bluuebunny/crossref_metadata_2025 huggingface dataset:
Substantial Near-Surface Spring Ozone Enhancement due to Stratospheric Intrusion in the Northeastern Qinghai–Tibet Plateau, China
Authors: Li Chaoqun , Ma Mingchen , Kou Wenbin , Zeng Xinran , Cheng Wenxuan , Wang Houwen , Zhang Jiankai , Wang Wuke , Lin Weili , Li Hong , Zhu Yuanyuan , Yao Xiaohong , Gao Huiwang , Gao Yang
Published: June 2022

Stratospheric ozone intrusion plays an important role in affecting the tropospheric ozone concentrations in the troposphere through stratosphere to troposphere transport (STT). Nevertheless, there are very limited studies on the quantification of the effect. Focusing on a typical event on 9–12 May 2015, when STT occurs over the northeastern Qinghai–Tibet Plateau of China, the observations and reanalysis data indicate that STT is accompanied by high potential vorticity and low specific humidity. In order to quantify the extent to which the STT may elevate the ozone concentrations, an inert tracer is added to the boundary conditions of the Community Multiscale Air Quality (CMAQ), which is driven by the Weather Research and Forecasting (WRF) model. The meteorological conditions simulated by WRF nicely reproduce the distributions of potential vorticity (PV) and water vapor in the upper troposphere. Through the physical processes of diffusion, advection, and dry and wet deposition, the ozone tracer concentrations simulated from CMAQ well capture the spatial propagation and evolution of stratospheric ozone intrusion over Qinghai–Tibet Plateau, warranting the confidence in interpreting the simulated results in quantifying the STT. The STT event indicates the near-surface ozone enhancement of approximately 10–20 ppbv covering half of Qinghai province, even spreading to a broader area of eastern China. For the typical remote mountain such as Waliguan, clear ozone enhancement is obtained over the lower level of the troposphere. The method used in this study is applicable to other regions as well, which can be applied in the future to detect the STT at a wider spatiotemporal scale and help the policymakers identify the ozone sources and make efficient strategies for the ozone pollution control.
Multiple Models Used to Deconstruct the Characteristics of Atmospheric Particles in Arid Region of Northwest China
Authors: Liu Chao , Zhang Tianhao , Lu Bingqing , Zheng Guozhong , Liu Xiaoyan , Gao Ying , Chen Ying , Li Xiang
Published: June 2022

Northwest China has a desert, arid and semi-arid climate that makes outdoor air sampling challenging. The region is also affected by intense dust storms. Monitoring challenges from the harsh climate have limited supplies of the data needed to inform appropriate regulatory actions to address air pollution in the region. Here we combine a comprehensive set of state-of-the-art offline analytical approaches and multiple models to deconstruct the chemical nature and sources of particulate matter at arid city in northwestern China. We collected 972 samples in Jiuquan during the period March 2019 through January 2020. The annual levels of PM10 (73.7 μg/m3) exceeded the Chinese Ambient Air Quality Standard (CAAQS) Grade II of 70 μg/m3. The percentages of the sum of sulfate, nitrate and ammonium, inorganic elements, organic carbon and elemental carbon in PM10 mass ranged 6.8–15.8%, 9.9–12.2%, 9.0–27.7%, and 1.5–4.7%, respectively. Analyses of sources indicated that soil dust was a major contributor to PM10 levels in Jiuquan city accounting for 24.8–30.5%. Fugitive dust and coal combustion were the second and third largest contributors to PM10, respectively. Our results suggest that natural emissions can make air quality regulation futile. In this comprehensive particulate pollution analysis, we present the view that the sizeable regional particulate sources warrant national and regional mitigation strategies to ensure compliance with air quality requirements.
Effects of Small Hydropower Stations Along Rivers on the Distribution of Aquatic Biodiversity
Authors: Gu Peng , Zhang Zhaochang , Liu Jing , Wang Tao , Xiao Yunxing , Yu YangJinzhi , Miao Hengfeng , Zhang Yumiao , Liao Fei , Yang Kunlun , Li Qi
Published: June 2022

At present, there is little research on the impact of small hydropower stations on aquatic biodiversity. In order to investigate whether the existence of small hydropower stations has a significant impact on the aquatic biodiversity of their watersheds, we conducted a systematic study on the abundance of plankton, benthic animal, fish and microorganism in the watersheds of 15 small hydropower stations in Qionglai City. The results showed that 59 species of phytoplankton from 3 divisions, 16 species of zooplankton from 4 categories, 25 species of benthic animal from 3 phyla and 30 species of fish were found in the study basin. The analysis of the physical and chemical indicators of water bodies and the distribution characteristics of aquatic organisms found that the operation of small diversion-type power stations in Qionglai City changed part of the aquatic habitat in the basin, with a greater impact on the activities of large aquatic animals (fish) and a smaller impact on plankton and microorganism, and the intensity of the impact was shown as fish > benthic animal > plankton > microorganism. The small hydropower stations in this study have an impact but not significant on the aquatic biodiversity in the Baimo and Wenjing River in the Qionglai City, and this study provides a data reference for the comprehensive assessment of the environmental impact of small hydropower stations.
Identification of Key Pyroptosis-Related Genes and Distinct Pyroptosis-Related Clusters in Periodontitis
Authors: Ning Wanchen , Acharya Aneesha , Li Simin , Schmalz Gerhard , Huang Shaohong
Published: June 2022

Aim

This study aims to identify pyroptosis-related genes (PRGs), their functional immune characteristics, and distinct pyroptosis-related clusters in periodontitis.

Methods

Differentially expressed (DE)-PRGs were determined by merging the expression profiles of GSE10334, GSE16134, and PRGs obtained from previous literatures and Molecular Signatures Database (MSigDB). Least absolute shrinkage and selection operator (LASSO) regression was applied to screen the prognostic PRGs and develop a prognostic model. Consensus clustering was applied to determine the pyroptosis-related clusters. Functional analysis and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological characteristics and immune activities of the clusters. The hub pyroptosis-related modules were defined using weighted correlation network analysis (WGCNA).

Results

Of the 26 periodontitis-related DE-PRGs, the highest positive relevance was for High-Mobility Group Box 1 (HMGB1) and SR-Related CTD Associated Factor 11 (SCAF11). A 14-PRG-based signature was developed through the LASSO model. In addition, three pyroptosis-related clusters were obtained based on the 14 prognostic PRGs. Caspase 3 (CASP3), Granzyme B (GZMB), Interleukin 1 Alpha (IL1A), IL1Beta (B), IL6, Phospholipase C Gamma 1 (PLCG1) and PYD And CARD Domain Containing (PYCARD) were dysregulated in the three clusters. Distinct biological functions and immune activities, including human leukocyte antigen (HLA) gene expression, immune cell infiltration, and immune pathway activities, were identified in the three pyroptosis-related clusters of periodontitis. Furthermore, the pink module associated with endoplasmic stress-related functions was found to be correlated with cluster 2 and was suggested as the hub pyroptosis-related module.

Conclusion

The study identified 14 key pyroptosis-related genes, three distinct pyroptosis-related clusters, and one pyroptosis-related gene module describing several molecular aspects of pyroptosis in the pathogenesis and immune micro-environment regulation of periodontitis and also highlighted functional heterogeneity in pyroptosis-related mechanisms.
Phosphorus Nutrition in Songpu Mirror Carp (Cyprinus carpio Songpu) During Chronic Carbonate Alkalinity Stress: Effects on Growth, Intestinal Immunity, Physical Barrier Function, and Intestinal Microflora
Authors: Fan Ze , Wu Di , Li Jinnan , Li Chenhui , Zheng Xianhu , Wang Liansheng
Published: June 2022

Carbonate alkalinity is a major environmental stress factor affecting aquatic feed configuration, which easily causes oxidative stress and hypoimmunity for fish. Hence, the purpose of the study is to assess the potential effect of phosphorus on growth, intestinal oxidation resistance, physical barrier function, and microflora for Songpu mirror carp (Cyprinus carpio Songpu) (initial average weight of 2.95 ± 0.21 g) reared at the high-concentration carbonate alkalinity environment. A two-factor, three-level (2 × 3) design was applied, in which diets with three different phosphorus levels (3.6, 7.0, and 10.5 g/kg dry matter) were randomly assigned to 0 and 15 mmol/L carbonate alkalinity groups with three replicate aquariums. After the 8-week trial, we found that weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and lipase and amylase activities in the intestine significantly (p < 0.05) declined with increasing carbonate alkalinity. Carbonate alkalinity of 15 mmol/L significantly reduced glutathione peroxidase (GSHPx) activities in the intestine (p < 0.05). The relative expressions of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), glutathione peroxidase 1a (GPX1a), Clautin3, Clautin11, and tumor necrosis factor β (TNF-β) in the intestine were markedly downregulated by increasing carbonate alkalinity levels (p < 0.05), whilst the relative expressions of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the intestine were markedly upregulated (p < 0.05). At the 15 mmol/L carbonate alkalinity treatment, Songpu mirror carp suffer from hypoimmunity status with failed digestion, antioxidant, inflammation, and immune response, thereby inducing impaired growth. Additionally, significant increments in the abundance of Proteobacteria and a significant decrease in the abundance of Fusobacteria and the Firmicutes/Bacteroidetes ratio were caused due to excessively high carbonate alkalinity (15 mmol/L) and excessively low dietary phosphorus supply (3.6 g/kg). Collectively, 7.0 g/kg dietary phosphorus supplementation was effective in promoting intestinal antioxidant enzyme activities and the corresponding gene expression via the Keap1-Nrf2 signaling pathway and in enhancing intestinal immunity by upregulating anti-inflammatory and downregulating pro-inflammatory genes. Appropriate dietary phosphorus supply could promote the formation of beneficial microflora in freshwater, and it has the potential ability to transfer the adverse effect of carbonate alkalinity stress to the structural composition of intestinal microflora. Hence, consideration should be given to suitable phosphorus supply for fish under the chronic carbonate alkalinity stress.
Endocrine Autoimmunity in Pregnancy
Authors: Świątkowska-Stodulska Renata , Berlińska Agata , Stefańska Katarzyna , Zieliński Maciej , Kwiatkowski Sebastian , Połom Joanna , Andrysiak-Mamos Elżbieta , Wydra Piotr , Sworczak Krzysztof
Published: June 2022

Human gestation leads to a number of physiological alterations which peak at the development of placentta known for, among many other functions, being a transient but highly potent endocrine organ. Hormonal activity of placenta is marked by its ability to continuously produce and secrete high levels of progesterone. Progesterone guards the well-being of the fetoplacental unit throughout the gestation and one of the proposed mechanisms of this principle involves the development of local and systemic immune tolerance mainly due to impediment of CD4+ lymphocyte activation. However, though these alterations are present and well-established, autoimmunity is not entirely rare and a wide spectrum of diseases can continue, or develop de novo, throughout the gestation or even after the delivery. Up-to-date data supports the existence of a relationship between the clinical course of chosen autoimmune diseases and levels of circulating sex steroids.

The most common autoimmune endocrinopathies in pregnant women are Hashimoto’s disease, Graves’ disease, and, more rarely, primary adrenal insufficiency in the form of Addison’s disease. Gestation can influence the clinical course of these endocrinopathies in patients who were diagnosed before conception. Multiple particles, like TSH-receptor stimulating antibodies, thyroid hormones, glucocorticoids, and anti-thyroid medications, can cross the placental barrier and evoke biological action in fetal tissues. Thyroid pathology in the form of postpartum thyroiditis is particularly prevalent in patients with positive anti-thyroperoxidase and anti-thyroglobulin antibodies. Certain populations are more at risk of developing numerous gestational complications and require regular follow-up. In our paper, we would like to address physiological, physiopathological, and clinical aspects of endocrine autoimmunity throughout human gestation, as well as special circumstances to consider in pregnant women.
Differentiation of Pluripotent Stem Cells Into Thymic Epithelial Cells and Generation of Thymic Organoids: Applications for Therapeutic Strategies Against APECED
Authors: Provin Nathan , Giraud Matthieu
Published: June 2022

The thymus is a primary lymphoid organ essential for the induction of central immune tolerance. Maturing T cells undergo several steps of expansion and selection mediated by thymic epithelial cells (TECs). In APECED and other congenital pathologies, a deficiency in genes that regulate TEC development or their ability to select non auto-reactive thymocytes results in a defective immune balance, and consequently in a general autoimmune syndrome. Restoration of thymic function is thus crucial for the emergence of curative treatments. The last decade has seen remarkable progress in both gene editing and pluripotent stem cell differentiation, with the emergence of CRISPR-based gene correction, the trivialization of reprogramming of somatic cells to induced pluripotent stem cells (iPSc) and their subsequent differentiation into multiple cellular fates. The combination of these two approaches has paved the way to the generation of genetically corrected thymic organoids and their use to control thymic genetic pathologies affecting self-tolerance. Here we review the recent advances in differentiation of iPSc into TECs and the ability of the latter to support a proper and efficient maturation of thymocytes into functional and non-autoreactive T cells. A special focus is given on thymus organogenesis and pathway modulation during iPSc differentiation, on the impact of the 2/3D structure on the generated TECs, and on perspectives for therapeutic strategies in APECED based on patient-derived iPSc corrected for AIRE gene mutations.
HP-NAP of Helicobacter pylori: The Power of the Immunomodulation
Authors: Codolo Gaia , Coletta Sara , D’Elios Mario Milco , de Bernard Marina
Published: June 2022

The miniferritin HP-NAP of Helicobacter pylori was originally described as a neutrophil-activating protein because of the capacity to activate neutrophils to generate oxygen radicals and adhere to endothelia. Currently, the main feature for which HP-NAP is known is the ability to promote Th1 responses and revert the immune suppressive profile of macrophages. In this review, we discuss the immune modulating properties of the protein regarding the H. pylori infection and the evidence that support the potential clinical application of HP-NAP in allergy and cancer immunotherapy.
Effects of Grain Boundary Engineering on the Microstructure and Corrosion Fatigue Properties of 316L Austenitic Stainless Steel
Authors: Zhang Mingxian , Zhang Chenxin , Wu Huanchun , Yang Bin
Published: June 2022

Grain boundary engineering (GBE) treatment was performed through thermomechanical processing (TMP) to optimize the grain boundary character distribution (GBCD) of 316L austenitic stainless steel. The effects of TMP on the GBCD and corrosion fatigue properties in high-temperature and high-pressure water were investigated. The results indicated that a high fraction (about 74%) of special boundaries as well as the interrupted network of random high-angle grain boundaries were obtained through 5% strain followed by annealing at 1,273 K for 90 min. The Σ9 and Σ27 boundaries were generated by the reaction of special boundaries. The highest corrosion fatigue life for 3,187 cycles was obtained when the TMP parameters of the 316L ASS were of 5% strain, annealing temperature of 1,273 K, and annealing time of 45 min. The low-energy special boundaries had strong intergranular corrosion resistance, but the strength of these boundaries was not enough to resist the propagation of transgranular fatigue cracks.
Potential Correlation Between Eczema and Hematological Malignancies Risk: A Systematic Review and Meta-Analysis
Authors: Liang Zuohui , Liu Jie , Jin Hongxia , Teng Yirong , Xu Shuangyan , Yan Weimin , Zhu Yun
Published: June 2022

Background

Eczema characterized by itch, sleeplessness, and adverse effects on quality of life is associated with a risk of hematological malignancies. However, there is a controversy pertaining to whether this association implies a greater or lesser risk of hematological cancers. We aimed to explore the link between eczema and hematological malignancies risk.

Methods

We systematically searched PubMed and Embase databases from their inception to February 17, 2022. Two reviewers independently screened articles, extracted data and assessed study quality, respectively. The odds ratios and 95% confidence intervals (CIs) were pooled by using fixed or random-effects models.

Results

29 studies involving 2,521,574 participants examined the contribution of eczema to hematological malignancies. We found that eczema significantly increased the risk of Hodgkin's lymphoma (1.44; 95% CI, 1.07–1.95), myeloma (1.15; 95% CI, 1.04–1.28), and significantly decreased the risk of lymphocytic leukemia (0.91; 95% CI, 0.84–0.99); however, it is not significantly associated with Non-Hodgkin's lymphoma, and myelocytic leukemia.

Conclusion

Eczema has been shown to be associated with the risk of hematological cancer, this association still needs to be verified in large randomized controlled trials.

Systematic Review Registration

https://inplasy.com/, INPLASY202260097.
An Agreement Study Between Point-of-Care and Laboratory Activated Partial Thromboplastin Time for Anticoagulation Monitoring During Extracorporeal Membrane Oxygenation
Authors: Teng Yuan , Yan Shujie , Liu Gang , Lou Song , Zhang Yang , Ji Bingyang
Published: June 2022

Background

Laboratory activated partial thromboplastin time (LAB-aPTT) is a widely used laboratory assay for monitoring unfractionated heparin (UFH) therapy during extracorporeal membrane oxygenation (ECMO). But LAB-aPTT is confined to a central laboratory, and the procedure is time-consuming. In comparison, point-of-care aPTT (POC-aPTT) is a convenient and quick assay, which might be a promising method for anticoagulation monitoring in ECMO. This study was aimed to evaluate the agreement between POC-aPTT (hemochron Jr. Signature instruments) and LAB-aPTT for anticoagulation monitoring in adult ECMO patients.

Methods

Data of ECMO-supported adult patients anticoagulated with UFH in our institute from January 2017 to December 2020 was retrospectively reviewed. POC-aPTT and LAB-aPTT results measured simultaneously were paired and included in the analysis. The correlation between POC-aPTT and LAB-aPTT was assessed using Spearman’s correlation coefficient. Bias between POC-aPTT and LAB-aPTT were described with the Bland-Altman method. Influence factors for bias were identified using multinomial logistic regression analysis.

Results

A total 286 pairs of aPTT results from 63 patients were included in the analysis. POC-aPTT and LAB-aPTT correlated weakly (r = 0.385, P < 0.001). The overall bias between POC-aPTT and LAB-aPTT was 7.78 [95%CI (−32.49, 48.05)] s. The overall bias between POC-aPTT and LAB-aPTT ratio (to normal value) was 0.54 [95%CI (−0.68, 1.76)]. A higher plasma fibrinogen level [OR 1.353 (1.057, 1.733), P = 0.017] was associated with a higher chance of POC-aPTT underestimating LAB-aPTT. While a lower plasma fibrinogen level [OR 0.809 (0.679, 0.963), P = 0.017] and lower UFH rate [OR 0.928 (0.868, 0.992), P = 0.029] were associated with a higher chance of POC-aPTT overestimating LAB-aPTT.

Conclusion

The present study showed poor agreement between POC-aPTT and LAB-aPTT. POC-aPTT was not suitable for anticoagulation monitoring in adult ECMO patients.
Accurate Interpretation of SARS-CoV-2 Antigen Detection by Immunochromatography
Authors: Shao Wenxia
Published: June 2022

SARS-CoV-2 is a serious infectious respiratory virus that can cause lung, heart, kidney, and liver damage and even cause death. Early diagnosis of SARS-CoV-2 infection is vital for epidemic prevention and control. At present, the gold standard of COVID-19 diagnosis is nucleic acid detection of SARS-CoV-2. However, the nucleic acid detection of SARS-CoV-2 requires high site requirements and technology requirements, and the detection is time-consuming and cannot fully meet clinical needs. Although SARS-CoV-2 antigen test results cannot be directly used to diagnose COVID-19, positive results can be used for the early triage and rapid management of suspected populations. However, due to the limitations of the methodology itself, the SARS-CoV-2 antigen test is prone to produce false-positive and false-negative results in the process of detection. It is urgent to develop a batch of SARS-CoV-2 antigen reagents based on new detection technology and detection principles to overcome the defects of existing technologies.
Bacterial Communities in the Endophyte and Rhizosphere of White Radish (Raphanus sativus) in Different Compartments and Growth Conditions
Authors: Sun Nan , Gu Yizhu , Jiang Guoxia , Wang Yuxin , Wang Pingzhi , Song Weitang , Ma Peifang , Duan Yabin , Jiao Ziyuan
Published: June 2022

Endophyte resources have important research value in multiresistance breeding, ecological protection, germicide development, and other fields. In this study, high-throughput sequencing (Illumina-MiSeq) technology was employed to analyse the diversity and community composition of white radish (Raphanus sativus) endophytes and rhizosphere bacteria in different compartments and cultivation conditions, including greenhouse and open field cultivation, at both the phylum and genus levels. Alpha diversity index analysis showed that the bacterial richness and diversity values of rhizosphere bacteria were higher than those of endophytes in different compartments. NMDS analysis and microbial co-occurrence network analysis showed that apart from the similarity in the endophytic bacterial composition of the leaf and root endosphere, the endophytic bacterial composition in flesh and epidermis of radish were also more similar. The dominant endophytic bacteria in white radish were Proteobacteria, Bacteroidetes, and Actinomycetes at the phylum level. We analyzed the effects of different ecological compartments and two cultivation environments on radish microorganisms, and found that ecological compartments played an important role, which was related to the mechanism of microbial assembly in plants. The same facility cultivation can also improve the diversity of radish microorganisms in different ecological compartments, and change the biomarkers that play a major role in rhizosphere microorganisms and endophytes of radish. Bacteria plays an important role in the process of plant growth, and the study of endophytes enriches the understanding of microbial diversity in white radish, which helps to provide insight into the ecological function and interaction mechanisms of plants and microorganisms.
Reprogramming Macrophage Metabolism and its Effect on NLRP3 Inflammasome Activation in Sepsis
Authors: Luo Ruiheng , Li Xizhe , Wang Dan
Published: June 2022

Sepsis, the most common life-threatening multi-organ dysfunction syndrome secondary to infection, lacks specific therapeutic strategy due to the limited understanding of underlying mechanisms. It is currently believed that inflammasomes play critical roles in the development of sepsis, among which NLRP3 inflammasome is involved to most extent. Recent studies have revealed that dramatic reprogramming of macrophage metabolism is commonly occurred in sepsis, and this dysregulation is closely related with the activation of NLRP3 inflammasome. In view of the fact that increasing evidence demonstrates the mechanism of metabolism reprogramming regulating NLRP3 activation in macrophages, the key enzymes and metabolites participated in this regulation should be clearer for better interpreting the relationship of NLRP3 inflammasome and sepsis. In this review, we thus summarized the detail mechanism of the metabolic reprogramming process and its important role in the NLRP3 inflammasome activation of macrophages in sepsis. This mechanism summarization will reveal the applicational potential of metabolic regulatory molecules in the treatment of sepsis.
High-Power Electromagnetic Pulse Exposure of Healthy Mice: Assessment of Effects on Mice Cognitions, Neuronal Activities, and Hippocampal Structures
Authors: Hao Yanhui , Liu Weiqi , Xu Zhengtao , Jin Xing , Ye Yumeng , Yu Chao , Hu Cuicui , Zuo Hongyan , Li Yang
Published: June 2022

Electromagnetic pulse (EMP) is a high-energy pulse with an extremely rapid rise time and a broad bandwidth. The brain is a target organ sensitive to electromagnetic radiation (EMR), the biological effects and related mechanisms of EMPs on the brain remain unclear. The objectives of the study were to assess the effects of EMP exposure on mouse cognitions, and the neuronal calcium activities in vivo under different cases of real-time exposure and post exposure. EMP-treated animal model was established by exposing male adult C57BL/6N mice to 300 kV/m EMPs. First, the effects of EMPs on the cognitions, including the spatial learning and memory, avoidance learning and memory, novelty-seeking behavior, and anxiety, were assessed by multiple behavioral experiments. Then, the changes in the neuronal activities of the hippocampal CA1 area in vivo were detected by fiber photometry in both cases of during real-time EMP radiation and post-exposure. Finally, the structures of neurons in hippocampi were observed by optical microscope and transmission electron microscope. We found that EMPs under this condition caused a decline in the spatial learning and memory ability in mice, but no effects on the avoidance learning and memory, novelty-seeking behavior, and anxiety. The neuron activities of hippocampal CA1 were disturbed by EMP exposure, which were inhibited during EMP exposure, but activated immediately after exposure end. Additionally, the CA1 neuron activities, when mice entered the central area in an Open field (OF) test or explored the novelty in a Novel object exploration (NOE) test, were inhibited on day 1 and day 7 after radiation. Besides, damaged structures in hippocampal neurons were observed after EMP radiation. In conclusion, EMP radiation impaired the spatial learning and memory ability and disturbed the neuronal activities in hippocampal CA1 in mice.
The Shape of μ—How Morphological Analyses Shape the Study of Microglia
Authors: Bosch Lance Fredrick Pahutan , Kierdorf Katrin
Published: June 2022

Microglia, the innate immune cells of the CNS parenchyma, serve as the first line of defense in a myriad of neurodevelopmental, neurodegenerative, and neuroinflammatory conditions. In response to the peripheral inflammation, circulating mediators, and other external signals that are produced by these conditions, microglia dynamically employ different transcriptional programs as well as morphological adaptations to maintain homeostasis. To understand these cells’ function, the field has established a number of essential analysis approaches, such as gene expression, cell quantification, and morphological reconstruction. Although high-throughput approaches are becoming commonplace in regard to other types of analyses (e.g., single-cell scRNA-seq), a similar standard for morphological reconstruction has yet to be established. In this review, we offer an overview of microglial morphological analysis methods, exploring the advantages and disadvantages of each, highlighting a number of key studies, and emphasizing how morphological analysis has significantly contributed to our understanding of microglial function in the CNS parenchyma. In doing so, we advocate for the use of unbiased, automated morphological reconstruction approaches in future studies, in order to capitalize on the valuable information embedded in the cellular structures microglia inhabit.
Synchronization in Multiplex Leaky Integrate-and-Fire Networks With Nonlocal Interactions
Authors: Anesiadis K. , Provata A.
Published: June 2022

We study synchronization phenomena in a multiplex network composed of two rings with identical Leaky Integrate-and-Fire (LIF) oscillators located on the nodes of the rings. Within each ring the LIF oscillators interact nonlocally, while between rings there are one-to-one inter-ring interactions. This structure is motivated by the observed connectivity between the two hemispheres of the brain: within each hemisphere the various brain regions interact with neighboring regions, while across hemispheres each region interacts, primarily, with the functionally homologous region. We consider both positive (excitatory) and negative (inhibitory) linking. We identify numerically various parameter regimes where the multiplex network develops coexistence of active and subthreshold domains, chimera states, solitary states, full coherence or incoherence. In particular, for weak inter-ring coupling (weak multiplexing) different synchronization patterns on the two rings are supported. These are stable and are obtained when the intra-ring coupling values are near the critical points separating qualitatively distinct synchronization regimes, e.g., between the travelling fronts regime and the chimera state one.
Brain MRI Volumetry Analysis in an Indonesian Family of SCA 3 Patients: A Case-Based Study
Authors: Sobana Siti Aminah , Huda Fathul , Hermawan Robby , Sribudiani Yunia , Koan Tan Siauw , Dian Sofiati , Ong Paulus Anam , Dahlan Nushrotul Lailiyya , Utami Nastiti , Pusparini Iin , Gamayani Uni , Mohamed Ibrahim Norlinah , Achmad Tri Hanggono
Published: June 2022

Introduction

Spinocerebellar ataxia type-3 (SCA3) is an adult-onset autosomal dominant neurodegenerative disease. It is caused by expanding of CAG repeat in ATXN3 gene that later on would affect brain structures. This brain changes could be evaluated using brain MRI volumetric. However, findings across published brain volumetric studies have been inconsistent. Here, we report MRI brain volumetric analysis in a family of SCA 3 patients, which included pre-symptomatic and symptomatic patients.

Methodology

The study included affected and unaffected members from a large six-generation family of SCA 3, genetically confirmed using PolyQ/CAG repeat expansion analysis, Sanger sequencing, and PCR. Clinical evaluation was performed using Scale for the Assessment and Rating of Ataxia (SARA). Subjects' brains were scanned using 3.0-T MRI with a 3D T1 BRAVO sequence. Evaluations were performed by 2 independent neuroradiologists. An automated volumetric analysis was performed using FreeSurfer and CERES (for the cerebellum).

Result

We evaluated 7 subjects from this SCA3 family, including 3 subjects with SCA3 and 4 unaffected subjects. The volumetric evaluation revealed smaller brain volumes (p < 0.05) in the corpus callosum, cerebellar volume of lobules I-II, lobule IV, lobule VIIB and lobule IX; and in cerebellar gray matter volume of lobule IV, and VIIIA; in the pathologic/expanded CAG repeat group (SCA3).

Conclusion

Brain MRI volumetry of SCA3 subjects showed smaller brain volumes in multiple brain regions including the corpus callosum and gray matter volumes of several cerebellar lobules.
Forgetting Alcohol: A Double-Blind, Randomized Controlled Trial Investigating Memory Inhibition Training in Young Binge Drinkers
Authors: Almeida-Antunes Natália , Vasconcelos Margarida , Crego Alberto , Rodrigues Rui , Sampaio Adriana , López-Caneda Eduardo
Published: June 2022

Background

Binge Drinking (BD) has been associated with altered inhibitory control and augmented alcohol-cue reactivity. Memory inhibition (MI), the ability to voluntarily suppress unwanted thoughts/memories, may lead to forgetting of memories in several psychiatric conditions. However, despite its potential clinical implications, no study to date has explored the MI abilities in populations with substance misuse, such as binge drinkers (BDs).

Method

This study—registered in the NIH Clinical Trials Database (ClinicalTrials.gov identifier: NCT05237414)—aims firstly to examine the behavioral and electroencephalographic (EEG) correlates of MI among college BDs. For this purpose, 45 BDs and 45 age-matched non/low-drinkers (50% female) will be assessed by EEG while performing the Think/No-Think Alcohol task, a paradigm that evaluates alcohol-related MI. Additionally, this work aims to evaluate an alcohol-specific MI intervention protocol using cognitive training (CT) and transcranial direct current stimulation (tDCS) while its effects on behavioral and EEG outcomes are assessed. BDs will be randomly assigned to one MI training group: combined [CT and verum tDCS applied over the right dorsolateral prefrontal cortex (DLPFC)], cognitive (CT and sham tDCS), or control (sham CT and sham tDCS). Training will occur in three consecutive days, in three sessions. MI will be re-assessed in BDs through a post-training EEG assessment. Alcohol use and craving will be measured at the first EEG assessment, and both 10-days and 3-months post-training. In addition, behavioral and EEG data will be collected during the performance of an alcohol cue reactivity (ACR) task, which evaluates attentional bias toward alcoholic stimuli, before, and after the MI training sessions.

Discussion

This study protocol will provide the first behavioral and neurofunctional MI assessment in BDs. Along with poor MI abilities, BDs are expected to show alterations in event-related potentials and functional connectivity patterns associated with MI. Results should also demonstrate the effectiveness of the protocol, with BDs exhibiting an improved capacity to suppress alcohol-related memories after both combined and cognitive training, along with a reduction in alcohol use and craving in the short/medium-term. Collectively, these findings might have major implications for the understanding and treatment of alcohol misuse.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT05237414].
A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease
Authors: Sun Liying , Ye Xuhui , Wang Linlin , Yu Junping , Wu Yan , Wang Minpeng , Dai Lihua
Published: June 2022

Cerebral small vessel disease (CSVD) is often referred to as “collaterals disease” in traditional Chinese medicine (TCM), and commonly includes ischemic and hemorrhagic CSVD. TCM has a long history of treating CSVD and has demonstrated unique efficacy. Buyang Huanwu Decoction (BHD) is a classical TCM formula that has been used for the prevention and treatment of stroke for hundreds of years. BHD exerts its therapeutic effects on CSVD through a variety of mechanisms. In this review, the clinical and animal studies on BHD and CSVD were systematically introduced. In addition, the pharmacological mechanisms, active components, and clinical applications of BHD in the treatment of CSVD were reviewed. We believe that an in-depth understanding of BHD, its pharmacological mechanism, disease-drug interaction, and other aspects will help in laying the foundation for its development as a new therapeutic strategy for the treatment of CSVD.
Association of Household Food Insecurity With Dietary Intakes and Nutrition-Related Knowledge, Attitudes, and Practices Among School-Aged Children in Gaza Strip, Palestine
Authors: El Bilbeisi Abdel Hamid , Al-Jawaldeh Ayoub , Albelbeisi Ali , Abuzerr Samer , Elmadfa Ibrahim , Nasreddine Lara
Published: June 2022

Background

The present study aimed to determine the association of household food insecurity with dietary intakes and nutrition-related knowledge, attitudes, and practices (KAP) among school-aged children.

Methods

This cross-sectional study was conducted among a representative sample of school-aged children. A total of 380 children and their parents were selected from all Gaza strip governorates, using a random sampling method. The demographic and socioeconomic characteristics; the Radimer/Cornell food security scale; two non-consecutive days of 24-h dietary recall; anthropometric measurements; and the Food and Agriculture Organization KAP-questionnaire (Module 3) were employed. Statistical analysis was performed using SPSS version 25.

Results

About 71.6% of school-aged children were household food-insecure, while 28.4% were household food-secure. Significant associations were found between living area, educational level, household monthly income, weight for age and BMI for age z-scores, underweight, malnutrition status, intakes of protein, iron, vitamin D, and zinc among household food-secure, and household food-insecure. After adjustment for confounding variables, having nutrition-related adequate KAP were associated with lower odds of being food-insecure household [OR = 0.519, 95% (CI = 0.320–0.841)], [OR = 0.510, 95% CI = (0.315–0.827)], and [OR = 0.466, 95% CI = (0.285–0.763), P < 0.05 for all], respectively.

Conclusions

Low socioeconomic status, low anthropometric indices, poor dietary intakes may be associated with a high level of food-insecurity; while having nutrition-related adequate KAP may be protective against food-insecurity among school-aged children.
Case Report: Initial Treatment Adjustments and Complications in Ovarian Cancer Patient With Inborn Error of Immunity
Authors: Mammadova Jamila , Redden Anna , Cruz Rachel , Ujhazi Boglarka , Gordon Sumai , Ellison Maryssa , Gatewood Tyra , Duff Carla , Cannella Anthony , Somboonwit Charurut , Sriaroon Chakrapol , Csomos Krisztian , Dasso Joseph F. , Harville Terry , Ismail-Khan Roohi , Walter Jolan E.
Published: June 2022

Background

Patients with inborn errors of immunity (IEI) have increased risk of developing cancers secondary to impaired anti-tumor immunity. Treatment of patients with IEI and cancer is challenging as chemotherapy can exacerbate infectious susceptibility. However, the literature on optimal cancer treatment in the setting of IEI is sparse.

Objectives

We present a patient with specific antibody deficiency with normal immunoglobins (SADNI), immune dysregulation (ID), and stage III ovarian carcinoma as an example of the need to modify conventional treatment in the context of malignancy, IEI, and ongoing infections.

Methods

This is a retrospective chart review of the patient’s clinical manifestations, laboratory evaluation and treatment course.

Results

Our patient is a female with SADNI and ID diagnosed with stage III ovarian carcinoma at 60 years of age. Her ID accounted for antinuclear antibody positive (ANA+) mixed connective tissue diseases, polyarthralgia, autoimmune neutropenia, asthma, autoimmune thyroiditis, and Celiac disease. Due to the lack of precedent in the literature, her treatment was modified with continuous input from infectious disease, allergy/immunology and oncology specialist using a multidisciplinary approach.

The patient completed debulking surgery and 6 cycles of chemotherapy. The dosing for immunoglobulin replacement therapy was increased for prophylaxis. Chemotherapy doses were lowered for all cycles preemptively for IEI. The therapy included carboplatin, paclitaxel, bevacizumab, and pegfilgrastim. The patient completed six-months of maintenance medication involving bevacizumab.

Her treatment course was complicated by Mycobacterium avium-complex (MAC) infection, elevated bilirubin and liver enzymes attributed to excessive immunoglobulin replacement therapy, and urinary tract infection (UTI) and incontinence.

Cancer genetic analysis revealed no targetable markers and primary immunodeficiency gene panel of 407 genes by Invitae was unrevealing. Lab tests revealed no evidence of Epstein-Barr Virus (EBV) infection. Post-chemotherapy imaging revealed no evidence of cancer for 1 year and 4 months, but the disease relapsed subsequently. The patient’s lung scarring requires vigilance.

Conclusions

Our patient with ovarian cancer and IEI required modified treatment and prevention of complications. In cases of IEI, optimal chemotherapy should be titrated to minimize immunosuppression yet treat cancer aggressively while decreasing the risk of infection with prophylactic antibiotics and prolonged post-treatment surveillance, including pulmonary evaluation.
Compassionate Use of Ripretinib for Patients With Metastatic Gastrointestinal Stromal Tumors: Taiwan and Hong Kong Experience
Authors: Lin Li-Ching , Huang Wen-Kuan , Yen Chueh-Chuan , Yang Ching-Yao , Sung Meng-Ta , Wong Natalie S. M. , Chua Daniel T. T. , Lee Sarah W. M. , Chen Jen-Shi , Yeh Chun-Nan
Published: June 2022

Background

Ripretinib was recently approved for the fourth-line targeted therapy for advanced gastrointestinal stromal tumor (GIST) refractory to imatinib, sunitinib, and regorafenib based on the pivotal INVICTUS phase III study. The INVICTUS study demonstrated significantly improved median progression-free survival (PFS) of 6.3 months and an overall survival (OS) insignificant benefit of ripretinib of 15.1 months as compared with placebo in 85 patients with advanced metastatic GIST. However, treatment outcome for the Chinese population, including in Taiwan and Hong Kong, was lacking.

Material and Method

A compassionate study regarding ripretinib use for patients with advanced/metastatic GIST was conducted from March 2020 to March 2021 to assess the treatment efficacy and safety in Taiwan and Hong Kong patients.

Result

Twenty evaluable patients (16 men and 4 women) with heavily pretreated metastatic GIST receiving ripretinib from March 2020 to March 2021 were enrolled to evaluate the treatment outcome. The response and clinical benefit rates to ripretinib were 25% (5/20) and 60% (12/20), respectively. The median PFS and OS in this compassionate cohort receiving ripretinib were 6.1 months and not reachable, respectively. Albumin less than 3.5 and disease progression after ripretinib use were the two independent unfavorable factors for PFS. There were 14 out of 20 (70%) experiencing any grade adverse event (AE). Loss of hair is the most common grade I to II AE with an incidence of 55%. Grade III AEs included diarrhea, skin rash, and anemia with one patient (5%) for each AE.

Conclusions

Late-line ripretinib use in pretreated Taiwan and Hong Kong patients with advanced GIST showed efficacy consistent with the INVICTUS study. Albumin less than 3.5 and disease progression after ripretinib use were the two independent unfavorable factors for PFS. Ripretinib is generally tolerable, with loss of hair being the most common AE.
The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract
Authors: Ferris William Frank
Published: June 2022

Data from GLOBOCAN 2020 estimates that there were 19.3 million new cases of cancer and 10.0 million cancer-related deaths in 2020 and that this is predicted to increase by 47% in 2040. The combined burden of cancers of the gastrointestinal (GI) tract, including oesophageal-, gastric- and colorectal cancers, resulted in 22.6% of the cancer-related deaths in 2020 and 18.7% of new diagnosed cases. Understanding the aetiology of GI tract cancers should have a major impact on future therapies and lessen this substantial burden of disease. Many cancers of the GI tract have suppression of the tumour suppressor Programmed Cell Death 4 (PDCD4) and this has been linked to the expression of microRNAs which bind to the untranslated region of PDCD4 mRNA and either inhibit translation or target the mRNA for degradation. This review highlights the properties of PDCD4 and documents the evidence for the regulation of PDCD4 expression by microRNAs in cancers of the GI tract.
The Management of Intraabdominal Testis: A Survey of the World Federation of Associations of Pediatric Surgeons (WOFAPS) Practices
Authors: Shehata Sameh , Hadziselimovic Faruk , Khater Doaa , Kotb Mostafa
Published: June 2022

Background and Objective

The optimal treatment protocol of intraabdominal testis is still a matter of debate and until now there are a lot of areas of controversy as regards this challenging subtype. The aim of this report is to document current practice patterns among surgeons from different continents through an online Redcap survey supervised the World Federation of the Association of Pediatric Surgeons (WOFAPS).

Methods

A 16-question-survey related to the management of intraabdominal testis was created and administered via RedCap. The WOFAPS headquarters sent an email to all members inviting voluntary survey participation. Data were entered using Microsoft EXCEL spreadsheet and analyzed. Descriptive statistics were performed for each survey item.

Results

There were 436 WOFAPS members who participated in this study with a response rate of 29%, and the vast majority were pediatric surgeons. Only 13% tried to use hormone therapy aiming to induce testicular descent or to improve future fertility. The choices of various surgical techniques were noted. During laparoscopy, if vessels and cord structure were seen entering the ipsilateral internal inguinal ring, most respondents chose to explore the groin. On the other hand, should there was an absent or atrophic testis, the respondents were split on whether to perform a contralateral orchiopexy.

Conclusion

This survey describes the current practices of a sample of pediatric surgeons and urologists in the management of intraabdominal testis. The use of hormonal treatment, timing of fixation and management in case of passing through vas and vessels through DIR were undisputable. However, management of low-lying and peeing testis together with the management of contralateral testis were still debatable.
Probabilistic Pocket Druggability Prediction via One-Class Learning
Authors: Aguti Riccardo , Gardini Erika , Bertazzo Martina , Decherchi Sergio , Cavalli Andrea
Published: June 2022

The choice of target pocket is a key step in a drug discovery campaign. This step can be supported by in silico druggability prediction. In the literature, druggability prediction is often approached as a two-class classification task that distinguishes between druggable and non-druggable (or less druggable) pockets (or voxels). Apart from obvious cases, however, the non-druggable class is conceptually ambiguous. This is because any pocket (or target) is only non-druggable until a drug is found for it. It is therefore more appropriate to adopt a one-class approach, which uses only unambiguous information, namely, druggable pockets. Here, we propose using the import vector domain description (IVDD) algorithm to support this task. IVDD is a one-class probabilistic kernel machine that we previously introduced. To feed the algorithm, we use customized DrugPred descriptors computed via NanoShaper. Our results demonstrate the feasibility and effectiveness of the approach. In particular, we can remove or mitigate biases chiefly due to the labeling.