bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the Geographical Distribution of Malaria-Associated Anopheles dirus in the South-East Asia and Western Pacific Regions Under Climate Change Scenarios
Authors: Liu Xin , Song Chao , Ren Zhoupeng , Wang Shaobin
Published: June 2022

Malaria occurrence is highly related to the geographical distribution of Anopheles dirus (An. dirus) in the South-East Asia Region and Western Pacific Region (SEAR/WPR). Future climate change has been shown to alter the geographical distribution of malaria vectors. However, few studies have investigated the impact of climate change on the potential distribution of An. dirus in the SEAR/WPR. We considered future climate and land-use data under two climate change scenarios for Representative Concentration Pathways (RCP 4.5 and RCP 8.5) and population data from five Shared Socioeconomic Pathways (SSPs), by using three machine learning models, namely, Random Forest (RF), Boosted Regression Trees (BRT), and Maximum entropy (Maxent) to project the geographical distribution of An. Dirus and to estimate the exposed population. A pseudo-absence dataset was generated based on the relationships between model performance and the distance from the pseudo-absence point to the occurrence point in order to improve model accuracy for projection of the Environmentally Suitable Area (ESA) and exposed human population. The results show that the pseudo-absence data corresponding to the distance of 250 km are appropriate for modeling. The RF method ultimately proved to have the highest accuracy. The predicted ESA of An. dirus would mainly be distributed across Myanmar, Thailand, the southern and eastern part of India, Vietnam, the northern part of Cambodia, and the southern part of Laos. The future ESA is estimated to be reduced under the RCP 4.5 climate change scenario. In the 2070s under RCP 8.5, the reduction of ESA is even greater, especially in Thailand (loss of 35.49 10,000 square kilometers), Myanmar (26.24), Vietnam (17.52), and India (15), which may prevent around 282.6 million people from the risk of malaria under the SSP3 scenarios in the SEAR/WPR. Our predicted areas and potential impact groups for An. dirus under future climate change may provide new insights into regional malaria transmission mechanisms and deployment of malaria control measures based on local conditions in the SEAR/WPR’s.
Intersexual Agonism in Gray Langurs Reflects Male Dominance and Feeding Competition
Authors: Koenig Andreas , Miles Angela , Riaz Durr-E-Ajam , Borries Carola
Published: June 2022

Male-female agonism varies throughout the primate order with males often dominating females, especially in sexually dimorphic species. While intersexual agonism has been attributed to sexually coercive contexts, it can also occur for other reasons and intersexual dominance may be influenced by the adult sex ratio. If the proportion of males is high, certain males will regularly lose against other males. Loser-effects may then pave the way for some females to dominate these males, an effect that has been described in a few primate species. Here we investigated the frequency, general style, and context of agonism among gray langurs (Semnopithecus spp.). Data were collected at two study sites, at Jodhpur, India (one group), and at Ramnagar, Nepal (two groups). The adult sex ratio varied between 0.077 and 1.000 males to females. At both sites, data on agonistic interactions (aggression and submission) were collected in continuous focal animal and ad libitum sampling techniques during 1,945 contact hours (including 1,220 focal animal hours, total). Although aggression intensity was low, high directional consistency and the rare occurrence of counteraggression suggested a despotic dominance style, a likely prerequisite for dominance effects based on adult sex ratio. Aggression by females against males was very rare and mainly occurred in the defense of offspring. We found little evidence for partial female dominance regardless of adult sex ratio. In a few cases in which a female had a higher dominance index than a male, she did not dominate this male in dyadic encounters. Agonism by males directed at females occurred mainly in a feeding context while male policing and a sexual context were both rare. The latter was mostly restricted to females after they had harassed a sexual interaction or after they had behaved proceptively toward a male. Our study suggests that across species the effect of adult sex ratio on female dominance might be more variable than previously suggested. The fact that most agonism between males and females occurred over food identifies intersexual feeding competition as a new research avenue with potentially important consequences for existing ideas on the costs and benefits of group life and composition.
Three New Species of Velvety Shore Bugs (Hemiptera: Heteroptera: Ochteroidea) From Mid-Cretaceous Kachin Amber Shed Light on the Evolution of Rostrum Length in Ochteroidea
Authors: Zhang Mao , Zhao Zhipeng , Ren Dong , Yao Yunzhi
Published: June 2022

Two new genera of velvety shore bugs, Arcochterus Zhang, Ren and Yao gen. nov. and Parvochterus Zhang, Ren and Yao gen. nov. are described, with three new species between them—Arcochterus fuscus Zhang, Ren and Yao sp. nov., Parvochterus reticulatus Ren and Yao sp. nov., and P. lanceolarus Zhang, Ren and Yao sp. nov. Based on the combination of fossil and extant taxa, a cladistic analysis is conducted to confirm the phylogenetic position of these species and allows reconstruction of the inter-genus relationships within the superfamily Ochteroidea. Major conclusions of the phylogenetic analysis: (1) these new species and Grimaldinia pronotalis belong to Ochteridae; (2) Ochteroidea is a monophyletic group, Ochteridae and Gelastocoridae are sister group and monophyletic, respectively. (3) The ancestral character state reconstruction (ACSR) shows that the length of the rostrum has occurred in at least three independent transitions during the evolution of the superfamily Ochteroidea.
Evaluation and Analysis of Bridge Modal Parameters Under Intelligent Monitoring Environment
Authors: Wang Tao , Guo Xuelian , Long Guanxu , Liu Xiaodong
Published: June 2022

After the bridge is completed, the structural materials will be gradually eroded or aged under the influence of climate, temperature, and building environment. Under long-term static and dynamic loads, the structural strength and stiffness of bridge structures, including bridge deck and bridge support, will decrease with the accumulation of time. Bridge modal parameter identification is not only the premise and foundation of health monitoring, but also the main part of bridge structure dynamic identification. Therefore, this paper proposes a bridge modal parameter identification model based on Bayesian method. The model fully considers the uncertainty of parameters and the selection of modal parameters, and identifies more local information through the probability distribution of model parameters and a posteriori confidence. The reliability of the bridge is monitored in real time through the Bayesian dynamic model, and the monitoring error is only 0.01, which can realize high-precision bridge modal parameter identification.
Experimental Investigation on Pedestrian Walking Load in Steel Footbridges
Authors: Deng Deyuan , Wang Zhijian , Zhang Xiaoqing , Lin Hongxin
Published: June 2022

Accurate simulation of walking load is of great significance in conducting human-induced vibration analyses. However, accurate pedestrian walking load data obtained from long-span footbridges is scarce and data reliability depends on the sensor used for measurement. In the current work, Yanluo Footbridge with 102 m span was adopted as test site and Xnode high-precision acceleration wireless sensor was applied for measurements. An experimental investigation was performed on walking loads according to bipedal walking force model. In experimental studies, single-person and multi-person walking tests were performed at Yanluo Footbridge to measure corresponding stride frequency and dynamic load factor. The acceleration time-histories of walking pedestrians were accurately recorded using three-axis wireless acceleration sensor Xnode. Furthermore, the equation of dynamic load factor was derived by analyzing time-histories and power spectra and the design models of pedestrian walking load and crowd load were developed based on a great number of experimental data. Time histories of pedestrian walking loads showed regular periodic changes and dynamic load factor increased by increasing stride frequency. Using the walking load model developed in this work, the reliable structure response of human-induced vibration analysis can be obtained.
Reactive Processing of Acrylic-Based Thermoplastic Composites: A Mini-Review
Authors: Bodaghi Masoud , Park Chung Hae , Krawczak Patricia
Published: June 2022

The demand for thermoplastic composites is continuously increasing because these materials offer many advantages over their thermoset counterparts, such as high toughness, long storage time, easy repairing and recycling, and ability to be thermoformed and heat-welded. However, the manufacturing of thermoplastic composite parts using liquid composite moulding techniques (e.g. resin transfer moulding, vacuum assisted resin transfer moulding … ) is often tricky in the case of melt processing where high temperature and pressure should be chosen to impregnate the fibre reinforcement because of the high melt viscosity of thermoplastics. These issues may be overcome by means of reactive processing where a fibrous preform is first impregnated by a low viscosity mono- or oligomeric precursor and the polymerization of the thermoplastic matrix then occurs in-situ. This article draws a state of the art on the manufacturing characteristics of continuous fibre reinforced acrylic-based reactive thermoplastics (e.g. polymethymethacrylate (PMMA) such as Elium®), which are becoming more and more popular compared to other fast curing thermosets and thermoplastics for in-situ polymerization. Techniques for the in-situ polymerization of methymethacrylate monomers, characterization and modelling of the rheological properties and polymerization kinetics, and some manufacturing related issues such as polymerization shrinkage are reviewed. Particular features of the use of reactive PMMA in different manufacturing techniques of continuous fibre reinforced composites and potential industrial applications are also introduced. Finally, some perspectives for the academic research and industrial development are proposed.
A Case Series of Pediatric Intestinal Ganglioneuromatosis With Novel Phenotypic and Genotypic Profile
Authors: Fang Yuan , Zhang Ye , Dong Rui , Wang Yi-zhen , Chen Lian , Chen Gong
Published: June 2022

Introduction

Intestinal ganglioneuromatosis (IGN) is a rare condition with enteric involvement. Herein, we report a case series of pediatric IGN with a novel phenotypic and genotypic profile.

Methods

The clinical presentation, histopathology, immunochemistry, molecular features, treatment, and prognosis of 3 cases of IGN were assessed.

Results

The cases involved 3 boys with an age range of 1 year and 4 months to 8 years, mimicking juvenile polyps or pseudomembranous enteritis. One patient carried a novel germline mutation in RTEL1 (c.296C > T/p.Pro99Leu) along with variants in F11 (c.1489C > T/p.Arg497Xaa), NBAS (c.1514delC/p.Pro505Hisfs*15), and FECH (c.315-48T > C/splicing), who died due to intractable inflammation. The other two patients underwent recurrence without significant signs of systemic syndrome or malignant progression.

Conclusion

This case series added to the phenotypic and genotypic spectrum of pediatric IGN, which requires the accumulation of more cases and research for in-depth understanding.
Traumatic Cardiac Arrest: Scoping Review of Utilization of Resuscitative Endovascular Balloon Occlusion of the Aorta
Authors: Aoki Makoto , Abe Toshikazu
Published: June 2022

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is increasingly used in trauma resuscitation for patients with life-threatening hemorrhage below the diaphragm and may also be used for patients with traumatic cardiac arrest (TCA). Resuscitative thoracotomy with aortic cross clamping (RT-ACC) maneuver was traditionally performed for patients with TCA due to hemorrhagic shock; however, REBOA has been substituted for RT-ACC in selected TCA cases. During cardiopulmonary resuscitation (CPR) in TCA, REBOA increases cerebral and coronary perfusion, and temporary bleeding control. Both animal and clinical studies have reported the efficacy of REBOA for TCA, and a recent observational study suggested that REBOA may contribute to the return of spontaneous circulation after TCA. Although multiple questions remain unanswered, REBOA has been applied to trauma fields as a novel technology.
Identification of Epigenetic-Dysregulated lncRNAs Signature in Osteosarcoma by Multi-Omics Data Analysis
Authors: Huang Junchao , Zhang Jingwei , Xiao Haijun
Published: June 2022

Background

Alterations of epigenetic modification patterns are potential markers of cancer. The current study characterized six histone modifications in osteosarcoma and identified epigenetically dysregulated long non-coding RNAs (epi-lncRNAs).

Methods

Multi-omics data were obtained from osteosarcoma cell line SJSA1 and a normal cell line. Differentially expressed lncRNAs (DElncRNAs) between osteosarcoma and normal skeletal muscle were analyzed using Limma. MACS2 was applied to identify the “peaks” modified by each histone in the cell. Promoters or enhancers of DElncRNA were overlapped with differential histone-modified regions (DHMR) to screen epi-lncRNAs. Univariate and multivariate Cox regression analysis were performed to detect the genes closely related to the prognosis of osteosarcoma and to construct risk models.

Results

A total of 17 symbolic epi-lncRNA in osteosarcoma were screened, and 13 of them were differentially expressed between osteosarcoma and normal samples. Eight epi-lncRNAs were retained by Univariate Cox regression analysis. Four of these epi-lncRNAs were used to construct an epi-lncRNA signature. The risk score of each osteosarcoma sample in the high- or low-risk group was estimated according to the epi-lncRNA signature. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group. The area under the receiver operating characteristic (ROC) curve of the model was 0.79 and 0.82 for 1-, 3-, and 5-year OS, respectively.

Conclusion

Our results revealed the histone modification pattern in osteosarcoma and developed 4-epi-lncRNA signature to predict the prognosis of osteosarcoma, laying a foundation for the identification of highly specific epigenetic biomarkers for osteosarcoma.
Rapid PCR-Based Nanopore Adaptive Sequencing Improves Sensitivity and Timeliness of Viral Clinical Detection and Genome Surveillance
Authors: Lin Yanfeng , Dai Yan , Liu Yuqi , Ren Zhuli , Guo Hao , Li Zhenzhong , Li Jinhui , Wang Kaiying , Yang Lang , Zhang Shuang , Liu Hongbo , Jia Leili , Ni Ming , Li Peng , Song Hongbin
Published: June 2022

Nanopore sequencing has been widely used for the real-time detection and surveillance of pathogens with portable MinION. Nanopore adaptive sequencing can enrich on-target sequences without additional pretreatment. In this study, the performance of adaptive sequencing was evaluated for viral genome enrichment of clinical respiratory samples. Ligation-based nanopore adaptive sequencing (LNAS) and rapid PCR-based nanopore adaptive sequencing (RPNAS) workflows were performed to assess the effects of enrichment on nasopharyngeal swab samples from human adenovirus (HAdV) outbreaks. RPNAS was further applied for the enrichment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from nasopharyngeal swab samples to evaluate sensitivity and timeliness. The RPNAS increased both the relative abundance (7.87–12.86-fold) and data yield (1.27–2.15-fold) of HAdV samples, whereas the LNAS increased only the relative abundance but had no obvious enrichment on the data yield. Compared with standard nanopore sequencing, RPNAS detected the SARS-CoV-2 reads from two low-abundance samples, increased the coverage of SARS-CoV-2 by 36.68–98.92%, and reduced the time to achieve the same coverage. Our study highlights the utility of RPNAS for virus enrichment directly from clinical samples, with more on-target data and a shorter sequencing time to recover viral genomes. These findings promise to improve the sensitivity and timeliness of rapid identification and genomic surveillance of infectious diseases.
Presenilin Deficiency Increases Susceptibility to Oxidative Damage in Fibroblasts
Authors: Zou Kun , Islam Sadequl , Sun Yang , Gao Yuan , Nakamura Tomohisa , Komano Hiroto , Tomita Taisuke , Michikawa Makoto
Published: June 2022

Alzheimer’s disease (AD) is a genetic and sporadic neurodegenerative disease characterized by extracellular amyloid-β-protein (Aβ) aggregates as amyloid plaques and neuronal loss in the brain parenchyma of patients. Familial AD (FAD) is found to be genetically linked to missense mutations either in presenilin (PS) or amyloid precursor protein (APP). Most of PS mutations increase Aβ42/Aβ40 ratio, which is thought to result in early amyloid deposition in brain. However, PS deficiency in the fore brain of adult mouse leads to neuronal loss in an Aβ independent manner and the underlying mechanism is largely unknown. In this study, we found that reactive oxygen species (ROS) are increased in PS deficient fibroblasts and that H2O2 and ferrous sulfate treatment produced more ROS in PS deficient fibroblasts than in wild-type fibroblasts. PS deficient fibroblasts showed significantly decreased cellular ferritin levels compared with wild-type fibroblasts, suggesting reduced iron sequestrating capability in PS deficient cells. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ferritin levels, indicating that γ-secretase activity is important for maintaining its levels. Moreover, overexpression PS1 mutants in wild-type fibroblasts decreased ferritin light chain levels and enhanced intracellular ROS levels. Our results suggest that dysfunction of PS may reduce intracellular ferritin levels and is involved in AD pathogenesis through increasing susceptibility to oxidative damage.
Spatial Attention Modulates Spike Count Correlations and Granger Causality in the Primary Visual Cortex
Authors: Hu Qiyi , Zheng Zhiyan , Sui Xiaohong , Li Liming , Chai Xinyu , Chen Yao
Published: June 2022

The influence of spatial attention on neural interactions has been revealed even in early visual information processing stages. It resolves the process of competing for sensory information about objects perceived as targets and distractors. However, the attentional modulation of the interaction between pairs of neurons with non-overlapping receptive fields (RFs) is not well known. Here, we investigated the activity of anatomically distant neurons in two behaving monkeys’ primary visual cortex (V1), when they performed a spatial attention task detecting color change. We compared attentional modulation from the perspective of spike count correlations and Granger causality among simple and complex cells. An attention-related increase in spike count correlations and a decrease in Granger causality were found. The results showed that spatial attention significantly influenced only the interactions between rather than within simple and complex cells. Furthermore, we found that the attentional modulation of neuronal interactions changed with neuronal pairs’ preferred directions differences. Thus, we found that spatial attention increased the functional communications and competing connectivities when attending to the neurons’ RFs, which impacts the interactions only between simple and complex cells. Our findings enrich the model of simple and complex cells and further understand the way that attention influences the neurons’ activities.
Effects of Ischemia on the Migratory Capacity of Microglia Along Collagen Microcontact Prints on Organotypic Mouse Cortex Brain Slices
Authors: Steiner Katharina , Humpel Christian
Published: June 2022

Ischemic stroke is a severe insult in the brain causing cell death, inflammation, and activation of microglia. Microglia are the immune cells of the brain and play a role in any inflammatory process during neurodegeneration. Microglia are round ameboid and migrate to the lesion site, where they differentiate into ramified forms and activated phagocytic microglia. On the other hand, microglia can also release growth factors to repair degeneration. The aim of the present study is to explore the migratory capacity of microglia after ischemic insults. Organotypic brain slices of the mouse cortex (300 μm) were prepared. In order to study migration, the slices were connected to collagen-loaded microcontact prints (with or without monocyte chemoattractant protein-1, MCP-1) on the membranes. Slices were stimulated with lipopolysaccharide (LPS) for maximal microglial activation. Ischemic insults were simulated with oxygen-glucose deprivation (OGD) and acidosis (pH 6.5) for 3 days. After 3 weeks in culture, slices were fixed and immunohistochemically stained for the microglial markers Iba1, CD11b and macrophage-like antigen. Our data show that Iba1+ microglia migrated along the microcontact prints, differentiate and phagocyte 1.0 μm fluorescent microbeads. LPS significantly enhanced the number of round ameboid migrating microglia, while OGD and acidosis enhanced the number of ramified activated microglia. The effect was not visible on slices without any μCP and was most potent in μCP with MCP-1. We conclude that OGD and acidosis activate ramification and exhibit a similar mechanism, while LPS only activates round ameboid microglia. Collagen-loaded microcontact prints connected to mouse brain slices are a potent method to study activation and migration of microgliaex vivo.
Early Intracranial Hemorrhage Predicts Poor Clinical Outcome in Community-Acquired Bacterial Meningitis
Authors: Weller Johannes , Enkirch Jonas Simon , Lehmann Felix , Radbruch Alexander , Klockgether Thomas , Zimmermann Julian
Published: June 2022

Background

Community-acquired bacterial meningitis in adults is associated with significant morbidity and mortality; therefore, early prognostication is important to identify severe cases and possibly allocate more intensive treatment. We hypothesized that early intracranial hemorrhage portends a poor prognosis. The objective of this study was to evaluate the prognostic impact of early intracranial hemorrhage regardless of size and location on clinical outcome.

Methods

Retrospective analysis of patients with community-acquired bacterial meningitis treated at a tertiary academic center between 2009 and 2019 about patient characteristics, cerebral imaging findings, and clinical outcome. Uni- and multivariable logistic regression analyses were performed to identify independent predictors of poor clinical outcomes defined as a modified Rankin scale score of 5 or 6 upon discharge.

Results

A total of 102 patients were included, of which 22.5% had poor clinical outcomes. Intracranial micro- or macrohemorrhages were present in 7.8% of cases and associated with poor clinical outcomes [odds ratio (OR) 55.75, 95% CI 3.08–1,008.48, p = 0.006] in multivariate analysis, further predictors included ischemic stroke (OR 15.06, 95% CI 1.32–172, p = 0.029), age (OR 2.56, 95% CI 1.4–4.67, p = 0.002), and reduced consciousness (OR 4.21, 95% CI 1.07–16.64, p = 0.04).

Conclusion

Early cerebral hemorrhage (ECHO) is a potential prognostic marker for clinicians confronted with decision-making in patients who are critically ill with community-acquired bacterial meningitis.
Are Brain and Cognitive Reserve Shaped by Early Life Circumstances?
Authors: de Rooij Susanne R.
Published: June 2022

When growing older, many people are faced with cognitive deterioration, which may even amount to a form of dementia at some point in time. Although neuropathological signs of dementia disorders can often be demonstrated in brains of patients, the degree to which clinical symptoms are present does mostly not accurately reflect the amount of neuropathology that is present. Sometimes existent pathology even goes without any obvious clinical presentation. An explanation for this phenomenon may be found in the concept of reserve capacity. Reserve capacity refers to the ability of the brain to effectively buffer changes that are associated with normal aging processes and to cope with pathological damage. A larger reserve capacity has been suggested to increase resilience against age-associated cognitive deterioration and dementia disorders. Traditionally, a division has been made between brain reserve, which is based on morphological characteristics of the brain, and cognitive reserve, which is based on functional characteristics of the brain. The present review discusses the premises that brain and cognitive reserve capacity are shaped by prenatal and early postnatal factors. Evidence is accumulating that circumstances during the first 1,000 days of life are of the utmost importance for the lifelong health of an individual. Cognitive deterioration and dementia disorders may also have their origin in early life and a potentially important pathway by which the early environment affects the risk for neurodegenerative diseases is by developmental programming of the reserve capacity of the brain. The basic idea behind developmental programming of brain and cognitive reserve is explained and an overview of studies that support this idea is presented. The review is concluded by a discussion of potential mechanisms, synthesis of the evidence and relevance and future directions in the field of developmental origins of reserve capacity.
“The Wandering Nerve Linking Heart and Mind” – The Complementary Role of Transcutaneous Vagus Nerve Stimulation in Modulating Neuro-Cardiovascular and Cognitive Performance
Authors: Dolphin Helena , Dukelow Tim , Finucane Ciaran , Commins Sean , McElwaine Paul , Kennelly Sean P.
Published: June 2022

The vagus nerve is the longest nerve in the human body, providing afferent information about visceral sensation, integrity and somatic sensations to the CNS via brainstem nuclei to subcortical and cortical structures. Its efferent arm influences GI motility and secretion, cardiac ionotropy, chonotropy and heart rate variability, blood pressure responses, bronchoconstriction and modulates gag and cough responses via palatine and pharyngeal innervation. Vagus nerve stimulation has been utilized as a successful treatment for intractable epilepsy and treatment-resistant depression, and new non-invasive transcutaneous (t-VNS) devices offer equivalent therapeutic potential as invasive devices without the surgical risks. t-VNS offers exciting potential as a therapeutic intervention in cognitive decline and aging populations, classically affected by reduced cerebral perfusion by modulating both limbic and frontal cortical structures, regulating cerebral perfusion and improving parasympathetic modulation of the cardiovascular system. In this narrative review we summarize the research to date investigating the cognitive effects of VNS therapy, and its effects on neurocardiovascular stability.
Brain Cell Type-Specific Nuclear Proteomics Is Imperative to Resolve Neurodegenerative Disease Mechanisms
Authors: Nelson Ruth S. , Dammer Eric B. , Santiago Juliet V. , Seyfried Nicholas T. , Rangaraju Srikant
Published: June 2022

Neurodegenerative diseases (NDs) involve complex cellular mechanisms that are incompletely understood. Emerging findings have revealed that disruption of nuclear processes play key roles in ND pathogenesis. The nucleus is a nexus for gene regulation and cellular processes that together, may underlie pathomechanisms of NDs. Furthermore, many genetic risk factors for NDs encode proteins that are either present in the nucleus or are involved in nuclear processes (for example, RNA binding proteins, epigenetic regulators, or nuclear-cytoplasmic transport proteins). While recent advances in nuclear transcriptomics have been significant, studies of the nuclear proteome in brain have been relatively limited. We propose that a comprehensive analysis of nuclear proteomic alterations of various brain cell types in NDs may provide novel biological and therapeutic insights. This may be feasible because emerging technical advances allow isolation and investigation of intact nuclei from post-mortem frozen human brain tissue with cell type-specific and single-cell resolution. Accordingly, nuclei of various brain cell types harbor unique protein markers which can be used to isolate cell-type specific nuclei followed by down-stream proteomics by mass spectrometry. Here we review the literature providing a rationale for investigating proteomic changes occurring in nuclei in NDs and then highlight the potential for brain cell type-specific nuclear proteomics to enhance our understanding of distinct cellular mechanisms that drive ND pathogenesis.
The Functional Neuroanatomy of Reading Intervention
Authors: Braid Jeremias , Richlan Fabio
Published: June 2022

The present article reviews the literature on the brain mechanisms underlying reading improvements following behavioral intervention for reading disability. This includes evidence of neuroplasticity concerning functional brain activation, brain structure, and brain connectivity related to reading intervention. Consequently, the functional neuroanatomy of reading intervention is compared to the existing literature on neurocognitive models and brain abnormalities associated with reading disability. A particular focus is on the left hemisphere reading network including left occipito-temporal, temporo-parietal, and inferior frontal language regions. In addition, potential normalization/compensation mechanisms involving right hemisphere cortical regions, as well as bilateral sub-cortical and cerebellar regions are taken into account. The comparison of the brain systems associated with reading intervention and the brain systems associated with reading disability enhances our understanding of the neurobiological basis of typical and atypical reading development. All in all, however, there is a lack of sufficient evidence regarding rehabilitative brain mechanisms in reading disability, which we discuss in this review.
Research Progress of Pyroptosis in Alzheimer’s Disease
Authors: Xue Weiyue , Cui Di , Qiu Ye
Published: June 2022

Alzheimer’s disease (AD) is a disease characterized by insidious and progressive neurodegeneration, with clinical syndromes of memory and visuospatial skills damage. The pathogenic mechanism of AD is complex in which neural inflammation and neuron death play important roles. Pyroptosis, an inflammatory programmed cell death, has been reported to be involved in neuron death. Pyroptosis is executed by the protein family of gasdermins which punch pores on plasma membrane when activated by the upstream signals including the activation of NLRP3 and caspases, and subsequently triggers the inflammatory cascades featured by the release of interleukin (IL) -1β and IL-18. Herein, we summarized the current research on the roles of neuron pyroptosis in AD, aiming to provide a comprehensive view of the molecular mechanisms underlying AD pathogenesis and potential therapeutic targets for AD.
Iron Neurotoxicity and Protection by Deferoxamine in Intracerebral Hemorrhage
Authors: Li Zhe , Liu Yang , Wei Ruixue , Khan Suliman , Zhang Ruiyi , Zhang Yan , Yong Voon Wee , Xue Mengzhou
Published: June 2022

Intracerebral hemorrhage (ICH) is a subtype of stroke that is characterized by high morbidity and mortality, for which clinical outcome remains poor. An extensive literature indicates that the release of ferrous iron from ruptured erythrocytes in the hematoma is a key pathogenic factor in ICH-induced brain injury. Deferoxamine is an FDA-approved iron chelator that has the capacity to penetrate the blood-brain barrier after systemic administration and binds to iron. Previous animal studies have shown that deferoxamine attenuates ICH-induced brain edema, neuronal death, and neurological deficits. This review summarizes recent progress of the mechanisms by which deferoxamine may alleviate ICH and discusses further studies on its clinical utility.
Evaluated Glomerular Filtration Rate Is Associated With Non-alcoholic Fatty Liver Disease: A 5-Year Longitudinal Cohort Study in Chinese Non-obese People
Authors: Cen Ji , Han Yong , Liu Yufei , Hu Haofei
Published: June 2022

Objective

Evidence regarding the association between evaluated glomerular filtration rate (eGFR) and non-alcoholic fatty liver disease (NAFLD) is still limited. On that account, the purpose of our research is to survey the link of evaluated eGFR on NAFLD.

Methods

This study is a retrospective cohort study. Which consecutively and non-selectively collected a total of 16,138 non-obese participants in a Chinese hospital from January 2010 to December 2014. We then used the Cox proportional-hazards regression model to explore the relationship between baseline eGFR and NAFLD risk. A Cox proportional hazards regression with cubic spline functions and smooth curve fitting (the cubic spline smoothing) was used to identify the non-linear relationship between eGFR and NAFLD. Additionally, we also performed a series of sensitivity analyses and subgroup analyses. Data had been uploaded to the DATADRYAD website.

Results

The mean age of the included individuals was 43.21 ± 14.95 years old, and 8,467 (52.47%) were male. The mean baseline eGFR was 98.83 ± 22.80 mL/min per 1.73m2. During a median follow-up time of 35.8 months, 2,317 (14.36%) people experienced NAFLD. After adjusting covariates, the results showed that eGFR was negatively associated with incident NAFLD (HR = 0.983, 95%CI: 0.980, 0.985). There was also a non-linear relationship between eGFR and NAFLD, and the inflection point of eGFR was 103.489 mL/min per 1.73 m2. The effect sizes (HR) on the left and right sides of the inflection point were 0.988 (0.984, 0.991) and 0.971 (0.963, 0.979), respectively. And the sensitive analysis demonstrated the robustness of our results. Subgroup analysis showed that eGFR was more strongly associated with incident NAFLD in diastolic blood pressure (DBP) < 90 mmHg, fasting plasma glucose (FPG) ≤ 6.1 mmol/L, high-density lipoprotein cholesterol (HDL-c) < 1 mmol/L, and alanine aminotransferase (ALT) ≥ 40 U/L participants. In contrast, the weaker association was probed in those with DBP ≥ 90 mmHg, ALT < 40 U/L, FPG > 6.1 mmol/L, and HDL-c ≥ 1 mmol/L.

Conclusion

This study demonstrates a negative and non-linear association between eGFR and incident NAFLD in the Chinese non-obese population. eGFR is strongly related to NAFLD when eGFR is above 103 mL/min per 1.73 m2. From a therapeutic perspective, it makes sense to maintain eGFR levels within the inflection point to 130 mL/min/1.73 m2.
Clinical Evaluation of Fiducial Marker Pre-Planning for Virtual Bronchoscopic Navigation Implantation in Lung Tumour Patients Treated With CyberKnife
Authors: Ku Ki Man , Lam Bing , Wu Vincent W. C. , Chan Kwok Ting , Chan Chloe Y. Y. , Cheng H. C. , Yuen Kamy M. Y. , Cai Jing
Published: June 2022

Purpose

For the treatment of invisible lung tumours with CyberKnife (CK), fiducial markers (FMs) were implanted as an internal surrogate under virtual bronchoscopic navigation (VBN). This research aims to study the benefits of introducing an additional procedure in assigning the optimal FM positions using a pre-procedure planning system and performing virtual simulation before implantation. The objectives were 1) to reduce the duration of the FM implantation procedure, 2) to reduce the radiation exposure in dose area product (DAP) (dGy*cm2) to patients, and 3) to increase the number of FMs implanted around the tumour.

Methods and Materials

This study is retrospective, single-centre, and observational in nature. A total of 32 patients were divided into two groups. In Group 1, 18 patients underwent conventional VBN FM implantation. In Group 2, 14 patients underwent additional pre-procedure planning and simulation. The steps of pre-procedure planning include 1) importing CT images into the treatment planning system (Eclipse, Varian Medical Systems, Inc.) and delineating five to six FMs in their ideal virtual positions and 2) copying the FM configuration into VBN planning software (LungPoint Bronchus Medical, Inc.) for verification and simulation. Finally, the verified FMs were deployed through VBN with the guidance of the LungPoint planning software.

Results

A total of 162 FMs were implanted among 35 lesions in 32 patients aged from 37 to 92 (median = 66; 16 men and 16 women). Results showed that 1) the average FM insertion time was shortened from 41 min (SD = 2.05) to 23 min (SD = 1.25), p = 0.00; 2) the average absorbed dose of patients in DAP was decreased from 67.4 cGy*cm2 (SD = 14.48) to 25.3 cGy*cm2 (SD = 3.82), p = 0.01 (1-tailed); and 3) the average number of FMs implanted around the tumour was increased from 4.7 (SD = 0.84) to 5.6 (SD = 0.76), p = 0.00 (1-tailed).

Conclusion

Pre-procedure planning reduces the FM implantation duration from 41.1 to 22.9 min, reduces the radiation exposure in DAP from 67.4 to 25.3 dGy*cm2, and increases the number of FMs inserted around the tumour from 4.7 to 5.6.
Metabolic Syndrome as a Risk Factor of Endometrial Cancer: A Nationwide Population-Based Cohort Study of 2.8 Million Women in South Korea
Authors: Jo HyunA , Kim Se Ik , Wang Wenyu , Seol Aeran , Han Youngjin , Kim Junhwan , Park In Sil , Lee Juwon , Yoo Juhwan , Han Kyung-Do , Song Yong Sang
Published: June 2022

Background

A positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort.

Methods

We enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk.

Results

The endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281–1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39–1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213–1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction <0.0001 respectively, and for fasting blood glucose, p for interaction 0.0188). The incidence of endometrial cancer positively correlated with the number of metabolic syndrome components (log-rank p <0.0001).

Conclusion

Our large population-based cohort study in Korean women suggests that metabolic syndrome and its accumulated components may be risk factors for endometrial cancer, particularly in the pre-menopausal women.
Functional Magnetic Resonance Urography in Ureteropelvic Junction Obstruction: Proposal for a Pediatric Quantitative Score
Authors: Damasio Maria Beatrice , Sertorio Fiammetta , Wong Michela Cing Yu , Campo Irene , Carlucci Marcello , Basso Luca , Anfigeno Lorenzo , Bodria Monica , Pistorio Angela , Piaggio Giorgio , Ghiggeri Gian Marco , Mattioli Girolamo
Published: June 2022

Background:

Ureteropelvic junction obstruction (UPJO) is one of the most frequent causes of congenital hydronephrosis. It is essential to distinguish UPJO which needs surgical treatment. fMRU combines high quality morphological details of the kidney and excretory pathways with functional data.

Objective

This study aims to introduce a new radiological score based on fMRU findings to be able to differentiate surgical from non-surgical kidneys.

Materials and Methods

We retrospectively selected patients with hydronephrosis due to UPJO who underwent fMRU (January 2009–June 2018). A multidisciplinary team identified a list of fMRU morpho-functional predictive variables to be included in the analysis. To evaluate the role of different independent variables in predicting the outcome, a multivariable logistic regression model has been performed; the outcome variable was the surgical intervention. For each predictive variable, Odds Ratio and 95% Confidence Intervals were calculated. The likelihood ratio test was used to assess the significance of the variables. Using the regression model, we assigned a numerical value to each predictive variable, rounding up the beta-coefficients. The cut-off value of the total score was obtained from the ROC curve analysis.

Results

A total of 192 patients were enrolled, corresponding to 200 pathological kidneys. All of them underwent fMRU; 135 were surgically treated, while 65 underwent ultrasound or MRU follow-up. Predictive variables significantly associated with surgery resulted to be the urographic phase, the presence of abnormal vessels, and a baseline anterior-posterior pelvic diameter >23 mm. Beta coefficients of the logistic regression model were then converted in scores. The ROC curve of the score showed high sensitivity (84.3%) and specificity (81.3%) with a cut-off > 2.5.

Conclusions

We propose a new fMRU score able to identify surgical vs. non-surgical kidneys with UPJO.
Congenital Co-infections Among HIV-Exposed Infants Born to Mothers on Antiretroviral Treatment in the United States
Authors: Smith Christiana , Silveira Lori , Crotteau Megan , Garth Krystle , Canniff Jennifer , Fetters Kirk B. , Lazarus Sarah , Capraro Shannon , Weinberg Adriana ,   the CHIP Perinatal Team
Published: June 2022

Background

Many women living with HIV (WLHIV) are co-infected with cytomegalovirus (CMV), Toxoplasma gondii (T gondii), and/or hepatitis C virus (HCV). The rates of congenital or perinatal transmission of these co-infections are not well defined in the current era, when most WLHIV receive antiretroviral therapy (ART) during pregnancy.

Methods

Retrospective review of infants of WLHIV born between 2009–2019. Mothers were screened for antibodies to CMV, T. gondii, and HCV; chronic HCV infection was confirmed using plasma RNA PCR. Infants whose mothers had positive/unknown serostatus were screened for CMV using urine or saliva DNA PCR or culture at ≤3 weeks of life; T. gondii using serology at ≤1 month; and HCV using plasma RNA PCR at ≤6 months and serology at ≥12 months.

Results

The study included 264 infants from 255 pregnancies in 191 mothers. At delivery, the median (IQR) CD4 count was 569 (406–748) cells/mm3 and plasma HIV load was 0 (0–24) RNA copies/mL. Among 243 infants born to CMV-seropositive (209) or CMV-missed serostatus (25) mothers, 163 (67.1%) were tested for CMV. Four infants had CMV detected, resulting in a rate of congenital infection of 2.5%. Among 65 infants from 54 (21.2%) pregnancies in T. gondii-seropositive women and 8 in women with unknown T. gondii-serostatus, one acquired congenital toxoplasmosis in the setting of acute maternal T. gondii infection. There were no episodes of vertical transmission from mothers with latent toxoplasmosis. Among 18 infants from 13 (5.1%) pregnancies in HCV RNA PCR-positive women and 4 in women with unknown HCV serostatus, there were no congenital or perinatal HCV transmissions.

Conclusions

In a US cohort of pregnant WLHIV on ART, we identified high maternal CMV seroprevalence and a high rate of congenital CMV infection. We did not identify any congenital or perinatal transmissions of T. gondii or HCV among mothers who had latent or chronic infections. Our data support screening pregnant WLHIV and their infants for CMV and suggest that the rates of congenital and perinatal T. gondii and HCV infections among infants born to WLHIV on ART may be lower in the era of effective ART.
Etiology, Clinical Phenotypes, Epidemiological Correlates, Laboratory Biomarkers and Diagnostic Challenges of Pediatric Viral Meningitis: Descriptive Review
Authors: Al-Qahtani Saleh M. , Shati Ayed A. , Alqahtani Youssef A. , Ali Abdelwahid Saeed
Published: June 2022

Meningitis is an inflammation of the brain and spinal cord meninges caused by infectious and non-infectious agents. Infectious agents causing meningitis include viruses, bacteria, and fungi. Viral meningitis (VM), also termed aseptic meningitis, is caused by some viruses, such as enteroviruses (EVs), herpesviruses, influenza viruses, and arboviruses. However, EVs represent the primary cause of VM. The clinical symptoms of this neurological disorder may rapidly be observed after the onset of the disease, or take prolonged time to develop. The primary clinical manifestations of VM include common flu-like symptoms of headache, photophobia, fever, nuchal rigidity, myalgia, and fatigue. The severity of these symptoms depends on the patient's age; they are more severe among infants and children. The course of infection of VM varies between asymptomatic, mild, critically ill, and fatal disease. Morbidities and mortalities of VM are dependent on the early recognition and treatment of the disease. There were no significant distinctions in the clinical phenotypes and symptoms between VM and meningitis due to other causative agents. To date, the pathophysiological mechanisms of VM are unclear. In this scientific communication, a descriptive review was performed to give an overview of pediatric viral meningitis (PVM). PVM may occasionally result in severe neurological consequences such as mental retardation and death. Clinical examinations, including Kernig's, Brudzinski's, and nuchal rigidity signs, were attempted to determine the clinical course of PVM with various success rates revealed. Some epidemiological correlates of PVM were adequately reviewed and presented in this report. They were seen depending mainly on the causative virus. The abnormal cytological and biochemical features of PVM were also discussed and showed potentials to distinguish PVM from pediatric bacterial meningitis (PBM). The pathological, developmental, behavioral, and neuropsychological complications of PVM were also presented. All the previously utilized techniques for the etiological diagnosis of PVM which include virology, serology, biochemistry, and radiology, were presented and discussed to determine their efficiencies and limitations. Finally, molecular testing, mainly PCR, was introduced and showed 100% sensitivity rates.