bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of data protection laws in the European Union and in California is associated with a move of clinical trials to countries with fewer data protections
Authors: Yom-Tov Elad , Ofran Yishai
Published: November 2022

The European Union implemented data privacy laws in mid-2018 and the state of California enacted a similar law several weeks later. These regulations affect medical data collection and analysis. It is unclear if they achieve this goal in the realm of clinical trials. Here we investigate the effect of these laws on clinical trials through analysis of clinical trials recorded on the US's ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform and scientific papers describing clinical trials. Our findings show that the number of phase 1 and 2 trials in countries not adhering to these data privacy laws rose significantly after implementation of these laws. The largest rise occurred in countries which are less free, as indicated by the negative correlation (−0.48, p = 0.008) between the civil liberties freedom score of countries and the increase in the number of trials. This trend was not observed in countries adhering to data privacy laws nor in the paper publication record. The rise was larger (and statistically significant) among industry funded trials and interventional trials. Thus, the implementation of data privacy laws is associated a change in the location of clinical trials, which are currently executed more often in countries where people have fewer protections for their data.
SARS-CoV-2 variants: Impact on biological and clinical outcome
Authors: Mahilkar Shakuntala , Agrawal Sachee , Chaudhary Sakshi , Parikh Swapneil , Sonkar Subash C. , Verma Dileep Kumar , Chitalia Vidushi , Mehta Divya , Koner Bidhan Chandra , Vijay Neetu , Shastri Jayanthi , Sunil Sujatha
Published: November 2022

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was first identified in December 2019, in Wuhan, China was found to be the etiological agent for a novel respiratory infection that led to a Coronavirus Induced Disease named COVID-19. The disease spread to pandemic magnitudes within a few weeks and since then we have been dealing with several waves across the world, due to the emergence of variants and novel mutations in this RNA virus. A direct outcome of these variants apart from the spike of cases is the diverse disease presentation and difficulty in employing effective diagnostic tools apart from confusing disease outcomes. Transmissibility rates of the variants, host response, and virus evolution are some of the features found to impact COVID-19 disease management. In this review, we will discuss the emerging variants of SARS-CoV-2, notable mutations in the viral genome, the possible impact of these mutations on detection, disease presentation, and management as well as the recent findings in the mechanisms that underlie virus-host interaction. Our aim is to invigorate a scientific debate on how pathogenic potential of the new pandemic viral strains contributes toward development in the field of virology in general and COVID-19 disease in particular.
Diversity in rhizospheric microbial communities in tea varieties at different locations and tapping potential beneficial microorganisms
Authors: Zhang Zheng , Ge ShiBei , Fan Li-Chao , Guo Shuai , Hu Qiang , Ahammed Golam Jalal , Yan Peng , Zhang Li-Ping , Li Zheng-Zhen , Zhang Jian-Yang , Fu Jianyu , Han Wenyan , Li Xin
Published: November 2022

Soil microenvironments and plant varieties could largely affect rhizosphere microbial community structure and functions. However, their specific effects on the tea rhizosphere microbial community are yet not clear. Beneficial microorganisms are important groups of microbial communities that hold ecological functionalities by playing critical roles in plant disease resistance, and environmental stress tolerance. Longjing43 and Zhongcha108 are two widely planted tea varieties in China. Although Zhongcha108 shows higher disease resistance than Longjing43, the potential role of beneficial tea rhizosphere microbes in disease resistance is largely unknown. In this study, the structure and function of rhizosphere microbial communities of these two tea varieties were compared by using the Illumina MiSeq sequencing (16S rRNA gene and ITS) technologies. Rhizosphere soil was collected from four independent tea gardens distributed at two locations in Hangzhou and Shengzhou cities in eastern China, Longjing43 and Zhongcha108 are planted at both locations in separate gardens. Significant differences in soil physicochemical properties as demonstrated by ANOVA and PCA, and distinct rhizosphere microbial communities by multiple-biotech analyses (PCoA, LEfSe, Co-occurrence network analyses) between both locations and tea varieties (p < 0.01) were found. Functions of bacteria were annotated by the FAPROTAX database, and a higher abundance of Nitrososphaeraceae relating to soil ecological function was found in rhizosphere soil in Hangzhou. LDA effect size showed that the abundance of arbuscular mycorrhizal fungi (AMF) was higher in Zhongcha108 than that in Longjing43. Field experiments further confirmed that the colonization rate of AMF was higher in Zhongcha108. This finding testified that AMF could be the major beneficial tea rhizosphere microbes that potentially function in enhanced disease resistance. Overall, our results confirmed that locations affected the microbial community greater than that of tea varieties, and fungi might be more sensitive to the change in microenvironments. Furthermore, we found several beneficial microorganisms, which are of great significance in improving the ecological environment of tea gardens and the disease resistance of tea plants. These beneficial microbial communities may also help to further reveal the mechanism of disease resistance in tea and potentially be useful for mitigating climate change-associated challenges to tea gardens in the future.
Identification and characterization of mixed infections of Chlamydia trachomatis via high-throughput sequencing
Authors: Zhao Jianhui , Shui Jingwei , Luo Lipei , Ao Cailing , Lin Hongqing , Liang Yuanhao , Wang Li , Wang Haiying , Chen Hongliang , Tang Shixing
Published: November 2022

Precise genotyping is necessary to understand epidemiology and clinical manifestations of Chlamydia trachomatis infection with different genotypes. Next-generation high-throughput sequencing (NGHTS) has opened new frontiers in microbial genotyping, but has been clinically characterized in only a few settings. This study aimed to determine C. trachomatis genotypes in particular mixed-genotype infections and their association with clinical manifestations and to characterize the sensitivity and accuracy of NGHTS. Cervical specimens were collected from 8,087 subjects from physical examination center (PEC), assisted reproductive technology center (ART) and gynecology clinics (GC) of Chenzhou Hospital of China. The overall prevalence of C. trachomatis was 3.8% (311/8087) whereas a prevalence of 2.8, 3.7 and 4.8% was found in PEC, ART and GC, respectively. The most frequent three C. trachomatis genotypes were E (27.4%, 83/303), F (21.5%, 65/303) and J (18.2%, 55/303). Moreover, NGHTS identified 20 (6.6%, 20/303) mixed-genotype infections of C. trachomatis. Genotype G was more often observed in the subjects with pelvic inflammatory disease than genotype E (adjusted OR = 3.61, 95%CI, 1.02–12.8, p = 0.046). Mixed-genotype infection was associated with severe vaginal cleanliness (degree IV) with an adjusted OR of 5.17 (95%CI 1.03–25.9, p = 0.046) whereas mixed-genotype infection with large proportion of minor genotypes was associated with cervical squamous intraepithelial lesion (SIL) with an adjusted OR of 5.51 (95%CI 1.17–26.01, p = 0.031). Our results indicated that NGHTS is a feasible tool to identity C. trachomatis mixed-genotype infections, which may be associated with worse vaginal cleanliness and cervical SIL.
Metabonomics reveals that entomopathogenic nematodes mediate tryptophan metabolites that kill host insects
Authors: Zhang Yuan , Wang Fang , Zhao Zihua
Published: November 2022

The entomopathogenic nematode (EPN) Steinernema feltiae, which carries the symbiotic bacterium Xenorhabdus bovienii in its gut, is an important biocontrol agent. This EPN could produce a suite of complex metabolites and toxin proteins and lead to the death of host insects within 24–48 h. However, few studies have been performed on the key biomarkers released by EPNs to kill host insects. The objective of this study was to examine what substances produced by EPNs cause the death of host insects. We found that all densities of nematode suspensions exhibited insecticidal activities after hemocoelic injection into Galleria mellonella larvae. EPN infection 9 h later led to immunosuppression by activating insect esterase activity, but eventually, the host insect darkened and died. Before insect immunity was activated, we applied a high-resolution mass spectrometry-based metabolomics approach to determine the hemolymph of the wax moth G. mellonella infected by EPNs. The results indicated that the tryptophan (Trp) pathway of G. mellonella was significantly activated, and the contents of kynurenine (Kyn) and 3-hydroxyanthranilic acid (3-HAA) were markedly increased. Additionally, 3-HAA was highly toxic to G. mellonella and resulted in corrected mortalities of 62.50%. Tryptophan metabolites produced by EPNs are a potential marker to kill insects, opening up a novel line of inquiry into exploring the infestation mechanism of EPNs.
Comparative virulence and antimicrobial resistance distribution of Streptococcus suis isolates obtained from the United States
Authors: Nicholson Tracy L. , Bayles Darrell O.
Published: November 2022

Streptococcus suis is a zoonotic bacterial swine pathogen causing substantial economic and health burdens to the pork industry worldwide. Most S. suis genome sequences available in public databases are from isolates obtained outside the United States. We sequenced the genomes of 106 S. suis isolates from the U.S. and analyzed them to identify their potential to function as zoonotic agents and/or reservoirs for antimicrobial resistance (AMR) dissemination. The objective of this study was to evaluate the genetic diversity of S. suis isolates obtained within the U.S., for the purpose of screening for genomic elements encoding AMR and any factors that could increase or contribute to the capacity of S. suis to transmit, colonize, and/or cause disease in humans. Forty-six sequence types (STs) were identified with ST28 observed as the most prevalent, followed by ST87. Of the 23 different serotypes identified, serotype 2 was the most prevalent, followed by serotype 8 and 3. Of the virulence genes analyzed, the highest nucleotide diversity was observed in sadP, mrp, and ofs. Tetracycline resistance was the most prevalent phenotypic antimicrobial resistance observed followed by macrolide-lincosamide-streptogramin B (MLSB) resistance. Numerous AMR elements were identified, many located within MGE sequences, with the highest frequency observed for ble, tetO and ermB. No genes encoding factors known to contribute to the transmission, colonization, and/or causation of disease in humans were identified in any of the S. suis genomes in this study. This includes the 89 K pathogenicity island carried by the virulent S. suis isolates responsible for human infections. Collectively, the data reported here provide a comprehensive evaluation of the genetic diversity among U.S. S. suis isolates. This study also serves as a baseline for determining any potential risks associated with occupational exposure to these bacteria, while also providing data needed to address public health concerns.
The first cultivated representatives of the actinobacterial lineage OPB41 isolated from subsurface environments constitute a novel order Anaerosomatales
Authors: Khomyakova Maria A. , Zavarzina Daria G. , Merkel Alexander Y. , Klyukina Alexandra A. , Pikhtereva Valeria A. , Gavrilov Sergey N. , Slobodkin Alexander I.
Published: November 2022

The continental subsurface harbors microbial populations highly enriched in uncultured taxa. OPB41 is an uncultured order-level phylogenetic lineage within the actinobacterial class Coriobacteriia. OPB41 bacteria have a wide geographical distribution, but the physiology and metabolic traits of this cosmopolitan group remain elusive. From two contrasting subsurface environments, a terrestrial mud volcano and a deep subsurface aquifer, located in the central part of Eurasia, within the Caucasus petroleum region, we have isolated two pure cultures of anaerobic actinobacteria belonging to OPB41. The cells of both strains are small non-motile rods forming numerous pili-like appendages. Strain M08DHBT is mesophilic, while strain Es71-Z0120T is a true thermophile having a broad temperature range for growth (25–77°C). Strain M08DHBT anaerobically reduces sulfur compounds and utilizes an aromatic compound 3,4-dihydroxybenzoic acid. Strain Es71-Z0120T is an obligate dissimilatory Fe(III) reducer that is unable to utilize aromatic compounds. Both isolates grow lithotrophically and consume molecular hydrogen or formate using either thiosulfate, elemental sulfur, or Fe(III) as an electron acceptor. Genomes of the strains encode the putative reductive glycine pathway for autotrophic CO2 fixation, Ni-Fe hydrogenases, putative thiosulfate/polysulfide reductases, and multiheme c-type cytochromes presumably involved in dissimilatory Fe(III) reduction. We propose to assign the isolated strains to the novel taxa of the species–order levels and describe strain M08DHBT as Anaerosoma tenue gen. nov., sp. nov., and strain Es71-Z0120T as Parvivirga hydrogeniphila gen. nov., sp. nov., being members of Anaerosomatales ord. nov. This work expands the knowledge of the diversity, metabolic functions, and ecological role of the phylum Actinomycetota.
Characterization of polyvalent Escherichia phage Sa157lw for the biocontrol potential of Salmonella Typhimurium and Escherichia coli O157:H7 on contaminated mung bean seeds
Authors: Liao Yen-Te , Zhang Yujie , Salvador Alexandra , Ho Kan-Ju , Cooley Michael B. , Wu Vivian C. H.
Published: November 2022

Seeds are one of the primary sources of contamination with foodborne pathogens, such as pathogenic Escherichia coli, and various Salmonella serovars, for produce, particularly sprouts. Due to the susceptibility of sprout growth to chemical-based antimicrobials and the rising issue of antimicrobial resistance, developing innovative antimicrobial interventions is an urgent need. Therefore, the objective of this study was to characterize Escherichia phage Sa157lw (or Sa157lw) for the biocontrol potential of Salmonella Typhimurium and E. coli O157:H7 on contaminated mung bean seeds. Phage Sa157lw was subjected to whole-genome sequencing and biological characterization, including morphology, one-step growth curve, and stress stability tests. Later, antimicrobial activity was determined in vitro and upon application on the mung bean seeds artificially contaminated with E. coli O157:H7 or Salmonella Typhimurium. Sa157lw possessed a contractile tail and belonged to the Kuttervirus genus under the Ackermannviridae family, sharing a close evolutionary relationship with E. coli phage ECML-4 and Kuttervirus ViI; however, tail spike genes (ORF_102 and ORF_104) were the primary region of difference. Comparative genomics showed that Sa157lw encoded a cluster of tail spike genes—including ORF_101, ORF_102, and ORF_104—sharing high amino acid similarity with the counterfeits of various Salmonella phages. Additionally, Sa157lw harbored a unique tail fiber (ORF_103), possibly related to the receptors binding of O157 strains. The genomic evidence accounted for the polyvalent effects of Sa157lw against E. coli O157:H7 and various Salmonella serovars (Typhimurium, Enteritidis, Agona, Saintpaul, and Heidelberg). Furthermore, the phage did not contain any virulence, antibiotic-resistant, or lysogenic genes. Sa157lw had a 30-min latent period on both E. coli O157:H7 and Salmonella Typhimurium, with an estimated burst size of 130 and 220 PFU/CFU, respectively, and was stable at a wide range of temperatures (4–60°C) and pH (pH4 to pH10). The phage application demonstrated a strong anti-E. coli O157:H7 and anti-Salmonella Typhimurium effects in 1.1 and 1.8 log reduction on the contaminated mung bean seeds after overnight storage at 22°C. These findings provide valuable insights into the polyvalent Sa157lw as a potential biocontrol agent of Salmonella Typhimurium and E. coli O157:H7 on sprout seeds.
Fungal outbreak in the Catacombs of SS. Marcellino and Pietro Rome (Italy): From diagnosis to an emergency treatment
Authors: De Leo Filomena , Dominguez-Moñino Irene , Jurado Valme , Bruno Laura , Saiz-Jimenez Cesareo , Urzì Clara
Published: November 2022

The present study reports a sudden fungal outbreak that occurred in the corridor near the entrance of the Catacombs of SS. Marcellino and Pietro in Rome (Italy) observed after 1 year of a restoration treatment that interested the walls of the entrance of the Catacombs and some artifacts placed in situ. The colonization was observed on the vault at the entrance and in correspondence with the restored marble pieces displayed on the left side of the corridor. No growth was observed on the right side where similarly treated marble slabs were placed. Samples taken in correspondence with fungal biofilm were analyzed through the combined use of microscopical, cultural, and molecular tools and showed that the vault and the left side of the corridor entrance were colonized by a complex fungal biofilm consisting mainly of Coniophora sp. and other genera, such as Hypomyces, Purpureocillium, Acremonium, Penicillium, and Alternaria, many of which are well known as responsible of biodeterioration of stone surfaces. Regarding the brown-rot basidiomycete Coniophora, it was able to form very large colonies on the substrata with a diameter of up to 57 cm. Although the direct observation under a light microscope evidenced the presence of abundant brown fungal conidia, several attempts to cultivate the microorganism failed, therefore only through DNA sequencing analyses, it was possible to identify and characterize this fungus. There is very little literature on the genus Coniophora which is reported as one of the causes of wet-rot decay of wood in buildings. A connection with calcium-containing materials such as bricks and mortars was demonstrated, but no data were available about the possible role of this species in the biodeterioration of stones. This study features the first finding of a strain related to the basidiomycetous genus of Coniophora in the order Boletales in association with evident phenomena of biodeterioration.
The application of exosomes in the treatment of triple-negative breast cancer
Authors: Weaver John W. , Zhang Jinyu , Rojas Juan , Musich Phillip R. , Yao Zhiqiang , Jiang Yong
Published: November 2022

Triple-negative breast cancer (TNBC) is a heterogeneous and invasive breast cancer (BC) subtype that is estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (Her2)-negative. So far, the treatment of TNBC is still ineffective due to the lack of well-defined molecular targets. Exosomes are nanosized extracellular vesicles composed of lipid bilayers. They originate from various types of donor cells and release a complex mixture of contents including diverse nucleic acid types (miRNA, LnRNA, siRNA, and DNA) and proteins; after binding to recipient cells the exosomes release their contents that execute their biological functions. Exosomes have been reported to play an important role in the tumorigenesis of TNBC, including tumor initiation, metastasis, angiogenesis, cell proliferation, immune escape, and drug resistance. On the other hand, exosomes can be valuable biomarkers for diagnosis, monitoring, and treatment of TNBC. More interestingly, exosomes can be harnessed as a nanosized drug-delivery system specifically targeting TNBC. In this review, we present the most recent mechanistic findings and clinical applications of exosomes in TNBC therapy, focusing on their use as diagnostic and prognostic biomarkers, nanoscale drug delivery platforms, and immunotherapeutic agents. In addition, the associated challenges and future directions of using exosomes for TNBC treatment will be discussed.
Pre-diabetes is associated with altered functional connectivity density in cortical regions of the default-mode network
Authors: Lopez-Vilaret Karel M. , Fernandez-Alvarez Marina , Shokri-Kojori Ehsan , Tomasi Dardo , Cantero Jose L. , Atienza Mercedes
Published: November 2022

Insulin resistance and glucose dysregulation are associated with patterns of regional brain hypometabolism characteristic of Alzheimer’s disease (AD). As predicted by evidence linking brain glucose metabolism to brain functional connectivity, type 2 diabetes is accompanied by altered functional connectivity density (FCD) in regions highly vulnerable to AD, but whether these alterations start at earlier stages such as pre-diabetes remain to be elucidated. Here, in addition to assessing whether pre-diabetes leads to a functional reorganization of densely connected cortical areas (hubs), we will assess whether such reorganization is conditioned by sex and/or insulin resistance, and contributes to improved cognition. One hundred and forty-four cognitively unimpaired middle-aged and older adults (55–78 years, 79 females), 73 with normoglycemia and 71 with pre-diabetes, underwent resting-state fMRI scanning. We first computed FCD mapping on cortical surfaces to determine the number of short- and long-range functional connections of every vertex in the cortex, and next used hubs showing aberrant FCD as seeds for the resting-state functional connectivity (rs-FC) calculation. ANCOVAs and linear multiple regression analyses adjusted by demographic and cardiometabolic confounders using frequentist and Bayesian approaches were applied. Analyses revealed higher long-range FCD in the right precuneus of pre-diabetic females and lower short-range FCD in the left medial orbitofrontal cortex (mOFC) of pre-diabetic individuals with higher insulin resistance. Although the mOFC also showed altered rs-FC patterns with other regions of the default mode network in pre-diabetic individuals, it was FCD of the precuneus and mOFC, and not the magnitude of their rs-FC, that was associated with better planning abilities and Mini-Mental State Examination (MMSE) scores. Results suggest that being female and/or having high insulin resistance exacerbate pre-diabetes-induced alterations in the FCD of hubs of the default-mode network that are particularly vulnerable to AD pathology. These changes in brain network organization appear to be compensatory for pre-diabetic females, likely assisting them to maintain cognitive functioning at early stages of glucose dysregulation.
Alzheimer’s disease and epilepsy: An increasingly recognized comorbidity
Authors: Yang Fei , Chen Liling , Yu Yanying , Xu Tingwan , Chen Lu , Yang Wenqian , Wu Qian , Han Yanbing
Published: November 2022

Both Alzheimer’s disease (AD) and epilepsy are common chronic diseases in older people. Seizures and epileptiform discharges are very prevalent in AD and can occur since any stage of AD. Increasing evidence indicates that AD and epilepsy may be comorbid. Several factors may be related to the underlying mechanism of the comorbidity. Identifying seizures in patients with AD is a challenge because seizures are often clinically non-motor and may overlap with some AD symptoms. Not only seizures but also epileptiform discharges may exacerbate the cognitive decline in AD patients, highlighting the importance of early recognition and treatment. This review provides a comprehensive overview of seizures in AD from multiple aspects to provide more insight.
Effect of human probiotics on memory, psychological and biological measures in elderly: A study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota)
Authors: Bartos Ales , Weinerova Josefina , Diondet Sofia , Vales Karel
Published: November 2022

Background

Gut microbiota may influence brain functions. Therefore, we prepared a study protocol for a double-blind, crossover, randomized clinical trial to determine the complex effects of human probiotics on memory, psychological, and biological measures in the elderly.

Methods

We selected eligible participants using an effective electronic questionnaire containing the inclusion and exclusion criteria and a brief electronic cognitive test. One-third of the respondents with the worst cognitive scores on the electronic test are randomized to group A, starting with a 3-month probiotic intervention, and to group B, starting with a placebo. In a crossover design, both groups change their intervention/placebo status after 3 months for the next 3 months. Participants refusing longer personal assessments due to the COVID-19 pandemic were randomly allocated to one of two subgroups assessed online. Participants in both groups are matched in age, education, gender, and cognitive scores on electronic testing at baseline. At three time points, participants are assessed using a neuropsychological battery, self-report measures of mood, a physical fitness test, blood, urine, and stool samples, and actigraphy. A subset of participants also provided their biological samples and underwent the neuropsychological battery in an extended testing phase 3 months after study termination to find out the long-term effect of the intervention.

Discussion

This is the first trial to address the comprehensive effects of human probiotics on memory and many other measures in the elderly. We assume that the probiotic group will have better outcomes than the placebo group after the first and second trimesters. We expect that the probiotic effect will persist for the next 3 months. These study’s findings will contribute to an interesting area of how to improve memory, psychological and biological and other factors naturally and will examine the importance of probiotics for overall health in the elderly.

Clinical trial registration

[clinicaltrials.gov], identifier [NCT05051501].
Fear conditioning in invertebrates
Authors: Pribadi Amy K. , Chalasani Sreekanth H.
Published: November 2022

Learning to identify and predict threats is a basic skill that allows animals to avoid harm. Studies in invertebrates like Aplysia californica, Drosophila melanogaster, and Caenorhabditis elegans have revealed that the basic mechanisms of learning and memory are conserved. We will summarize these studies and highlight the common pathways and mechanisms in invertebrate fear-associated behavioral changes. Fear conditioning studies utilizing electric shock in Aplysia and Drosophila have demonstrated that serotonin or dopamine are typically involved in relaying aversive stimuli, leading to changes in intracellular calcium levels and increased presynaptic neurotransmitter release and short-term changes in behavior. Long-term changes in behavior typically require multiple, spaced trials, and involve changes in gene expression. C. elegans studies have demonstrated these basic aversive learning principles as well; however, fear conditioning has yet to be explicitly demonstrated in this model due to stimulus choice. Because predator–prey relationships can be used to study learned fear in a naturalistic context, this review also summarizes what is known about predator-induced behaviors in these three organisms, and their potential applications for future investigations into fear conditioning.
G-Exos: A wearable gait exoskeleton for walk assistance
Authors: Zorkot Mouhamed , Dac Léa Ho , Morya Edgard , Brasil Fabrício Lima
Published: November 2022

Stroke is the second leading cause of death and one of the leading causes of disability in the world. According to the World Health Organization, 11 million people suffer a stroke yearly. The cost of the disease is exorbitant, and the most widely used treatment is conventional physiotherapy. Therefore, assistive technology emerges to optimize rehabilitation and functional capabilities, but cost, robustness, usability, and long-term results still restrict the technology selection. This work aimed to develop a low-cost ankle orthosis, the G-Exos, a wearable exoskeleton to increase motor capability by assisting dorsiflexion, plantarflexion, and ankle stability. A hybrid system provided near-natural gait movements using active, motor, and passive assistance, elastic band. The system was validated with 10 volunteers with foot drop: seven with stroke, two with incomplete spinal cord injury (SCI), and one with acute inflammatory transverse myelitis (ATM). The G-Exos showed assistive functionality for gait movement. A Friedman test showed a significant difference in dorsiflexion amplitude with the use of the G-Exos compared to gait without the use of the G-Exos [x2(3) = 98.56, p < 0.001]. In addition, there was also a significant difference in ankle eversion and inversion comparing walking with and without the G-Exos [x2(3) = 36.12, p < 0.001]. The G-Exos is a robust, lightweight, and flexible assistive technology device to detect the gait phase accurately and provide better human-machine interaction. G-Exos training improved capability to deal with gait disorders, usability, and motor and functional recovery. Wearable assistive technologies lead to a better quality of life and contribute using in activities of daily living.
Case report and review of literature: Isolated intramedullary spinal neurocysticercosis
Authors: Andino Diana , Tsiang John T. , Pecoraro Nathan C. , Jani Ronak , Iordanou Jordan C. , Zakaria Jehad , Borys Ewa , Pasquale David D. , Nockels Russ P. , Schneck Michael J.
Published: November 2022

Background

Cases of isolated intramedullary spinal neurocysticercosis are extremely rare. Only 25 cases have been reported before 2022. Due to its rarity, the diagnosis of spinal neurocysticercosis may be missed.

Case presentation

We describe a 37-year-old female patient who developed back pain and lower extremity weakness and was found to have an intramedullary thoracic spine cystic lesion. She was taken to the operating room for resection of the lesion. Pathology revealed a larval cyst wall consistent with neurocysticercosis. The patient was started on albendazole and dexamethasone. Her exam improved post-operatively, and she was able to ambulate with minimal difficulty at the time of follow up.

Conclusion

The case provides insights on the diagnosis and treatment of isolated intramedullary spinal neurocysticercosis. Review of the literature suggests that combined surgical and medical intervention results in significant improvement in the patient's neurological exam, and decreases morbidity associated with the disease. We propose a treatment paradigm for this rare manifestation of neurocysticercosis.
Response to subsequent antiseizure medications after first antiseizure medication failure in newly diagnosed epilepsy
Authors: Hersi Hire , Saarinen Jukka T. , Raitanen Jani , Peltola Jukka
Published: November 2022

Objective

There is a lack of studies using the International League Against Epilepsy (ILAE) recommendation to define drug-resistant epilepsy (DRE). This study evaluated the seizure freedom rates of substitution or add-on and subsequent antiseizure medication (ASM) therapies using different proposed definitions of DRE or ASM trials in patients with a failed first ASM. We also identified prognostic factors for 1-year seizure freedom.

Methods

This study included 459 patients with epilepsy of whom 151 were not seizure-free after the first ASM. Multilevel mixed-effects logistic regression was used to examine the correlation between observations from the same patient.

Results

The overall seizure freedom rate with the first and subsequent ASMs was 88.0% (404/459). The rate of DRE when defined as the failure of two ASMs for any reason was 20.0%, and according to the ILAE definition of DRE, it was 16.3%. After failing the first ASM, 63.6% of patients (96/151) became seizure free with subsequent ASMs and tried an average of 1.9 ASMs (range 1–5). Of the patients who achieved 1-year seizure freedom, 10.1% (41/404) were taking polytherapy and there was no difference between substitution and add-on. All the patients with generalized epilepsy were seizure-free. A favorable prognostic factor was age >60 years and an EEG without epileptiform activity. The efficacies of the different ASMs were largely similar, but drugs that enhanced GABA-mediated inhibitory neurotransmission had the lowest seizure freedom rate.

Significance

In adults with newly-diagnosed epilepsy, 1-year seizure freedom was achieved for almost 90% of the patients. After failing the first ASM, two-thirds of the patients responded to subsequent ASM regimens. Our results support the feasibility and applicability of the ILAE concept of an adequate ASM trial and the failure of two ASMs as a definition of DRE.
The effect of interictal epileptic discharges and following spindles on motor sequence learning in epilepsy patients
Authors: Okadome Toshiki , Yamaguchi Takahiro , Mukaino Takahiko , Sakata Ayumi , Ogata Katsuya , Shigeto Hiroshi , Isobe Noriko , Uehara Taira
Published: November 2022

Purpose

Interictal epileptic discharges (IEDs) are known to affect cognitive function in patients with epilepsy, but the mechanism has not been elucidated. Sleep spindles appearing in synchronization with IEDs were recently demonstrated to impair memory consolidation in rat, but this has not been investigated in humans. On the other hand, the increase of sleep spindles at night after learning is positively correlated with amplified learning effects during sleep for motor sequence learning. In this study, we examined the effects of IEDs and IED-coupled spindles on motor sequence learning in patients with epilepsy, and clarified their pathological significance.

Materials and methods

Patients undergoing long-term video-electroencephalography (LT-VEEG) at our hospital from June 2019 to November 2021 and age-matched healthy subjects were recruited. Motor sequence learning consisting of a finger-tapping task was performed before bedtime and the next morning, and the improvement rate of performance was defined as the sleep-dependent learning effect. We searched for factors associated with the changes in learning effect observed between the periods of when antiseizure medications (ASMs) were withdrawn for LT-VEEG and when they were returned to usual doses after LT-VEEG.

Results

Excluding six patients who had epileptic seizures at night after learning, nine patients and 11 healthy subjects were included in the study. In the patient group, there was no significant learning effect when ASMs were withdrawn. The changes in learning effect of the patient group during ASM withdrawal were not correlated with changes in sleep duration or IED density; however, they were significantly negatively correlated with changes in IED-coupled spindle density.

Conclusion

We found that the increase of IED-coupled spindles correlated with the decrease of sleep-dependent learning effects of procedural memory. Pathological IED-coupled sleep spindles could hinder memory consolidation, that is dependent on physiological sleep spindles, resulting in cognitive dysfunction in patients with epilepsy.
Inflammatory rheumatic diseases and the risk of Parkinson's disease: A systematic review and meta-analysis
Authors: He Lili , Zhao Hecong , Wang Fuli , Guo Xiaoyan
Published: November 2022

Background

Several studies showed inconsistencies in the relationships between inflammatory rheumatic diseases (IRDs) and the risk of Parkinson's disease (PD). Therefore, we carried out a meta-analysis to investigate the associations between different IRDs and PD risk.

Methods

A comprehensive search was undertaken on PubMed, Embase, Cochrane Library, and Web of Science databases up to June 2022. Studies reporting the relationships between IRDs and PD risk were included. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated by using random-effects models.

Results

Twenty-two publications covering seven IRDs containing data from 833,004 patients were identified for quantitative analysis. The pooled results indicated that ankylosing spondylitis (RR = 1.55, 95% CI: 1.31–1.83, I2 = 32.1%, P < 0.001), Sjögren's syndrome (RR = 1.34, 95% CI: 1.22–1.47, I2 = 58.5%, P < 0.001), and Behcet's disease (RR = 1.93, 95% CI: 1.07–3.49, I2 = 57.6%, P = 0.030) were associated with an increased PD risk. However, no significant associations were observed between gout, rheumatoid arthritis, systemic lupus erythematosus, as well as polymyalgia rheumatica and the subsequent development of PD.

Conclusion

Ankylosing spondylitis, Sjögren's syndrome, and Behcet's disease may increase PD risk.
Normalized compression distance to measure cortico-muscular synchronization
Authors: Pascarella Annalisa , Gianni Eugenia , Abbondanza Matteo , Armonaite Karolina , Pitolli Francesca , Bertoli Massimo , L’Abbate Teresa , Grifoni Joy , Vitulano Domenico , Bruni Vittoria , Conti Livio , Paulon Luca , Tecchio Franca
Published: November 2022

The neuronal functional connectivity is a complex and non-stationary phenomenon creating dynamic networks synchronization determining the brain states and needed to produce tasks. Here, as a measure that quantifies the synchronization between the neuronal electrical activity of two brain regions, we used the normalized compression distance (NCD), which is the length of the compressed file constituted by the concatenated two signals, normalized by the length of the two compressed files including each single signal. To test the NCD sensitivity to physiological properties, we used NCD to measure the cortico-muscular synchronization, a well-known mechanism to control movements, in 15 healthy volunteers during a weak handgrip. Independently of NCD compressor (Huffman or Lempel Ziv), we found out that the resulting measure is sensitive to the dominant-non dominant asymmetry when novelty management is required (p = 0.011; p = 0.007, respectively) and depends on the level of novelty when moving the non-dominant hand (p = 0.012; p = 0.024). Showing lower synchronization levels for less dexterous networks, NCD seems to be a measure able to enrich the estimate of functional two-node connectivity within the neuronal networks that control the body.
Transcranial magnetic stimulation set-up for small animals
Authors: Nieminen Jaakko O. , Pospelov Alexey S. , Koponen Lari M. , Yrjölä Pauliina , Shulga Anastasia , Khirug Stanislav , Rivera Claudio
Published: November 2022

Transcranial magnetic stimulation (TMS) is widely applied on humans for research and clinical purposes. TMS studies on small animals, e.g., rodents, can provide valuable knowledge of the underlying neurophysiological mechanisms. Administering TMS on small animals is, however, prone to technical difficulties, mainly due to their small head size. In this study, we aimed to develop an energy-efficient coil and a compatible experimental set-up for administering TMS on rodents. We applied a convex optimization process to develop a minimum-energy coil for TMS on rats. As the coil windings of the optimized coil extend to a wide region, we designed and manufactured a holder on which the rat lies upside down, with its head supported by the coil. We used the set-up to record TMS–electromyography, with electromyography recorded from limb muscles with intramuscular electrodes. The upside-down placement of the rat allowed the operator to easily navigate the TMS without the coil blocking their field of view. With this paradigm, we obtained consistent motor evoked potentials from all tested animals.
Application of 5-aminolevulinic acid promotes ripening and accumulation of primary and secondary metabolites in postharvest tomato fruit
Authors: Wang Junwen , Yuan Hong , Wu Yue , Yu Jihua , Ali Basharat , Zhang Jing , Tang Zhongqi , Xie Jianming , Lyu Jian , Liao Weibiao
Published: November 2022

5-Aminolevulinic acid (ALA) plays a vital role in promoting plant growth, enhancing stress resistance, and improving fruit yield and quality. In the present study, tomato fruits were harvested at mature green stage and sprayed with 200 mg L–1 ALA on fruit surface. During ripening, the estimation of primary and secondary metabolites, carotenoids, and chlorophyll contents, and the expression levels of key genes involved in their metabolism were carried out. The results showed that ALA significantly promoted carotenoids accumulation by upregulating the gene expression levels of geranylgeranyl diphosphate synthase (GGPPS, encoding geranylgeranyl diphosphate synthase), phytoene synthase 1 (PSY1, encoding phytoene synthase), phytoene desaturase (PDS, encoding phytoene desaturase), and lycopeneβ-cyclase (LCYB, encoding lycopene β-cyclase), whereas chlorophyll content decreased by downregulating the expression levels of Mg-chelatase (CHLH, encoding Mg-chelatase) and protochlorophyllide oxidoreductase (POR, encoding protochlorophyllide oxidoreductase). Besides, the contents of soluble solids, vitamin C, soluble protein, free amino acids, total soluble sugar, organic acid, total phenol, and flavonoid were increased in ALA-treated tomato fruit, but the fruit firmness was decreased. These results indicated that the exogenous ALA could not only promote postharvest tomato fruit ripening but also improve the internal nutritional and flavor quality of tomato fruit.
Bioassay-guided isolation of Fenghuang Dancong tea constituents with α-glucosidase inhibition activities
Authors: Zhou Hua , Liao Jin , Ou Juanying , Lin Jiayu , Zheng Jie , Li Yifei , Ou Shiyi , Liu Fu
Published: November 2022

An α-glucosidase inhibition assay showed the ethanolic extract of Fenghuang Dancong tea had potential α-glucosidase inhibitory activity. The most bioactive fraction, which was obtained via bioassay-guided isolation of the extract, was further purified to create five compounds, including three novel compounds (1–3). These compounds were analyzed and identified in detail using high-resolution-mass spectrometry and extensive one-dimensional and two-dimensional NMR spectroscopy experiments. Among the compounds, compound 1 contained cis double bonds and showed the strongest α-glucosidase inhibitory activity with an IC50 value of 7.51 μM, which is significantly lower than that of compound 2 with trans double bonds. Enzyme kinetic experiments showed that 1 was a reversible non-competitive α-glucosidase inhibitor.
Inverse association of a traditional Korean diet composed of a multigrain rice-containing meal with fruits and nuts with metabolic syndrome risk: The KoGES
Authors: Kim Min Jung , Hur Haeng Jeon , Jang Dai Ja , Kim Myung-Sunny , Park Sunmin , Yang Hye Jeong
Published: November 2022

Background

Hansik, a traditional Korean diet, may have a beneficial impact on metabolic syndrome (MetS) risk as dietary westernization increases its prevalence. We examined the hypothesis that adherence to the hansik diet may be inversely associated with the risk of MetS and its components and sought to understand the gender differences in 58,701 men and women aged over 40.

Materials and methods

Hansik was defined using 14 components from which the Korean dietary pattern index (Kdiet-index) was generated by summing their scores. Low-hansik intake was defined as the Kdiet-index with <8. MetS was categorized based on the 2005 revised NCEP-ATP III criteria modified for Asians.

Results

The Kdiet-index score was negatively associated with the dietary inflammation index and showed that the high intake of a meal with multigrain rice, fruits, and their products, and nuts, and low intake of fried foods were inversely associated with MetS by 0.707, 0.864, 0.769, and 0.918 times, respectively, after adjusting for covariates. More women and participants with more educated and lower income belonged to the high-hansik group, and participants with high self-rated health scores consumed more hansik. All participants on a high-hansik diet were associated with a 0.87 time lower risk of MetS. Specifically, the association between hansik intake and MetS risk was not significant among men following stratification by gender. Body composition, including the body mass index, waist circumference, and fat mass, was inversely associated with hansik intake, while the skeletal muscle mass index was positively associated with the hansik intake in each gender and all participants. In all the participants in the high-hansik group, no significant changes were seen in the serum glucose and HDL concentration. However, a high-hansik intake showed lower blood pressure and serum LDL and triglyceride concentrations only in men and a higher glomerular filtration rate in both genders.

Conclusions

Hansik intake might improve MetS risk, with its primary beneficial effects on body composition, dyslipidemia, and blood pressure gender-dependently.
Mapping global epidemiology of thyroid nodules among general population: A systematic review and meta-analysis
Authors: Mu Chunyang , Ming Xin , Tian Ye , Liu Yang , Yao Menglin , Ni Yinyun , Liu Yong , Li Zhihui
Published: November 2022

Introduction

An emerging public health issue is brought on by the worldwide increase of thyroid nodules (TNs). The goal of the current study is to determine the global prevalence of TNs among the general population.

Methods

We screened articles published from January 2000 to May 2022. TN prevalence was calculated with the DerSimonian–Laird random effects model with arcsine transformation.

Results

A total of 20,358 entries were found in our research, and 102 of them met our inclusion criteria. A total of 9,276,178 individuals have been diagnosed as TNs; the overall prevalence was 24.83% (95% CI 21.44–28.55), regardless of the diagnostic techniques. TNs have become more prevalent during 2012–2022 (29.29%) compared with 2000–2011 (21.53%, p = 0.02). In addition, we discovered that women (36.51%) were more likely to have TNs than men (23.47%, p < 0.01). Interestingly, we found that obesity was correlated with the prevalence of TNs. Additionally, age-specific-stratified TN prevalence was found in our results.

Discussion

This meta-analysis shows that, regardless of country development and economic status, TNs are spreading more widely over the world. Our findings showed a strong correlation between rising TN prevalence and older age, female sex, and elevated weight. To stop the TN epidemic from spreading over the world, increased awareness, the understanding of the disease, and quick action are required.
Four circadian rhythm-related genes predict incidence and prognosis in hepatocellular carcinoma
Authors: Wu Zhenyu , Hu Hao , Zhang Qiang , Wang Tengfei , Li Huixing , Qin Yugang , Ai Xiangnan , Yi Wen , Wei Xiaojun , Gao Wei , Ouyang Caiguo
Published: November 2022

Circadian dysregulation can be involved in the development of malignant tumors, though its relationship with the progression of hepatocellular carcinoma is not yet fully understood. We identified genes related to circadian rhythms from the Cancer Genome Atlas (TCGA), measured gene expression, and conducted genomic difference analysis to construct a circadian rhythm-related signature. The resulting prognosis model proved to be an effective biomarker, as demonstrated by Kaplan-Meier survival analysis for both the training (n = 370, P = 2.687e-10) and external validation cohorts (n = 230, P = 1.45e-02). Further, we found that patients considered ‘high risk’, with an associated poor prognosis, displayed elevated levels of immune checkpoint genes and immune filtration. We also conducted functional enrichment, which indicated that the risk model showed a significant positive correlation with certain malignant phenotypes, including G2M checkpoint, MYC targets, and the MTORC1 signaling pathway. In summary, we identified a novel circadian rhythm-related signature allowing assessment of prognosis for hepatocellular carcinoma patients, and further can be used to predict immune infiltration sensitivity.