bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultivable oral bacteriota dysbiosis in mechanically ventilated COVID-19 patients
Authors: Gregorczyk-Maga Iwona , Fiema Mateusz , Kania Michal , Kędzierska Jolanta , Jachowicz Estera , Romaniszyn Dorota , Wójkowska-Mach Jadwiga
Published: October 2022

Potential interactions between the SARS-CoV-2 virus and the human oral microbiota are currently investigated widely. Patients with COVID-19 requiring mechanical ventilation in an intensive care unit (ICU) setting are at high risk of developing severe complications, including ventilator-associated pneumonia, thus making oral health management important. The aim of this study was to evaluate the oral health status and assess the dysbiosis of cultivable oral bacteriota in COVID-19 patients hospitalized in an ICU with acute respiratory distress within 36 h following intubation. In this prospective cohort study, we recruited 56 adult COVID-19 patients that qualified for mechanical ventilation in the Temporary ICU for COVID-19 Patients of the University Hospital in Krakow. On admission to the ICU, oral health of patients was assessed using the modified Beck Oral Assessment Score (BOAS). Four oral habitats were sampled, namely the buccal mucosa, tongue, buccal dental surface and gingival pocket. Microorganisms were identified by MALDI/TOF mass spectrometry. The mean age of the study population was 66.5 ± 12.7 years, there were 24 (42.9%) females. All patients included in this study were intubated and ventilated in the ICU, with a corresponding high mortality rate (76.8%). On admission to ICU, 76.8% subjects scored 11–20 on the BOAS scale (median 12 [IQR 10–14]), indicating moderate or severe dysfunction of oral health. Potentially pathogenic bacteria were identified in the oral microbiota samples, including Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli and Klebsiella pneumoniae in 23.2%, 39.3%, 17.9%, and 19.6% of patients, respectively. Lactobacillus spp. were present in 57.1% subjects. The mean CFU counts of all bacteria strains in dental brushes were 9.3E+5 (1.4E+6) and in gingival pockets 7.6E+5 (1.4E+6). The highest CFU counts were observed for Enterococcus spp. and, Lactobacillus spp., although these did not differ significantly from CFU counts of Streptococcus spp. and Staphylococcus spp. In this report we comprehensively characterized the oral health condition and cultivable oral bacteriota in COVID-19 patients hospitalized in an ICU with acute respiratory distress within 36 h following intubation. The oral bacteriota showed significant qualitative and quantitative dysbiosis. Hospitalization in an ICU and mechanical ventilation are important factors leading to oral dysbiosis in SARS-CoV-2 patients.
Linkages and key factors between soil bacterial and fungal communities along an altitudinal gradient of different slopes on mount Segrila, Tibet, China
Authors: Ma Tiantian , Zhang Xinjun , Wang Ruihong , Liu Rui , Shao Xiaoming , Li Ji , Wei Yuquan
Published: October 2022

Soil microbes are of great significance to many energy flow and material circulation processes in alpine forest ecosystems. The distribution pattern of soil microbial community along altitudinal gradients is an essential research topic for the Tibetan Plateau. Yet our understanding of linkages between soil microbial communities and key factors along an altitudinal gradient of different slopes remains limited. Here, the diversity, composition and interaction of bacterial and fungal communities and in response to environmental factors were compared across five elevation sites (3,500 m, 3,700 m, 3,900 m, 4,100 m, 4,300 m) on the eastern and western slopes of Mount Segrila, by using Illumina MiSeq sequencing. Our results showed that microbial community composition and diversity were distinct at different elevations, being mainly influenced by soil total nitrogen and carbonate. Structural equation models indicated that elevation had a greater influence than slope upon the soil microbial community. Co-occurrence network analysis suggested that fungi were stable but bacteria contributed more to among interactions of bacterial and fungal communities. Ascomycota was identified as a key hub for the internal interactions of microbial community, which might affect the soil microbial co-occurrence network resilience of alpine forest ecosystems on the Tibetan Plateau.
Horizontal transfer and phylogenetic distribution of the immune evasion factor tarP
Authors: Gerlach David , Sieber Raphael N. , Larsen Jesper , Krusche Janes , De Castro Cristina , Baumann Juliane , Molinaro Antonio , Peschel Andreas
Published: October 2022

Methicillin-resistant Staphylococcus aureus (MRSA), a major human pathogen, uses the prophage-encoded tarP gene as an important immune evasion factor. TarP glycosylates wall teichoic acid (WTA) polymers, major S. aureus surface antigens, to impair WTA immunogenicity and impede host defence. However, tarP phages appear to be restricted to only a few MRSA clonal lineages, including clonal complexes (CC) 5 and 398, for unknown reasons. We demonstrate here that tarP-encoding prophages can be mobilized to lysogenize other S. aureus strains. However, transfer is largely restricted to closely related clones. Most of the non-transducible clones encode tarM, which generates a WTA glycosylation pattern distinct from that mediated by TarP. However, tarM does not interfere with infection by tarP phages. Clonal complex-specific Type I restriction-modification systems were the major reasons for resistance to tarP phage infection. Nevertheless, tarP phages were found also in unrelated S. aureus clones indicating that tarP has the potential to spread to distant clonal lineages and contribute to the evolution of new MRSA clones.
Genomic diversity of resistant and virulent factors of Burkholderia pseudomallei clinical strains recovered from Guangdong using whole genome sequencing
Authors: Shafiq Muhammad , Ke Bixia , Li Xin , Zeng Mi , Yuan Yumeng , He Dongmei , Deng Xiaoling , Jiao Xiaoyang
Published: October 2022

Background

Burkholderia pseudomallei (B. pseudomallei) is a highly infectious agent and causes melioidosis, in both humans and animals, which is endemic in Southeast Asia and Northern Australia.

Objectives

This study aims to determine the molecular epidemiology, resistant determinants, and genomic diversity of the clinical isolates of B. pseudomallei to further elucidate the phylogenetic and evolutionary relationship of the strains with those in other endemic regions.

Methods

In this study, we obtained eight clinical B. pseudomallei isolates from Guangdong province from 2018 to 2019. All the isolates were sequenced using the Illumina NovaSeq platform. The draft genomes of B. pseudomallei were further used to find antibiotic-resistant genes (ARGs), virulence factors, and gene mutations. Multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis were performed to characterize the diversity and epidemiology of the strains.

Results

All isolates were susceptible to antibiotics commonly used for melioidosis treatment. Class D beta-lactamases genes OXA-57 and OXA-59, as well as various mutation factors such as amrA, amrB, omp38, gyrA, and ceoB were identified. MLST analysis of the B. pseudomallei strains identified eight different sequence types (STs): ST1774, ST1775, ST271, ST562, ST46, ST830, ST1325, and ST10. Phylogenetic analysis found that the strains used in this study showed high genetic diversity. We also report 165 virulence factors among B. pseudomallei strains responsible for different neurological disorders, pneumonia, skin lesions, and abscesses. All strains recovered in this study were susceptible to commonly used antibiotics. However, high genetic diversity exists among the isolates. The surveillance, diagnosis, and clinical features of melioidosis varied in different geographical locations. These regional differences in the clinical manifestations have implications for the practical management of the disease.

Conclusion

The present study reports the identification of different mutation and virulence factors among B. pseudomallei strains responsible for different neurological disorders, pneumonia, skin lesions, and abscesses.
MetaGT: A pipeline for de novo assembly of metatranscriptomes with the aid of metagenomic data
Authors: Shafranskaya Daria , Kale Varsha , Finn Rob , Lapidus Alla L. , Korobeynikov Anton , Prjibelski Andrey D.
Published: October 2022

While metagenome sequencing may provide insights on the genome sequences and composition of microbial communities, metatranscriptome analysis can be useful for studying the functional activity of a microbiome. RNA-Seq data provides the possibility to determine active genes in the community and how their expression levels depend on external conditions. Although the field of metatranscriptomics is relatively young, the number of projects related to metatranscriptome analysis increases every year and the scope of its applications expands. However, there are several problems that complicate metatranscriptome analysis: complexity of microbial communities, wide dynamic range of transcriptome expression and importantly, the lack of high-quality computational methods for assembling meta-RNA sequencing data. These factors deteriorate the contiguity and completeness of metatranscriptome assemblies, therefore affecting further downstream analysis.

Here we present MetaGT, a pipeline for de novo assembly of metatranscriptomes, which is based on the idea of combining both metatranscriptomic and metagenomic data sequenced from the same sample. MetaGT assembles metatranscriptomic contigs and fills in missing regions based on their alignments to metagenome assembly. This approach allows to overcome described complexities and obtain complete RNA sequences, and additionally estimate their abundances. Using various publicly available real and simulated datasets, we demonstrate that MetaGT yields significant improvement in coverage and completeness of metatranscriptome assemblies compared to existing methods that do not exploit metagenomic data. The pipeline is implemented in NextFlow and is freely available from https://github.com/ablab/metaGT.
Oral treatment with 10% potassium iodide solution for refractory cutaneous-disseminated sporotrichosis in an immunocompetent adult: Case report
Authors: Zhuang Kaiwen , Dai Yaling , Zhou Yike , Ke Yujing , Ran Xin , Ran Yuping
Published: October 2022

Sporotrichosis has multiple clinical manifestations, and its cutaneous-disseminated form is uncommon and, in most cases, related to immunosuppressive conditions. We report the case of a 47-year-old male patient who presented with multiple cutaneous nodules and ulcers on the left upper limb and the right thigh, with no other comorbidities. Until the diagnosis was confirmed, the patient was initially given empiric antifungal treatment with itraconazole, which showed unsatisfactory results at a local hospital. Then, he was treated with voriconazole, which led to the slow improvement of his skin lesions. At one point during the voriconazole treatment course, the patient briefly self-discontinued voriconazole for economic reasons, and the lesions recurred and worsened. The patient was finally diagnosed with cutaneous-disseminated sporotrichosis based on the isolation and identification of Sporothrix globosa. Susceptibility testing revealed that the isolate was resistant to itraconazole, fluconazole, voriconazole, terbinafine, and amphotericin. Considering the patient's poor financial condition, potassium iodide was administered. After 1-month of therapy with potassium iodide, he reported rapid improvement of his skin lesions. The patient continued potassium iodide treatment for another 5 months until the full resolution of lesions was achieved.
Genomic and phenotypic biology of a novel Dickeya zeae WH1 isolated from rice in China: Insights into pathogenicity and virulence factors
Authors: Tan Xiao-Juan , Zhang Zhi-Wei , Xiao Jing-Jing , Wang Wei , He Feng , Gao Xuan , Jiang Bin , Shen Liang , Wang Xu , Sun Yang , Zhu Guo-Ping
Published: October 2022

Soft rot caused by Dickeya zeae is an important bacterial disease affecting rice and other plants worldwide. In this study, Nanopore and Illumina sequencing platforms were used to sequence the high-quality complete genome of a novel D. zeae strain WH1 (size: 4.68 Mb; depth: 322.37x for Nanopore, 243.51x for Illumina; GC content: 53.59%), which was isolated from healthy rice root surface together with Paenibacillus polymyxa, a potential biocontrol bacterium against D. zeae strain WH1. However, the pure WH1 culture presented severe pathogenicity. Multilocus sequence analysis (MLSA) indicated that strains WH1, EC1, and EC2 isolated from rice were grouped into a clade differentiated from other D. zeae strains. The average nucleotide identity (ANI) and DNA-DNA hybridization (DDH) analyses demonstrated that WH1 was phylogenetically closest to EC2. Furthermore, the pathogenicity determinants and virulence factors of WH1 were mainly analyzed through genomic comparison with complete genomes of other D. zeae strains with high virulence (EC1, EC2, MS1, and MS2). The results revealed that plant cell wall-degrading extracellular enzymes (PCWDEs), flagellar and chemotaxis, and quorum sensing were highly conserved in all analyzed genomes, which were confirmed through phenotypic assays. Besides, WH1 harbored type I, II, III, and VI secretion systems (T1SS, T2SS, T3SS, and T6SS), but lost T4SS and T5SS. Like strains MS1 and MS2 isolated from bananas, WH1 harbored genes encoding both capsule polysaccharide (CPS) and exopolysaccharide (EPS) biosynthesis. The results of pathogenicity assays demonstrated that WH1 produced severe soft rot symptoms on potato tubers, carrots, radishes, and Chinese cabbage. Meanwhile, WH1 also produced phytotoxin(s) to inhibit rice seed germination with an 87% inhibitory rate in laboratory conditions. More importantly, we confirmed that phytotoxin(s) produced by WH1 are different from zeamines produced by EC1. Comparative genomics analyses and phenotypic and pathogenicity assays suggested that WH1 likely evolved through a pathway different from the other D. zeae strains from rice, producing a new type of rice foot rot pathogen. These findings highlight the emergence of a new type of D. zeae strain with high virulence, causing soft rot in rice and other plants.
A systematic review on machine learning methods for root cause analysis towards zero-defect manufacturing
Authors: Papageorgiou Konstantinos , Theodosiou Theodosios , Rapti Aikaterini , Papageorgiou Elpiniki I. , Dimitriou Nikolaos , Tzovaras Dimitrios , Margetis George
Published: October 2022

The identification of defect causes plays a key role in smart manufacturing as it can reduce production risks, minimize the effects of unexpected downtimes, and optimize the production process. This paper implements a literature review protocol and reports the latest advances in Root Cause Analysis (RCA) toward Zero-Defect Manufacturing (ZDM). The most recent works are reported to demonstrate the use of machine learning methodologies for root cause analysis in the manufacturing domain. The popularity of these technologies is then summarized and presented in the form of visualizing graphs. This enables us to identify the most popular and prominent methods used in modern industry. Although artificial intelligence gains more and more attraction in smart manufacturing, machine learning methods for root cause analysis seem to be under-explored. The literature survey revealed that only limited reviews are available in the field of RCA towards zero-defect manufacturing using AI and machine learning; thus, it attempts to fill this gap. This work also presents a set of open challenges to determine future developments.
Alterations of mitochondrial dynamics in serotonin transporter knockout rats: A possible role in the fear extinction recall mechanisms
Authors: Brivio Paola , Gallo Maria Teresa , Karel Peter , Cogi Giulia , Fumagalli Fabio , Homberg Judith R. , Calabrese Francesca
Published: October 2022

Stress-related mental disorders encompass a plethora of pathologies that share the exposure to a negative environment as trigger for their development. The vulnerability to the effects of a negative environment is not equal to all but differs between individuals based on the genetic background makeup. Here, to study the molecular mechanisms potentially underlying increased threat anticipation, we employed an animal model showing this symptom (5-HTT knockout rats) which we exposed to Pavlovian fear conditioning (FC). We investigated the role of mitochondria, taking advantage of the recent evidence showing that the dynamic of these organelles is dysregulated after stress exposure. Behavioral experiments revealed that, during the second day of extinction of the FC paradigm, 5-HTT knockout (5-HTT–/–) animals showed a lack of fear extinction recall. From a mechanistic standpoint, we carried out our molecular analyses on the amygdala and prefrontal cortex, given their role in the management of the fear response due to their tight connection. We demonstrated that mitochondrial dynamics are impaired in the amygdala and prefrontal cortex of 5-HTT–/– rats. The dissection of the potential contributing factors revealed a critical role in the mechanisms regulating fission and fusion that are dysregulated in transgenic animals. Furthermore, mitochondrial oxidative phosphorylation, mitochondrial biogenesis, and the production of antioxidant enzymes were altered in these brain regions in 5-HTT–/– rats. In summary, our data suggest that increased extracellular 5-HT levels cause an unbalance of mitochondrial functionality that could contribute to the reduced extinction recall of 5-HTT–/– rats, pointing out the role of mitochondrial dynamics in the etiology of psychiatric disorders. Our findings, also, provide some interesting insights into the targeted development of drugs to treat such disorders.
Case report: Long-term follow-up of two patients with LHON caused by DNAJC30:c.152G>A pathogenic variant-case series
Authors: Petrovic Pajic Sanja , Jarc-Vidmar Martina , Fakin Ana , Sustar Habjan Maja , Brecelj Jelka , Volk Marija , Maver Ales , Peterlin Borut , Hawlina Marko
Published: October 2022

Background

We present the disease course and long-term follow-up of two patients who were phenotypically diagnosed with atypical Leber Hereditary Optic Neuropathy (LHON) 14 and 12 years ago, respectively, whereby whole exome sequencing revealed recently described recessive DNAJC30:c.152G>A 152 A>G (p.Tyr51Cys) homozygous pathogenic variant with significant spontaneous visual acuity recovery in one.

Case presentation

Two presented unrelated males with atypical LHON with sequential visual acuity (VA) loss were followed for many years. Both patients had negative family history. At the presentation at ages 17 (Case 1) and 18 years (Case 2), both had reduced visual acuity (Snellen): (Case 1) right eye (RE):CF 3m, left eye (LE):0.6, (Case 2) RE:0.2, LE:0.15; and color vision (Ishihara): (Case 1) 1/15 and 13/15; (Case 2) 2/15 and 3/15. Both had hyperemic optic disks (PNO) and central scotoma in their visual fields. Electrophysiology in the acute phase showed reduced and delayed visually evoked potentials (VEP) P100 in both patients, with reduced N95 amplitude in Case 2, and initially normal N95 amplitude in Case 1. Fluorescein angiography showed no early leakage with some late pooling at optic disks. Extensive clinical workout, including brain magnetic resonance imaging (MRI), aquaporin 4 (Aq4), and anti-myelin oligodendrocyte protein (anti-MOG) antibodies, was negative. Intravenous corticosteroids did not improve vision. Both experienced further deterioration several months after the onset accompanied by thinning of the peripapillary retinal nerve fiber layer (RNFL). Genetic testing for typical LHON pathogenic variants and whole mitochondrial DNA (mtDNA) sequencing was negative. 1 year after the onset, modest VA improvement began in Case 2 and continued over the next 3 years. VA improved bilaterally to 0.7, color vision 15/15, and islands of vision appeared within the visual field scotoma. VEP P100 peak time shortened, and amplitude increased, despite further RNFL thinning on optical coherent tomography (OCT). The patient's visual function remained stable during the entire 12-year follow-up period. Case 1 experienced modest VA improvement to 0.1 with some improvement in the visual field seven years after the disease onset, remaining stable during the entire 14-year follow-up period. VEP P100 wave remained undetectable.

Conclusions

Presented are two autosomal recessive LHON (arLHON, OMIM:619382) cases with the same DNAJC30:c.152G>A pathogenic variant and different degrees of spontaneous visual recovery despite progressive RNFL thinning during a long-term follow-up. This mutation should be screened in every atypical LHON patient.
Effect of transcutaneous posterior tibial nerve stimulation and repetitive transcranial magnetic stimulation on neurogenic overactive bladder symptoms in female patients with multiple sclerosis: The study protocol of a randomized controlled study
Authors: Atak Çakir Pinar , Mutluay Fatma , Hanoğlu Lütfü , Güzelburç Vahit
Published: October 2022

Introduction

Neurogenic bladder is frequently seen in patients with multiple sclerosis (MS). Electrical stimulation methods (neuromodulation) can be used for patients that have persistent symptoms despite pharmacological treatment. This study aims to compare the effects of two different neuromodulation techniques used in the treatment of neurogenic bladder.

Methods and analysis

This is a single-center randomized controlled trial for MS patients with neurogenic bladder. Patients determined to be eligible according to the study criteria will be randomized into two treatment groups: the transcutaneous posterior tibial nerve stimulation (PTNS) and repetitive transcranial magnetic stimulation (rTMS) groups. Each group will include eight patients. The patients will be treated for a total of 10 sessions for two consecutive weeks. The pressure-flow study will be used to compare the initial and final urodynamic results as the primary outcome. All the participants will fill in a 3-day bladder diary before and after the treatments in each group. Patients will also be asked to complete specific questionnaires for incontinence and quality of life (QOL): Overactive Bladder Questionnaire-V8 score (OAB-V8), Incontinence Severity Index (ISI), Incontinence Quality of Life Scale score (I-QOL), International Incontinence Questionnaire (ICIQ-SF) score, and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) score) as the secondary outcomes.

Ethics and dissemination

An ethical approval number was obtained from the Non-Invasive Clinical Research Ethics Committee of Istanbul Medipol University (ethical approval number: 768). Support was received within the scope of the Istanbul Medipol University Scientific Research Project with project number 2020—2017. The result of this study will be published in a peer-reviewed journal.

Trial registration

NCT05312138.
Critical COVID-19 disease: Clinical course and rehabilitation of neurological deficits
Authors: Wimmer Corinna , Egger Marion , Bergmann Jeannine , Huge Volker , Müller Friedemann , Jahn Klaus
Published: October 2022

Background

The COVID-19 disease frequently causes neurological symptoms. Critically ill patients often require neurorehabilitation for manifestations like intensive care unit (ICU) acquired weakness or encephalopathy. The outcome of these patients, however, is largely unknown. Here we report the clinical course of critical affected COVID-19 patients from hospital admission to discharge from inpatient neurorehabilitation.

Methods

Prospective cohort study. COVID-19 patients admitted to neurorehabilitation were included based on a laboratory-confirmed SARS-CoV-2 infection. Assessments [modified Rankin Scale (mRS), Barthel-Index, Fatigue-Severity-Scale-7 and health-related quality of life (EQ-5D-5L)] were conducted at admission and before discharge from inpatient care. Data were compared to the preclinical health status.

Results

Sixty-one patients (62 ± 13 years, 16 female) were included in the analysis. Most patients had been treated on ICU (n = 58; 57 ± 23 days) and had received invasive ventilation (n = 57; 46 ± 21 days). After discharge from ICU, patients spent on average 57 ± 26 days in neurorehabilitation. The most frequent neurological diagnoses were ICU-acquired weakness (n = 56) and encephalopathy (n = 23). During rehabilitation overall disability improved [mRS median (IQR) 4.0 (1.0) at inclusion and 2.0 (1.0) at discharge]. However, the preclinical health state [mRS 0.0 (0.0)] was not regained (p < 0.001). This was also reflected by the Barthel-Index [preclinical 100.0 (0.0), at inclusion 42.5 (35.0), at discharge 65.0 (7.5); p < 0.001]. Patients had only minor fatigue during inpatient care. Quality of life generally improved but was still low at discharge from hospital.

Conclusion

Patients with neurological sequelae after critical COVID-19 disease showed substantial deficits at discharge from inpatient care up to 4 months after the initial infection. They were restricted in activities of daily living and had reduced health-related quality of life. All patients needed continued medical support and physical treatment.
Cerebral venous thrombosis in Latin America: A critical review of risk factors, clinical and radiological characteristics
Authors: Bezerra Gabriel Marinheiro dos Santos , Cavalcante Yasmin da Silveira , Matos-Neto Paulo Roberto , Cavalcante-Neto Joaquim Francisco , Ponte Keven Ferreira da , Aguiar de Sousa Diana , Leal Paulo Roberto Lacerda , Ribeiro Espártaco Moraes Lima
Published: October 2022

Background

Cerebral venous thrombosis (CVT) is a rare disease that frequently occurs in young women of childbearing age, with variable clinical presentation in regions with limited access to diagnostic imaging or specialized neurological care. In the last decade, there has been an increase in the number of studies on CVT in Latin America, which may contribute to a better epidemiological description of the disease in this region and, consequently, its early diagnosis.

Objectives

Our study aims to review the risk factors, clinical and radiological characteristics of CVT in Latin America, being critically compared with data from world literature.

Methods

PubMed, ScienceDirect, BVS, and Scopus were searched to identify studies reporting CVT in Latin American countries published up to July 2022. We excluded case reports and case series reporting <5 patients later in the final analysis.

Results

We identified a total of 3714 studies and 26 qualified for the quantitative analysis, which described 1486 cases of CVT. Headache was the most frequent symptom (82.1%) and the use of oral contraceptives in women was the main risk factor (46.7%). The transverse sinus was the most frequent location of the thrombus (52%). The treatment used most in the acute phase was heparin (88.5%) and oral anticoagulation was widely used at hospital discharge (67.8%). The mortality was low (6.5%), and most patients achieved complete recovery (75.3%).

Conclusion

Despite considerable dissimilarities in studies between countries, particularities were identified in the risk factors of CVT in Latin America compared to other regions of the world.
High-risk features of basilar artery atherosclerotic plaque
Authors: Li Shaojun , Wei Jiana , Huang Ruiyun , Li Chenghao , Chen Hongbing , Qiu Zhihua , Jiang Yongjun , Wu Li
Published: October 2022

Introduction

High-resolution magnetic resonance imaging (HR-MRI) is used to characterize atherosclerotic plaque. The present study aimed to determine the high-risk features of the basilar artery (BA) atherosclerotic plaque.

Methods

Patients with advanced BA stenosis were screened. The features including the ruptured fibrous cap (RFC), lipid core, intraplaque hemorrhage (IPH), plaque enhancement, and calcification were assessed by using high-resolution MRI. The relationship between the features and acute infarction was analyzed.

Results

From 1 June 2014 to 31 December 2018, a total of 143 patients with 76 new strokes were included. RFC was identified in 25% of symptomatic and 10.4% of asymptomatic patients. IPH was identified in 48.7% of symptomatic and 25.4% of asymptomatic patients. RFC (3.157, 95% CI 1.062 to 9.382, p = 0.039) and IPH (2.78, 95% CI 1.127 to 6.505, p = 0.026) were independent risk factors for acute infarction.

Conclusion

Our study showed that RFC and IPH of BA plaque were independent risk factors for acute infarction.
Potential mechanisms of acupuncture in enhancing cerebral perfusion of ischemic stroke
Authors: Wang Lu , Su Xin-Tong , Cao Yan , Yang Na-Na , Hao Xiao-Wan , Li Hong-Ping , Wang Qing-Yong , Yang Jing-Wen
Published: October 2022

Ischemic stroke is the predominant cause of long-term disability and death worldwide. It is attributable to the sudden interruption of regional cerebral blood flow, resulting in brain cell death and neurological impairment. Acupuncture is a widely used adjuvant treatment for ischemic stroke in China and shows promising efficacy in clinical practice. This review mainly focused on the evidence to illustrate several possible mechanisms of acupuncture therapy on cerebral perfusion in ischemic stroke. Studies have shown that acupuncture is probably effective in the enhancement of cerebral perfusion after ischemic stroke. It promotes the improvement of hemodynamics, the release of vasoactive substances, the formation of new blood vessels, as well as the restitution of microcirculation. Multiple factors may contribute to the variability in acupuncture's therapeutic effects, including the acupoint selection, stimulation frequency and intensity, and retaining needle time. Acupuncture has the potential to become a non-pharmacological adjuvant approach to enhance cerebral perfusion in ischemic stroke. Future studies are required to gain our insight into acupuncture as well as accelerate its clinical translation.
Adult dural arteriovenous fistulas in Galen region: More to be rediscovered
Authors: Tu Tianqi , Song Zihao , Ma Yongjie , Yang Chengbin , Su Xin , He Chuan , Li Guilin , Hong Tao , Sun Liyong , Hu Peng , Zhang Peng , Ye Ming , Zhang Hongqi
Published: October 2022

Background

Dural arteriovenous fistulas (DAVFs) in the Galen region are the most deeply located and most complex type of dural arteriovenous fistulas. However, cases of DAVFs in this region have not been well described. Thus, we aimed to summarize the characteristics of Galenic DAVFs involving clinical symptoms, anatomical architecture, and drainage patterns, providing experientially therapeutic strategies for these lesions based on our 20 years of clinical experience.

Methods

We retrospectively examined 31 patients with Galenic DAVFs between January 2000 and June 2021. A comprehensive analysis was carried out based on the symptoms, imaging features, feeding arteries, draining veins, number and location of the fistulas, choice of treatment methods, and prognosis assessment.

Results

Twenty-nine patients received endovascular embolization, and no perioperative deaths occurred. A transarterial approach was performed in 27 patients, and a combined transarterial and transvenous approach in one. And in one case, access was established by surgical drilling and embolization was done via the venous route. Twenty-four cases were completely obliterated after first embolization, and another five cases received a second period treatment. Only one patient developed cognitive dysfunction after embolization, and the outcomes of the remaining patients were improved at long-term follow-up.

Conclusion

The understanding of symptoms of non-hemorrhagic neurological deficits in DAVF needs to be further clarified. Lesions with pial feeders may be considered first when determining surgical orders. Multi-approach and multi-stage embolization would be safe and effective. Excessive embolization and deep-vein system obstruction should be avoided. Approach creation by surgery would be an innovative interventional therapy.
Oligoclonal M bands and cervical spinal cord lesions predict early secondary progressive multiple sclerosis
Authors: Alcalá Vicente Carmen , Lacruz Laura , Gascón Francisco , Carratalà Sara , Quintanilla-Bordás Carlos , Sanz Maria T. , Carcelén-Gadea María , Mallada Javier , Carreres Joan , Gabaldón Torres Laura , Dominguez Jose Andres , Cañizares Emmanuel , Gil-Perotin Sara , Cubas Laura , Gasqué Rubio Raquel , Castillo-Villalba Jéssica , Pérez-Miralles Francisco Carlos , Casanova Bonaventura
Published: October 2022

Objective

To determine baseline cerebrospinal fluid and magnetic resonance imaging (MRI) variables at the onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) that predict evolution to secondary progressive MS (SPMS).

Methods

276 CIS patients with a minimum follow-up of 10 years were studied. Baseline presence of oligoclonal IgG and IgM bands (OCGB and OCMB respectively); number of brain T2 lesions (B-T2L), brain gadolinium enhancement lesions (brain-GEL), cervical spinal cord T2 lesions (cSC-T2L); and fulfillment of 2017 McDonald criteria among other variables were collected.

Results

14 patients ended up with a non-MS condition. 138/276 CIS patients fulfilled 2017 McDonald criteria. Mean age was 32.4 years, 185 female. 227 received treatment, 95 as CIS. After a mean follow-up of 12 years, 36 patients developed SPMS. Conversion to SPMS was associated with OCGB (p = 0.02), OCMB (p = 0.0001); ≥ 9 B-T2L (p = 0.03), brain-GEL (p = 0.03), and cSC-T2L (p = 0.03). However, after adjusting for sex, age, BT2L, brain-GEL, SC-T2, and OCMB status, only OCMB (HR 4.4, 1.9–10.6) and cSC-T2L (HR 2.2, 1.0–6.2) suggested an independent association with risk of conversion to SPMS. Patients with both risk factors had a HR of 6.12 (2.8–12.9).

Discussion

OCMB and SC-T2 lesions are potential independent predictors of conversion to SPMS.
Extended liquid state machines for speech recognition
Authors: Deckers Lucas , Tsang Ing Jyh , Van Leekwijck Werner , Latré Steven
Published: October 2022

A liquid state machine (LSM) is a biologically plausible model of a cortical microcircuit. It exists of a random, sparse reservoir of recurrently connected spiking neurons with fixed synapses and a trainable readout layer. The LSM exhibits low training complexity and enables backpropagation-free learning in a powerful, yet simple computing paradigm. In this work, the liquid state machine is enhanced by a set of bio-inspired extensions to create the extended liquid state machine (ELSM), which is evaluated on a set of speech data sets. Firstly, we ensure excitatory/inhibitory (E/I) balance to enable the LSM to operate in edge-of-chaos regime. Secondly, spike-frequency adaptation (SFA) is introduced in the LSM to improve the memory capabilities. Lastly, neuronal heterogeneity, by means of a differentiation in time constants, is introduced to extract a richer dynamical LSM response. By including E/I balance, SFA, and neuronal heterogeneity, we show that the ELSM consistently improves upon the LSM while retaining the benefits of the straightforward LSM structure and training procedure. The proposed extensions led up to an 5.2% increase in accuracy while decreasing the number of spikes in the ELSM up to 20.2% on benchmark speech data sets. On some benchmarks, the ELSM can even attain similar performances as the current state-of-the-art in spiking neural networks. Furthermore, we illustrate that the ELSM input-liquid and recurrent synaptic weights can be reduced to 4-bit resolution without any significant loss in classification performance. We thus show that the ELSM is a powerful, biologically plausible and hardware-friendly spiking neural network model that can attain near state-of-the-art accuracy on speech recognition benchmarks for spiking neural networks.
The interplay between the gut-brain axis and the microbiome: A perspective on psychiatric and neurodegenerative disorders
Authors: Bashir Yasir , Khan Asad U.
Published: October 2022

What is the effect of our gut microbial flora on brain? Does the gut microbiome have any role in the causation of psychiatric and neurodegenerative diseases? Does the effect of gut microbiota traverse the gut-brain axis? Questions like these have captured the interest and imagination of the scientific community for quite some time now. Research in the quest for answers to these questions, to unravel the potential role of the microbiota inhabiting the gut in controlling brain functions, has progressed manifold over the last two decades. Although the possibility of microbiome as a key susceptibility factor for neurological disorders viz. Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and autism spectrum disorder has bolstered by an increase in the clinical and preclinical evidence, the field is still in its infancy. Given the fact that the diversity of the gut microbiota is affected by various factors including the diet and exercise, the interpretation of such data becomes all the more difficult. Also, such studies have been mostly conducted on animal models, so there is a need for randomized controlled trials in human subjects, corroborated by longitudinal studies, to establish if modulating the gut microbiota can unravel novel therapeutic interventions. Exploring the genomic, metagenomic and metabolomic data from clinical subjects with psychiatric and neurological diseases can prove to be a helpful guide in individual treatment selection.
Assessing brain and biological aging trajectories associated with Alzheimer’s disease
Authors: Liang Winnie S. , Goetz Laura H. , Schork Nicholas J.
Published: October 2022

The development of effective treatments to prevent and slow Alzheimer’s disease (AD) pathogenesis is needed in order to tackle the steady increase in the global prevalence of AD. This challenge is complicated by the need to identify key health shifts that precede the onset of AD and cognitive decline as these represent windows of opportunity for intervening and preventing disease. Such shifts may be captured through the measurement of biomarkers that reflect the health of the individual, in particular those that reflect brain age and biological age. Brain age biomarkers provide a composite view of the health of the brain based on neuroanatomical analyses, while biological age biomarkers, which encompass the epigenetic clock, provide a measurement of the overall health state of an individual based on DNA methylation analysis. Acceleration of brain and biological ages is associated with changes in cognitive function, as well as neuropathological markers of AD. In this mini-review, we discuss brain age and biological age research in the context of cognitive decline and AD. While more research is needed, studies show that brain and biological aging trajectories are variable across individuals and that such trajectories are non-linear at older ages. Longitudinal monitoring of these biomarkers may be valuable for enabling earlier identification of divergent pathological trajectories toward AD and providing insight into points for intervention.
Bayesian multisource data integration for explainable brain-behavior analysis
Authors: Chen Rong
Published: October 2022

Different data sources can provide complementary information. Moving from a simple approach based on using one data source at a time to a systems approach that integrates multiple data sources provides an opportunity to understand complex brain disorders or cognitive processes. We propose a data fusion method, called Bayesian Multisource Data Integration, to model the interactions among data sources and behavioral variables. The proposed method generates representations from data sources and uses Bayesian network modeling to associate representations with behavioral variables. The generated Bayesian network is transparent and easy to understand. Bayesian inference is used to understand how the perturbation of representation is related to behavioral changes. The proposed method was assessed on the simulated data and data from the Adolescent Brain Cognitive Development study. For the Adolescent Brain Cognitive Development study, we found diffusion tensor imaging and resting-state functional magnetic resonance imaging were synergistic in understanding the fluid intelligence composite and the total score composite in healthy youth (9–11 years of age).
Chronic exercise remodels the lysine acetylome in the mouse hippocampus
Authors: Qian Ping , Ma Feifei , Zhang Wanyu , Cao Dingding , Li Luya , Liu Zhuo , Pei Pei , Zhang Ting , Wang Shan , Wu Jianxin
Published: October 2022

Physical exercise benefits hippocampal function through various molecular mechanisms. Protein acetylation, a conserved and widespread post-translational modification, is involved in the synaptic plasticity and memory. However, whether exercise can change global acetylation and the role of acetylated proteins in the hippocampus have remained largely unknown. Herein, using healthy adult mice running for 6 weeks as exercise model and sedentary mice as control, we analyzed the hippocampal lysine acetylome and proteome by Liquid chromatography-tandem mass spectrometry. As a result, we profiled the lysine acetylation landscape for the hippocampus and identified 3,876 acetyl sites and 1,764 acetylated proteins. A total of 272 acetyl sites on 252 proteins were differentially regulated by chronic exercise, among which 18.58% acetylated proteins were annotated in mitochondria. These proteins were dominantly deacetylated and mainly associated with carbon-related metabolism, the Hippo signaling pathway, ribosomes, and protein processing. Meanwhile, 21 proteins were significantly expressed and enriched in the pathway of complement and coagulation cascades. Our findings provide a new avenue for understanding the molecular mechanisms underlying the benefits of exercise for hippocampal function and can contribute to the promotion of public health.
Wnt-5a induces the conversion of silent to functional synapses in the hippocampus
Authors: Álvarez-Ferradas Carla , Wellmann Mario , Morales Koyam , Fuenzalida Marco , Cerpa Waldo , Inestrosa Nibaldo C. , Bonansco Christian
Published: October 2022

Synapse unsilencing is an essential mechanism for experience-dependent plasticity. Here, we showed that the application of the ligand Wnt-5a converts glutamatergic silent synapses into functional ones by increasing both α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) currents (IAMPA and INMDA, respectively). These effects were mimicked by the hexapeptide Foxy-5 and inhibited by secreted frizzled-related protein sFRP-2. INMDA potentiation was produced by increased synaptic potency, followed by an increase in the probability of release (Pr), even in the presence of 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX). At a longer time of Wnt-5a exposure, the Pr increments were higher in INMDA than in IAMPA. In the presence of NMDAR inhibitors, Wnt-5a-induced conversion was fully inhibited in 69.0% of silent synapses, whereas in the remaining synapses were converted into functional one. Our study findings showed that the Wnt-5a-activated pathway triggers AMPAR insertion into mammalian glutamatergic synapses, unsilencing non-functional synapses and promoting the formation of nascent synapses during the early postnatal development of the brain circuits.
The transforming growth factor beta ligand TIG-2 modulates the function of neuromuscular junction and muscle energy metabolism in Caenorhabditis elegans
Authors: Cheng Xinran , Yan Zhenzhen , Su Zexiong , Liu Jie
Published: October 2022

Deciphering the physiological function of TGF-β (the transforming growth factor beta) family ligands is import for understanding the role of TGF-β in animals’ development and aging. Here, we investigate the function of TIG-2, one of the ligands in Caenorhabditis elegans TGF-β family, in animals’ behavioral modulation. Our results show that a loss-of-function mutation in tig-2 gene result in slower locomotion speed in the early adulthood and an increased density of cholinergic synapses, but a decreased neurotransmitter release at neuromuscular junctions (NMJs). Further tissue-specific rescue results reveal that neuronal and intestinal TIG-2 are essential for the formation of cholinergic synapses at NMJs. Interestingly, tig-2(ok3416) mutant is characterized with reduced muscle mitochondria content and adenosine triphosphate (ATP) production, although the function of muscle acetylcholine receptors and the morphology muscle fibers in the mutant are comparable to that in wild-type animals. Our result suggests that TIG-2 from different neuron and intestine regulates worm locomotion by modulating synaptogenesis and neurotransmission at NMJs, as well as energy metabolism in postsynaptic muscle cells.
Active fractions of golden-flowered tea (Camellia nitidissima Chi) inhibit epidermal growth factor receptor mutated non-small cell lung cancer via multiple pathways and targets in vitro and in vivo
Authors: Wang Ziling , Hou Xiaoying , Li Min , Ji Rongsheng , Li Zhouyuan , Wang Yuqiao , Guo Yujie , Liu Dahui , Huang Bisheng , Du Hongzhi
Published: October 2022

As a medicine-food homology (MFH) plant, golden-flowered tea (Camellia nitidissima Chi, CNC) has many different pharmacologic activities and is known as “the queen of the tea family” and “the Panda of the Plant world”. Several studies have revealed the pharmacologic effects of CNC crude extract, including anti-tumor, anti-oxidative and hepatoprotective activity. However, there are few studies on the anti-tumor active fractions and components of CNC, yet the underlying mechanism has not been investigated. Thus, we sought to verify the anti-non-small cell lung cancer (NSCLC) effects of four active fractions of CNC. Firstly, we determined the pharmacodynamic material basis of the four active fractions of CNC (Camellia. leave. saponins, Camellia. leave. polyphenols, Camellia. flower. saponins, Camellia. flower. polyphenols) by UPLC-Q-TOF-MS/MS and confirmed the differences in their specific compound contents. Then, MTT, colony formation assay and EdU incorporation assay confirmed that all fractions of CNC exhibit significant inhibitory on NSCLC, especially the Camellia. leave. saponins (CLS) fraction on EGFR mutated NSCLC cell lines. Moreover, transcriptome analysis revealed that the inhibition of NSCLC cell growth by CLS may be via three pathways, including “Cytokine-cytokine receptor interaction,” “PI3K-Akt signaling pathway” and “MAPK signaling pathway.” Subsequently, quantitative real-time PCR (RT-qPCR) and Western blot (WB) revealed TGFB2, INHBB, PIK3R3, ITGB8, TrkB and CACNA1D as the critical targets for the anti-tumor effects of CLS in vitro. Finally, the xenograft models confirmed that CLS treatment effectively suppressed tumor growth, and the key targets were also verified in vivo. These observations suggest that golden-flowered tea could be developed as a functional tea drink with anti-cancer ability, providing an essential molecular mechanism foundation for MFH medicine treating NSCLC.
Effect of lactylation on functional and structural properties of gluten
Authors: Wang Yu , Li Yan , Fan Mingcong , Wang Li , Qian Haifeng
Published: October 2022

Gluten is widely used as a high-quality protein material in the food industry, however, low solubility restricts its development and applications. In this study, gluten was treated with lactate and sodium lactate for lactylation. Lactylation of gluten altered surface charges of the protein, leading to a significant improvement in the solubility. An improvement in oil absorption capacity (OAC) could be attributed to a decrease in protein folding degree after lactylation. In addition, the emulsifying properties of gluten were significantly enhanced. The introduction of lactate group also significantly increased the viscoelasticity of gluten. Fourier transform infrared spectroscopy (FTIR) showed there was a significant decrease in β-turns content and a significant increase in β-sheets content. The folded conformation of gluten was gradually extended after lactation by fluorescence spectroscopy measurement. Both in lactate and sodium lactate treatment, the maximum emission wavelength indicated a blue shift, and the UV intensity showed an increase. These results could demonstrate that lactylation could extend the structure and improve the functional property.