bluuebunny/crossref_metadata_2025 huggingface dataset:
Microplastics in the Mediterranean: Variability From Observations and Model Analysis
Authors: Tsiaras Kostas , Costa Elisa , Morgana Silvia , Gambardella Chiara , Piazza Veronica , Faimali Marco , Minetti Roberta , Zeri Christina , Thyssen Melilotus , Ben Ismail Sana , Hatzonikolakis Yannis , Kalaroni Sofia , Garaventa Francesca
Published: March 2022

In this study, the abundance and properties (size, shape, and polymer type) of microplastics (MPs) in sea surface water samples, collected during two sampling campaigns over 2018–2019, in four coastal areas of the Mediterranean Sea (Saronikos Gulf, LIgurian Sea, Gulf of Lion, and Gabes Gulf) were investigated. Coupled hydrodynamic/particle drift model simulations with basin-scale Mediterranean and high resolution nested models were used to provide a better understanding on the variability of the abundance/size of MPs, originating from wastewater and river runoff, in the four areas. Different size classes of MPs were considered in the model, taking into account biofouling induced sinking, as a possible mechanism of MPs removal from the surface. The Gabes Gulf showed the highest mean MPs abundance (0.073–0.310 items/m2), followed by Ligurian Sea (0.061–0.134 items/m2), Saronikos Gulf (0.047–0.080 items/m2), and Gulf of Lion (0.029–0.032 items/m2). Overall, the observed MPs abundance and size distribution was reasonably well reproduced by the model in the four different areas, except an overestimation of small size contribution in Saronikos Gulf. The basin-scale simulation revealed a strong decrease of smaller size MPs in offshore areas, due to biofouling induced sinking, with larger (floating) MPs being able to travel longer distances in the open sea. A significant impact of waves drift and advection of MPs from non-local sources was identified from model simulations, particularly in the Gulfs of Lion and Gabes, having a stronger effect on larger microplastics. In Gabes Gulf, most MPs originated from offshore areas, being mainly (floating) larger size classes, as suggested by the observed quite small contribution of <1 mm particles. The MPs observed abundance distribution in each area could be partly explained by the adopted sources distribution. The modeling tools proposed in this study provide useful insight to gain a better understanding on MPs dynamics in the marine environment and assess the current status of plastic pollution on basin and regional scale to further develop environmental management action for the mitigation of plastic pollution in the Mediterranean Sea.
Ecotoxicological Characterization of Type C Killer Whales From Terra Nova Bay (Ross Sea, Antarctica): Molecular Biomarkers, Legacy, and Emerging Persistent Organic Contaminants
Authors: Panti Cristina , Muñoz-Arnanz Juan , Marsili Letizia , Panigada Simone , Baini Matteo , Jiménez Begoña , Fossi Maria Cristina , Lauriano Giancarlo
Published: March 2022

Among killer whale forms, type C is a fish-eating form and is the most common in the Ross Sea. In the austral summer 2015, a study was conducted to evaluate the toxicological hazard these marine mammals face in the Antarctic ecosystem. Seven biopsy samples were collected from adult individuals (five males and two females) in the surroundings of the Italian Research Station Mario Zucchelli, Terra Nova Bay, by remote dart sampling from the pack ice. The accumulation levels of persistent organic pollutants (POPs) such as legacy (DDTs, PCBs, and HCB) and emerging (PBDEs and DP) were measured. Moreover, the protein expression of cytochrome P450 (CYP1A1 and 2B) and the mRNA level variations of the peroxisome proliferator-activated receptors α and γ (PPARα-γ) and the estrogen receptor α (ERα), aryl hydrocarbon receptor (AhR), andCyp1awere evaluated. Twenty PCB congeners, six DDTs, HCB, three HCHs, and fourteen brominated BDEs and DP-syn and anti-isomers were analyzed on freeze-dried blubber biopsy samples by GC-MS. The protein expression was evaluated by Western Blot and the mRNA levels were quantified by quantitative real-time PCR. The average abundance pattern for the contaminants was DDTs > PCBs > HCB > HCHs ≈ PBDEs >> DP. Contaminant levels resulted to be lower when compared to the existing data from the Antarctic type C killer whales from the McMurdo Sound (Ross Sea) and those reported for fish-eating killer whales worldwide. The mRNA levels of the five target genes were successfully quantified, but no statistical correlation was found with POP levels, suggesting that either the low levels of quantified POPs in blubber may not significantly affect the biological responses investigated, or that other stressors could contribute to the alterations of the molecular biomarkers. Although the results showed a lower risk related to contamination compared to more impacted areas, this study provides baseline data for the conservation of this species in an area with high ecological value, recently declared as the largest Marine Protected Area in Antarctica, where pollutants should remain at minimum levels despite increasing multiple stresses existing in the region.
Oxidative Stress: A Putative Link Between Lower Urinary Tract Symptoms and Aging and Major Chronic Diseases
Authors: Xu Zhenqun , Elrashidy Rania A. , Li Bo , Liu Guiming
Published: March 2022

Aging and major chronic diseases are risk factors for lower urinary tract symptoms (LUTS). On the other hand, oxidative stress (OS) is one of the fundamental mechanisms of aging and the development of chronic diseases. Therefore, OS might be a candidate mechanism linking these two clinical entities. This article aims to summarize the studies on the prevalence of LUTS, the role of OS in aging and chronic diseases, and the potential mechanisms supporting the putative link. A comprehensive literature search was performed to identify recent reports investigating LUTS and OS in major chronic diseases. In addition, studies on the impact of OS on the lower urinary tract, including bladder, urethra, and prostate, were collected and summarized. Many studies showed LUTS are prevalent in aging and major chronic diseases, including obesity, metabolic syndrome, diabetes, cardiovascular disease, hypertension, obstructive sleep apnea, autoimmune diseases, Alzheimer’s disease, and Parkinson’s disease. At the same time, OS is a key component in the pathogenesis of those chronic diseases and conditions. Recent studies also provided evidence that exacerbated OS can cause functional and/or structural changes in the bladder, urethra, and prostate, leading to LUTS. The reviewed data support the concept that OS is involved in multiple risk factors-associated LUTS, although further studies are needed to confirm the causative relationship. The specific ROS/RNS and corresponding reactions/pathways involved in chronic diseases and associated LUTS should be identified in the future and could serve as therapeutic targets.
Case Report: Challenges in the Diagnosis of a Case of Mal de Meleda and a Therapeutic Attempt of Ixekizumab and Adalimumab
Authors: Dai Yuwei , Zheng Xiaodong , Zhang Qi , Hu Xia , Wang Peiguang , Yang Sen
Published: March 2022

Background

Mal de Meleda (MDM, OMIM 248300) is an autosomal recessive disease characterized by symmetrical and progressive palmoplantar hyperkeratosis soon after birth. Mutations in SLURP1 gene could lead to MDM. Clinically, MDM is easily misdiagnosed as other types of keratoderma due to phenotypic variation and overlap.

Objective and Methods

A patient with suspected MDM was confirmed by the combination of next-generation sequencing and Exomiser, and the patient was attempted with the treatment of Ixekizumab and Adalimumab.

Results

A homozygous mutation c.256G>A (p.Gly86Arg) in the SLURP1 gene was identified in the patient. The inflammatory erythemas on his hands, feet and buttocks were mildly relieved after the treatment of high dose of Ixekizumab.

Conclusions

Our findings helps to enhance the understanding of MDM. Ixekizumab may be a potential strategy to treat MDM.
Comparison of SARS-CoV-2 Variants of Concern Alpha (B.1.1.7) vs. Beta (B.1.351) in Critically Ill Patients: A Multicenter Cohort Study
Authors: Louis Guillaume , Belveyre Thibaut , Goetz Christophe , Gibot Sébastien , Dunand Paul , Conrad Marie , Gaci Rostane , Gette Sébastien , Ouamara Nadia , Perez Pascale , Cadoz Cyril , Picard Yoann , Mellati Nouchan
Published: March 2022

Objectives

The clinical outcomes of the Beta (B.1.351) variant of concern (VOC) of the SARS-CoV-2 virus remain poorly understood. In early 2021, northeastern France experienced an outbreak of Beta that was not observed elsewhere. This outbreak slightly preceded and then overlapped with a second outbreak of the better understood VOC Alpha (B.1.1.7) in the region. This situation allowed us to contemporaneously compare Alpha and Beta in terms of the characteristics, management, and outcomes of critically ill patients.

Methods

A multicenter prospective cohort study was conducted on all consecutive adult patients who had laboratory confirmed SARS CoV-2 infection, underwent variant screening, and were admitted to one of four intensive care units (ICU) for acute respiratory failure between January 9th and May 15th, 2021. Primary outcome was 60-day mortality. Differences between Alpha and Beta in terms of other outcomes, patient variables, management, and vaccination characteristics were also explored by univariate analysis. The factors that associated with 60-day death in Alpha- and Beta-infected patients were examined with logistic regression analysis.

Results

In total, 333 patients (median age, 63 years; 68% male) were enrolled. Of these, 174 and 159 had Alpha and Beta, respectively. The two groups did not differ significantly in terms of 60-day mortality (19 vs. 23%), 28-day mortality (17 vs. 20%), need for mechanical ventilation (60 vs. 61%), mechanical ventilation duration (14 vs. 15 days), other management variables, patient demographic variables, comorbidities, or clinical variables on ICU admission. The vast majority of patients were unvaccinated (94%). The remaining 18 patients had received a partial vaccine course and 2 were fully vaccinated. The vaccinated patients were equally likely to have Alpha and Beta.

Conclusions

Beta did not differ from Alpha in terms of patient characteristics, management, or outcomes in critically ill patients.

Trial Registration

ClinicalTrials.gov, identifier: NCT04906850.
Incidence Rates of Myomectomy-Related Mortality and Venous Thromboembolism in South Korea: A Population-Based Study
Authors: Yuk Jin-Sung , Kim Myounghwan
Published: March 2022

Background

Uterine leiomyomas are the most commonly observed pathologies, with an estimated prevalence of 4. 5–68.6%. We aimed to calculate myomectomy-related mortality and venous thromboembolism incidence rates in the Republic of Korea.

Methods

The data of patients who underwent myomectomy (2009–2018) were obtained from the Health Insurance Review and Assessment Service-National Inpatient Sample. The mortality rate after myomectomy was calculated using the leiomyoma diagnostic codes and myomectomy procedure codes. The incidence rates of venous thromboembolism, deep vein thrombosis, and pulmonary embolism were calculated using their diagnostic codes, with concomitant use of an antithrombotic agent during the same period or within 90 days after myomectomy.

Results

The data of 23,549 women aged 15–55 years who underwent myomectomy were extracted. The myomectomy rate was 14.6 ± 0.1 per 10,000 patients. The average age was 39.39 ± 0.04 years. One patient who underwent myomectomy died; this patient did not have concomitant venous thromboembolism. The post-myomectomy mortality rate was 1.3 ± 0.8 per 10,000 patients. The incidence rates of venous thromboembolism, deep vein thrombosis, and pulmonary embolism after myomectomy were 5.7 ± 1.6 per 10,000 patients, 4.4 ± 1.4 per 10,000 patients, and 2.5 ± 1 per 10,000 patients, respectively. The conversion rate to hysterectomy was 2.9 ± 1.1 per 10,000 patients.

Conclusion

The current mortality rate after myomectomy (0.013%) is substantially lower than that described in previous studies at the turn of the 20th century. The incidence of venous thromboembolism is also considerably lower than that in the general population worldwide.
Oregano Oil and Harmless Blue Light to Synergistically Inactivate Multidrug-Resistant Pseudomonas aeruginosa
Authors: Lu Min , Wong Ka Ioi , Li Xin , Wang Fei , Wei Li , Wang Shen , Wu Mei X.
Published: March 2022

Blue light (BL) at 405 nm and oregano essential oil (OEO) have shown bactericidal activity by its own. Here, we demonstrated that the two synergistically killed multidrug-resistant (MDR) Pseudomonas aeruginosa (Pa). Pa ATCC19660 and HS0065 planktonic cells and mature biofilms were reduced by more than 7 log10 after treatment by BL combined with OEO, in sharp contrast to no significant bacterial reduction with the monotreatment. The duo also sufficiently eliminated acute or biofilm-associated infection of open burn wounds in murine without incurring any harmful events in the skin. The synergic bactericide was attributed mainly to the ability of OEO to magnify cytotoxic reactive oxygen species (ROS) production initiated by BL that excited endogenous tetrapyrrole macrocycles in bacteria while completely sparing the surrounding tissues from the phototoxic action. OEO ingredient analysis in combination with microbial assays identified carvacrol and its isomer thymol to be the major phytochemicals that cooperated with BL executing synergic killing. The finding argues persuasively for valuable references of carvacrol and thymol in assessing and standardizing the bactericidal potential of various OEO products.
The Antimicrobial Effect of Melissa officinalis L. Essential Oil on Vibrio parahaemolyticus: Insights Based on the Cell Membrane and External Structure
Authors: Yu Huijie , Pei Juxin , Qiu Weiqiang , Mei Jun , Xie Jing
Published: March 2022

The study was to evaluate the antimicrobial impacts on Melissa officinalis L. essential oil (MOEO) against Vibrio parahaemolyticus. The minimum inhibitory concentration (MIC) of MOEO on Vibrio parahaemolyticus was 1 μL⋅mL–1. The kill-time curve exhibited that MOEO had good antimicrobial activity. The analysis of cellular ingredients leakage and cell viability illustrated that MOEO has destruction to the morphology of the cell membrane. The damage to the membrane integrity by MOEO has been confirmed by transmission and scanning electron microscopy, obvious morphological and ultrastructural changes were observed in the treated bacterial cells. The MOEO at 0.5 μL⋅mL–1 can inhibit the biofilm formation, biofilm motility, and extracellular polysaccharide production. Meanwhile, the qPCR results exhibited MOEO inhibited the expression of virulence genes. The findings showed that MOEO exerted its antimicrobial effect mainly by destroying the membrane, which indicated its potential as a natural food preservative.
Effect of Changes in Photoperiods on Melatonin Expression and Gut Health Parameters in Laying Ducks
Authors: Cui Yao-ming , Wang Jing , Zhang Hai-jun , Qi Guang-hai , Qiao Han-zhen , Gan Li-ping , Wu Shu-geng
Published: March 2022

We investigated the effect of photoperiod on ileal morphology, barrier function, short-chain fatty acid (SCFA) contents, microbial flora, melatonin expression, and synthesis in laying ducks. After adaption, a total of 180 Jinding laying ducks (252 days old) were randomly divided into three treatments, receiving 12L (hours of light):12D (hours of darkness), 16L:8D, or 20L:4D. Each treatment had six replicates with 10 birds each. The formal experiment lasted 58 days. Compared with 12L:12D, the significantly higher values of villus height and goblet cell percentage (GCP) were observed in 16L:8D treatment, accompanied with the higher mRNA relative expression of zonula occludens-1, zonula occludens-2, zonula occludens-3, claudin-1, occludin, and mucin 2 (P < 0.05). Besides, significantly higher values of acetate and propionate, butyrate and total SCFA concentrations were simultaneously observed in ileal chyme of 16L:8D treatment (P < 0.05). For the ileal microbial community, the results of principal coordinate analysis (PCoA) visually presented that three photoperiod groups were mainly scattered into three clusters, indicating that the microbiota composition in different photoperiod treatments were quite dissimilar. Lower values of Shannon indicators were observed in the 20L:4D treatment (P < 0.05), meaning that the microbiota α-diversity decreased in the 20-h photoperiod. The relative abundance of Actinobacteria, Fusobacteria, and Proteobacteria at phylum level and Fusobacterium, Clostridium_sensu_stricto_1, and Pectobacterium at genus level kept an appropriate balance in the 16L:8D photoperiod. Melatonin level in serum decreased with the increasing photoperiods at 6:00 and 12:00, which was consistent with melatonin receptor expressions in the hypothalamus and ileal tissue. Meanwhile, the adenosine 3′,5′-cyclic phosphate (cAMP) contents were significantly downregulated in the pineal gland (P < 0.05), in response to the increase in photoperiod. In conclusion, an appropriate photoperiod could improve ileal morphology, barrier function, SCFA profile, and microbial flora, which may be attributed to the appropriate regulation of the circadian rhythm through melatonin as well as its receptor expression, and 16 h could be an adequate photoperiod for laying ducks.
Novel Collaborative Weighted Non-negative Matrix Factorization Improves Prediction of Disease-Associated Human Microbes
Authors: Xu Da , Xu Hanxiao , Zhang Yusen , Gao Rui
Published: March 2022

Extensive clinical and biomedical studies have shown that microbiome plays a prominent role in human health. Identifying potential microbe–disease associations (MDAs) can help reveal the pathological mechanism of human diseases and be useful for the prevention, diagnosis, and treatment of human diseases. Therefore, it is necessary to develop effective computational models and reduce the cost and time of biological experiments. Here, we developed a novel machine learning-based joint framework called CWNMF-GLapRLS for human MDA prediction using the proposed collaborative weighted non-negative matrix factorization (CWNMF) technique and graph Laplacian regularized least squares. Especially, to fuse more similarity information, we calculated the functional similarity of microbes. To deal with missing values and effectively overcome the data sparsity problem, we proposed a collaborative weighted NMF technique to reconstruct the original association matrix. In addition, we developed a graph Laplacian regularized least-squares method for prediction. The experimental results of fivefold and leave-one-out cross-validation demonstrated that our method achieved the best performance by comparing it with 5 state-of-the-art methods on the benchmark dataset. Case studies further showed that the proposed method is an effective tool to predict potential MDAs and can provide more help for biomedical researchers.
Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation
Authors: Wong Lilly M. , Li Dajiang , Tang Yuyang , Méndez-Lagares Gema , Thompson George R. , Hartigan-O’Connor Dennis J. , Dandekar Satya , Jiang Guochun
Published: March 2022

Human Immunodeficiency Virus-1 (HIV) remains a global health challenge due to the latent HIV reservoirs in people living with HIV (PLWH). Dormant yet replication competent HIV harbored in the resting CD4+ T cells cannot be purged by antiretroviral therapy (ART) alone. One approach of HIV cure is the “Kick and Kill” strategy where latency reversal agents (LRAs) have been implemented to disrupt latent HIV, expecting to eradicate HIV reservoirs by viral cytopathic effect or immune-mediated clearance. Protein Kinase C agonists (PKCa), a family of LRAs, have demonstrated the ability to disrupt latent HIV to an extent. However, the toxicity of PKCa remains a concern in vivo. Early growth response protein 1 (EGR1) is a downstream target of PKCa during latency reversal. Here, we show that PKCa induces EGR1 which directly drives Tat-dependent HIV transcription. Resveratrol, a natural phytoalexin found in grapes and various plants, induces Egr1 expression and disrupts latent HIV in several HIV latency models in vitro and in CD4+ T cells isolated from ART-suppressed PLWH ex vivo. In the primary CD4+ T cells, resveratrol does not induce immune activation at the dosage that it reverses latency, indicating that targeting EGR1 may be able to reverse latency and bypass PKCa-induced immune activation.
Regulation of Escherichia coli Group 2 Capsule Gene Expression: A Mini Review and Update
Authors: Aldawood Esraa , Roberts Ian S.
Published: March 2022

The expression of a group 2 capsule (K antigen), such as the K1 or K5 antigen, is a key virulence factor of Escherichia coli responsible for extra-intestinal infections. Capsule expression confers resistance to innate host defenses and plays a critical role in invasive disease. Capsule expression is temperature-dependent being expressed at 37°C but not at 20°C when outside the host. Group 2 capsule gene expression involves two convergent promoters PR1 and PR3, the regulation of which is critical to capsule expression. Temperature-dependent expression is controlled at transcriptional level directly by the binding of H-NS to PR1 and PR3 and indirectly through BipA with additional input from IHF and SlyA. More recently, other regulatory proteins, FNR, Fur, IHF, MprA, and LrhA, have been implicated in regulating capsule gene expression in response to other environmental stimuli and there is merging data for the growth phase-dependent regulation of the PR1 and PR3 promoters. The aim of the present Mini Review is to provide a unified update on the latest data on how the expression of group 2 capsules is regulated in response to a number of stimuli and the growth phase something that has not to date been addressed.
Modification Patterns of DNA Methylation-Related lncRNAs Regulating Genomic Instability for Improving the Clinical Outcomes and Tumour Microenvironment Characterisation of Lower-Grade Gliomas
Authors: Maimaiti Aierpati , Aili Yirizhati , Turhon Mirzat , Kadeer Kaheerman , Aikelamu Paziliya , Wang Zhitao , Niu Weiwei , Aisha Maimaitili , Kasimu Maimaitijiang , Wang Yongxin , Wang Zengliang
Published: March 2022

Background: DNA methylation is an important epigenetic modification that affects genomic instability and regulates gene expression. Long non-coding RNAs (lncRNAs) modulate gene expression by interacting with chromosomal modifications or remodelling factors. It is urgently needed to evaluate the effects of DNA methylation-related lncRNAs (DMlncRNAs) on genome instability and further investigate the mechanism of action of DMlncRNAs in mediating the progression of lower-grade gliomas (LGGs) and their impact on the immune microenvironment.

Methods: LGG transcriptome data, somatic mutation profiles and clinical features analysed in the present study were obtained from the CGGA, GEO and TCGA databases. Univariate, multivariate Cox and Lasso regression analyses were performed to establish a DMlncRNA signature. The KEGG and GO analyses were performed to screen for pathways and biological functions associated with key genes. The ESTIMATE and CIBERSORT algorithms were used to determine the level of immune cells in LGGs and the immune microenvironment fraction. In addition, DMlncRNAs were assessed using survival analysis, ROC curves, correlation analysis, external validation, independent prognostic analysis, clinical stratification analysis and qRT-PCR.

Results: We identified five DMlncRNAs with prognostic value for LGGs and established a prognostic signature using them. The Kaplan–Meier analysis revealed 10-years survival rate of 10.10% [95% confidence interval (CI): 3.27–31.40%] in high-risk patients and 57.28% (95% CI: 43.17–76.00%) in low-risk patients. The hazard ratio (HR) and 95% CI of risk scores were 1.013 and 1.009–1.017 (p < 0.001), respectively, based on the univariate Cox regression analysis and 1.009 and 1.004–1.013 (p < 0.001), respectively, based on the multivariate Cox regression analysis. Therefore, the five-lncRNAs were identified as independent prognostic markers for patients with LGGs. Furthermore, GO and KEGG analyses revealed that these lncRNAs are involved in the prognosis and tumorigenesis of LGGs by regulating cancer pathways and DNA methylation.

Conclusion: The findings of the study provide key information regarding the functions of lncRNAs in DNA methylation and reveal that DNA methylation can regulate tumour progression through modulation of the immune microenvironment and genomic instability. The identified prognostic lncRNAs have high potential for clinical grouping of patients with LGGs to ensure effective treatment and management.
Highly Expressed Soluble Recombinant Anti-GFP VHHs in Escherichia coli via Optimized Signal Peptides, Strains, and Inducers
Authors: Chao Shuangying , Liu Yuhang , Ding Ning , Lin Yue , Wang Qian , Tan Junwen , Li Wei , Zheng Yang , Hu Xuejun , Li Junming
Published: March 2022

Antigen-binding variable domains of the H chain of heavy-chain antibodies (VHHs), also known as nanobodies (Nbs), are of great interest in imaging technique, disease prevention, diagnosis, and therapy. High-level expression of soluble Nbs is very important for its industrial production. In this study, we optimized the expression system of anti-green fluorescent protein (GFP) VHHs with three different signal peptides (SPs), outer-membrane protein A (OmpA), pectate lyase B (PelB), and L-asparaginase II SP (L-AsPsII), in different Escherichia coli strains via isopropyl β-D-thiogalactoside (IPTG) induction and auto-induction, respectively. The solubility of recombinant anti-GFP VHHs with PelB or OmpA was significantly enhanced to the same extent by IPTG induction and auto-induction in BL21 (DE3) E. coli strain and the maximum yield of target protein reached approximately 0.4 mg/l in a shake flask. The binding activity of recombinant anti-GFP VHHs was also confirmed to be retained by native-polyacrylamide gel electrophoresis (PAGE). These results suggest that SPs like OmpA and PelB could efficiently improve the recombinant anti-GFP VHH solubility without changing its bioactivity, providing a novel strategy to optimize the E. coli expression system of soluble VHHs, and lay the foundation for the industrial production of soluble recombinant anti-GFP VHHs and the research of other VHHs in the future.
Functional Brain Connectivity in Mild Cognitive Impairment With Sleep Disorders: A Study Based on Resting-State Functional Magnetic Resonance Imaging
Authors: Luo Yuxi , Qiao Mengyuan , Liang Yuqing , Chen Chongli , Zeng Lichuan , Wang Lin , Wu Wenbin
Published: March 2022

Purpose

To investigate the effect of sleep disorder (SD) on the changes of brain network dysfunction in mild cognitive impairment (MCI), we compared network connectivity patterns among MCI, SD, and comorbid MCI and sleep disorders (MCI-SD) patients using resting state functional magnetic resonance imaging (RS-fMRI).

Patients and Methods

A total of 60 participants were included in this study, 20 each with MCI, SD, or MCI-SD. And all participants underwent structural and functional MRI scanning. The default-mode network (DMN) was extracted by independent component analysis (ICA), and regional functional connectivity strengths were calculated and compared among groups.

Results

Compared to MCI patients, The DMN of MCI-SD patients demonstrated weaker functional connectivity with left middle frontal gyrus, right superior marginal gyrus, but stronger connectivity with the left parahippocampus, left precuneus and left middle temporal gyrus. Compared to the SD group, MCI-SD patients demonstrated weaker functional connectivity with right transverse temporal gyrus (Heschl’s gyrus), right precentral gyrus, and left insula, but stronger connectivity with posterior cerebellum, right middle occipital gyrus, and left precuneus.

Conclusion

Patients with MCI-SD show unique changes in brain network connectivity patterns compared to MCI or SD alone, likely reflecting a broader functional disconnection and the need to recruit more brain regions for functional compensation.
Emerging Potential of Exosomal Non-coding RNA in Parkinson’s Disease: A Review
Authors: Zhang Peng , Rasheed Madiha , Liang Junhan , Wang Chaolei , Feng Lin , Chen Zixuan
Published: March 2022

Exosomes are extracellular vesicles that are released by cells and circulate freely in body fluids. Under physiological and pathological conditions, they serve as cargo for various biological substances such as nucleotides (DNA, RNA, ncRNA), lipids, and proteins. Recently, exosomes have been revealed to have an important role in the pathophysiology of several neurodegenerative illnesses, including Parkinson’s disease (PD). When secreted from damaged neurons, these exosomes are enriched in non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs) and display wide distribution characteristics in the brain and periphery, bridging the gap between normal neuronal function and disease pathology. However, the current status of ncRNAs carried in exosomes regulating neuroprotection and PD pathogenesis lacks a systematic summary. Therefore, this review discussed the significance of ncRNAs exosomes in maintaining the normal neuron function and their pathogenic role in PD progression. Additionally, we have emphasized the importance of ncRNAs exosomes as potential non-invasive diagnostic and screening agents for the early detection of PD. Moreover, bioengineered exosomes are proposed to be used as drug carriers for targeted delivery of RNA interference molecules across the blood-brain barrier without immune system interference. Overall, this review highlighted the diverse characteristics of ncRNA exosomes, which may aid researchers in characterizing future exosome-based biomarkers for early PD diagnosis and tailored PD medicines.
Serotonergic Neurons in the Brain and Gnathal Ganglion of Larval Spodoptera frugiperda
Authors: Zhang Jia-Jia , Sun Long-Long , Wang Ya-Nan , Xie Gui-Ying , An Shi-Heng , Chen Wen-Bo , Tang Qing-Bo , Zhao Xin-Cheng
Published: March 2022

The fall armyworm Spodoptera frugiperda (S. frugiperda) (Lepidoptera: Noctuidae) is a worldwide, disruptive, agricultural pest species. The larvae of S. frugiperda feed on seedling, leave, and kernel of crops with chewing mouthparts, resulting in reduced crop yields. Serotonin is an important biogenic amine acting as a neural circuit modulator known to mediate lots of behaviors including feeding in insects. In order to explore the serotonergic neural network in the nervous system of larval S. frugiperda, we performed immunohistochemical experiments to examine the neuropil structure of the brain and the gnathal ganglion with antisynapsin and to examine their serotonergic neurons with antiserotonin serum. Our data show that the brain of larval S. frugiperda contains three neuromeres: the tritocerebrum, the deutocerebrum, and the protocerebrum. The gnathal ganglion also contains three neuromeres: the mandibular neuromere, the maxillary neuromere, and the labial neuromere. There are about 40 serotonergic neurons in the brain and about 24 serotonergic neurons in the gnathal ganglion. Most of these neurons are wide-field neurons giving off processes in several neuropils of the brain and the gnathal ganglion. Serotonergic neuron processes are mainly present in the protocerebrum. A pair of serotonergic neurons associated with the deutocerebrum has arborizations in the contralateral antennal lobe and bilateral superior lateral protocerebra. In the gnathal ganglion, the serotonergic neuron processes are also widespread throughout the neuropil and some process projections extend to the tritocerebrum. These findings on the serotonergic neuron network in larval S. frugiperda allow us to explore the important roles of serotonin in feeding and find a potential approach to modulate the feeding behavior of the gluttonous pest and reduce its damage.
Loneliness and Health Indicators in Middle-Aged and Older Females and Males
Authors: Crespo-Sanmiguel Isabel , Zapater-Fajarí Mariola , Garrido-Chaves Ruth , Hidalgo Vanesa , Salvador Alicia
Published: March 2022

Loneliness is a complex and uncomfortable feeling that results from the perception of a lack of desired personal and social ties. Loneliness is accentuated with aging. It has been related to a wide range of objective and subjective health indicators and is a risk factor for morbidity and mortality. One of the proposed underlying mechanisms through which loneliness affects health is the dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. However, the relationship between loneliness and cortisol, the main product of the HPA axis, is unclear and requires more research. The aims of this cross-sectional study were to investigate the relationships between loneliness, subjective health, and cortisol indexes, taking the sex into account, and investigate whether the HPA axis mediates the relationship between loneliness and subjective health. For this purpose, 79 participants (between 55 and 75 years old) completed several scales on loneliness, depression, perceived stress, psychological and physical health, and social relationships. Various salivary cortisol measurements were obtained on two consecutive days. The initial results showed that loneliness was related to psychological and physical health in the mixed-sex sample. However, when covariates were introduced, loneliness was only associated with psychological health in males. In addition, the cortisol indexes employed were not related to loneliness and did not mediate the relationship between loneliness and subjective health. Hence, we did not find a relevant role of the HPA axis in the association between loneliness and subjective health. More severe perceptions of loneliness would probably be necessary to detect this role. Overall, these results also show that the expected negative outcomes of loneliness associated with aging can be countered by an active life that can compensate for the natural losses experienced with age or at least delay these negative outcomes. Finally, some sex differences were found, in line with other studies, which warrants further examination of social variables and dimensions related to gender in future research.
SentiMedQAer: A Transfer Learning-Based Sentiment-Aware Model for Biomedical Question Answering
Authors: Zhu Xian , Chen Yuanyuan , Gu Yueming , Xiao Zhifeng
Published: March 2022

Recent advances have witnessed a trending application of transfer learning in a broad spectrum of natural language processing (NLP) tasks, including question answering (QA). Transfer learning allows a model to inherit domain knowledge obtained from an existing model that has been sufficiently pre-trained. In the biomedical field, most QA datasets are limited by insufficient training examples and the presence of factoid questions. This study proposes a transfer learning-based sentiment-aware model, named SentiMedQAer, for biomedical QA. The proposed method consists of a learning pipeline that utilizes BioBERT to encode text tokens with contextual and domain-specific embeddings, fine-tunes Text-to-Text Transfer Transformer (T5), and RoBERTa models to integrate sentiment information into the model, and trains an XGBoost classifier to output a confidence score to determine the final answer to the question. We validate SentiMedQAer on PubMedQA, a biomedical QA dataset with reasoning-required yes/no questions. Results show that our method outperforms the SOTA by 15.83% and a single human annotator by 5.91%.
Designing Prosthetic Hands With Embodied Intelligence: The KIT Prosthetic Hands
Authors: Weiner Pascal , Starke Julia , Rader Samuel , Hundhausen Felix , Asfour Tamim
Published: March 2022

Hand prostheses should provide functional replacements of lost hands. Yet current prosthetic hands often are not intuitive to control and easy to use by amputees. Commercially available prostheses are usually controlled based on EMG signals triggered by the user to perform grasping tasks. Such EMG-based control requires long training and depends heavily on the robustness of the EMG signals. Our goal is to develop prosthetic hands with semi-autonomous grasping abilities that lead to more intuitive control by the user. In this paper, we present the development of prosthetic hands that enable such abilities as first results toward this goal. The developed prostheses provide intelligent mechatronics including adaptive actuation, multi-modal sensing and on-board computing resources to enable autonomous and intuitive control. The hands are scalable in size and based on an underactuated mechanism which allows the adaptation of grasps to the shape of arbitrary objects. They integrate a multi-modal sensor system including a camera and in the newest version a distance sensor and IMU. A resource-aware embedded system for in-hand processing of sensory data and control is included in the palm of each hand. We describe the design of the new version of the hands, the female hand prosthesis with a weight of 377 g, a grasping force of 40.5 N and closing time of 0.73 s. We evaluate the mechatronics of the hand, its grasping abilities based on the YCB Gripper Assessment Protocol as well as a task-oriented protocol for assessing the hand performance in activities of daily living. Further, we exemplarily show the suitability of the multi-modal sensor system for sensory-based, semi-autonomous grasping in daily life activities. The evaluation demonstrates the merit of the hand concept, its sensor and in-hand computing systems.
Microglia-Specific Promoter Activities of HEXB Gene
Authors: Shah Sahil , Wong Lilly M. , Ellis Kendra , Bodnar Brittany , Saribas Sami , Ting Julia , Wei Zhengyu , Tang Yuyang , Wang Xianwei , Wang Hong , Ling Binhua , Margolis David M. , Garcia J. Victor , Hu Wenhui , Jiang Guochun
Published: March 2022

Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5’ untranslated region (−97 bp related to the first ATG) in driving transcriptional activity of the mouse Hexb gene. The native promoter region of mouse, human, and monkey HEXB are located at −135, −134, and −170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS.
Histone Acetylation and Methylation Underlie Oligodendroglial and Myelin Susceptibility in Schizophrenia
Authors: Li Mei , Xiao Lan , Chen Xianjun
Published: March 2022

Schizophrenia is a complex neuropsychiatric disorder affected by both genetic and epigenetic factors. Except for neuronal dysfunction, oligodendroglial abnormalities also contribute to the disease pathogenesis, characterized by a robust dysregulation of oligodendrocyte and myelin related genes. Accumulating evidence shows that histone modifications play important roles in transcriptional regulation of the genes crucial for oligodendrocyte differentiation and myelination. Specifically, the histone acetylation and methylation were two well-recognized histone modification abnormalities in the schizophrenic brains. In this mini-review, we will describe the dynamic changes of histone acetylation and methylation in schizophrenia, which may coordinate and induce deleterious epigenetic memory in oligodendroglial cells, and further lead to oligodendrocyte and myelin deficits. Precise modulation of histone modification status in oligodendroglial cells needs to secure the balance of epigenetic marks, which may revise the therapeutic strategy for the white matter etiology of neuropsychiatric disorders.
White Matter Abnormalities and Cognitive Deficit After Mild Traumatic Brain Injury: Comparing DTI, DKI, and NODDI
Authors: Huang Sihong , Huang Chuxin , Li Mengjun , Zhang Huiting , Liu Jun
Published: March 2022

White matter (WM) disruption is an important determinant of cognitive impairment after mild traumatic brain injury (mTBI), but traditional diffusion tensor imaging (DTI) shows some limitations in assessing WM damage. Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) show advantages over DTI in this respect. Therefore, we used these three diffusion models to investigate complex WM changes in the acute stage after mTBI. From 32 mTBI patients and 31 age-, sex-, and education-matched healthy controls, we calculated eight diffusion metrics based on DTI (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), DKI (mean kurtosis), and NODDI (orientation dispersion index, volume fraction of intracellular water (Vic), and volume fraction of the isotropic diffusion compartment). We used tract-based spatial statistics to identify group differences at the voxel level, and we then assessed the correlation between diffusion metrics and cognitive function. We also performed subgroup comparisons based on loss of consciousness. Patients showed WM abnormalities and cognitive deficit. And these two changes showed positive correlation. The correlation between Vic of the splenium of the corpus callosum and Digit Symbol Substitution Test scores showed the smallest p-value (p = 0.000, r = 0.481). We concluded that WM changes, especially in the splenium of the corpus callosum, correlate to cognitive deficit in this study. Furthermore, the high voxel count of NODDI results and the consistency of mean kurtosis and the volume fraction of intracellular water in previous studies and our study showed the functional complementarity of DKI and NODDI to DTI.
Impaired Color Recognition in HCN1 Epilepsy: A Single Case Report
Authors: Mckenzie Chaseley E. , Ho Chen-Jui , Forster Ian C. , Soh Ming S. , Phillips A. Marie , Chang Ying-Chao , Scheffer Ingrid E. , Reid Christopher A. , Tsai Meng-Han
Published: March 2022

Variants in HCN1 are associated with a range of epilepsy syndromes including developmental and epileptic encephalopathies. Here we describe a child harboring a novel de novo HCN1 variant, E246A, in a child with epilepsy and mild developmental delay. By parental report, the child had difficulty in discriminating between colors implicating a visual deficit. This interesting observation may relate to the high expression of HCN1 channels in rod and cone photoreceptors where they play an integral role in shaping the light response. Functional analysis of the HCN1 E246A variant revealed a right shift in the voltage dependence of activation and slowing of the rates of activation and deactivation. The changes in the biophysical properties are consistent with a gain-of-function supporting the role of HCN1 E246A in disease causation. This case suggests that visual function, including color discrimination, should be carefully monitored in patients with diseases due to HCN1 pathogenic variants.
Generalized Fast Discharges Along the Genetic Generalized Epilepsy Spectrum: Clinical and Prognostic Significance
Authors: Cerulli Irelli Emanuele , Barone Francesca Antonietta , Mari Luisa , Morano Alessandra , Orlando Biagio , Salamone Enrico Michele , Marchi Angela , Fanella Martina , Fattouch Jinane , Placidi Fabio , Giallonardo Anna Teresa , Izzi Francesca , Di Bonaventura Carlo
Published: March 2022

Objective

To investigate the electroclinical characteristics and the prognostic impact of generalized fast discharges in a large cohort of genetic generalized epilepsy (GGE) patients studied with 24-h prolonged ambulatory electroencephalography (paEEG).

Methods

This retrospective multicenter cohort study included 202 GGE patients. The occurrence of generalized paroxysmal fast activity (GPFA) and generalized polyspike train (GPT) was reviewed. GGE patients were classified as having idiopathic generalized epilepsy (IGE) or another GGE syndrome (namely perioral myoclonia with absences, eyelid myoclonia with absences, epilepsy with myoclonic absences, generalized epilepsy with febrile seizures plus, or GGE without a specific epilepsy syndrome) according to recent classification proposals.

Results

GPFA/GPT was found in overall 25 (12.4%) patients, though it was significantly less frequent in IGE compared with other GGE syndromes (9.3 vs. 25%,p= 0.007). GPFA/GPT was found independently of seizure type experienced during history, the presence of mild intellectual disability/borderline intellectual functioning, or EEG features. At multivariable analysis, GPFA/GPT was significantly associated with drug resistance (p= 0.04) and with a higher number of antiseizure medications (ASMs) at the time of paEEG (p< 0.001) and at the last medical observation (p< 0.001). Similarly, GPFA/GPT, frequent/abundant generalized spike-wave discharges during sleep, and a higher number of seizure types during history were the only factors independently associated with a lower chance of achieving 2-year seizure remission at the last medical observation. Additionally, a greater number of GPFA/GPT discharges significantly discriminated between patients who achieved 2-year seizure remission at the last medical observation and those who did not (area under the curve = 0.77, 95% confidence interval 0.57–0.97,p= 0.02)

Conclusion

We found that generalized fast discharges were more common than expected in GGE patients when considering the entire GGE spectrum. In addition, our study highlighted that GPFA/GPT could be found along the entire GGE continuum, though their occurrence was more common in less benign GGE syndromes. Finally, we confirmed that GPFA/GPT was associated with difficult-to-treat GGE, as evidenced by the multivariable analysis and the higher ASM load during history.
Pacemaker Implantation in Juvenile Neuronal Ceroid Lipofuscinosis (CLN3)–A Long-Term Follow-Up Study
Authors: Handrup Mette Møller , Mølgaard Henning , Andersen Brian N. , Ostergaard John R.
Published: March 2022

It is well documented that deteriorating heart function due to deposition of ceroid lipopigment is a significant co-morbidity in Juvenile Neuronal Ceroid Lipofuscinosis (CLN3 disease) although the exact disease mechanisms remain unknown in any NCL form. An increasing frequency of cardiac conduction disorders including severe bradycardia and sinus arrest is seen in the late teens, as is a left ventricular hypertrophy in the early 20s. Only a few case reports of pacemaker implantation have been published, and so far, no long-term follow-up study exists. As new treatment options emerge, more patients will live longer and the need for pacemaker will likely increase, why knowledge of long-term outcome is needed. In the present study, we present the course of six patients from the original Danish CLN3-heart population study (n = 29) published in 2011 in whom pacemaker implantation was indicated from a cardiac point of view. In two cases, the families deselected pacemaker implantation. In four males, aged 19-29 years, all having a good general condition, a dual-chamber pacemaker (St. Jude Medical™ Accent/Assurity MRI™) was implanted in general anesthesia without any complications. At follow-up 9 years later, three were still alive. According to the parents' opinion they still have a good quality of life, now 26, 30, and 36 years old. Pacemaker treatment is safe and may have great impact on quality of life. However, the medical indication for pacemaker treatment is relative and it is important that various aspects, including the patient's general condition and family preferences, are thoroughly discussed before making the final decision.