bluuebunny/crossref_metadata_2025 huggingface dataset:
The possibility of the no-hair theorem being violated
Authors: CHEN WEN-XIANG , Zheng Yao-Guang
Published: August 2023

Recently, one of my articles presented intriguing findings on the superradiant stability of Kerr black holes. These findings drew conclusions that appear to challenge the established ``No Hair Theorem". As is widely known, the ``No Hair Theorem" stems from the principles of general relativity. In this paper, we thoroughly examine the nexus between Bell's theorem and the uncertainty principle. By delving deep into the theoretical underpinnings of both concepts, we illustrate that Bell's theorem occupies a more foundational stance within the landscape of uncertainty. This gives rise to a particular probability, shedding light on why the no-hair theorem might not hold in the face of quantum effects. It's possible that while the no-hair theorem remains valid, the combined effects of classical and quantum mechanics introduce additional variations to the three parameters of the black hole. This nuance could represent a modest advancement in cosmological research.
CENÁRIOS PARA INVESTIGAÇÃO E OS LIVROS DIDÁTICOS: UM OLHAR PARA AS PESQUISAS REALIZADAS
Authors: Krefta Silvana , Paulo Trevisan Eberson , Trevisan Andreia
Published: August 2023

O presente artigo tem como objetivo apresentar o Estado do Conhecimento sobre pesquisas que possuem, como objeto de estudo, a relação entre os cenários para investigação de Ole Skovsmose e os livros e/ou materiais didáticos. O recorte temporal para averiguação deu-se entre 2010 e 2022. As buscas foram realizadas no catálogo de teses e de dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); em revistas nacionais, em formato on-line, com foco em ensino e pesquisa, que possuem estratos Qualis Capes A1, A2 e B1, somando 112 revistas analisadas; e nos anais do X, XI, XII e XIII Encontro Nacional da Educação Matemática (ENEM). Na busca inicial de pesquisas que exploraram a teoria de Ole Skovsmose, identificamos 234 trabalhos, destes, 20 se relacionam com livros didáticos e/ou materiais didáticos. Após análise, observou-se que os resultados demonstram grande concentração no tema Educação Financeira e que as pesquisas foram preponderantes ao Ensino Fundamental. Ainda assim, as pesquisas indicam que os livros didáticos podem favorecer os cenários para investigação em diversas temáticas e etapas de ensino, mas que ainda existem lacunas quanto ao suporte para o professor que pretende avançar aos ambientes investigativos.
Seismic performance of Chilean concentrically braced frame industrial structures: effects of recent code modifications
Authors: Riquelme Roberto , Herrera Ricardo
Published: August 2023

Few seismic design codes for industrial structures exist worldwide. Among them, the Chilean design code was put to the test by the Maule earthquake of 2010, one of the largest seismic events in recent years. Although the seismic performance of industrial steel structures designed under these provisions was satisfactory, the standard was revised based on the accumulated evidence on the performance after the event and the advances in seismic design since the code was released in 2003. The revision process led to a number of modifications to the provisions, including those for structures based on concentrically braced frames (CBFs), a structural typology widely used in the industry. The modifications, mainly aimed at improving seismic performance in severe events, ranged from the seismic demand to the provisions for sizing structural elements and connections. This work evaluates the effect of these modifications on the design and seismic performance of CBFs. For this purpose, six industrial steel structures were designed using the current standard and the proposed version. The performance was evaluated through static non-linear analyses in 3D models according to the methodology prescribed by the FEMA P695 standard. The models included the non-linearity of braces, columns, beams or struts, and anchor bolts. The results showed similar performance between the structures designed using the proposed and the current version of the standard, in terms of overstrength and response modification factors. However, the performance improved when comparing the maximum drift that the structures can reach and the energy levels they are able to accumulate at these drifts. In terms of the cost–performance ratio, the improvement in performance is associated with moderate increases in cost.
Utilizing metagenomic next-generation sequencing for diagnosis and lung microbiome probing of pediatric pneumonia through bronchoalveolar lavage fluid in pediatric intensive care unit: results from a large real-world cohort
Authors: Shen Huili , Liu Tingyan , Shen Meili , Zhang Yi , Chen Weiming , Chen Hanlin , Wang Yixue , Liu Jing , Tao Jinhao , He Liming , Lu Guoping , Yan Gangfeng
Published: August 2023

Background

Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples.

Methods

A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients’ lung BALF microbiomes were explored using the mNGS data.

Results

Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%).

Conclusions

mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.
Case report: Magnetocardiography as a potential method of therapy monitoring in amyloidosis
Authors: Golpour Ainoosh , Suwalski Phillip , Landmesser Ulf , Heidecker Bettina
Published: August 2023

Amyloidosis is characterized by a disorder of protein conformation and metabolism, resulting in deposits of insoluble fibrils in various organs causing functional disturbances. Amyloidosis can also affect the heart. Cardiac amyloidosis tends to have a poor prognostic outcome if diagnosed at a late stage. Therefore, early diagnosis and initiation of therapy as well as monitoring of treatment response are crucial to improve outcomes and to learn more about its pathophysiology and clinical course. We present an 83-year-old woman with cardiac transthyretin amyloidosis (ATTR) who was treated with tafamidis. The patient significantly improved 18 months after initiation of therapy with regards to exercise capacity and quality of life. In addition to standard diagnostic methods, we used magnetocardiography (MCG) to monitor potential treatment response by detecting changes in the magnetic field of the heart. MCG is a non-invasive method that detects the cardiac magnetic field generated by electrical currents in the heart with high sensitivity. We have recently shown that this magnetic field changes in various types of cardiomyopathies may be used as a non-invasive screening tool. We determined previously that an MCG vector ≥0.052 was the optimal threshold to detect cardiac amyloidosis. The patient's MCG was measured at various time points during therapy. At the time of diagnosis, the patient's MCG vector was 0.052. After starting therapy, the MCG vector increased to 0.090, but improved to 0.037 after 4 months of therapy. The MCG vector reached a value of 0.017 after 5 months of therapy with tafamidis, and then increased slightly after 27 months to a value of 0.027 (<0.052). Data from this case support our previous findings that MCG may be used to monitor treatment response non-invasively. Further research is needed to understand the unexpected changes in the MCG vector that were observed at the beginning of therapy and later in the course. Larger studies will be necessary to determine how these changes in the electromagnetic field of the heart are related to structural changes and how they affect clinical outcomes.
Technology and older adults in British loneliness policy and political discourse
Authors: Jentoft Elian Eve
Published: August 2023

Introduction

This article provides an analysis of recent loneliness policy and political discourses from the United Kingdom pertaining to older adults. Although government asserts that several groups in society are “at risk” of loneliness, older adults remain the most frequent targets of policy interventions. Technology is positioned as playing a role in the causation and alleviation of loneliness. Little research has examined loneliness in political discourses.

Methods

With a focus on how loneliness intersects with themes of technology and aging, this article presents an analysis of discourses guided by Bacchi's What is the Problem Represented to Be (WPR) framework. It endeavors to answer the following questions: What is the problem of loneliness among older adults represented to be, and what is the role of technology in this context – problem or solution?

Results

In the discourses, assertions are made that issues of loneliness, societal change and digital exclusion are intertwined. Lonely older adults are problematized as hard to find and thus connect with interventions, warranting surveillance measures like loneliness heatmaps. Technological interventions to assist older adults in maintaining independence and connections to social networks are often proposed as solutions. The findings indicate dominant discourses position older adults primarily as subjects in need of care and as non-users of technology. Technology is positioned as a cost-effective tool to fill gaps in an overburdened and under-funded social care system that compounds issues of loneliness.

Discussion

The author argues the neoliberal and stigmatizing undertones within the corpus may undermine efforts to combat loneliness. Further, austerity is silent in the dominant problematizations of loneliness, foreclosing upon alternatives that problematize loneliness as resulting from neoliberal policies that continue to dismantle public infrastructure and social care.
Usability and performance expectancy govern spine surgeons’ use of a clinical decision support system for shared decision-making on the choice of treatment of common lumbar degenerative disorders
Authors: Eiskjær Søren , Pedersen Casper Friis , Skov Simon Toftgaard , Andersen Mikkel Østerheden
Published: August 2023

Study design

Quantitative survey study is the study design.

Objectives

The study aims to develop a model for the factors that drive or impede the use of an artificial intelligence clinical decision support system (CDSS) called PROPOSE, which supports shared decision-making on the choice of treatment of ordinary spinal disorders.

Methods

A total of 62 spine surgeons were asked to complete a questionnaire regarding their behavioral intention to use the CDSS after being introduced to PROPOSE. The model behind the questionnaire was the Unified Theory of Acceptance and Use of Technology. Data were analyzed using partial least squares structural equation modeling.

Results

The degree of ease of use associated with the new technology (effort expectancy/usability) and the degree to which an individual believes that using a new technology will help them attain gains in job performance (performance expectancy) were the most important factors. Social influence and trust in the CDSS were other factors in the path model. r2 for the model was 0.63, indicating that almost two-thirds of the variance in the model was explained. The only significant effect in the multigroup analyses of path differences between two subgroups was for PROPOSE use and social influence (p = 0.01).

Conclusion

Shared decision-making is essential to meet patient expectations in spine surgery. A trustworthy CDSS with ease of use and satisfactory predictive ability promoted by the leadership will stand the best chance of acceptance and bridging the communication gap between the surgeon and the patient.
Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs
Authors: Chen Chen , Ren Huibo , Li Huali , Deng Yuan , Cui Qingming , Zhu Ji , Zhang Siyang , Yu Jine , Wang Huiming , Yu Xiaodan , Yang Shiliu , Hu Xionggui , Peng Yinglin
Published: August 2023

Fat deposition is an economically important trait in pigs. Ningxiang pig, one of the four famous indigenous breeds in China, is characterized by high fat content. The underlying gene expression pattern in different developmental periods of backfat tissue remains unclear, and the purpose of this investigation is to explore the potential molecular regulators of backfat tissue development in Ningxiang pigs. Backfat tissue (three samples for each stage) was initially collected from different developmental stages (60, 120, 180, 240, 300, and 360 days after birth), and histological analysis and RNA sequencing (RNA-seq) were then conducted. Fragments per kilobase of transcript per million (FPKM) method was used to qualify gene expressions, and differentially expressed genes (DEGs) were identified. Furthermore, strongly co-expressed genes in modules, which were named by color, were clustered by Weighted gene co-expression network analysis (WGCNA) based on dynamic tree cutting algorithm. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment were subsequently implemented, and hub genes were described in each module. Finally, QPCR analysis was employed to validate RNA-seq data. The results showed that adipocyte area increased and adipocyte number decreased with development of backfat tissue. A total of 1,024 DEGs were identified in five comparison groups (120 days vs. 60 days, 180 days vs. 120 days, 240 days vs. 180 days, 300 days vs. 240 days, and 360 days vs. 300 days). The turquoise, red, pink, paleturquoise, darkorange, and darkgreen module had the highest correlation coefficient with 60, 120, 180, 240, 300, and 360 days developmental stage, while the tan, black and turquoise module had strong relationship with backfat thickness, adipocyte area, and adipocyte number, respectively. Thirteen hub genes (ACSL1, ACOX1, FN1, DCN, CHST13, COL1A1, COL1A2, COL6A3, COL5A1, COL14A1, OAZ3, DNM1, and SELP) were recognized. ACSL1 and ACOX1 might perform function in the early developmental stage of backfat tissue (60 days), and FN1, DCN, COL1A1, COL1A2, COL5A1, COL6A3, and COL14A1 have unignorable position in backfat tissue around 120 days developmental stage. Besides, hub genes SELP and DNM1 in modules significantly associated with backfat thickness and adipocyte area might be involved in the process of backfat tissue development. These findings contribute to understand the integrated mechanism underlying backfat tissue development and promote the progress of genetic improvement in Ningxiang pigs.
The effect of novel antimicrobial agents on the normal functioning of human intestinal microbiota: a systematic review
Authors: Girma Abayeneh
Published: August 2023

Antimicrobial agents have significant effects on the ecological balance of the human microbiota through incomplete absorption (e.g., orally administered antimicrobial agents) or secretion (e.g., by the salivary glands, in the bile, or from the intestinal mucosa) of the agents. This study aimed to examine the effects of novel antimicrobial agents on the normal functioning of the intestinal microbiota. The articles, written in English, were recovered from PubMed, ScienceDirect, Web of Science, Google Scholar, and DOAJ, as well as from manual searches using a reference list. “Microbiota”, “Intestinal Microbiota”, “Eubiotic Microbiota”, “Ecological Impact”, “Antimicrobial Agents,”, “Antibiotics”, “Dysbiosis”, “Gut Microbiota”, and “Probiotics” were the search terms used to retrieve the articles. The PRISMA 2009 checklist was applied for article search strategy, article selection, data extraction, and result reporting for the review process. A total of eight original research articles were included from a total of 379 articles obtained in different search strategies. The eight new antimicrobial agents demonstrated significant impacts on the ecological balance of the human intestinal microbiota. Therefore, eubiosis is crucial in preventing the establishment of exogenous antimicrobial-resistant strains as well as their gene transfer.

Systematic review registration

[PRISMA], identifier [2009].
Cytotoxic CD4 T cells in the mucosa and in cancer
Authors: Venkatesh Hrishi , Tracy Sean I. , Farrar Michael A.
Published: August 2023

CD4 T cells were initially described as helper cells that promote either the cellular immune response (Th1 cells) or the humoral immune response (Th2 cells). Since then, a plethora of functionally distinct helper and regulatory CD4 T cell subsets have been described. CD4 T cells with cytotoxic function were first described in the setting of viral infections and autoimmunity, and more recently in cancer and gut dysbiosis. Regulatory CD4 T cell subsets such as Tregs and T-regulatory type 1 (Tr1) cells have also been shown to have cytotoxic potential. Indeed, Tr1 cells have been shown to be important for maintenance of stem cell niches in the bone marrow and the gut. This review will provide an overview of cytotoxic CD4 T cell development, and discuss the role of inflammatory and Tr1-like cytotoxic CD4 T cells in maintenance of intestinal stem cells and in anti-cancer immune responses.
Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan
Authors: Tani Yuta , Takita Morihito , Wakui Masatoshi , Saito Hiroaki , Nishiuchi Takamitsu , Zhao Tianchen , Yamamoto Chika , Kawamura Takeshi , Sugiyama Akira , Nakayama Aya , Kaneko Yudai , Kodama Tatsuhiko , Shinaha Ryuzaburo , Tsubokura Masaharu
Published: August 2023

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.
Canada and ocean climate adaptation: tracking law and policy responses, charting future directions
Authors: VanderZwaag David L. , Seck Sara L. , Graham Laura , Frontain Jonathon , Simpson Kieran
Published: August 2023

This research article provides a law and policy summary of climate change adaptation initiatives in Canada at the ocean-climate nexus. Three levels of governance are examined (national, provincial, and Indigenous) with a focus on the Atlantic region. The research method was the review of relevant and newly amended laws, regulations and policy statements, and related commentaries. The roles of the federal government are first described with key developments including the launch of a Climate Adaptation Platform in 2012 to share adaptation experiences and information and release of a National Adaptation Strategy and accompanying Adaptation Action Plan in November 2022. Federal adaptation efforts in the areas of fisheries, aquaculture and shipping are also reviewed along with progress in establishing marine protected areas (MPAs) and other effective area-based conservation measures. Provincial adaptation initiatives are next summarized with a focus on the four Atlantic provinces. Those provinces have established a regional hub, CLIMAtlantic, to provide climate information and advance climate-related research and training. Each province has developed a climate action plan which includes climate adaptation priorities. Indigenous-led climate engagement and adaptation initiatives are finally described including the publication in 2019 of a National Inuit Climate Change Strategy, regional initiatives of the Atlantic Policy Congress of First Nations Chiefs Secretariat, and the development of climate adaptation plans by select First Nation communities in the Atlantic region. The paper concludes by discussing future law and policy directions to make Canada more “climate ready.” Adoption of climate adaptation strategies for governmental departments and agencies with ocean and coastal responsibilities should be a priority. Incorporating climate change adaptation responsibilities through legislative and regulatory changes also needs to be considered, for example, by amending Canada’s Oceans Act to recognize the role of oceans in climate adaptations and mitigation, to authorize the designation of MPAs as climate refuges and to require adaptive and dynamic MPA management plans through strict monitoring and timely review provisions. Indigenous peoples must be effectively included in all climate adaptation discussions and planning.
Reactive molecular dynamics simulation on the disintegration of Kapton and Upilex-S during atomic oxygen impact
Authors: Qiao Shiying , Jiang Lixiang , Jiang Haifu , Liu Yuming , Xu Yanlin , Jiao Zilong , Cui Naiyuan , Wang Lu
Published: August 2023

Polyimides are polymeric materials that are widely used in spacecraft applications owing to their unique properties. However, exposure to a low-Earth-orbit environment containing atomic oxygen (AO) results in the disintegration of polymeric materials on the surface of spacecraft, thereby affecting the lifespan. Along with the development of theoretical research, the reactive force-field (ReaxFF) interatomic potential has become a robust computational method for exploring, developing and optimizing the material properties. This study employs the ReaxFF reactive-force-field molecular dynamics simulation (ReaxFF MD) program to investigate and compare the performance of two typical polyimide materials, Kapton and Upilex-S, under the impact of AO. Various aspects such as variations in the temperature, mass loss, decomposition products, and damage propagation depth were examined. Although these materials have similar elemental composition (C/H/O/N), they have different structures. Our results indicate that AO is initially adsorbed on the surfaces of both Kapton and Upilex-S. The continuous impact of AO leads to chemical reactions between AO and Kapton/Upilex-S. Erosion proceeds from the surface toward the interior of the materials. Similar to the findings of Experiment 2 conducted by the Materials International Space Station, our results also reveal that Upilex-S exhibits a lower mass loss and erosion yield than Kapton under the same AO conditions. This difference is primarily attributed to the distinct molecular structures of both Kapton and Upilex-S. Our study could provide valuable technical support for the extensive application of Upilex-S in spacecraft.
CDK6 is essential for mesenchymal stem cell proliferation and adipocyte differentiation
Authors: Hu Alexander J. , Li Wei , Pathak Apana , Hu Guo-Fu , Hou Xiaoli , Farmer Stephen R. , Hu Miaofen G.
Published: August 2023

Background: Overweight or obesity poses a significant risk of many obesity-related metabolic diseases. Among all the potential new therapies, stem cell-based treatments hold great promise for treating many obesity-related metabolic diseases. However, the mechanisms regulating adipocyte stem cells/progenitors (precursors) are unknown. The aim of this study is to investigate if CDK6 is required for mesenchymal stem cell proliferation and adipocyte differentiation.

Methods: Cyclin-dependent kinase 6 (Cdk6) mouse models together with stem cells derived from stromal vascular fraction (SVF) or mouse embryonic fibroblasts (MEFs) of Cdk6 mutant mice were used to determine if CDK6 is required for mesenchymal stem cell proliferation and adipocyte differentiation.

Results: We found that mice with a kinase inactive CDK6 mutants (K43M) had fewer precursor residents in the SVF of adult white adipose tissue (WAT). Stem cells from the SVF or MEFs of K43M mice had defects in proliferation and differentiation into the functional fat cells. In contrast, mice with a constitutively active kinase CDK6 mutant (R31C) had the opposite traits. Ablation of RUNX1 in both mature and precursor K43M cells, reversed the phenotypes.

Conclusion: These results represent a novel role of CDK6 in regulating precursor numbers, proliferation, and differentiation, suggesting a potential pharmacological intervention for using CDK6 inhibitors in the treatment of obesity-related metabolic diseases.
The immunological and structural epidermal barrier dysfunction and skin microbiome in atopic dermatitis-an update
Authors: Çetinarslan Tubanur , Kümper Lisa , Fölster-Holst Regina
Published: August 2023

Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations and combinations of symptoms. The pathophysiology of AD is complex and multifactorial. There are several factors involved in the etiopathogenesis of AD including structural and immunological epidermal barrier defect, imbalance of the skin microbiome, genetic background and environmental factors. Alterations in structural proteins, lipids, proteases, and their inhibitors, lead to the impairment of the stratum corneum which is associated with the increased skin penetration and transepidermal water loss. The elevated serum immunoglobulin E levels and blood eosinophilia have been shown in the majority of AD patients. Type 2 T-helper cell immune pathway with increased expression of interleukin (IL)-4, IL-5, and IL-13, has an important role in the etiopathogenesis of AD. Both T cells and keratinocytes contribute to epidermal barrier impairment in AD via a dynamic interaction of cytokines and chemokines. The skin microbiome is another factor of relevance in the etiopathogenesis of AD. It has been shown that during AD flares, Staphylococcus aureus (S. aureus) colonization increased, while Staphylococcus epidermidis (S. epidermidis) decreased. On the contrary, S. epidermidis and species of Streptococcus, Corynebacterium and Propionibacterium increased during the remision phases. However, it is not clear whether skin dysbiosis is one of the symptoms or one of the causes of AD. There are several therapeutic options, targeting these pathways which play a critical role in the etiopathogenesis of AD. Although topical steroids are the mainstay of the treatment of AD, new biological therapies including IL-4, IL-13, and IL-31 inhibitors, as well as Janus kinase inhibitors (JAKi), increasingly gain more importance with new advances in the therapy of AD. In this review, we summarize the role of immunological and structural epidermal barrier dysfunction, immune abnormalities, impairment of lipids, filaggrin mutation and skin microbiome in the etiopathogenesis of AD, as well as the therapeutic options for AD and their effects on these abnormalities in AD skin.
Surgical treatment of traumatic frontal hematoma: comparison of the endoscopic supraorbital approach with frontotemporal approach
Authors: Yang Qiang , Cui Min , Xiong WeiMing , Wang YangLingXi , Liu Yang , Zhou WeiDuo , Chen Peng , Tang XiaoYong
Published: August 2023

Background

The objective of this study was to compare the efficacy, safety, and outcomes of the endoscopic supraorbital approach and frontotemporal approach for the treatment of traumatic frontal hematoma, with the aim of demonstrating the feasibility of the endoscopic supraorbital approach.

Methods

A total of 24 cases underwent hematoma evacuation, including 10 cases using the endoscopic supraorbital approach and 14 cases using the frontotemporal approach. Baseline demographic data, hematoma clearance rate, blood loss, postoperative complications, and 6-month outcomes were retrospectively analyzed.

Results

Both approaches effectively evacuated the hematoma, with hematoma clearance rates of 90.97 ± 10.23% in the endoscopic supraorbital group and 85.29 ± 16.15% in the frontotemporal approach group (p > 0.05). The supraorbital approach group demonstrated significantly shorter operation times compared to the frontotemporal approach group (116.50 ± 28.19 min vs. 193.29 ± 72.55 min, p < 0.05), as well as significantly less blood loss (55.00 ± 33.08 mL vs. 685.71 ± 840.20 mL, p < 0.05). There was no significant difference in the rate of postoperative complications between the two groups, and the majority of patients achieved favorable outcomes with a Glasgow Outcome Scale score of 4 or 5 in both groups.

Conclusion

Compared to the frontotemporal approach, the endoscopic supraorbital approach offers advantages such as shorter operation times, reduced blood loss, similar treatment effects, and comparable complication rates. Therefore, the endoscopic supraorbital approach may serve as a viable alternative for the treatment of traumatic frontal hematoma.
Fluctuations in Parkinson’s disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale
Authors: Schmitt Emmanuelle , Debu Bettina , Castrioto Anna , Kistner Andrea , Fraix Valerie , Bouvard Martine , Moro Elena
Published: August 2023

Background

Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson’s disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score.

Objective

To evaluate the psychometric properties of the NFS in PD.

Methods

PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I–IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach’s alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores.

Results

In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32–35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001).

Conclusion

The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.
Reduced attentional inhibition for peripheral distractors of angry faces under central perceptual load in deaf individuals: evidence from an event-related potentials study
Authors: Huang Jun , Yang Linhui , Li Kuiliang , Li Yaling , Dai Lan , Wang Tao
Published: August 2023

Background

Studies have shown that deaf individuals distribute more attention to the peripheral visual field and exhibit enhanced visual processing for peripheral stimuli relative to hearing individuals. This leads to better detection of peripheral target motion and simple static stimuli in hearing individuals. However, when threatening faces that represent dangerous signals appear as non-targets in the periphery, it remains unclear whether deaf individuals would retain an advantage over hearing individuals in detecting them.

Methods

In this study, 23 deaf and 28 hearing college students were included. A modified perceptual load paradigm and event-related potentials (ERPs) were adopted. In the task, participants were instructed to search for a target letter in a central letter array, while task-irrelevant face distractors (happy, neutral, and angry faces) were simultaneously presented in the periphery while the central perceptual load was manipulated.

Results

Behavioral data showed that angry faces slowed deaf participants' responses to the target while facilitating the responses of hearing participants. At the electrophysiological level, we found modulation of P1 amplitude by central load only in hearing individuals. Interestingly, larger interference from angry face distractors was associated with higher P1 differential amplitude only in deaf individuals. Additionally, the amplitude of N170 for happy face distractors was smaller than that for angry and neutral face distractors in deaf participants.

Conclusion

The present data demonstrates that, despite being under central perceptual load, deaf individuals exhibit less attentional inhibition to peripheral, goal-irrelevant angry faces than hearing individuals. The result may reflect a compensatory mechanism in which, in the absence of auditory alertness to danger, the detection of visually threatening information outside of the current attentional focus has a high priority.
Neural correlates and predictors of speech and language development in infants at elevated likelihood for autism: a systematic review
Authors: Morrel Jessica , Singapuri Kripi , Landa Rebecca J. , Reetzke Rachel
Published: August 2023

Autism spectrum disorder (ASD) is an increasingly prevalent and heterogeneous neurodevelopmental condition, characterized by social communicative differences, and a combination of repetitive behaviors, focused interests, and sensory sensitivities. Early speech and language delays are characteristic of young autistic children and are one of the first concerns reported by parents; often before their child’s second birthday. Elucidating the neural mechanisms underlying these delays has the potential to improve early detection and intervention efforts. To fill this gap, this systematic review aimed to synthesize evidence on early neurobiological correlates and predictors of speech and language development across different neuroimaging modalities in infants with and without a family history of autism [at an elevated (EL infants) and low likelihood (LL infants) for developing autism, respectively]. A comprehensive, systematic review identified 24 peer-reviewed articles published between 2012 and 2023, utilizing structural magnetic resonance imaging (MRI; n = 2), functional MRI (fMRI; n = 4), functional near-infrared spectroscopy (fNIRS; n = 4), and electroencephalography (EEG; n = 14). Three main themes in results emerged: compared to LL infants, EL infants exhibited (1) atypical language-related neural lateralization; (2) alterations in structural and functional connectivity; and (3) mixed profiles of neural sensitivity to speech and non-speech stimuli, with some differences detected as early as 6 weeks of age. These findings suggest that neuroimaging techniques may be sensitive to early indicators of speech and language delays well before overt behavioral delays emerge. Future research should aim to harmonize experimental paradigms both within and across neuroimaging modalities and additionally address the feasibility, acceptability, and scalability of implementing such methodologies in non-academic, community-based settings.
Cortical excitability in human somatosensory and visual cortex: implications for plasticity and learning – a minireview
Authors: Dinse Hubert R. , Höffken Oliver , Tegenthoff Martin
Published: August 2023

The balance of excitation and inhibition plays a key role in plasticity and learning. A frequently used, reliable approach to assess intracortical inhibition relies on measuring paired-pulse behavior. Moreover, recent developments of magnetic resonance spectroscopy allows measuring GABA and glutamate concentrations. We give an overview about approaches employed to obtain information about excitatory states in human participants and discuss their putative relation. We summarize paired-pulse techniques and basic findings characterizing paired-pulse suppression in somatosensory (SI) and (VI) visual areas. Paired-pulse suppression describes the effect of paired sensory stimulation at short interstimulus intervals where the cortical response to the second stimulus is significantly suppressed. Simultaneous assessments of paired-pulse suppression in SI and VI indicated that cortical excitability is not a global phenomenon, but instead reflects the properties of local sensory processing. We review studies using non-invasive brain stimulation and perceptual learning experiments that assessed both perceptual changes and accompanying changes of cortical excitability in parallel. Independent of the nature of the excitation/inhibition marker used these data imply a close relationship between altered excitability and altered performance. These results suggest a framework where increased or decreased excitability is linked with improved or impaired perceptual performance. Recent findings have expanded the potential role of cortical excitability by demonstrating that inhibition markers such as GABA concentrations, paired-pulse suppression or alpha power predict to a substantial degree subsequent perceptual learning outcome. This opens the door for a targeted intervention where subsequent plasticity and learning processes are enhanced by altering prior baseline states of excitability.
Antiproliferative effect of boldine on neural progenitor cells and on glioblastoma cells
Authors: Jiménez-Madrona Enrique , Morado-Díaz Camilo J. , Talaverón Rocío , Tabernero Arantxa , Pastor Angel M. , Sáez Juan C. , Matarredona Esperanza R.
Published: August 2023

Introduction

The subventricular zone (SVZ) is a brain region that contains neural stem cells and progenitor cells (NSCs/NPCs) from which new neurons and glial cells are formed during adulthood in mammals. Recent data indicate that SVZ NSCs are the cell type that acquires the initial tumorigenic mutation in glioblastoma (GBM), the most aggressive form of malignant glioma. NSCs/NPCs of the SVZ present hemichannel activity whose function has not yet been fully elucidated. In this work, we aimed to analyze whether hemichannel-mediated communication affects proliferation of SVZ NPCs and GBM cells.

Methods and Results

For that purpose, we used boldine, an alkaloid derived from the boldo tree (Peumus boldus), that inhibits connexin and pannexin hemichannels, but without affecting gap junctional communication. Boldine treatment (50 μM) of rat SVZ NPCs grown as neurospheres effectively inhibited dye uptake through hemichannels and induced a significant reduction in neurosphere diameter and in bromodeoxyuridine (BrdU) incorporation. However, the differentiation pattern was not modified by the treatment. Experiments with specific blockers for hemichannels formed by connexin subunits (D4) or pannexin 1 (probenecid) revealed that probenecid, but not D4, produced a decrease in BrdU incorporation similar to that obtained with boldine. These results suggest that inhibition of pannexin 1 hemichannels could be partially responsible for the antiproliferative effect of boldine on SVZ NPCs. Analysis of the effect of boldine (25–600 μM) on different types of primary human GBM cells (GBM59, GBM96, and U87-MG) showed a concentration-dependent decrease in GBM cell growth. Boldine treatment also induced a significant inhibition of hemichannel activity in GBM cells.

Discussion

Altogether, we provide evidence of an antimitotic action of boldine in SVZ NPCs and in GBM cells which may be due, at least in part, to its hemichannel blocking function. These results could be of relevance for future possible strategies in GBM aimed to suppress the proliferation of mutated NSCs or glioma stem cells that might remain in the brain after tumor resection.
Understanding the effects of cortical gyrification in tACS: insights from experiments and computational models
Authors: Cabrera-Álvarez Jesús , Sánchez-Claros Jaime , Carrasco-Gómez Martín , del Cerro-León Alberto , Gómez-Ariza Carlos J. , Maestú Fernando , Mirasso Claudio R. , Susi Gianluca
Published: August 2023

The alpha rhythm is often associated with relaxed wakefulness or idling and is altered by various factors. Abnormalities in the alpha rhythm have been linked to several neurological and psychiatric disorders, including Alzheimer's disease. Transcranial alternating current stimulation (tACS) has been proposed as a potential tool to restore a disrupted alpha rhythm in the brain by stimulating at the individual alpha frequency (IAF), although some research has produced contradictory results. In this study, we applied an IAF-tACS protocol over parieto-occipital areas to a sample of healthy subjects and measured its effects over the power spectra. Additionally, we used computational models to get a deeper understanding of the results observed in the experiment. Both experimental and numerical results showed an increase in alpha power of 8.02% with respect to the sham condition in a widespread set of regions in the cortex, excluding some expected parietal regions. This result could be partially explained by taking into account the orientation of the electric field with respect to the columnar structures of the cortex, showing that the gyrification in parietal regions could generate effects in opposite directions (hyper-/depolarization) at the same time in specific brain regions. Additionally, we used a network model of spiking neuronal populations to explore the effects that these opposite polarities could have on neural activity, and we found that the best predictor of alpha power was the average of the normal components of the electric field. To sum up, our study sheds light on the mechanisms underlying tACS brain activity modulation, using both empirical and computational approaches. Non-invasive brain stimulation techniques hold promise for treating brain disorders, but further research is needed to fully understand and control their effects on brain dynamics and cognition. Our findings contribute to this growing body of research and provide a foundation for future studies aimed at optimizing the use of non-invasive brain stimulation in clinical settings.
Ion channels in cancer-induced bone pain: from molecular mechanisms to clinical applications
Authors: Lu Huan-Jun , Wu Xiao-Bo , Wei Qian-Qi
Published: August 2023

Cancer-induced bone pain (CIBP) caused by bone metastasis is one of the most prevalent diseases, and current treatments rely primarily on opioids, which have significant side effects. However, recent developments in pharmaceutical science have identified several new mechanisms for CIBP, including the targeted modification of certain ion channels and receptors. Ion channels are transmembrane proteins, which are situated on biological cell membranes, which facilitate passive transport of inorganic ions across membranes. They are involved in various physiological processes, including transmission of pain signals in the nervous system. In recent years, there has been an increasing interest in the role of ion channels in chronic pain, including CIBP. Therefore, in this review, we summarize the current literature on ion channels, related receptors, and drugs and explore the mechanism of CIBP. Targeting ion channels and regulating their activity might be key to treating pain associated with bone cancer and offer new treatment avenues.
Pre-clinical delivery of gene therapy products to the cerebrospinal fluid: challenges and considerations for clinical translation
Authors: Salegio Ernesto A. , Hancock Kelli , Korszen Stephanie
Published: August 2023

While the majority of gene therapy studies in neurological indications have focused on direct gene transfer to the central nervous system (CNS), there is growing interest in the delivery of therapeutics using the cerebrospinal fluid (CSF) as a conduit. Historically, direct CNS routes-of-administration (RoAs) have relied on tissue dynamics, displacement of interstitial fluid, and regional specificity to achieve focal delivery into regions of interest, such as the brain. While intraparenchymal delivery minimizes peripheral organ exposure, one perceived drawback is the relative invasiveness of this approach to drug delivery. In this mini review, we examine the CSF as an alternative RoA to target CNS tissue and discuss considerations associated with the safety of performing such procedures, biodistribution of therapeutics following single administration, and translation of findings given differences between small and large animals. These factors will help delineate key considerations for translating data obtained from animal studies into clinical settings that may be useful in the treatment of neurological conditions.