bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic Kisspeptin Neurons Regulates Energy Metabolism and Reproduction Under Chronic Stress
Authors: Huang Yinqiong , Liu Qinyu , Huang Guifeng , Wen Junping , Chen Gang
Published: May 2022

Background

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, affecting energy homeostasis and reproduction. The aim of this study was to investigate whether stress affected energy metabolism and reproduction through the glucocorticoid receptor on Kisspeptin neurons in the hypothalamus.

Methods

Four groups included control group, chronic restraint stress group, Kisspeptin specific glucocorticoid receptor knock out group (KGRKO) and KGRKO+stress group. Body weight, food intake, estrous cycle of female mice, serum sex hormone levels, serum corticosterone and prolactin, Kisspeptin expression in the hypothalamus were measured.

Results

The restraint stress group showed a significant weight loss compared with the control group. KGRKO+restraint stress group had a reduced weight loss, suggesting that restraint stress might partially affect the energy metabolism through GR on Kisspeptin neurons. In terms of reproductive function, the restraint stress group and the KGRKO+restraint stress group showed missing pre-estrus period or prolonged estrous cycles. Serum LH and FSH in KGRKO + restraint stress group decreased significantly compared with KGRKO group. However, no significant difference in the level of serum testosterone was observed. After restraint stress, the levels of serum cortisol and prolactin in male and female mice were significantly higher than the control group, and the hypothalamus Kiss1 gene mRNA expression and Kisspeptin protein expression were significantly decreased.

Conclusion

Chronic restraint stress induced weight loss and negative changes in reproduction, which were partially mediated by glucocorticoid receptor on Kisspeptin neurons in the hypothalamus.
Birthweight After Frozen Embryos Formed on the Fifth Day Versus the Sixth Day: A Retrospective Analysis Including 17,127 Singleton Newborns
Authors: Yang Junlan , Wang Ze , Cao Hairu , Liu Lu , Yuan Qiaona , Xu Haiyan , Tang Rong
Published: May 2022

Background

Transferring blastocysts frozen on day 6 (D6) may adversely affect the pregnancy rate compared with day 5 (D5). Moreover, it remains unclear whether delayed embryo transfer affects neonatal birth weight.

Methods

A retrospective cohort study consisting of 17,127 singleton births from single frozen embryo transfer (FET) cycles, between January 2011 and January 2020, was performed including 14,166 blastocysts frozen on D5 and 2,961 on D6. The primary outcomes of this study were neonatal birth weight and incidence of small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), and macrosomia.

Results

The mean neonatal birth weight in the D5 group (3.47 ± 0.49 kg) was significantly higher compared with the D6 group (3.45 ± 0.50 kg), although the discrepancy was only 0.02 kg. Multiple linear regression analysis for birth weight between the two groups showed no statistically significant difference (β= -0.01 t= -1.218; P>0.05). Logistic regression analysis revealed that the risks of SGA (OR 1.166; 95%CI, 0.911-1.491; P>0.05), LGA (OR 0.917; 95%CI, 0.831-1.012; P>0.05), LBW (OR 1.192; 95%CI, 0.926-1.533; P>0.05), and macrosomia (OR 0.975; 95%CI, 0.864-1.100; P>0.05) were similar in the two groups after adjusting for confounders.

Conclusions

In the FET cycle, the neonatal birth weight and incidence of LGA, SGA, LBW, or macrosomia were similar between the D5 and D6 groups, suggesting that delayed blastocyst transfer would not affect the neonatal birth weight.
Global, Regional, and National Burden of Low Bone Mineral Density From 1990 to 2019: Results From the Global Burden of Disease Study 2019
Authors: Dong Yimin , Kang Honglei , Peng Renpeng , Song Kehan , Guo Qian , Guan Hanfeng , Zhu Meipeng , Ye Dawei , Li Feng
Published: May 2022

Objective

We aim to explore the global spatial prevalence and temporal trends of the burden of low bone mineral density (LBMD) worldwide, due to a lack of related studies.

Design

Cross-sectional study.

Methods

We used data from the Global Burden of Disease Study 2019 to conduct this study. LBMD in the GBD study includes both osteopenia and osteoporosis. The estimation for the prevalence, measured by the summary exposure value (SEV), and burden of LBMD was made in DisMod-MR 2.1, a Bayesian meta-regression tool. Correlation analysis was performed using the Spearman rank order correlation methods. The temporal trends were represented by the estimated annual percentage change (EAPC).

Results

In 2019, there were 438 thousand deaths and 16.6 million DALYs attributable to LBMD, increasing by 111.1% and 93.8% respectively, compared to that in 1990. From 1990 to 2019, the prevalence of LBMD has decreased worldwide, but has increased in high-income North America. Some countries, such as the United States, Australia, Canada, and China had increased disability and mortality rates of LBMD with time. Countries with low socio-demographic index (SDI) had higher incidence and mortality rate than those with high SDI. The prevalence of LBMD was lower in males, but the attributable disability and mortality were higher in males in all years from 1990 to 2019.

Conclusion

With population aging, countries worldwide, especially those with low-SDI, will face increasing challenges in reducing the burden attributable to LBMD and osteoporosis. The treatment of osteoporosis has been overlooked in men for a long time. Effective measures are warranted to control the prevalence and burden of LBMD.
A Validated Model for Individualized Prediction of Live Birth in Patients With Adenomyosis Undergoing Frozen–Thawed Embryo Transfer
Authors: Wu Yaoqiu , Yang Rong , Lin Haiyan , Cao Chunwei , Jiao Xuedan , Zhang Qingxue
Published: May 2022

Purpose

This study aimed to develop a predictive tool for live birth in women with adenomyosis undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment.

Methods

A total of 424 patients with adenomyosis who underwent frozen–thawed embryo transfer (FET) from January 2013 to December 2019 at a public university hospital were included. The patients were randomly divided into training (n = 265) and validation (n = 159) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression (MLR) was developed on the basis of clinical covariates assessed for their association with live birth.

Results

In total, 183 (43.16%) patients became pregnant, and 114 (26.88%) had a live birth. The MLR showed that the probability of live birth was significantly correlated with age [odds ratio (OR), 3.465; 95% confidence interval (CI), 1.215–9.885, P = 0.020], uterine volume (OR, 8.141; 95% CI, 2.170–10.542; P = 0.002), blastocyst transfer (OR, 3.231; 95% CI, 1.065–8.819, P = 0.023), twin pregnancy (OR, 0.328; 95% CI, 0.104–0.344, P = 0.005), and protocol in FET (P < 0.001). The statistical nomogram was built based on age, uterine volume, twin pregnancy, stage of the transferred embryo, and protocol of FET, with an area under the curve (AUC) of 0.837 (95% CI: 0.741–0.910) for the training cohort. The AUC for the validation cohort was 0.737 (95% CI: 0.661–0.813), presenting a well-pleasing goodness-of-fit and stability in this model.

Conclusions

This visual and easily applied nomogram built on the risk factors of live birth in patients with adenomyosis provides useful and precise information for physicians on individualized decision-making during the IVF/ICSI procedure.
Optimal Allocation of Emergency Repair Resources for Producer–Consumer Communities Considering Fault Risk Classification and Emergency Repair Response Capability
Authors: Mao Donghua , Qiu Jinyi
Published: May 2022

With the construction of new power systems, distributed power sources are connected in large numbers and the possibility of faults increases. The optimal allocation of repair resources is important to improve the fault management efficiency and the quality of power supply services in the producer–consumer community. Using a large number of historical fault resources accumulated in the producer–consumer community, we first preprocess the fault information by the rough set theory, then establish an optimal allocation model that minimizes the total fault loss, consider fault risk classification and repair response capability, and finally use the improved gray wolf optimization algorithm to perform the optimal calculation. To address the problems of the traditional gray wolf algorithm, tent mapping is introduced in the generation of the initial population to enhance the uniformity of the initial population. The cooperative competition mechanism is introduced to improve the utilization of effective information among individuals. Finally, the feasibility and superiority of the algorithm are verified through the analysis of calculation cases. Finally, the feasibility of this configuration method is verified through the analysis of arithmetic cases.
A New Test for Ridge Wind Directional Data Under Neutrosophic Statistics
Authors: Aslam Muhammad , Al-Marshadi Ali Hussein
Published: May 2022

The statistical tests under classical statistics can be only applied when the data is linear and has certain observations. The existing statistical tests cannot be applied for circular/angles data. In this paper, the Watson-Williams test under neutrosophic is introduced to analyze having uncertain, imprecise, and indeterminate circular/angles data. The neutrosophic test statistic is introduced and applied to wind direction data. From the real example and simulation study, it can be concluded the proposed neutrosophic Watson-Williams test performs better than the Watson-Williams test under classical statistics.
Intelligent Command Filter Design for Strict Feedback Unmodeled Dynamic MIMO Systems With Applications to Energy Systems
Authors: Feng Xuxiang , Shi Lu , Zhang Yumeng
Published: May 2022

This study presents a command filtered control scheme for multi-input multi-output (MIMO) strict feedback nonlinear unmodeled dynamical systems with its applications to power systems. To deal with dynamic uncertainties, a dynamic signal is introduced, together with radial basis function neural networks (RBFNNs) to overcome the influences of the dynamic uncertainties. Command filters (CFs) are used to prevent the explosion of complexity, where the compensating signals can eliminate the effect of filter errors. Compared with single-input single-output strict feedback nonlinear systems, the method proposed in this study has more suitability. In the end, the simulation experiments are carried out by applying the developed algorithm to power systems, where the simulation results verify the efficacy of the approach proposed.
Identification of Novel Genetic Variants and Comorbidities Associated With ICD-10-Based Diagnosis of Hypertrophic Cardiomyopathy Using the UK Biobank Cohort
Authors: Gyftopoulos Alex , Chen Yi-Ju , Wang Libin , Williams Charles H. , Chun Young Wook , O’Connell Jeffery R. , Perry James A. , Hong Charles C.
Published: May 2022

Objectives: To identify previously unrecognized genetic variants and clinical variables associated with the ICD-10 (International Classification of Diseases 10)-based diagnosis of hypertrophic cardiomyopathy in the UK Biobank cohort.

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder with more than 2000 known mutations in one of eight genes encoding sarcomeric proteins. However, there is considerable variation in disease manifestation, suggesting the role of additional unrecognized contributors, genetic and otherwise. There is substantial interest in the use of real-world data, such as electronic health records to better understand disease mechanisms and discover new treatment strategies, but whether ICD-10-based diagnosis can be used to study HCM genetics is unknown.

Methods: In a genome-wide association study (GWAS) using the UK Biobank, we analyzed the genomes of 363 individuals diagnosed with HCM based on ICD-10 coding compared to 7,260 age, ancestry, and sex-matched controls in a 1:20 case:control design. Genetic variants were analyzed by Plink’s firth logistic regression and assessed for association with HCM. We also examined 61 biomarkers and other diagnoses in the 363 HCM cases and matched controls.

Results: The prevalence of ICD-10-based diagnosis of HCM in the UK Biobank cohort was 1 in 1,342, suggesting disease assignment based on the two ICD-10 codes underestimates HCM prevalence. In addition, common cardiovascular comorbidities were more prevalent in ICD-10-based HCM cases in comparison to controls. We identified two novel, non-sarcomeric genetic variants in KMT2C rs78630626, and PARD3B rs188937806 that were associated with ICD-10 codes for HCM with genome-wide significance (p < 5 x 10−8). These are associated with an increased odds ratio (OR) of ∼3.8 for being diagnosed with HCM. Minor allele frequency (MAF) of each variant was >1%.

Discussion: Disease assignment based strictly on ICD-10 codes may underestimate HCM prevalence. Individuals with HCM were more frequently diagnosed with several comorbid conditions, such as hypertension, atherosclerotic heart disease, diabetes, and kidney failure, suggesting they may contribute to disease manifestation. This UK Biobank database-based GWAS identified common variants in KMT2C and PARD3B that are associated with HCM diagnosis, which may represent novel modifier genes. Our study demonstrates the feasibility and limitations of conducting phenotypic and genotypic characterization of HCM based on ICD-10 diagnosis in a large population-based cohort.
An Integrative Pan-Cancer Analysis Revealing MLN4924 (Pevonedistat) as a Potential Therapeutic Agent Targeting Skp2 in YAP-Driven Cancers
Authors: Lan Chungen , Ni Bo , Zhao Tiansuo , Li Zekun , Wang Junjin , Ma Ying , Li Weidong , Wang Xiuchao
Published: May 2022

Background: YAP, coded by YAP1 gene, is critical in the Hippo pathway. It has been reported to be involved in the tumorigenesis and progression of several cancers. However, its roles on tumor cell proliferation in diverse cancers remain to be elucidated. And there is currently no clinically feasible drug that can directly target YAP in cancers. This research aimed to explore the regulatory mechanism of YAP in promoting tumor proliferation of multiple cancers, in order to find new strategies for inhibiting the overgrowth of YAP-driven cancers.

Methods: We investigated the expression pattern of YAP1 in pan-cancer across numerous databases and our cohorts. First, univariate Cox regression analysis and survival analysis were used to evaluate the effect of YAP1 on the prognosis of cancer patients. Second, TIMER was used to explore the relationship between YAP1 expression and tumor cell proliferation. Third, functional and pathway enrichment was performed to search for targets of YAP involved in cell cycle in cancers. At last, GDSC and CCLE datasets were used to assess the correlation between SKP2 expression and MLN4924 IC50 values.

Results: Differential expression analysis of multiple databases and qPCR validation showed that YAP1 was generally overexpressed in pan-cancers. Survival analysis revealed that YAP1 over-expression was significantly related to poor prognosis of patients with PAAD. The expression level of YAP1 was positively correlated with the proliferation in varieties of tumors. Further, SKP2 was confirmed as a target of YAP in promoting tumor cell proliferation. In addition, SKP2 expression was negatively correlated with MLN4924 IC50 values in almost all cancer types.

Conclusion:YAP1 is frequently overexpressed in human cancers. YAP promoted tumor cell proliferation by up-regulating SKP2 expression in multiple cancers. The comprehensive pan-cancer analysis suggested that inhibition of Skp2 with MLN4924 might be an effective therapeutic strategy for attenuating tumor cell proliferation in YAP-driven cancers.
Proteomic and Metabolomic Signatures Associated With the Immune Response in Healthy Individuals Immunized With an Inactivated SARS-CoV-2 Vaccine
Authors: Wang Yi , Wang Xiaoxia , Luu Laurence Don Wai , Chen Shaojin , Jin Fu , Wang Shufang , Huang Xiaolan , Wang Licheng , Zhou Xiaocui , Chen Xi , Cui Xiaodai , Li Jieqiong , Tai Jun , Zhu Xiong
Published: May 2022

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results help us to understand the host response to vaccination of CoronaVac and highlight the utility of a systems biology approach in defining molecular correlates of protection to vaccination.
Immune-Associated Gene Signatures Serve as a Promising Biomarker of Immunotherapeutic Prognosis for Renal Clear Cell Carcinoma
Authors: Wang Qi , Tang Hanmin , Luo Xuehui , Chen Jie , Zhang Xinyue , Li Xinyue , Li Yuesen , Chen Yuetong , Xu Yungang , Han Suxia
Published: May 2022

As the most common type of renal cell carcinoma (RCC), the renal clear cell carcinoma (ccRCC) is highly malignant and insensitive to chemotherapy or radiotherapy. Although systemic immunotherapies have been successfully applied to ccRCC in recent years, screening for patients who can benefit most from these therapies is still essential and challenging due to immunological heterogeneity of ccRCC patients. To this end, we implemented a series of deep investigation on the expression and clinic data of ccRCC from The Cancer Genome Atlas (TCGA) International Consortium for Cancer Genomics (ICGC). We identified a total of 946 immune-related genes that were differentially expressed. Among them, five independent genes, including SHC1, WNT5A, NRP1, TGFA, and IL4R, were significantly associated with survival and used to construct the immune-related prognostic differential gene signature (IRPDGs). Then the ccRCC patients were categorized into high-risk and low-risk subgroups based on the median risk score of the IRPDGs. IRPDGs subgroups displays distinct genomic and immunological characteristics. Known immunotherapy-related genes show different mutation burden, wherein the mutation rate of VHL was higher than 40% in the two IRPDGs subgroups, and SETD2 and BAP1 mutations differed most between two groups with higher frequency in the high-risk subgroup. Moreover, IRPDGs subgroups had different abundance in tumor-infiltrating immune cells (TIICs) with distinct immunotherapy efficacy. Plasma cells, regulatory cells (Tregs), follicular helper T cells (Tfh), and M0 macrophages were enriched in the high-risk group with a higher tumor immune dysfunction and rejection (TIDE) score. In contrast, the low-risk group had abundant M1 macrophages, mast cell resting and dendritic cell resting infiltrates with lower TIDE score and benefited more from immune checkpoint inhibitors (ICI) treatment. Compared with other biomarkers, such as TIDE and tumor inflammatory signatures (TIS), IRPDGs demonstrated to be a better biomarker for assessing the prognosis of ccRCC and the efficacy of ICI treatment with the promise in screening precise patients for specific immunotherapies.
Estuarine Ichthyoplankton Studies – A Review
Authors: Zhang Hui , Wang Yibang , Liang Cui , Liu Shude , Xian Weiwei
Published: May 2022

Estuaries are nutrient-rich environments with a gradient of fresh to salt water. They support high primary productivity and an abundance of zooplankton. Estuaries are used by many fish as nursery grounds because their environmental conditions provide abundant food for larval and adult fish. Ichthyoplankton, which comprise fish eggs and larvae, are important for the recruitment of fish species. At present, there are no systematic reviews on ichthyoplankton in estuaries from a global perspective. Here, research on ichthyoplankton over the last 60 years (1951–2022) was reviewed, focusing on three aspects: evaluation of ichthyoplankton published studies, community structure, and factors affecting community structure. The results show that research on estuarine ichthyoplankton has increased, from less than 1 article per year in the 1950s to more than 30 articles per year in the 2020s. The keyword used most commonly was ‘community structure’ and ‘dynamics’ and the word used most recently was ‘climate change’. Regarding the geographical distribution of the studies carried out on estuarine ichthyoplankton, USA had the most (32.9% of all studies), followed by Australia (8.1%), South Africa (6.1%), Brazil (5.6%), Japan (5.1%), China (4.9%), Canada (4.8%), and Portugal (4.8%). Salinity and turbidity were the main factors affecting the ichthyoplankton community structure in estuaries. Climate change indirectly affected the community structure of estuarine ichthyoplankton by changing the spawning time, spawning location, and hatching time of species. The movement of spawning sites poleward and the advance of spawning time showed a consistent trend. In addition, the development of DNA barcoding techniques will be a useful supplement to traditional taxonomic methods for identifying ichthyoplankton and will provide new opportunities for the development of systematic taxonomy in this field. Our review contributes to a broader understanding of estuarine ichthyoplankton and provides theoretical support for estuarine environmental protection and the sustainable use of estuarine fishery resources.
Identifying Scaling Pathways and Research Priorities for Kelp Aquaculture Nurseries Using a Techno-Economic Modeling Approach
Authors: Coleman Struan , Gelais Adam T. St. , Fredriksson David W. , Dewhurst Tobias , Brady Damian C.
Published: May 2022

Aquaculture of seaweeds, particularly in emerging farming regions such as North America, Europe, and South America, is steadily increasing. The growth of the sector has been supported by public and private R&D investment with the long-term goal of reducing farm-gate production costs. Reducing expenses would potentially allow growers to target high volume, low value markets, such as hydrocolloids, animal feeds, food thickening agents, biofuels, and carbon dioxide removal (CDR), as well as the higher value, “whole foods” markets. Regardless of the eventual fate of farmed seaweed, nursery production must increase in parallel with ocean cultivation to support the raw materials needs of the expanding industry. We quantified S. latissima (hereafter kelp) nursery production costs and identified potential barriers to cost-effective scaling using a techno-economic model (TEM). Semi-structured interviews with nursery operators in the U.S. and Europe were supplemented by an extensive literature review to parameterize the TEM. Reducing the sporophyte grow-out duration, increasing labor capacity, de-risking energy efficient flow-through systems, and optimizing tank and PVC “spool” size emerged as the most important research priorities based on our analysis. We point towards expanded gametophyte culture, and an associated policy framework to protect wild kelp population structure from monocultures, as necessary elements to support these potential improvements. The results of this work, as well as the open-source nursery TEM, are relevant to seaweed aquaculture producers, policy makers, and researchers, and can be used to guide future decision making regarding the cost-benefit of best available nursery technology.
Catalpol Attenuates Pulmonary Fibrosis by Inhibiting Ang II/AT1 and TGF-β/Smad-Mediated Epithelial Mesenchymal Transition
Authors: Yu Qun , Zhu Dewei , Zou Yang , Wang Kai , Rao Peili , Shen Yunhui
Published: May 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating chronic lung condition affecting over 3 million people worldwide with a high mortality rate and there are no effective drugs. Angiotensin II (Ang II), as a major effector peptide of the renin angiotensin aldosterone system, has been shown to act in tandem with the transforming growth factor-β (TGF-β) signaling pathway to promote the infiltration of inflammatory cells, production of reactive oxygen species (ROS) and profibrotic factors after lung injury, and to participate in the process of epithelial mesenchymal transition (EMT). Catalpol (CAT) has been shown to have anti-inflammatory and antifibrotic effects. However, the effects and mechanisms of CAT on pulmonary fibrosis are not clear.

Purpose

To assess the effects and mechanisms of catalpol on bleomycin-induced pulmonary fibrosis in mice.

Methods

We used bleomycin-induced mouse model of pulmonary fibrosis to evaluate the alleviation effect of CAT at 7, 14, 28d, respectively. Next, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, immunofluorescence, Masson trichrome staining and western blotting were used to study the underlying mechanism of CAT on bleomycin-induced pulmonary fibrosis.

Results

It's demonstrated that CAT exerted a potent anti-fibrotic function in BLM-induced mice pulmonary fibrosis via alleviating inflammatory, ameliorating collagen deposition, reducing the level of Ang II and HYP and alleviating the degree of EMT. Moreover, CAT attenuate BLM-induced fibrosis by targeting Ang II/AT1 and TGF-β/Smad signaling in vivo.

Conclusion

CAT may serve as a novel therapeutic candidate for the simultaneous blockade of Ang II and TGF-β pathway to attenuate pulmonary fibrosis.
Unearthing Shifts in Microbial Communities Across a Soil Disturbance Gradient
Authors: Seitz Taylor J. , Schütte Ursel M. E. , Drown Devin M.
Published: May 2022

Permafrost, an important source of soil disturbance, is particularly vulnerable to climate change in Alaska where 85% of the land is underlained with discontinuous permafrost. Boreal forests, home to plants integral to subsistence diets of many Alaska Native communities, are not immune to the effects of climate change. Soil disturbance events, such as permafrost thaw, wildfires, and land use change can influence abiotic conditions, which can then affect active layer soil microbial communities. In a previous study, we found negative effects on boreal plants inoculated with microbes impacted by soil disturbance compared to plants inoculated with microbes from undisturbed soils. Here, we identify key shifts in microbial communities altered by soil disturbance using 16S rRNA gene sequencing and make connections between microbial community changes and previously observed plant growth. Additionally, we identify further community shifts in potential functional mechanisms using long read metagenomics. Across a soil disturbance gradient, microbial communities differ significantly based on the level of soil disturbance. Consistent with the earlier study, the family Acidobacteriaceae, which consists of known plant growth promoters, was abundant in undisturbed soil, but practically absent in most disturbed soil. In contrast, Comamonadaceae, a family with known agricultural pathogens, was overrepresented in most disturbed soil communities compared to undisturbed. Within our metagenomic data, we found that soil disturbance level is associated with differences in microbial community function, including mechanisms potentially involved in plant pathogenicity. These results indicate that a decrease in plant growth can be linked to changes in the microbial community and functional composition driven by soil disturbance and climate change. Together, these results build a genomic understanding of how shifting soil microbiomes may affect plant productivity and ecosystem health as the Arctic warms.
Niche Partitioning of Labyrinthulomycete Protists Across Sharp Coastal Gradients and Their Putative Relationships With Bacteria and Fungi
Authors: Xie Ningdong , Wang Zhao , Hunt Dana E. , Johnson Zackary I. , He Yaodong , Wang Guangyi
Published: May 2022

While planktonic microbes play key roles in the coastal oceans, our understanding of heterotrophic microeukaryotes’ ecology, particularly their spatiotemporal patterns, drivers, and functions, remains incomplete. In this study, we focus on a ubiquitous marine fungus-like protistan group, the Labyrinthulomycetes, whose biomass can exceed that of bacterioplankton in coastal oceans but whose ecology is largely unknown. Using quantitative PCR and amplicon sequencing of their 18S rRNA genes, we examine their community variation in repeated five-station transects across the nearshore-to-offshore surface waters of North Carolina, United States. Their total 18S rRNA gene abundance and phylotype richness decrease significantly from the resource-rich nearshore to the oligotrophic offshore waters, but their Pielou’s community evenness appears to increase offshore. Similar to the bacteria and fungi, the Labyrinthulomycete communities are significantly structured by distance from shore, water temperature, and other environmental factors, suggesting potential niche partitioning. Nevertheless, only several Labyrinthulomycete phylotypes, which belong to aplanochytrids, thraustochytrids, or unclassified Labyrinthulomycetes, are prevalent and correlated with cohesive bacterial communities, while more phylotypes are patchy and often co-occur with fungi. Overall, these results complement previous time-series observations that resolve the Labyrinthulomycetes as persistent and short-blooming ecotypes with distinct seasonal preferences, further revealing their partitioning spatial patterns and multifaceted roles in coastal marine microbial food webs.
Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease
Authors: Bellanti Francesco , Bukke Vidyasagar Naik , Moola Archana , Villani Rosanna , Scuderi Caterina , Steardo Luca , Palombelli Gianmauro , Canese Rossella , Beggiato Sarah , Altamura Mario , Vendemiale Gianluigi , Serviddio Gaetano , Cassano Tommaso
Published: May 2022

The therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) was investigated in young (6-month-old) and adult (12-month-old) 3 × Tg-AD mice, which received um-PEA for 3 months via a subcutaneous delivery system. Mitochondrial bioenergetics, ATP homeostasis, and magnetic resonance imaging/magnetic resonance spectroscopy were evaluated in the frontal cortex (FC) and hippocampus (HIPP) at the end of um-PEA treatment. Glutamate release was investigated by in vivo microdialysis in the ventral HIPP (vHIPP). We demonstrated that chronic um-PEA treatment ameliorates the decrease in the complex-I respiration rate and the FoF1-ATPase (complex V) activity, as well as ATP content depletion in the cortical mitochondria. Otherwise, the impairment in mitochondrial bioenergetics and the release of glutamate after depolarization was not ameliorated by um-PEA treatment in the HIPP of both young and adult 3 × Tg-AD mice. Moreover, progressive age- and pathology-related changes were observed in the cortical and hippocampal metabolism that closely mimic the alterations observed in the human AD brain; these metabolic alterations were not affected by chronic um-PEA treatment. These findings confirm that the HIPP is the most affected area by AD-like pathology and demonstrate that um-PEA counteracts mitochondrial dysfunctions and helps rescue brain energy metabolism in the FC, but not in the HIPP.
Comparison of Clinical Balance and Visual Dependence Tests in Patients With Chronic Dizziness With and Without Persistent Postural-Perceptual Dizziness: A Cross-Sectional Study
Authors: De Vestel Charlotte , De Hertogh Willem , Van Rompaey Vincent , Vereeck Luc
Published: May 2022

Background

The diagnosis of persistent postural-perceptual dizziness (PPPD) is primarily based on medical history taking. Research on the value of clinical balance and visual dependence tests in identifying PPPD is scarce.

Objectives

(1) to contrast clinical balance and visual dependence tests between PPPD patients, dizzy non-PPPD patients, and healthy persons; and (2) to evaluate whether these clinical tests can help to identify PPPD in patients with chronic dizziness.

Methods

Consecutive patients with chronic dizziness (38 PPPD and 21 non-PPPD) and 69 healthy persons underwent Static Balance tests, the Timed Up and Go test, the Tandem Gait test, and the Functional Gait Assessment (FGA). Visual dependence tests included the Visual Vertigo Analog Scale (VVAS), the Rod-and-Disc test (RDT), and postural sway while facing rotating dots. Groups were compared using ANOVA with post-hoc Tukey, or independent samples t-tests. The value of the clinical tests for PPPD identification was evaluated through logistic regression and Partial Least Squares Discriminant (PLS-DA) analyses.

Results

PPPD patients had significantly higher VVAS scores than dizzy non-PPPD patients (p = 0.006). Facing rotating dots, PPPD and dizzy non-PPPD patients had increased postural sway compared to healthy persons (PPPD vs. healthy: center of pressure (COP) velocity p < 0.001, and COP area p < 0.001; but non-PPPD vs. healthy: COP velocity p = 0.116 and COP area p = 0.207). PPPD patients had no significantly increased postural sway compared to dizzy non-PPPD patients. PPPD and dizzy non-PPPD patients also scored significantly worse on balance tests compared to healthy persons (PPPD vs. healthy: for all balance tests p < 0.001; non-PPPD vs. healthy: FGA p < 0.001, for all other tests p < 0.05). Differences were insignificant in balance scores between PPPD and dizzy non-PPPD patients, or in RDT scores between the three study groups. In patients with chronic dizziness, a higher VVAS score was most associated with PPPD [odds ratio 1.04; 95% CI (1.01; 1.07); p = 0.010]. The cross-validated (CV) PLS-DA model with all clinical tests included, had fair discriminative ability (CVerror = 47%).

Conclusion

PPPD patients were more visually dependent, but did not have worse postural balance compared to dizzy non-PPPD patients. Elevated VVAS scores characterized PPPD most in patients with chronic dizziness.
Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature
Authors: Stram Michelle N. , Seifert Alan C. , Cortes Etty , Akyatan Alara , Woodoff-Leith Emma , Borukhov Valeriy , Tetlow Amber , Alyemni Dimath , Greenberg Michael , Gupta Avneesh , Krausert Amanda , Mecca Lauren , Rodriguez Sophia , Stahl-Herz Jay , Guzman Miguel A. , Delman Bradley , Crary John F. , Dams-O'Connor Kristen , Folkerth Rebecca D.
Published: May 2022

Two years into the COVID-19 pandemic, there are few published accounts of postmortem SARS-CoV-2 pathology in children. We report 8 such cases (4 infants aged 7–36 weeks, 4 children aged 5–15 years). Four underwent ex vivo magnetic resonance neuroimaging, to assist in identification of subtle lesions related to vascular compromise. All infants were found unresponsive (3 in unsafe sleeping conditions); all but 1 had recent rhinitis and/or influenza-like illness (ILI) in the family; 1 had history of sickle cell disease. Ex vivo neuroimaging in 1 case revealed white matter (WM) signal hyperintensity and diffuse exaggeration of perivascular spaces, corresponding microscopically to WM mineralization. Neurohistology in the remaining 3 infants variably encompassed WM gliosis and mineralization; brainstem gliosis; perivascular vacuolization; perivascular lymphocytes and brainstem microglia. One had ectopic hippocampal neurons (with pathogenic variant in DEPDC5). Among the children, 3 had underlying conditions (e.g., obesity, metabolic disease, autism) and all presented with ILI. Three had laboratory testing suggesting multisystem inflammatory syndrome (MIS-C). Two were hospitalized for critical care including mechanical ventilation and extracorporeal membrane oxygenation (ECMO); one (co-infected with adenovirus) developed right carotid stroke ipsilateral to the ECMO cannula and the other required surgery for an ingested foreign body. Autopsy findings included: acute lung injury in 3 (1 with microthrombi); and one each with diabetic ketoacidosis and cardiac hypertrophy; coronary and cerebral arteritis and aortitis, resembling Kawasaki disease; and neuronal storage and enlarged fatty liver. All 4 children had subtle meningoencephalitis, focally involving the brainstem. On ex vivo neuroimaging, 1 had focal pontine susceptibility with corresponding perivascular inflammation/expanded perivascular spaces on histopathology. Results suggest SARS-CoV-2 in infants may present as sudden unexpected infant death, while in older children, signs and symptoms point to severe disease. Underlying conditions may predispose to fatal outcomes. As in adults, the neuropathologic changes may be subtle, with vascular changes such as perivascular vacuolization and gliosis alongside sparse perivascular lymphocytes. Detection of subtle vascular pathology is enhanced by ex vivo neuroimaging. Additional analysis of the peripheral/autonomic nervous system and investigation of co-infection in children with COVID-19 is necessary to understand risk for cardiovascular collapse/sudden death.
Case Report: Infra-Low-Frequency Neurofeedback for PTSD: A Therapist's Perspective
Authors: Spreyermann Regula
Published: May 2022

The practical use of a combination of trauma psychotherapy and neurofeedback [infra-low-frequency (ILF) neurofeedback and alpha-theta training] is described for the treatment of patients diagnosed with complex post-traumatic stress disorder (C-PTSD). The indication for this combined treatment is the persistence of symptoms of a hyper-aroused state, anxiety, and sleep disorders even with adequate trauma-focused psychotherapy and supportive medication, according to the Guidelines of the German Society of Psycho-Traumatology (DeGPT). Another indication for a supplementary treatment with neurofeedback is the persistence of dissociative symptoms. Last but not least, the neurofeedback treatment after a trauma-focused psychotherapy session helps to calm the trauma-related reactions and to process the memories. The process of the combined therapy is described and illustrated using two representative case reports. Overall, a rather satisfying result of this outpatient treatment program can be seen in the qualitative appraisal of 7 years of practical application.
Putative Roles of SETBP1 Dosage on the SET Oncogene to Affect Brain Development
Authors: Antonyan Lilit , Ernst Carl
Published: May 2022

Mutations in SET BINDING PROTEIN 1 (SETBP1) cause two different clinically distinguishable diseases called Schinzel–Giedion syndrome (SGS) or SETBP1 deficiency syndrome (SDD). Both disorders are disorders of protein dosage, where SGS is caused by decreased rate of protein breakdown due to mutations in a proteosome targeting domain, and SDD is caused by heterozygous loss-of-function mutations leading to haploinsufficiency. While phenotypes of affected individuals support a role for SETBP1 in brain development, little is known about the mechanisms that might underlie this. The binding partner which gave SETBP1 its name is SET and there is extensive literature on this important oncogene in non-neural tissues. Here we describe different molecular complexes in which SET is involved as well as the role of these complexes in brain development. Based on this information, we postulate how SETBP1 protein dosage might influence these SET-containing molecular pathways and affect brain development. We examine the roles of SET and SETBP1 in acetylation inhibition, phosphatase activity, DNA repair, and cell cycle control. This work provides testable hypotheses for how altered SETBP1 protein dosage affects brain development.
How Brain Infarction Links With the Microbiota–Gut–Brain Axis: Hints From Studies Focusing on the Risk Factors for Ischemic Stroke
Authors: Liu Yunpeng , Dong Jing , Zhang Ziqing , Liu Yiqi , Wang Yang
Published: May 2022

Ischemic stroke (IS) is among the top prevalent neurologic disorders globally today. Risk factors such as hypertension, diabetes, and aging, contribute to the development of IS, and patients with these risk factors face heavier therapeutic burden and worse prognosis. Microbiota–gut–brain axis describes the crosstalk between the gut flora, intestine, and center nervous system, which conduct homeostatic effects through the bacterial metabolites, the regulation of immune activity, also the contact with enteric nerve ends and vagus nerve. Nowadays, more studies have paid attention to the important roles that microbiota–gut–brain axis played in the risk factors of IS. In the current article, we will review the recent works focusing on the bi-directional impacts of gut dysbiosis and the pathogenic process of IS-related risk factors, for the purpose to summarize some novel findings in this area, and try to understand how probiotics could limit the development of IS via different strategies.
Three-Photon Adaptive Optics for Mouse Brain Imaging
Authors: Sinefeld David , Xia Fei , Wang Mengran , Wang Tianyu , Wu Chunyan , Yang Xusan , Paudel Hari P. , Ouzounov Dimitre G. , Bifano Thomas G. , Xu Chris
Published: May 2022

Three-photon microscopy (3PM) was shown to allow deeper imaging than two-photon microscopy (2PM) in scattering biological tissues, such as the mouse brain, since the longer excitation wavelength reduces tissue scattering and the higher-order non-linear excitation suppresses out-of-focus background fluorescence. Imaging depth and resolution can further be improved by aberration correction using adaptive optics (AO) techniques where a spatial light modulator (SLM) is used to correct wavefront aberrations. Here, we present and analyze a 3PM AO system for in vivo mouse brain imaging. We use a femtosecond source at 1300 nm to generate three-photon (3P) fluorescence in yellow fluorescent protein (YFP) labeled mouse brain and a microelectromechanical (MEMS) SLM to apply different Zernike phase patterns. The 3P fluorescence signal is used as feedback to calculate the amount of phase correction without direct phase measurement. We show signal improvement in the cortex and the hippocampus at greater than 1 mm depth and demonstrate close to diffraction-limited imaging in the cortical layers of the brain, including imaging of dendritic spines. In addition, we characterize the effective volume for AO correction within brain tissues, and discuss the limitations of AO correction in 3PM of mouse brain.
Dynamic Effective Connectivity Patterns During Rapid Face Stimuli Presentation in Body Dysmorphic Disorder
Authors: Wong Wan-wa , Rangaprakash D. , Moody Teena D. , Feusner Jamie D.
Published: May 2022

In individuals with body dysmorphic disorder (BDD), perceptual appearance distortions may be related to imbalances in global vs. local visual processing. Understanding the mechanistic brain effects of potential interventions is crucial for rational treatment development. The dorsal visual stream (DVS) is tuned to rapid image presentation, facilitating global/holistic processing, whereas the ventral visual stream (VVS), responsible for local/detailed processing, reduces activation magnitude with shorter stimulus duration. This study tested a strategy of rapid, short-duration face presentation on visual system connectivity. Thirty-eight unmedicated adults with BDD and 29 healthy controls viewed photographs of their faces for short (125 ms, 250 ms, 500 ms) and long (3000 ms) durations during fMRI scan. Dynamic effective connectivity in DVS and VVS was analyzed. BDD individuals exhibited weaker connectivity from occipital to parietal DVS areas than controls for all stimuli durations. Short compared with long viewing durations (125 ms vs. 3,000 ms and 500 ms vs. 3,000 ms) resulted in significantly weaker VVS connectivity from calcarine cortex to inferior occipital gyri in controls; however, there was only a trend for similar results in BDD. The DVS to VVS ratio, representing a balance between global and local processing, incrementally increased with shorter viewing durations in BDD, although it was not statistically significant. In sum, visual systems in those with BDD are not as responsive as in controls to rapid face presentation. Whether rapid face presentation could reduce connectivity in visual systems responsible for local/detailed processing in BDD may necessitate different parameters or strategies. These results provide mechanistic insights for perceptual retraining treatment designs.
Neural Cell Type Diversity in Cnidaria
Authors: Sprecher Simon G.
Published: May 2022

Neurons are the fundamental building blocks of nervous systems. It appears intuitive that the human brain is made up of hundreds, if not thousands different types of neurons. Conversely, the seemingly diffuse nerve net of Cnidaria is often assumed to be simple. However, evidence that the Cnidaria nervous system is indeed simple is sparse. Recent technical advances make it possible to assess the diversity and function of neurons with unprecedented resolution. Transgenic animals expressing genetically encoded Calcium sensors allow direct physiological assessments of neural responses within the nerve net and provide insight into the spatial organization of the nervous system. Moreover, response and activity patterns allow the characterization of cell types on a functional level. Molecular and genetic identities on the other hand can be assessed combining single-cell transcriptomic analysis with correlations of gene expression in defined neurons. Here I review recent advances on these two experimental strategies focusing on Hydra, Nematostella, and Clytia.
Translocator Protein Ligand Etifoxine Attenuates MPTP-Induced Neurotoxicity
Authors: Tian Qi , Yang Xiaoxia , Du Juan , Huang Huachen , Liu Wei , Zhao Peng
Published: May 2022

Parkinson’s disease (PD) is a neurodegenerative disease, but the currently available treatments for this disease are symptomatic treatments. There is evidence that translocator protein (18 kDa) (TSPO) expression is upregulated in some neurodegenerative diseases, and TSPO ligands have obvious neuroprotective effects. However, the neuroprotective effects and other potential effects of the TSPO ligand etifoxine in PD remain unclear. Therefore, the present study was designed to explore the impacts of etifoxine on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that etifoxine significantly reduced motor function deficits, decreased the loss of tyrosine hydroxylase-positive neurons in the substantia nigra, and attenuated the decrease in striatal dopamine levels in mice that received MPTP. Etifoxine diminished the production of inflammatory mediators and infiltration of leukocytes in the brain after MPTP exposure. In vitro studies suggested that microglia contribute to etifoxine’s neuroprotective effect. The results showed that etifoxine can alleviate MPTP-induced neurotoxicity and neuroinflammation, providing a new idea for the treatment of PD.