bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonstationary Laguerre–Gaussian states in a Magnetic Field
Authors: Sizykh G K , Chaikovskaia A D , Grosman D V , Pavlov I I , Karlovets D V
Published: April 2024

The Landau states of electrons with orbital angular momentum in magnetic fields are important in the quantum theories of metals and of synchrotron radiation at storage rings, in relativistic astrophysics of neutron stars, and in many other areas. In realistic scenarios, electrons are often born inside the field or injected from a field-free region, requiring nonstationary quantum states to account for boundary or initial conditions. This study presents nonstationary Laguerre–Gaussian (NSLG) states in a longitudinal magnetic field, characterizing vortex electrons after their transfer from vacuum to the field. Comparisons with Landau states and calculations of observables such as mean energy and root-mean-square (r.m.s.) radius show that the r.m.s. radius of the electron packet in the NSLG state oscillates in time around a significantly larger value than that of the Landau state. This quantum effect of oscillations is due to boundary conditions and can potentially be observed in various problems, particularly when using magnetic lenses of electron microscopes and linear accelerators. Analogies are drawn between a quantum wave packet and a classical beam of many particles in phase space, including the calculation of mean emittance of the NSLG state as a measure of its quantum nature.
On the Magnitudes of some CKM Matrix Elements
Authors: Ligeti Zoltan
Published: April 2024

This write-up follows the presentation at the symposium, with emphasis on topics and ideas discussed there. It is purposefully informal, not a review of the field, and neither does it include a complete list of references. However, I hope that readers might find somwe comments useful or amusing, and may appreciate the challenges and reasons for excitement about recent progress and future opportunities in flavor physics.
Changes over time of fruit, vegetable and sweets consumption among European adolescents and associations with sociodemographic characteristics: an HBSC study
Authors: Queral Judit , Wargers Annemieke , Tarro Lucia , Llauradó Elisabet , Solà Rosa , Jansen Wilma
Published: April 2024

Background

European adolescents do not eat enough fruits and vegetables and have a high sweets consumption. This study aims to analyse the changes in time of dietary behaviours related to sociodemographic characteristics, among European adolescents.

Methods

Health Behaviour in School Age Children data (2013/14 to 2017/18), of European adolescents, aged 11- to15-year-old, were used. Family Affluence Scale identified socioeconomic status (SES). Changes in time of dietary behaviours and associations with sociodemographic characteristics were estimated by binary and multilevel logistic regression.

Results

182 719 adolescents were included, and 10/36 European countries showed a significant increase in daily fruit and vegetable consumption and 12/36 countries a significant decrease in sweets consumption over 4 years. The multilevel analysis showed that 13- and 15-year-old adolescents consumed fewer daily fruits and vegetables (P < 0.001) and more daily sweets (P < 0.001) than 11-year-old adolescents. Also, 15-year-old adolescents’ sweets consumption change over time was less favourable (P = 0.006). Girls consumed more daily fruits, vegetables and sweets than boys (P < 0.001).

Low SES adolescents consumed fewer daily fruits and vegetables than medium/high SES adolescents. Additionally, the low SES adolescents’ vegetable consumption change over time was less favourable (P < 0.001).

Conclusions

Dietary behaviour policy recommendations should be adapted for the sex, age and SES of the population.
Registered reports and associated benefits for agricultural economics
Authors: Arpinon Thibaut , Lefebvre Marianne
Published: April 2024

The distribution of published scientific evidence is biased. There is accumulating evidence of the frequent use of questionable publishing practices and questionable research practices, and current solutions are limited. This has important undesirable consequences for policy-oriented areas such as agricultural economics. In this article, we discuss a potential solution: Registered Reports. We first provide an overview of the Registered Report publication format. We demonstrate how Registered Reports outperform pre-registration, while also efficiently contributing to reducing questionable research practices, canceling questionable publishing practices, and providing more reliable results that can inform evidence-based policymaking. Second, we present a benchmark of Registered Reports in economics today and discuss potential barriers using survey data from economic journal editors. Lastly, we highlight the importance of developing the Registered Report publication format in agricultural economics.
Evaluation of Social Interventions with People with Disabilities: A Systematic Literature Review
Authors: Mira-Aladrén Marta , Martín-Peña Javier , Gil-Lacruz Marta
Published: April 2024

This article aims to review the scientific production on social interventions (SI) in the field of persons with disabilities (PWD) and their families and to analyze its evaluations. To do so, it starts from the context of the social model of care of the United Nation’s Convention on the Rights of Persons with Disabilities and the sustainable development goals, and the evaluation of SI. The methodology proposes a systematic review of the existing literature on SI with PWD and their evaluation, based on the preferred reporting items for systematic review and meta-analysis (or PRISMA) model, including 19 articles. The results highlight issues such as the scarcity of publications with evaluations, the lack of homogeneity in the evaluation indicators used, the large number of interventions related to intellectual disability, and a large proportion of community interventions. This scoping review assists future research to consider different questions about evaluation indicators and implementation of the social model or social inclusion, among others.
Blessing applications: a new interventionism?
Authors: Holden Andrew
Published: April 2024

The court’s traditional approach to applications by trustees to approve or ‘bless’ the exercise of their fiduciary discretions is one of judicial restraint, but in recent authority, there has been an increasing trend towards judicial intervention in the merits of the trustee’s decision. This article analyses that trend and considers how practitioners can maximise the prospects of successfully securing the court’s blessing for important trustee decisions.
Testamentary undue influence in Australia: should it be reformed?
Authors: de Mestre Mary-Ann , Kha Henry
Published: April 2024

Testamentary undue influence is a doctrine distinct from the equitable doctrine of undue influence. The requirements to prove testamentary undue influence have caused academic and judicial criticism questioning whether the doctrine adequately safeguards the vulnerable testator. As the aged population increases, it is increasingly important to re-examine the level of protection afforded by the doctrine. The doctrine of testamentary undue influence should be modified to be closer in line with equitable undue influence in inter vivos transfers to enable succession law to promote more just outcomes that uphold the true intention of testators in contemporary Australia.
Tempol effect on oxidative and mitochondrial markers in preclinical models for prostate cancer
Authors: Rossetto Isabela Maria Urra , Santos Felipe Rabelo , da Silva Heloina Mariano , Minatel Elaine , Mesquitta Mariana , Salvador Marcos José , Montico Fábio , Cagnon Valéria Helena Alves
Published: April 2024

Background

Tempol is a redox-cycling nitroxide considered a potent antioxidant. The present study investigated the tempol effects on oxidative stress and mitochondrial markers on prostate cancer (PCa).

Methods

PC-3 and LnCaP cells were exposed to tempol. Cell viability test, western blot and Amplex Red analyses were performed. In vivo, five experimental groups evaluated tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol doses. Control groups received water as the vehicle. The ventral lobe of the prostate and the blood were collected and submitted to western blotting or enzymatic activity analyses.

Results

In vitro, tempol decreased cell viability and differentially altered the H2O2 content for PC-3 and LNCaP. Tempol increased SOD2 levels in both cell lines and did not alter Catalase protein levels. In vivo, tempol increased SOD2 levels in the early stage and did not change Catalase levels in the different PCa stages. Systemically, tempol decreased SOD2 levels in the late-stage and improved redox status in the early and late stages, which was confirmed by reduced LDH in tempol groups. Alterations on energetic metabolism and oxidative phosphorylation were observed in TRAMP model.

Conclusion

Tempol can be considered a beneficial therapy for PCa treatment considering its antioxidant and low toxicity properties, however the PCa progression must be evaluated to get successful therapy.
Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation
Authors: Xie Hongliang , Zhang Aolin , Li Junwei , Mou Xuan , He Tao , Yeung Tsz Ching , Lau Clara Bik San , Zuo Zhong , Li Ping , Kennelly Edward J , Leung Ping Chung , Tang Yu , Fan Xiaohui , Wang Chi Chiu , Li Lu
Published: April 2024

Objective

The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR.

Methods

The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS).

Results

In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms.

Conclusions

Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.
Patterns and outcomes of acute toxicological cases before, during, and after COVID-19 lockdown in Sohag University hospitals, Egypt
Authors: Shokry Zaghary Meray Medhat , Abd ElKader Mai M , Mousa Rasha Elhaddad Ali , Said Ahmed M
Published: April 2024

Background

Toxicologists manage poisoning by preventing, detecting, and treating it, which requires continuous data collection and analysis of toxicological hazards.

Aim of the work

The study aims to report and compare the pattern and outcome of acute toxicological cases admitted to Sohag University Hospitals during the COVID-19 lockdown (2020–2021) with the year before (2019) and the year after (2022).

Methods

This comparative study reviewed the sociodemographic and clinical data in the medical records. The study showed that Sohag University Hospitals received 670 toxicological cases between 2019 and 2022; 105 cases in 2019, 347 cases in 2020–2021, and 218 cases in 2022.

Results

Most of patients were below seven years with no sex differences. Accidental poisoning was the most frequent toxicity. The oral route was the most common in the three studied periods. During the lockdown, metal phosphide was the most frequent (19.0%), while therapeutic agents were the most reported after the lockdown (23.9%). The delay time showed a significant difference between the studied periods (p-value < 0.001). In the three studied periods, complete recovery was achieved in more than 70% of cases; however, the mortality rate and the rate of complications during the lockdown period (10.4% and 9.5%, respectively) were almost twice those of the year before and the year after the pandemic with significant odds ratio of mortality during pandemic (OR) 0.07 CI 95% (0.02, 0.11).

Conclusion

The pandemic had a bad impact on outcomes as showed the highest percentage of mortality compared to before and after COVID-19 periods.
Unravelling the veil of traffic safety: a comprehensive analysis of factors influencing crash frequency across US states
Authors: Obeidat Mohammed Said , Obeidat Rahma Mohammad , Dweiri Fikri
Published: April 2024

Traffic crashes are a prominent cause of fatalities around the world. This study focuses on the dynamics of traffic safety by analysing factors influencing crash frequency during both nighttime and daytime conditions. Four years' data derived from the Fatality Analysis Reporting System (FARS) database were analysed statistically based on the negative binomial regression model, to identify the contributions of several factors affecting crash outcomes. The findings reveal significant related factors, including area type, roadway alignment, speeding-related factors, sex of driver, number of lanes, grade, surface type and weather conditions, that contributed to the expected crash frequency during both daytime and nighttime conditions. Through quantitative analysis, the extent to which each factor contributes to the expected crash frequency was determined, offering effective insights for policymaking to boost roadway safety. The findings highlight the necessity of implementing targeted strategies to minimize the risk of crashes by creating safer road environments.
Patterns of use of a myoelectric prosthesis in a cohort of children with transverse defects below the level of the elbow
Authors: Ros Dopico Lucía , Alfonso Barrera Ejessie , Valero Telleria Berta , Ruiz-Zurita Gonzalo , Martinez Moreno Mercedes
Published: April 2024

Background:

Myoelectric prostheses have become the accepted standard of care for pediatric upper-limb amputees.

Objectives:

To describe the clinical characteristics and patterns of prosthesis use and to analyze the changes that occur during the growth process of these patients.

Study design:

This is a longitudinal retrospective study comparing the results of surveys carried out in 2015 and 2022.

Methods:

The variables measured included clinical and demographic characteristics, patterns of use, and satisfaction with the prosthesis.

Results:

Twenty-one patients with transverse defects were fitted with myoelectric prostheses. With increasing age, there was a statistically nonsignificant decrease in the duration of use and a decrease in the number of patients using the prosthesis for activities of daily living from 13 to 10 (p = 0.045), with a 28% dropout rate, higher in patients with more distal defects.

Conclusions:

Since 2015, we have observed a decrease in the number of hours of prosthesis use, while maintaining a high percentage of patients using the prosthesis.
Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel
Authors: Gregori Alessandro , Bergonzini Cecilia , Capula Mjriam , de Mercado Rick Rodrigues , Danen Erik H. J. , Giovannetti Elisa , Schmidt Thomas
Published: April 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) acquired resistance to chemotherapy poses a major limitation to patient survival. Despite understanding of some biological mechanisms of chemoresistance, much of those mechanisms remain to be uncovered. Mechanobiology, which studies physical properties of cells, holds promise as a potential target for addressing challenges of chemoresistance in PDAC. Therefore, we here in an initial step, assessed the altered mechanobiology of PDAC cells with acquired chemoresistance to gemcitabine and paclitaxel.

Methods

Five PDAC cell lines and six stably-resistant subclones were assessed for force generation on elastic micropillar arrays. Those measurements of mechanical phenotype were complemented by single-cell motility and invasion in collagen matrix were investigated using 2D models and 3D extracellular matrix-mimetic, respectively. Further the nuclear translocation of Yes-associted protein (YAP), as a measure of active mechanical status, was compared, and biomarkers of the epithelial-to-mesenchymal transition (EMT) were evaluated using RT-PCR.

Results

PDAC cells with acquired chemoresistance exert higher traction forces than their parental/wild-type (WT) cells. In 2D, single-cell motility was altered for all chemoresistant cells, with a cell-type specific pattern. In 3D, spheroids of chemoresistant PDAC cells were able to invade the matrix, and remodel collagen more than their WT clones. However, YAP nuclear translocation and EMT were not significantly altered in relation to changes in other physical parameters.

Conclusion

This is the first study to investigate and report on the altered mechanobiological features for PDAC cells that have acquired chemoresistance. A better understanding of mechanical features could help in identifying future targets to overcome chemoresistance in PDAC.
Sleep deprivation and the rodent psychomotor vigilance test (rPVT): Assessing lapses in attention, the response stimulus interval effect, and time on task in rats using food reinforcement
Authors: Davis Catherine M. , Elliott Victoria , Smith Joan
Published: April 2024

Study objective

Sleep deprivation (SD) impairs sustained attention when assessed with the psychomotor vigilance test (PVT). Food restriction attenuates the effects of SD on sustained attention in rats, possibly limiting translation of rodent tests. Our goal was to determine if an rPVT requiring high baseline performance was sensitive to the effects of SD when using food restriction and reinforcement.

Methods

rPVT-trained rats experienced SD and were tested the following day.

Results

SD significantly increased lapses, and this effect was specific to shorter response-stimulus intervals. Decreased percent correct responses and increased slow reaction times were also found following SD.

Conclusion

The rPVT is sensitive to the performance impairing effects of SD in food restricted rats, a common methodology used to train and maintain performance on operant tests.
E.PathDash, pathway activation analysis of publicly available pathogen gene expression data
Authors: Taub Lily , Hampton Thomas H. , Sarkar Sharanya , Doing Georgia , Neff Samuel L. , Finger Carson E. , Fukutani Kiyoshi Ferreira , Stanton Bruce A.
Published: April 2024

E.PathDash facilitates re-analysis of gene expression data from pathogens clinically relevant to chronic respiratory diseases, including a total of 48 studies, 548 samples, and 404 unique treatment comparisons. The application enables users to assess broad biological stress responses at the KEGG pathway or Gene Ontology level and also provides data for individual genes. E.PathDash reduces the time required to gain access to data from multiple hours per dataset to seconds. Users can download high quality images such as volcano plots and boxplots, differential gene expression results and raw count data, making it fully interoperable with other tools. Importantly, users can rapidly toggle between experimental comparisons and different studies of the same phenomenon, enabling them to judge the extent to which observed responses are reproducible. As a proof of principle, we invited two cystic fibrosis scientists to use the application to explore scientific questions relevant to their specific research areas. Reassuringly, pathway activation analysis recapitulated results reported in original publications, but it also yielded new insights into pathogen responses to changes in their environments, validating the utility of the application. All software and data are freely accessible and the application is available at scangeo.dartmouth.edu/EPathDash.

Importance

Chronic respiratory illnesses impose a high disease burden on our communities and people with respiratory diseases are susceptible to robust bacterial infections from pathogens, includingPseudomonas aeruginosaandStaphylococcus aureus, that contribute to morbidity and mortality. Public gene expression datasets generated from these and other pathogens are abundantly available and an important resource for synthesizing existing pathogenic research, leading to interventions that improve patient outcomes. However, it can take many hours or weeks to render publicly available datasets usable; significant time and skills are needed to clean, standardize, and apply reproducible and robust bioinformatic pipelines to the data. Through collaboration with two microbiologists we have shown that E.PathDash addresses this problem, enabling them to elucidate pathogen responses to a variety of over 400 experimental conditions and generate mechanistic hypotheses for cell-level behavior in response to disease-relevant exposures, all in a fraction of the time.
Gaze inversion effect: Sex invariance and difference in gaze direction sensitivity
Authors: Matsuyoshi Daisuke , Kuraguchi Kana , Ashida Hiroshi , Watanabe Katsumi
Published: April 2024

Even though humans are adept at distinguishing various faces, inversion dramatically spoils the ability. This face inversion effect is remarkably robust across observers; however, whether inversion impairs the perception of facial parts (particularly the eye) is inconsistent across studies. Some studies have shown that featural processing remains preserved or even enhanced when faces are inverted, while others have shown that inversion impairs featural processing. These mixed findings may result from confounding factors such as a small number of participants, an imbalanced participant sex ratio, and the varying nature of the tasks in previous reports. To address these issues, we assessed the effect sizes of face orientation, sex, and their interaction in low-level psychophysical discrimination of briefly presented gaze stimuli in a well-powered cohort with a balanced sex ratio (N = 190). The results revealed a medium-to-large-sized effect of inversion (f= 0.35) and a small-to-medium-sized effect of sex (f= 0.17) on gaze direction discrimination but no meaningful interaction (f= 0.05). Thus, our results demonstrated an almost equivalent gaze inversion effect between females and males (sex invariance) and a female superiority in overall gaze direction sensitivity (sex difference). We suggest that inversion impairs sensitivity to gaze direction, but whether it leads to a change in explicit behavioral performance may depend on specific task settings rather than the participant’s sex.
FLASH Irradiation Regulates IFN-β induction by mtDNA via Cytochrome c Leakage
Authors: Lv Jianfeng , Sun Jianhan , Luo Yunbin , Liu Juntao , Wu Di , Fang Yiyu , Lan Haoyang , Diao Longfei , Ma Yuqi , Li Yuan , Wang Meizhi , Zhao Ziming , Wang Heming , Morris Austin , Zhang Wenkang , Zhang Zihao , Lin Lin , Jia Haoyan , Wang Chao , Li Tianyi , Mourou Gerard , Huang Senlin , Yang Gen , Yan Xueqing
Published: April 2024

Ultrahigh dose rate radiotherapy (FLASH-RT) is under intensive investigation for its biological benefits. The mechanisms underlying its ability to spare normal tissues while suppress tumor growth still remain controversial. Here we reveal that compared to the low dose rate electron irradiation (0.36 Gy/s), FLASH electron irradiation at 61 or 610 Gy/s enhances the cytochrome c leakage from mitochondria in human breast cells MCF-10A, which elicits substantial caspase activation, suppresses both the cytosolic mitochondrial DNA (mtDNA) accumulation and IFN-β secretion. Besides, the deletion of mtDNA severely decreases the radiation-induced cGAS-STING activation. Conversely, the cytochrome c leakage in carcinoma cells MDA-MB-231 post electron irradiation is limited, especially for the case of FLASH irradiation, resulting in less cytosolic cytochrome c but stronger cGAS-STING activation than those in MCF-10A cells. The enhanced difference of cytochrome c leakage between cancer cells and normal cells post FLASH irradiation indicates a potential mechanism of FLASH effect by regulating the apoptotic and inflammatory pathway.
Motor Learning Mechanisms are not modified by Feedback Manipulations in a Real-World Task
Authors: Nardi Federico , Faisal A. Aldo , Haar Shlomi
Published: April 2024

Error-based and reward-based mechanisms of motor learning co-occur in real-world scenarios but are traditionally isolated in laboratory tasks via feedback manipulations. This study examines the distinctiveness of these mechanisms by applying a lab-based feedback manipulation to a real-world task. Using Embodied Virtual Reality (EVR) of pool billiards - allowing for full proprioception via interaction with the physical pool table, cue stick, and balls - we introduced visual perturbations to a real-world task. 32 participants (12 F) underwent two sessions learning a visuomotor rotation, once with error and once with reward feedback. While naive participants corrected the entire rotation with error feedback, only partial correction was observed with reward feedback, highlighting the influence of the feedback regime on learning. However, the reward-dependent motor variability, lag-1 autocorrelation decay, and inter-trial variability decay - all indicators of reward-based and skill learning - were higher in the error feedback session, suggesting that the provided visual feedback did not exclusively engage specific learning mechanisms. Analysis of post-movement beta rebound (PMBR), a brain activity marker of learning mechanisms, revealed a decrease in PMBR with reward feedback but no consistent trend during error feedback sessions. These findings support the behavioural results, suggesting that while reward feedback was absent in error conditions, participants still engaged in reward-based learning. This study underscores the complexity of motor learning processes and highlights that visual feedback by itself can not elucidate the interplay between error-based and reward-based mechanisms in real-world contexts.
Sustaining microglial reparative function enhances stroke recovery
Authors: Tsuyama Jun , Sakai Seiichiro , Kurabayashi Kumiko , Koyama Ryuki , Hara Yuichiro , Kawakami Ito , Kawaji Hideya , Shichita Takashi
Published: April 2024

Neurological symptoms after brain injury can remain as lifelong detrimental sequelae since most spontaneous brain recovery disappears within a few months after brain injury. Microglia play an essential role in recovery processes after brain injury; however, cellular and molecular mechanisms that diminish spontaneous brain functional recovery remain unknown. We discovered by cellular fate analysis that reparative myeloid cells remained in the post-stroke brain even after losing their reparative function. ZFP384 was identified as a pivotal transcriptional regulator that diminished recovery phase–associated gene expression in reparative myeloid cells, turning them into ruined cells which lost reparative functions. ZFP384 diminished the YY1-mediated chromatin interaction necessary for expressing recovery phase–associated genes. Antisense oligonucleotide againstZfp384sustained the broad range of neural repair effects of myeloid cells and enhanced stroke recovery, even in the chronic phase of ischemic stroke recovery. Thus, therapeutics preventing the myeloid reparative immunity from reaching a ruined state sustains brain functional recovery.
Increased functional integration of emotional control network in late adulthood
Authors: Bätz Leona Rahel , Ye Shuer , Lan Xiaqing , Ziaei Maryam
Published: April 2024

Across the adult lifespan, emotion regulation ability remains stable or even improves. The corresponding effects, however, in the emotion regulation networks in the brain remain underexplored. By utilizing large-scale datasets such as the Human Connectome Project (HCP-Aging, N=621, 349 females) and Cambridge Centre for Ageing and Neuroscience (Cam-CAN, N=333, 155 females), we were able to investigate how emotion regulation networks’ functional topography differs across the entire adult lifespan. Based on previous meta-analytic work that identified four large-scale functional brain networks involved in emotion generation and regulation, we investigated the association between the integration of these emotion regulation networks and measures of mental wellbeing with age in the HCP-Aging dataset. We found an increase in the functional integration of the emotional control network among older adults, which was replicated using the Cam-CAN data set. Further we found that the network that is mediating emotion generative and regulative processes, and carries our introspective and reflective functions, is less integrated in higher age. Our study highlights the importance of identifying topological changes in the functional emotion network architecture across the lifespan, as it allows for a better understanding of functional brain network changes that accompany emotional aging.

Highlights

- We aimed to identify age-related differences in the functional integration of large-scale emotion regulation brain networks across the adult lifespan, and its implications for well-being.

- Frontal emotion control network showed increased while interoception network showed decreased functional integration with higher age in the HCP-Aging dataset.

- Increased integration of emotion control network was replicated and validated in the Cam-CAN dataset.
NSCLC patients with oligo-metastatic brain disease show an altered CD4 T-cells immune profile
Authors: Alsousli Mais , Maire Cecile L. , Piffko Andras , Matschke Jakob , Glau Laura , Reetz Merle , Schneegans Svenja , Emurlai Gresa , Asey Benedikt , Rünger Alessandra , Peine Sven , Kropidlowski Jolanthe , Gempt Jens , Glatzel Markus , Westphal Manfred , Tolosa Eva , Lamszus Katrin , Pantel Klaus , Joosse Simon A. , Mohme Malte , Wikman Harriet
Published: April 2024

Background

Lung cancer is the leading cause of cancer-related deaths worldwide, with brain metastasis (BM) occurring in 40% of advanced non-small cell lung cancer (NSCLC) patients. In 15% of these patients, the brain is the only affected organ (oligo-metastasis), corresponding to improved prognosis compared to widespread disease. Thus far, it is unknown if the metastatic dissemination to the brain without systemic metastases is a consequence of the immune system’s ability to control systemic tumor outgrowth.

Methods

Here, we investigated the local and peripheral immune cell composition in NSCLC BM patients, and identified new immune patterns related to the occurrence of brain metastases either as oligo- or poly-metastatic disease.

Results

The multi-parametric immune phenotyping of peripheral blood revealed a downregulation of KLRG1 in CD8+T-cells and an increase in CD4+TH17 cells and elevated IL-17 levels in the blood of all NSCLC BM patients compared to healthy individuals. In addition, BM patients CD4+T cells showed less CD73 expression with reduced effector memory differentiation. Furthermore, we observed less intra-tumoral infiltration in tumor tissues and a distinctive CD4+ T-cell profile in oligo-synchronous BM, both in the tumor microenvironment and peripheral blood compared to poly-metastatic BM patients. Moreover, 5′-ectonucleotidase CD73 was significantly upregulated in CD4 and T-regulatory cells of oligo-synchronous BM.

Conclusions

These results indicate that oligo-synchronous BM exhibits a more pronounced alteration in the CD4 T-cell immune profile both locally at the tumor site and systemically.

Key Points

BM patients exhibit a skewed systemic immune profile, characterized by downregulation of KLRG1 in CD8+and induction of TH17/IL-17 axis and CD73 in CD4+T-cells.

Oligo-synchronous BM displayed a distinct CD4+T-cell profile in both TME and peripheral blood.

Importance of the Study

This study presents a novel insight into immune profiles of brain metastasis types in NSCLC patients. Examining tissues and PBMCs sheds light on the disease and uncovers unique immune responses within distinct brain metastasis patterns. This research offers valuable knowledge for improved understanding and identifying potential prognosis markers.
A mathematical description of non-self for biallelic genetic systems in pregnancy, transfusion, and transplantation
Authors: Rieneck Klaus
Published: April 2024

A central issue in immunology is the immunological response against non-self. The prerequisite for a specific immunological response is the exposure to the immune system of a non-self-antigen. Mathematical equations are presented, that define the fraction of all outcomes with a non-self-allele in biallelic systems at the population level in pregnancy and transfusion/transplantation medicine. When designing assays, the mathematical descriptions can be used for estimating the number of genetic markers necessary to obtain a predetermined probability level in detecting non-self-alleles of a given frequency. For instance, the equations can be helpful in the design of assays, where the non-self-allele can be detected by analysis of cfDNA in plasma from pregnant women, to estimate fetal fraction or to monitor changes in cfDNA in plasma of transplantation patients.

The equations give exact, quantitative descriptions of all non-self-situations in pregnancy and transfusion/transplantation.
Marine protected areas promote resilience of kelp forests to marine heatwaves by preserving trophic cascades
Authors: Kumagai Joy A. , Goodman Maurice C. , Villaseñor-Derbez Juan Carlos , Schoeman David S. , Cavanuagh Kyle C. , Bell Tom W. , Micheli Fiorenza , De Leo Giulio , Arafeh-Dalmau Nur
Published: April 2024

Under accelerating threats from climate change impacts, marine protected areas (MPAs) have been proposed as climate adaptation tools to enhance the resilience of marine ecosystems. Yet, debate persists as to whether and how MPAs may promote resilience to climate shocks. Here, we empirically assess whether a network of 85 temperate MPAs in coastal waters promotes resilience against marine heatwaves in Central and Southern California. We use 38 years of satellite-derived kelp cover to test whether MPAs enhance the resistance of kelp forest ecosystems to, and recovery from, the unprecedented 2014–2016 marine heatwave regime. We also leverage a 20-year time series of subtidal community surveys to understand whether protection and recovery of sea urchin predators within MPAs explain emergent patterns in kelp forest resilience through trophic cascades. We find that fully protected MPAs (i.e. no-take marine reserves) significantly enhance the resistance to and recovery of kelp forests to marine heatwaves in Southern California, but not in Central California. Differences in regional responses to the heatwaves may be partly explained by three-level trophic interactions comprising kelp, urchins, and predators of urchins. Urchin abundances in Southern California MPAs are significantly lower within fully protected MPAs during and after the heatwave, while the abundance of their predators are higher. In Central California, there is no significant difference in urchin abundances within protected areas as the current urchin predator, sea otters, are unilaterally protected. Therefore, we provide evidence that fully protected MPAs can be effective climate adaptation tools, but their ability to enhance resilience to extreme climate events depends upon region-specific environmental and ecological dynamics. As nations progress to protect 30% of the oceans by 2030 scientists and managers should consider whether protection will increase resilience to climate-change impacts given their local ecological contexts, and what additional measures may be needed.
Large scale analysis of predicted protein structures links model features toin vivobehaviour
Authors: Stam Michael J. , Oyarzún Diego A. , Laohakunakorn Nadanai , Wood Christopher W.
Published: April 2024

Rapid advancements in protein structure prediction methods have ushered in a new era of abundant and accurate structural data, providing opportunities to analyse proteins at a scale that has not been possible before. Here we show that features derived solely from predicted structures can be used to understandin vivoprotein behaviour using data-driven methods. We found that these features were predictive ofin vivoprotein production for a set of designed antibodies, enabling identification of high-quality designs. Following on from this result, we calculated these features for a diverse set of ≈500,000 predicted structures, and our analysis showed systematic variation between proteins from different organisms to such an extent that the tree of life could be recapitulated from these data. Given the high degree of functional constraint around the chemistry of proteins, this result is surprising, and could have important implications for the design and engineering of novel proteins.
MicroRNA-27a-5p downregulates the expression of proinflammatory cytokines in lipopolysaccharide-stimulated human dental pulp cells via NF-κB signaling pathway
Authors: Wang Shihan , Kawashima Nobuyuki , Han Peifeng , Sunada-Nara Keisuke , Yu Ziniu , Tazawa Kento , Fujii Mayuko , Kieu Thoai Quoc , Okiji Takashi
Published: April 2024

Aim

To investigate the effect of microRNA-27a-5p (miR-27a-5p) on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS).

Methodology

Expression of miR-27a-5p was evaluated in LPS-stimulated hDPCs isolated from third molars of healthy patients by a TaqMan microRNA assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and a cytometric bead array were used to measure mRNA and protein expression levels, respectively, of proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemotactic protein 1 (MCP1). Luciferase assays and western blotting were conducted to assess nuclear factor κB (NF-κB) activity. Gene/protein expression of NF-κB signaling activators, i.e., transforming growth factor beta-activated kinase 1 binding protein 1 (TAB1), IL-1 receptor-associated kinase 4 (IRAK4), NF-κB p65 (RELA), and follistatin-like 1 (FSTL1), was evaluated by RT-qPCR and western blotting. Transfection of an miR-27a-5p mimic was performed using Lipofectamine RNAiMax reagent. Wildtype and mutated 3□-untranslated region (UTR) of TAB1-contained luciferase reporter vectors were co-transfected with the miR-27a-5p mimic. Small interfering RNA against TAB1 (siTAB1) was designed to block its expression. One-way analysis of variance and Student’st-test were used to determine statistical significance (α = .05).

Results

LPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-κB inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated expression of proinflammatory cytokines, NF-κB activity, and expression of NF-κB signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3□-UTR of TAB1. siTAB1 downregulated NF-κB activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-κB activity, and NF-κB signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimicex vivo.

Conclusions

MiR-27a-5p, whose expression was induced by NF-κB signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-κB signaling. In particular, TAB1, a potent NF-κB activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-κB signaling pathway, on pulp inflammation.
Juvenile agile frogs spatially avoid ranavirus-infected conspecifics, but do not show generalized social distancing or self-isolation
Authors: Herczeg Dávid , Horváth Gergely , Bókony Veronika , Herczeg Gábor , Kásler Andrea , Holly Dóra , Mikó Zsanett , Ujhegyi Nikolett , Ujszegi János , Papp Tibor , Hettyey Attila
Published: April 2024

Exposure to contagious pathogens can result in behavioural changes, which can alter the spread of infectious diseases. Healthy individuals can express generalized social distancing or actively avoid the sources of infection, while infected individuals can show passive or active self-isolation. Amphibians are globally threatened by serious contagious diseases, yet their behavioural responses to infections are very scarcely known. We studied behavioural changes in agile frog (Rana dalmatina) juveniles upon exposure to aRanavirus(Rv). We performed classic choice tests in chambers containing a conspecific infected withRvin one end compartment and a non-infected conspecific in the other end, with anRv-infected or non-infected focal individual in the central compartment. We found that both non-infected andRv- infected focal individuals spatially avoided infected conspecifics, while there were no signs of generalized social distancing, nor self-isolation. Spatial avoidance of infected conspecifics may effectively hinder disease transmission. On the other hand, the absence of self-isolation by infected individuals may facilitate it. Our finding that infected individuals spent more time near the non-infected than infected conspecifics suggests that the strong behavioural drive to avoid infected conspecifics may not be silenced by infection, possibly to prevent secondary infections. The observation that infected focal individuals did not spend more time near conspecifics than non-infected focals renders it unlikely that the pathogen manipulated host behaviour to aid disease spread. More research is urgently needed to understand under what circumstances behavioural responses can help amphibians cope with infections, and how that affects disease dynamics in natural populations.

GRAPHICAL ABSTRACT
A 3T investigation ofB1+-inhomogeneity tolerance in MP2RAGE-basedR1-mapping by calculating second contrast that permits previously problematic sequence parameters
Authors: Ruijters Lenno , Lund Torben Ellegaard , Vinding Mads Sloth
Published: April 2024

Purpose

Regarding in vivo, robustR1-mapping, the goal of the present paper is twofold. First, to verify that non-bijective mapping in MP2RAGE imaging can be resolved through a 2D look-up-table approach. Second, that the expanded parameter space from this can be used to improveB1+-inhomogeneity tolerance without other prerequisites.

Theory

By deriving a second contrast from the magnitude images of the MP2RAGE acquisition, ambiguities in the original MP2RAGE image resulting from non-bijective transfer curves can be resolved. Such ambiguities may occur when protocols are optimised, e.g., for higherB1+-inhomogeneity tolerance. A 2D look-up-table approach combines the available information to resolve these ambiguities during mapping.

Methods

At 3T, we acquired MP2RAGE images with standard acquisition parameters and (non-bijective) parameters optimised forB1+-inhomogeneity tolerance. From three subjects across multiple sessions, we assessed theB1+-inhomogeneity tolerance through excitation pulse amplitude scalings.

Results

TheR1-maps resulting from theB1+-optimised protocols showed greatly reducedB1+-effects across images, but without additional scanner time. Meanwhile these maps could only successfully be derived by a 2D look-up-table approach.

Conclusion

We show that it is possible to optimise forB1+-inhomogeneity tolerance in MP2RAGE through sequence parameter settings, while still successfully estimating theR1-map with a 2D look-up-table approach. This without the need for an additionalB1+-map. The increased parameter space enabled by the 2D look-up-table approach may further be used to adjust MP2RAGE acquisitions for improved scan times, SNR and/or CNR.
Four centuries of commercial whaling eroded 11,000 years of population stability in bowhead whales
Authors: Westbury Michael V. , Brown Stuart C , Cabrera Andrea A. , Morales Hernán E , Ma Jilong , Rey-Iglesia Alba , Dyke Arthur , Scharff-Olsen Camilla Hjorth , Scott Michael B. , Wiig Øystein , Bachmann Lutz , Kovacs Kit M. , Lydersen Christian , Ferguson Steven H. , Racimo Fernando , Szpak Paul , Fordham Damien A. , Lorenzen Eline D.
Published: April 2024

The bowhead whale, an Arctic endemic, was heavily overexploited during commercial whaling between the 16th-20th centuries1. Current climate warming, with Arctic amplification of average global temperatures, poses a new threat to the species2. Assessing the vulnerability of bowhead whales to near-future predictions of climate change remains challenging, due to lacking data on population dynamics prior to commercial whaling and responses to past climatic change. Here, we integrate palaeogenomics and stable isotope (δ13C andδ15N) analysis of 201 bowhead whale fossils from the Atlantic Arctic with palaeoclimate and ecological modelling based on 823 radiocarbon dated fossils, 151 of which are new to this study. We find long-term resilience of bowhead whales to Holocene environmental perturbations, with no obvious changes in genetic diversity or population structure, despite large environmental shifts and centuries of whaling by Indigenous peoples prior to commercial harvests. Leveraging our empirical data, we simulated a time-series model to quantify population losses associated with commercial whaling. Our results indicate that commercial exploitation induced population subdivision and losses of genetic diversity that are yet to be fully realised; declines in genetic diversity will continue, even without future population size reductions, compromising the species’ resilience to near-future predictions of Arctic warming.