bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-coding RNAs Regulate the Pathogenesis of Aortic Dissection
Authors: Hu Yu-Yuan , Cheng Xin-Meng , Wu Nan , Tao Yang , Wang Xue-Ning
Published: April 2022

Aortic dissection (AD) is a fatal cardiovascular disease. It is caused by a rupture of the aortic intima or bleeding of the aortic wall that leads to the separation of different aortic wall layers. Patients with untreated AD have a mortality rate of 1–2% per hour after symptom onset. Therefore, effective biomarkers and therapeutic targets are needed to reduce AD-associated mortality. With the development of molecular technology, researchers have begun to explore the pathogenesis of AD at gene and protein levels, and have made some progress, but the pathogenesis of AD remains unclear. Non-coding RNAs, such as microRNAs, lncRNAs, and circRNAs, have been identified as basic regulators of gene expression and are found to play a key role in the pathogenesis of AD. Thus, providing a theoretical basis for developing these non-coding RNAs as clinical biomarkers and new therapeutic targets for AD in the future. Previous studies on the pathogenesis of AD focused on miRNAs, but recently, there have been an increasing number of studies that explore the role of lncRNAs, and circRNAs in AD. This review summarizes the existing knowledge on the roles of various non-coding RNAs in the pathogenesis of AD, discusses their potential role as clinical biomarkers and therapeutic targets, states the limitations of existing evidence, and recommends future avenues of research on the pathogenesis of AD.
Dendrochronology of Ancient Pine Trunks Exposed at the Coastal Bluff: Dating Problems and Possible Causes
Authors: Zunde Māris
Published: April 2022

Coastal erosion and slumping of the coastal bluff occur at the present day along certain stretches of the Baltic Sea coastal belt in western Latvia. The coast currently being eroded is regarded as consisting partly of a cover of wind-blown sand formed 250–300 years ago, a period that saw intensive landward aeolian sand transport as a result of forest cutting and forest fires in the coastal belt and other factors relating to human activity. Within the frame of a short-term research project, dendrochronological dating work was undertaken on remnants of pine trunks discovered at various locations on the coastal bluff that appeared to be remains of ancient trees exposed by erosion, with the aim of determining where and when these natural processes had occurred. This study did not succeed in demonstrating dendrochronologically that the apparently ancient tree trunk remnants observable along certain stretches of the coast at the present day are remains of pines buried by sand more than 250 years ago. It has been established that certain of these are remnants of pines that died in the 20th century or even just a few years ago, but in the majority of cases an unambiguous old date could not be obtained. In order to ascertain the possible reasons why dendro-dating had produced such limited results, in the further part of the study a comparison was undertaken of the patterns of variation in annual radial trunk growth of pines growing in the dune belt along the whole of the Latvian seaboard at the present day. Also considered are the previous findings of short-term studies in all three Baltic States concerning the influence of specific environmental factors on the radial growth of pine. It has been established that the reasons why dendro-dating was problematic relate to the specific character and variation in the environmental factors significantly affecting tree growth, as well as the slope processes on the coastal bluffs. It is envisaged that the findings obtained and brought together in this study will be useful in future, when undertaking or planning dendro-dating work for the purpose of tracing the history of dune migration or assessing the radial growth of pines growing in dunes.
Range Size and Niche Breadth as Predictors of Climate-Induced Habitat Change in Epipactis (Orchidaceae)
Authors: Evans Alexandra , Jacquemyn Hans
Published: April 2022

While there is mounting evidence that ongoing changes in the climate system are shifting species ranges poleward and to higher altitudes, responses to climate change vary considerably between species. In general, it can be expected that species responses to climate change largely depend on how broad their ecological niches are, but evidence is still scant. In this study, we investigated the effects of predicted future climate change on the availability of suitable habitat for 14 Epipactis (Orchidaceae) species, and tested whether habitat specialists would experience greater changes in the extent of their habitats than habitat generalists. We used Maxent to model the ecological niche of each species in terms of climate, soil, elevation and land-use and projected it onto climate scenarios predicted for 2061–2080. To test the hypothesis that temperate terrestrial orchid species with small ranges or small niche breadths may be at greater risk under climate change than species with wide ranges or large niche breadths, we related niche breadth in both geographic and environmental space to changes in size and location of suitable habitat. The habitat distributions of half of the species shifted northwards in future projections. The area of suitable habitat increased for eight species but decreased for the remaining six species. If expansion at the leading edge of the distribution was not possible, the area of suitable habitat decreased for 12 species. Species with wide niche breadth in geographic space experienced greater northwards expansions and higher habitat suitability scores than species with small niche breadth. Niche breadth in environmental space was not significantly related to change in habitat distribution. Overall, these results indicate that terrestrial orchid species with a wide distribution will be more capable of shifting their distributions under climate change than species with a limited distribution, but only if they are fully able to expand into habitats at the leading edge of their distributions.
Age-Related Changes in Culm Respiration of Phyllostachys pubescens Culms With Their Anatomical and Morphological Traits
Authors: Uchida Eiko M. , Katayama Ayumi , Yasuda Yuko , Enoki Tsutomu , Otsuki Kyoichi , Koga Shinya , Utsumi Yasuhiro
Published: April 2022

Compared to trees, little is known about the respiratory characteristics of bamboo, especially culm respiration. In this study, we measured the respiration rates of current year, 2, 3, and above 4-year-old Moso bamboo (Phyllostachys pubescens) culms and examined its relation to culm morphology and anatomical structure. Current year culms had substantially higher respiration rates (1.9 ± 0.46 μmol m–2 s–1) compared to older culms (2, 3, and above 4-year-old average: 0.17 ± 0.09 μmol m–2 s–1). Culm wood density increased with age, with the concurrent thickening of parenchyma cell walls in the culm tissue. Nitrogen content in the culm tissue decreased with culm age. Both culm wood density and nitrogen content had significant relationships with culm respiration rate. On the other hand, culm height, wall thickness, and circumference did not affect culm respiration rate. Although bamboo culms did not change in size through the year, anatomical changes in the culm tissue that accompanied the aging of a culm affected the respiration. The culm age would have a significant effect on the evaluation of the respiratory characteristics of the bamboo forest. Our results suggested that young culms required a large amount of respiration to grow “inward” as cell wall thickening and also to maintain the relatively large amount of active tissue.
Molecular Imaging of Aortic Aneurysm and Its Translational Power for Clinical Risk Assessment
Authors: Rastogi Vinamr , Stefens Sanne J. M. , Houwaart Judith , Verhagen Hence J. M. , de Bruin Jorg L. , van der Pluijm Ingrid , Essers Jeroen
Published: April 2022

Aortic aneurysms (AAs) are dilations of the aorta, that are often fatal upon rupture. Diagnostic radiological techniques such as ultrasound (US), magnetic resonance imaging (MRI), and computed tomography (CT) are currently used in clinical practice for early diagnosis as well as clinical follow-up for preemptive surgery of AA and prevention of rupture. However, the contemporary imaging-based risk prediction of aneurysm enlargement or life-threatening aneurysm-rupture remains limited as these are restricted to visual parameters which fail to provide a personalized risk assessment. Therefore, new insights into early diagnostic approaches to detect AA and therefore to prevent aneurysm-rupture are crucial. Multiple new techniques are developed to obtain a more accurate understanding of the biological processes and pathological alterations at a (micro)structural and molecular level of aortic degeneration. Advanced anatomical imaging combined with molecular imaging, such as molecular MRI, or positron emission tomography (PET)/CT provides novel diagnostic approaches for in vivo visualization of targeted biomarkers. This will aid in the understanding of aortic aneurysm disease pathogenesis and insight into the pathways involved, and will thus facilitate early diagnostic analysis of aneurysmal disease. In this study, we reviewed these molecular imaging modalities and their association with aneurysm growth and/or rupture risk and their limitations. Furthermore, we outline recent pre-clinical and clinical developments in molecular imaging of AA and provide future perspectives based on the advancements made within the field. Within the vastness of pre-clinical markers that have been studied in mice, molecular imaging targets such as elastin/collagen, albumin, matrix metalloproteinases and immune cells demonstrate promising results regarding rupture risk assessment within the pre-clinical setting. Subsequently, these markers hold potential as a future diagnosticum of clinical AA assessment. However currently, clinical translation of molecular imaging is still at the onset. Future human trials are required to assess the effectivity of potentially viable molecular markers with various imaging modalities for clinical rupture risk assessment.
Clinical Characteristics, Laboratory Findings, and Prognosis in Patients With Talaromyces marneffei Infection Across Various Immune Statuses
Authors: Li Dianwu , Liang Huaying , Zhu Yiqun , Chang Qinyu , Pan Pinhua , Zhang Yan
Published: April 2022

Objective

Talaromyces marneffei (TM) is an opportunistic fungus that is predominantly prevalent among patients who are HIV-positive in South-East Asia. However, few studies focused on the clinical features, laboratory findings, and prognosis across varying immune states.

Methods

A total of 54 patients with TM infection in Xiangya Hospital of Central South University from January 1, 2006 to October 31, 2021 were retrospectively analyzed. Clinical profiles were compared across the different immune statuses by HIV-positive (HIV group, n = 18), HIV negative but with immunocompromised conditions (Non-HIV with IC Group, n = 11), and immunocompetent patients (n = 25).

Results

All the patients were diagnosed by pathogen culture or by metagenomic next-generation sequencing (mNGS). The median age was 50, and patients with HIV were much younger compared to the other two groups. The most common symptom at presentation was fever (79.6%), followed by cough (70.4%), weight loss (61.1%), and expectoration (53.7%). The patients with HIV were more likely to develop into a subtype of disseminated TM affecting multiple organs including lymph node, liver, skin, and spleen, thus, resulting in higher hospital mortality compared to the other two groups. Patients without HIV but with immunocompromised conditions presented similar hospital mortality rates compared to immunocompetent patients, while experiencing longer days of hospitalization to recover from the diseases. Additionally, in this study, the pathogen culture easily confirmed the patients with HIV. However, mNGS presented as a promising tool to confirm TM infection in those suspicious patients without HIV.

Conclusions

In summary, patients with HIV were more likely to develop into disseminated TM, resulting in higher mortality compared to those patients without HIV. Additionally, mNGS presented as an important supplementary tool to confirm TM infection in patients without HIV, particularly in those with immunocompromised diseases.
The Effect of Chinese Medicinal Formulas on Biomarkers of Oxidative Stress in STZ-Induced Diabetic Kidney Disease Rats: A Meta-Analysis and Systematic Review
Authors: Zhou Qian , Han Chuyi , Wang Yanmei , Fu Shunlian , Chen Yiding , Chen Qiu
Published: April 2022

Background

Diabetic kidney disease (DKD), defined broadly as persistent proteinuria with low estimated glomerular filtration rate in patients with diabetes, is a main cause of end-stage renal disease. Excessive production of reactive oxygen species is an important mechanism underlying the pathogenesis of DKD and many antioxidants have been investigated as therapeutic agents. Among them, Chinese medicine antioxidative stress therapies have been widely used to combat DKD, which may offer new insights into therapeutic development of DKD. There are several discrepancies among the efficacy of Western medicine (WM) and Chinese medicinal formula (CMF) action.

Methods

We searched PubMed, Cochrane Library, the Web of Science databases, Embase, and Scopus from inception to December 2021 using relevant keywords and a comprehensive search for randomized controlled trials (RCTs) was performed. Calculating the pooled weighted mean difference (MD) and 95% CI by the method of inverse-variance with a random-effect. All the related statistical analyses were performed using Stata version 15.1 software (Stata Corporation) and Rvman version 5.3 (Nordic Cochrane Center).

Results

A total of 8 articles with the 9 groups including 106 in the model group, 105 in the CMF group, and 99 in the WM group. Pooled data from 8 studies (9 groups) showed a statistical improvement in superoxide dismutase compared with the model group [standardized MD (SMD) = 1.57; 95 CI: 1.16–1.98; P < 0.05] and the WM group (SMD = 0.56; 95 CI: 0.19–0.92; P < 0.05). For glutathione peroxidase (GSH-Px), it was significantly improved in the CMF group vs. the model group and the WM group. For malondialdehyde (MDA), it was significantly reduced in the CMF group (CMF vs. model group: SMD = −1.52; 95 CI: −1.88 −1.17; P < 0.05; CMF vs. WM group: SMD = −0.64; 95 CI: −0.95 −0.33; P < 0.05).

Conclusion

This systematic review and meta-analysis have demonstrated that the therapy of CMF had a notable curative effect on relieving oxidative stress in STZ-induced DKD rats and CMF was significantly more effective than the WM control group. For the clinical application, the results providing confidence and some theoretical reference for DKD via evaluating the efficacy of CMF to a certain extent.

Systematic Review Registration

[PROSPERO], identifier [CRD42022313737].
Clinicopathological and Prognostic Significance of Stromal Patterns in Oral Squamous Cell Carcinoma
Authors: Amano Yusuke , Kihara Atsushi , Hasegawa Masayo , Miura Tamaki , Matsubara Daisuke , Fukushima Noriyoshi , Nishino Hiroshi , Mori Yoshiyuki , Niki Toshiro
Published: April 2022

Background

Stromal patterns (SP), especially desmoplastic reactions, have recently gained attention as indicators of malignant potential in cancer. In this study, we explored the clinicopathological and prognostic significance of the SP in oral squamous cell carcinoma (OSCC).

Materials and Methods

We reviewed 232 cases of surgically resected OSCC that were not treated with neoadjuvant chemoradiotherapy. We categorized the SP of the OSCC into four groups: immune/inflammatory (84 cases), mature (14 cases), intermediate (78 cases), or immature (56 cases).

Results

The SP category was significantly associated with various clinicopathological factors, such as the histological grade, lymphovascular invasion, neural invasion, and a diffuse invasion pattern. For each of the factors, the immune/inflammatory type was associated with favorable categories, while the immature type was associated with unfavorable categories (p ≤ 0.001). The SP category was also shown to be a prognostic predictor: the 5-year relapse-free survival (RFS) rate was 72.0% for the immune/inflammatory type, 66.7% for the intermediate/mature type, and 31.2% for the immature type (p < 0.0001), and the 5-year overall survival (OS) rate was 85.1% for the immune/inflammatory type, 76.4% for the intermediate/mature type, and 50.0% for the immature type (p < 0.0001). In multivariate analyses, the SP category was identified as an independent prognostic factor for RFS and OS.

Conclusion

Our SP categorization method provides valuable prognostic information in OSCC.
Deep Learning-Powered Prediction of Human-Virus Protein-Protein Interactions
Authors: Yang Xiaodi , Yang Shiping , Ren Panyu , Wuchty Stefan , Zhang Ziding
Published: April 2022

Identifying human-virus protein-protein interactions (PPIs) is an essential step for understanding viral infection mechanisms and antiviral response of the human host. Recent advances in high-throughput experimental techniques enable the significant accumulation of human-virus PPI data, which have further fueled the development of machine learning-based human-virus PPI prediction methods. Emerging as a very promising method to predict human-virus PPIs, deep learning shows the powerful ability to integrate large-scale datasets, learn complex sequence-structure relationships of proteins and convert the learned patterns into final prediction models with high accuracy. Focusing on the recent progresses of deep learning-powered human-virus PPI predictions, we review technical details of these newly developed methods, including dataset preparation, deep learning architectures, feature engineering, and performance assessment. Moreover, we discuss the current challenges and potential solutions and provide future perspectives of human-virus PPI prediction in the coming post-AlphaFold2 era.
An Alliance of Trifolium repens—Rhizobium leguminosarum bv. trifolii—Mycorrhizal Fungi From an Old Zn-Pb-Cd Rich Waste Heap as a Promising Tripartite System for Phytostabilization of Metal Polluted Soils
Authors: Oleńska Ewa , Małek Wanda , Sujkowska-Rybkowska Marzena , Szopa Sebastian , Włostowski Tadeusz , Aleksandrowicz Olgierd , Swiecicka Izabela , Wójcik Małgorzata , Thijs Sofie , Vangronsveld Jaco
Published: April 2022

The Bolesław waste heap in South Poland, with total soil Zn concentrations higher than 50,000 mg kg–1, 5,000 mg Pb kg–1, and 500 mg Cd kg–1, is a unique habitat for metallicolous plants, such as Trifolium repens L. The purpose of this study was to characterize the association between T. repens and its microbial symbionts, i.e., Rhizobium leguminosarum bv. trifolii and mycorrhizal fungi and to evaluate its applicability for phytostabilization of metal-polluted soils. Rhizobia originating from the nutrient-poor waste heap area showed to be efficient in plant nodulation and nitrogen fixation. They demonstrated not only potential plant growth promotion traits in vitro, but they also improved the growth of T. repens plants to a similar extent as strains from a non-polluted reference area. Our results revealed that the adaptations of T. repens to high Zn-Pb-Cd concentrations are related to the storage of metals predominantly in the roots (excluder strategy) due to nodule apoplast modifications (i.e., thickening and suberization of cell walls, vacuolar storage), and symbiosis with arbuscular mycorrhizal fungi of a substantial genetic diversity. As a result, the rhizobia-mycorrhizal fungi-T. repens association appears to be a promising tool for phytostabilization of Zn-Pb-Cd-polluted soils.
The Mycoplasma spp. ‘Releasome’: A New Concept for a Long-Known Phenomenon
Authors: Gaurivaud Patrice , Tardy Florence
Published: April 2022

The bacterial secretome comprises polypeptides expressed at the cell surface or released into the extracellular environment as well as the corresponding secretion machineries. Despite their reduced coding capacities, Mycoplasma spp. are able to produce and release several components into their environment, including polypeptides, exopolysaccharides and extracellular vesicles. Technical difficulties in purifying these elements from the complex broth media used to grow mycoplasmas have recently been overcome by optimizing growth conditions and switching to chemically defined culture media. However, the secretion pathways responsible for the release of these structurally varied elements are still poorly described in mycoplasmas. We propose the use of the term ‘releasome,’ instead of secretome, to refer to molecules released by mycoplasmas into their environment. The aim of this review is to more precisely delineate the elements that should be considered part of the mycoplasmal releasome and their role in the interplay of mycoplasmas with host cells and tissues.
Beneficial Alteration in Growth Performance, Immune Status, and Intestinal Microbiota by Supplementation of Activated Charcoal-Herb Extractum Complex in Broilers
Authors: Wang Lixue , Zhang Ying , Guo Xiangyue , Gong Limin , Dong Bing
Published: April 2022

This study aimed to examine the effects of activated charcoal-herb extractum complex (CHC) on the growth performance of broilers, inflammatory status, microbiota, and their relationships. A total of 864 1-day-old Arbor Acres male broilers (41.83 ± 0.64 g) were distributed to eight dietary treatments with six replicates (18 birds per replicate), which were a corn-soybean meal-based diet (NCON); basal diets supplemented with 250, 500, 750, or 1,000 mg/kg CHC, and three positive controls; basal diets supplemented with 200 mg/kg antibacterial peptide (AMP), 200 mg/kg calsporin (Probio) or 500 mg/kg montmorillonite. The study period was 42 days including the starter (day 0–21) and grower (day 22–42) phases. Compared with the NCON group, CHC supplementation (optimal dose of 500 mg/kg) increased (p < 0.05) growth performance and tended to increase feed conversion rate in broilers. CHC (optimal dose of 500 mg/kg) decreased the level of the interleukin-1β (IL-1β) and interferon-γ (IFN-γ) in serum and improved the levels of immunoglobulins A (IgA) and immunoglobulins A (IgM) in serum, and secretory immunoglobulin A (SIgA) in the mucosa of duodenum and jejunum (p < 0.05). In the ileum, CHC supplementation decreased community abundance represented by lower Sobs, Chao 1, Ace, and Shannon compared with NCON (p < 0.05). At the phylum level, CHC supplementation increased the abundance of Firmicutes, while decreasing the abundance of Bacteroidetes in ileum and cecum (p < 0.05). At the genus level, compared with the NCON group, CHC markedly reduced (p < 0.05) the abundances of pathogenic bacteria Alistipes in the ileum, which were negatively associated with the levels of SIgA and IL-1β in ileum mucosa. In conclusion, CHC had beneficial effects on growth performance, immune status, and intestinal microbiota composition. CHC had dual functions of absorption like clays and antibacterial like antibacterial peptides.
Assessing the Mobility of Severe Acute Respiratory Syndrome Coronavirus-2 Spike Protein Glycans by Structural and Computational Methods
Authors: Stagnoli Soledad , Peccati Francesca , Connell Sean R. , Martinez-Castillo Ane , Charro Diego , Millet Oscar , Bruzzone Chiara , Palazon Asis , Ardá Ana , Jiménez-Barbero Jesús , Ereño-Orbea June , Abrescia Nicola G. A. , Jiménez-Osés Gonzalo
Published: April 2022

Two years after its emergence, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several vaccines. The extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates host cell entry by binding to the angiotensin converting enzyme 2 (ACE2) through its receptor binding domain (RBD), is the major target of neutralizing antibodies. Like to many other viral fusion proteins, the SARS-CoV-2 spike protein utilizes a glycan shield to thwart the host immune response. To grasp the influence of chemical signatures on carbohydrate mobility and reconcile the cryo-EM density of specific glycans we combined our cryo-EM map of the S ectodomain to 4.1 Å resolution, reconstructed from a limited number of particles, and all-atom molecular dynamics simulations. Chemical modifications modeled on representative glycans (defucosylation, sialylation and addition of terminal LacNAc units) show no significant influence on either protein shielding or glycan flexibility. By estimating at selected sites the local correlation between the full density map and atomic model-based maps derived from molecular dynamics simulations, we provide insight into the geometries of the α-Man-(1→3)-[α-Man-(1→6)-]-β-Man-(1→4)-β-GlcNAc(1→4)-β-GlcNAc core common to all N-glycosylation sites.
Alterations of Striatal Subregions in a Prion Protein Gene V180I Mutation Carrier Presented as Frontotemporal Dementia With Parkinsonism
Authors: Chen Zhongyun , Ma Jinghong , Liu Li , Liu Shuying , Zhang Jing , Chu Min , Wang Zhen , Chan Piu , Wu Liyong
Published: April 2022

Objective

To explore the roles of striatal subdivisions in the pathogenesis of frontotemporal dementia with parkinsonism (FTDP) in a patient resulting from prion protein gene (PRNP) mutation.

Methods

This patient received clinical interviews and underwent neuropsychological assessments, genetic testing, [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET)/MRI, and [18F]-dihydrotetrabenazine positron emission tomography ([18F]-DTBZ PET)/CT. Region-of-interest analysis was conducted concerning metabolism, and dopamine transport function between this patient and 12 controls, focusing on the striatum subregions according to the Oxford-GSK-Imanova Striatal Connectivity Atlas.

Results

A 64-year-old man initially presented with symptoms of motor dysfunction and subsequently behavioral and personality changes. FTDP was initially suspected. Sequence analysis disclosed a valine to isoleucine at codon 180 in PRNP. Compared to controls, this patient had a severe reduction (> 2SD) of standard uptake value ratio (SUVR) in the limbic and executive subregions but relative retention of metabolism in rostral motor and caudal motor subregions using [18F]-FDG PET/MRI, and the SUVR decreased significantly across the striatal in [18F]-DTBZ PET/CT, especially in the rostral motor and caudal motor subregions.

Conclusion

The alteration of frontal striatal loops may be involved in cognitive impairment in FTDP, and the development of parkinsonism in FTDP may be primarily due to the involvement of the presynaptic nigrostriatal loops in PRNP V180I mutation.
The Impact of Genes and Environment on Brain Ageing in Males Aged 51 to 72 Years
Authors: Gillespie Nathan A. , Hatton Sean N. , Hagler Donald J. , Dale Anders M. , Elman Jeremy A. , McEvoy Linda K. , Eyler Lisa T. , Fennema-Notestine Christine , Logue Mark W. , McKenzie Ruth E. , Puckett Olivia K. , Tu Xin M. , Whitsel Nathan , Xian Hong , Reynolds Chandra A. , Panizzon Matthew S. , Lyons Michael J. , Neale Michael C. , Kremen William S. , Franz Carol
Published: April 2022

Magnetic resonance imaging data are being used in statistical models to predicted brain ageing (PBA) and as biomarkers for neurodegenerative diseases such as Alzheimer’s Disease. Despite their increasing application, the genetic and environmental etiology of global PBA indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 51–72 years. Biometrical genetic analyses “twin models” revealed significant and highly correlated estimates of additive genetic heritability ranging from 59 to 75%. Multivariate longitudinal modeling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences.
Estrogen, the Peripheral Immune System and Major Depression – A Reproductive Lifespan Perspective
Authors: Engler-Chiurazzi Elizabeth B. , Chastain Wesley H. , Citron Kailen K. , Lambert Lillian E. , Kikkeri Divya N. , Shrestha Sharhana S.
Published: April 2022

Major depression is a significant medical issue impacting millions of individuals worldwide. Identifying factors contributing to its manifestation has been a subject of intense investigation for decades and several targets have emerged including sex hormones and the immune system. Indeed, an extensive body of literature has demonstrated that sex hormones play a critical role in modulating brain function and impacting mental health, especially among female organisms. Emerging findings also indicate an inflammatory etiology of major depression, revealing new opportunities to supplement, or even supersede, currently available pharmacological interventions in some patient populations. Given the established sex differences in immunity and the profound impact of fluctuations of sex hormone levels on the immune system within the female, interrogating how the endocrine, nervous, and immune systems converge to impact women’s mental health is warranted. Here, we review the impacts of endogenous estrogens as well as exogenously administered estrogen-containing therapies on affect and immunity and discuss these observations in the context of distinct reproductive milestones across the female lifespan. A theoretical framework and important considerations for additional study in regards to mental health and major depression are provided.
Effects of Rhythmic Auditory Stimulation on Gait and Motor Function in Parkinson's Disease: A Systematic Review and Meta-Analysis of Clinical Randomized Controlled Studies
Authors: Wang Lei , Peng Jin-lin , Ou-Yang Jian-bin , Gan Li , Zeng Shuai , Wang Hong-Yan , Zuo Guan-Chao , Qiu Ling
Published: April 2022

Objective

This study aimed to summarize the effectiveness of rhythmic auditory stimulation (RAS) for the treatment of gait and motor function in Parkinson's disease (PD) through a systematic review and meta-analysis.

Methods

All studies were retrieved from eight databases. The effects of RAS on PD were determined using the following indicators: gait parameters including step length, stride width, step cadence, velocity, stride length; motor function including 6 min walk test (6MWT) and timed up-and-go test (TUGT); the Unified Parkinson's Disease Rating Scale (UPDRS); and the Berg Balance Scale (BBS). The risk map of bias of the quality of the studies and the meta-analysis results of the indicators was prepared with RevMan 5.2 software.

Results

Twenty-one studies were included in the systematic review, and 14 studies were included in the meta-analysis. In the meta-analysis, the results of gait parameters, namely, velocity, step length, and stride length, were statistically significant (P < 0.05), whereas the results of cadence and stride width were not statistically significant (P ≧ 0.05). The results of 6MWT and TUGT for motor function as well as UPDRS-II, UPDRS-III, and BBS were statistically significant (P < 0.05).

Conclusions

RAS could improve gait parameters, walking function, balance function, and daily living activities of individuals with PD. The application of RAS in conventional rehabilitation approaches can enhance motor performance in PD. Future studies should use a large sample size and a rigorous design to obtain strong conclusions about the advantages of RAS for the treatment of gait and motor function in PD.
Creutzfeldt-Jakob Disease: Alterations of Gut Microbiota
Authors: Guo Yanjun , Xu Yichen , Lin Xue , Zhen Zhen , Yi Fang , Guan Hongzhi , Shi Qi , Sun Wenjie , Yang Anchao , Dong Xiaoping , Wang Jiawei
Published: April 2022

Introduction

Human gut dysbiosis has been implicated with the onset of many neurodegenerative disorders. However, the current data focused on the gut microbiota of patients with Creutzfeldt-Jakob disease (CJD) are still lacking. In our study, we explored the gut microbiota alteration in patients with CJD.

Method

We performed 16S ribosomal RNA MiSeq sequencing in stool samples of patients with CJD and controls. Functional analysis of the gut microbiota between these two groups was based on Kyoto Encyclopedia of Genes and Genomes and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. Clinical rating scales were used to evaluate the association between cognitive impairment and gut microbiota alteration.

Result

We identified a significant alteration in both the structure and the richness of the CJD group. Function analysis revealed that the gut microbiota of patients with CJD enriched in immune signaling molecule interactions and xenobiotics biodegradation. MoCA and survival times were found to be associated with gut microbiota in patients with CJD.

Conclusion

We demonstrated an altered gut microbiota in patients with CJD, which was associated with the cognitive impairment and the survival time of these patients.
Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Function in Patients With Stress-Related Depression: A Randomized Double-Blind fMRI and 1H-MRS Study
Authors: Chen Yuxin , Li Xiuzhen , Wang Lubin , Tian Shushi , Chen Yuanwang , Wang Feng , Gu Kesheng , Wang Ying , Xu Guangkai , Zhang Shangrong , Liu Jie , Wang Haipeng , Jia Zongxin , Li Liqing , Wang Xiaohui , Xie Fang , Wang Xue , Wang Shida , Xue Cong , Zhao Yun , Qian Lingjia
Published: April 2022

Objectives

To reveal the effects of repetitive transcranial magnetic stimulation (rTMS) on the improvement of cognitive function in patients with stress-related depression, and to enrich the neural mechanism(s) underlying rTMS so as to improve cognitive function in patients with stress-related depression.

Methods

We conducted a randomized, double-blind, placebo-controlled study of rTMS in patients with stress-related depression who were 18–40 years of age. Patients were randomly allocated to either a sham or experimental group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Clinical assessments (HAMD, HAMA, DASS, MoCA), neuropsychologic (Stroop, WCST), and resting state fMRI and 1H-MRS assessments were executed at two time points—baseline and after the 10th rTMS session.

Results

rTMS relieved the mental symptoms of patients in both groups. The MoCA score of patients in the experimental group increased; the number of correct answers increased significantly in Stroop testing, and the number of errors and omissions decreased significantly; the number of persistent errors decreased significantly; and the time used to complete the test decreased to an even greater extent in the WCST experimental group. The ReHo value in the lingual gyrus of the right hemisphere and the cuneus of the left and right hemispheres in the experimental group decreased after treatment. The DC value in the left and right hemispheric cuneus and postcentral gyrus of the left hemisphere in the experimental group diminished after treatment. The functional connections of these brain regions also changed as the Cho and NAA/Cr of the left DLPFC changed, with alterations related to the improvement in cognitive function. The level of choline (Cho) in the left DLPFC of the experimental group was significantly lower than that of the control group, and the level of N-acetylaspartate/creatine (NAA/Cr) in the left DLPFC of the control group was significantly higher than that of the experimental group. These changes were related to the overall improvement in cognitive function.

Conclusions

Ten-Hz rTMS over the left DLPFC improved the cognitive function of patients with stress-related depression. The governing mechanism for this phenomenon may be via rTMS effects on multiple visual-related brain regions and their functional connections, and on the somatosensory cortex and its functional connection with visual and auditory cortex, reducing the level of Cho and stabilizing the level of NAA/Cr in the left DLPFC.
Treatment Challenges in Multiple Sclerosis – A Continued Role for Glatiramer Acetate?
Authors: Mirabella Massimiliano , Annovazzi Pietro , Brownlee Wallace , Cohen Jeffrey A. , Kleinschnitz Christoph , Wolf Christian
Published: April 2022

Earlier diagnosis, access to disease-modifying therapies (DMTs), and improved supportive care have favorably altered the disease course of multiple sclerosis (MS), leading to an improvement in long-term outcomes for people with MS (PwMS). This success has changed the medical characteristics of the population seen in MS clinics. Comorbidities and the accompanying polypharmacy, immune senescence, and the growing number of approved DMTs make selecting the optimal agent for an individual patient more challenging. Glatiramer acetate (GA), a moderately effective DMT, interacts only minimally with comorbidities, other medications, or immune senescence. We describe here several populations in which GA may represent a useful treatment option to overcome challenges due to advanced age or comorbidities (e.g., hepatic or renal disease, cancer). Further, we weigh GA's potential merits in other settings where PwMS and their neurologists must base treatment decisions on factors other than selecting the most effective DMT, e.g., family planning, conception and pregnancy, or the need for vaccination.
Case Report: Cerebrospinal Fluid Dynamics in the Optic Nerve Subarachnoid Space and the Brain Applying Diffusion Weighted MRI in Patients With Idiopathic Intracranial Hypertension—A Pilot Study
Authors: Berberat Jatta , Pircher Achmed , Gruber Philipp , Lovblad Karl-Olof , Remonda Luca , Killer Hanspeter Esriel
Published: April 2022

Purpose

The aim of this study was to examine the cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) and the brain in patients with idiopathic intracranial hypertension (IIH) and papilledema (PE) compared to healthy controls by applying non-invasive diffusion-weighted MRI.

Methods

A retrospective analysis of diffusion-weighted MR images of 5 patients with IIH (10 ONs), mean age: 31 ± 10 years (5 women), and 11 healthy controls (22 ONs, mean age: 60 ± 13 years, 5 women) was performed. The flow velocity flow-range ratio (FRR) between the intracranial cavity and the SAS of the ON was calculated in both groups and then compared.

Results

The mean FRR was 0.55 ± 0.08 in patients with IIH and 0.63 ± 0.05 in healthy controls. The difference between patients with IIH and healthy controls was statistically significant (p < 0.05).

Conclusions

The CSF flow velocity was decreased in patients with IIH with PE compared to healthy controls. The reduced CSF flow dynamics might be involved in the pathophysiology of PE in IIH and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON.

Idiopathic intracranial hypertension is a neurological disease, where vision loss is the most feared complication of this disorder. The pathophysiology of IIH is not fully understood but is strongly linked to a reduced uptake of CSF into the central dural sinus veins. In this study, we examined the CSF flow rates in the SAS ON and the brain in patients with IIH and PE compared to healthy controls by applying non-invasive diffusion-weighted MRI. Knowing about the flow ratio of CSF may be of clinical relevance for the treatment decisions of IIH. If medical treatment fails, surgical options for lowering the ICP pressure need to be taken into consideration. As the primary goal of treatment is to prevent the loss of vision and visual field, it is important to know whether the communication of CSF between the intracranial CSF and the CSF in the perioptic space is intact. We showed that the CSF flow velocity was decreased in IIH patients with PE compared to healthy controls. The reduced CSF flow might be involved in the pathophysiology of PE in IIH, and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON.
Purification of Fibroblasts From the Spiral Ganglion
Authors: Anacker Annett , Esser Karl-Heinz , Lenarz Thomas , Paasche Gerrit
Published: April 2022

Using cultures of freshly isolated spiral ganglion cells (SGC) is common to investigate the effect of substances on spiral ganglion neurons (SGN) in vitro. As these cultures contain more cell types than just neurons, and it might be beneficial to have cochlear fibroblasts available to further investigate approaches to reduce the growth of fibrous tissue around the electrode array after cochlear implantation, we aimed at the purification of fibroblasts from the spiral ganglion in the current study. Subcultivation of the primary SGC culture removed the neurons from the culture and increased the fibroblast to glial cell ratio in the preparations, which was revealed by staining for vimentin, the S100B-protein, and the 200-kD neurofilament. We performed direct immunolabeling for the Thy1-glycoprotein and the p75NGFR-enabled fluorescence-based cell sorting. This procedure resulted in a cell culture of cochlear fibroblasts with a purity of more than 99%. The received fibroblasts can be subcultivated for up to 10 passages before proliferation rates drop. Additionally, 80% of the cells survived the first attempt of cryopreservation and exhibited a fibroblast-specific morphology. Using the described approach provides a purified preparation of cochlear fibroblasts, which can now be used in vitro for further investigations.
Abnormal Large-Scale Neuronal Network in High Myopia
Authors: Ji Yu , Shi Ling , Cheng Qi , Fu Wen-wen , Zhong Pei-pei , Huang Shui-qin , Chen Xiao-lin , Wu Xiao-rong
Published: April 2022

Aim

Resting state functional magnetic resonance imaging (rs-fMRI) was used to analyze changes in functional connectivity (FC) within various brain networks and functional network connectivity (FNC) among various brain regions in patients with high myopia (HM).

Methods

rs-fMRI was used to scan 82 patients with HM (HM group) and 59 healthy control volunteers (HC group) matched for age, sex, and education level. Fourteen resting state networks (RSNs) were extracted, of which 11 were positive. Then, the FCs and FNCs of RSNs in HM patients were examined by independent component analysis (ICA).

Results

Compared with the HC group, FC in visual network 1 (VN1), dorsal attention network (DAN), auditory network 2 (AN2), visual network 3 (VN3), and sensorimotor network (SMN) significantly increased in the HM group. FC in default mode network 1 (DMN1) significantly decreased. Furthermore, some brain regions in default mode network 2 (DMN2), default mode network 3 (DMN3), auditory network 1 (AN1), executive control network (ECN), and significance network (SN) increased while others decreased. FNC analysis also showed that the network connection between the default mode network (DMN) and cerebellar network (CER) was enhanced in the HM group.

Conclusion

Compared with HCs, HM patients showed neural activity dysfunction within and between specific brain networks, particularly in the DMN and CER. Thus, HM patients may have deficits in visual, cognitive, and motor balance functions.
Redistribution of Histone Marks on Inflammatory Genes Associated With Intracerebral Hemorrhage-Induced Acute Brain Injury in Aging Rats
Authors: Zhang Qin , Kong Wei-lin , Yuan Jun-Jie , Chen Qiong , Gong Chang-Xiong , Liu Liang , Wang Fa-Xiang , Huang Jia-Cheng , Yang Guo-Qiang , Zhou Kai , Xu Rui , Xiong Xiao-Yi , Yang Qing-Wu
Published: April 2022

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.
Substance P Increases the Excitability of Dorsal Motor Nucleus of the Vagus Nerve via Inhibition of Potassium Channels
Authors: Yang Eunhee , Kim Woojin , Park Yong Seek , Jin Young-Ho
Published: April 2022

Increases in the substance P (SP) concentration in the medial portion of the dorsal motor nucleus of the vagus nerve (mDMV) in the brainstem are closely associated with chemotherapy induced nausea and vomiting (CINV). However, the underlying cellular and molecular mechanisms of action are not well understood. In this study, we investigated the effects of SP on mDMV neurons using whole-cell patch-clamp recordings from rat brainstem slices. Application of different concentrations of SP induced tonic and phasic responses. Submicromolar concentrations of induced an inward shift of the holding current by increasing membrane input resistance. The response was mimicked by acidification of the extracellular solution and inhibited by a neurokinin type 1 receptor antagonist. These responses have equilibrium potentials close to the K+ equilibrium potential. In addition, a TWIK-related acid-sensitive K+ channel 3 (TASK-3) inhibitor, PK-THPP, induced responses similar to those produced by submicromolar SP concentrations. Micromolar concentrations of SP facilitated γ-aminobutyric acid (GABA) release but diminished glutamate release; these changes were blocked by a GABAB receptor antagonist and a neurokinin type 3 receptor antagonist, respectively. In current-clamp recordings, submicromolar SP concentrations increased neuronal excitability by depolarizing membrane potentials. However, neither the increase in SP concentration to the micromolar range nor the addition of GABAA and ionotropic glutamate receptor antagonists affected neuronal excitability. Thus, SP increases the excitability of mDMV neurons by inhibiting K+ conductance.