bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaboration between schools and museums for inclusive cultural education: Findings from the INARTdis-project
Authors: Gigerl Monika , Sanahuja-Gavaldà Josep M. , Petrinska-Labudovikj Rozita , Moron-Velasco Mar , Rojas-Pernia Susana , Tragatschnig Ulrich
Published: October 2022

The increasing heterogeneity in our communities is a reality and a foundational element of modern societies. This article deals with different aspects of political, social and cultural participation, processes of integration and inclusion. The aim of inclusion of all marginalized groups, among others integrating migrant communities, has to be a process of involving all sides—the local communities with publicly funded cultural institutions, the marginalized groups like migrant communities and the educational institutions in the local area. Therefore, the local community and schools have to be willing to make efforts in addressing interests and needs of all people, especially migrants or persons with disabilities. This paper presents the findings of the data collection in the project INARTdis in the countries Austria, Spain, North Macedonia and Portugal. Firstly, educators from the school and extracurricular sector as well as people from the fields of culture were asked to answer the question:What is inclusive arts education and how can this be promoted through cooperation? The analysis of inclusive access to cultural institutions and arts education was conducted in 2021 using a mixed-method design. Secondly, during museum visits, results on the learners’ perspectives were collected. The aim was to find out what makes it easier for visitors to access the museum? The results show that, although the institutions and their professionals assume the principles of inclusion, their implementation is complex, either due to a lack of resources or due to the organizational structure of the arts institutions. All professionals consider that arts education promotes inclusive spaces as it allows for the participation and free expression of its participants. Likewise, they consider that accessibility is not really implemented and that the implementation of activities in arts institutions should favor the participation of users. In conclusion, there is a need to train professionals in inclusive arts education, to encourage collaboration between professionals and to implement inclusive strategies to promote participation and social inclusion.
Effect of agricultural subsidies on heterogeneous farmers’ fertilizer application intensity and its mediating mechanism: Based on China household finance survey database
Authors: He Guoping , Feng Jie , Xiao Taofen
Published: October 2022

Agricultural subsidies have an important effect on the farmer’s fertilizer application behavior, but the differences in the effect on different farmers and its mediating mechanism have not been sufficiently studied. Using relevant data from the CFHS database in 2015, this paper focused on the differences in the effect of agricultural subsidies on fertilizer application intensity among farmers with different operation scales and planting structures, as well as the mediating mechanism of the effect of agricultural subsidies on farmers’ fertilizer application intensity. It was found that agricultural subsidies in general helped farmers reduce fertilizer application. This finding still held after replacing the explanatory variables. However, the effect of agricultural subsidies on fertilizer application intensity varied significantly across farmers with different operation scales and planting structures. The fertilizer reduction effect of agricultural subsidies was weakened by the increase in the operation scale and the share of food crop cultivation, i.e., the fertilizer reduction effect of agricultural subsidies on smaller farmers and cash crop cultivation was greater relative to larger farmers and food crop cultivation. Farmers’ operation scale, planting structure and farm machinery inputs are important mediating variables of the effect of agricultural subsidies on farmers’ fertilizer application intensity. The agricultural subsidies played a role in reducing fertilizer application intensity by encouraging farmers to expand their operation scale and increase food crop cultivation, and increased fertilizer application intensity by incentivizing farmers to purchase farm machinery and adopt mechanical farming. Finally, some suggestions were put forward to play the fertilizer reduction effect of agricultural subsidies based on the findings of the study.
Modularity clustering of economic development and ESG attributes in prefabricated building research
Authors: Li Rita Yi Man , Li Bo , Zhu Xiaoe , Zhao Jingjing , Pu Ruihui , Song Lingxi
Published: October 2022

One major change in the modern construction industry worldwide in recent years is moving toward prefabricated buildings (offsite construction) to achieve sustainable development. Despite an increase in attention to ESG due to global stock markets’ requirements and prefabricated buildings aid industries in achieving the ESG goal, few or even no research investigated the ESG attributes of the prefabricated buildings. Additionally, ESG subitems in different industries receive varying attention. Developed countries are primarily subject to ESG rules, but ESG laws in developing countries are at their infant stages. No study examined the effects of economic progress on prefabricated buildings’ ESG attributes. The research gaps are filled by visualising and clustering the WoS and Scopus articles’ keywords, themes, and authors’ locations. This article also studied the evolution of this field. Based on the science map modularity cluster analysis, cost control is the most concerned issue in developed and developing countries. There are far more articles related to sustainability and environmental aspects of prefabricated buildings. Although the governance aspects of prefabricated buildings have not been thoroughly studied, inadequate governance increases bond yields. Therefore, future research on prefabricated buildings may expand to governance aspect to benefit industry and academia.
COVID-19 in the U.S. during pre-vaccination period: Shifting impact of sociodemographic factors and air pollution
Authors: Chaipitakporn Chaya , Athavale Prashant , Kumar Vijay , Sathiyakumar Thevasha , Budišić Marko , Sur Shantanu , Mondal Sumona
Published: October 2022

Pandemic “wave” usually refers to the rise and fall of the infections with time, however, for a large country, the variations due to geographical location could be considerable. In this work, we investigated COVID-19 infection and fatality across the U.S. during the pandemic waves in the pre-vaccination period (January 2020–December 2020). Focusing on counties with a population ≥100,000, the data from the entire period were first segmented into two equal phases roughly corresponding to the first pandemic wave and subsequent surge, and each phase was further divided into two zones based on infection rate. We studied the potential influences of six sociodemographic variables (population density, age, poverty, education, and percentage of Hispanic and African American population) and four air pollutants (PM2.5, NO2, SO2, and O3) on the differences in infection and fatality observed among different phases and zones. We noticed a distinct difference in the overall impact of COVID-19 between the two phases of the pre-vaccination period with a substantial decrease in the fatality in the second phase despite an increase in the infection. Analysis using log-linear regression modeling further revealed a shift in the impact of several risk factors considered in this study. For example, population density and lesser education were found to be significant for infection during the first phase of the pandemic alone. Furthermore, population density and lesser education along with poverty and NO2 level had a significant contribution to fatality during the first phase of the pandemic, while age over 65 years was important in both phases. Interestingly, the effects of many of these factors were found to be significant only in the zones with higher infection rates. Our findings indicate that the impacts of several well-known sociodemographic and environmental risk factors for COVID-19 are not constant throughout the course of the pandemic, and therefore, careful considerations should be made about their role when developing preventative and mitigative measures.
Assessing tree species diversity in forest ecosystems: A new approach
Authors: Zhao Zhonghua , Hui Gangying , Yang Aimin , Zhang Gongqiao , Hu Yanbo
Published: October 2022

The significance of biodiversity research is to understand the structure and function of the community, and then to protect and monitor the community. The metric of biodiversity is the base of biodiversity conservation. Species richness and evenness are the most common descriptors of biodiversity. Whether it is diversity information measure, probability measure or geometric measure, they all express the combination of species richness and evenness in different ways. This study presents a new biologically meaningful measure of species diversity, which evaluates species richness and evenness independently, designated as DRE. The novelty of our method is to use “absolute discrepancy” to express the dissimilarity between the observed community and the uniform distribution community with the same species composition and same abundance of each species, and then measure the species evenness. The logarithmic transformation of the species number is used to measure species richness with values ranging between 0 and 1. We test the performance of this measure using simulated data and observations of natural and planted forests in different climatic zones. The results showed that the new diversity index (DRE) has superior statistical qualities compared with the traditional indices. Especially, in extremely uneven communities, the new measure describes the causes of diversity changes than the traditional DRE. In addition, DRE is more sensitive to the abundance changes of rare species in the simulated community, and the interpretation of the results is more intuitive and meaningful. It is an improved method to evaluate the species diversity of any ecosystem.
Genome-wide identification and expression analysis of BrAGC genes in Brassica rapa reveal their potential roles in sexual reproduction and abiotic stress tolerance
Authors: Wu Xiaoyu , Pan Lianhui , Guo Xinping , Li Ting , Li Jiali , Duan Qiaohong , Huang Jiabao
Published: October 2022

AGC protein kinases play important roles in regulating plant growth, immunity, and cell death. However, the function of AGC in Brassica rapa has not yet been clarified. In this study, 62 BrAGC genes were identified, and these genes were distributed on 10 chromosomes and divided into six subfamilies. Analysis of gene structure and conserved motifs showed that the activation segment of BrAGC genes was highly conserved, and genes of the same subfamily showed higher sequence and structural similarity. Collinearity analysis revealed that BrAGCs were more closely related to AtAGCs than to OsAGCs. Expression profile analysis revealed that BrAGCs were preferentially expressed in flowers and BrAGC26, BrAGC33, and BrAGC04 were preferentially expressed in the stigma; the expression of these genes was significantly upregulated after self-incompatibility pollination, and the expression of BrAGC13 and BrAGC32 was significantly upregulated after cross-pollination. In addition, several typical cis-elements involved in the stress response were identified in BrAGC promoters. The expression levels of BrAGC37 and BrAGC44 significantly varied under different types of abiotic stress. Collectively, we identified that BrAGC26, BrAGC33, and BrAGC44 have the greatest potential in regulating pollen-pistil interaction and abiotic stress tolerance, respectively. Our findings will aid future functional investigations of BrAGCs in B. rapa.
Genetic variants associated with circulating liver injury markers in Mexican Americans, a population at risk for non-alcoholic fatty liver disease
Authors: Sabotta Caroline M. , Kwan Suet-Ying , Petty Lauren E. , Below Jennifer E. , Joon Aron , Wei Peng , Fisher-Hoch Susan P. , McCormick Joseph B. , Beretta Laura
Published: October 2022

Objective: Mexican Americans are disproportionally affected by non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma. Noninvasive means to identify those in this population at high risk for these diseases are urgently needed.

Approach: The Cameron County Hispanic Cohort (CCHC) is a population-based cohort with high rates of obesity (51%), type 2 diabetes (28%) and NAFLD (49%). In a subgroup of 564 CCHC subjects, we evaluated 339 genetic variants previously reported to be associated with liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in United Kingdom and Japanese cohorts.

Results: Association was confirmed for 86 variants. Among them, 27 had higher effect allele frequency in the CCHC than in the United Kingdom and Japanese cohorts, and 16 had stronger associations with AST and ALT than rs738409 (PNPLA3). These included rs17710008 (MYCT1), rs2519093 (ABO), rs1801690 (APOH), rs10409243 (S1PR2), rs1800759 (LOC100507053) and rs2491441 (RGL1), which were also associated with steatosis and/or liver fibrosis measured by vibration-controlled transient elastography. Main contributors to advanced fibrosis risk were rs11240351 (CNTN2), rs1800759 (LOC100507053), rs738409 (PNPLA3) and rs1801690 (APOH), with advanced fibrosis detected in 37.5% of subjects with 3 of these 4 variants [AOR = 11.6 (95% CI) = 3.8–35.3]. AST- and ALT-associated variants implicated distinct pathways (ethanol and galactose degradation versus antigen presentation and B cell development). Finally, 8 variants, including rs62292950 (DNAJC13), were associated with gut microbiome changes.

Conclusion: These genotype-phenotype findings may have utility in risk modeling and disease prevention in this high-risk population.
Microwave ablation combined with apatinib and camrelizumab in patients with advanced hepatocellular carcinoma: A single-arm, preliminary study
Authors: Li Xin , Zhang Qiao , Lu Qiaorui , Cheng Zhigang , Liu Fangyi , Han Zhiyu , Yu Xiaoling , Yu Jie , Liang Ping
Published: October 2022

Purpose

The aim of this study was to assess the safety and efficacy of microwave ablation combined with apatinib [vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor] and camrelizumab [anti-programmed death-1 (PD-1) antibody] in patients with advanced hepatocellular carcinoma (HCC).

Patients and methods

Patients (age, >18 years) with histologically confirmed HCC and refractory to at least the standard first-line therapy were enrolled from 2 September 2018 to 17 January 2022. They first received ultrasound-guided subtotal microwave ablation. Then, beginning at 7–14 days after ablation, they were given apatinib (250 mg once daily) and camrelizumab (200 mg once every 2 weeks) until unacceptable toxicity or disease progression or death. The coprimary end points were progression-free survival (PFS) and overall survival (OS).

Results

Fourteen HCC patients with Barcelona Clinic of Liver Cancer (BCLC) B and C stages were retrospectively enrolled. At data cutoff, follow-up period ranged from 3.8 to 41.3 months (median, 17.4 months), and the median (95% confidence interval) duration of exposure (DE) was 6.4 (4.0–8.9) months. The PFS and OS were 10.8 (0–23.5) months and 19.3 (2.4–36.2) months, respectively. Three (21.4%) patients achieved a confirmed complete response (CR). Confirmed partial response (PR), stable disease (SD), and progression of disease (PD) were achieved in four (28.6%), four (28.6%), and three (21.4%) patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were 50.0% (20.0%-80.0%) and 78.6% (54.0%-100%), respectively. The serious treatment-related adverse events included one (7.1%) case with reactive capillary hemangiomas (grade 4), one (7.1%) with hypertension (grade 3), two (14.3%) with elevated transaminase and bilirubin (grade 4), one (7.1%) with platelet count decrease (grade 4), one (7.1%) with hepatic failure (grade 4), and two (14.3%) with gastrointestinal bleeding (grades 3 and 4).

Conclusions

Microwave ablation combined with apatinib and camrelizumab treatment in advanced HCC patients demonstrated intriguing clinical activity and resulted in durable antitumor responses and significantly improved PFS and OS. The combination therapy is well tolerated, enabling further clinical studies.
Benthic biology in the Polish exploration contract area of the Mid-Atlantic Ridge: The knowns and the unknowns. A review
Authors: Radziejewska Teresa , Błażewicz Magdalena , Włodarska-Kowalczuk Maria , Jóźwiak Piotr , Pabis Krzysztof , Węsławski Jan Marcin
Published: October 2022

In February 2018, the Government of Poland and the International Seabed Authority signed a 15-year contract for exploration of polymetallic sulfide deposits on a section of the Mid-Atlantic Ridge extending between the Hayes, Atlantic and Kane transform faults (32°45.378’ N, 39°57.760’ W to 26°14.411’ N, 44°18.008’ W). The contractor is obliged to collect data on the contract area environment and its ecosystem components. In this context, it is important that the contractor establishes a sound starting point which further baseline investigations can be referred to. Such a starting point involves assessment of currently held information and, most importantly, knowledge gaps on the ecosystem components in the area of exploration (and of potential future exploitation). Of major importance here is the knowledge on benthic communities, as it is the benthos that will be most affected by any human intervention in the area of interest. Based on available published evidence, we have reviewed the present state of knowledge on benthic communities in the Polish exploration contract area (PECA). In the process, we have identified important knowledge gaps that will need to be addressed during exploration surveys. These include, but are not limited to, the distribution and structure of benthic communities throughout the contract area, the spatial and temporal variability of those communities, possible differences between communities inhabiting active and inactive vent fields, connectivity issues and the recovery potential. Special consideration should be given to Lost City, a geologically and ecologically unique hydrothermal field which has been a focus of international research and an important conservation target.
Single-cell RNA-seq reveals the communications between extracellular matrix-related components and Schwann cells contributing to the earlobe keloid formation
Authors: Gong Taogen , Wang Yayu , Dong Shaowei , Ma Xiaoshi , Du Danfeng , Zou Chang , Zheng Qijun , Wen Zhong
Published: October 2022

Keloid is a major type of skin fibrotic disease, with one prominent feature of extensive accumulation of extracellular matrix (ECM) components, and another feature of pain/itching, which is closely related to the peripheral nervous system (PNS). However, the molecular pathogenesis of these two prominent features still needs to be further explored. In the present study, we performed single-cell RNA sequencing (scRNA-seq) on clinical earlobe keloid samples and adjacent normal skin samples and constructed a keloid atlas of 31,379 cells. All cells were clustered into 13 major cell types using cell-type-specific markers. Among them, fibroblast, vascular endothelial cells, and smooth muscle cells were defined as the ECM-related populations according to their ECM-associated functions. Also, we found that Schwann cells (SCs) were the main neuron cells of PNS in the skin. Interestingly, the cell proportions of ECM-related populations, as well as SC were increased significantly in the earlobe keloid compared to the adjacent normal tissues, suggesting an important role of these cell types in the development of the earlobe keloid. Comprehensive cell–cell interaction analysis at the single-cell level revealed a strong interaction between SC and ECM-related subgroups which might be mediated by SEMA3C signaling pathways and MK/PTN gene family, which are found to be mainly involved in promoting cell proliferation and migration. Moreover, further exploration of the interactions of ECM-related populations and SC in different keloids, including earlobe keloid, back keloid, and chest keloid revealed an increasing amount of TGFβ–TGFβ receptor interactions in chest/back keloids as compared to earlobe keloid, which suggested the anatomic site-specific pathogenesis in different keloids. Altogether, these findings suggested the interactions between ECM-related populations and SC contributing to the earlobe keloid formation and helped us to better understand the pathogenesis of keloids.
Effect of idiopathic epiretinal membrane on macular ganglion cell complex measurement in eyes with glaucoma
Authors: Nakakura Shunsuke , Asaoka Ryo , Oogi Satomi , Aoki Ryota , Terao Etsuko , Ueda Kanae , Kiuchi Yoshiaki
Published: October 2022

Background/objectives

Co-existing idiopathic epiretinal membrane (ERM) and glaucoma complicate the estimation of glaucoma severity via optical coherence tomography (OCT). We investigated the effect of ERM and a new associated parameter, SUKIMA (space between the ERM and retinal surface), on ganglion cell complex (GCC) thickness in eyes with glaucoma, based on a matched comparison of visual field defects.

Subjects/methods

We retrospectively recruited 41 eyes from 34 glaucoma patients with idiopathic ERM and 41 eyes from 41 glaucoma patients without ERM as controls (matched by age, axial length, and mean visual field deviation). The thicknesses of GCC layers [retinal nerve fiber layer (RNFL), ganglion cell layer + inner plexiform layer (GCIPL), and GCC (RNFL + GCIPL)] were measured with swept-source OCT. We investigated the presence of SUKIMA and its effect on GCC measurements.

Results

RNFL, GCIPL, and GCC were thicker in ERM (+) eyes than in control eyes (31.0 ± 12.3 μm vs. 22.7 ± 10.8 μm, 62.6 ± 12.2 μm vs. 53.8 ± 5.9 μm, and 91.8 ± 16.6 μm vs. 76.8 ± 13.3 μm, respectively; P < 0.01). Eyes in the ERM-associated SUKIMA (+) group had thicker GCIPL and GCC than those in the ERM-associated SUKIMA (−) and control groups (P < 0.01).

Conclusion

ERM-associated SUKIMA affects GCC thickness and can result in underestimations of glaucoma severity. We should check for the presence of ERM using a B mode scan as well as check for the SKIMA sign.
Application of problem-based learning combined with a virtual simulation training platform in clinical biochemistry teaching during the COVID-19 pandemic
Authors: Xie Hongxiang , Wang Li , Pang Zhenzhen , Chen Sufeng , Xu Guoying , Wang Sumei
Published: October 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has had a great impact on the traditional teaching mode (Lecture-based Learning, LBL) and laboratory teaching. To address this challenge, the researchers conducted online Problem-based learning (PBL) teaching and virtual simulation laboratory teaching through DingTalk, and evaluated the effectiveness of this method in teaching clinical biochemistry.

Methods

With the method of cluster sampling, the researchers randomly selected 60 students from two classes of the Class 2019 as the experimental group for this prospective experimental study. The theory class was taught online PBL through DingTalk, and experimental lectures were given by virtual simulation. After the experimental teaching, students were assessed for theory and operation. Self-administered questionnaires were administered through DingTalk. 65 students from our 2018 medical laboratory class were randomly selected as the control group, and offline LBL and traditional experimental teaching methods were used. Examination results were obtained through teaching portfolios.

Results

The experimental group had significantly better examination scores in theoretical knowledge and experimental operational skills than the control group (87.45 ± 5.91 vs. 83.52 ± 9.94, P = 0.0095; 87.08 ± 12.42 vs. 80.18 ± 14.04, P = 0.0044). The results of the questionnaire survey revealed that the experimental group was more receptive to the DingTalk-PBL teaching method and virtual simulation laboratory teaching. Moreover, this hybrid teaching method was more effective in promoting basic knowledge understanding (95.0%, 57/60), facilitating the mastery of operational skills (93.3, 56/60), cultivating interest in learning (96.7%, 58/60), training clinical thinking (95.0%, 57/60), improving communication skills (95.0%, 57/60), and enhancing self-learning ability (91.7%, 55/60) and was more satisfying than traditional teaching method (all P < 0.05).

Conclusion

The DingTalk-based PBL method combined with virtual simulation experiments was an effective and acceptable teaching strategy during the pandemic compared with the traditional teaching method.
Ocular effects caused by viral infections and corresponding vaccines: An overview of varicella zoster virus, measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2
Authors: Scalabrin Simona , Becco Alice , Vitale Alessio , Nuzzi Raffaele
Published: October 2022

Many viral infections can affect vision and the visual system. Vaccination to prevent diseases is commonplace today, acting by stimulating an immune response without developing the pathology. It involves the production of persisting antibodies against the pathogen and the activation of T cells. Certain diseases have already been eradicated by rigorous vaccination campaigns, while others are hoped to be eliminated soon. Vaccines currently available on the market are largely safe, even if they can rarely cause some adverse effects, such as ocular complications. Analyzing existing literature, we aimed to compare the pathological effects on the eye due to the most common viral infections [in particular varicella zoster virus (VZV), measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2] with the possible ocular adverse effects of their relative vaccines, in order to establish a risk-benefit relationship from an ophthalmological point of view.
Erythrocyte tropism of malarial parasites: The reticulocyte appeal
Authors: Leong Yew Wai , Russell Bruce , Malleret Benoit , Rénia Laurent
Published: October 2022

Erythrocytes are formed from the enucleation of erythroblasts in the bone marrow, and as erythrocytes develop from immature reticulocytes into mature normocytes, they undergo extensive cellular changes through their passage in the blood. During the blood stage of the malarial parasite life cycle, the parasite sense and invade susceptible erythrocytes. However, different parasite species display varying erythrocyte tropisms (i.e., preference for either reticulocytes or normocytes). In this review, we explore the erythrocyte tropism of malarial parasites, especially their predilection to invade reticulocytes, as shown from recent studies. We also discuss possible mechanisms mediating erythrocyte tropism and the implications of specific tropisms to disease pathophysiology. Understanding these allows better insight into the role of reticulocytes in malaria and provides opportunities for targeted interventions.
Localization of the neuropeptides pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal peptide, and their receptors in the basal brain blood vessels and trigeminal ganglion of the mouse CNS; an immunohistochemical study
Authors: Lund Anne Marie , Hannibal Jens
Published: October 2022

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are structurally related neuropeptides that are widely expressed in vertebrate tissues. The two neuropeptides are pleiotropic and have been associated with migraine pathology. Three PACAP and VIP receptors have been described: PAC1, VPAC1, and VPAC2. The localization of these receptors in relation to VIP and PACAP in migraine-relevant structures has not previously been shown in mice. In the present study, we used fluorescence immunohistochemistry, well-characterized antibodies, confocal microscopy, and three-dimensional reconstruction to visualize the distribution of PACAP, VIP, and their receptors in the basal blood vessels (circle of Willis), trigeminal ganglion, and brain stem spinal trigeminal nucleus (SP5) of the mouse CNS. We demonstrated a dense network of circularly oriented VIP fibers on the basal blood vessels. PACAP nerve fibers were fewer in numbers compared to VIP fibers and ran along the long axis of the blood vessels, colocalized with calcitonin gene-related peptide (CGRP). The nerve fibers expressing CGRP are believed to be sensorial, with neuronal somas localized in the trigeminal ganglion and PACAP was found in a subpopulation of these CGRP-neurons. Immunostaining of the receptors revealed that only the VPAC1 receptor was present in the basal blood vessels, localized on the surface cell membrane of vascular smooth muscle cells and innervated by VIP fibers. No staining was seen for the PAC1, VPAC1, or VPAC2 receptor in the trigeminal ganglion. However, distinct PAC1 immunoreactivity was found in neurons innervated by PACAP nerve terminals located in the spinal trigeminal nucleus. These findings indicate that the effect of VIP is mediated via the VPAC1 receptor in the basal arteries. The role of PACAP in cerebral arteries is less clear. The localization of PACAP in a subpopulation of CGRP-expressing neurons in the trigeminal ganglion points toward a primary sensory function although a dendritic release cannot be excluded which could stimulate the VPAC1 receptor or the PAC1 and VPAC2 receptors on immune cells in the meninges, initiating neurogenic inflammation relevant for migraine pathology.
Age- and sex-specific effects of maternal separation on the acoustic startle reflex in rats: early baseline enhancement in females and blunted response to ambiguous threat
Authors: Granata Lauren , Parakoyi Abigail , Brenhouse Heather C.
Published: October 2022

Early life adversity (ELA) increases the incidence of later-life anxiety disorders. Dysregulated threat processing, including responsivity to ambiguous threats, is an indicator of anxiety disorders and can be influenced by childhood experiences. The acoustic startle response is a defensive reflex displayed by mammals when exposed to sudden intense stimuli reflecting individual variations in vigilance. These measures can be altered by previous experience and experimental modifications, including the introduction of unconditioned aversive stimuli. Rats emit ultrasonic vocalizations (USVs) in the 22 KHz range in negative contexts. As such, 22 KHz USVs are an ethologically relevant social cue of environmental threat shown to induce anxiety-like behavior in recipient rats. Because the timing of symptom manifestation after early life adversity can differ between sexes, the current study sought to identify the age- and sex-specific effects of daily maternal separation (MS) on responsivity to ambiguous threat in rats. In Experiment 1, rat pups underwent MS or control rearing from postnatal day (P) 2–20, then underwent behavioral testing beginning on P24, 34, or 54 to determine whether MS modified the baseline startle response or the modulation of startle by 22 KHz USVs. In Experiment 2, rats were tested in a light-enhanced startle paradigm at P54 after MS or control rearing to determine whether MS influenced light-enhanced startle. Results show an enhancement of the baseline startle magnitude by MS in females at P34. At P54, MS reduced the modulation of the startle response by 22 KHz USVs and prevented light-enhanced startle, indicating an MS-induced deficit in defensive responsivity when exposed to potential threat.
Association of enlarged perivascular spaces with upper extremities and gait impairment: An observational, prospective cohort study
Authors: Hou Yutong , Yang Shuna , Li Yue , Qin Wei , Yang Lei , Hu Wenli
Published: October 2022

Background and objective

Gait disturbances are common in the elderly and can lead to the loss of functional independence and even death. Enlarged perivascular space (EPVS) and motor performance may be related, but only few studies have explored this relationship. The aim of our study was to investigate the effects of both the severity and location of EPVS on movement disorders.

Method

Two hundred and six participants aged between 45 and 85 years old with complete magnetic resonance imaging (MRI) data were included in our analysis. EPVS were divided into basal ganglia (BG) and centrum semiovale (CSO), and their grades were measured. Gait was assessed quantitatively using a 4-m walkway and TUG test as well as semi-quantitatively using the Tinetti and SPPB tests. The function of upper extremities was evaluated by 10-repeat pronation–supination, 10-repeat finger-tapping, and 10-repeat opening and closing of the hands.

Results

Both high-grade EPVS, whether in BG and CSO, were independently correlated with gait parameters, the TUG time, Tinetti, and SPPB tests. The EPVS located in BG had a significant association with 10-repeat finger-tapping time (β = 0.231, P = 0.025) and a similar association was also observed between CSO-EPVS and 10-repeat pronation–supination time (β = 0.228, P = 0.014).

Conclusion

Our results indicated that EPVS was associated with gait disturbances, and a further investigation found that EPVS has an association with upper extremities disorder. EPVS should be considered as a potential target for delaying gait and upper extremities damage since CSVD can be prevented to some extent.
Mental fatigue decreases complexity: Evidence from multiscale entropy analysis of instantaneous frequency variation in alpha rhythm
Authors: Zhai Yawen , Li Yan , Zhou Shengyi , Zhang Chenxu , Luo Erping , Tang Chi , Xie Kangning
Published: October 2022

Mental fatigue (MF) jeopardizes performance and safety through a variety of cognitive impairments and according to the complexity loss theory, should represent “complexity loss” in electroencephalogram (EEG). However, the studies are few and inconsistent concerning the relationship between MF and loss of complexity, probably because of the susceptibility of brain waves to noise. In this study, MF was induced in thirteen male college students by a simulated flight task. Before and at the end of the task, spontaneous EEG and auditory steady-state response (ASSR) were recorded and instantaneous frequency variation (IFV) in alpha rhythm was extracted and analyzed by multiscale entropy (MSE) analysis. The results show that there were significant differences in IFV in alpha rhythm either from spontaneous EEG or from ASSR for all subjects. Therefore, the proposed method can be effective in revealing the complexity loss caused by MF in spontaneous EEG and ASSR, which may serve as a promising analyzing method to mark mild mental impairments.
Neuromagnetic representation of melodic contour processing in human auditory cortex
Authors: Taddeo Sabrina , Schulz Martin , Andermann Martin , Rupp André
Published: October 2022

The pattern of ups and downs in a sequence with varying pitch can be heard as a melodic contour. Contrary to single pitch, the neural representation of melodic contour information in the auditory cortex is rarely investigated, and it is not clear whether the processing entails a hemispheric asymmetry. The present magnetoencephalography study assessed the neuromagnetic responses of N = 18 normal-hearing adults to four-note sequences with fixed vs. varying pitch that were presented either monaurally or diotically; data were analyzed using minimum-norm reconstructions. The first note of the sequences elicited prominent transient activity in posterior auditory regions (Planum temporale), especially contralateral to the ear of entry. In contrast, the response to the subsequent notes originated from more anterior areas (Planum polare) and was larger for melodic contours than for fixed pitch sequences, independent from the ear of entry and without hemispheric asymmetry. Together, the results point to a gradient in the early cortical processing of melodic contours, both in spatial and functional terms, where posterior auditory activity reflects the onset of a pitch sequence and anterior activity reflects its subsequent notes, including the difference between sequences with fixed pitch and melodic contours.
Localization of beta power decrease as measure for lateralization in pre-surgical language mapping with magnetoencephalography, compared with functional magnetic resonance imaging and validated by Wada test
Authors: Herfurth Kirsten , Harpaz Yuval , Roesch Julie , Mueller Nadine , Walther Katrin , Kaltenhaeuser Martin , Pauli Elisabeth , Goldstein Abraham , Hamer Hajo , Buchfelder Michael , Doerfler Arnd , Prell Julian , Rampp Stefan
Published: October 2022

Objective:Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task.

Methods:Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects.

Results:Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen’s Kappa = 1,p< 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca’s area (Cohen’s Kappa = 0.71,p= 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke’s area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest.

Conclusion:Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions.
Significantly different noun-verb distinguishing mechanisms in written Chinese and Chinese sign language: An event-related potential study of bilingual native signers
Authors: Xu Lewen , Gong Tao , Shuai Lan , Feng Jun
Published: October 2022

Little is known about: (a) whether bilingual signers possess dissociated neural mechanisms for noun and verb processing in written language (just like native non-signers), or they utilize similar neural mechanisms for those processing (due to general lack of part-of-speech criterion in sign languages); and (b) whether learning a language from another modality (L2) influences corresponding neural mechanism of L1. In order to address these issues, we conducted an electroencephalogram (EEG) based reading comprehension study on bimodal bilinguals, namely Chinese native deaf signers, whose L1 is Chinese Sign Language and L2 is written Chinese. Analyses identified significantly dissociated neural mechanisms in the bilingual signers’ written noun and verb processing (which also became more explicit along with increase in their written Chinese understanding levels), but not in their understanding of verbal and nominal meanings in Chinese Sign Language. These findings reveal relevance between modality-based linguistic features and processing mechanisms, which suggests that: processing modality-based features of a language is unlikely affected by learning another language in a different modality; and cross-modal language transfer is subject to modal constraints rather than explicit linguistic features.
Treatment with vascular endothelial growth factor-A worsens cognitive recovery in a rat model of mild traumatic brain injury
Authors: Sun Mujun , Baker Tamara L. , Wilson Campbell T. , Brady Rhys D. , Mychasiuk Richelle , Yamakawa Glenn R. , Vo Anh , Wilson Trevor , McDonald Stuart J. , Shultz Sandy R.
Published: October 2022

Mild traumatic brain injury (mTBI) is a common and unmet clinical issue, with limited treatments available to improve recovery. The cerebrovascular system is vital to provide oxygen and nutrition to the brain, and a growing body of research indicates that cerebrovascular injury contributes to mTBI symptomatology. Vascular endothelial growth factor-A (VEGF-A) is a potent promoter of angiogenesis and an important modulator of vascular health. While indirect evidence suggests that increased bioavailability of VEGF-A may be beneficial after mTBI, the direct therapeutic effects of VEGF-A in this context remains unknown. This study therefore aimed to determine whether intracerebroventricular administration of recombinant VEGF-A could improve recovery from mTBI in a rat model. Male and female Sprague–Dawley rats were assigned to four groups: sham + vehicle (VEH), sham + VEGF-A, mTBI + VEH, mTBI + VEGF-A. The mTBI was induced using the lateral impact model, and treatment began at the time of the injury and continued until the end of the study. Rats underwent behavioral testing between days 1 and 10 post-injury, and were euthanized on day 11 for post-mortem analysis. In males, the mTBI + VEGF-A group had significantly worse cognitive recovery in the water maze than all other groups. In females, the VEGF treatment worsened cognitive performance in the water maze regardless of mTBI or sham injury. Analysis of hippocampal tissue found that these cognitive deficits occurred in the presence of gene expression changes related to neuroinflammation and hypoxia in both male and female rats. These findings indicate that the VEGF-A treatment paradigm tested in this study failed to improve mTBI outcomes in either male or female rats.
In vitro models for investigating itch
Authors: Mießner Hendrik , Seidel Judith , Smith Ewan St. John
Published: October 2022

Itch (pruritus) is a sensation that drives a desire to scratch, a behavior observed in many animals. Although generally short-lasting and not causing harm, there are several pathological conditions where chronic itch is a hallmark symptom and in which prolonged scratching can induce damage. Finding medications to counteract the sensation of chronic itch has proven difficult due to the molecular complexity that involves a multitude of triggers, receptors and signaling pathways between skin, immune and nerve cells. While much has been learned about pruritus fromin vivoanimal models, they have limitations that corroborate the necessity for a transition to more human disease-like models. Also, reducing animal use should be encouraged in research. However, conducting humanin vivoexperiments can also be ethically challenging. Thus, there is a clear need for surrogate models to be used in pre-clinical investigation of the mechanisms of itch. Mostin vitromodels used for itch research focus on the use of known pruritogens. For this, sensory neurons and different types of skin and/or immune cells are stimulated in 2D or 3D co-culture, and factors such as neurotransmitter or cytokine release can be measured. There are however limitations of such simplisticin vitromodels. For example, not all naturally occurring cell types are present and there is also no connection to the itch-sensing organ, the central nervous system (CNS). Nevertheless,in vitromodels offer a chance to investigate otherwise inaccessible specific cell–cell interactions and molecular pathways. In recent years, stem cell-based approaches and human primary cells have emerged as viable alternatives to standard cell lines or animal tissue. Asin vitromodels have increased in their complexity, further opportunities for more elaborated means of investigating itch have been developed. In this review, we introduce the latest concepts of itch and discuss the advantages and limitations of currentin vitromodels, which provide valuable contributions to pruritus research and might help to meet the unmet clinical need for more refined anti-pruritic substances.
Serum albumin to globulin ratio prior to treatment as a potential non-invasive prognostic indicator for urological cancers
Authors: Xia Zhongyou , Fu Xueqin , Yuan Xinzhu , Li Jinze , Wang Hao , Sun Jing , Wu Ji , Tang Lingtong
Published: October 2022

Background

Numerous clinical studies have reported an association between the pretreatment albumin to globulin ratio (AGR) and survival outcomes of urological cancers. However, these conclusions remain controversial. Therefore, we performed a meta-analysis to explore the prognostic value of the AGR in urinary system tumors.

Methods

We retrieved eligible studies published up to June 2022 through a comprehensive search of multiple databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and biochemical recurrence-free survival (BRFS) were used to evaluated the predictive effect of the AGR before treatment in urinary system tumors. Heterogeneity test, random-effects models, fixed-effects models and sensitivity tests were used for analyses.

Results

A total of 21 studies with 18,269 patients were enrolled in our meta-analysis. We found that patients with urinary system cancer with low AGR prior to treatment had poor OS [HR = 1.93, 95% CI (1.56–2.39), p < 0.001], CSS [HR = 2.22, 95% CI (1.67–2.96), p < 0.001], RFS [HR = 1.69, 95% CI (1.29–2.22), p < 0.001], and PFS [HR = 1.29, 95% CI (0.54–3.07), p < 0.001]. For prostate cancer (PCa), a low pretreatment AGR was associated with poor BRFS [HR = 1.46, 95% CI (1.28–1.67), p < 0.001]. Also, a subgroup analysis, stratified by ethnicity, cancer type, cutoff value, sample size and publication year, was conducted. The results showed that worse OS and CSS were significantly associated with these factors.

Conclusion

Our meta-analysis revealed that the AGR before treatment could be used as a non-invasive predictive biomarker to evaluate the prognosis of urological cancer patients in clinical practice.