bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of microbial community of surface and deep chlorophyll maximum to nutrients and light in South China Sea
Authors: Gong Fahui , Zhang Yafeng , Xie Wei , Wu Xiuqin , Zhang Han , Huang Suixuan , Gong Jun , Yin Kedong
Published: March 2023

In oligotrophic seas such as South China Sea, the subsurface or deep chlorophyll maximum (DCM) is always present. The surface planktonic community receives sufficient light, but is short of nutrients. The DCM layer is under light limitation, but frequent supply of nutrients. Therefore, vertical mixing becomes critical in determining their community composition and drives their changes by responding to light and nutrients. In this study, we conducted an onboard experiment by collecting seawater samples at surface and the DCM layer and adding nutrients, and incubated them under full sunlight and 10% light, and examined the diversity of bacterial and eukaryotic communities and their cell abundance using 16/18S high throughput sequencing and FCM approaches. Our study found large differences in bacterial and eukaryotic community structure and cell abundance between the surface and DCM. After 72 hours of culture, taxonomically the incubated surface water was dominated by pico-eukaryotic phytoplankton, while the incubated DCM layer water is dominated by diatoms, which suggests diatoms are the main functional group of phytoplankton bloom after a vertical mixing event. These findings indicate that phytoplankton at the DCM respond to enhanced light and frequent supplied nutrients due to vertical mixing and thus maintain primary productivity in the otherwise oligotrophic oceans.
Dissolved organic matter in the northwestern Pacific marginal seas: Insight into the distribution of its optical properties
Authors: Han Heejun , Kim Hyung Bo , Kim Jeonghyun , Kim Guebuem , Hwang Jeomshik , Nam SungHyun
Published: March 2023

Dissolved organic carbon (DOC) and the optical properties of dissolved organic matter (chromophoric- and fluorescent dissolved organic matter; CDOM and FDOM) were measured to determine the distributions and drivers of DOM in the northwestern Pacific marginal seas, including the East China Sea, the Yellow Sea, and the East/Japan Sea, in August 2020. In this study, the concentrations of DOC and CDOM/FDOM in surface water showed good correlations with salinity, indicating a predominant contribution from the Changjiang River. However, significantly high concentrations of DOC and FDOM were also observed in the central Yellow Sea region, which seems to be produced mainly from the continental shelf-water and enriched over the water residence time of the Yellow Sea, while the lowest concentrations of DOC and CDOM/FDOM were found in high-salinity waters near the southern sea of Korea. In addition, the East/Japan Sea showed relatively low DOC concentrations and high FDOM values. To distinguish the physical mixing and biogeochemical processes of DOM, we estimated the water mass fractions using an optimum multi-parameter analysis with hydrological and DOM parameters of the major water masses in this region. Our results showed that five primary external drivers of DOM distribution were intrusions of (1) the Changjiang diluted water and (2) the Kuroshio Current water in the surface water, the mixing of (3) the Yellow Sea bottom cold water and (4) the Kuroshio sub-surface water in the bottom layer, and (5) upwelling of the East/Japan Sea water. We conclude that the distribution of DOM is significantly influenced by the mixing of multiple water masses, and the optical signature of DOM can be an effective proxy for tracing the origins and characteristics of DOM in this region.
Zonally heated tooling for moulding complex and highly tapered composite parts
Authors: Maes Vincent K. , Radhakrishnan Arjun , Lombetti Diego , Kratz James
Published: March 2023

Curing of composite material parts often rely on slow cure cycles to manage exotherms and avoid hot or cold spots in the part. This is especially true for larger, thicker and/or geometrically complex parts, which suffer from unevenness in heating between different regions of the part stemming from thickness variations and made worse by the use of convection heating in ovens and autoclaves. An alternative technology for moulding is using heated tooling, which improves the energy efficiency of the process but can also significantly increase the tooling costs. However, the true power of heated tooling is in the ability to tailor the temperature profile in different regions. By introducing zonal heating, significantly faster process cycles can be achieved, hence improving production rates. Using cure simulation, two identical components are analysed, one part produced using convection heating (i.e., oven) and the second made using direct heating (i.e., heated tooling). The zonal approach was tuned based on numerical models and shows a reduction of 17.5% in terms of cure time and the experimental trials found an approximate 45% reduction in energy consumption.
Oxypurinol protects renal ischemia/reperfusion injury via heme oxygenase-1 induction
Authors: Kang Hye Bin , Lim Chae Kyu , Kim Jongwan , Han Sang Jun
Published: March 2023

Renal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) by increasing oxidative stress, inflammatory responses, and tubular cell death. Oxypurinol, an active metabolite of allopurinol, is a potent anti-inflammatory and antioxidant agent. To investigate the therapeutic potential and underlying mechanism of oxypurinol in ischemic AKI, C57BL/6 male mice were intraperitoneally injected with oxypurinol and subjected to renal I/R or sham surgery. We found that oxypurinol-treated mice had lower plasma creatinine and blood urea nitrogen levels and tubular damage (hematoxylin-and-eosin staining) compared to vehicle-treated mice after renal I/R injury. Furthermore, oxypurinol treatment reduced kidney inflammation (i.e., neutrophil infiltration and MIP-2 mRNA induction), oxidative stress (i.e., 4-HNE, heme oxygenase-1 [HO-1], 8-OHdG expression, and Catalase mRNA induction), and apoptosis (i.e., TUNEL or cleaved caspase-3-positive renal tubular cells), compared to vehicle-treated mice. Mechanistically, oxypurinol induced protein expressions of HO-1, which is a critical cytoprotective enzyme during ischemic AKI, and oxypurinol-mediated protection against ischemic AKI was completely eliminated by pretreatment with tin protoporphyrin IX, an HO-1 inhibitor. In conclusion, oxypurinol protects against renal I/R injury by reducing oxidative stress, inflammation, and apoptosis via HO-1 induction, suggesting its preventive potential in ischemic AKI.
Which are the most frequently involved peripheral joints in calcium pyrophosphate crystal deposition at imaging? A systematic literature review and meta-analysis by the OMERACT ultrasound – CPPD subgroup
Authors: Adinolfi Antonella , Sirotti Silvia , Sakellariou Garifallia , Cipolletta Edoardo , Filippucci Emilio , Porta Francesco , Zanetti Anna , Ughi Nicola , Sarzi-Puttini Piercarlo , Scirè Carlo Alberto , Keen Helen , Pineda Carlos , Terslev Lene , D’Agostino Maria Antonietta , Filippou Georgios
Published: March 2023

Objectives

To identify the prevalence of calcium pyrophosphate crystal deposition (CPPD) using ultrasound and conventional radiology at peripheral joints in patients with suspected or definite CPPD.

Methods

A systematic literature search was performed in PubMed and Embase using pre-defined search strategies from inception to April 2021 to identify studies that evaluated conventional radiology and ultrasound in detecting CPPD at peripheral joints, including definite or suspected CPPD [Research question 1 (RQ1) and Research Question 2 (RQ2), respectively]. For the meta-analysis, the first, second, and third sub-analysis included studies with the knee, and knee or wrist as the index joint for CPPD (without restrictions on the reference standard) and synovial fluid analysis or histology as a reference standard (without restrictions on the index joint), respectively.

Results

One-thousand eight hundred and twenty-seven manuscripts were identified, of which 94 articles were finally included. Twenty-two and seventy-two papers were included in RQ1 and RQ2, respectively. The knee had the highest prevalence for RQ1 and RQ2 by both conventional radiology and ultrasound, followed by the wrist with the highest prevalence for RQ1. The hand had the lowest CPPD prevalence. The third sub-analysis showed a higher CPPD prevalence on ultrasound than conventional radiology at the knee (only data available).

Conclusion

Among all peripheral joints, the knees and wrists could be regarded as the target joints for CPPD detection by imaging. Furthermore, ultrasound seems to detect a higher number of calcium pyrophosphate deposits than conventional radiology, even when using a more restrictive reference standard.
Telomere-related genes as potential biomarkers to predict endometriosis and immune response: Development of a machine learning-based risk model
Authors: Zhang He , Kong Weimin , Xie Yunkai , Zhao Xiaoling , Luo Dan , Chen Shuning , Pan Zhendong
Published: March 2023

Introduction

Endometriosis (EM) is an aggressive, pleomorphic, and common gynecological disease. Its clinical presentation includes abnormal menstruation, dysmenorrhea, and infertility, which seriously affect the patient's quality of life. However, the pathogenesis underlying EM and associated regulatory genes are unknown.

Methods

Telomere-related genes (TRGs) were uploaded from TelNet. RNA-sequencing (RNA-seq) data of EM patients were obtained from three datasets (GSE5108, GSE23339, and GSE25628) in the GEO database, and a random forest approach was used to identify telomere signature genes and build nomogram prediction models. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the pathways involved in the action of the signature genes. Finally, the CAMP database was used to screen drugs for potential use in EM treatment.

Results

Fifteen total genes were screened as EM–telomere differentially expressed genes. Further screening by machine learning obtained six genes as characteristic predictive of EM. Immuno-infiltration analysis of the telomeric genes showed that expressions including macrophages and natural killer cells were significantly higher in cluster A. Further enrichment analysis showed that the differential genes were mainly enriched in biological pathways like cell cycle and extracellular matrix. Finally, the Connective Map database was used to screen 11 potential drugs for EM treatment.

Discussion

TRGs play a crucial role in EM development, and are associated with immune infiltration and act on multiple pathways, including the cell cycle. Telomere signature genes can be valuable predictive markers for EM.
Effects of resistance and balance exercises for athletic ability and quality of life in people with osteoporotic vertebral fracture: Systematic review and meta-analysis of randomized control trials
Authors: Li Xuefei , Chen Wenhua , Chen Qian , Li Fangfang , Chen Chen , Li Pan , Li Fangyu , Guo Suxia , Chen Pinghua , Yuan Weina , Liu Dan , Wang Shiyun , Hu Zhijun
Published: March 2023

Purpose

This study aimed to use meta-analysis to determine the impact of resistance and balance training on athletic ability and quality of life for patients with osteoporotic vertebral fracture (OVF).

Methods

This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria for systematic reviews and meta-analyzes. The PubMed, Web of science, Cochrane, Embase, and CNKI databases were searched for randomized controlled trials (RCTs) up to September 2022. The search strategy was related to the intervention measures, population, and results, and was structured around the search terms: “Exercise,” “Osteoporotic vertebral fracture,” and “activities of function.” Two reviewers strictly implemented the inclusion and exclusion criteria. Subgroup analyzes of age and training duration were performed for the main outcomes.

Results

We included 12 RCTs (n = 1,289) of resistance and balance training in patients with OVF. Compared with controls, the intervention group showed improvements on the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis, visual analog pain scale, Timed Up and Go, falls efficacy scale international (FES-I), kyphosis, and functional reach. On subgroup analysis, the effect was more significant when training continued >10 weeks.

Conclusion

Resistance and balance exercise training improved function and balance, and reduced fall risk in patients with OVF. We recommend resistance and balance training for at least 10 weeks. Future multicenter, large sample trials are needed for more reliable conclusions.
An untargeted exometabolomics approach to characterize dissolved organic matter in groundwater of the Samail Ophiolite
Authors: Seyler Lauren M. , Kraus Emily A. , McLean Craig , Spear John R. , Templeton Alexis S. , Schrenk Matthew O.
Published: March 2023

The process of serpentinization supports life on Earth and gives rise to the habitability of other worlds in our Solar System. While numerous studies have provided clues to the survival strategies of microbial communities in serpentinizing environments on the modern Earth, characterizing microbial activity in such environments remains challenging due to low biomass and extreme conditions. Here, we used an untargeted metabolomics approach to characterize dissolved organic matter in groundwater in the Samail Ophiolite, the largest and best characterized example of actively serpentinizing uplifted ocean crust and mantle. We found that dissolved organic matter composition is strongly correlated with both fluid type and microbial community composition, and that the fluids that were most influenced by serpentinization contained the greatest number of unique compounds, none of which could be identified using the current metabolite databases. Using metabolomics in conjunction with metagenomic data, we detected numerous products and intermediates of microbial metabolic processes and identified potential biosignatures of microbial activity, including pigments, porphyrins, quinones, fatty acids, and metabolites involved in methanogenesis. Metabolomics techniques like the ones used in this study may be used to further our understanding of life in serpentinizing environments, and aid in the identification of biosignatures that can be used to search for life in serpentinizing systems on other worlds.
The role of periodontitis in the link between alpha-tocopherol intake and cognitive performance: A mediation analysis in older adults
Authors: Zhang Heming , Sun Li , Zhang Lin , Li Jiangjing , Liu Yongfei , Chen Zhiyang , Wang Shuang , Gao Changjun , Sun Xude
Published: March 2023

Background

Epidemiological evidence on alpha (α)-tocopherol intake and cognitive performance in older individuals is controversial and the effect of periodontitis in this chain is sparse and limited. The goal of this study was to characterize the association between α-tocopherol intake and cognitive performance and the mediating role of periodontitis in a nationally representative sample of older adults.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES), 2011–2014, were used. Multivariate logistic regression analysis was performed to explore the association of α-tocopherol intake, periodontal measures (mean attachment loss [AL] and mean probing depth [PD]), and clinical periodontitis defined by the European Workshop in Periodontology with poor cognitive performance evaluated by Consortium to Establish a Registry for Alzheimer’s disease (CERAD); the animal fluency test (AFT); and the Digit Symbol Substitution test (DSST) and the correlation between α-tocopherol intake and clinical periodontitis. Multiple linear regression analysis was used to explore the relationship between α-tocopherol intake and periodontal measures. Mediation analysis was used to test the effects of periodontal measures on the association between α-tocopherol intake and cognitive measures.

Results

A total of 1,749 older participants (≥60 years of age) with complete periodontal diagnosis, dietary retrospective survey, and cognitive tests were included. In the fully adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of CERAD score, AFT score and DSST score were 0.214 (0.137–0.327), 0.378 (0.241–0.585) and 0.298 (0.169–0.512) for the highest versus lowest tertile of α-tocopherol intake, respectively. And participants with clinical periodontitis were more likely to exhibit lower DSST score (OR = 1.689; 95 CI%: 1.018–2.771) than those without periodontitis. Mean AL (OR = 1.296; 95 CI%: 1.102–1.524) and PD (OR = 1.667; 95 CI%: 1.18–2.363) were negatively correlated with DSST, and were estimated to mediate 9.1 and 8.2% of the total association between α-tocopherol intake and cognitive performance, respectively.

Conclusion

Finding of the present study suggested that participants with low α-tocopherol intake were at higher risk for developing cognitive decline. Moreover, periodontitis mediated the association between α-tocopherol intake and cognitive performance.
Mechanisms underlying TDP-43 pathology and neurodegeneration: An updated Mini-Review
Authors: Nilaver Benjamin I. , Urbanski Henryk F.
Published: March 2023

TAR DNA binding protein 43 kDa (TDP-43) plays an important role in several essential cell functions. However, TDP-43 dysfunction has been implicated in the development of various brain diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Recent investigations into the individual components of TDP-43 pathology show how broader TDP-43 dysfunction may precede these disease end states, and therefore could help to explain why TDP-43 dysfunction continues to be implicated in a rapidly expanding category of neurodegenerative diseases. The literature reviewed in this article suggests that dysregulation of TDP-43 initiated by some environmental and/or genetic insults can lead to a snowballing dysfunction across the cell, involving impaired gene expression, mRNA stability, as well as the function and coordination of those pathways directly regulated by TDP-43. Furthermore, the hallmarks of TDP-43 pathology, such as hyperphosphorylation and insoluble cytoplasmic accumulation of the protein may actually be artifacts of an upstream impairment in TDP-43’s normal function. Overall, the present article summarizes current knowledge regarding TDP-43’s normal and pathological cell functions and sheds light on possible mechanisms that underlie its causal role in neurodegeneration.
Anoxic spreading depolarization in the neonatal rat cortex in vitro
Authors: Gainutdinov Azat , Juzekaeva Elvira , Mukhtarov Marat , Khazipov Roustem
Published: March 2023

Anoxic spreading depolarization (aSD) is a hallmark of ischemic injury in the cerebral cortex. In adults, aSD is associated with rapid and nearly complete neuronal depolarization and loss of neuronal functions. While ischemia also evokes aSD in the immature cortex, developmental aspects of neuronal behavior during aSD remain largely unknown. Here, using oxygen-glucose deprivation (OGD) ischemia model in slices of the postnatal rat somatosensory cortex, we found that immature neurons displayed much more complex behaviors: they initially moderately depolarized during aSD, then transiently repolarised (for up to tens of minutes), and only then passed to terminal depolarization. The ability to fire action potentials was maintained in neurons mildly depolarized during aSD without reaching the level of depolarization block, and these functions were regained in the majority of immature neurons during post-aSD transient repolarization. The amplitude of depolarization and the probability of depolarization block during aSD increased, whereas transient post-SD repolarization levels and duration, and associated recovery in neuronal firing decreased with age. By the end of the first postnatal month, aSD acquired an adult-like phenotype, where depolarization during aSD merged with terminal depolarization and the phase of transient recovery was lost. Thus, changes in neuronal function during aSD undergo remarkable developmental changes that may contribute to lower susceptibility of the immature neurons to ischemia.
Approximate solutions to several classes of Volterra and Fredholm integral equations using the neural network algorithm based on the sine-cosine basis function and extreme learning machine
Authors: Lu Yanfei , Zhang Shiqing , Weng Futian , Sun Hongli
Published: March 2023

In this study, we investigate a new neural network method to solve Volterra and Fredholm integral equations based on the sine-cosine basis function and extreme learning machine (ELM) algorithm. Considering the ELM algorithm, sine-cosine basis functions, and several classes of integral equations, the improved model is designed. The novel neural network model consists of an input layer, a hidden layer, and an output layer, in which the hidden layer is eliminated by utilizing the sine-cosine basis function. Meanwhile, by using the characteristics of the ELM algorithm that the hidden layer biases and the input weights of the input and hidden layers are fully automatically implemented without iterative tuning, we can greatly reduce the model complexity and improve the calculation speed. Furthermore, the problem of finding network parameters is converted into solving a set of linear equations. One advantage of this method is that not only we can obtain good numerical solutions for the first- and second-kind Volterra integral equations but also we can obtain acceptable solutions for the first- and second-kind Fredholm integral equations and Volterra–Fredholm integral equations. Another advantage is that the improved algorithm provides the approximate solution of several kinds of linear integral equations in closed form (i.e., continuous and differentiable). Thus, we can obtain the solution at any point. Several numerical experiments are performed to solve various types of integral equations for illustrating the reliability and efficiency of the proposed method. Experimental results verify that the proposed method can achieve a very high accuracy and strong generalization ability.
Case report: Functional analysis of the p.Arg507Trp variant of the PIGT gene supporting the moderate epilepsy phenotype of mutations in the C-terminal region
Authors: Ben Ayed Ikhlas , Jallouli Olfa , Murakami Yoshiko , Souissi Amal , Mallouli Salma , Bouzid Amal , Kamoun Fatma , Elloumi Ines , Frikha Fakher , Tlili Abdelaziz , Weckhuysen Sarah , Kinoshita Taroh , Triki Chahnez Charfi , Masmoudi Saber
Published: March 2023

Pathogenic germline variants in the PIGT gene are associated with the “multiple congenital anomalies–hypotonia-seizures syndrome 3” (MCAHS3) phenotype. So far, fifty patients have been reported, most of whom suffer from intractable epilepsy. Recently, a comprehensive analysis of a cohort of 26 patients with PIGT variants has broadened the phenotypical spectrum and indicated that both p.Asn527Ser and p.Val528Met are associated with a milder epilepsy phenotype and less severe outcomes. Since all reported patients are of Caucasian/Polish origin and most harbor the same variant (p.Val528Met), the ability to draw definitive conclusions regarding the genotype–phenotype correlation remains limited. We report a new case with a homozygous variant p.Arg507Trp in the PIGT gene, detected on clinical exome sequencing. The North African patient in question displays a predominantly neurological phenotype with global developmental delay, hypotonia, brain abnormalities, and well-controlled epileptic seizures. Homozygous and heterozygous variants in codon 507 have been reported to cause PIGT deficiency without biochemical confirmation. In this study, FACS analysis of knockout HEK293 cells that had been transfected with wild-type or mutant cDNA constructs demonstrated that the p.Arg507Trp variant leads to mildly reduced activity. Our result confirm the pathogenicity of this variant and strengthen recently reported evidence on the genotype–phenotype correlation of the PIGT variant.
Factors contributing to sleep disturbances and excessive daytime sleepiness in patients with Parkinson's disease
Authors: Ogaki Keitaro , Fujita Hiroaki , Nozawa Narihiro , Shiina Tomohiko , Sakuramoto Hirotaka , Suzuki Keisuke
Published: March 2023

Background

Sleep disturbances and excessive daytime sleepiness (EDS) are common non-motor symptoms in patients with Parkinson's disease (PD). The purpose of this study was to identify the contributors to sleep disturbances, including insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder (RBD), sleep-disordered breathing, nocturnal akinesia and EDS, in patients with PD.

Methods

We conducted a cross-sectional study including 128 consecutive Japanese patients with PD. Sleep disturbances and EDS were defined as a PD Sleep Scale-2 (PDSS-2) total score ≥15 and an Epworth Sleepiness Scale (ESS) score >10, respectively. The patients were divided into four groups according to the presence or absence of sleep disturbances and EDS. We evaluated the disease severity, motor symptoms, cognition, olfactory test, the Scales for Outcomes in PD-Autonomic dysfunction (SCOPA-AUT), the Beck Depression Inventory-II (BDI-II), and the RBD Screening Questionnaire Japanese version (RBDSQ-J).

Results

Of 128 patients, 64 had neither EDS nor sleep disturbances, 29 had sleep disturbances without EDS, 14 had EDS without sleep disturbances, and 21 had both EDS and sleep disturbances. Patients with sleep disturbances had higher BDI-II scores than those without sleep disturbances. Probable RBD was more frequent in patients with both sleep disturbances and EDS than in those with neither EDS nor sleep disturbances. The SCOPA-AUT score was lower in patients with neither EDS nor sleep disturbances than in patients in the other three groups. Using multivariable logistic regression analysis with neither sleep disturbances nor EDS as a reference group, that the SCOPA-AUT score was an independent contributor to sleep disturbances (adjusted OR, 1.192; 95% CI, 1.065–1.333; P = 0.002) or EDS (OR, 1.245; 95% CI, 1.087–1.424; P = 0.001) and that the BDI-II (OR, 1.121; 95% CI, 1.021–1.230; P = 0.016) and RBDSQ-J scores (OR, 1.235; 95% CI, 1.007–1.516; P = 0.043) as well as the SCOPA-AUT score (OR, 1.137; 95% CI, 1.006–1.285; P = 0.040) were independent contributors to both sleep disturbances and EDS.

Conclusions

Autonomic symptoms were associated with patients with sleep disturbances or EDS, and depressive and RBD symptoms in addition to autonomic symptoms were associated with patients with both sleep disturbances and EDS.
Genetic variants and phenotype analysis in a five-generation Chinese pedigree with PCDH19 female-limited epilepsy
Authors: Zhou Wenjuan , Ouyang Yuzhen , Ji Yuqiao , Xi Qiong , Zhao Lingling
Published: March 2023

Objective

Albeit the gene of PCDH19-FE was ascertained, the correlation of gene mutation, PCDH19 protein structure, and phenotype heterogeneity remained obscure. This study aimed to report a five-generation pedigree of seven female patients of PCDH19-FE and tried to explore whether two variants were correlated with PCDH19 protein structure and function alteration, and PCDH19-FE phenotype.

Methods

We analyzed the clinical data and genetic variants of a PCDH19-FE pedigree, to explore the phenotype heterogeneity of PCDH19-FE and underlying mechanisms. In addition to the clinical information of family members, next-generation sequencing was adopted to detect the variant sites of probands with validation by sanger sequencing. And the sanger sequencing was conducted in other patients in this pedigree. The biological conservation analysis and population polymorphism analysis of variants were also performed subsequently. The structure alteration of mutated PCDH19 protein was predicted by AlphaFold2.

Results

Based on a five-generation pedigree of PCDH19-FE, missense variants of c.695A>G and c.2760T>A in the PCDH19 gene were found in the heterozygous proband (V:1), which resulted in the change of amino acid 232 from Asn to Ser (p.Asn232Ser) and amino acid 920 from Asp to Glu (p.Asp920Glu) influencing PCDH19 function. The other six females in the pedigree (II:6, II:8, IV:3, IV:4, IV:5, IV:11) exhibited different clinical phenotypes but shared the same variant. Two males with the same variant have no clinical manifestations (III:3, III:10). The biological conservation analysis and population polymorphism analysis demonstrated the highly conservative characteristics of these two variants. AlphaFold2 predicted that the variant, p.Asp920Glu, led to the disappearance of the hydrogen bond between Asp at position 920 and His at position 919. Furthermore, the hydrogen bond between Asp920 and His919 also disappeared when the Asn amino acid mutated to Ser at position 232.

Conclusion

A strong genotype-phenotype heterogeneity was observed among female patients with the same genotype in our PCDH19-FE pedigree. And two missense variants, c.695A > G and c.2760T>A in the PCDH19 gene, have been identified in our pedigree. The c.2760T>A variant was a novel variant site probably related to the PCDH19-FE.
Factors affecting variability in vestibulo-ocular reflex gain in the Video Head Impulse Test in individuals without vestibulopathy: A systematic review of literature
Authors: Money-Nolan Laurel Elise , Flagge Ashley Gaal
Published: March 2023

Introduction

The purpose of this systematic review was to summarize and synthesize published evidence examining variations in vestibulo-ocular reflex (VOR) gain outcomes for the Video Head Impulse Test (vHIT) in healthy individuals without vestibulopathy in order to describe factors that may influence test outcomes.

Methods

Computerized literature searches were performed from four search engines. The studies were selected based on relevant inclusion and exclusion criteria, and were required to examine VOR gain in healthy adults without vestibulopathy. The studies were screened using Covidence (Cochrane tool) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards (PRISMA-2020).

Results

A total of 404 studies were initially retrieved, of which a total of 32 studies met inclusion criteria. Four major categories were identified which lead to significant variation in VOR gain outcomes: participant-based factors, tester/examiner-based factors, protocol-based factors, and equipment-based factors.

Discussion

Various subcategories are identified within each of these classifications and are discussed, including recommendations for decreasing VOR gain variability in clinical practice.
Causal relationship between human blood omega-3 fatty acids and the risk of epilepsy: A two-sample Mendelian randomization study
Authors: Liang Zhen , Lou Yingyue , Li Zijian , Liu Songyan
Published: March 2023

Background

Though omega-3 fatty acids reduce seizures in several animal models, considerable controversy exists regarding the association between omega-3 fatty acids and epilepsy in human.

Objective

To assess whether genetically determined human blood omega-3 fatty acids are causally associated with the risk of epilepsy outcomes.

Methods

We conducted a two-sample Mendelian randomization (MR) analysis by applying summary statistics of genome-wide association study datasets of both exposure and outcomes. Single nucleotide polymorphisms significantly associated with blood omega-3 fatty acids levels were selected as instrumental variables to estimate the causal effects on epilepsy. Five MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) were conducted as the complement to IVW. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy.

Results

Genetically predicted the increase of human blood omega-3 fatty acids levels was associated with a higher risk of epilepsy (OR = 1.160, 95%CI = 1.051–1.279, P = 0.003).

Conclusions

This study revealed a causal relationship between blood omega-3 fatty acids and the risk of epilepsy, thus providing novel insights into the development mechanism of epilepsy.
A novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves
Authors: Shemonti Abida Sanjana , Plebani Emanuele , Biscola Natalia P. , Jaffey Deborah M. , Havton Leif A. , Keast Janet R. , Pothen Alex , Dundar M. Murat , Powley Terry L. , Rajwa Bartek
Published: March 2023

A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial arrangement of myelinated and unmyelinated axons in peripheral nerves is random, however, in reality the axonal organization is inhomogeneous and anisotropic. Present quantitative neuroanatomy methods analyze peripheral nerves in terms of the number of axons and the morphometric characteristics of the axons, such as area and diameter. In this study, we employed spatial statistics and point process models to describe the spatial arrangement of axons and Sinkhorn distances to compute the similarities between these arrangements (in terms of first- and second-order statistics) in various vagus and pelvic nerve cross-sections. We utilized high-resolution transmission electron microscopy (TEM) images that have been segmented using a custom-built high-throughput deep learning system based on a highly modified U-Net architecture. Our findings show a novel and innovative approach to quantifying similarities between spatial point patterns using metrics derived from the solution to the optimal transport problem. We also present a generalizable pipeline for quantitative analysis of peripheral nerve architecture. Our data demonstrate differences between male- and female-originating samples and similarities between the pelvic and abdominal vagus nerves.
Lifting as we climb: Experiences and recommendations from women in neural engineering
Authors: Jantz Maria K. , Mak Jennifer , Dalrymple Ashley N. , Farooqui Juhi , Grigsby Erinn M. , Herrera Angelica J. , Pirondini Elvira , Collinger Jennifer L.
Published: March 2023

Neural engineering is an emerging and multidisciplinary field in which engineering approaches are applied to neuroscience problems. Women are underrepresented in engineering fields, and indeed in science, technology, engineering, and mathematics (STEM) fields generally. Underrepresentation of women is particularly notable at later academic career stages, suggesting that even though women are interested in the field, barriers exist that ultimately cause them to leave. Here, we investigate many of the obstacles to women’s success in the field of neural engineering and provide recommendations and materials to overcome them. We conducted a review of the literature from the past 15 years regarding the experiences of women in academic careers, as well as reports on the number of women in fields closely related to neural engineering from the National Science Foundation (NSF) and the American Society for Engineering Education (ASEE). Additionally, we interviewed six women in neural engineering who are involved in initiatives and outreach concerning the inclusion and experiences of women in engineering. Throughout the literature and interviews, we identified common themes spanning the role of identity and confidence, professional relationships, career-related hurdles, and personal and professional expectations. We explore each of these themes in detail and provide resources to support the growth of women as they climb within the field of neural engineering.
Combined effect of transcutaneous auricular vagus nerve stimulation and 0.1 Hz slow-paced breathing on working memory
Authors: Tian Qian-Qian , Cheng Chen , Liu Peng-Hui , Yin Zi-Xin , Zhang Meng-Kai , Cui Ya-Peng , Zhao Rui , Deng Hui , Lu Li-Ming , Tang Chun-Zhi , Xu Neng-Gui , Yang Xue-Juan , Sun Jin-Bo , Qin Wei
Published: March 2023

Background

Previous research has found that transcutaneous auricular vagus nerve stimulation (taVNS) can improve working memory (WM) performance. It has also been shown that 0.1 Hz slow-paced breathing (SPB, i.e., breathing at a rate of approximately 6 breaths/min) can significantly influence physical state and cognitive function via changes in autonomic afferent activity. In the present study, we investigated the synergistic effects of taVNS and SPB on WM performance.

Methods

A total of 96 healthy people participated in this within-subjects experiment involving four conditions, namely taVNS, SPB, combined taVNS with SPB (taVNS + SPB), and sham. Each participant underwent each intervention for 30 min and WM was compared pre- and post-intervention using the spatial and digit n-back tasks in a random order four times. Permutation-based analysis of variance was used to assess the interaction between time and intervention.

Results

For the spatial 3-back task, a significant interaction between time and intervention was found for the accuracy rate of matching trials (mACC, p = 0.03). Post hoc analysis suggested that both taVNS and taVNS + SPB improved WM performance, however, no significant difference was found in the SPB or sham groups.

Conclusion

This study has replicated the effects of taVNS on WM performance reported in previous studies. However, the synergistic effects of combined taVNS and SPB warrant further research.
EARDS: EfficientNet and attention-based residual depth-wise separable convolution for joint OD and OC segmentation
Authors: Zhou Wei , Ji Jianhang , Jiang Yan , Wang Jing , Qi Qi , Yi Yugen
Published: March 2023

Background

Glaucoma is the leading cause of irreversible vision loss. Accurate Optic Disc (OD) and Optic Cup (OC) segmentation is beneficial for glaucoma diagnosis. In recent years, deep learning has achieved remarkable performance in OD and OC segmentation. However, OC segmentation is more challenging than OD segmentation due to its large shape variability and cryptic boundaries that leads to performance degradation when applying the deep learning models to segment OC. Moreover, the OD and OC are segmented independently, or pre-requirement is necessary to extract the OD centered region with pre-processing procedures.

Methods

In this paper, we suggest a one-stage network named EfficientNet and Attention-based Residual Depth-wise Separable Convolution (EARDS) for joint OD and OC segmentation. In EARDS, EfficientNet-b0 is regarded as an encoder to capture more effective boundary representations. To suppress irrelevant regions and highlight features of fine OD and OC regions, Attention Gate (AG) is incorporated into the skip connection. Also, Residual Depth-wise Separable Convolution (RDSC) block is developed to improve the segmentation performance and computational efficiency. Further, a novel decoder network is proposed by combining AG, RDSC block and Batch Normalization (BN) layer, which is utilized to eliminate the vanishing gradient problem and accelerate the convergence speed. Finally, the focal loss and dice loss as a weighted combination is designed to guide the network for accurate OD and OC segmentation.

Results and discussion

Extensive experimental results on the Drishti-GS and REFUGE datasets indicate that the proposed EARDS outperforms the state-of-the-art approaches. The code is available at https://github.com/M4cheal/EARDS.
Demonstrating a link between diet, gut microbiota and brain: 14C radioactivity identified in the brain following gut microbial fermentation of 14C-radiolabeled tyrosine in a pig model
Authors: Murray Margaret , Barlow Christopher K. , Blundell Scott , Buecking Mark , Gibbon Anne , Goeckener Bernd , Kaminskas Lisa M. , Leitner Patricia , Selby-Pham Sophie , Sinclair Andrew , Waktola Habtewold D. , Williamson Gary , Bennett Louise E.
Published: March 2023

Background

There is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods.

Methods

We developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain.

Results

Radioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose).

Conclusion

Metabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.
Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity
Authors: Rodrigues Fernanda da Silva , Jantsch Jeferson , Fraga Gabriel de Farias , Dias Victor Silva , Eller Sarah , De Oliveira Tiago Franco , Giovenardi Márcia , Guedes Renata Padilha
Published: March 2023

Introduction

The implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed.

Methods

Here we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats.

Results

We have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1β in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes.

Discussion

Together, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.
The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer
Authors: Cusenza Vincenza Ylenia , Tameni Annalisa , Neri Antonino , Frazzi Raffaele
Published: March 2023

Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) and 2’-O-methylation (Nm) are some of the lncRNAs epigenetic modifications. The epigenetic modifications of RNA are controlled by three classes of enzymes, each playing a role in a specific phase of the modification. These enzymes are defined as “writers”, “readers” and “erasers”. m6A and m5C are the most studied epigenetic modifications in RNA. These modifications alter the structure and properties, thus modulating the functions and interactions of lncRNAs. The aberrant expression of several lncRNAs is linked to the development of a variety of cancers and the epigenetic signatures of m6A- or m5C-related lncRNAs are increasingly recognized as potential biomarkers of prognosis, predictors of disease stage and overall survival. In the present manuscript, the most up to date literature is reviewed with the focus on m6A and m5C modifications of lncRNAs and their significance in cancer.
Case report: Vitiligo-like toxicity due to ribociclib during first-line treatment of metastatic breast cancer: two cases of premature interruption of therapy and exceptional response
Authors: Pasqualoni Mariangela , Orlandi Armando , Palazzo Antonella , Garufi Giovanna , Cannizzaro Maria Chiara , Pontolillo Letizia , Pannunzio Sergio , Cutigni Claudia , Sollena Pietro , Federico Francesco , Bria Emilio , Tortora Giampaolo
Published: March 2023

Cancer treatment-related adverse events (AEs) are sometimes associated with outcomes for cancer patients, especially with the newest therapies such as target therapy and immunotherapy. A few years ago, the first-line therapy for hormone-receptor-positive metastatic breast cancer (mBC) patients has been deeply changed by the introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors, and now, we are improving our knowledge about their AEs and significance in clinical practice. Here, we report our experience with two cases of vitiligo-like lesions that occur early during treatment with ribociclib. We tried to change the CDK4/6 inhibitor for one patient, but the skin reaction persisted. Both patients retained only the endocrine therapy alone and had an unexpected durable progression-free survival (PFS). Some data on skin toxicities, including vitiligo-like lesions by CDK4/6 inhibitors, have recently been reported in the literature, but for the first time, we highlight a possible correlation with improved survival outcomes of patients. Uncovering the etiology of this toxicity, verifying the involvement of the immune system, and demonstrating a possible positive impact in survival represent an intriguing research objective for the near future.