bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM
Authors: Petronek Michael S. , Monga Varun , Bodeker Kellie L. , Kwofie Michael , Lee Chu-Yu , Mapuskar Kranti A. , Stolwijk Jeffrey M. , Zaher Amira , Wagner Brett A. , Smith Mark C. , Vollstedt Sandy , Brown Heather , Chandler Meghan L. , Lorack Amanda C. , Wulfekuhle Jared S. , Sarkaria Jann N. , Flynn Ryan T. , Greenlee Jeremy D.W. , Howard Matthew A. , Smith Brian J. , Jones Karra A. , Buettner Garry R. , Cullen Joseph J. , St-Aubin Joel , Buatti John M. , Magnotta Vincent A. , Spitz Douglas R. , Allen Bryan G. 
Published: September 2023

Abstract

Purpose:
Pharmacologic ascorbate (P-AscH−) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH− with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH− in humans.

Patients and Methods:
The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan–Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker.

Results:
Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7–26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation &lt; 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P &lt; 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems.

Conclusions:
P-AscH− combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes.
See related commentary by Nabavizadeh and Bagley, p. 255
Comparative Genomic Analysis and Clinical Outcomes ofBRAF-mutated Advanced Biliary Tract Cancers
Authors: Tang Tin-Yun , Nichetti Federico , Kaplan Ben , Lonardi Sara , Pietrantonio Filippo , Salvatore Lisa , Vivaldi Caterina , Rimassa Lorenza , de Braud Filippo , Rizzato Mario Domenico , Pavlick Dean , Chu Randy , Danner De Armas Anaemy , Sharaf Radwa , Sokol Ethan , Rodon Ahnert Jordi , Ross Jeffrey S. , Javle Milind , Niger Monica 
Published: September 2023

AbstractPurpose:BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic landscape of BRAF class I, II, and III mutations in the intrahepatic cholangiocarcinoma (iCCA) subgroup of BTC.Experimental Design:We analyzed two nonoverlapping cohorts. We examined the genomic landscape of BRAF-mutated iCCA in a “genomic cohort” [187 class I, 82 class II, 113 class III BRAF mutants and 8,026 wildtype (WT)]. We also analyzed median progression-free survival (PFS) and overall survival (OS) on first-line chemotherapy in a separate multi-institutional “clinical cohort” of patients with BTC (including iCCA and extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer; 41 class I, 32 class II+III BRAF mutants and 1,042 WT).Results:In the entire BTC clinical cohort, the median PFS was shorter for class I [HR, 2.11 (P &lt; 0.001)] and class II+III [HR, 1.72 (P = 0.007)] as compared with BRAF WT. OS was also shorter in class I [HR, 2.04 (P = 0.011)] and class II+III [HR, 1.86 (P = 0.002)] as compared with BRAF WT. In the iCCA subgroup, class I alterations were mutually exclusive with FGFR2, IDH1/2, ERBB2, and KRAS mutations. Class II+III mutations appear to be mutually exclusive with FGFR2 and KRAS.Conclusions:In BTC, all classes of BRAF mutations are associated with a worse prognosis. BRAF mutations occur in 5% of iCCA subgroup and may be mutually exclusive with other targetable mutations.
An Eye-Tracking Study on Viewer Compliance with the Gestalt Closure Principle: Analyzing the Impact of Gap Size and the Golden Ratio
Authors: Hu Xinran 
Published: September 2023

Abstract
The Gestalt principle of closure refers to brain activity filling in missing information to perceive objects as complete, even when partially hidden. Designers leverage this principle to imply shapes without explicitly showing them. However, evaluating viewer responses poses challenges. The author conducted a comprehensive eye-tracking experiment to determine when viewers mentally completed a gap in a circle and explored the potential influence of the golden ratio on the closure principle. The golden ratio, approximately 1.618, is associated with visual harmony and is used in art and design to create pleasing proportions. Findings showed that viewers tend to mentally close gaps up to 135° but avoid closure beyond 150°. This suggests the golden ratio’s relevance in applying the closure principle to design.
Testing Causal Effects of Empathy on Children’s Prosociality in Politeness Dilemmas - An Intervention Study
Authors: Thiede Noemi , Stengelin Roman , Seibold Astrid , Haun Daniel B. M. 
Published: September 2023

Abstract
Empathy is commonly considered a driver of prosociality in child ontogeny, but causal assumptions regarding this effect mostly rely on correlational research designs. Here, 96 urban German children (5–8 years; 48 girls; predominantly White; from mid-to-high socioeconomic backgrounds) participated in an empathy intervention or a control condition before prosocial behaviors (polite lie-telling: rating the drawing as good; prosocial encouragement: utterances interpreted as cheering up the artist) were assessed in an art-rating task. Contrasting children’s empathy at baseline with their empathy after the intervention indicated promoted empathy compared to the control group. Despite the intervention’s effect on children’s empathy, there were no simultaneous changes in prosocial behaviors. At the same time, children’s empathy at baseline was associated with their prosocial encouragement. These results indicate conceptual associations between children’s empathy and prosociality. However, they do not support strict causal claims regarding this association in middle childhood. Further applications of the novel short-time intervention to address causal effects of empathy on prosociality and other developmental outcomes are discussed.
Everything is Infinite: Children’s Beliefs About Endless Space, Time, and Number
Authors: Sullivan Jessica , Cramer-Benjamin Sophie , Alvarez Joseph , Barner David 
Published: September 2023

Abstract
How do children form beliefs about the infinity of space, time, and number? We asked whether children held similar beliefs about infinity across domains, and whether beliefs in infinity for domains like space and time might be scaffolded upon numerical knowledge (e.g., knowledge successors within the count list). To test these questions, 112 U.S. children (aged 4;0–7;11) completed an interview regarding their beliefs about infinite space, time, and number. We also measured their knowledge of counting, and other factors that might impact performance on linguistic assessments of infinity belief (e.g., working memory, ability to respond to hypothetical questions). We found that beliefs about infinity were very high across all three domains, suggesting that infinity beliefs may arise early in development for space, time, and number. Second, we found that—across all three domains—children were more likely to believe that it is always possible to add a unit than to believe that the domain is endless. Finally, we found that understanding the rules underlying counting predicted children’s belief that it is always possible to add 1 to any number, but did not predict any of the other elements of infinity belief.
Kanon und Klassiker der Frühen Neuzeit?
Authors: Bach Oliver 
Published: September 2023

Abstract
The aim of this article is to outline several aspects of a canon of early modern German literature as they had been discussed by a volume Klassiker der Frühen Neuzeit (ed. Regina Toepfer) in 2022. In the light of recent criticism of any conception of canon as an outcome of hegemonial thinking as well as considering the increasing disregard of early modern literature even in universities, it is foremost the Early Modern Literature Studies who are urged to discuss the question of whether there are sufficient reasons for upholding a literary canon at least to a certain degree and whether texts of the early modern period can or must be part of such a canon.
Religious School Education in Brazilian Supreme Federal Court Voting
Authors: Montero Paula 
Published: September 2023

Abstract
This article examines the arguments made by the eleven Justices of the Supreme Federal Court who, in 2017, decided on the constitutionality of offering confessional education in public schools. We will explore how long-term disputed ethical and legal values are rearticulated in these votes concerning the notion of belief, almost 40 years after defining Religious Education as a fundamental human right by the Constitution. It is not a matter of harking back to the topic of secularism, as a social process or as a legal norm or political doctrine. The discursive analysis of the ministers’ votes formulations aims, on the contrary, to unveil the different religious constructions implied in their uses of the terms religion and rights and to understand how they operate when putting forward an idea of citizenship and/or the nation. The aim is to clarify, from this systematic examination of the votes, the configuration of common legal sense when issuing value judgments about religion and its protection. Therefore, our primary focus will be to circumscribe what counts as religion in these legal narratives.
Historical Analogies
Authors: Keulen Sjoerd 
Published: September 2023

Abstract
Historical analogies are amongst the most important tools in applied history. On the one hand, they are applauded as decision-making tools, on the other hand they are criticised by the historical discipline. In the discipline of applied history, historical analogies remain deconceptualised. This article defines and classifies the various forms of historical analogy. Classification is based on people and events, on how history is learned and on the depth of the lessons learned from historical analogies. The functions of historical analogies in policymaking and decision-making are discussed and clarified by means of historical examples. The article then reflects on the limitations of historical analogies and, to conclude, suggests ways to encourage the correct use of historical analogies.
Nadir Shah Afshar’s Policy towards the Armenian Community
Authors: Gozalova Nigar R. 
Published: September 2023

Abstract
Based on the primary sources, the article examined the position and status of the Christian population during the reign of Nadir Shah Afshar (1688–1747). Special attention is paid to the question of privileges and patronage of the Armenian community. it is argued that the supportive policy of Nadir Shah towards representatives of Christian churches and monasteries was expressed in numerous decrees and firmans of the Afshar ruler. Thanks to the patronage of Nadir Shah, the possessions of the diocese of Uch-Kilsa (Echmiadzin) were exempted from taxes; they were allowed not only to rebuild churches, but even to build new ones. Nadir Shah also patronized the resettlement of the Armenian population from the neighboring Ottoman Empire, etc. An analysis of the sources helps to examine religious freedom in the Afshar’s state, including its tax policy in relation to Christian churches and monasteries.
The Emergence of a New Identity
Authors: Yengimolki Ahmad 
Published: September 2023

Abstract
This present study aims to challenge simplistic views of division and boundaries between Muslims and Christians. It delves into the cultural and artistic relationship between the Safavid ruling elite and the newly arrived Armenians in seventeenth-century Isfahan. The primary goal is to understand how the Armenian population merged with the predominantly Muslim community of Isfahan. An insightful perspective is gained by examining the Armenian architecture in Isfahan, where Armenians adapted and appropriated local architectural elements, creating a sense of belonging and shared identity. To gain a comprehensive understanding, the study delves into the wider cultural and political context of Isfahan during that time, drawing from a diverse array of European, Persian, and Armenian sources. By adopting this inclusive approach, the study explores the complex interplay of Christian and Muslim, as well as Safavid and Armenian elements within Isfahani society, thereby shedding light on the multifaceted identities at play.
Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups
Authors: Shah Urvi A. , Moshier Erin , Derkach Andriy , Huang Yuanhui , Mailankody Sham , Tan Carlyn R. , Maclachlan Kylee , Hultcrantz Malin , Korde Neha , Hassoun Hani , Thibaud Santiago , Sanchez Larysa , Rodriguez Cesar , Richard Shambavi , Richter Joshua , Rossi Adriana , Cho Hearn Jay , Lesokhin Alexander , Chari Ajai , Usmani Saad Z. , Jagannath Sundar , Parekh Samir , Gallagher Emily J. 
Published: September 2023

Abstract
Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (hazard ratio, 1.27; 95% confidence interval, 1.11-1.47; P &lt; .001). This appeared to be driven by a marked difference in OS between White patients with and without DM but not in Black patients. In contrast, obesity was associated with better OS in Black patients but not in White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised nonobese diabetic (Rag1−/−/muscle creatinine kinase promoter expression of a human IGF1R [M] with a lysine [K] to arginine [R] point mutation) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1−/−/MKR mice and grew more rapidly in the Rag1−/−/MKR mice compared with in controls. Western blot analysis found that MM1.S xenografts from Rag1−/−/MKR mice had higher phosphorylated S6 ribosomal protein (Ser235/236) levels, indicating greater activation of the mammalian target of rapamycin pathway. Our study is, to our knowledge, the first to evaluate racial differences in DM prevalence and survival in MM, as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients; and to improve survival in MM, DM management cannot be ignored.
A large-scale targeted proteomics of serum and tissue shows the utility of classifying high grade and low grade meningioma tumors
Authors: Halder Ankit , Biswas Deeptarup , Chauhan Aparna , Saha Adrita , Auromahima Shreeman , Yadav Deeksha , Nissa Mehar Un , Iyer Gayatri , Parihari Shashwati , Sharma Gautam , Epari Sridhar , Shetty Prakash , Moiyadi Aliasgar , Ball Graham Roy , Srivastava Sanjeeva 
Published: September 2023

Abstract
Background
Meningiomas are the most prevalent primary brain tumors. Due to their increasing burden on healthcare, meningiomas have become a pivot of translational research globally. Despite many studies in the field of discovery proteomics, the identification of grade-specific markers for meningioma is still a paradox and requires thorough investigation. The potential of the reported markers in different studies needs further verification in large and independent sample cohorts to identify the best set of markers with a better clinical perspective.

Methods
A total of 53 fresh frozen tumor tissue and 51 serum samples were acquired from meningioma patients respectively along with healthy controls, to validate the prospect of reported differentially expressed proteins and claimed markers of Meningioma mined from numerous manuscripts and knowledgebases. A small subset of Glioma/Glioblastoma samples were also included to investigate inter-tumor segregation. Furthermore, a simple Machine Learning (ML) based analysis was performed to evaluate the classification accuracy of the list of proteins.

Results
A list of 15 proteins from tissue and 12 proteins from serum were found to be the best segregator using a feature selection-based machine learning strategy with an accuracy of around 80% in predicting low grade (WHO grade I) and high grade (WHO grade II and WHO grade III) meningiomas. In addition, the discriminant analysis could also unveil the complexity of meningioma grading from a segregation pattern, which leads to the understanding of transition phases between the grades.

Conclusions
The identified list of validated markers could play an instrumental role in the classification of meningioma as well as provide novel clinical perspectives in regard to prognosis and therapeutic targets.
Work-related outcomes in individuals with and without lower limb osteoarthritis: an online survey
Authors: Alyousef Yousef S. , Johnston Venerina , Smith Michelle D. 
Published: September 2023

Abstract
Objective
While osteoarthritis (OA) affects people who are still participating in the workforce, there is limited data about the impact of OA on work. The aim of this study was to compare work participation in individuals with and without lower limb OA.

Methods
This cross-sectional study included workers with (n = 124) and without (n = 106) lower limb OA. Work participation was assessed as work status (full/part time work), work ability (Work Ability Index (WAI)), absenteeism and presenteeism (World Health Organization’s Health and Work Performance Questionnaire (WHO-HPQ)), and perceived difficulties meeting work demands (Work Role Functioning Questionnaire (WRFQ)). The data were analyzed using an analysis of covariance with age, body mass index and physical job demands included as covariates.

Results
Work ability was poorer (p < 0.001) and loss of work performance (p < 0.001) was higher among workers with OA than healthy controls. There was no statistical difference in absenteeism or overall ability to meet work demands between participants with and without lower limb OA. However, workers with lower limb OA had more difficulty with work scheduling demands (p = 0.05) and physical demands (p = 0.003) than healthy workers.

Conclusion
Lower limb OA was associated with poorer work ability, loss of work performance and difficulty in meeting physical and work scheduling demands. Health professionals and employers should consider these challenges when managing individuals with lower limb OA and supporting them to remain in the workforce.
Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism
Authors: Yoon Dongwon , Jeong Han Eol , Park Sohee , You Seng Chan , Bang Soo-Mee , Shin Ju-Young 
Published: September 2023

Abstract
Background
Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).

Methods
Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel–Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.

Results
Compared to trial populations, real-world study populations were older (range: 63–69 years [RWE] vs. 54–59 years [RCT]), with more females (55–60.5% vs. 39–48.3%) and had a higher prevalence of active cancer (4.2–15.4% vs. 2.5–9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70–0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37–0.96; Hokusai-VTE: 0.49, 0.31–0.78; EINSTEIN-DVT: 0.54, 0.33–0.89; EINSTEIN-PE: 0.50, 0.34–0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.

Conclusions
This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.
Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress
Authors: Shi Yu , Wu Wen 
Published: September 2023

AbstractBackgroundChronic pain conditions impose significant burdens worldwide. Pharmacological treatments like opioids have limitations. Non-invasive non-pharmacological therapies (NINPT) encompass diverse interventions including physical, psychological, complementary and alternative approaches, and other innovative techniques that provide analgesic options for chronic pain without medications.Main bodyThis review elucidates the mechanisms of major NINPT modalities and synthesizes evidence for their clinical potential across chronic pain populations. NINPT leverages peripheral, spinal, and supraspinal mechanisms to restore normal pain processing and limit central sensitization. However, heterogeneity in treatment protocols and individual responses warrants optimization through precision medicine approaches.ConclusionFuture adoption of NINPT requires addressing limitations in standardization and accessibility as well as synergistic combination with emerging therapies. Overall, this review highlights the promise of NINPT as a valuable complementary option ready for integration into contemporary pain medicine paradigms to improve patient care and outcomes.