bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: Lessons from the French POLA cohort
Authors: Figarella-Branger Domique , Colin Carole , Mokhtari Karima , Uro-Coste Emmanuelle , Idbaih Ahmed , Appay Romain , Tabouret Emeline , Touat Mehdi , Seyve Antoine , Carpentier Catherine , Dehais Caroline , Ducray François ,   the POLA network, Desenclos C , Guillain N , Menei P , Rousseau A , Cruel T , Lopez S , Abad M , Hamdan N , Adam C , Parker F , Seizeur R , Quintin-Roué I , Chotard G , Bronnimann C , Ricard D , Godfraind C , Khallil T , Cazals-Hatem D , Faillot T , Gaultier C , Tortel MC , Carpiuc I , Richard P , Aubriot-Lorton H , Ghiringhelli F , Djelad A , Maurage CA , Gueye EM , Labrousse F , Ducray F , Meyronet D , Figarella-Branger D , Chinot O , Bauchet L , Rigau V , Gauchotte G , Taillandier L , Campone M , Loussouarn D , Bourg V , Vandenbos-Burel F , Guillamo J-S , Roger P , Blechet C , Adle-Biassette H , Bielle F , Carpentier A , Dehais C , Milin S , Wager M , Colin P , Diebold MD , Chiforeanu D , Vauleon E , Marguet F , Langlois O , Forest F , Motso-Fotso MJ , Andraud M , Khettab M , Lhermitte B , Noel G , Bernier M , Younan N , Rousselot-Denis C , Zemmoura I , Joubert C , Cohen-Moyal E , Uro-Coste E , Dhermain F 
Published: October 2024

Abstract

Background
In the POLA cohort, 3 pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis).

Methods
494 patients from the POLA cohort, with a median follow-up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement (CE) in group 1 on overall survival (OS) or progression-free survival (PFS), survival curves were obtained (Kaplan–Meier method) and compared (log-rank test). The prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed.

Results
Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P = .01) and overall survival (OS P = .001). In group 1, patients with CE (1CE+) had a poorer prognosis compared to those without (OS P = .028, PFS P = .006). Further stratification into group 1CE−, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P = .002, PFS P &lt; .0001). Other prognostic factors included age (OS P &lt; .0001, PFS P = .002), extent of surgical resection (OS P = .001, PFS P = .003), KPS (OS P &lt; .0001, PFS P = 0.002), postoperative treatment (OS P = .007, PFS P &lt; .0001), and CDKN2A HD (OS and PFS P &lt; .0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis.

Conclusions
Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH-mutant, and 1p/19q co-deleted. Besides, in group 1 patients, lack of CE is a factor of better prognosis.
The leucine-rich repeat receptor kinase QSK1 regulates PRR-RBOHD complexes targeted by the bacterial effector HopF2Pto
Authors: Goto Yukihisa , Kadota Yasuhiro , Mbengue Malick , Lewis Jennifer D , Matsui Hidenori , Maki Noriko , Ngou Bruno Pok Man , Sklenar Jan , Derbyshire Paul , Shibata Arisa , Ichihashi Yasunori , Guttman David S , Nakagami Hirofumi , Suzuki Takamasa , Menke Frank L H , Robatzek Silke , Desveaux Darrell , Zipfel Cyril , Shirasu Ken 
Published: October 2024

Abstract
Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) such as ELONGATION Factor-TU (EF-TU) RECEPTOR (EFR) and FLAGELLIN SENSING 2 (FLS2), which recognize bacterial EF-Tu and flagellin, respectively. These PRRs belong to the leucine-rich repeat receptor kinase (LRR-RK) family and activate the production of reactive oxygen species via the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogen effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative coimmunoprecipitation analysis using EFR, FLS2, and RBOHD in Arabidopsis thaliana. We identified QIAN SHOU KINASE 1 (QSK1), an LRR-RK, as a PRR-RBOHD complex-associated protein. QSK1 downregulated FLS2 and EFR abundance, functioning as a negative regulator of PRR-triggered immunity (PTI). QSK1 was targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, reducing FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto transcriptionally downregulated PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack.
Mechanistic effects of lipid binding pockets within soluble signaling proteins: lessons from acyl-CoA-binding and START-domain-containing proteins
Authors: Lung Shiu-Cheung , Chye Mee-Len 
Published: October 2024

Abstract
While lipids serve as important energy reserves, metabolites, and cellular constituents in all forms of life, these macromolecules also function as unique carriers of information in plant communication given their diverse chemical structures. The signal transduction process involves a sophisticated interplay between messengers, receptors, signal transducers, and downstream effectors. Over the years, an array of plant signaling proteins have been identified for their crucial roles in perceiving lipid signals. However, the mechanistic effects of lipid binding on protein functions remain largely elusive. Recent literature has presented numerous fascinating models that illustrate the significance of protein–lipid interactions in mediating signaling responses. This review focuses on the category of lipophilic signaling proteins that encompass a hydrophobic binding pocket located outside of cellular membranes and provides an update on the lessons learned from two of these structures, namely the acyl-CoA–binding and steroidogenic acute regulatory protein-related lipid transfer domains. It begins with a brief overview of the latest advances in understanding the functions of the two protein families in plant communication. The second part highlights five functional mechanisms of lipid ligands in concert with their target signaling proteins.
Competition and Certification: Theory and Evidence from the Audit Market
Authors: Geng Heng (Griffin) , Zhang Cheng , Zhou Frank S 
Published: October 2024

Abstract
We study how financial certifier competition influences loan contracting in the context of financial auditing. Exploiting the unexpected demise of Arthur Andersen that exogenously decreased auditor competition, we find a greater decrease in loan spread for borrowers in markets in which certifier competition declined more. Additional analyses suggest the result stems from enhanced audit quality and reduced credit risk. The effect of certifier competition is stronger for borrowers with weaker external monitoring and those generating significant revenue for their auditors. Our evidence highlights negative consequences of financial certifier competition. (JEL D43, G21, M42, M49)
RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells
Authors: Valenzuela-Bezanilla Daniela , Mardones Muriel D , Galassi Maximiliano , Arredondo Sebastian B , Santibanez Sebastian H , Gutierrez-Jimenez Stephanie , Merino-Véliz Nicolás , Bustos Fernando J , Varela-Nallar Lorena 
Published: October 2024

Abstract
In the dentate gyrus of the adult hippocampus, neurogenesis from neural stem cells (NSCs) is regulated by Wnt signals from the local microenvironment. The Wnt/β-catenin pathway is active in NSCs, where it regulates proliferation and fate commitment, and subsequently its activity is strongly attenuated. The mechanisms controlling Wnt activity are poorly understood. In stem cells from adult peripheral tissues, secreted R-spondin proteins (RSPO1-4) interact with LGR4-6 receptors and control Wnt signaling strength. Here, we found that RSPO1-3 and LGR4-6 are expressed in the adult dentate gyrus and in cultured NSCs isolated from the adult mouse hippocampus. LGR4-5 expression decreased in cultured NSCs upon differentiation, concomitantly with the reported decrease in Wnt activity. Treatment with RSPO1-3 increased NSC proliferation and the expression of Cyclin D1 but did not induce the expression of Axin2 or RNF43, 2 well-described Wnt target genes. However, RSPOs enhanced the effect of Wnt3a on Axin2 and RNF43 expression as well as on Wnt/β-catenin reporter activity, indicating that they can potentiate Wnt activity in NSCs. Moreover, RSPO1-3 was found to be expressed by cultured dentate gyrus astrocytes, a crucial component of the neurogenic niche. In co-culture experiments, the astrocyte-induced proliferation of NSCs was prevented by RSPO2 knockdown in astrocytes and LGR5 knockdown in hippocampal NSCs. Additionally, RSPO2 knockdown in the adult mouse dentate gyrus reduced proliferation of neural stem and progenitor cells in vivo. Altogether, our results indicate that RSPO/LGR signaling is present in the dentate gyrus and plays a crucial role in regulating neural precursor cell proliferation.
Astrocytes in the rostral ventromedial medulla mediate the analgesic effect of electroacupuncture in a rodent model of chemotherapy-induced peripheral neuropathic pain
Authors: Chen Xuejiao , Mi Wenli , Gao Tianchi , Ding Fengfei , Wang Wei 
Published: October 2024

Abstract
Chemotherapy-induced peripheral neuropathic pain aggravates cancer survivors' life burden. Electroacupuncture (EA) has exhibited promising analgesic effects on neuropathic pain in previous studies. We investigated whether EA was effective in a paclitaxel-induced neuropathic pain mouse model. We further explored the functional role of astrocytes in the rostral ventromedial medulla (RVM), a well-established pain modulation center, in the process of neuropathic pain as well as the analgesic effect of EA. We found that paclitaxel induced mechanical allodynia, astrocytic calcium signaling, and neuronal activation in the RVM and spinal cord, which could be suppressed by EA treatment. Electroacupuncture effectively alleviated paclitaxel-induced mechanical allodynia, and the effect was attenuated by the chemogenetic activation of astrocytes in the RVM. In addition, inhibiting astrocytic calcium activity by using either IP3R2 knockout (IP3R2 KO) mice or microinjection of AAV-mediated hPMCA2 w/b into the RVM to reduce non–IP3R2-dependent Ca2+ signaling in astrocytes exhibited an analgesic effect on neuropathic pain, which mimicked the EA effect. The current study revealed the pivotal role of the RVM astrocytes in mediating the analgesic effects of EA on chemotherapy-induced peripheral neuropathic pain.
Widespread hyperexcitability of nociceptor somata outlasts enhanced avoidance behavior after incision injury
Authors: Bavencoffe Alexis , Lopez Elia R. , Johnson Kayla N. , Tian Jinbin , Gorgun Falih M. , Shen Breanna Q. , Domagala Drue M. , Zhu Michael X. , Dessauer Carmen W. , Walters Edgar T. 
Published: October 2024

AbstractNociceptors with somata in dorsal root ganglia (DRGs) readily switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Spontaneous activity (SA) during this state is present in vivo in rats months after spinal cord injury (SCI) and has been causally linked to SCI pain. Intrinsically generated SA and, more generally, ongoing activity (OA) are induced by various neuropathic conditions in rats, mice, and humans and are retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. The present study shows that long-lasting hyperexcitability that can generate OA during modest depolarization in probable nociceptors dissociated from DRGs of male and female rats is induced by plantar incision injury. OA occurred when the soma was artificially depolarized to a level within the normal range of membrane potentials where large, transient depolarizing spontaneous fluctuations (DSFs) can approach AP threshold. This hyperexcitability persisted for at least 3 weeks, whereas behavioral indicators of affective pain—hind paw guarding and increased avoidance of a noxious substrate in an operant conflict test—persisted for 1 week or less. The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. An unexpected discovery after plantar incisions was hyperexcitability in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to contribute to hyperalgesic priming and to drive anxiety-related hypervigilance.
Gaming the System? A Qualitative Exploration of Physician Assistant Learner Perceptions of Virtual Patient Education
Authors: Kanofsky Sharona , Hodwitz Kathryn , Tzakas Peter , Nyhof-Young Joyce M. , Walsh Catharine M. 
Published: October 2024

Introduction
Virtual patients (VPs) are increasingly used in health professions education. How learners engage with VPs and the relationship between engagement and authenticity is not well understood. We explored learners' perceptions of VP education to gain an understanding of the characteristics promoting meaningful engagement in learning, including perceived authenticity.

Methods
Using a constructivist grounded theory approach, we conducted interviews and focus groups with 11 students from 2 Canadian Physician Assistant programs, where VP learning was implemented to supplement clinical education during the COVID-19 pandemic. We explored trainee perspectives on the use of VPs as an educational modality. Data were iteratively collected and descriptively analyzed thematically using a constant comparison approach until theoretical sufficiency was reached.

Results
We identified 3 groups of factors influencing these students' VP learning experiences: (1) technical factors related to the VP platform influenced the perceived authenticity of the patient interactions; (2) individual factors of learners' attitudes influenced their engagement and motivation; and (3) contextual factors related to the learning environment influenced the acceptability and perceived value of the learning experience. Overall, the psychological authenticity of the learning platform and students' motivation for self-directed learning were perceived as most important for students' learning experiences.

Conclusions
Implementing VP learning as a supplement to clinical education should be done with consideration of factors that enhance the psychological authenticity of the learning platform, promote learner engagement and accountability, and encourage acceptability of the learning modality through curricular placement and messaging.
Active Choice Nudge to Increase Screening for Primary Aldosteronism in At-Risk Patients
Authors: Passman Jesse E , Hwang Jasmine , Tang Justin , Fagen Madeline , Epps Mika , Peifer MaryAnne , Howell John T , Cohen Jordana B , Delgado M Kit , Wachtel Heather , Herman Daniel S 
Published: October 2024

BACKGROUND:
Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe (1) PA screening practices in a large, diverse health system, (2) the development of a computable phenotype for PA screening, and (3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening.

STUDY DESIGN:
A multidisciplinary team developed a multipronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening. The intervention included EHR-based tools to automatically identify screen-eligible patients, an active choice nudge recommending screening for these patients, and screening result interpretation. The intervention was piloted across 2 primary care practices for 7 months. Screening frequencies were compared with clinics not receiving the intervention.

RESULTS:
The baseline frequency of screening of eligible patients within 1 year was 1.4%. Higher mean systolic blood pressure (odds ratio [OR] 1.4; p < 0.001), more antihypertensive medications (OR 1.3; p = 0.002), lower minimum serum potassium (OR 2.0; p = 0.001), specialist care (OR 3.0; p < 0.001), and Black race (OR 1.5; p = 0.001) were associated with a higher likelihood of screening. The refined computable phenotype identified a subcohort with a higher frequency of positive screening (8.6% vs 4.1%; p = 0.03). In a pilot study of an active choice nudge, a greater proportion of eligible patients were screened in the intervention clinics (16.4%) than in the nonintervention clinics (1.8%; p < 0.001).

CONCLUSIONS:
PA screening rates are low. This pilot study suggests an EHR-based nudge leveraging a precise computable phenotype can dramatically increase appropriate PA screening.
From lab to life: challenges and perspectives of fNIRS for haemodynamic-based neurofeedback in real-world environments
Authors: Klein Franziska , Kohl Simon H. , Lührs Michael , Mehler David M. A. , Sorger Bettina 
Published: October 2024

Neurofeedback allows individuals to monitor and self-regulate their brain activity, potentially improving human brain function. Beyond the traditional electrophysiological approach using primarily electroencephalography, brain haemodynamics measured with functional magnetic resonance imaging (fMRI) and more recently, functional near-infrared spectroscopy (fNIRS) have been used (haemodynamic-based neurofeedback), particularly to improve the spatial specificity of neurofeedback. Over recent years, especially fNIRS has attracted great attention because it offers several advantages over fMRI such as increased user accessibility, cost-effectiveness and mobility—the latter being the most distinct feature of fNIRS. The next logical step would be to transfer haemodynamic-based neurofeedback protocols that have already been proven and validated by fMRI to mobile fNIRS. However, this undertaking is not always easy, especially since fNIRS novices may miss important fNIRS-specific methodological challenges. This review is aimed at researchers from different fields who seek to exploit the unique capabilities of fNIRS for neurofeedback. It carefully addresses fNIRS-specific challenges and offers suggestions for possible solutions. If the challenges raised are addressed and further developed, fNIRS could emerge as a useful neurofeedback technique with its own unique application potential—the targeted training of brain activity in real-world environments, thereby significantly expanding the scope and scalability of haemodynamic-based neurofeedback applications.
This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
Online self-evaluation of fMRI-based neurofeedback performance
Authors: Muñoz-Moldes Santiago , Tursic Anita , Lührs Michael , Eck Judith , Benitez Andonegui Amaia , Peters Judith , Cleeremans Axel , Goebel Rainer 
Published: October 2024

This study explores the subjective evaluation of supplementary motor area (SMA) regulation performance in a real-time functional magnetic resonance imaging neurofeedback (fMRI-NF) task. In fMRI-NF, people learn how to self-regulate their brain activity by performing mental actions to achieve a certain target level (TL) of blood-oxygen-level-dependent (BOLD) activation. Here, we studied two types of self-evaluation: performance predictions and perceived confidence in the prediction judgement. Participants completed three sessions of SMA regulation in a 7 T fMRI scanner, performing a mental drawing task. During each trial, they modulated their imagery strategy to achieve one of two different levels of SMA activation and reported a performance prediction and their confidence in the prediction before receiving delayed BOLD-activation feedback. Results show that participants’ performance predictions improved with learning throughout the three sessions, and that these improvements were not driven exclusively by their knowledge of previous performance. Confidence reports on the other hand showed no change throughout training and did not correlate with better and worse predictions. In addition to shedding light on mechanisms of internal self-evaluation during neurofeedback training, these results also point to a dissociation between predictions of performance and confidence reports in the presence of feedback.
This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
APOEGenotype and Biological Age Impact Inter-Omic Associations Related to Bioenergetics
Authors: Ellis Dylan , Watanabe Kengo , Wilmanski Tomasz , Lustgarten Michael S. , Korat Andres V Ardisson , Glusman Gwênlyn , Hadlock Jennifer J. , Fiehn Oliver , Sebastiani Paola , Price Nathan D. , Hood Leroy , Magis Andrew T. , Evans Simon J. , Pflieger Lance , Lovejoy Jennifer C. , Gibbons Sean M. , Funk Cory C. , Baloni Priyanka , Rappaport Noa 
Published: October 2024

AbstractApolipoprotein E (APOE) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer’s disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. Herein, we analyzed inter-omic, context-dependent association patterns acrossAPOEgenotypes, sex, and health axes in 2,229 community-dwelling individuals to testAPOEgenotypes for variation in metabolites and metabolite-associations tied to a previously-validated metric of biological aging (BA) based on blood biomarkers. Our analysis, supported by validation in an independent cohort, identified topAPOE-associated plasma metabolites as diacylglycerols, which were increased in ε2-carriers and trended higher in ε4-carriers compared to ε3-homozygotes, despite the known opposing aging effects of the allele variants. ‘Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying increased associations between insulin resistance markers and energy-generating pathway metabolites. These results provide an atlas ofAPOE-related ‘omic associations and support the involvement of bioenergetic pathways in mediating the impact ofAPOEon aging.
From Beeps to Streets: Unveiling Sensory Input and Relevance Across Auditory Contexts
Authors: Korte Silvia , Jaeger Manuela , Rosenkranz Marc , Bleichner Martin G. 
Published: October 2024

AbstractThis study investigates the neural basis of sound perception in everyday life using EEG data recorded in an office-like environment over 3.5 hours. We investigated how contextual factors such as personal relevance, task complexity and stimulus properties influence auditory processing in ecologically valid settings. By systematically increasing the complexity of acoustic scenes and tasks, we analysed changes in neural responses, particularly in the N100 and P300 components. Our results show that while the P300 is a stable marker of attention in both isolated sounds and complex soundscapes, the N100 is more sensitive to task complexity and environmental factors. This highlights the importance of context in shaping auditory perception. Furthermore, our results suggest that laboratory-based findings can be partially generalised to real-world settings, although task demands significantly influence neural markers. These findings provide new opportunities to study sound perception in naturalistic settings, without sacrificing the control typically afforded by laboratory studies.