bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Does Time Pressure Influence Risk Preferences? Answers from a Meta-Analysis
Authors: Belli Alex , Carrillat François A , Zlatevska Natalina , Cowley Elizabeth 
Published: September 2023

Abstract
Four decades of research into the influences of time pressure on risky decisions have produced widely contrasting findings: 38.5% of the effects indicate that time pressure increases risk preferences, whereas 61.5% show the opposite. A theoretical framework with four conceptual categories of moderators is proposed to explain these heterogeneous findings: nature of the time constraint, negative outcome salience, negative outcome severity, and vulnerability to the outcomes. This framework is tested through a meta-analysis of 213 effect sizes reported in 83 papers, representing 65,574 unique respondents. The four categories of moderators effectively resolve notable conflicts. For example, regarding the nature of the time constraint, an absolute versus relative constraint increases risk preferences, but an ambiguous versus objective constraint decreases risk preferences. In terms of negative outcome salience, risk preferences decrease if the risk is learned about from a description (vs. experience) or the outcome is framed as a loss (vs. gain). Negative outcome severity also exerts an effect, as discrete choices lower risk preferences compared with attitudinal risk. In addition to managerial and public policy implications based on simulations, a comprehensive research agenda that builds on the robust insights of this meta-analysis is offered.
Germline pathogenic variants in neuroblastoma patients are enriched in BARD1 and predict worse survival
Authors: Kim Jung , Vaksman Zalman , Egolf Laura E , Kaufman Rebecca , Evans J Perry , Conkrite Karina L , Danesh Arnavaz , Lopez Gonzalo , Randall Michael P , Dent Maiah H , Farra Lance M , Menghani Neil L , Dymek Malwina , Desai Heena , Hausler Ryan , Hicks Belynda , Guidry Auvil Jaime M , Gerhard Daniela S , Hakonarson Hakon , Maxwell Kara N , Cole Kristina A , Pugh Trevor J , Bosse Kristopher R , Khan Javed , Wei Jun S , Maris John M , Stewart Douglas R , Diskin Sharon J 
Published: September 2023

Abstract

Background
Neuroblastoma is an embryonal cancer of the developing sympathetic nervous system. The genetic contribution of rare pathogenic or likely pathogenic germline variants in patients without a family history remains unclear.

Methods
Germline DNA sequencing was performed on 786 neuroblastoma patients. The frequency of rare cancer predisposition gene pathogenic or likely pathogenic variants in patients was compared with 2 cancer-free control cohorts. Matched tumor DNA sequencing was evaluated for second hits, and germline DNA array data from 5585 neuroblastoma patients and 23 505 cancer-free control children were analyzed to identify rare germline copy number variants. Patients with germline pathogenic or likely pathogenic variants were compared with those without to test for association with clinical characteristics, tumor features, and survival.

Results
We observed 116 pathogenic or likely pathogenic variants involving 13.9% (109 of 786) of neuroblastoma patients, representing a statistically significant excess burden compared with cancer-free participants (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.27 to 2.00). BARD1 harbored the most statistically significant enrichment of pathogenic or likely pathogenic variants (OR = 32.30, 95% CI = 6.44 to 310.35). Rare germline copy number variants disrupting BARD1 were identified in patients but absent in cancer-free participants (OR = 29.47, 95% CI = 1.52 to 570.70). Patients harboring a germline pathogenic or likely pathogenic variant had a worse overall survival compared with those without (P = 8.6 x 10−3).

Conclusions
BARD1 is an important neuroblastoma predisposition gene harboring both common and rare germline pathogenic or likely pathogenic variations. The presence of any germline pathogenic or likely pathogenic variant in a cancer predisposition gene was independently predictive of worse overall survival. As centers move toward paired tumor-normal sequencing at diagnosis, efforts should be made to centralize data and provide an infrastructure to support cooperative longitudinal prospective studies of germline pathogenic variation.
Repeated patterns of gamma-ray flares suggest structured jets of blazars as likely neutrino sources
Authors: Novikova Polina , Shishkina Ekaterina , Blinov Dmitry 
Published: September 2023

ABSTRACT
Fermi-Large Area Telescope (LAT) observations provide continuous and regularly sampled measurements of gamma-ray photon flux for hundreds of blazars. Many of these light curves, spanning almost 15 yr, have been thoroughly examined for periodicity in multiple studies. However, the possibility that blazars may exhibit irregularly repeating flaring patterns in their gamma-ray light curves has not been systematically explored. In this study, we aim to find repeating episodes of flaring activity in the 100 brightest blazars using Fermi-LAT light curves with various integration times. We use a Bayesian Blocks representation to convert the time series into strings of symbols and search for repeating sub-strings using a fuzzy search algorithm. As a result, we identify 27 repeated episodes in the gamma-ray light curves of 10 blazars. We find that the patterns are most likely produced in structured jets composed of a fast spine and a slower sheath. When individual emission features propagate in the spine, they scatter seed photons produced in the non-uniform sheath through the inverse Compton mechanism, resulting in a set of gamma-ray flares with a similar profile every such passage. Additionally, we explore the theoretically predicted possibility that the spine-sheath structure facilitates the production of high-energy neutrinos in blazar jets. Using the catalogue of track-like events detected by the IceCube neutrino telescope, we find evidence supporting this hypothesis at a 2.8σ significance level.
Single-cell RNA sequencing identifies senescence as therapeutic target in rhabdomyolysis-induced acute kidney injury
Authors: Rao Snigdha N , Zahm Margot , Casemayou Audrey , Buleon Marie , Faguer Stanislas , Feuillet Guylène , Iacovoni Jason S , Joffre Olivier P , Gonzalez-Fuentes Ignacio , Lhuillier Emeline , Martins Frédéric , Riant Elodie , Zakaroff-Girard Alexia , Schanstra Joost P , Saulnier-Blache Jean Sébastien , Belliere Julie 
Published: September 2023

ABSTRACT

Background
The role of macrophages in the development of rhabdomyolysis-induced acute kidney injury (RM-AKI) has been established, but an in-depth understanding of the changes in the immune landscape could help to improve targeted strategies. Whereas senescence is usually associated with chronic kidney processes, we also wished to explore whether senescence could also occur in AKI and whether senolytics could act on immune cells.

Methods
Single-cell RNA sequencing was used in the murine glycerol-induced RM-AKI model to dissect the transcriptomic characteristics of CD45+ live cells sorted from kidneys 2 days after injury. Public datasets from murine AKI models were reanalysed to explore cellular senescence signature in tubular epithelial cells (TECs). A combination of senolytics (dasatinib and quercetin, DQ) was administered to mice exposed or not to RM-AKI.

Results
Unsupervised clustering of nearly 17 000 single-cell transcriptomes identified seven known immune cell clusters. Sub-clustering of the mononuclear phagocyte cells revealed nine distinct cell sub-populations differently modified with RM. One macrophage cluster was particularly interesting since it behaved as a critical node in a trajectory connecting one major histocompatibility complex class IIhigh (MHCIIhigh) cluster only present in Control to two MHCIIlow clusters only present in RM-AKI. This critical cluster expressed a senescence gene signature, that was very different from that of the TECs. Senolytic DQ treatment blocked the switch from a F4/80highCD11blow to F4/80lowCD11bhigh phenotype, which correlated with prolonged nephroprotection in RM-AKI.

Conclusions
Single-cell RNA sequencing unmasked novel transitional macrophage subpopulation associated with RM-AKI characterized by the activation of cellular senescence processes. This work provides a proof-of-concept that senolytics nephroprotective effects may rely, at least in part, on subtle immune modulation.
Youth Exposure and Response to the FDA Health Warning Label on Electronic Cigarettes Packaging: Policy Implications
Authors: Asfar Taghrid , Oluwole Olusanya J , Pan Yue , Casas Alejandra , Garayua Adriana Maite Hernandez , Schmidt Michael , Noar Seth M 
Published: September 2023

Abstract

Introduction
Youth represent a high-priority group for e-cigarette health communication. This study examined youth exposure to the Food and Drug Administration (FDA) e-cigarette warning label over 4 years and its association with change in youth harm perception and intention.

Aims and Methods
We pooled data from the 2018–2021 National Youth Tobacco Survey (age 10–17; n = 67 159). Participants were divided into four groups: never users (58.5%), susceptible nonusers (16.3%), former users (12.7%), and current users (12.5%). We examined the prevalence, time-trend, correlates, and association of youth exposure to the warning with addictiveness and harm perception, intention to use e-cigarettes, and intention to quit all tobacco products.

Results
Only 24.5% of youth were exposed to the warning. Exposure increased from 14.9% in 2018 to 30.8% in 2019, then declined to 25.2% in 2021. Hispanic (adjusted odds ratio (aOR) = 0.76 [95% CI = 0.641 to 0.89]) and non-Hispanic black current users (0.53 [0.40 to 0.69]) were less likely to be exposed to the warning than white current users. Youth exposure was positively associated with a higher perception of e-cigarette addictiveness (1.12 [1.04 to 1.19]) and intention to quit all tobacco products (1.28 [1.13 to 1.46]). However, exposure was negatively associated with harm perception (0.91 [0.85 to 0.96]) and the intention to use e-cigarettes among e-cigarette nonusers (2.38 [1.99 to 2.84]).

Conclusions
The decline in youth exposure to the warning indicates wear-out effects. Strengthening the label by using compelling designs, adding themes on e-cigarette harm to youth, periodically rotating warning content, and using culturally tailored messaging may improve its impact on youth and address racial/ethnic disparities.

Implications
The FDA e-cigarette label reached only 24.5% of youth, and exposure to the warning declined to indicate wear-out effects. Exposure was significantly lower among minorities. Exposure was associated with a higher perception of e-cigarette addictiveness and intention to quit all tobacco products. Still, it did not increase harm perception or reduce intention to use e-cigarettes among nonusers. Strengthening the label by using more compelling designs, including diverse themes focusing on e-cigarette harm relevant to youth, and periodically rotating warning content may improve its impact on youth. Continued surveillance of the implementation of e-cigarette policies is needed to ensure that they equally affect youth across racial/ethnic subpopulations.
Research Models to Mimic Necrotizing Enterocolitis and Inflammatory Bowel Diseases: Focus on Extracellular Vesicles Action
Authors: Duci Miriam , De Cesare Ludovica , Hochuli Agner Henrique Dorigo , Muraca Maurizio , Cananzi Mara , Gamba Piergiorgio , Fascetti-Leon Francesco , Pozzobon Michela 
Published: September 2023

Abstract
This review focuses on the crucial role of the intestinal epithelium in maintaining intestinal homeostasis and its significance in the pathogenesis of necrotizing enterocolitis (NEC) and inflammatory bowel diseases (IBD). NEC is a devastating neonatal disease, while IBD represents a global healthcare problem with increasing incidence. The breakdown of the intestinal barrier in neonates is considered pivotal in the development and progression of both disorders. This review provides an overview of the current state of in vitro, ex vivo, and animal models to study epithelial injury in NEC and IBD, addressing pertinent questions that engage clinicians and researchers alike. Despite significant advancements in early recognition and aggressive treatment, no single therapy has been conclusively proven effective in reducing the severity of these disorders. Although early interventions have improved clinical outcomes, NEC and IBD continue to impose substantial morbidity, mortality, and economic burdens on affected individuals and society. Consequently, exploring alternative therapeutic options capable of preventing and treating the sequelae of NEC and IBD has become a pressing necessity. In recent decades, extracellular vehicles (EVs) have emerged as a potential solution to modulate the pathogenic mechanism in these multifactorial and complex disorders. Despite the diverse array of proposed models, a comprehensive model to investigate and decelerate the progression of NEC and IBD remains to be established. To bridge the translational gap between preclinical studies and clinical applications, enhancements in the technical development of gut-on-a-chip models and EVs hold considerable promise.
From Gene-for-Gene to Resistosomes: Flor's Enduring Legacy
Authors: Dodds Peter N. 
Published: September 2023

The gene-for-gene model proposed by H. H. Flor has been one of the fundamental precepts of plant-pathogen interactions that has underpinned decades of research towards our current concepts of plant immunity. The broad validity of this model as an elegant and accurate genetic description of specific recognition events between the products of plant resistance ( R) and pathogen avirulence ( Avr) genes has been demonstrated many times over in a wide variety of plant disease systems. In recent years detailed molecular and structural analyses have provided a deep understanding of the principles by which plant immune receptors recognize pathogen effectors, including providing molecular descriptions of many of the genetic loci in flax and flax rust characterized by Flor. Recent advances in molecular and structural understanding of immune receptor recognition and activation mechanisms have brought the field to a new level, where rational design of novel receptors through engineering approaches is becoming a realizable goal. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Histone deacetylase 9 plays a role in sevoflurane‐induced neuronal differentiation inhibition by inactivating cAMP‐response element binding protein transcription and inhibiting the expression of neurotrophin‐3
Authors: Li Xinlei , Wang Gongming , Li Wei , Wang Xu , Wu Jiangnan , He Yingxue , Li Xiaowei , Sun Xiaobin , Zhang Mengyuan , Guo Yanjing 
Published: September 2023

AbstractPostoperative cognitive decline (POCD) is a common and serious complication following anesthesia and surgery; however, the precise mechanisms of POCD remain unclear. Our previous research showed that sevoflurane impairs adult hippocampal neurogenesis (AHN) and thus cognitive function in the aged brain by affecting neurotrophin‐3 (NT‐3) expression; however, the signaling mechanism involved remains unexplored. In this study, we found a dramatic decrease in the proportion of differentiated neurons with increasing concentrations of sevoflurane, and the inhibition of neural stem cell differentiation was partially reversed after the administration of exogenous NT‐3. Understanding the molecular underpinnings by which sevoflurane affects NT‐3 is key to counteracting cognitive dysfunction. Here, we report that sevoflurane administration for 2 days resulted in upregulation of histone deacetylase 9 (HDAC9) expression, which led to transcriptional inactivation of cAMP‐response element binding protein (CREB). Due to the colocalization of HDAC9 and CREB within cells, this may be related to the interaction between HDAC9 and CREB. Anyway, this ultimately led to reduced NT‐3 expression and inhibition of neural stem cell differentiation. Furthermore, knockdown of HDAC9 rescued the transcriptional activation of CREB after sevoflurane exposure, while reversing the downregulation of NT‐3 expression and inhibition of neural stem cell differentiation. In summary, this study identifies a unique mechanism by which sevoflurane can inhibit CREB transcription through HDAC9, and this process reduces NT‐3 levels and ultimately inhibits neuronal differentiation. This finding may reveal a new strategy to prevent sevoflurane‐induced neuronal dysfunction.
Nintedanib ameliorates osteoarthritis in mice by inhibiting synovial inflammation and fibrosis caused by M1 polarization of synovial macrophages via the MAPK/PI3K‐AKT pathway
Authors: Yan Jiangbo , Feng Gangning , Yang Yong , Zhao Xin , Ma Long , Guo Haohui , Chen Xiaolei , Wang Hui , Chen Zhirong , Jin Qunhua 
Published: September 2023

AbstractSynovial inflammation and fibrosis are important pathological changes associated with osteoarthritis (OA). Herein, we investigated if nintedanib, a drug specific for pulmonary fibrosis, plays a positive role in osteoarthritic synovial inflammation and fibrosis. We assessed the effect of nintedanib on osteoarthritic synovial inflammation and fibrosis in a mouse model of OA created by destabilization of the medial meniscus and a macrophage M1 polarization model created by stimulating RAW264.7 cells with lipopolysaccharide. Histological staining showed that daily gavage administration of nintedanib significantly alleviated articular cartilage degeneration, reduced the OARSI score, upregulated matrix metalloproteinase‐13 and downregulated collagen II expression, and significantly reduced the synovial score and synovial fibrosis in a mouse OA model. In addition, immunofluorescence staining showed that nintedanib significantly decreased the number of M1 macrophages in the synovium of a mouse model of OA. In vitro results showed that nintedanib downregulated the phosphorylation levels of ERK, JNK, p38, PI3K, and AKT while inhibiting the expression of macrophage M1 polarization marker proteins (CD86, CD80, and iNOS). In conclusion, this study suggests that nintedanib is a potential candidate for OA treatment. The mechanisms of action of nintedanib include the inhibition of M1 polarization in OA synovial macrophages via the MAPK/PI3K‐AKT pathway, inhibition of synovial inflammation and fibrosis, and reduction of articular cartilage degeneration.
Is Cervical Disk Arthroplasty a Suitable Alternative to Treat Degenerative Cervical Myelopathy?
Authors: Schupper Alexander J , Boylan Arianne J , Houten John K 
Published: September 2023

Study Design:
Systemic review

Objective:
To understand the role of cervical disk arthroplasty in the treatment of cervical myelopathy.

Summary of Background Data:
The surgical management of degenerative cervical myelopathy (DCM) most frequently involves decompression and fusion, but stiffness introduced by the fusion and adjacent segment degeneration remain problems that can result in significant morbidity. Cervical disk arthroplasty (CDA) is a newer procedure that has been demonstrated to be safe and effective for the management of cervical spine degenerative disk disease, but it has not been traditionally considered as a treatment option for DCM and the use for this indication has not been extensively studied.

Materials and Methods:
A systematic review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using a search strategy to query all relevant articles on the use of cervical disk arthroplasty in the setting of cervical myelopathy over a 20-year period (2004–2023). This review examines the literature to assess our current understanding of the appropriateness, safety, and value of CDA in the treatment of DCM.

Results:
A total of 844 patients received CDA across the 14 studies that met inclusion criteria, with an average of 60.3±40.4 patients per study (range: 11–152 subjects). Featured studies included 5 (35.7%) prospective studies, of which 2 were randomized. All studies had primary outcome measures of disability and/or pain scores, with the Japanese Orthopedic Association myelopathy score and neck disability index as the most commonly assessed. Four (26.7%) studies compared arthroplasty with arthrodesis. Safety of CDA for DCM was found in all studies with improvement in clinical outcome measurements.

Conclusion:
Cervical disk arthroplasty appears to be a safe and effective surgical option in the management of degenerative cervical myelopathy. Further study is needed to assess if arthroplasty provides clinical improvement in DCM of comparable magnitude and durability as traditional fusion strategies.
PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography—Tandem Mass Spectrometry
Authors: De Gregori Simona , Capone Mara , De Silvestri Annalisa , Albertini Riccardo 
Published: September 2023

Background:
Busulfan (Bu), an alkylating agent commonly used in chemotherapy and transplantation, exhibits high intraindividual pharmacokinetic variability and possible time-dependent variations in clearance, which complicate therapeutic drug monitoring. Numerous analytical methods have been developed to reduce analysis time and facilitate timely decision-making regarding treatment changes; however, the validation procedures rarely involve analysis of potentially interfering excipients. Macrogol 400 (PEG 400) should be considered as a possible interfering agent in the detection of plasma Bu levels, especially as an ionization suppressor.

Methods:
Six intravenous formulations of Bu were compared with identify at least 1 common excipient (PEG 400). During the 176 therapeutic drug monitoring analyses of Bu, one of the PEG 400 specific mass-to-charge ratio transitions was determined using an instrumental method. After coelution with Bu and its internal standard (Bu-d8) was confirmed, all analyses were repeated using a different experimental setup free of ion suppression induced by PEG. The concentration–time profile of PEG 400 was also analyzed.

Results:
The area under the curve obtained from the 2 data sets was compared and analyzed using Lin concordance correlation coefficient and Bland–Altman plot analysis. The results from the 2 analytical methods were comparable: PEG 400 negatively affected the Bu-d8 coefficient of variation but not the Bu/Bu-d8 ratio.

Conclusions:
The possible interference of PEG 400 should be thoroughly investigated, especially with respect to analytical methods that cannot be supported by correction of the stable isotopically labeled internal standard analog.