bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body plan evolvability: The role of variability in gene regulatory networks
Authors: Spirov Alexander V. , Myasnikova Ekaterina M. , Holloway David M. 
Published: May 2024

Recent computational modeling of early fruit fly (Drosophila) development has characterized the degree to which gene regulation networks can be robust to natural variability. In the first few hours of development, broad spatial gradients of maternally derived transcription factors activate embryonic gap genes. These gap patterns determine the subsequent segmented insect body plan through pair-rule gene expression. Gap genes are expressed with greater spatial precision than the maternal patterns. Computational modeling of the gap–gap regulatory interactions provides a mechanistic understanding for this robustness to maternal variability in wild-type (WT) patterning. A long-standing question in evolutionary biology has been how a system which is robust, such as the developmental program creating any particular species’ body plan, is also evolvable, i.e. how can a system evolve or speciate, if the WT form is strongly buffered and protected? In the present work, we use the WT model to explore the breakdown of such Waddington-type ‘canalization’. What levels of variability will push the system out of the WT form; are there particular pathways in the gene regulatory mechanism which are more susceptible to losing the WT form; and when robustness is lost, what types of forms are most likely to occur (i.e. what forms lie near the WT)? Manipulating maternal effects in several different pathways, we find a common gap ‘peak-to-step’ pattern transition in the loss of WT. We discuss these results in terms of the evolvability of insect segmentation, and in terms of experimental perturbations and mutations which could test the model predictions. We conclude by discussing the prospects for using continuum models of pattern dynamics to investigate a wider range of evo-devo problems.
Data from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors
Authors: Gonzalez Nicole , Rao Nina , Dean Michael , Lee Donghyuk , Hurson Amber N. , Baris Dalsu , Schwenn Molly , Johnson Alison , Prokunina-Olsson Ludmila , Friesen Melissa C. , Zhu Bin , Rothman Nathaniel , Silverman Debra T. , Koutros Stella 
Published: May 2024

<div>Background:<p>Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors.</p>Methods:<p>Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study. Using data on 797 cases and 1,418 controls, two-stage polytomous logistic regression was used to evaluate etiologic heterogeneity between bladder cancer subtypes and quantitative, lifetime estimates of respirable elemental carbon (REC), a surrogate for diesel exposure. Poisson regression was used to evaluate associations between REC and mutational signatures.</p>Results:<p>We observed significant heterogeneity in the diesel-bladder cancer risk relationship, with a strong positive association among cases with high-grade, nonmuscle invasive <i>TP53</i>-mutated tumors compared with controls [OR<sub>Top Tertile vs.Unexposed</sub>, 4.8; 95% confidence interval (CI), 2.2–10.5; <i>P</i><sub>trend</sub> < 0.001; <i>P</i><sub>heterogeneity</sub> = 0.002]. In muscle-invasive tumors, we observed a positive association between diesel exposure and the nitro-PAH signatures of 1,6-dintropyrene (RR, 1.93; 95% CI, 1.28–2.92) and 3-nitrobenzoic acid (RR, 1.97; 95% CI, 1.33–2.92).</p>Conclusions:<p>The relationship between diesel exhaust and bladder cancer was heterogeneous based on the presence of <i>TP53</i> mutations in tumors, further supporting the link between PAH exposure and <i>TP53</i> mutations in carcinogenesis. Future studies that can identify nitro-PAH signatures in exposed tumors are warranted to add human data supporting the link between diesel and bladder cancer.</p>Impact:<p>This study provides additional insight into the etiology and possible mechanisms related to diesel exhaust-induced bladder cancer.</p></div>
MLLT6/ATF2 Axis Restrains Breast Cancer Progression by Driving DDIT3/4 Expression
Authors: Yu Qing , Zhao Jiayi , Yang Anli , Li Xiangxin 
Published: May 2024

Abstract
Epigenetic deregulation is strongly associated with tumor progression. The identification of natural tumor suppressors to overcome cancer metastasis is urgent for cancer therapy. We investigate whether myeloid/lymphoid or mixed-lineage leukemia translocated (MLLT) family members contribute to breast cancer progression and found that high MLLT6 expression predicted a better prognosis and that gradually decreased MLLT6 expression was accompanied by breast cancer malignancy. MLLT6 was downregulated by hypoxia-induced enrichment of DNMT1 at the MLLT6 promoter. The results of in vitro functional experiments indicated that MLLT6 depletion promoted colony formation and cell migration, probably by hampering apoptosis. RNA profiling revealed that the apoptotic pathway was downregulated following stable knockdown of MLLT6. DNA damage-inducible transcript 3/4 (DDIT3/4) were among the top 10 downregulated genes and may have expression patterns similar to that of MLLT6. Restoring DDIT3/4 expression in cells with MLLT6 depletion blocked colony formation and cell migration and attenuated the successful colonization of breast cancer cells in vivo. We also determined that the transcription factor activating transcription factor 2 is a binding partner of MLLT6 and participates in the MLLT6/ATF2 axis, which was reinforced by inhibition of AKT signaling, in turn inducing DDIT3/4 expression by establishing an active chromatin structure at the DDIT3/4 gene promoters. As MLLT6 promotes breast cancer cell apoptosis by inducing DDIT3/4 expression during metastasis, it could be a novel tumor suppressor.
Implications: Control of MLLT6 expression via inhibition of PI3K/AKT kinase activity is a potential therapeutic approach for the management of metastatic breast cancer.
Relações de trabalho no Brasil: aspectos de sua evolução histórica (1822-1917)
Authors: Debes Célio 
Published: May 2024

Until the Civil Code carne into force in Brazil (1917), labour relations were ruled by norms of the Philippine Ordinances (1603), laws aiming at governing agricultura! activities (1830, 1837 and 1879), the Commercial Code (1850), and norms of a merely local nature. After the Republic was implanted, with the increasing number of foreign immigrants and the emergence of urban industries, besides lax measures to protect workers under age and the freedom to organize labour unions,there was a legislation concerning the expulsion of foreigners (its norms were aggravated with the suppression of the guarantee offered to those who had married Brazilian women or whose children had been born here).The situation of helplessness in which workers used to live in Brazil has its roots in the generalized contempt devoted to manual labour. Manual labour was regarded as debasing, whereas idleness was surrounded by an aureole of nobility. In spite of everything, the proletariafs struggles contributed to agreat extern to the guarantees offered them by the legislation.
Association Between Remnant Cholesterol and Risk of Incident Atrial Fibrillation: Population‐Based Evidence From a Large‐Scale Prospective Cohort Study
Authors: Li Likang , Wang Chuangshi , Ye Zebing , Van Spall Harriette G. C. , Zhang Jingyi , Lip Gregory Y. H. , Li Guowei 
Published: May 2024

Background
Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited.

Methods and Results

Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow‐up of 11.9 years (first quartile–third quartile, 11.6–13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person‐years (95% CI, 4.86–4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91–1.00) for second quartile; HR=0.92 (95% CI, 0.88–0.96) for third quartile; and HR=0.85 (95% CI, 0.81–0.89) for fourth quartile (
P
for trend <0.001). The association between RC quartiles and risk of incident AF was stronger in participants aged ≥65 years, in men, and in participants without history of diabetes when compared with control groups (
P
<0.001 for interaction).

Conclusions
On the basis of data from this large‐scale prospective cohort study, elevated RC was associated with a lower risk of incident AF.
A European Feminist Foreign and Security Policy? Norm Contestation and Norm Negotiations in the European Parliament
Authors: Elgström Ole , Sundström Malena Rosén 
Published: May 2024

Abstract
In 2020, the European Parliament (ep) issued a resolution calling for all European Union (EU) Member States to adopt feminist foreign and security policies, and for a gender-transformative vision in the EU’s own external policy. Drawing on the literatures on negotiations and norm contestation, this article3 asks why the resolution was so progressive. It also asks how we can characterize and explain the nature of the negotiations leading to the resolution. The findings demonstrate a low level of contestation and negotiations mainly characterized by integrative strategies and solutions. The main opponents to the resolution, the populist radical right groups, were more or less absent from the negotiations but opposed by verbal contestation in plenum and through amendments to the text. We find that individual- and organizational level factors have high explanatory power: the gender equality-friendly institutional culture in the ep was further strengthened by the entrepreneurship of two committed rapporteurs.
Is Front associated with Above and Back with Below? Association between Allocentric Representations of Spatial Dimensions
Authors: Vainio Lari , Vainio Martti 
Published: May 2024

Abstract
Previous research has revealed congruency effects between different spatial dimensions such as right and up. In the audiovisual context, high-pitched sounds are associated with the spatial dimensions of up/above and front, while low-pitched sounds are associated with the spatial dimensions of down/below and back. This opens the question of whether there could also be a spatial association between above and front and/or below and back. Participants were presented with a high- or low-pitch stimulus at the time of the onset of the visual stimulus. In one block, participants responded according to the above/below location of the visual target stimulus if the target appeared in front of the reference object, and in the other block, they performed these above/below responses if the target appeared at the back of the reference. In general, reaction times revealed an advantage in processing the target location in the front–above and back–below locations. The front–above/back–below effect was more robust concerning the back–below component of the effect, and significantly larger in reaction times that were slower rather than faster than the median value of a participant. However, the pitch did not robustly influence responding to front/back or above/below locations. We propose that this effect might be based on the conceptual association between different spatial dimensions.
Diagnosing Radial Ventilation in Dropsonde Observations of Hurricane Sam (2021)
Authors: Tang Brian H. , Rios-Berrios Rosimar , Zhang Jun A. 
Published: May 2024

Abstract
This study presents a method to diagnose radial ventilation, the horizontal flux of relatively low-θe air into tropical cyclones, from dropsonde observations. We used this method to investigate ventilation changes over three consecutive sampling periods in Hurricane Sam (2021), which underwent substantial intensity changes over 3 days. During the first and last periods, coinciding with intensification, the ventilation was relatively small due to a lack of spatial correlation between radial flow and θe azimuthal asymmetries. During the second period, coinciding with weakening, the ventilation was relatively large. The increased ventilation was caused by greater shear associated with an upper-level trough, tilting the vortex, along with dry, low-θe air wrapping in upshear. The spatial correlation of the radial inflow and anomalously low-θe air resulted in large ventilation at mid- to upper levels. Additionally, at low to midlevels, there was evidence of mesoscale inflow of low-θe air in the stationary band complex. The location of these radial ventilation pathways and their effects on Sam’s intensity are consistent with previous idealized and real-case modeling studies. More generally, this method offers a way to monitor ventilation changes in tropical cyclones, particularly when there is full-troposphere sampling around and within a tropical cyclone’s core.

Significance Statement
Ventilation, the injection of relatively dry and/or cool air into a tropical cyclone, may weaken a storm. In contrast, the lack of ventilation is favorable for intensification. The purpose of this study is to present a method to diagnose ventilation using aircraft dropsonde observations. Using dropsonde observations collected in Hurricane Sam (2021), there was a period of increased lateral ventilation in two regions around the storm that coincided with when the storm rapidly weakened. The results suggest that monitoring ventilation from dropsonde observations, when available, may be useful for anticipating ventilation-induced intensity changes in tropical cyclones and further studying ventilation pathways.
Laryngeal Cancer Screening During Flexible Video Laryngoscopy Using Large Computer Vision Models
Authors: Mamidi Ishwarya S. , Dunham Michael E. , Adkins Lacey K. , McWhorter Andrew J. , Fang Zhide , Banh Britney T. 
Published: May 2024

Objective: Develop an artificial intelligence assisted computer vision model to screen for laryngeal cancer during flexible laryngoscopy. Methods: Using laryngeal images and flexible laryngoscopy video recordings, we developed computer vision models to classify video frames for usability and cancer screening. A separate model segments any identified lesions on the frames. We used these computer vision models to construct a video stream annotation system. This system classifies findings from flexible laryngoscopy as “potentially malignant” or “probably benign” and segments any detected lesions. Additionally, the model provides a confidence level for each classification. Results: The overall accuracy of the flexible laryngoscopy cancer screening model was 92%. For cancer screening, it achieved a sensitivity of 97.7% and a specificity of 76.9%. The segmentation model attained an average precision at a 0.50 intersection-over-union of 0.595. The confidence level for positive screening results can assist clinicians in counseling patients regarding the findings. Conclusion: Our model is highly sensitive and adequately specific for laryngeal cancer screening. Segmentation helps endoscopists identify and describe potential lesions. Further optimization is required to enable the model’s deployment in clinical settings for real-time annotation during flexible laryngoscopy.
Brain injury plasma biomarkers in patients on veno-arterial extracorporeal membrane oxygenation: A pilot prospective observational study
Authors: Ahmad Syed Ameen , Kapoor Shrey , Muquit Siam , Gusdon Aaron , Khanduja Shivalika , Ziai Wendy , Everett Allen D. , Whitman Glenn , Cho Sung-Min , on behalf of HERALD investigators  
Published: May 2024

Introduction Early diagnosis of acute brain injury (ABI) is critical for patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation. Methods In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and tubulin associated unit (Tau) were collected daily after V-A ECMO cannulation and measured using a multiplex platform. Primary outcomes were occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS). Results Of 20 consented patients (median age = 48.5°years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcome at discharge. 10 (50%) patients were centrally cannulated. Median duration on ECMO was 4.5°days (IQR: 2.5–9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI. Conclusion Further studies are warranted to determine how plasma biomarkers may facilitate early detection of ABIs in V-A ECMO to assist timely clinical decision-making.
Major brain injuries at term continue to influence DTI parameters in adolescents born very preterm: a 13-year follow-up study
Authors: Setänen Sirkku , Merisaari Harri , Saunavaara Virva , Uusitalo Karoliina , Lahti Katri , Ngum Peter , Haataja Leena , Parkkola Riitta 
Published: May 2024

Background Major brain injuries in structural brain magnetic resonance imaging (MRI) at term affect concurrent diffusion tensor imaging (DTI) parameters in very preterm infants. White matter is known to gradually maturate along with increasing gestational age, which is characterized by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). Purpose To study the difference between DTI parameters at term and 13 years in adolescents born very preterm with and without major pathologies in structural brain MRI at term. Material and Methods Adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) in 2004–2006 at Turku University Hospital, Finland were included. We evaluated FA and MD at term and 13 years in 18 regions of interest using the JHU-neonate-SS atlas to compare the differences in these parameters between adolescents with and without major injuries identified on MRI at term. Results A total of 24 adolescents underwent brain MRI including DTI both at term and 13 years. Adolescents with major brain injury pathologies (n = 6) in structural MRI at term had decreased FA in the left corpus callosum and right cingulate gyrus part, and increased MD in the left corpus callosum, right anterior limb of internal capsule, and right posterior limb of the internal capsule at 13 years, in comparison with adolescents without major brain injuries (n = 18) in structural MRI at term. Conclusion Our findings suggest that major brain injuries identified on structural MRI at term affect brain maturation, with adverse effects in FA and MD still during adolescence.
Neurofilament Light Chain as a Biomarker of Global Cognition in Individuals With Possible Vascular Mild Cognitive Impairment
Authors: Gaur Amish , Gallagher Damien , Herrmann Nathan , Chen Jinghan Jenny , Marzolini Susan , Oh Paul , Amemiya Yutaka , Seth Arun , Kiss Alex , Lanctôt Krista L. 
Published: May 2024

Background Neurofilament Light Chain (NfL) is a biomarker of axonal injury elevated in mild cognitive impairment (MCI) and Alzheimer’s disease dementia. Blood NfL also inversely correlates with cognitive performance in those conditions. However, few studies have assessed NfL as a biomarker of global cognition in individuals demonstrating mild cognitive deficits who are at risk for vascular-related cognitive decline. Objective To assess the relationship between blood NfL and global cognition in individuals with possible vascular MCI (vMCI) throughout cardiac rehabilitation (CR). Additionally, NfL levels were compared to age/sex-matched cognitively unimpaired (CU) controls. Method Participants with coronary artery disease (vMCI or CU) were recruited at entry to a 24-week CR program. Global cognition was measured using the Montreal Cognitive Assessment (MoCA) and plasma NfL level (pg/ml) was quantified using a highly sensitive enzyme-linked immunosorbent assay. Results Higher plasma NfL was correlated with worse MoCA scores at baseline ( β = −.352, P = .029) in 43 individuals with vMCI after adjusting for age, sex, and education. An increase in NfL was associated with worse global cognition ( b[SE] = −4.81[2.06], P = .023) over time, however baseline NfL did not predict a decline in global cognition. NfL levels did not differ between the vMCI (n = 39) and CU (n = 39) groups ( F(1, 76) = 1.37, P = .245). Conclusion Plasma NfL correlates with global cognition at baseline in individuals with vMCI, and is associated with decline in global cognition during CR. Our findings increase understanding of NfL and neurobiological mechanisms associated with cognitive decline in vMCI.