bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma
Authors: de la Fuente Macarena I , Touat Mehdi , van den Bent Martin J , Preusser Matthias , Peters Katherine B , Young Robert J , Huang Raymond Y , Ellingson Benjamin M , Capper David , Phillips Joanna J , Halasz Lia M , Shih Helen A , Rudà Roberta , Lim-Fat Mary Jane , Blumenthal Deborah T , Weller Michael , Arakawa Yoshiki , Whittle James R , Ducray François , Reardon David A , Bi Wenya Linda , Minniti Giuseppe , Rahman Rifaquat , Hervey-Jumper Shawn , Chang Susan M , Wen Patrick Y 
Published: December 2024

Abstract
Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence. Consequently, there is an urgent need for innovative strategies that delay progression and the use of radiation therapy and chemotherapy. The recent Federal Drug Administration (FDA) approval of vorasidenib, a brain-penetrant small molecule targeting mutant IDH1/2 proteins, heralds a shift in the therapeutic landscape for IDH-mutant gliomas. In this review, we address the role of vorasidenib in the treatment of IDH-mutant gliomas, providing a roadmap for its incorporation into daily practice. We discuss ongoing clinical trials with vorasidenib and other IDH inhibitors, as single-agent or in combination with other therapies, as well as current challenges and future directions.
Omics-based identification of the broader effects of 2-hydroxyisoflavanone synthase gene editing on a gene regulatory network beyond isoflavonoid loss in soybean hairy roots
Authors: Uchida Kai , Fuji Yushiro , Tabeta Hiromitsu , Akashi Tomoyoshi , Hirai Masami Yokota 
Published: December 2024

Abstract
Soybean (Glycine max) is a leguminous crop cultivated worldwide that accumulates high levels of isoflavones. Although previous research has often focused on increasing the soybean isoflavone content because of the estrogen-like activity of dietary soy in humans, the rapidly increasing demand for soybean as a plant-based meat substitute has raised concerns about excessive isoflavone intake. Therefore, the production of isoflavone-free soybean has been anticipated. However, there have been no reports of an isoflavone-free soybean until now. Here, 2-hydroxyisoflavanone synthase (IFS), which is essential for isoflavone biosynthesis, was targeted for genome editing in soybean. A novel CRISPR/Cas9 system using Staphylococcus aureus Cas9 instead of the commonly used Streptococcus pyogenes Cas9 was established and customized. Through Agrobacterium rhizogenes–mediated transformation, IFS-edited hairy roots were generated in which all three IFS genes contained deletion mutations. Metabolome analyses of IFS-edited hairy roots revealed that isoflavone content significantly decreased, whereas levels of flavonoids, including a novel chalcone derivative, increased. A transcriptome analysis revealed changes in the expression levels of a large number of genes, including jasmonic acid–inducible genes. In addition, the functions of selected transcription factor genes (MYB14-L, GmbHLH112, and GmbHLH113), which were dramatically upregulated by IFS editing, were investigated by multiomics analyses of their over-expressing hairy root lines. They appear to be involved in flavonoid and triterpene saponin biosynthesis, salicylic acid metabolism, and central carbon metabolism. Overall, the results indicated that editing IFS genes caused the redirection of the metabolic flux from isoflavonoid biosynthesis to flavonoid accumulation, as well as dynamic changes in gene regulatory networks.
What makes life go well? A network topic modeling analysis of well-being practices in adults with chronic pain
Authors: Cintron Dakota W , Ong Anthony D , Reid M Carrington 
Published: December 2024

Abstract

Objective
This study leverages natural language processing techniques to identify specific practices older adults with chronic pain adopt to enhance well-being.

Method
We applied network topic modeling to open-ended survey responses from 683 adults (57% female) who reported experiencing chronic pain in the Midlife in the United States (MIDUS) study, analyzing responses to the question “What do you do to make your life go well?” Structural equation modeling was used to examine the relationships between identified topics and measures of pain interference and prescription pain medication use, adjusting for sociodemographics and well-being indicators.

Results
The analyses revealed 12 key topics, including avoiding stress, maintaining social connections, and practicing spirituality and faith. Notably, maintaining social connections was negatively associated with pain interference (β = −0.14, SE = 0.05, P &lt; .05) and prescription pain medication use (β = −0.11, SE = 0.04, P &lt; .05).

Conclusion
The findings demonstrate the utility of network topic modeling in identifying complex psychosocial dimensions influencing chronic pain management, providing insights into the distinct role of well-being practices in shaping pain outcomes.
Scientizing the world: on mechanisms and outcomes of the institutionalization of science
Authors: Marques Marcelo , Macasaet Bea Treena , Powell Justin J.W , Dusdal Jennifer , Baker David P 
Published: December 2024

Abstract
Scientific reasoning has emerged as a powerful social force, particularly due to the institutionalization of science, a process that has significantly accelerated since the late 20th century. This phenomenon, known as scientization in the social sciences, encapsulates how scientific reasoning has become the dominant medium for shaping science-society relationships. Despite its growing prominence, the mechanisms and outcomes of scientization remain less well understood. A systematic search of Elsevier’s Scopus database reveals a sharp increase in references to scientization since the late 1970s, with 296 publications doing so by 2020. This study examines how mechanisms such as rationalization, professionalization, technologization, commercialization, and actorhood have driven the institutionalization of science, impacting culture, academic disciplines, and policy-making. Our findings highlight the critical need for more nuanced understandings of how scientization influences modern societies, particularly within the policy sphere, where the interplay between science and policy has substantial and far-reaching consequences.
The effects of individual and collective labor market status on employment and earnings during the COVID-19 crisis
Authors: Kristal Tali , Mundlak Guy , Cohen Yinon , Haberfeld Yitchak , Yaish Meir 
Published: December 2024

Abstract
Based on a unique longitudinal survey conducted between April 2020 and April 2021 in Israel, this study estimated the effect of labor market status during the outbreak of COVID-19 on continuity of employment, worktime and earnings throughout the crisis. Labor market status has both an individual dimension (the type of employment contract) and a collective one (membership in a trade union or coverage by a collective agreement). Findings from curvilinear growth models show that those whose labor market status was more precarious, characterized by deviations from the standard employment relationship and the absence of collective representation and voice, fared less well than those whose labor market status was more secure. At the same time, evidence suggests a negotiated compromise whereby workers with collective representation enjoyed greater employment security but also experienced greater earnings reductions than their counterparts who remained employed but had no collective representation.
Restrictions by object under Article 101(1) TFEU: From dark art to administrable framework
Authors: Ibáñez Colomo Pablo 
Published: December 2024

Abstract
This article presents the principles underpinning the approach followed by the Court of Justice (ECJ) when evaluating whether a practice has, as its object, the restriction of competition. It discusses, inter alia, what an authority (or claimant) needs to prove and explains what the evaluation of the economic and legal context involves in concrete terms. The analysis shows that the ECJ’s overall approach is both predictable (in the sense that the notion has clear and finite boundaries) and administrable (in the sense that the said approach places adequate and workable demands on authorities and claimants). It appears, on the other hand, that there are ways in which some principles underpinning the case law could be streamlined and made more explicit so as to guarantee the uniform application of Article 101(1) TFEU across the European Union at a time when private enforcement is on the rise.
Nomenclatural addendum to ‘The systematics and nomenclature of the Dodo and the Solitaire (Aves: Columbidae), and an overview of columbid family-group nomina’
Authors: Young Mark T , Gregory Steven M S , Dickinson Edward C , Hume Julian P , Day Michael O , Douglas Robert P , Simmons Zoë M , White Judith , Heller Markus O , Gostling Neil J 
Published: December 2024

Abstract
Columbidae (the pigeon and dove family) are a speciose clade of non-passerine birds with a near global distribution. Recently, Young et al. (2024) undertook an evaluation of the systematics and nomenclature of the Dodo and its sister species the Rodrigues Solitaire. Therein, they also investigated the validity of columbid family-group names. Since publication, we have been made aware of corrections to that survey of columbid family-group names. As such, this erratum is a nomenclatural addendum to Young et al. (2024) and should be consulted alongside the original publication.
Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments
Authors: Smith Hannah L. , Beers Stephen A. , Kanczler Janos M. , Gray Juliet C. 
Published: December 2024

AbstractOsteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi‐agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3‐dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches. An osteosarcoma 3D bone core model was developed using human trabecular bone and the chorioallantoic membrane (CAM), to form a functioning vasculature. A tri‐culture of cells, stromal cells, macrophages, and the Saos‐2 osteosarcoma cell line, were implanted into this model to simulate components of the tumor microenvironment, and mifamurtide was tested in this context. Immunohistochemistry and micro‐CT were performed to assess phenotypic and structural effects of implantation. Successful integration and angiogenesis of the bone cores were observed after incubation on the CAM. The 3D bone model also showed similar characteristics to osteosarcoma patient samples including CD68 and CD105 expression. Incubating bone cores with mifamurtide induced a reduction of cellular markers and an increase in bone volume. This 3D bone core model has the potential to investigate osteosarcoma tumor microenvironment and provides a representative model for evaluation of novel therapies.
Caring for Patients Seeking Asylum: Early Data From the Safety Net System in New York City
Authors: Newton-Dame Remle , Jacobson Laura , Wallach Andrew B. , Silverman Erica , Dreyer Benard , Long Theodore 
Published: December 2024

Context:
Over 200 000 people seeking asylum have arrived in New York City from 2022 to 2024.

Program:
As the safety net hospital system for our city, New York City (NYC) Health + Hospitals (H + H) has taken the lead in caring for newly arrived asylum seekers. We used electronic medical record data to gain early insights into utilization and needs among these patients.

Implementation:
We developed a hybrid definition to identify patients who are asylum seekers and examined their demographics, insurance, utilization, primary billing diagnoses, and immunizations from the Epic EMR. We included data on other patients as a point of comparison and analyzed data separately for adult and pediatric patients.

Evaluation:
In 2023, 15 233 or 1.4% of H + H patients were asylum seekers. Asylum seekers had fewer visits than other patients in 2023, and utilization was particularly driven by pregnancy and childbirth. Children seeking asylum were engaged in primary care at high rates. Documented childhood vaccinations were higher among asylum-seeking children engaged in primary care compared to those who were not. The majority of adults and children were insured. Adult primary care engagement was low, as were visits for those seeking care for behavioral health issues.

Discussion:
For adult asylum seekers, pregnancy and childbirth are key needs for adults. Increasing vaccination rates among children is critical and promoting engagement in primary care is a promising way to do so. Coordinated efforts are required to meet the varied needs of migrant arrivals, and safety net hospitals can play a key role in addressing their health care needs.
Incremental Value of Pericoronary Adipose Tissue Radiomics Models in Identifying Vulnerable Plaques
Authors: Zhu Jinke , Zhu Xiucong , Lv Sangying , Guo Danling , Li Huaifeng , Zhao Zhenhua 
Published: December 2024

Objective
Inflammatory characteristics in pericoronary adipose tissue (PCAT) may enhance the diagnostic capability of radiomics techniques for identifying vulnerable plaques. This study aimed to evaluate the incremental value of PCAT radiomics scores in identifying vulnerable plaques defined by intravascular ultrasound imaging (IVUS).

Methods
In this retrospective study, a PCAT radiomics model was established and validated using IVUS as the reference standard. The dataset consisted of patients with coronary artery disease who underwent both coronary computed tomography angiography and IVUS examinations at a tertiary hospital between March 2023 and January 2024. The dataset was randomly assigned to the training and validation sets in a 7:3 ratio. The diagnostic performance of various models was evaluated on both sets using the area under the curve (AUC).

Results
From 88 lesions in 79 patients, we selected 9 radiomics features (5 texture features, 1 shape feature, 1 gray matrix feature, and 2 first-order features) from the training cohort (n = 61) to build the PCAT model. The PCAT radiomics model demonstrated moderate to high AUCs (0.847 and 0.819) in both the training and test cohorts. Furthermore, the AUC of the PCAT radiomics model was significantly higher than that of the fat attenuation index model (0.847 vs 0.659, P < 0.05). The combined model had a higher AUC than the clinical model (0.925 vs 0.714, P < 0.01).

Conclusions
The PCAT radiomics signature of coronary CT angiography enabled the detection of vulnerable plaques defined by IVUS.
Effects of Electric Field Direction on TMS-based Motor Cortex Mapping
Authors: Jing Ying , Numssen Ole , Hartwigsen Gesa , Knösche Thomas R. , Weise Konstantin 
Published: December 2024

AbstractBackgroundTranscranial magnetic stimulation (TMS) modulates brain activity by inducing electric fields (E-fields) that can elicit action potentials in cortical neurons. Neuronal responses to TMS depend not only on the magnitude of the induced E-field but also on various physiological factors. In this study, we incorporated a novel average response model that efficiently estimates the firing threshold of neurons based on their orientation relative to the applied E-field, thereby advancing TMS mapping for motor function.MethodsWe conducted a regression-based TMS mapping experiment with fourteen subjects to localize cortical origins of motor evoked potential (MEP) on the first dorsal interosseous (FDI) muscle. Firing thresholds were estimated for excitatory neurons in cortical layers 2/3 and 5 via an average response model. Regression was performed between MEPs and three E-field quantities: the magnitude (magnitude model), the normal component (cosine model), and the effective E-field, which scales the E-field magnitude based on the firing thresholds specific to the neuronal orientation (neuron model). To validate, we applied TMS to ten subjects with optimized coil placements based on these three models to determine which model could yield the highest MEPs.ResultsThe magnitude and neuron models performed similarly, while the cosine model showed lower explained variance in regression results, required more TMS trials for stable mapping, and yielded the lowest MEP in the validation.ConclusionThis study is the first to advance TMS modeling by incorporating neuron-specific factors at the individual level. Results show that on the motor cortex, the magnitude model is–as expected–a good approximation of cortical TMS effects as it shows similar results as the neuron model. In contrast, the classic cosine model exhibited lower performance and required more TMS trials for stable results, and is not recommended for future studies.
5G Radio-Frequency-Electromagnetic-Field Effects on the Human Sleep Electroencephalogram: A Randomized Controlled Study inCACNA1CGenotyped Healthy Volunteers
Authors: Sousouri Georgia , Eicher Corinne , D’ Angelo Rachele Maria , Billecocq Marie , Fussinger Thomas , Studler Mirjam , Capstick Myles , Kuster Niels , Achermann Peter , Huber Reto , Landolt Hans-Peter 
Published: December 2024

AbstractBackgroundThe introduction of 5G technology as the latest standard in mobile telecommunications has raised concerns about its potential health effects. Prior studies of earlier generations of radiofrequency electromagnetic fields (RF-EMF) demonstrated narrowband spectral increases in the electroencephalographic (EEG) spindle frequency range (11-16 Hz) in non-rapid-eye-movement (NREM) sleep. However, the impact of 5G RF-EMF on sleep remains unexplored. Additionally, RF-EMF can activate L-type voltage-gated calcium channels (LTCC), which have been linked to sleep quality and EEG oscillatory activity.ObjectiveThis study investigates whether the allelic variant rs7304986 in theCACNA1Cgene, encoding the α1C subunit of LTCC, modulates 5G RF-EMF effects on EEG spindle activity during NREM sleep.MethodsThirty-four healthy, matched participants, genotyped for rs7304986 (15 T/C and 19 T/T carriers), underwent a double-blind, sham-controlled study with standardized left-hemisphere exposure to two 5G RF-EMF signals (3.6 GHz and 700 MHz) for 30 min before sleep. Sleep spindle activity was analyzed using high-density EEG and the Fitting Oscillations & One Over f (FOOOF) algorithm.ResultsT/C carriers reported longer sleep latency compared to T/T carriers. A significant interaction between RF-EMF exposure and rs7304986 genotype was observed, with 3.6 GHz exposure in T/C carriers inducing a faster spindle center frequency in the central, parietal, and occipital cortex compared to sham.ConclusionThese findings suggest 3.6 GHz 5G RF-EMF modulates spindle center frequency during NREM sleep in aCACNA1Cgenotype-dependent manner, implicating LTCC in the physiological response to RF-EMF and underscoring the need for further research into 5G effects on brain health.
A freely accessible, adaptable hollow-fiber setup to reproduce first-order absorption: illustration with linezolid cerebrospinal fluid pharmacokinetic data
Authors: Prébonnaud N. , Chauzy A. , Grégoire N. , Dahyot-Fizelier C. , Adier C. , Marchand S. , Aranzana-Climent V. 
Published: December 2024

AbstractThe main objective of this study was to validate an algorithm and experimental setup to simulate first-order absorption pharmacokinetic profiles without altering the standardin vitrohollow fiber infection model (HFIM). For that, clinical cerebrospinal fluid (CSF) linezolid concentrations after 30-minute infusions at dosing regimens 600 mg q12 h, 900 mg q12 h, and 900 mg q8 h were reproduced in the HFIM over 4 days.To approximate the apparent first-order absorption observed on CSF pharmacokinetic profiles, we split the dosing interval into a series of sub-intervals during which continuous infusions were delivered to the system. During each sub-interval, the same amount of linezolid was delivered but the sub-intervals had different durations and flow rates which were computed by a newly developed algorithm.In addition, we independently reproduced plasma concentrations to validate our system.Samples were collected from the central reservoir and the extracapillary space (ECS) of the cartridge of the HFIM and assayed by liquid chromatography-tandem mass spectrometry. Observed pharmacokinetic parameters and concentrations in the ECS were compared with the target clinical pharmacokinetic parameters and concentrations.Observed pharmacokinetic parameters were within 20 % of target pharmacokinetic parameters for all experiments, thus validating the ability of our experimental setup to reproduce plasma and CSF linezolid pharmacokinetic profiles.The algorithm and setup are available in the open-source web applicationhttps://varacli.shinyapps.io/hollow_fiber_app/to easily design other HFIM experiments.
The yield on re-interpretation of genetic variants in pediatric cardiomyopathy
Authors: Suzuki Takanori , Lesurf Robert , Akilen Raj , Xu Xiaoqiao , Jobling Rebekah , Zahavich Laura , Mital Seema 
Published: December 2024

ABSTRACTBackgroundRegular re-interpretation of disease-causing genetic variants is recommended to determine if variant pathogenicity changes as new information becomes available. Our aim was to determine the yield on systematic re-evaluation of genetic variants in pediatric patients with cardiomyopathy.MethodsThe study cohort included 227 unrelated pediatric patients with cardiomyopathy enrolled in the Heart Centre Biobank who harbored a pathogenic/likely pathogenic (P/LP) variant and/or a variant of uncertain significance (VUS) on clinical genetic testing between 2005-2022. Variant pathogenicity was re-evaluated using the American College of Medical Genetics and Genomics (ACMG) guidelines. The re-evaluation included updates to ClinGen gene curation, ClinVar variant interpretation, population allele frequency, in silico tools for variant deleteriousness, segregation with disease or de novo status, and genotype-phenotype evaluation.ResultsRe-evaluation was performed in 382 variants (110 P/LP, 272 VUS) reported in the study cohort of 227 patients. 12 of 110 P/LP (10.9%) variants were downgraded to VUS in 14 patients. Leading criteria were high population allele frequency and variant not located in mutational hotspot or critical functional gene domain. 37 of 272 VUS (13.6%) were upgraded to P/LP in 35 patients. Leading criteria were variant in mutational hotspot for gene, variant interpreted as deleterious using in silico prediction and novel missense change at an amino acid residue where a different missense change was previously determined to be pathogenic. Overall, the reclassification of 49 variants affected 49 of 227 (21.6%) patients. Of note, only 8 reclassified variants had been reported back by the clinical genetic testing laboratory.ConclusionsOne in five patients with cardiomyopathy had a clinically relevant change from the original variant classification on systematic re-evaluation. This has implications for clinical screening and cascade genetic testing of family members of affected patients. These findings underscore the importance of regular variant re-interpretation on follow-up in cardiomyopathy patients.