Jie , Chen Jian 
Published: April 2023

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized.MethodsThis article performed a network meta‐analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N‐methyl‐d‐aspartate (NMDA), anti‐amyloid‐beta (Aβ), and some new targeted therapeutic drugs.ResultsA total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta‐analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22–1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS‐cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%).ConclusionCompared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic.
Determination of vc and mating types of Cryphonectria parasitica isolates by multiplex PCR and their genetic diversity in 13 chestnut‐growing provinces of Turkey
Authors: Çakar Deniz , Özer Göksel , Akıllı Şimşek Seçil , Maden Salih 
Published: April 2023

AbstractVegetative compatibility (vc) and mating types and genetic diversity of Cryphonectria parasitica isolates were determined using 183 isolates obtained from 215 infected chestnut trees growing in 13 provinces of Turkey. Based on the cultural aspects, 143 of these isolates were evaluated as virulent whereas the remaining 40 isolates were hypovirulent. When vc types of 183 isolates were classically differentiated, 135 of them matched to EU‐1 (82.3%), 29 of them to EU‐12 (17.6%) vc type, whereas 19 of them did not match to the two. When molecular vic markers were used, all the isolates were assigned to two EU vc types; 149 to EU‐1 (81.4%) and 34 (18.5%) to EU‐12. Of the majority of the isolates, 134 (73.2%) had mating‐type MAT‐1, while 44 (24%) isolates had MAT‐2 and 5 (2.8%) isolates had both mating types. The population analysis based on two DNA marker systems, Inter‐Primer Binding Site and Start Codon Targeted Polymorphism, showed no intraspecific genetic variation among the C. parasitica isolates. The prevalence of two dominant vc types revealed by this study shows that biological control with hypovirulent EU‐1 and EU‐12 isolates will be significant for the country. The results might be helpful to chestnut breeders carrying out resistance breeding studies to manage this disease based on hypovirulence attributed to Cryphonectria hypovirus 1.
Impact of newly diagnosed extramedullary myeloma on outcome after first autograft followed by maintenance: A CMWP‐EBMT study
Authors: Gagelmann Nico , Eikema Dirk‐Jan , Koster Linda , Netelenbos Tanja , McDonald Andrew , Stoppa Anne‐Marie , Fenk Roland , Anagnostopoulos Achilles , van Gorkom Gwendolyn , Deconinck Eric , Bulabois Claude‐Eric , Delforge Michel , Bunjes Donald , Arcese William , Reményi Péter , Itälä‐Remes Maija , Thurner Lorenz , Bolaman Ali Zahit , Nabil Yafour , Lund Johan , Labussière‐Wallet Hélène , Hayden Patrick J. , Beksac Meral , Schönland Stefan , Yakoub‐Agha Ibrahim 
Published: April 2023

AbstractBackgroundNo adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy.MethodsWe identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib.ResultsThe median follow‐up from maintenance start was 44 months. Three‐year progression‐free survival (PFS) was 52% (48%–57%) for no EMD, 56% (44%–69%) for paraskeletal involvement, and 45% (22%–68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three‐year overall survival (OS) was 81% (77%–84%), 88% (80%–96%), and 68% (47%–89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD.ConclusionLenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start.
Does character's gender matter in inspirational brand story? Exploring the moderating effect of gender role conformity
Authors: Chen Xiang , Wang Cheng Lu , Zhou Liying 
Published: April 2023

AbstractInspirational brand story is a widely used marketing strategy in brand building. However, few empirical studies have investigated the underlying mechanism and boundary conditions of a successful brand story strategy. The current study examined the influence of lead character's gender in inspirational brand story on consumer–brand identification based on the social identity theory, benevolent sexism, and gender schema theory. Results from two experiments demonstrated that the gender of inspirational brand stories has an impact on consumer brand identity through the mediation effect of sympathy. Compared with a male character, a female character elicits viewers' sympathy, which results in high brand identification. Such a gender effect is stronger when there is a high level of perceived gender role conformity. Theoretical and managerial implications are discussed.
Theorising moderation in the configurational approach: A guide for identifying and interpreting moderating influences in QCA
Authors: Ma Teng , Cheng Yue , Guan Zhengzhi , Li Boying , Hou Fangfang , Lim Eric Tze Kuan 
Published: April 2023

AbstractGiven the multifaceted nature of digital phenomena, theorising has shifted from the correlational view toward the configurational approach, which embraces equifinality and seeks to identify conjunctural causal conditions culminating in a given outcome. Despite growing scholarly interest in the configurational approach, little is known about how moderation functions in conjunctural causation. Although there is a growing urgency for elucidating the boundary conditions of conjunctural causation to bolster the precision of theoretical explanations, a systematic approach to theorising, identifying, and interpreting moderation in configurational theories is missing. To bridge this knowledge gap, we first establish the theoretical grounding for moderation in the configurational approach. We then articulate the theoretical mechanism underlying how the interdependence of causal factors in a causal recipe is altered by the presence of a moderator. We also offer guidance on how to validate and interpret moderation in the configurational approach based on Qualitative Comparative Analysis (QCA). We conduct an illustrative study in the context of technostress to showcase the utility of our proposed guidelines and their value in aiding theory development. Our study hence contributes to extant literature by attesting to the significance of moderation in the configurational approach and offering recommendations for theorising such moderations. Insights from this study can be harnessed to guide future theory development by identifying and validating moderated configurational relationships, which in turn can further enhance our understanding of nuances in multifaceted digital phenomena.
The persistence and consequences of share repurchases
Authors: El Ghoul Sadok , Guedhami Omrane , Kim Hyunseok , Suh Jungwon 
Published: April 2023

AbstractFirms use cash flow primarily to finance increasingly persistent share repurchases. Such internal financing is accompanied by gradual increases in retained earnings in the capital structure, and results in high (low) repurchase (investment) sensitivity to cash flow. These effects are particularly pronounced among financially mature firms. The repurchase–cash flow sensitivity of US firms has increased steadily in recent decades, with steeper increases for financially mature firms. We find that repurchases are not generally associated with underinvestment. Moreover, a nontrivial number of firms would have depleted their retained earnings if they paid dividends instead of repurchased shares.
Does question order matter on online math assessments? A big data analysis of undergraduate mathematics final exams
Authors: Gruss Richard , Clemons Josh 
Published: April 2023

AbstractBackgroundThe sudden growth in online instruction due to COVID‐19 restrictions has given renewed urgency to questions about remote learning that have remained unresolved. Web‐based assessment software provides instructors an array of options for varying testing parameters, but the pedagogical impacts of some of these variations has yet to be examined.ObjectivesThe current study examines whether question order affects student performance on online college math assessments. Drawing on the literature of testing and math anxiety, we hypothesized that difficult questions near the beginning of an assessment would have a destructive effect on student confidence, which would in turn have a deleterious effect on their performance.MethodsWe employed an observational ‘big data’ methodology, analysing 23,468 final exams completed by students in 10 different courses over eight semesters at a Math Emporium in a large technical university in the eastern United States. Students were freshmen and sophomores enrolled in non‐engineering math courses. We regressed the final score on the difficulty level of the first and second questions, controlling for several other factors.Results and ConclusionsWe found that several factors—day of the week, amount of time before the deadline, number of minutes spent on the exam—have more of an impact on score than question order. This pattern was consistent across sexes.TakeawaysOur findings contradict some previous studies, which have found that difficult early questions degrade student performance, and that this affect is more pronounced in females. This work enriches our understanding of how students respond to online assessment.
Capturing cognitive load management during authentic virtual reality flight training with behavioural and physiological indicators
Authors: Lämsä Joni , Mannonen Joonas , Tuhkala Ari , Heilala Ville , Helovuo Arto , Tynkkynen Ilkka , Lampi Emilia , Sipiläinen Katriina , Kärkkäinen Tommi , Hämäläinen Raija 
Published: April 2023

AbstractBackgroundCognitive load (CL) management is essential in safety‐critical fields so that professionals can monitor and control their cognitive resources efficiently to perform and solve scenarios in a timely and safe manner, even in complex and unexpected circumstances. Thus, cognitive load theory (CLT) can be used to design virtual reality (VR) training programmes for professional learning in these fields.ObjectivesWe studied CL management performance through behavioural indicators in authentic VR flight training and explored if and to what extent physiological data was associated with CL management performance.MethodsThe expert (n = 8) and novice pilots (n = 6) performed three approach and landing scenarios with increasing element interactivity. We used video recordings of the training to assess CL management performance based on the behavioural indicators. Then, we used the heart rate (HR) and heart rate variability (HRV) data to study the associations between the physiological data and CL management performance.Results and ConclusionsThe pilots performed effectively in CL management. The experience of the pilots did not remarkably explain the variation in CL management performance. The scenario with the highest element interactivity and an increase in the very low‐frequency band of HRV were associated with decreased performance in CL management.TakeawaysOur study sheds light on the association between physiological indicators and CL management performance, which has traditionally been assessed with behavioural indicators in professional learning in safety‐critical fields. Thus, physiological measurements can be used to supplement the assessment of CL management performance, as relying solely on behavioural indicators can be time consuming.
Comparison of different skin care regimens in patients with moderate to severe atopic dermatitis receiving systemic treatment: A randomized controlled trial
Authors: Magnolo Nina , Jaenicke Thomas , Tsianakas Athanasios , Czech Wolfgang , Thaçi Diamant , Pinter Andreas , Kerob Delphine , Salah Samir , Luger Thomas A. 
Published: April 2023

AbstractBackgroundModerate to severe AD can be successfully managed by systemic treatments. Current guidelines also recommend emollients or emollients ‘plus’ and eudermic cleansers for all AD patients to improve the skin barrier and provide anti‐irritant and anti‐pruritic effects.ObjectivesTo investigate the efficacy of skin care (in addition to systemic treatment) with an Emollient ‘plus’ balm designed to improve the skin barrier and skin microbiome plus a corresponding syndet compared to usual commercial emollients and cleansers.MethodsIn a randomized controlled multicenter study, patients with moderate to severe AD (Severity scoring of atopic dermatitis [SCORAD] score ≥ 40) receiving systemic treatment (cyclosporin A, dupilumab or a Janus kinase inhibitor) were randomized 1:1 to apply twice daily for 10 weeks Emollient ‘plus’ after pre‐cleaning with the syndet (Emollient ‘plus’ group) or to continue with their usual emollient and cleanser (Control group). Assessments included SCORAD, pruritus on a Visual Analog Scale, Dermatology quality of life questionnaire (DLQI), efficacy and tolerance questionnaires.ResultsIncluded were 57 patients with mean age of 38 years (range 19–70 years). The mean amount of emollient used after 10 weeks was 447.3 g (range 29–1099 g) and 613.2 g (range 97–2565 g) for the Emollient ‘plus’ versus the Control, respectively (p = 0.0277). After 10 weeks, subjects in the Emollient ‘plus’ had a significantly greater reduction in current pruritus (p = 0.0277) and a greater reduction in some DLQI items compared to the Control group.ConclusionsIn patients with moderate to severe AD receiving systemic treatment, the Emollient ‘plus’ regimen significantly improved pruritus and quality of life items compared to the control, while using 23% less product over a 10‐week period. These results stress the importance of daily use of emollients, especially emollients ‘plus’ to improve signs, symptoms and quality of life in patients with AD.