bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil metatranscriptome demonstrates a shift in C, N, and S metabolisms of a grassland ecosystem in response to elevated atmospheric CO2
Authors: Rosado-Porto David , Ratering Stefan , Moser Gerald , Deppe Marianna , Müller Christoph , Schnell Sylvia
Published: August 2022

Soil organisms play an important role in the equilibrium and cycling of nutrients. Because elevated CO2 (eCO2) affects plant metabolism, including rhizodeposition, it directly impacts the soil microbiome and microbial processes. Therefore, eCO2 directly influences the cycling of different elements in terrestrial ecosystems. Hence, possible changes in the cycles of carbon (C), nitrogen (N), and sulfur (S) were analyzed, alongside the assessment of changes in the composition and structure of the soil microbiome through a functional metatranscriptomics approach (cDNA from mRNA) from soil samples taken at the Giessen free-air CO2 enrichment (Gi-FACE) experiment. Results showed changes in the expression of C cycle genes under eCO2 with an increase in the transcript abundance for carbohydrate and amino acid uptake, and degradation, alongside an increase in the transcript abundance for cellulose, chitin, and lignin degradation and prokaryotic carbon fixation. In addition, N cycle changes included a decrease in the transcript abundance of N2O reductase, involved in the last step of the denitrification process, which explains the increase of N2O emissions in the Gi-FACE. Also, a shift in nitrate (NO3-) metabolism occurred, with an increase in transcript abundance for the dissimilatory NO3- reduction to ammonium (NH4+) (DNRA) pathway. S metabolism showed increased transcripts for sulfate (SO42-) assimilation under eCO2 conditions. Furthermore, soil bacteriome, mycobiome, and virome significantly differed between ambient and elevated CO2 conditions. The results exhibited the effects of eCO2 on the transcript abundance of C, N, and S cycles, and the soil microbiome. This finding showed a direct connection between eCO2 and the increased greenhouse gas emission, as well as the importance of soil nutrient availability to maintain the balance of soil ecosystems.
Effects of intestinal microbiota on physiological metabolism and pathogenicity of Vibrio
Authors: Sun Han , Zhu Changliang , Fu Xiaodan , Khattak Shakir , Wang Jingyu , Liu Zhihao , Kong Qing , Mou Haijin , Secundo Francesco
Published: August 2022

Vibrio species are disseminated broadly in the marine environment. Some of them can cause severe gastroenteritis by contaminating seafood and drinking water, such as Vibrio parahaemolyticus, Vibrio cholerae, and Vibrio vulnificus. However, their pathogenic mechanism still needs to be revealed to prevent and reduce morbidity. This review comprehensively introduces and discusses the common pathogenic process of Vibrio including adhesion, cell colonization and proliferation, and resistance to host immunity. Vibrio usually produces pathogenic factors including hemolysin, type-III secretion system, and adhesion proteins. Quorum sensing, a cell molecular communication system between the bacterial cells, plays an important role in Vibrio intestinal invasion and colonization. The human immune system can limit the virulence of Vibrio or even kill the bacteria through different responses. The intestinal microbiota is a key component of the immune system, but information on its effects on physiological metabolism and pathogenicity of Vibrio is seldom available. In this review, the effects of intestinal microorganisms and their metabolites on the invasion and colonization of common pathogenic Vibrio and VBNC status cells are discussed, which is conducive to finding the next-generation prebiotics. The strategy of dietary intervention is discussed for food safety control. Finally, future perspectives are proposed to prevent Vibrio infection in aquaculture.
Contribution of the genomic and nutritional differentiation to the spatial distribution of bacterial colonies
Authors: Hitomi Kenya , Weng Jieruiyi , Ying Bei-Wen
Published: August 2022

Colony growth is a common phenomenon of structured populations dispersed in nature; nevertheless, studies on the spatial distribution of colonies are largely insufficient. Here, we performed a systematic survey to address the questions of whether and how the spatial distribution of colonies was influenced by the genome and environment. Six Escherichia coli strains carrying either the wild-type or reduced genomes and eight media of varied nutritional richness were used to evaluate the genomic and environmental impacts, respectively. The genome size and nutritional variation contributed to the mean size and total area but not the variation and shape of size distribution of the colonies formed within the identical space and of equivalent spatial density. The spatial analysis by means of the Voronoi diagram found that the Voronoi correlation remained nearly constant in common, in comparison to the Voronoi response decreasing in correlation to genome reduction and nutritional enrichment. Growth analysis at the single colony level revealed positive correlations of the relative growth rate to both the maximal colony size and the Voronoi area, regardless of the genomic and nutritional variety. This result indicated fast growth for the large space assigned and supported homeostasis in the Voronoi correlation. Taken together, the spatial distribution of colonies might benefit efficient clonal growth. Although the mechanisms remain unclear, the findings provide quantitative insights into the genomic and environmental contributions to the growth and distribution of spatially or geographically isolated populations.
2,3-Dehydrokievitone combats methicillin-resistant Staphylococcus aureus infection by reducing alpha-hemolysin expression
Authors: Yu Hangqian , Liu Jingyu , Wang Li , Guan Shuhan , Jin Yajing , Zheng Jianze , Xiang Hua , Wang Dacheng , Liu Dianfeng
Published: August 2022

Due to powerful drug resistance and fatal toxicity of methicillin-resistant Staphylococcus aureus (MRSA), therapeutic strategies against virulence factors present obvious advantages since no evolutionary pressure will induce bacterial resistance. Alpha-hemolysin (Hla) is an extracellular toxin secreted by Staphylococcus aureus and contributes to bacterial pathogenicity. Herein, we identified a natural product 2,3-dehydrokievitone (2,3-DHKV) for inhibiting Hla activity of MRSA strain USA300 but not affecting bacteria growth. 2,3-DHKV significantly decreased hemolysin expression in a dose-dependent manner, but it did not potently neutralize hemolysin activity. Subsequently, cellular thermal shift and heptamer formation assays confirmed that 2,3-DHK affects hemolytic activity through indirect binding to Hla. RT-qPCR and western blot revealed that 2,3-DHKV suppressed Hla expression at the mRNA and protein levels, and further decreased accessory gene regulator A (agrA) transcription levels. We also observed that 2,3-DHK significantly attenuated the damage of A549 cells by S. aureus and reduced the release of lactate dehydrogenase (LDH). Moreover, in the MRSA-induced pneumonia mouse model, 2,3-DHK treatment prolonged the life span of mice and reduced the bacterial load in the lungs, which significantly alleviated the damage to the lungs. In summary, this study proved that 2,3-DHK as a Hla inhibitor is a potential antivirulence agent against MRSA infection.
The application of enzymatic fermented soybean effectively regulates associated microbial communities in tea soil and positively affects lipid metabolites in tea new shoots
Authors: Zhang Shuning , Sun Litao , Shi Yujie , Song Yujie , Wang Yu , Fan Kai , Zong Rui , Li Yusheng , Wang Linjun , Bi Caihong , Ding Zhaotang
Published: August 2022

Compared with traditional organic fertilizer, fermented soybean is a better fertilizer resource in tea plantations. The application of organic fertilizer is a feasible practice to mitigate the soil degradation caused by the overuse of chemical fertilizers, which can effectively regulate soil microbial communities in tea plantations. However, the effects of fermented soybean on soil microbial communities, soil metabolites and metabolites in tea new shoots have not been systematically demonstrated, and their interactions have never been studied. Here, we investigated the responses of the soil microbial community, soil metabolites and metabolites of tea new shoots to urea fertilization (UF), naturally fermented soybean fertilization (NFS) and enzymatic fermented soybean fertilization (EFS), and analyzed the relationships between soil microbes, soil metabolites and metabolites in tea new shoots. The results showed that soil bacterial communities were dominated by Pseudomonas, Romboutsia, Candidatus_Nitrosotalea and Helicobacter, and soil fungal communities were dominated by Peziza, Fusarium, Candida and Cheilymenia at the genus level. In EFS, bacterial genera (Glutamicibacter and Streptomyces) and fungal genera (Candida and Actinomucor) presented high abundances, which were correlated with soil carbohydrate and lipid including D-Mannitol, D-Sorbitol, 9,12-Octadecadienoic acid and (Z)-13-Docosenoic acid. Enzymatic fermented soybean fertilization also affected the lipid metabolites in tea new shoots. Glycerolipids and glycerophospholipids significantly increased in EFS, which positively correlated with some soil microbial communities. Besides, the application of fermented soybean fertilizer could increase the contents of TP, AP and AK, which were also important environmental factors affecting the structure of soil microbial community in tea plantation. It was concluded that fermented soybean fertilization could improve soil nutrition, regulate associated microbial communities, and positively affect lipid metabolites in tea new shoots. This study not only explores the relationships between soil microbes and metabolites in tea plants, but also provides feasible technical guidance to cultivate high-quality tea using soybean as high-grade fertilizer.
Differential effect of SARS-CoV-2 infection on stress granule formation in Vero and Calu-3 cells
Authors: Kim Dongbum , Maharjan Sony , Kang Mijeong , Kim Jinsoo , Park Sangkyu , Kim Minyoung , Baek Kyeongbin , Kim Suyeon , Suh Jun Gyo , Lee Younghee , Kwon Hyung-Joo
Published: August 2022

Stress granule formation is induced by numerous environmental stressors, including sodium arsenite treatment and viral infection. Accordingly, stress granules can inhibit viral propagation and function as part of the antiviral host response to numerous viral infections. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antagonizes stress granule formation, in part, via interaction between SARS-CoV-2 nucleocapsid (N) protein and Ras-GTPase-activating SH3-domain-binding protein 1 (G3BP1). However, it is unclear whether there are differential effects in different cell types. In this study, we assessed interaction between the N protein of SARS-CoV-2 S clade and G3BP1/2 in Vero and Calu-3 cells and investigated the effect of various SARS-CoV-2 strains on sodium arsenite-induced stress granule formation. Our data show that SARS-CoV-2 S clade N protein interacts with both G3BP1 and G3BP2 more strongly in Calu-3 vs. Vero cells. Consistent with this observation, infection with SARS-CoV-2 S clade induces stress granule formation in Vero but not in Calu-3 cells. However, infection with SARS-CoV-2 S clade, as well as other SARS-CoV-2 variants, inhibits sodium arsenite-induced stress granule formation in both cell lines. Taken together, our results show differential effects of SARS-CoV-2 infection on stress granule formation that is dependent on host cell type, rather than virus strain type.
Shared pathobiology identifies AMPK as a therapeutic target for obesity and autosomal dominant polycystic kidney disease
Authors: Iliuta Ioan-Andrei , Song Xuewen , Pickel Lauren , Haghighi Amirreza , Retnakaran Ravi , Scholey James , Sung Hoon-Ki , Steinberg Gregory R. , Pei York
Published: August 2022

Autosomal dominant polycystic kidney disease (ADPKD) is the most common Mendelian kidney disease, affecting approximately one in 1,000 births and accounting for 5% of end-stage kidney disease in developed countries. The pathophysiology of ADPKD is strongly linked to metabolic dysregulation, which may be secondary to defective polycystin function. Overweight and obesity are highly prevalent in patients with ADPKD and constitute an independent risk factor for progression. Recent studies have highlighted reduced AMP-activated protein kinase (AMPK) activity, increased mammalian target of rapamycin (mTOR) signaling, and mitochondrial dysfunction as shared pathobiology between ADPKD and overweight/obesity. Notably, mTOR and AMPK are two diametrically opposed sensors of energy metabolism that regulate cell growth and proliferation. However, treatment with the current generation of mTOR inhibitors is poorly tolerated due to their toxicity, making clinical translation difficult. By contrast, multiple preclinical and clinical studies have shown that pharmacological activation of AMPK provides a promising approach to treat ADPKD. In this narrative review, we summarize the pleiotropic functions of AMPK as a regulator of cellular proliferation, macromolecule metabolism, and mitochondrial biogenesis, and discuss the potential for pharmacological activation of AMPK to treat ADPKD and obesity-related kidney disease.
Neural basis of visuospatial tests in behavioral variant frontotemporal dementia
Authors: Delgado-Álvarez Alfonso , Cabrera-Martín María Nieves , Valles-Salgado María , Delgado-Alonso Cristina , Gil María José , Díez-Cirarda María , Matías-Guiu Jorge , Matias-Guiu Jordi A.
Published: August 2022

Background

Recent models of visuospatial functioning suggest the existence of three main circuits emerging from the dorsal (“where”) route: parieto-prefrontal pathway, parieto-premotor, and parieto-medial temporal. Neural underpinnings of visuospatial task performance and the sparing of visuospatial functioning in bvFTD are unclear. We hypothesized different neural and cognitive mechanisms in visuospatial tasks performance in bvFTD and AD.

Methods

Two hundred and sixteen participants were enrolled for this study: 72 patients with bvFTD dementia and 144 patients with AD. Visual Object and Space Perception Battery Position Discrimination and Number Location (VOSP-PD and VOSP-NL) and Rey-Osterrieth Complex Figure (ROCF) were administered to examine visuospatial functioning, together with a comprehensive neuropsychological battery. FDG-PET was acquired to evaluate brain metabolism. Voxel-based brain mapping analyses were conducted to evaluate the brain regions associated with visuospatial function in bvFTD and AD.

Results

Patients with AD performed worst in visuospatial tasks in mild dementia, but not at prodromal stage. Attention and executive functioning tests showed higher correlations in bvFTD than AD with ROCF, but not VOSP subtests. Visuospatial performance in patients with bvFTD was associated with bilateral frontal regions, including the superior and medial frontal gyri, supplementary motor area, insula and middle cingulate gyrus.

Conclusion

These findings support the role of prefrontal and premotor regions in visuospatial processing through the connection with the posterior parietal cortex and other posterior cortical regions. Visuospatial deficits should be interpreted with caution in patients with bvFTD, and should not be regarded as hallmarks of posterior cortical dysfunction.
Anodal and cathodal transcranial direct current stimulations of prefrontal cortex in a rodent model of Alzheimer’s disease
Authors: Duan Mengsi , Meng Zhiqiang , Yuan Dong , Zhang Yunfan , Tang Tao , Chen Zhuangfei , Fu Yu
Published: August 2022

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly, with no effective treatment currently available. Transcranial direct current stimulation (tDCS), a non-drug and non-invasive therapy, has been testified efficient in cognitive enhancement. This study aims to examine the effects of tDCS on brain function in a mouse model of AD. The amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice (7–8 months old) were subjected to 20-min anodal and cathodal tDCS (atDCS and ctDCS; 300 μA, 3.12 mA/cm2) for continuous five days. tDCS was applied on the left frontal skull of the animals, targeting on their prefrontal cortex (PFC). Behavioral performances were assessed by open-field, Y-maze, Barnes maze and T-maze paradigms; and their PFC electroencephalogram (EEG) activities were recorded under spontaneous state and during Y-maze performance. Behaviorally, atDCS and ctDCS improved spatial learning and/or memory in AD mice without affecting their general locomotion and anxiety-like behaviors, but the effects depended on the testing paradigms. Interestingly, the memory improvements were accompanied by decreased PFC EEG delta (2–4 Hz) and increased EEG gamma (20–100 Hz) activities when the animals needed memory retrieval during task performance. The decreased EEG delta activities could also be observed in animals under spontaneous state. Specifically, atDCS increased PFC EEG activity in the alpha band (8–12 Hz) for spontaneous state, whereas ctDCS increased that in alpha-beta band (8–20 Hz) for task-related state. In addition, some EEG changes after ctDCS could be found in other cortical regions except PFC. These data indicate that tDCS can reverse the situation of slower brain activity in AD mice, which may further lead to cognitive improvement. Our work highlights the potential clinical use of tDCS to restore neural network activity and improve cognition in AD.
The efficacy of therapies for post-stroke depression in aging: An umbrella review
Authors: Xie Jinlu , Geng Xiwen , Fan Fangcheng , Fu Xuyan , He Shuaibing , Li Tao
Published: August 2022

Post-stroke depression (PSD) is a common complication after stroke. PSD is associated with emotional disorders and psychological dependence, which are potential risk factors for stroke recurrence and suicidality. This study aimed to perform an umbrella review of therapies for PSD through a comprehensive literature search. A systematic search was conducted in the PubMed and Web of Science by two independent authors. We examined the Hamilton Depression Scale (HAMD), Activities of daily living (ADL), Neurologic function as efficacy endpoints, and the incidence of adverse events as safety profiles. Seventeen eligible studies, including 267 clinical trials were included in this study. The results showed that High-Frequency Repetitive Transcranial Magnetic Stimulation (HfrTMS), Acupuncture/EA+conventional treatment, Escitalopram, Modified Sini San, Moxibustion, Xiaoyao Formula, Paroxetine, Chinese herbal medicine, Exercise, Citalopram, and Cognitive behavioral therapy are beneficial for improving the depression symptoms of patients with PSD. HfrTMS and Sertraline may have an impact on slowing the scores of activities of daily living or neurologic function. In addition, Acupuncture/EA+conventional, Escitalopram, Citalopram, Sertraline, and Fluoxetine showed no serious adverse events in PSD patients. Our study demonstrated that 11 treatment methods can effectively improve the condition of PSD patients.
Front and center: Maturational dysregulation of frontal lobe functional neuroanatomic connections in attention deficit hyperactivity disorder
Authors: Leisman Gerry , Melillo Robert
Published: August 2022

Frontal lobe function may not universally explain all forms of attention deficit hyperactivity disorder (ADHD) but the frontal lobe hypothesis described supports an internally consistent model for integrating the numerous behaviors associated with ADHD. The paper examines the developmental trajectories of frontal and prefrontal lobe development, framing ADHD as maturational dysregulation concluding that the cognitive, motor, and behavioral abilities of the presumptive majority of ADHD children may not primarily be disordered or dysfunctional but reflect maturational dysregulation that is inconsistent with the psychomotor and cognitive expectations for the child’s chronological and mental age. ADHD children demonstrate decreased activation of the right and middle prefrontal cortex. Prefrontal and frontal lobe regions have an exuberant network of shared pathways with the diencephalic region, also having a regulatory function in arousal as well as with the ascending reticular formation which has a capacity for response suppression to task-irrelevant stimuli. Prefrontal lesions oftentimes are associated with the regulatory breakdown of goal-directed activity and impulsivity. In conclusion, a presumptive majority of childhood ADHD may result from maturational dysregulation of the frontal lobes with effects on the direct, indirect and/or, hyperdirect pathways.
Machine learning algorithm performance evaluation in structural magnetic resonance imaging-based classification of pediatric bipolar disorders type I patients
Authors: Dou Ruhai , Gao Weijia , Meng Qingmin , Zhang Xiaotong , Cao Weifang , Kuang Liangfeng , Niu Jinpeng , Guo Yongxin , Cui Dong , Jiao Qing , Qiu Jianfeng , Su Linyan , Lu Guangming
Published: August 2022

The diagnosis based on clinical assessment of pediatric bipolar disorder (PBD) may sometimes lead to misdiagnosis in clinical practice. For the past several years, machine learning (ML) methods were introduced for the classification of bipolar disorder (BD), which were helpful in the diagnosis of BD. In this study, brain cortical thickness and subcortical volume of 33 PBD-I patients and 19 age-sex matched healthy controls (HCs) were extracted from the magnetic resonance imaging (MRI) data and set as features for classification. The dimensionality reduced feature subset, which was filtered by Lasso or f_classif, was sent to the six classifiers (logistic regression (LR), support vector machine (SVM), random forest classifier, naïve Bayes, k-nearest neighbor, and AdaBoost algorithm), and the classifiers were trained and tested. Among all the classifiers, the top two classifiers with the highest accuracy were LR (84.19%) and SVM (82.80%). Feature selection was performed in the six algorithms to obtain the most important variables including the right middle temporal gyrus and bilateral pallidum, which is consistent with structural and functional anomalous changes in these brain regions in PBD patients. These findings take the computer-aided diagnosis of BD a step forward.
Case report: Sodium and chloride muscle channelopathy coexistence: A complicated phenotype and a challenging diagnosis
Authors: Pagliarani Serena , Meola Giovanni , Filareti Melania , Comi Giacomo Pietro , Lucchiari Sabrina
Published: August 2022

Non-dystrophic myotonias (NDM) encompass chloride and sodium channelopathy. Mutations in CLCN1 lead to either the autosomal dominant form or the recessive form of myotonia congenita (MC). The main symptom is stiffness worsening after rest and improving by physical exercise. Patients with recessive mutations often show muscle hypertrophy, and transient weakness mostly in their lower limbs. Mutations in SCN4A can lead to Hyper-, Hypo- or Normo-kalemic Periodic Paralysis or to different forms of myotonia (Paramyotonia Congenita-PMC and Sodium Channel Myotonia-SCM and severe neonatal episodic laryngospasm-SNEL). SCM often presents facial muscle stiffness, cold sensitivity, and muscle pain, whereas myotonia worsens in PMC patients with the repetition of the muscle activity and cold. Patients affected by chloride or sodium channelopathies may show similar phenotypes and symptoms, making the diagnosis more difficult to reach. Herein we present a woman in whom sodium and chloride channelopathies coexist yielding a complex phenotype with features typical of both MC and PMC. Disease onset was in the second decade with asthenia, weakness, warm up and limb stiffness, and her symptoms had been worsening through the years leading to frequent heavy retrosternal compression, tachycardia, stiffness, and symmetrical pain in her lower limbs. She presented severe lid lag myotonia, a hypertrophic appearance at four limbs and myotonic discharges at EMG. Her symptoms have been triggered by exposure to cold and her daily life was impaired. All together, clinical signs and instrumental data led to the hypothesis of PMC and to the administration of mexiletine, then replaced by acetazolamide because of gastrointestinal side effects. Analysis of SCN4A revealed a new variant, p.Glu1607del. Nonetheless the severity of myotonia in the lower limbs and her general stiffness led to hypothesize that the impairment of sodium channel, Nav1.4, alone could not satisfactorily explain the phenotype and a second genetic “factor” was hypothesized. CLCN1 was targeted, and p.Met485Val was detected in homozygosity. This case highlights that proper identification of signs and symptoms by an expert neurologist is crucial to target a successful genetic diagnosis and appropriate therapy.
Endovascular treatment of intracranial vertebral artery unruptured dissecting aneurysms: Comparison of flow diversion and stent-assisted coiling or stenting alone
Authors: Li Li , Xu Gang-Qin , Gao Hui-Li , Gao Bu-Lang , Zhang Kun , Wang Zi-Liang , Li Tian-Xiao
Published: August 2022

Purpose

To investigate the effect and safety of flow diverters in the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery in comparison with stent-assisted coiling or stenting alone.

Materials and methods

Patients with unruptured dissecting intracranial aneurysms of the vertebral artery treated with the flow diverter, stent-assisted coiling, or stenting alone were retrospectively enrolled. The clinical data were analyzed and compared.

Results

Twenty-five patients were enrolled in the flow diversion group and 42 patients in the stenting group. Twenty-six flow diverters were deployed in the flow diversion group. Immediate angiography revealed contrast agent retention within the aneurysm cavity in all patients. In the stenting group, 48 stents were deployed, and immediate angiographic outcome showed O'Kelly-Marotta (OKM) grade D in 18 (42.9%) aneurysms, grade C in 16 (38.1%), and grade B in 8 (19.0%). Periprocedural ischemic complications of thrombosis occurred in two (4.8%) patients and were treated with thrombolysis. In the flow diversion group, 19 (76%) patients underwent angiographic follow-up 3–46 (median 24) months after the procedure, with the OKM grade D in 11 (57.9%) patients, C in two (10.5%), and B in six (31.6%). The aneurysm recurrence rate was zero, and all diverters remained patent. Asymptomatic instent stenosis occurred in two (10.5%) patients. In seven of the ten patients with mild or moderate parent artery stenosis before the procedure who experienced angiographic follow-up, the stenosis was improved in five (71.4%) patients. In the stenting group, angiographic follow-up was carried out in 33 (78.6%) patients 6–58 months (median 34) after the procedure, with OKM grade D in 22 (66.7%) patients, grade C in five (15.2%), grade B in three (9.1%), and aneurysm recurrence (grade B, with increased contrast agent into the aneurysm cavity) in three (9.1%). Five (16.7%) patients experienced asymptomatic instent stenosis, and six of the 12 patients (50%) with parent artery stenosis were improved.

Conclusion

Flow diverters with or without selective adjunctive coiling for the treatment of unruptured dissecting intracranial aneurysms of the vertebral artery may be safe and effective with good occlusion effects not inferior to those of stent-assisted coiling and stenting alone even though the long-term effect still warrants confirmation.
Vestibular function in children with cochlear implant: Impact and evaluation
Authors: Deng Jianhang , Zhu Qianchen , Zhang Kangjia , Xie Dinghua , Wu Weijing
Published: August 2022

Over the last 30 years, cochlear implant (CI) has been dedicated to improving the rehabilitation of hearing impairments. However, CI has shown potential detrimental effects on vestibular function. For children, due to atypical symptoms and difficulty in cooperating with vestibular function tests, systematic and objective assessments of vestibular function with CI have been conducted sparsely. This review focuses on the impact of vestibular function in children with CI and summarized the evaluation of vestibular function in children. In addition, some recommended strategies are summarized and proposed.
Expert validation of prediction models for a clinical decision-support system in audiology
Authors: Buhl Mareike , Akin Gülce , Saak Samira , Eysholdt Ulrich , Radeloff Andreas , Kollmeier Birger , Hildebrandt Andrea
Published: August 2022

For supporting clinical decision-making in audiology, Common Audiological Functional Parameters (CAFPAs) were suggested as an interpretable intermediate representation of audiological information taken from various diagnostic sources within a clinical decision-support system (CDSS). Ten different CAFPAs were proposed to represent specific functional aspects of the human auditory system, namely hearing threshold, supra-threshold deficits, binaural hearing, neural processing, cognitive abilities, and a socio-economic component. CAFPAs were established as a viable basis for deriving audiological findings and treatment recommendations, and it has been demonstrated that model-predicted CAFPAs, with machine learning models trained on expert-labeled patient cases, are sufficiently accurate to be included in a CDSS, but it requires further validation by experts. The present study aimed to validate model-predicted CAFPAs based on previously unlabeled cases from the same data set. Here, we ask to which extent domain experts agree with the model-predicted CAFPAs and whether potential disagreement can be understood in terms of patient characteristics. To these aims, an expert survey was designed and applied to two highly-experienced audiology specialists. They were asked to evaluate model-predicted CAFPAs and estimate audiological findings of the given audiological information about the patients that they were presented with simultaneously. The results revealed strong relative agreement between the two experts and importantly between experts and the prediction for all CAFPAs, except for the neural processing and binaural hearing-related ones. It turned out, however, that experts tend to score CAFPAs in a larger value range, but, on average, across patients with smaller scores as compared with the machine learning models. For the hearing threshold-associated CAFPA in frequencies smaller than 0.75 kHz and the cognitive CAFPA, not only the relative agreement but also the absolute agreement between machine and experts was very high. For those CAFPAs with an average difference between the model- and expert-estimated values, patient characteristics were predictive of the disagreement. The findings are discussed in terms of how they can help toward further improvement of model-predicted CAFPAs to be incorporated in a CDSS for audiology.
The safety/tolerability of opicapone when used early in Parkinson's disease patients with levodopa-induced motor fluctuations: A post-hoc analysis of BIPARK-I and II
Authors: Rocha José-Francisco , Ebersbach Georg , Lees Andrew , Tolosa Eduardo , Ferreira Joaquim J. , Poewe Werner , Rascol Olivier , Stocchi Fabrizio , Antonini Angelo , Magalhães Diogo , Gama Helena , Soares-da-Silva Patrício
Published: August 2022

Introduction

Post-hoc analyses of the BIPARK-I and II trials previously demonstrated that opicapone (OPC) 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations, with enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway. Complementary post-hoc analyses were performed to evaluate the safety/tolerability of OPC following the same pre-defined segmentation of the wide spectrum of duration of both PD and levodopa therapy, as well as of motor fluctuation history, in this patient population.

Materials and methods

Data from matching treatment arms in BIPARK-I and II were combined for the placebo (PLC) and OPC 50 mg groups and exploratory post-hoc analyses were performed to investigate the safety/tolerability of OPC 50 mg and PLC in 22 subgroups of patients who were in “earlier” vs. “later” stages of both their disease course (e.g., duration of PD <6 years vs. ≥6 years) and levodopa treatment pathway (e.g., levodopa treatment duration <4 vs. ≥4 years). Safety/tolerability assessments included evaluation of treatment-emergent adverse events (TEAEs).

Results

The Safety Set included 522 patients (PLC, n = 257; OPC 50 mg, n = 265). For OPC 50 mg, incidences of TEAEs, related TEAEs, related serious TEAEs, and related TEAEs leading to discontinuation were lower for patients in earlier vs. later stages of their disease course and levodopa treatment pathway in 86.4, 86.4, 63.6, and 68.2% of the 22 pairwise comparisons conducted, respectively (compared with 63.6, 77.3, 18.2, and 45.5%, respectively, in the 22 corresponding PLC comparisons).

Conclusion

OPC 50 mg was generally well-tolerated when used to treat patients with PD with end-of-dose fluctuations, with an even more favorable tolerability profile in patients who were earlier, as opposed to later, in their disease course and levodopa treatment pathway, further supporting its use as an early adjunct to levodopa in PD.
State-dependent modulation of thalamocortical oscillations by gamma light flicker with different frequencies, intensities, and duty cycles
Authors: Wang Kun , Wei Aili , Fu Yu , Wang Tianhui , Gao Xiujie , Fu Bo , Zhu Yingwen , Cui Bo , Zhu Mengfu
Published: August 2022

Rhythmic light flickers have emerged as useful tools to modulate cognition and rescue pathological oscillations related to neurological disorders by entrainment. However, a mechanistic understanding of the entrainment for different brain oscillatory states and light flicker parameters is lacking. To address this issue, we proposed a biophysical neural network model for thalamocortical oscillations (TCOs) and explored the stimulation effects depending on the thalamocortical oscillatory states and stimulation parameters (frequency, intensity, and duty cycle) using the proposed model and electrophysiology experiments. The proposed model generated alpha, beta, and gamma oscillatory states (with main oscillation frequences at 9, 25, and 35 Hz, respectively), which were successfully transmitted from the thalamus to the cortex. By applying light flicker stimulation, we found that the entrainment was state-dependent and it was more prone to induce entrainment if the flicker perturbation frequency was closer to the endogenous oscillatory frequency. In addition, endogenous oscillation would be accelerated, whereas low-frequency oscillatory power would be suppressed by gamma (30–50 Hz) flickers. Notably, the effects of intensity and duty cycle on entrainment were complex; a high intensity of light flicker did not mean high entrainment possibility, and duty cycles below 50% could induce entrainment easier than those above 50%. Further, we observed entrainment discontinuity during gamma flicker stimulations with different frequencies, attributable to the non-linear characteristics of the network oscillations. These results provide support for the experimental design and clinical applications of the modulation of TCOs by gamma (30–50 Hz) light flicker.
Oligomeropathies, inflammation and prion protein binding
Authors: Forloni Gianluigi , La Vitola Pietro , Balducci Claudia
Published: August 2022

The central role of oligomers, small soluble aggregates of misfolded proteins, in the pathogenesis of neurodegenerative disorders is recognized in numerous experimental conditions and is compatible with clinical evidence. To underline this concept, some years ago we coined the term oligomeropathies to define the common mechanism of action of protein misfolding diseases like Alzheimer, Parkinson or prion diseases. Using simple experimental conditions, with direct application of synthetic β amyloid or α-synuclein oligomers intraventricularly at micromolar concentrations, we could detect differences and similarities in the biological consequences. The two oligomer species affected cognitive behavior, neuronal dysfunction and cerebral inflammatory reactions with distinct mechanisms. In these experimental conditions the proposed mediatory role of cellular prion protein in oligomer activities was not confirmed. Together with oligomers, inflammation at different levels can be important early in neurodegenerative disorders; both β amyloid and α-synuclein oligomers induce inflammation and its control strongly affects neuronal dysfunction. This review summarizes our studies with β-amyloid or α-synuclein oligomers, also considering the potential curative role of doxycycline, a well-known antibiotic with anti-amyloidogenic and anti-inflammatory activities. These actions are analyzed in terms of the therapeutic prospects.
Abnormal physiological responses toward sensory stimulus are related to the attention deficits in children with sluggish cognitive tempo
Authors: Yung Trevor W. K. , Lai Cynthia Y. Y. , Chan Chetwyn C. H.
Published: August 2022

Previous studies have found that sluggish cognitive tempo (SCT) is often associated with difficulties in real-life functioning, such as social problems, emotional difficulties, and academic learning difficulties. However, the underlying mechanisms contributing to the SCT symptoms and its associated real-life difficulties have still not been clearly understood. A previous study has found that SCT symptoms were associated with hypoarousal and hyperarousal toward the sensory stimulus. However, it is still unclear whether such abnormal arousal regulation is related to sustained attention difficulties that have been found to be related to social difficulties and withdrawn behavior in children with SCT. In this study, arousal regulation deficit in SCT is examined by the physiological responses quantified by HRV and EEG in the sensory challenge paradigm. This study aimed to establish a linkage between arousal regulation reflected by HRV and EEG and attention difficulties in children with SCT. The results of this study showed that higher theta power in the auditory stimulation condition than in the resting condition was associated with higher omission errors in sustained attention tasks in the SCT group. It was also found that higher parasympathetic activities during sensory stimulation conditions were associated with higher commission errors in the SCT group. These results reflected that hypersensitivity toward stressful sensitivity toward a stressful sensory stimulus is associated with attention difficulties in children with SCT. This further supported the notion that SCT should be conceptualized as a condition characterized by multiple deficits in different biological systems, such as the cognitive system, the negative valence system, and the arousal regulatory system.
Patched-Related Is Required for Proper Development of Embryonic Drosophila Nervous System
Authors: Bolatto Carmen , Nieves Sofía , Reyes Agustina , Olivera-Bravo Silvia , Cambiazo Verónica
Published: August 2022

Patched-related (Ptr), classified primarily as a neuroectodermal gene, encodes a protein with predicted topology and domain organization closely related to those of Patched (Ptc), the canonical receptor of the Hedgehog (Hh) pathway. To investigate the physiological function of Ptr in the developing nervous system, Ptr null mutant embryos were immunolabeled and imaged under confocal microscopy. These embryos displayed severe alterations in the morphology of the primary axonal tracts, reduced number, and altered distribution of the Repo-positive glia as well as peripheral nervous system defects. Most of these alterations were recapitulated by downregulating Ptr expression, specifically in embryonic nerve cells. Because similar nervous system phenotypes have been observed in hh and ptc mutant embryos, we evaluated the Ptr participation in the Hh pathway by performing cell-based reporter assays. Clone-8 cells were transfected with Ptr-specific dsRNA or a Ptr DNA construct and assayed for changes in Hh-mediated induction of a luciferase reporter. The results obtained suggest that Ptr could act as a negative regulator of Hh signaling. Furthermore, co-immunoprecipitation assays from cell culture extracts premixed with a conditioned medium revealed a direct interaction between Ptr and Hh. Moreover, in vivo Ptr overexpression in the domain of the imaginal wing disc where Engrailed and Ptc coexist produced wing phenotypes at the A/P border. Thus, these results strongly suggest that Ptr plays a crucial role in nervous system development and appears to be a negative regulator of the Hh pathway.
Research progress on the pharmacological effects of matrine
Authors: Sun Yanan , Xu Lu , Cai Qihan , Wang Mengmeng , Wang Xinliang , Wang Siming , Ni Zhiyu
Published: August 2022

Matrine possesses anti-cancer properties, as well as the prevention and treatment of allergic asthma, and protection against cerebral ischemia-reperfusion injury. Its mechanism of action may be (1) regulation of cancer cell invasion, migration, proliferation, and cell cycle to inhibit tumor growth; (2) reduction of oxidized low-density lipoprotein and advanced glycation end products from the source by exerting anti-inflammatory and antioxidant effects; (3) protection of brain damage and cortical neurons by regulating apoptosis; (4) restoration of the intestinal barrier and regulation of the intestinal microbiota. This article aims to explore matrine’s therapeutic potential by summarizing comprehensive information on matrine’s pharmacology, toxicity, and bioavailability.
Myelin damage and cortical atrophy in watershed regions in patients with moyamoya angiopathy
Authors: Filimonova Elena , Ovsiannikov Konstantin , Sosnov Alexsey , Perfilyev Artem , Gafurov Rustam , Galaktionov Dmitriy , Bervickiy Anatoliy , Kiselev Vitaly , Rzaev Jamil
Published: August 2022

Background

Despite it being known that chronic ischemia results in myelin damage and gray matter atrophy, data regarding patients with moyamoya angiopathy is limited. We hypothesized that chronic ischemia in moyamoya angiopathy leads to myelin damage, especially in anterior watershed regions, as well as cortical atrophy in these areas.

Materials and methods

Twenty adult patients with moyamoya angiopathy and 17 age- and sex-matched healthy controls were evaluated using the T1w/T2w mapping method and surface-based MR-morphometry. The T1w/T2w signal intensity ratio, which reflects the white matter integrity, and the cortical thickness, were calculated in watershed regions and compared between the patients and controls. In the patients with moyamoya angiopathy, the correlations between these parameters and the Suzuki stage were also evaluated.

Results

The regional T1w/T2w ratio values from centrum semiovale in patients with MMA were significantly lower than those in healthy controls (p < 0.05); there was also a downward trend in T1w/T2w ratio values from middle frontal gyrus white matter in patients compared with the controls (p < 0.1). The cortical thickness of the middle frontal gyrus was significantly lower in patients than in healthy controls (p < 0.05). There were negative correlations between the Suzuki stage and the T1w/T2w ratio values from the centrum semiovale and middle frontal white matter.

Conclusion

T1w/T2w mapping revealed that myelin damage exists in watershed regions in patients with moyamoya angiopathy, in association with cortical atrophy according to MR-morphometry. These changes were correlated with the disease stage.
Antidepressant-like effects of trophic factor receptor signaling
Authors: Sathyanesan Monica , Newton Samuel S.
Published: August 2022

A significant body of research has demonstrated that antidepressants regulate neurotrophic factors and that neurotrophins themselves are capable of independently producing antidepressant-like effects. While brain derived neurotrophic factor (BDNF) remains the best studied molecule in this context, there are several structurally diverse trophic factors that have shown comparable behavioral effects, including basic fibroblast growth factor (FGF-2), insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF). In this review we discuss the structural and biochemical signaling aspects of these neurotrophic factors with antidepressant activity. We also include a discussion on a cytokine molecule erythropoietin (EPO), widely known and prescribed as a hormone to treat anemia but has recently been shown to function as a neurotrophic factor in the central nervous system (CNS).
Breakfast and psychosocial behavioural problems in young population: The role of status, place, and habits
Authors: López-Gil José Francisco , Smith Lee , López-Bueno Rubén , Tárraga-López Pedro Juan
Published: August 2022

The aim of this study was to examine whether breakfast status, place and habits are associated with psychosocial behavioural problems in a nationally representative sample of young people aged 4–14 years residing in Spain. This study analysed secondary data from the Spanish National Health Survey (2017), including 3,772 Spanish children and adolescents. Breakfast status, place, and habits were assessed by ad hoc questions answered by parents/guardians. The Strengths and Difficulties Questionnaire (SDQ) parents’ version form was applied to evaluate the psychosocial health of their children. Skipping breakfast and eating breakfast out of home were linked to greater odds of psychosocial behavioural problems (skipping breakfast: OR = 3.29; CI 95%, 1.47–7.35; breakfast out of home: OR = 2.06; CI 95%, 1.27–3.33) than eating breakfast at home. Similarly, not consuming coffee, milk, tea, chocolate, cocoa, yogurt, etc., for breakfast was related to greater odds of psychosocial behavioural problems (OR = 1.76; CI 95%, 1.21–2.55). This association was also found for those who did not eat bread, toast, cereals, pastries, etc., for breakfast (OR = 1.31; CI 95%, 1.01–1.73). Conversely, not consuming eggs, cheese, ham, etc., was associated with lower odds of psychosocial behavioural problems (OR = 0.56; CI 95%, 0.38–0.83). Our results show that eating breakfast (specifically at home) and breakfast habits related to the intake of certain food/beverages groups were associated with higher or lower odds of psychosocial behavioural problems.
Association of sugar-sweetened beverages with executive function in autistic children
Authors: Pan Shuolin , Wang Xin , Lin Lizi , Chen Jiajie , Zhan Xiaoling , Jin Chengkai , Ou Xiaoxuan , Gu Tingfeng , Jing Jin , Cai Li
Published: August 2022

The association between sugar-sweetened beverages (SSBs) consumption and executive function (EF) among typically developing (TD) children has been investigated in previous studies but with inconsistent results. Furthermore, this relationship has been less investigated among autistic children who perform worse in EF compared with TD children. In this study, we aimed to investigate the association between SSB consumption and EF in autistic children, and whether the association between SSB and EF in autistic children is different from that in TD children. We recruited 106 autistic children and 207 TD children aged 6–12 years in Guangzhou, China. Children’s EF was assessed by using the Chinese version of parent-reported Behavior Rating Inventory of Executive Function, Stroop Color–Word Test, and working memory subscales of the Chinese version of Wechsler Intelligence Scale for children, Fourth edition. Meanwhile, we assessed children’s dietary intake and SSB consumption with a validated Food Frequency Questionnaire. In this study, 70 (66.0%) autistic children consumed SSB and 20 (18.9%) of them consumed more than two servings SSB a week. Among autistic children, over two servings per week SSB consumption was associated with poorer performance in emotional control [β = 7.20, 95% confidence interval (CI): 0.94–13.46] and plan/Organize (β = 6.45, 95% CI: 0.27–12.63). The association between over two servings/week SSB consumption and emotional control among autistic children was significantly different from that among TD children (βASD = 7.20; βTD = −3.09, Z = 2.72, p = 0.006). Results of this study show that SSB consumption was associated with an impairment in some subscales of EF in autistic children. Furthermore, the association between SSB and EF in autistic children might be different from that in TD children.