bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered resting-state functional connectivity patterns in late middle-aged and older adults with obstructive sleep apnea
Authors: Martinez Villar Guillermo , Daneault Véronique , Martineau-Dussault Marie-Ève , Baril Andrée-Ann , Gagnon Katia , Lafond Chantal , Gilbert Danielle , Thompson Cynthia , Marchi Nicola Andrea , Lina Jean-Marc , Montplaisir Jacques , Carrier Julie , Gosselin Nadia , André Claire
Published: June 2023

Introduction

Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cognitive decline, and has been associated with structural brain alterations in regions relevant to memory processes and Alzheimer’s disease. However, it is unclear whether OSA is associated with disrupted functional connectivity (FC) patterns between these regions in late middle-aged and older populations. Thus, we characterized the associations between OSA severity and resting-state FC between the default mode network (DMN) and medial temporal lobe (MTL) regions. Second, we explored whether significant FC changes differed depending on cognitive status and were associated with cognitive performance.

Methods

Ninety-four participants [24 women, 65.7 ± 6.9 years old, 41% with Mild Cognitive Impairment (MCI)] underwent a polysomnography, a comprehensive neuropsychological assessment and a resting-state functional magnetic resonance imaging (MRI). General linear models were conducted between OSA severity markers (i.e., the apnea-hypopnea, oxygen desaturation and microarousal indices) and FC values between DMN and MTL regions using CONN toolbox. Partial correlations were then performed between OSA-related FC patterns and (i) OSA severity markers in subgroups stratified by cognitive status (i.e., cognitively unimpaired versus MCI) and (ii) cognitive scores in the whole sample. All analyzes were controlled for age, sex and education, and considered significant at a p < 0.05 threshold corrected for false discovery rate.

Results

In the whole sample, a higher apnea-hypopnea index was significantly associated with lower FC between (i) the medial prefrontal cortex and bilateral hippocampi, and (ii) the left hippocampus and both the posterior cingulate cortex and precuneus. FC patterns were not associated with the oxygen desaturation index, or micro-arousal index. When stratifying the sample according to cognitive status, all associations remained significant in cognitively unimpaired individuals but not in the MCI group. No significant associations were observed between cognition and OSA severity or OSA-related FC patterns.

Discussion

OSA severity was associated with patterns of lower FC in regions relevant to memory processes and Alzheimer’s disease. Since no associations were found with cognitive performance, these FC changes could precede detectable cognitive deficits. Whether these FC patterns predict future cognitive decline over the long-term needs to be investigated.
EEG phase synchronization during absence seizures
Authors: Glaba Pawel , Latka Miroslaw , Krause Małgorzata J. , Kroczka Sławomir , Kuryło Marta , Kaczorowska-Frontczak Magdalena , Walas Wojciech , Jernajczyk Wojciech , Sebzda Tadeusz , West Bruce J.
Published: June 2023

Absence seizures—generalized rhythmic spike-and-wave discharges (SWDs) are the defining property of childhood (CAE) and juvenile (JAE) absence epilepsies. Such seizures are the most compelling examples of pathological neuronal hypersynchrony. All the absence detection algorithms proposed so far have been derived from the properties of individual SWDs. In this work, we investigate EEG phase synchronization in patients with CAE/JAE and healthy subjects to explore the possibility of using the wavelet phase synchronization index to detect seizures and quantify their disorganization (fragmentation). The overlap of the ictal and interictal probability density functions was high enough to preclude effective seizure detection based solely on changes in EEG synchronization. We used a machine learning classifier with the phase synchronization index (calculated for 1 s data segments with 0.5 s overlap) and the normalized amplitude as features to detect generalized SWDs. Using 19 channels (10-20 setup), we identified 99.2% of absences. However, the overlap of the segments classified as ictal with seizures was only 83%. The analysis showed that seizures were disorganized in approximately half of the 65 subjects. On average, generalized SWDs lasted about 80% of the duration of abnormal EEG activity. The disruption of the ictal rhythm can manifest itself as the disappearance of epileptic spikes (with high-amplitude delta waves persisting), transient cessation of epileptic discharges, or loss of global synchronization. The detector can analyze a real-time data stream. Its performance is good for a six-channel setup (Fp1, Fp2, F7, F8, O1, O2), which can be implemented as an unobtrusive EEG headband. False detections are rare for controls and young adults (0.03% and 0.02%, respectively). In patients, they are more frequent (0.5%), but in approximately 82% cases, classification errors are caused by short epileptiform discharges. Most importantly, the proposed detector can be applied to parts of EEG with abnormal EEG activity to quantitatively determine seizure fragmentation. This property is important because a previous study reported that the probability of disorganized discharges is eight times higher in JAE than in CAE. Future research must establish whether seizure properties (frequency, length, fragmentation, etc.) and clinical characteristics can help distinguish CAE and JAE.
Hierarchical deconvolution for extensive cell type resolution in the human brain using DNA methylation
Authors: Zhang Ze , Wiencke John K. , Kelsey Karl T. , Koestler Devin C. , Molinaro Annette M. , Pike Steven C. , Karra Prasoona , Christensen Brock C. , Salas Lucas A.
Published: June 2023

Introduction

The human brain comprises heterogeneous cell types whose composition can be altered with physiological and pathological conditions. New approaches to discern the diversity and distribution of brain cells associated with neurological conditions would significantly advance the study of brain-related pathophysiology and neuroscience. Unlike single-nuclei approaches, DNA methylation-based deconvolution does not require special sample handling or processing, is cost-effective, and easily scales to large study designs. Existing DNA methylation-based methods for brain cell deconvolution are limited in the number of cell types deconvolved

Methods

Using DNA methylation profiles of the top cell-type-specific differentially methylated CpGs, we employed a hierarchical modeling approach to deconvolve GABAergic neurons, glutamatergic neurons, astrocytes, microglial cells, oligodendrocytes, endothelial cells, and stromal cells.

Results

We demonstrate the utility of our method by applying it to data on normal tissues from various brain regions and in aging and diseased tissues, including Alzheimer’s disease, autism, Huntington’s disease, epilepsy, and schizophrenia.

Discussion

We expect that the ability to determine the cellular composition in the brain using only DNA from bulk samples will accelerate understanding brain cell type composition and cell-type-specific epigenetic states in normal and diseased brain tissues.
Functionalized hydrogels in neural injury repairing
Authors: Zhao Wenqian , Tu Hui , Chen Jianxiao , Wang Jing , Liu Haoting , Zhang Fengshou , Li Jing
Published: June 2023

Repairing injuries to the nervous system has always been a prominent topic in clinical research. Direct suturing and nerve displacement surgery are the primary treatment options, but they may not be suitable for long nerve injuries and may require sacrificing the functionality of other autologous nerves. With the emergence of tissue engineering, hydrogel materials have been identified as a promising technology with clinical translation potential for repairing nervous system injuries due to their excellent biocompatibility and ability to release or deliver functional ions. By controlling their composition and structure, hydrogels can be Functionalized and almost fully matched with nerve tissue and even simulate nerve conduction function and mechanical properties. Thus, they are suitable for repairing injuries to both the central and peripheral nervous systems. This article provides a review of recent research progress in functionalized hydrogels for nerve injury repair, highlighting the design differences among various materials and future research directions. We strongly believe that the development of functionalized hydrogels has great potential for improving the clinical treatment of nerve injuries.
A semi-independent policies training method with shared representation for heterogeneous multi-agents reinforcement learning
Authors: Zhao Biao , Jin Weiqiang , Chen Zhang , Guo Yucheng
Published: June 2023

Humans do not learn everything from the scratch but can connect and associate the upcoming information with the exchanged experience and known knowledge. Such an idea can be extended to cooperated multi-reinforcement learning and has achieved its success on homogeneous agents by means of parameter sharing. However, it is difficult to straightforwardly apply parameter sharing when dealing with heterogeneous agents thanks to their individual forms of input/output and their diverse functions and targets. Neuroscience has provided evidence that our brain creates several levels of experience and knowledge-sharing mechanisms that not only exchange similar experiences but also allow for sharing of abstract concepts to handle unfamiliar situations that others have already encountered. Inspired by such a brain's functions, we propose a semi-independent training policy method that can well tackle the conflict between parameter sharing and specialized training for heterogeneous agents. It employs a shared common representation for both observation and action, enabling the integration of various input and output sources. Additionally, a shared latent space is utilized to maintain a balanced relationship between the upstream policy and downstream functions, benefiting each individual agent's target. From the experiments, it can approve that our proposed method outperforms the current mainstream algorithms, especially when handling heterogeneous agents. Empirically, our proposed method can also be improved as a more general and fundamental heterogeneous agents' reinforcement learning structure for curriculum learning and representation transfer. All our code is open and released on https://gitlab.com/reinforcement/ntype.
Characterization, antioxidant activity, and mineral profiling of Auricularia cornea mushroom strains
Authors: Khan Asif Ali , Lu Li-Xin , Yao Fang-Jie , Fang Ming , Wang Peng , Zhang You-Min , Meng Jing-Jing , Ma Xiao-Xu , He Qi , Shao Kai-Sheng , Wei Yun-hui , Xu Baojun
Published: June 2023

Background

Mushrooms are considered as next-generation healthy food components. Owing to their low-fat content, high-quality proteins, dietary fiber, and rich source of nutraceuticals. They are ideally preferred in formulation of low-caloric functional foods. In this view, the breeding strategies of mushroom Auricularia cornea (A. cornea) focusing on high yield and higher quality with rich nutritional values and health benefits are still needed.

Materials and methods

A total of 50 strains of A. cornea were used to analyze the bio efficiency and the time required for fruiting body formation following the cultivation experiment. The calorimetric method was used to evaluate the antioxidant activity and quantify the crude polysaccharides and minerals content thereafter.

Results

The results showed that the time required for fruiting body formation and biological efficiency varied significantly among the selected strains. Noticeably, the wild domesticated strain Ac13 of A. cornea mushroom showed the shortest fruit development time (80 days). Similarly, the hybrid strains including Ac3 and Ac15 possessed the highest biological efficiency (82.40 and 94.84%). Hybrid strains Ac18 (15.2%) and cultivated strains Ac33 (15.6%) showed the highest content of crude polysaccharides, while cultivated strains Ac1 and Ac33, demonstrated the highest content of total polysaccharides in the fruiting body (216 mg. g−1 and 200 mg. g−1). In the case of mineral content, the highest zinc contents were observed from the cultivated strain Ac46 (486.33 mg·kg−1). The maximum iron content was detected from the hybrid strain Ac3 (788 mg·kg−1), and the wild domesticated strain Ac28 (350 mg·kg−1). The crude polysaccharides of the A. cornea strain showed significant antioxidant potential, and the ability of Ac33 and Ac24 to scavenge DPPH radicals and ABTS, which was significantly improved compared to other strains, respectively. Principal component analysis was applied to examine the agronomic traits and chemical compounds of various strains of A. cornea mushrooms. The results revealed that cultivated, wild domesticated, and hybrid strains of A. cornea exhibited distinct characteristics in terms of growth, yield, and nutritional properties.

Conclusion

The crude polysaccharides from A. cornea mushroom strains act as natural antioxidants, the wild, hybrid, and commercial A. cornea mushroom strains can achieve rapid growth, early maturation, and high yields. The evaluation of biochemical indexes and nutritional characteristics of strains with excellent traits provided a scientific basis for initiating high-quality breeding, provided germplasm resources for the production of “functional food” with real nutritional and health value.
Preoperative staging of uterine cancer: can transvaginal ultrasonography play a role?
Authors: Rei Mariana , Costa-Santos Cristina , Bernardes João , Costa Antónia
Published: June 2023

Introduction

Preoperative staging of uterine cancer has recently been implied as an important contribution to an accurate selection of low-risk cases, ultimately avoiding unnecessary lymph node debulking. The aim of this study was to evaluate the validity of transvaginal ultrasonography (TVS) in preoperative staging of uterine cancer in comparison to pelvic magnetic resonance imaging (MRI) and permanent section.

Methods

We conducted a prospective longitudinal multicenter trial between 2017 and 2018. Inclusion criteria comprised cases of endometrial neoplasia histologically confirmed or strong imaging suspicion, candidates for elective surgery as primary treatment. Proportions of Agreement (PA), kappa statistic (K), sensitivity, specificity and accuracy were calculated with 95% confidence intervals (95%CI).

Results

Eighty-two patients were eligible for the study, presenting a mean age of 68 years (standard deviation 11). In what concerns the TVS evaluation of myometrial invasion, the subjective and objective methods of Gordon and Karlsson presented a sensitivity of 79%, 79% and 67% [95%CI 63-91; 63-91; 50-81], a specificity of 65%, 58% and 79% [95%CI 49-79; 42-73; 64-89] and an overall accuracy of 72%, 68% and 73% [95%CI 61-81; 57-78; 63-82]. MRI presented respectively a sensitivity, specificity and overall accuracy of 92%, 70% and 82% [95%CI 77-98; 52-85; 71-90]. Regarding cervical involvement, the sensitivity was respectively 31%, 50% and 67% [95%CI 9-61; 21-79; 35-90] for the subjective method, objective TVS and MRI, and the specificity was 98%, 90% and 100% [95%CI 92-100; 77-97; 94;100]. Agreement between TVS and MRI was superior in the assessment of cervical invasion, with PA ranging from 0.82 to 0.93 and K from 0.45 to 0.58, in comparison to myometrial invasion with PA ranging from 0.68 to 0.73 and K from 0.31 to 0.50. Considering the assessment of cervical involvement, as MRI showed a specificity of 100% it is not possible to increase the specificity. However, it was possible to increase the sensitivity, considering the combination of TVS with objective approach and MRI.

Conclusion

TVS may have a promising role as a tool for preoperative staging of endometrial carcinoma, presenting a performance that approximates to MRI, with a higher agreement in the assessment of cervical invasion.
Application of a three-dimensional printed pelvic model in laparoscopic radical resection of rectal cancer
Authors: Lu Feng , Qiu Lei , Yu Peng , Xu Da-Lai , Miao Yong-Chang , Wang Gang
Published: June 2023

Introduction

To investigate the application value of a three-dimensional (3D) printed pelvic model in laparoscopic radical resection of rectal cancer.

Methods

Clinical data of patients undergoing laparoscopic radical rectal cancer surgery in The Second People's Hospital of Lianyungang City from May 2020 to April 2022 were selected. Patients were randomly divided into general imaging examination group (control group, n=25) and 3D printing group (observation group, n=25) by random number table method, and the perioperative situation of patients in the two groups was compared.

Results

There was no significant difference in general data between the two groups (p>0.05). Operation time, intraoperative blood loss, intraoperative time to locate inferior mesenteric artery, intraoperative time to locate left colic artery, first postoperative exhaust time and length of hospital stay in the observation group were all lower than those in the control group (P < 0.05); There were no significant differences in the total number of lymph nodes and complications between the two groups (P > 0.05).

Discussion

The application of 3D printed pelvic model in laparoscopic radical resection of rectal cancer is conducive to understanding pelvic structure and mesenteric vascular anatomy, reducing intraoperative bleeding and shortening operation time, which is worthy of further clinical application.
Lestaurtinib inhibits Citron kinase activity and medulloblastoma growth through induction of DNA damage, apoptosis and cytokinesis failure
Authors: Pallavicini Gianmarco , Iegiani Giorgia , Parolisi Roberta , Ferraro Alessia , Garello Francesca , Bitonto Valeria , Terreno Enzo , Gai Marta , Di Cunto Ferdinando
Published: June 2023

Introduction

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is currently treated with surgery followed by radiation and chemotherapy, which is accompanied by severe side effects, raising the need for innovative therapies. Disruption of the microcephaly-related gene Citron kinase (CITK) impairs the expansion of xenograft models as well as spontaneous MB arising in transgenic mice. No specific CITK inhibitors are available.

Methods

Lestaurtinib, a Staurosporine derivative also known as CEP-701, inhibits CITK with IC50 of 90 nM. We therefore tested the biological effects of this molecule on different MB cell lines, as well as in vivo, injecting the drug in MBs arising in SmoA1 transgenic mice.

Results

Similar to CITK knockdown, treatment of MB cells with 100 nM Lestaurtinib reduces phospho-INCENP levels at the midbody and leads to late cytokinesis failure. Moreover, Lestaurtinib impairs cell proliferation through CITK-sensitive mechanisms. These phenotypes are accompanied by accumulation of DNA double strand breaks, cell cycle block and TP53 superfamily activation in vitro and in vivo. Lestaurtinib treatment reduces tumor growth and increases mice survival.

Discussion

Our data indicate that Lestaurtinib produces in MB cells poly-pharmacological effects extending beyond the inhibition of its validated targets, supporting the possibility of repositioning this drug for MB treatment.
Identification of a six-gene signature to predict survival and immunotherapy effectiveness of gastric cancer
Authors: Wang Qi , Zhang Biyuan , Wang Haiji , Hu Mingming , Feng Hui , Gao Wen , Lu Haijun , Tan Ye , Dong Yinying , Xu Mingjin , Guo Tianhui , Ji Xiaomeng
Published: June 2023

Background

Gastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients.

Methods

We studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature’s performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.

Results

There were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.

Conclusion

In conclusion, we discovered a 6 gene signature to forecast GC patients’ OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice.
Assisted reproductive techniques do not impact late neurodevelopmental outcomes of preterm children
Authors: Lefebvre Tiphaine , Flamant Cyril , Olivier Marion , Gascoin Géraldine , Bouet Pierre-Emmanuel , Roze Jean-Christophe , Barrière Paul , Fréour Thomas , Muller Jean-Baptiste
Published: June 2023

Objective

Assisted reproductive technology (ART) increases the rate of preterm births, though few studies have analyzed outcomes for these infants. No data are available on 4-year-old children born prematurely after ART. The objective was to investigate whether ART affect the neurodevelopmental outcomes at 4 years in preterm infants born before 34 weeks of gestational age (GA).

Methods and results

A total of 166 ART and 679 naturally conceived preterm infants born before 34 weeks GA between 2013 and 2015 enrolled in the Loire Infant Follow-up Team were included. Neurodevelopment was assessed at 4 years using the age and stage questionnaire (ASQ) and the need for therapy services. The association between the socio-economic and perinatal characteristics and non-optimal neurodevelopment at 4 years was estimated. After adjustment, the ART preterm group remained significantly associated with a lower risk of having at least two domains in difficulty at ASQ: adjusted odds ratio (aOR) 0.34, 95% confidence interval (CI) (0.13–0.88), p = 0.027. The factors independently associated with non-optimal neurodevelopment at 4 years were male gender, low socio-economic level, and 25–30 weeks of GA at birth. The need for therapy services was similar between groups (p = 0.079). The long-term neurodevelopmental outcomes of preterm children born after ART are very similar, or even better than that of the spontaneously conceived children.
Tuberculosis in 0–5-year-old children following TB contact investigations: a retrospective study in a low burden setting
Authors: Pasqualini Cassandre , Cohen Laure , Le Roux Enora , Caseris Marion , Faye Albert
Published: June 2023

Introduction

We assessed the risk of tuberculosis (TB), the management and the outcomes of 0–5-year-old children after TB contact investigations in a low-burden setting.

Method

All 0–5-year-old children who attended the TB clinic of Robert Debre Hospital, Paris, France, for a TB contact investigation between June 2016 and December 2019 were included in this retrospective study. The risk factors for TB were assessed using univariate and multivariate analyses.

Results

A total of 261 children were included. Forty-six (18%) had TB, including 37 latent tuberculosis infections (LTBIs) and 9 active TB diseases. The prevalence of TB was 21% among high-risk contacts, i.e., household or close contacts and regular or casual contacts. There was no TB among intermediate- or low-risk contacts (0/42). Living under the same roof with (OR: 19.8; 95% CI: 2.6–153), the BCG vaccine (OR: 3.2; 95% CI: 1.2–8.3), contact duration >40 h (OR: 7.6; 95% CI: 2.3–25.3) and sleeping in the room of the index case (OR: 3.9; 95% CI: 1.3–11.7) were independently associated with TB. The BCG vaccine was no longer associated when the analysis was restricted to interferon gamma release assay results. Among children without initial LTBI, antibiotic prophylaxis was not prescribed for 2–5-year-old children or for 32/36 (89%) of 0–2-year-old children who had intermediate- or low-risk contact. Overall, none of these children experienced TB.

Conclusion

In our low prevalence setting, the risk of TB in 0–5-year-old children following a household or close contact was high. Further studies are needed to better assess prophylaxis recommendations in intermediate or low risk contact.
Covid-19 omicron variant infection in neonates of Guangdong province-a report of 52 cases
Authors: Yang Yi-Kang , Lin Fen , Lin Jian-Feng , Lin Chun-Fan , Liu Li-Li , Ma Yu-Bin , Wang Xian-Yao , Liao Yu-Wei , Huang Yu-Chan , Zeng Guang-Kuan , Xiao Bei-Ru , Huang Shan-Hua , Xu Yu-Mei , Chen Yue-E , Cao Yan-Bin , Yang Li-Ye
Published: June 2023

Objective

To analyze the clinical characteristics of neonatal infection during the outbreak of COVID-19 omicron variant in Guangdong province of China.

Method

The clinical data of neonates infected with COVID-19 omicron variant were collected from three hospitals of Guangdong province, their epidemiological history, clinical manifestation and prognosis were summarized.

Results

From December 12, 2022 to January 15, 2023, a total of 52 neonates with COVID-19 infection were identified across three hospitals in Guangdong Province, including 34 males and 18 females. The age of diagnosis was 18.42 ± 6.32 days. 24 cases had clear contact history with adults who were suspected to be infected with COVID-19. The most common clinical manifestation was fever (43/52, 82.7%), the duration of fever was 1–8 days. The other clinical manifestations were cough (27/52, 51.9%), rales (21/52, 40.4%), nasal congestion (10/52, 19.2%), shortness of breath (2/52, 3.8%), and vomiting (4/52, 7.7%). C-reactive protein was only increased in 3 cases. Chest radiological examination was performed in 42 neonates, twenty-three cases showed abnormal chest radiographic findings, including ground-glass opacity and consolidation. Fifty cases were admitted with COVID-19 presentation, two cases were admitted for jaundice. The hospital stay was 6.59 ± 2.77 days. The clinical classification included 3 cases of severe COVID-19 and one critical case. Fifty-one cases were cured and discharged after general treatment, and one critical case with respiratory failure was intubated and transferred to another hospital.

Conclusion

The COVID-19 omicron variant infection in neonates is usually mild. The clinical manifestation and laboratory results are not specific, and the short-term prognosis is good.
Laser-driven muon production for material inspection and imaging
Authors: Calvin Luke , Tomassini Paolo , Doria Domenico , Martello Daniele , Deas Robert M. , Sarri Gianluca
Published: June 2023

We numerically show that laser-wakefield accelerated electron beams obtained using a PetaWatt-scale laser system can produce high-flux sources of relativistic muons that are suitable for radiographic applications. Scalings of muon energy and flux with the properties of the wakefield electron beams are presented. Applying these results to the expected performance of the 10-PW class laser at the Extreme Light Infrastructure Nuclear Physics (ELI-NP) demonstrates that ultra-high power laser facilities currently in the commissioning phase can generate ultra-relativistic muon beams with more than 104 muons per shot reaching the detector plane. Simple magnetic beamlines are shown to be effective in separating the muons from noise, allowing for their detection using, for example, silicon-based detectors. It is shown that a laser facility like the one at ELI-NP can produce high-fidelity and spatially resolved muon radiographs of enclosed strategically sensitive materials in a matter of minutes.
Functional differences in human aortic valve interstitial cells from patients with varying calcific aortic valve disease
Authors: Tuscher Robin , Khang Alex , West Toni M. , Camillo Chiara , Ferrari Giovanni , Sacks Michael S.
Published: June 2023

Calcific aortic valve disease (CAVD) is characterized by progressive stiffening of aortic valve (AV) tissues, inducing stenosis and insufficiency. Bicuspid aortic valve (BAV) is a common congenital defect in which the AV has two leaflets rather than three, with BAV patients developing CAVD decades years earlier than in the general population. Current treatment for CAVD remains surgical replacement with its continued durability problems, as there are no pharmaceutical therapies or other alternative treatments available. Before such therapeutic approaches can be developed, a deeper understanding of CAVD disease mechanisms is clearly required. It is known that AV interstitial cells (AVICs) maintain the AV extracellular matrix and are typically quiescent in the normal state, transitioning into an activated, myofibroblast-like state during periods of growth or disease. One proposed mechanism of CAVD is the subsequent transition of AVICs into an osteoblast-like phenotype. A sensitive indicator of AVIC phenotypic state is enhanced basal contractility (tonus), so that AVICs from diseased AV will exhibit a higher basal tonus level. The goals of the present study were thus to assess the hypothesis that different human CAVD states lead to different biophysical AVIC states. To accomplish this, we characterized AVIC basal tonus behaviors from diseased human AV tissues embedded in 3D hydrogels. Established methods were utilized to track AVIC-induced gel displacements and shape changes after the application of Cytochalasin D (an actin polymerization inhibitor) to depolymerize the AVIC stress fibers. Results indicated that human diseased AVICs from the non-calcified region of TAVs were significantly more activated than AVICs from the corresponding calcified region. In addition, AVICs from the raphe region of BAVs were more activated than from the non-raphe region. Interestingly, we observed significantly greater basal tonus levels in females compared to males. Furthermore, the overall AVIC shape changes after Cytochalasin suggested that AVICs from TAVs and BAVs develop different stress fiber architectures. These findings are the first evidence of sex-specific differences in basal tonus state in human AVICs in varying disease states. Future studies are underway to quantify stress fiber mechanical behaviors to further elucidate CAVD disease mechanisms.
Advances in computational and translational approaches for malignant glioma
Authors: Bhargav Adip G. , Domino Joseph S. , Alvarado Anthony M. , Tuchek Chad A. , Akhavan David , Camarata Paul J.
Published: June 2023

Gliomas are the most common primary brain tumors in adults and carry a dismal prognosis for patients. Current standard-of-care for gliomas is comprised of maximal safe surgical resection following by a combination of chemotherapy and radiation therapy depending on the grade and type of tumor. Despite decades of research efforts directed towards identifying effective therapies, curative treatments have been largely elusive in the majority of cases. The development and refinement of novel methodologies over recent years that integrate computational techniques with translational paradigms have begun to shed light on features of glioma, previously difficult to study. These methodologies have enabled a number of point-of-care approaches that can provide real-time, patient-specific and tumor-specific diagnostics that may guide the selection and development of therapies including decision-making surrounding surgical resection. Novel methodologies have also demonstrated utility in characterizing glioma-brain network dynamics and in turn early investigations into glioma plasticity and influence on surgical planning at a systems level. Similarly, application of such techniques in the laboratory setting have enhanced the ability to accurately model glioma disease processes and interrogate mechanisms of resistance to therapy. In this review, we highlight representative trends in the integration of computational methodologies including artificial intelligence and modeling with translational approaches in the study and treatment of malignant gliomas both at the point-of-care and outside the operative theater in silico as well as in the laboratory setting.
Microcosm experiment combined with process-based modeling reveals differential response and adaptation of aquatic primary producers to warming and agricultural run-off
Authors: López Moreira Mazacotte Gregorio A. , Polst Bastian H. , Gross Elisabeth M. , Schmitt-Jansen Mechthild , Hölker Franz , Hilt Sabine
Published: June 2023

Fertilizers, pesticides and global warming are threatening freshwater aquatic ecosystems. Most of these are shallow ponds or slow-flowing streams or ditches dominated by submerged macrophytes, periphyton or phytoplankton. Regime shifts between the dominance of these primary producers can occur along a gradient of nutrient loading, possibly triggered by specific disturbances influencing their competitive interactions. However, phytoplankton dominance is less desirable due to lower biodiversity and poorer ecosystem function and services. In this study, we combined a microcosm experiment with a process-based model to test three hypotheses: 1) agricultural run-off (ARO), consisting of nitrate and a mixture of organic pesticides and copper, differentially affects primary producers and enhances the risk of regime shifts, 2) warming increases the risk of an ARO-induced regime shift to phytoplankton dominance and 3) custom-tailored process-based models support mechanistic understanding of experimental results through scenario comparison. Experimentally exposing primary producers to a gradient of nitrate and pesticides at 22°C and 26°C supported the first two hypotheses. ARO had direct negative effects on macrophytes, while phytoplankton gained from warming and indirect effects of ARO like a reduction in the competitive pressure exerted by other groups. We used the process-based model to test eight different scenarios. The best qualitative fit between modeled and observed responses was reached only when taking community adaptation and organism acclimation into account. Our results highlight the importance of considering such processes when attempting to predict the effects of multiple stressors on natural ecosystems.
Biochar-extracted liquor stimulates nitrogen related gene expression on improving nitrogen utilization in rice seedling
Authors: Gao Jian , Ge Shaohua , Wang Hailong , Fang Yunying , Sun Luming , He Tianyi , Cheng Xiaoyi , Wang Di , Zhou Xuanwei , Cai Heqing , Li Caibin , Liu Yanxiang , E Yang , Meng Jun , Chen Wenfu
Published: June 2023

Introduction

Biochar has been shown to be an effective soil amendment for promoting plant growth and improving nitrogen (N) utilization. However, the physiological and molecular mechanisms behind such stimulation remain unclear.

Methods

In this study, we investigated whether biochar-extracted liquor including 21 organic molecules enhance the nitrogen use efficiency (NUE) of rice plants using two N forms (NH4+-N and NO3--N). A hydroponic experiment was conducted, and biochar-extracted liquor (between 1 and 3% by weight) was applied to rice seedlings.

Results

The results showed that biochar-extracted liquor significantly improved phenotypic and physiological traits of rice seedlings. Biochar-extracted liquor dramatically upregulated the expression of rice N metabolism-related genes such as OsAMT1.1, OsGS1.1, and OsGS2. Rice seedlings preferentially absorbed NH4+-N than NO3--N (p < 0.05), and the uptake of NH4+-N by rice seedlings was significantly increased by 33.60% under the treatment of biochar-extracted liquor. The results from molecular docking showed that OsAMT1.1protein can theoretically interact with 2-Acetyl-5-methylfuran, trans-2,4-Dimethylthiane, S, S-dioxide, 2,2-Diethylacetamide, and 1,2-Dimethylaziridine in the biochar-extracted liquor. These four organic compounds have similar biological function as the OsAMT1.1 protein ligand in driving NH4+-N uptakes by rice plants.

Discussion

This study highlights the importance of biochar-extracted liquor in promoting plant growth and NUE. The use of low doses of biochar-extracted liquor could be an important way to reduce N input in order to achieve the purpose of reducing fertilizer use and increasing efficiency in agricultural production.
Living yeast-based biostimulants: different genes for the same results?
Authors: Chambard Marie , Albert Benjamin , Cadiou Mickaël , Auby Sarah , Profizi Camille , Boulogne Isabelle
Published: June 2023

Nowadays, many products are available in the plant biostimulants market. Among them, living yeast-based biostimulants are also commercialized. Given the living aspect of these last products, the reproducibility of their effects should be investigated to ensure end-users’ confidence. Therefore, this study aimed to compare the effects of a living yeast-based biostimulant between two different soybean cultures. These two cultures named C1 and C2 were conducted on the same variety and soil but in different locations and dates until the VC developmental stage (unifoliate leaves unrolled), with Bradyrhizobium japonicum (control and Bs condition) and with and without biostimulant coating seed treatment. The foliar transcriptomic analysis done first showed a high gene expression difference between the two cultures. Despite this first result, a secondary analysis seemed to show that this biostimulant led to a similar pathway enhancement in plants and with common genes even if the expressed genes were different between the two cultures. The pathways which seem to be reproducibly impacted by this living yeast-based biostimulant are abiotic stress tolerance and cell wall/carbohydrate synthesis. Impacting these pathways may protect the plant from abiotic stresses and maintain a higher level of sugars in plant.
Barley stripe mosaic virus-mediated somatic and heritable gene editing in barley (Hordeum vulgare L.)
Authors: Tamilselvan-Nattar-Amutha Suriya , Hiekel Stefan , Hartmann Franziska , Lorenz Jana , Dabhi Riddhi Vijay , Dreissig Steven , Hensel Goetz , Kumlehn Jochen , Heckmann Stefan
Published: June 2023

Genome editing strategies in barley (Hordeum vulgare L.) typically rely on Agrobacterium-mediated genetic transformation for the delivery of required genetic reagents involving tissue culture techniques. These approaches are genotype-dependent, time-consuming, and labor-intensive, which hampers rapid genome editing in barley. More recently, plant RNA viruses have been engineered to transiently express short guide RNAs facilitating CRISPR/Cas9-based targeted genome editing in plants that constitutively express Cas9. Here, we explored virus-induced genome editing (VIGE) based on barley stripe mosaic virus (BSMV) in Cas9-transgenic barley. Somatic and heritable editing in the ALBOSTRIANS gene (CMF7) resulting in albino/variegated chloroplast-defective barley mutants is shown. In addition, somatic editing in meiosis-related candidate genes in barley encoding ASY1 (an axis-localized HORMA domain protein), MUS81 (a DNA structure-selective endonuclease), and ZYP1 (a transverse filament protein of the synaptonemal complex) was achieved. Hence, the presented VIGE approach using BSMV enables rapid somatic and also heritable targeted gene editing in barley.
Phonetic entrainment in L2 human-robot interaction: an investigation of children with and without autism spectrum disorder
Authors: Hong Yitian , Chen Si , Zhou Fang , Chan Angel , Tang Tempo
Published: June 2023

Phonetic entrainment is a phenomenon in which people adjust their phonetic features to approach those of their conversation partner. Individuals with Autism Spectrum Disorder (ASD) have been reported to show some deficits in entrainment during their interactions with human interlocutors, though deficits in terms of significant differences from typically developing (TD) controls were not always registered. One reason related to the inconsistencies of whether deficits are detected or not in autistic individuals is that the conversation partner’s speech could hardly be controlled, and both the participants and the partners might be adjusting their phonetic features. The variabilities in the speech of conversation partners and various social traits exhibited might make the phonetic entrainment (if any) of the participants less detectable. In this study, we attempted to reduce the variability of the interlocutors by employing a social robot and having it do a goal-directed conversation task with children with and without ASD. Fourteen autistic children and 12 TD children participated the current study in their second language English. Results showed that autistic children showed comparable vowel formants and mean fundamental frequency (f0) entrainment as their TD peers, but they did not entrain their f0 range as the TD group did. These findings suggest that autistic children were capable of exhibiting phonetic entrainment behaviors similar to TD children in vowel formants and f0, particularly in a less complex situation where the speech features and social traits of the interlocutor were controlled. Furthermore, the utilization of a social robot may have increased the interest of these children in phonetic entrainment. On the other hand, entrainment of f0 range was more challenging for these autistic children even in a more controlled situation. This study demonstrates the viability and potential of using human-robot interactions as a novel method to evaluate abilities and deficits in phonetic entrainment in autistic children.
Integrated science, technology, engineering, and mathematics project-based learning for physics learning from neuroscience perspectives
Authors: Uden Lorna , Sulaiman Fauziah , Ching Gregory S. , Rosales Jeffry Juan
Published: June 2023

For many students, learning physics is difficult because of its abstractness. To help students to learn physics, we have developed the Integrated Science, Technology, Engineering, and Mathematics Projects Based Learning (STEM-PjBL) method based on principles from neuroscience. We believe that incorporating principles from educational neuroscience would help students learn better. This paper describes our experiments of implementing the integrated STEM-PjBL Module in physics, i.e., classical mechanics, to secondary school students in Malaysia and South Korea. The study consists of two groups of students: the experiment group, 77 in total, comprising those who have undergone the integrated STEM-PjBL, and the control group, again 77 in total, who experienced the traditional approach. The Colorado Learning Attitudes Science Survey (CLASS) was conducted for the two groups on students’ beliefs about physics and learning physics before and after the implementation. The paired sample t-test from the pre-survey and post-survey shows that the integrated STEM-PjBL group has a more positive shift in belief about physics and learning physics than the traditional group. The results of the independent samples t-test for students’ beliefs about physics and learning physics, compared with the post-survey between the experimental group and the traditional group for both Malaysian and Korean perspectives, show that the experimental group has a higher mean compared to the traditional group. This paper explains why the integrated STEM-PjBL has improved students’ beliefs about physics and learning physics, from the neuroscience education perspective. Finally, the paper concludes with guidelines for teachers who wish to implement the integrated STEM-PjBL in the classroom.
Factors affecting the acculturation strategies of unaccompanied refugee minors in Germany
Authors: Garbade Maike , Eglinsky Jenny , Kindler Heinz , Rosner Rita , Sachser Cedric , Pfeiffer Elisa
Published: June 2023

Background

Different acculturation strategies might be related to different mental health outcomes and social participation of unaccompanied refugee minors (URMs), but little is known about which factors influence this acculturation process. Therefore, the aim of this investigation was to examine the impact of individual, stress-related, and contextual factors on the acculturation process of URMs in Germany.

Methods

A sample of N = 132 URMs living in child and youth welfare service facilities in Germany completed questionnaires about their acculturation orientation, traumatic experiences, daily stressors, asylum stress, and perceived social support between June 2020 and October 2021. This investigation is part of the multi-center randomized control trial BETTER CARE. Data were analyzed descriptively and via multiple hierarchical regression.

Results

Integration (43.5%) and Assimilation (37.1%) were the most common acculturation strategies used by URMs. Multiple hierarchical regression models showed that daily stressors (e.g., the lack of money) were associated with a stronger orientation toward the home country, whereas traumatic events were associated with a weaker orientation toward their home country. No significant predictors were found for the orientation toward the host country.

Discussion

Overall, URMs in Germany showed favorable acculturation strategies. Nevertheless, daily stressors and traumatic experiences might influence this process. The implications for practitioners and policymakers are discussed with a view to further improving the acculturation process of URMs in Germany.

Clinical Trial Registration: German Clinical Trials Register, DRKS00017453 https://drks.de/search/de/trial/DRKS00017453. Registered on December 11, 2019.
Preschool teachers’ psychological wellbeing, emotion regulation, and emotional responsiveness: a US-Korea comparison
Authors: Byun Sooyeon , Jeon Lieny
Published: June 2023

Introduction

Psychological wellbeing is an essential indicator of early care and education (ECE) teachers’ positive practices across countries. Moreover, previous studies suggest that teachers’ wellbeing and practice may be indirectly associated via emotion regulation. However, teachers in various contexts demonstrate different patterns of psychological wellbeing, emotion regulation, and emotional responsiveness, and the ways these factors associate with each other also vary.

Methods

The current study investigates whether the indirect associations between ECE teachers’ psychological wellbeing (i.e., emotional exhaustion, job-related competence, and personal stress) and their responsiveness toward children’s emotions via emotion regulation (i.e., reappraisal and suppression) appear differently in two national contexts, the United States (US) and South Korea (SK). Multi-group path analysis was conducted to compare the mediation models between US teachers (n = 1,129) and SK teachers (n = 322).

Results

We found significant indirect associations among wellbeing, emotion regulation, and responsiveness in both countries. However, significant associations were more prominent among SK teachers, and the patterns of indirect associations had substantial cross-country differences. Furthermore, the roles of reappraisal and suppression emotion regulation found to be different among ECE teachers in SK and US.

Discussion

The cross-country variations in the associations among wellbeing, emotion regulation, and responsiveness suggest that differential policy efforts and intervention strategies are needed for ECE teachers in the US and SK.