bluuebunny/crossref_metadata_2025 huggingface dataset:
Gendered Issues or Partisan Priorities? The Policy Priorities of Men and Women at Partisan Think Tanks
Authors: Fagan E.J. , Manning Andrea
Published: April 2023

This paper examines the relationship between gender, partisanship, and authorship of partisan think tank reports. Scholars often observe a gendered dimension to issues, where women are associated with issues related to child-rearing, education, and social welfare while men are associated with issues related to violent state action, such as foreign policy and crime. However, these studies are often limited by the confounding variable of partisanship, where political parties tend to prioritize certain issues, and gender gaps between parties. We introduce a new dataset of 15,589 authors of 9,944 reports from the American Enterprise Institute, Center for American Progress, Center on Budget and Policy Priorities, and Heritage Foundation. We find that while women elites tend to prioritize issues often associated with women in both parties, prioritization of issues by sex is more complicated than much of the literature suggests.
Do advanced glycation end products contribute to food allergy?
Authors: Smith P. K. , Venter C. , O’Mahony L. , Canani R. Berni , Lesslar O. J. L.
Published: April 2023

Sugars can bind non-enzymatically to proteins, nucleic acids or lipids and form compounds called Advanced Glycation End Products (AGEs). Although AGEs can form in vivo, factors in the Western diet such as high amounts of added sugars, processing methods such as dehydration of proteins, high temperature sterilisation to extend shelf life, and cooking methods such as frying and microwaving (and reheating), can lead to inordinate levels of dietary AGEs. Dietary AGEs (dAGEs) have the capacity to bind to the Receptor for Advanced Glycation End Products (RAGE) which is part of the endogenous threat detection network. There are persuasive epidemiological and biochemical arguments that correlate the rise in food allergy in several Western countries with increases in dAGEs. The increased consumption of dAGEs is enmeshed in current theories of the aetiology of food allergy which will be discussed.
Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade
Authors: Conte J. G. , Tellechea M. L. , Park B. , Ballerini M. G. , Jaita G. , Peluffo M. C.
Published: April 2023

The epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte chemoattractant protein-1, MCP1) as novel mediators of the ovulatory cascade. Our previous results demonstrate that the gonadotropins (GNT), amphiregulin (AREG), and prostaglandin E2 (PGE2) stimulation of periovulatory gene mRNA levels occurs, at least in part, through the CCR2/MCP1 pathway, proposing the CCR2 receptor as a novel mediator of the ovulatory cascade in a feline model. For that purpose, feline cumulus-oocyte complexes (COCs) were cultured in the presence or absence of an EGFR inhibitor, recombinant chemokine MCP1, and gonadotropins [as an inducer of cumulus-oocyte expansion (C-OE), and oocyte maturation] to further assess the mRNA expression of periovulatory key genes, C-OE, oocyte nuclear maturation, and steroid hormone production. We observed that MCP1 was able to revert the inhibition of AREG mRNA expression by an EGFR inhibitor within the feline COC. In accordance, the confocal analysis showed that the GNT-stimulated hyaluronic acid (HA) synthesis, blocked by the EGFR inhibitor, was recovered by the addition of recombinant MCP1 in the C-OE culture media. Also, MCP1 was able to revert the inhibition of progesterone (P4) production by EGFR inhibitor in the C-OE culture media. Regarding oocyte nuclear maturation, recombinant MCP1 could also revert the inhibition triggered by the EGFR inhibitor, leading to a recovery in the percentage of metaphase II (MII)-stage oocytes. In conclusion, our results confirm the chemokine receptor CCR2 as a novel intermediate in the ovulatory cascade and demonstrate that the EGFR/AREG and the CCR2/MCP1 signaling pathways play critical roles in regulating feline C-OE and oocyte nuclear maturation, with CCR2/MCP1 signaling pathway being downstream EGFR/AREG pathway within the ovulatory cascade.
Responses of hepatic sinusoidal cells to liver ischemia–reperfusion injury
Authors: Ito Yoshiya , Hosono Kanako , Amano Hideki
Published: April 2023

The liver displays a remarkable regenerative capacity in response to acute liver injury. In addition to the proliferation of hepatocytes during liver regeneration, non-parenchymal cells, including liver macrophages, liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) play critical roles in liver repair and regeneration. Liver ischemia–reperfusion injury (IRI) is a major cause of increased liver damage during liver resection, transplantation, and trauma. Impaired liver repair increases postoperative morbidity and mortality of patients who underwent liver surgery. Successful liver repair and regeneration after liver IRI requires coordinated interplay and synergic actions between hepatic resident cells and recruited cell components. However, the underlying mechanisms of liver repair after liver IRI are not well understood. Recent technological advances have revealed the heterogeneity of each liver cell component in the steady state and diseased livers. In this review, we describe the progress in the biology of liver non-parenchymal cells obtained from novel technological advances. We address the functional role of each cell component in response to liver IRI and the interactions between diverse immune repertoires and non-hematopoietic cell populations during the course of liver repair after liver IRI. We also discuss how these findings can help in the design of novel therapeutic approaches. Growing insights into the cellular interactions during liver IRI would enhance the pathology of liver IRI understanding comprehensively and further develop the strategies for improvement of liver repair.
Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans
Authors: Luther Christian H. , Brandt Philipp , Vylkova Slavena , Dandekar Thomas , Müller Tobias , Dittrich Marcus
Published: April 2023

Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.
A computational analysis of crosslinguistic regularity in semantic change
Authors: Fugikawa Olivia , Hayman Oliver , Liu Raymond , Yu Lei , Brochhagen Thomas , Xu Yang
Published: April 2023

Semantic change is attested commonly in the historical development of lexicons across the world's languages. Extensive research has sought to characterize regularity in semantic change, but existing studies have typically relied on manual approaches or the analysis of a restricted set of languages. We present a large-scale computational analysis to explore regular patterns in word meaning change shared across many languages. We focus on two levels of analysis: (1) regularity in directionality, which we explore by inferring the historical direction of semantic change between a source meaning and a target meaning; (2) regularity in source-target mapping, which we explore by inferring the target meaning given a source meaning. We work with DatSemShift, the world's largest public database of semantic change that records thousands of meaning changes from over hundreds of languages. For directionality inference, we find that concreteness explains directionality in more than 70% of the attested cases of semantic change and is the strongest predictor among the alternatives including frequency and valence. For target inference, we find that a parallelogram-style analogy model based on contextual embeddings predicts the attested source-target mappings substantially better than chance and similarity-based models. Clustering the meaning pairs of semantic change reveals regular meaning shiftings between domains, such as body parts to geological formations. Our study provides an automated approach and large-scale evidence for multifaceted regularity in semantic change across languages.
Healthcare professionals' perceptions of a digital parental support, Childbirth Journey, constructed as a serious game—An intervention study
Authors: Bäckström Caroline , Knez Rajna , Larsson Margaretha
Published: April 2023

Background

Globally, the digital sources developed and available in antenatal care differ, and infrastructure challenges may impede the further development of such sources. Challenges accompanying digital developments can include the commonly occurring high workload, which affects healthcare professionals' ability to acquire professional knowledge about how to best support parents in using digital sources. Including healthcare professionals in the development process of digital sources may increase the likelihood that such sources will be adopted and employed by these professionals in their future care work. Therefore, the present research explored healthcare professionals' perceptions of the digital support intervention Childbirth Journey, which was constructed as a serious game for expectant parents.

Methods

Data were collected through semi-structured focus-group interviews with 11 midwives at antenatal, labour and postnatal clinics as well as with child healthcare nurses. Prior to the interviews, all participants were provided the intervention, Childbirth Journey, which is a serious game in a mobile application format consisting of two distinct parts: (1) a story-driven game and (2) a Knowledge Portal. The data were analysed using phenomenographic methods.

Results

The perceptions of Childbirth Journey by healthcare professionals, midwives and child healthcare nurses are presented in four descriptive categories: extended professional support, trustworthy contents, diversity or individuality, and both appealing and in need of development.

Conclusions

Current study revealed that Childbirth Journey may be utilised as a digital support for parents, allowing healthcare professionals to offer a digital solution as a complementary support to standard, face-to-face meetings with caregivers. However, the research results also revealed that some elements of Childbirth Journey must be improved, thereby representing a main contribution of this study: insights into how to better develop digital tools under the umbrella of health care. Thus, we conclude that in order to create sustainable and safe digital care solutions that function as trustworthy professional supports instead of technical products that risk harming users, the perspectives of both patients and healthcare professionals should be considered in the exploration and development of these solutions.
Metabolic dysfunction-associated fatty liver disease increased the risk of subclinical carotid atherosclerosis in China
Authors: Lei Fang , Wang Xiao-Ming , Wang Changquan , Huang Xuewei , Liu Ye-Mao , Qin Juan-Juan , Zhang Peng , Ji Yan-Xiao , She Zhi-Gang , Cai Jingjing , Li Huo-ping , Zhang Xiao-Jing , Li Hongliang
Published: April 2023

Background and aims

Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to substitute NAFLD in 2020. This new term highlights the systematic metabolic disturbances that accompany fatty liver. We evaluated the correlations between MAFLD and subclinical carotid atherosclerosis (SCA) based on a nationwide health examination population in China.

Methods

We performed a nationwide cross-sectional population and a Beijing retrospective cohort from 2009 to 2017. SCA was defined as elevated carotid intima-media thickness. The multivariable logistic and Cox models were used to analyze the association between MAFLD and SCA.

Results

153,482 participants were included in the cross-sectional study. MAFLD was significantly associated with SCA in fully adjusted models, with an odds ratio of 1.66; 95% confidence interval (CI): 1.62-1.70. This association was consistent in the cohort, with a hazard ratio (HR) of 1.31. The association between baseline MAFLD and incident SCA increased with hepatic steatosis severity. Subgroup analysis showed an interaction between age and MAFLD, with a higher risk in younger groups (HR:1.67, 95% CI: 1.17-2.40).

Conclusion

In this large cross-section and cohort study, MAFLD was significantly associated with the presence and development of SCA. Further, the risk was higher among MAFLD individuals with high hepatic steatosis index and young adults.
Study of Xuanhuang Pill in protecting against alcohol liver disease using ultra-performance liquid chromatography/time-of-flight mass spectrometry and network pharmacology
Authors: Cui Xuejie , Du Maobo , Wei Kunhua , Dai Chen , Yang Rachel Y. H. , Zhou Bingxue , Luo Zhaojing , Yang Xiaonan , Yu Yi , Lin Wei , Wu Yi , Liu Yuhong
Published: April 2023

Introduction

Xuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.

Methods

The hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.

Results

The current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.

Conclusion

In summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.
A planted forest in the mountain steppe of Tabriz, Iran: Visitor’s perceptions of Eynali Urban Woodland Park
Authors: Sabouri Ramin , Breuste Jürgen , Rahimi Akbar
Published: April 2023

Eynali Urban Woodland Park (EWP) is a large mountain park in Tabriz, Iran, and is the largest urban woodland park in Iran. It was developed to increase the urban green space in the growing city of Tabriz for recreation, climate improvement, biodiversity, and ecological connection between the city and its natural surroundings. The planted hilly woodland is located in a natural mountain steppe in a semi-arid region and needs intensive management, including irrigation. By questioning 277 randomly selected park visitors’ frequency of visits, activities, accessibility, preferences, and especially nature preferences were analyzed using visualization of different nature types by photographs. The management targets were compared to visitors’ perceptions, preferences, and acceptances. The results show, that visitors prefer natural surroundings instead of artificial landscape design. Expectations of visitors for specific natural design attractions are lower than the actual status offers, and higher for social security, quality of infrastructure, accessibility, and utilization. Especially important are security by monitoring and guarding, enhancing picnic sites, improving the lighting system for evening visits, continuing forestry, public transport, and providing natural risk protection. Most visitors prefer nature-near vegetation, dry grassland with shrubs partly planted with trees and bushes, followed by planted forest. The planted forest is not the preferred preference. Vistors’ mental nature imagination matches quite well with the nature experience they have from the surrounding mountain steppe with forest patches. The use of the visitors’ expectations can improve the park landscape management can reduce the management costs.
Evaluating the performance of a web-based vehicle blind zone estimation application: Validation and policy implications
Authors: Drake Juwon , Vennema Alessandra , Slonim Lily , Englin Eric , Brodeur Alyssa , Epstein Alexander K. , Fisher Donald L.
Published: April 2023

Pedestrian fatalities have been increasing in the United States over the past decade; in 2021 they reached a 40-year high and together with an increasing number of bicyclist fatalities surged to over 8,400 vulnerable road users (VRUs) killed by motor vehicle crashes. There is widespread recognition of the link between passenger fleets transitioning from sedans to SUVs and pick-up trucks and the increase in vulnerable road user fatalities. Larger light-duty vehicles generally have larger blind zones, and larger blind zones are prominently linked to crashes with vulnerable road users. Heavy-duty commercial trucks, which comprise only four percent of vehicles on the road, are disproportionally associated with over eight percent of vulnerable road user deaths. With direct vision unregulated in the United States, there is a limited domestic market for large trucks with high direct vision despite research showing that one-quarter of the approximately 620 annual truck-involved pedestrian and bicyclist fatalities result from low-speed maneuvers with impaired direct vision and could be prevented by higher vision truck cabs. Communicating the seriousness of this problem is critical. This methods article presents an easy-to-use tool designed to give the public and fleet managers information to assess vehicle safety by quantifying driver blind zones using whatever driver eye positions are thought to be most applicable and with the option to standardize said eye position. Previously, measures of the percentage of volume surrounding the vehicle that cannot be seen or the number of people outside the vehicle that can fit in the blind zone could only be made with specialized instrumentation. The web-based application described, VIEW or visibility in elevated wide vehicles, can be used by anyone with a camera and access to the internet to obtain within approximately 15 min a reasonably accurate measure of the blind zone size, considerably faster than manual measurement methods. This article details the app usage procedure as well as the validation work conducted. In summary, the safety culture around SUVs, pickup trucks, and heavy-duty commercial trucks may change if drivers had an easy-to-use method to determine how much situational awareness they would be missing before they purchased a particular vehicle.
Manipulation of host immune defenses by effector proteins delivered from multiple secretion systems of Salmonella and its application in vaccine research
Authors: Zhou Guodong , Zhao Yuying , Ma Qifeng , Li Quan , Wang Shifeng , Shi Huoying
Published: April 2023

Salmonella is an important zoonotic bacterial species and hazardous for the health of human beings and livestock globally. Depending on the host, Salmonella can cause diseases ranging from gastroenteritis to life-threatening systemic infection. In this review, we discuss the effector proteins used by Salmonella to evade or manipulate four different levels of host immune defenses: commensal flora, intestinal epithelial-mucosal barrier, innate and adaptive immunity. At present, Salmonella has evolved a variety of strategies against host defense mechanisms, among which various effector proteins delivered by the secretory systems play a key role. During its passage through the digestive system, Salmonella has to face the intact intestinal epithelial barrier as well as competition with commensal flora. After invasion of host cells, Salmonella manipulates inflammatory pathways, ubiquitination and autophagy processes with the help of effector proteins. Finally, Salmonella evades the adaptive immune system by interfering the migration of dendritic cells and interacting with T and B lymphocytes. In conclusion, Salmonella can manipulate multiple aspects of host defense to promote its replication in the host.
The regulation of self-tolerance and the role of inflammasome molecules
Authors: Ke Qi , Greenawalt Ashley Nicole , Manukonda Veera , Ji Xingqi , Tisch Roland Michael
Published: April 2023

Inflammasome molecules make up a family of receptors that typically function to initiate a proinflammatory response upon infection by microbial pathogens. Dysregulation of inflammasome activity has been linked to unwanted chronic inflammation, which has also been implicated in certain autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, and related animal models. Classical inflammasome activation-dependent events have intrinsic and extrinsic effects on both innate and adaptive immune effectors, as well as resident cells in the target tissue, which all can contribute to an autoimmune response. Recently, inflammasome molecules have also been found to regulate the differentiation and function of immune effector cells independent of classical inflammasome-activated inflammation. These alternative functions for inflammasome molecules shape the nature of the adaptive immune response, that in turn can either promote or suppress the progression of autoimmunity. In this review we will summarize the roles of inflammasome molecules in regulating self-tolerance and the development of autoimmunity.
T cell aging and Alzheimer’s disease
Authors: Guo Lin , Li Xiaoting , Gould Timothy , Wang Zhan-You , Cao Wenqiang
Published: April 2023

The brain has long been considered an immune-privileged organ due to the presence of the blood-brain barrier (BBB). However, recent discoveries have revealed the underestimated role of T cells in the brain through the meningeal lymphatic system. Age is the primary risk factor for Alzheimer’s disease (AD), resulting in marked age-dependent changes in T cells. Manipulating peripheral T cell immune response has been shown to impact AD, but the relationship between T cell aging and AD remains poorly understood. Given the limited success of targeting amyloid beta (Aβ) and the growing evidence of T cells’ involvement in non-lymphoid organ aging, a deeper understanding of the relationship between T cells and AD in the context of aging is crucial for advancing therapeutic progress. In this review, we comprehensively examine existing studies on T cells and AD and offer an integrated perspective on their interconnections in the context of aging. This understanding can inform the development of new interventions to prevent or treat AD.
Estimating precision and accuracy of automated video post-processing: A step towards implementation of AI/ML for optics-based fish sampling
Authors: Prior Jack H. , Campbell Matthew D. , Dawkins Matthew , Mickle Paul F. , Moorhead Robert J. , Alaba Simegnew Y. , Shah Chiranjibi , Salisbury Joseph R. , Rademacher Kevin R. , Felts A. Paul , Wallace Farron
Published: April 2023

Increased necessity to monitor vital fish habitat has resulted in proliferation of camera-based observation methods and advancements in camera and processing technology. Automated image analysis through computer vision algorithms has emerged as a tool for fisheries to address big data needs, reduce human intervention, lower costs, and improve timeliness. Models have been developed in this study with the goal to implement such automated image analysis for commercially important Gulf of Mexico fish species and habitats. Further, this study proposes adapting comparative otolith aging methods and metrics for gauging model performance by comparing automated counts to validation set counts in addition to traditional metrics used to gauge AI/ML model performance (such as mean average precision - mAP). To evaluate model performance we calculated percent of stations matching ground-truthed counts, ratios of false-positive/negative detections, and coefficient of variation (CV) for each species over a range of filtered outputs using model generated confidence thresholds (CTs) for each detected and classified fish. Model performance generally improved with increased annotations per species, and false-positive detections were greatly reduced with a second iteration of model training. For all species and model combinations, false-positives were easily identified and removed by increasing the CT to classify more restrictively. Issues with occluded fish images and reduced performance were most prevalent for schooling species, whereas for other species lack of training data was likely limiting. For 23 of the examined species, only 7 achieved a CV less than 25%. Thus, for most species, improvements to the training library will be needed and next steps will include a queried learning approach to bring balance to the models and focus during training. Importantly, for select species such as Red Snapper (Lutjanus campechanus) current models are sufficiently precise to begin utilization to filter videos for automated, versus fully manual processing. The adaption of the otolith aging QA/QC process for this process is a first step towards giving researchers the ability to track model performance through time, thereby giving researchers who engage with the models, raw data, and derived products confidence in analyses and resultant management decisions.
Anti-schistosomal immunity to core xylose/fucose in N-glycans
Authors: Prasanphanich Nina Salinger , Leon Kristoffer , Secor W. Evan , Shoemaker Charles B. , Heimburg-Molinaro Jamie , Cummings Richard D.
Published: April 2023

Schistosomiasis is a globally prevalent, debilitating disease that is poorly controlled by chemotherapy and for which no vaccine exists. While partial resistance in people may develop over time with repeated infections and treatments, some animals, including the brown rat (Rattus norvegicus), are only semi-permissive and have natural protection. To understand the basis of this protection, we explored the nature of the immune response in the brown rat to infection by Schistosoma mansoni. Infection leads to production of IgG to parasite glycoproteins with complex-type N-glycans that contain a non-mammalian-type modification by core α2-Xylose and core α3-Fucose (core Xyl/Fuc). These epitopes are expressed on the surfaces of schistosomula and adult worms. Importantly, IgG to these epitopes can kill schistosomula by a complement-dependent process in vitro. Additionally, sera from both infected rhesus monkey and infected brown rat were capable of killing schistosomula in a manner inhibited by glycopeptides containing core Xyl/Fuc. These results demonstrate that protective antibodies to schistosome infections in brown rats and rhesus monkeys include IgG responses to the core Xyl/Fuc epitopes in surface-expressed N-glycans, and raise the potential of novel glyco-based vaccines that might be developed to combat this disease.
Transcranial direct current stimulation regulates phenotypic transformation of microglia to relieve neuropathic pain induced by spinal cord injury
Authors: Tan Mingliang , Feng Zhou , Chen Hui , Min Lingxia , Wen Huizhong , Liu Hongliang , Hou Jingming
Published: April 2023

Objective

Neuropathic pain is a common complication after spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) has been confirmed to be effective in relieving neuropathic pain in patients with SCI. The aim of this study is to investigate the effect of tDCS on neuropathic pain induced by SCI and its underlying mechanism.

Materials and methods

The SCI model was induced by a clip-compression injury and tDCS stimulation was performed for two courses (5 days/each). The motor function was evaluated by Basso-Beattie-Bresnahan (BBB) score, and the thermal withdrawal threshold was evaluated by the thermal radiation method. The effects of tDCS on the cerebral cortex, thalamus, midbrain, and medulla were detected by the enzyme-linked immunosorbent assay (ELISA) and immunofluorescence.

Results

The results showed that SCI reduced the thermal withdrawal threshold and increased the concentration of inflammatory cytokines in the cortex, thalamus, midbrain, and medulla, including the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In addition, the activation of microglia and the proportion of M1 phenotypic polarization increased significantly in the ventral posterolateral (VPL), ventral tegmental (VTA), and periaqueductal gray (PAG) regions after SCI. After tDCS treatment, the thermal withdrawal threshold and motor function of SCI rats were significantly improved compared to the vehicle group. Meanwhile, tDCS effectively reduced the concentration of pro-inflammatory cytokines in the cortex, thalamus, midbrain, and medulla and increased the concentration of anti-inflammatory cytokines interleukin-10 (IL-10) in the thalamus. In addition, tDCS reduced the proportion of the M1 phenotype of microglia in VPL, VTA, and PAG regions and increase the proportion of the M2 phenotype.

Conclusion

The results suggest that tDCS can effectively relieve SCI-induced neuropathic pain. Its mechanism may be related to regulating the inflammatory and anti-inflammatory cytokines in corresponding brain regions via promoting the phenotypic transformation of microglia.
Subacute myoclonic measles encephalitis – An opportunistic HIV-associated infection
Authors: Ene Luminita , Duiculescu Dan , Radoi Roxana , Lazar Mihaela , Tardei Gratiela , Ungureanu Eugenia , Ruta Simona , Vinters Harry V. , Letendre Scott , Grant Igor , Ellis Ronald J. , Achim Cristian L.
Published: April 2023

Introduction

An unusual cluster of myoclonic epilepsy was observed in a Romanian pediatric HIV cohort concurrent with measles outbreaks. We describe this particular form of subacute measles encephalitis (SME) in a group of HIV-infected children and adolescents with severe immunosuppression.

Methods

This is a single-center study, starting in 1997 and covering 4 measles outbreaks in Romania. The presumptive diagnosis of subacute myoclonic measles encephalitis (SMME) was based on: (1) epidemiological data, previous measles episode or presumed contact with measles virus (MV), (2) clinical presentation with initial localized myoclonic jerks with rapid extension and subsequent motor deficit with preserved mental status, and (3) neuroimaging studies revealing cortical gray matter lesions. Definitive diagnosis was based on a neuropathological exam and immunohistochemistry of brain tissues, and measles RNA detection in the cerebrospinal fluid (CSF).

Results

Thirty-six patients were diagnosed with a particular form of SME during consecutive measles outbreaks in Romania: 1996–1998 (22); 2005–2008 (12); 2010–2011 (1) and 2016-2018 (1). Most children were born in the late 80s and had parenterally acquired HIV infection in early childhood. Before the episode of SMME, 11 patients had confirmed measles, while the rest, without typical rash, had a respiratory tract infection and/or presumed previous measles contact. In all patients, the clinical onset was sudden, with unilateral myoclonus. MRI findings revealed mainly focal cortical gray matter lesions. Neurologic symptoms progressed rapidly to coma and death in most patients. Three patients survived SMME, they had higher CD4 count at onset, slower progression of neurological symptoms, and benefit of immune recovery with cART. Immunocytochemistry studies revealed MV in the brain with a pattern suggesting an ascending viral neural infection. MV was isolated from CSF in 7 out of 8 patients. Sequence analysis of MV RNA from both nasopharyngeal swabs and CSF was available for one patient with similar N-450 strain characteristics.

Conclusion

During an outbreak of measles, neurological manifestations, especially myoclonus in immunosuppressed patients, can be related to measles even in the absence of an acute episode. This particular form of subacute myoclonic measles encephalitis is an opportunistic fatal disease. Immune recovery due to effective antiretroviral treatment might increase survival.
Studying memory processes at different levels with simultaneous depth and surface EEG recordings
Authors: Barborica Andrei , Mindruta Ioana , López-Madrona Víctor J. , Alario F-Xavier , Trébuchon Agnès , Donos Cristian , Oane Irina , Pistol Constantin , Mihai Felicia , Bénar Christian G.
Published: April 2023

Investigating cognitive brain functions using non-invasive electrophysiology can be challenging due to the particularities of the task-related EEG activity, the depth of the activated brain areas, and the extent of the networks involved. Stereoelectroencephalographic (SEEG) investigations in patients with drug-resistant epilepsy offer an extraordinary opportunity to validate information derived from non-invasive recordings at macro-scales. The SEEG approach can provide brain activity with high spatial specificity during tasks that target specific cognitive processes (e.g., memory). Full validation is possible only when performing simultaneous scalp SEEG recordings, which allows recording signals in the exact same brain state. This is the approach we have taken in 12 subjects performing a visual memory task that requires the recognition of previously viewed objects. The intracranial signals on 965 contact pairs have been compared to 391 simultaneously recorded scalp signals at a regional and whole-brain level, using multivariate pattern analysis. The results show that the task conditions are best captured by intracranial sensors, despite the limited spatial coverage of SEEG electrodes, compared to the whole-brain non-invasive recordings. Applying beamformer source reconstruction or independent component analysis does not result in an improvement of the multivariate task decoding performance using surface sensor data. By analyzing a joint scalp and SEEG dataset, we investigated whether the two types of signals carry complementary information that might improve the machine-learning classifier performance. This joint analysis revealed that the results are driven by the modality exhibiting best individual performance, namely SEEG.
Effects of transcranial combined with peripheral repetitive magnetic stimulation on limb spasticity and resting-state brain activity in stroke patients
Authors: Qin Yin , Liu Xiaoying , Zhang Yinxin , Wu Jiwei , Wang Xiaoyang
Published: April 2023

Background and objective

Transcranial magnetic stimulation and peripheral repetitive magnetic stimulation (rPMS), as non-invasive neuromodulation techniques, can promote functional recovery in patients with post-stroke spasticity (PSS), but the effects of transcranial magnetic stimulation combined with peripheral magnetic stimulation on PSS remain largely unknown. Therefore, we examined the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) combined with rPMS on PSS patients and its potential neural correlates to behavioral improvements.

Methods

Forty-nine PSS patients were divided randomly into three groups: a combined group (n = 20), a LF-rTMS group (n = 15), and a control group (n = 14). The combined group received LF-rTMS and rPMS treatment, the rTMS group received LF-rTMS treatment, and the control group received only routine rehabilitation. All patients underwent Ashworth Spasm Scale (MAS), upper extremity Fugl-Meyer (FMA-UE), and modified Barthel Index (MBI) assessments before and after intervention. In addition, resting-state functional magnetic resonance imaging data were collected pre- and post-treatment to observe changes in the amplitude of low-frequency fluctuation (ALFF).

Results

The MAS score was decreased, FMA-UE score and MBI scores were increased in the three groups after therapy than before therapy (all P < 0.05). In particular, the combined group showed significant effect on improved motor function and relieved spasticity in PSS (P < 0.01). Moreover, the combined treatment increased ALFF values mainly in the right supplementary motor area, right middle frontal gyrus, and right cerebellum, while reduced ALFF values mainly in the right post-central gyrus compared with pre-treatment. Compared with the LF-rTMS and control groups, the combined treatment increased ALFF values in the right cerebellum and reduced ALFF values mainly in the frontoparietal cortex. Improvements in the MAS score were positively correlated with the change in ALFF values in the right cerebellum (r = 0.698, P = 0.001) and the right supplementary motor area (r = 0.700, P = 0.001) after combined treatment.

Conclusion

Transcranial combined with peripheral repetitive magnetic stimulation could improve spastic state and motor function in PSS patients, and this effect may be associated with altered cerebellar and frontoparietal cortical activity.

Clinical trial registration

http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800019452.
n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not: NHANES 2007–2016
Authors: Zeng Guixing , You Dongxin , Ye Lingyan , Wu Yuchi , Shi Hualin , Lin Jiarong , Jiang Ziyan , Wei Junping
Published: April 2023

Background and aims

Gout, the most prevalent inflammatory arthritis, has undesirable effects on the quality of life. Omega-3 polyunsaturated fatty acids (n-3 PUFA) has a strong link with anti-inflammatory impacts. However, whether the harmful effects of seafood in relation to gout may vary owing to different levels of n-3 PUFA in seafood is still unclear. It was the goal of this study to examine the relationship between n-3 PUFA poor/rich seafood consumption and gout.

Methods

Between 2007 and 2016, five NHANES cycles were performed, with 12,505 subjects having complete data for gout and two 24-h dietary intake interviews. The 24-h dietary recalls were utilized to evaluate dietary habits. Gout was defined based on questionnaires. Weighted logistic regression models were conducted to investigate the association between n-3 PUFA poor/rich seafood consumption and gout. Moreover, subgroup analysis was utilized to estimate the stability of results. Covariates including age, gender, race/ethnicity, income, education, body mass index, chronic kidney disease, diabetes mellitus, hypertension, smoking status, and drinking status were stratified in different models.

Results

In the fully adjusted model, each unit of increase of n-3 PUFA poor seafood intake was associated with an 8.7% increased risk of gout (OR = 1.087, 95% CI: 1.039, 1.138, P < 0.001), whereas, no correlation was found between n-3 PUFA rich seafood consumption and gout. It also provided a proof-of-concept regarding the potential for n-3 PUFA rich seafood to counteract harmful effects of purines in relation to gout. A dose-response analysis showed that there was a non-linear relationship between n-3 PUFA rich seafood intake and the risk of gout in the female group.

Conclusion

Findings suggest that n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not.
Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer
Authors: Feliciano Josephine Louella , McLoone Dylan , Xu Yingxin , Quek Ruben G.W. , Kuznik Andreas , Pouliot Jean-Francois , Gullo Giuseppe , Rietschel Petra , Guyot Patricia , Konidaris Gerasimos , Chan Keith , Keeping Sam , Wilson Florence R. , Freemantle Nick
Published: April 2023

Objectives

In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression.

Methods

Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring).

Results

In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction—the most suitable method based on published guidelines and trial characteristics—produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction.

Conclusions

After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.
Investigating miR-9 as a mediator in laryngeal cancer health disparities
Authors: Gobin Christina , Inkabi Samuel , Lattimore Chayil C. , Gu Tongjun , Menefee James N. , Rodriguez Mayrangela , Kates Heather , Fields Christopher , Bian Tengfei , Silver Natalie , Xing Chengguo , Yates Clayton , Renne Rolf , Xie Mingyi , Fredenburg Kristianna M.
Published: April 2023

Background

For several decades, Black patients have carried a higher burden of laryngeal cancer among all races. Even when accounting for sociodemographics, a disparity remains. Differentially expressed microRNAs have been linked to racially disparate clinical outcomes in breast and prostate cancers, yet an association in laryngeal cancer has not been addressed. In this study, we present our computational analysis of differentially expressed miRNAs in Black compared with White laryngeal cancer and further validate microRNA-9-5p (miR-9-5p) as a potential mediator of cancer phenotype and chemoresistance.

Methods

Bioinformatic analysis of 111 (92 Whites, 19 Black) laryngeal squamous cell carcinoma (LSCC) specimens from the TCGA revealed miRNAs were significantly differentially expressed in Black compared with White LSCC. We focused on miR-9-5 p which had a significant 4-fold lower expression in Black compared with White LSCC (p<0.05). After transient transfection with either miR-9 mimic or inhibitor in cell lines derived from Black (UM-SCC-12) or White LSCC patients (UM-SCC-10A), cellular migration and cell proliferation was assessed. Alterations in cisplatin sensitivity was evaluated in transient transfected cells via IC50 analysis. qPCR was performed on transfected cells to evaluate miR-9 targets and chemoresistance predictors, ABCC1 and MAP1B.

Results

Northern blot analysis revealed mature miR-9-5p was inherently lower in cell line UM-SCC-12 compared with UM-SCC-10A. UM -SCC-12 had baseline increase in cellular migration (p < 0.01), proliferation (p < 0.0001) and chemosensitivity (p < 0.01) compared to UM-SCC-10A. Increasing miR-9 in UM-SCC-12 cells resulted in decreased cellular migration (p < 0.05), decreased proliferation (p < 0.0001) and increased sensitivity to cisplatin (p < 0.001). Reducing miR-9 in UM-SCC-10A cells resulted in increased cellular migration (p < 0.05), increased proliferation (p < 0.05) and decreased sensitivity to cisplatin (p < 0.01). A significant inverse relationship in ABCC1 and MAP1B gene expression was observed when miR-9 levels were transiently elevated or reduced in either UM-SCC-12 or UM-SCC-10A cell lines, respectively, suggesting modulation by miR-9.

Conclusion

Collectively, these studies introduce differential miRNA expression in LSCC cancer health disparities and propose a role for low miR-9-5p as a mediator in LSCC tumorigenesis and chemoresistance.