bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and Population Structures of Prevalent Methicillin-Resistant Staphylococcus aureus in Taiwan
Authors: Chen Chih-Jung , Yang Lauderdale Tsai-Ling , Huang Yhu-Chering
Published: September 2021

Global methicillin-resistant Staphylococcus aureus (MRSA) strains were dominated by few genetic lineages, suggesting their inherent advantage of competitive fitness. The information of genome evolution and population structures of prevalent MRSA strains can help gain a better understanding of the success of the pandemic clones. Whole-genome sequencing was performed in 340 MRSA isolates belonging to three prevalent lineages, including ST59 (129 isolates), ST239/241 (140 isolates), and ST5 (71 isolates), collected from 1996 to 2016 in Taiwan. The time-scaled phylogeny and evolutionary pathways were estimated by Bayesian analysis using Markov chain Monte Carlo. The toxome, resistome, and plasmids were characterized by screening the raw reads with a public database. ST59, ST239/241, and ST5 MRSA were estimated to emerge in 1974, 1979, and 1995, respectively, in Taiwan. ST59 evolved through two major pathways, generating two subclones in 1980 and 1984. Both ST59 subclones remained prevalent in the healthcare and community environments in late 2010s. ST239/241 diverged into three subclones, respectively, in 1989, 1993, and 1995. The 1995-emerging ST239 subclone predominated after 2000 by replacing two previous early subclones. ST5 could be subdivided into two clades within 3 years of introduction, but no substantial difference of genomic profiles was identified in the strains of distinct clades. Each of the three pandemic MRSA lineages harbored its own specific toxome, resistome, and plasmids. The frequently identified genetic diversities between the subclones of the same lineage were genes mediating immune evasion, leukocidins, enterotoxins, and resistance to aminoglycosides. In conclusion, MRSA ST59 and ST239/241 emerged in the 1970s and evolved drastically during 1980 and 1995, resulting in three successful subclones prevailing in Taiwan. ST5 was introduced late in 1995 without a significant genetic drift during 20 years of evolution.
Colonizing Microbes, IL-10 and IL-22: Keeping the Peace at the Mucosal Surface
Authors: Kidess Evelien , Kleerebezem Michiel , Brugman Sylvia
Published: September 2021

Our world is filled with microbes. Each multicellular organism has developed ways to interact with this microbial environment. Microbes do not always pose a threat; they can contribute to many processes that benefit the host. Upon colonization both host and microbes adapt resulting in dynamic ecosystems in different host niches. Regulatory processes develop within the host to prevent overt inflammation to beneficial microbes, yet keeping the possibility to respond when pathogens attempt to adhere and invade tissues. This review will focus on microbial colonization and the early (innate) host immune response, with special emphasis on the microbiota-modifying roles of IL-10 and IL-22 in the intestine. IL-10 knock out mice show an altered microbial composition, and spontaneously develop enterocolitis over time. IL-22 knock out mice, although not developing enterocolitis spontaneously, also have an altered microbial composition and increase of epithelial-adherent bacteria, mainly caused by a decrease in mucin and anti-microbial peptide production. Recently interesting links have been found between the IL-10 and IL-22 pathways. While IL-22 can function as a regulatory cytokine at the mucosal surface, it also has inflammatory roles depending on the context. For example, lack of IL-22 in the IL-10–/– mice model prevents spontaneous colitis development. Additionally, the reduced microbial diversity observed in IL-10–/– mice was also reversed in IL-10/IL-22 double mutant mice (Gunasekera et al., 2020). Since in early life, host immunity develops in parallel and in interaction with colonizing microbes, there is a need for future studies that focus on the effect of the timing of colonization in relation to the developmental phase of the host. To illustrate this, examples from zebrafish research will be compared with studies performed in mammals. Since zebrafish develop from eggs and are directly exposed to the outside microbial world, timing of the development of host immunity and subsequent control of microbial composition, is different from mammals that developin uteroand only get exposed after birth. Likewise, colonization studies using adult germfree mice might yield different results from those using neonatal germfree mice. Lastly, special emphasis will be given to the need for host genotype and environmental (co-housing) control of experiments.
Antimicrobial Resistance and CRISPR Typing Among Salmonella Isolates From Poultry Farms in China
Authors: Li Cui , Wang Yulong , Gao Yufeng , Li Chao , Ma Boheng , Wang Hongning
Published: September 2021

Although knowledge of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system has been applied in many research areas, comprehensive studies of this system in Salmonella, particularly in analysis of antibiotic resistance, have not been reported. In this work, 75 Salmonella isolates obtained from broilers or broilers products were characterized to determine their antimicrobial susceptibilities, antibiotic resistance gene profiles, and CRISPR array diversities, and genotyping was explored. In total, 80.00% (60/75) of the strains were multidrug resistant, and the main pattern observed in the isolates was CN-AZM-AMP-AMC-CAZ-CIP-ATM-TE-SXT-FOS-C. The resistance genes of streptomycin (aadA), phenicol (floR-like and catB3-like), β-lactams (blaTEM, blaOXA, and blaCTX), tetracycline [tet(A)-like], and sulfonamides (sul1 and sul2) appeared at higher frequencies among the corresponding resistant isolates. Subsequently, we analyzed the CRISPR arrays and found 517 unique spacer sequences and 31 unique direct repeat sequences. Based on the CRISPR spacer sequences, we developed a novel typing method, CRISPR locus three spacer sequences typing (CLTSST), to help identify sources of Salmonella outbreaks especially correlated with epidemiological data. Compared with multi-locus sequence typing (MLST), conventional CRISPR typing (CCT), and CRISPR locus spacer pair typing (CLSPT), discrimination using CLTSST was weaker than that using CCT but stronger than that using MLST and CLSPT. In addition, we also found that there were no close correlations between CRISPR loci and antibiotics but had close correlations between CRISPR loci and antibiotic resistance genes in Salmonella isolates.
Analysis of the Genetic Diversity Associated With the Drug Resistance and Pathogenicity of Influenza A Virus Isolated in Bangladesh From 2002 to 2019
Authors: Hossain Md. Golzar , Akter Sharmin , Dhole Priya , Saha Sukumar , Kazi Taheruzzaman , Majbauddin Abir , Islam Md. Sayeedul
Published: September 2021

The subtype prevalence, drug resistance- and pathogenicity-associated mutations, and the distribution of the influenza A virus (IAV) isolates identified in Bangladesh from 2002 to 2019 were analyzed using bioinformatic tools. A total of 30 IAV subtypes have been identified in humans (4), avian species (29), and environment (5) in Bangladesh. The predominant subtypes in human and avian species are H1N1/H3N2 and H5N1/H9N2, respectively. However, the subtypes H5N1/H9N2 infecting humans and H3N2/H1N1 infecting avian species have also been identified. Among the avian species, the maximum number of subtypes (27) have been identified in ducks. A 3.56% of the isolates showed neuraminidase inhibitor (NAI) resistance with a prevalence of 8.50, 1.33, and 2.67% in avian species, humans, and the environment, respectively, the following mutations were detected: V116A, I117V, D198N, I223R, S247N, H275Y, and N295S. Prevalence of adamantane-resistant IAVs was 100, 50, and 30.54% in humans, the environment, and avian species, respectively, the subtypes H3N2, H1N1, H9N2, and H5N2 were highly prevalent, with the subtype H5N1 showing a comparatively lower prevalence. Important PB2 mutations such D9N, K526R, A588V, A588I, G590S, Q591R, E627K, K702R, and S714R were identified. A wide range of IAV subtypes have been identified in Bangladesh with a diversified genetic variation in the NA, M2, and PB2 proteins providing drug resistance and enhanced pathogenicity. This study provides a detailed analysis of the subtypes, and the host range of the IAV isolates and the genetic variations related to their proteins, which may aid in the prevention, treatment, and control of IAV infections in Bangladesh, and would serve as a basis for future investigations.
Biocontrol Ability and Mechanism of a Broad-Spectrum Antifungal Strain Bacillus safensis sp. QN1NO-4 Against Strawberry Anthracnose Caused by Colletotrichum fragariae
Authors: Li Xiaojuan , Zhang Miaoyi , Qi Dengfeng , Zhou Dengbo , Qi Chunlin , Li Chunyu , Liu Siwen , Xiang Dandan , Zhang Lu , Xie Jianghui , Wang Wei
Published: September 2021

Strawberry is a very popular fruit with a special taste, color, and nutritional value. Anthracnose caused by Colletotrichum fragariae severely limits fruit shelf life during post-harvest storage. Use of traditional chemical fungicides leads to serious environment pollution and threatens food safety. Biocontrol is considered as a promising strategy to manage the post-harvest fruit diseases. Here, strain QN1NO-4 isolated from noni (Morinda citrifolia L.) fruit exhibited a high antifungal activity against C. fragariae. Based on its physicochemical profiles and phylogenetic tree of the 16S rRNA sequence, strain QN1NO-4 belonged to the genus Bacillus. The average nucleotide identity (ANI) calculated by comparing two standard strain genomes was below 95–96%, suggesting that the strain might be a novel species of the genus Bacillus and named as Bacillus safensis sp. QN1NO-4. Its extract effectively reduced the incidence of strawberry anthracnose of harvested fruit. Fruit weight and TSS contents were also maintained significantly. The antifungal mechanism assays indicated that the extract of the test antagonist inhibited mycelial growth and spore germination of C. fragariae in vitro. Cells of strain QN1NO-4 demonstrated the cytoplasmic heterogeneity, disappeared organelles, and ruptured ultrastructure. Notably, the strain extract also had a broad-spectrum antifungal activity. Compared with the whole genome of strain QN1NO-4, several functional gene clusters involved in the biosynthesis of active secondary metabolites were observed. Fifteen compounds were identified by gas chromatography–mass spectrometry (GC-MS). Hence, the fruit endophyte B. safensis sp. QN1NO-4 is a potential bio-agent identified for the management of post-harvest disease of strawberry fruit.
Translation of a Leaderless Reporter Is Robust During Exponential Growth and Well Sustained During Stress Conditions in Mycobacterium tuberculosis
Authors: Grabowska Anna D. , Andreu Nuria , Cortes Teresa
Published: September 2021

Mycobacterium tuberculosis expresses a large number of leaderless mRNA transcripts; these lack the 5′ leader region, which usually contains the Shine–Dalgarno sequence required for translation initiation in bacteria. In M. tuberculosis, transcripts encoding proteins like toxin–antitoxin systems are predominantly leaderless and the overall ratio of leaderless to Shine–Dalgarno transcripts significantly increases during growth arrest, suggesting that leaderless translation might be important during persistence in the host. However, whether these two types of transcripts are translated with differing efficiencies during optimal growth conditions and during stress conditions that induce growth arrest, is unclear. Here, we have used the desA1 (Rv0824c) and desA2 (Rv1094) gene pair as representative for Shine–Dalgarno and leaderless transcripts in M. tuberculosis respectively; and used them to construct bioluminescent reporter strains. We detect robust leaderless translation during exponential in vitro growth, and we show that leaderless translation is more stable than Shine–Dalgarno translation during adaptation to stress conditions. These changes are independent from transcription, as transcription levels did not significantly change following quantitative real-time PCR analysis. Upon entrance into nutrient starvation and after nitric oxide exposure, leaderless translation is significantly less affected by the stress than Shine–Dalgarno translation. Similarly, during the early stages of infection of macrophages, the levels of leaderless translation are transiently more stable than those of Shine–Dalgarno translation. These results suggest that leaderless translation may offer an advantage in the physiology of M. tuberculosis. Identification of the molecular mechanisms underlying this translational regulation may provide insights into persistent infection.
Clinical Evaluation of a Metagenomics-Based Assay for Pneumonia Management
Authors: Zhan Yangqing , Xu Teng , He Fusheng , Guan Wei-jie , Li Zhengtu , Li Shaoqiang , Xie Mingzhou , Li Xiaolei , Chen Rongchang , Cheng Linling , Zhong Nanshan , Ye Feng
Published: September 2021

Clinical value of metagenomic next-generation sequencing (mNGS) in pneumonia management is still controversial. A prospective study was conducted to evaluate the clinical impact of PneumoSeq in 57 immunocompetent (ICO) and 75 immunocompromised (ICH) pneumonia patients. The value of PneumoSeq for both etiological and clinical impact investigation in pneumonia was assessed. Among the 276 potential pathogens detected with PneumoSeq in our cohort, 251 (90.9%) were cross-validated. Clinical diagnoses of the causative pathogens were obtained for 97 patients, 90.7% of which were supported by PneumoSeq. Compared to conventional testing, PneumoSeq suggested potentially missed diagnoses in 16.7% of cases (22/132), involving 48 additional pathogenic microorganisms. In 58 (43.9%) cases, PneumoSeq data led to antimicrobial treatment de-escalation (n = 12 in ICO, n = 18 in ICH) and targeted treatment initiation (n = 7 in ICO, n = 21 in ICH). The PneumoSeq assay benefited the diagnosis and clinical management of both ICH and ICO pneumonia patients in real-world settings.
GeneTrail: A Framework for the Analysis of High-Throughput Profiles
Authors: Gerstner Nico , Kehl Tim , Lenhof Kerstin , Eckhart Lea , Schneider Lara , Stöckel Daniel , Backes Christina , Meese Eckart , Keller Andreas , Lenhof Hans-Peter
Published: September 2021

Experimental high-throughput techniques, like next-generation sequencing or microarrays, are nowadays routinely applied to create detailed molecular profiles of cells. In general, these platforms generate high-dimensional and noisy data sets. For their analysis, powerful bioinformatics tools are required to gain novel insights into the biological processes under investigation. Here, we present an overview of the GeneTrail tool suite that offers rich functionality for the analysis and visualization of (epi-)genomic, transcriptomic, miRNomic, and proteomic profiles. Our framework enables the analysis of standard bulk, time-series, and single-cell measurements and includes various state-of-the-art methods to identify potentially deregulated biological processes and to detect driving factors within those deregulated processes. We highlight the capabilities of our web service with an analysis of a single-cell COVID-19 data set that demonstrates its potential for uncovering complex molecular mechanisms.

GeneTrail can be accessed freely and without login requirements athttp://genetrail.bioinf.uni-sb.de.
Quantitative Susceptibility Mapping of the Basal Ganglia and Thalamus at 9.4 Tesla
Authors: Kumar Vinod Jangir , Scheffler Klaus , Hagberg Gisela E. , Grodd Wolfgang
Published: September 2021

The thalamus (Th) and basal ganglia (BG) are central subcortical connectivity hubs of the human brain, whose functional anatomy is still under intense investigation. Nevertheless, both substructures contain a robust and reproducible functional anatomy. The quantitative susceptibility mapping (QSM) at ultra-high field may facilitate an improved characterization of the underlying functional anatomy in vivo. We acquired high-resolution QSM data at 9.4 Tesla in 21 subjects, and analyzed the thalamic and BG by using a prior defined functional parcellation. We found a more substantial contribution of paramagnetic susceptibility sources such as iron in the pallidum in contrast to the caudate, putamen, and Th in descending order. The diamagnetic susceptibility sources such as myelin and calcium revealed significant contributions in the Th parcels compared with the BG. This study presents a detailed nuclei-specific delineation of QSM-provided diamagnetic and paramagnetic susceptibility sources pronounced in the BG and the Th. We also found a reasonable interindividual variability as well as slight hemispheric differences. The results presented here contribute to the microstructural knowledge of the Th and the BG. In specific, the study illustrates QSM values (myelin, calcium, and iron) in functionally similar subregions of the Th and the BG.
Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice
Authors: Reiss David , Maurin Hervé , Audouard Emilie , Martínez-Navarro Miriam , Xue Yaping , Herault Yann , Maldonado Rafael , Cabañero David , Gaveriaux-Ruff Claire
Published: September 2021

Background: The delta opioid receptor (DOR) contributes to pain control, and a major challenge is the identification of DOR populations that control pain, analgesia, and tolerance. Astrocytes are known as important cells in the pathophysiology of chronic pain, and many studies report an increased prevalence of pain in women. However, the implication of astrocytic DOR in neuropathic pain and analgesia, as well as the influence of sex in this receptor activity, remains unknown.

Experimental Approach: We developed a novel conditional knockout (cKO) mouse line wherein DOR is deleted in astrocytes (named GFAP-DOR-KO), and investigated neuropathic mechanical allodynia as well as analgesia and analgesic tolerance in mutant male and female mice. Neuropathic cold allodynia was also characterized in mice of both sexes lacking DOR either in astrocytes or constitutively.

Results: Neuropathic mechanical allodynia was similar in GFAP-DOR-KO and floxed DOR control mice, and the DOR agonist SNC80 produced analgesia in mutant mice of both sexes. Interestingly, analgesic tolerance developed in cKO males and was abolished in cKO females. Cold neuropathic allodynia was reduced in mice with decreased DOR in astrocytes. By contrast, cold allodynia was exacerbated in full DOR KO females.

Conclusions: These findings show that astrocytic DOR has a prominent role in promoting cold allodynia and analgesic tolerance in females, while overall DOR activity was protective. Altogether this suggests that endogenous- and exogenous-mediated DOR activity in astrocytes worsens neuropathic allodynia while DOR activity in other cells attenuates this form of pain. In conclusion, our results show a sex-specific implication of astrocytic DOR in neuropathic pain and analgesic tolerance. These findings open new avenues for developing tailored DOR-mediated analgesic strategies.
A Neurological Outpatient Clinic for Patients With Post-COVID-19 Syndrome — A Report on the Clinical Presentations of the First 100 Patients
Authors: Boesl Fabian , Audebert Heinrich , Endres Matthias , Prüss Harald , Franke Christiana
Published: September 2021

Background and Objectives: Neurological and psychiatric symptoms are frequent in patients with post-COVID-19 syndrome (PCS). Here, we report on the clinical presentation of the first 100 patients who presented to our PCS Neurology outpatient clinic ≥12 weeks after the acute infection with SARS-CoV-2. To date, PCS is only defined by temporal connection to SARS-CoV-2 infection. Identification of clinical phenotypes and subgroups of PCS is urgently needed.

Design: We assessed clinical data of our first 100 ambulatory patients regarding clinical presentations; self-questionnaires focusing on daytime sleepiness, mood, and fatigue; and a screening assessment for detecting cognitive impairment.

Results: A total of 89% of the patients presenting to the Neurology outpatient clinic had an initially mild course of COVID-19 and had not been hospitalized. The majority of the patients were female (67 vs. 33% male). The most frequent symptom reported was cognitive impairment (72%). There were 30% of patients who reported cognitive deficits and scored below 26 points on the Montreal Cognitive Assessment Scale. Fatigue (67%), headache (36%), and persisting hyposmia (36%) were also frequently reported; 5.5% of all patients showed signs of severe depression.

Discussion: To our knowledge, this is the first report of patient data of a PCS Neurology outpatient clinic. Neurological sequelae also exist for more than 3 months after mainly mild SARS-CoV-2 acute infections. The reported symptoms are in accordance with recently published data of hospitalized patients.
A Neural Network Model of Lexical-Semantic Competition During Spoken Word Recognition
Authors: Duta Mihaela , Plunkett Kim
Published: September 2021

Visual world studies show that upon hearing a word in a target-absent visual context containing related and unrelated items, toddlers and adults briefly direct their gaze toward phonologically related items, before shifting toward semantically and visually related ones. We present a neural network model that processes dynamic unfolding phonological representations of words and maps them to static internal lexical, semantic, and visual representations. The model, trained on representations derived from real corpora, simulates this early phonological over semantic/visual preference. Our results support the hypothesis that incremental unfolding of a spoken word is in itself sufficient to account for the transient preference for phonological competitors over both unrelated and semantically and visually related ones. Phonological representations mapped dynamically in a bottom-up fashion to semantic-visual representations capture the early phonological preference effects reported in visual world tasks. The semantic visual preference typically observed later in such a task does not require top-down feedback from a semantic or visual system.
Investigating Language and Domain-General Processing in Neurotypicals and Individuals With Aphasia — A Functional Near-Infrared Spectroscopy Pilot Study
Authors: Gilmore Natalie , Yücel Meryem Ayse , Li Xinge , Boas David A. , Kiran Swathi
Published: September 2021

Brain reorganization patterns associated with language recovery after stroke have long been debated. Studying mechanisms of spontaneous and treatment-induced language recovery in post-stroke aphasia requires a network-based approach given the potential for recruitment of perilesional left hemisphere language regions, homologous right hemisphere language regions, and/or spared bilateral domain-general regions. Recent hardware, software, and methodological advances in functional near-infrared spectroscopy (fNIRS) make it well-suited to examine this question. fNIRS is cost-effective with minimal contraindications, making it a robust option to monitor treatment-related brain activation changes over time. Establishing clear activation patterns in neurotypical adults during language and domain-general cognitive processes via fNIRS is an important first step. Some fNIRS studies have investigated key language processes in healthy adults, yet findings are challenging to interpret in the context of methodological limitations. This pilot study used fNIRS to capture brain activation during language and domain-general processing in neurotypicals and individuals with aphasia. These findings will serve as a reference when interpreting treatment-related changes in brain activation patterns in post-stroke aphasia in the future. Twenty-four young healthy controls, seventeen older healthy controls, and six individuals with left hemisphere stroke-induced aphasia completed two language tasks (i.e., semantic feature, picture naming) and one domain-general cognitive task (i.e., arithmetic) twice during fNIRS. The probe covered bilateral frontal, parietal, and temporal lobes and included short-separation detectors for scalp signal nuisance regression. Younger and older healthy controls activated core language regions during semantic feature processing (e.g., left inferior frontal gyrus pars opercularis) and lexical retrieval (e.g., left inferior frontal gyrus pars triangularis) and domain-general regions (e.g., bilateral middle frontal gyri) during hard versus easy arithmetic as expected. Consistent with theories of post-stroke language recovery, individuals with aphasia activated areas outside the traditional networks: left superior frontal gyrus and left supramarginal gyrus during semantic feature judgment; left superior frontal gyrus and right precentral gyrus during picture naming; and left inferior frontal gyrus pars opercularis during arithmetic processing. The preliminary findings in the stroke group highlight the utility of using fNIRS to study language and domain-general processing in aphasia.
A Reinforcement Learning Approach to Understanding Procrastination: Does Inaccurate Value Approximation Cause Irrational Postponing of a Task?
Authors: Feng Zheyu , Nagase Asako Mitsuto , Morita Kenji
Published: September 2021

Procrastination is the voluntary but irrational postponing of a task despite being aware that the delay can lead to worse consequences. It has been extensively studied in psychological field, from contributing factors, to theoretical models. From value-based decision making and reinforcement learning (RL) perspective, procrastination has been suggested to be caused by non-optimal choice resulting from cognitive limitations. Exactly what sort of cognitive limitations are involved, however, remains elusive. In the current study, we examined if a particular type of cognitive limitation, namely, inaccurate valuation resulting from inadequate state representation, would cause procrastination. Recent work has suggested that humans may adopt a particular type of state representation called the successor representation (SR) and that humans can learn to represent states by relatively low-dimensional features. Combining these suggestions, we assumed a dimension-reduced version of SR. We modeled a series of behaviors of a “student” doing assignments during the school term, when putting off doing the assignments (i.e., procrastination) is not allowed, and during the vacation, when whether to procrastinate or not can be freely chosen. We assumed that the “student” had acquired a rigid reduced SR of each state, corresponding to each step in completing an assignment, under the policy without procrastination. The “student” learned the approximated value of each state which was computed as a linear function of features of the states in the rigid reduced SR, through temporal-difference (TD) learning. During the vacation, the “student” made decisions at each time-step whether to procrastinate based on these approximated values. Simulation results showed that the reduced SR-based RL model generated procrastination behavior, which worsened across episodes. According to the values approximated by the “student,” to procrastinate was the better choice, whereas not to procrastinate was mostly better according to the true values. Thus, the current model generated procrastination behavior caused by inaccurate value approximation, which resulted from the adoption of the reduced SR as state representation. These findings indicate that the reduced SR, or more generally, the dimension reduction in state representation, can be a potential form of cognitive limitation that leads to procrastination.
Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome
Authors: Salcedo-Arellano Maria Jimena , Sanchez Desiree , Wang Jun Yi , McLennan Yingratana A. , Clark Courtney Jessica , Juarez Pablo , Schneider Andrea , Tassone Flora , Hagerman Randi J. , Martínez-Cerdeño Verónica
Published: September 2021

This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (FMR1) gene, in addition to an apolipoprotein E (APOE) ε4 allele. FXTAS and Alzheimer's Disease (AD) are late-onset neurodegenerative diseases that share overlapping cognitive deficits including processing speed, working memory and executive function. The prevalence of coexistent FXTAS-AD pathology remains unknown. The clinical picture in this case was marked with rapid cognitive decline between age 67 and 71 years in addition to remarkable MRI changes. Over the 16 months between the two clinical evaluations, the brain atrophied 4.12% while the lateral ventricles increased 26.4% and white matter hyperintensities (WMH) volume increased 15.6%. Other regions atrophied substantially faster than the whole brain included the thalamus (−6.28%), globus pallidus (−10.95%), hippocampus (−6.95%), and amygdala (−7.58%). A detailed postmortem assessment included an MRI with confluent WMH and evidence of cerebral microbleeds (CMB). The histopathological study demonstrated FXTAS inclusions in neurons and astrocytes, a widespread presence of phosphorylated tau protein and, amyloid β plaques in cortical areas and the hippocampus. CMBs were noticed in the precentral gyrus, middle temporal gyrus, visual cortex, and brainstem. There were high amounts of iron deposits in the globus pallidus and the putamen consistent with MRI findings. We hypothesize that coexistent FXTAS-AD neuropathology contributed to the steep decline in cognitive abilities.
5-HT7 Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord
Authors: Yuan Xiao-Cui , Yan Xiang-Ji , Tian Li-Xia , Guo Yi-Xiao , Zhao Yu-Long , Baba Sani Sa’idu , Wang Yu-Ying , Liang Ling-Li , Jia Hong , Xu Lin-Ping , Li Li , Lin Han , Huo Fu-Quan
Published: September 2021

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in EA analgesia. The 5-HT7 receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs–cAMP–PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.
Assessment of Nutritional Status of Children With Congenital Heart Disease: A Comparative Study
Authors: Chinawa Awoere T. , Chinawa Josephat M. , Duru Chika Onyinyechi , Chukwu Bartholomew F. , Obumneme-Anyim Ijeoma
Published: September 2021

Background: Malnutrition poses a great burden to children in the tropics. However, this seems to be accentuated in children with congenital heart disease.

Objectives: The present study is therefore aimed at determining the nutritional status of children with congenital heart disease and to compare them with those without congenital heart disease.

Methods: This is a cross-sectional study, where congenital heart disease was diagnosed by means of echocardiograph. Anthro software was used to calculate Z scores for weight for age (WAZ), height for age (HAZ), and weight for height (WHZ). Body mass index (BMI) was calculated by the formula BMI = Weight (Kg)/height (M2).

Results: The body mass index-for-age z-score (BAZ) and height/length-for-age z-score (HAZ) were calculated for both subjects and controls to determine their nutritional status. It was observed that 38.5% (112/291) of the subjects were wasted (BAZ < −2SD) compared to 6.25% (16/256) of the controls and the difference was statistically significant (χ2 = 81.2, p < 0.001). Stunting (height/length-for-age z-score < −2SD) was also observed in a greater proportion of subjects than controls as 37.8% (107/291) of subjects were stunted compared with 7.0% (18/256) of the controls (χ2 = 69.9, p < 0.001). The under-five subjects had more cases of malnutrition than the controls of same age group as illustrated in Table 6. Whereas 42.9% (96/224) of the under-five subjects were wasted, only 6.2% (12/192) of the controls were wasted. On the other hand, 4.2% (8/192) of the under-five controls were obese compared to 0.9% (2/224) of the subjects of similar age group.

Conclusion: Children with congenital heart disease present with varying degrees of malnutrition that is worse compared with children without congenital heart disease. The impact of malnutrition is worse among children under the age of five. Wasting is more prevalent in children with cyanotic heart disease compared with those with acyanotic congenital heart disease. Overweight and obesity were notable features of malnutrition in children with congenital heart disease, but this is worse in children without congenital heart disease.
Neurofibromatosis: Molecular Pathogenesis and Natural Compounds as Potential Treatments
Authors: Amaravathi Anusha , Oblinger Janet L. , Welling D. Bradley , Kinghorn A. Douglas , Chang Long-Sheng
Published: September 2021

The neurofibromatosis syndromes, including NF1, NF2, and schwannomatosis, are tumor suppressor syndromes characterized by multiple nervous system tumors, particularly Schwann cell neoplasms. NF-related tumors are mainly treated by surgery, and some of them have been treated by but are refractory to conventional chemotherapy. Recent advances in molecular genetics and genomics alongside the development of multiple animal models have provided a better understanding of NF tumor biology and facilitated target identification and therapeutic evaluation. Many targeted therapies have been evaluated in preclinical models and patients with limited success. One major advance is the FDA approval of the MEK inhibitor selumetinib for the treatment of NF1-associated plexiform neurofibroma. Due to their anti-neoplastic, antioxidant, and anti-inflammatory properties, selected natural compounds could be useful as a primary therapy or as an adjuvant therapy prior to or following surgery and/or radiation for patients with tumor predisposition syndromes, as patients often take them as dietary supplements and for health enhancement purposes. Here we review the natural compounds that have been evaluated in NF models. Some have demonstrated potent anti-tumor effects and may become viable treatments in the future.
Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors
Authors: Li Minde , Li Shaoyang , Zhou Lin , Yang Le , Wu Xiao , Tang Bin , Xie Shenhao , Fang Linchun , Zheng Suyue , Hong Tao
Published: September 2021

Background

Matrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes.

Methods

In this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan–Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.

Results

MMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.

Conclusion

MMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.
Histiocytic Necrotizing Lymphadenitis Mimicking Acute Appendicitis in a Child: A Case Report
Authors: Hua Chun-Zhen , Chen Yu-Kai , Chen Shun-Zhi , Gu Wei-Zhong , Shu Qiang
Published: September 2021

Background: Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a self-limiting inflammatory disease with low incidence and high misdiagnosis rate in children. Furthermore, cases where the clinical presentation resembles acute appendicitis are very rare.

Case Presentation: A 14-year-old boy was misdiagnosed as acute appendicitis and received operative treatment at his early visit. He suffered from abdominal pain, vomiting, diarrhea, fever, and lymphadenitis at the ileocecal junction, which were found by B-ultrasonography examination and surgery. Lymphadenectomy, as well as appendectomy, was performed, and KFD was identified by pathological examination. The patient was transferred to our hospital for further therapy because of recurrent fever and abdominal pain after the appendectomy. His temperature became normal after methylprednisolone was administered, and no recurrence was observed till now during follow-up.

Conclusions: Necrotizing lymphadenitis involving mesenteric lymph nodes may cause acute-appendicitis-like symptom; KFD should be a diagnostic consideration for mesenteric lymphadenitis.
Non-Coding RNA Polymorphisms (rs2910164 and rs1333049) Associated With Prognosis of Lung Cancer Under Platinum-Based Chemotherapy
Authors: Chen Yi-Xin , Chen Juan , Yin Ji-Ye , Zhou Hong-Hao , He Bai-Mei , Liu Zhao-Qian
Published: September 2021

Purpose: Lung cancer is the largest cause of cancer deaths in the world. Platinum-based chemotherapy is a foundation of first-line chemotherapy. However, the prognosis of lung cancer treated with platinum-based chemotherapy is still a challenge. Single nucleotide polymorphism of non-coding RNA has the potential to be a biomarker, but its effectiveness has yet to be comprehensively assessed. In this study, we explored the association between polymorphisms of non-coding RNA and prognosis of lung cancer patients receiving platinum-based chemotherapy.

Materials and Methods: For 446 lung cancer patients receiving platinum-based chemotherapy, 22 single nucleotide polymorphisms of microRNA and long noncoding RNA were genotyped by MALDI-TOF mass spectrometry. Cox regression analysis, Kaplan-Meier method, and long-rank test have been performed to assess the association of overall and progression-free survival with polymorphisms.

Results: In the additive and dominant models, genetic polymorphism of ANRIL rs1333049 (G > C) was significantly associated with progression-free survival. Additive model: CC vs GC vs GG [HR = 0.84, p = 0.021, 95% CI (0.73–0.97)]; Recessive model: CC vs GG + GC [HR = 0.77, p = 0.026, 95% CI (0.61–0.97)]. In the dominant model, compared with the CC genotype patients, lower risk of death [HR = 0.81, p = 0.036, 95% CI (0.66–0.99)] and lower risk of progression [HR = 0.81, p = 0.040, 95% CI (0.67–0.99)] have been observed on the patients with CG or GG genotype in miR-146A rs2910164.

Conclusion: Our research demonstrated the potential of using ANRIL rs1333049 (G > C) and miR-146A rs2910164 (C > G) as biomarkers to support the prediction of a better prognosis for lung cancer patients receiving platinum-based chemotherapy.
The Essential Oil of Artemisia argyi H.Lév. and Vaniot Attenuates NLRP3 Inflammasome Activation in THP-1 Cells
Authors: Chen Pengxiao , Bai Qi , Wu Yanting , Zeng Qiongzhen , Song Xiaowei , Guo Yuying , Zhou Pengjun , Wang Yao , Liao Xiaofeng , Wang Qiaoli , Ren Zhe , Wang Yifei
Published: September 2021

Artemisia argyiH. Lév. and Vaniot is a traditional medical herb that has been used for a long time in China and other Asian counties. Essential oil is the main active fraction ofArtemisia argyiH. Lév. and Vaniot, and its anti-inflammatory potential has been observedin vitroandin vivo. Here, we found that the essential oil ofArtemisia argyiH. Lév. and Vaniot (EOAA) inhibited monosodium urate (MSU)- and nigericin-induced NLRP3 inflammasome activation. EOAA suppressed caspase-1 and IL-1β processing and pyroptosis. NF-κB p65 phosphorylation and translocation were also inhibited. In addition, EOAA suppressed nigericin-induced NLRP3 inflammasome activation without blocking ASC oligomerization, suggesting that it may inhibit NLRP3 inflammasome activation by preventing caspase-1 processing. Our study thus indicates that EOAA inhibits NLRP3 inflammasome activation and has therapeutic potential against NLRP3-driven diseases.
Fetal Sex and Fetal Environment Interact to Alter Diameter, Myogenic Tone, and Contractile Response to Thromboxane Analog in Rat Umbilical Cord Vessels
Authors: Sicotte Benoit , Brochu Michèle
Published: September 2021

Fetal growth needs adequate blood perfusion from both sides of the placenta, on the maternal side through the uterine vessels and on the fetal side through the umbilical cord. In a model of intrauterine growth restriction (IUGR) induced by reduced blood volume expansion, uterine artery remodeling was blunted. The aim of this study is to determine if IUGR and fetus sex alter the functional and mechanical parameters of umbilical cord blood vessels. Pregnant rats were given a low sodium (IUGR) or a control diet for the last 7 days of pregnancy. Umbilical arteries and veins from term (22 day) fetal rats were isolated and set-up in wire myographs. Myogenic tone, diameter, length tension curve and contractile response to thromboxane analog U46619 and serotonin (5-HT) were measured. In arteries from IUGR fetuses, myogenic tone was increased in both sexes while diameter was significantly greater only in male fetuses. In umbilical arteries collected from the control group, the maximal contraction to U46619 was lower in females than males. Compared to the control groups, the maximal response decreased in IUGR male arteries and increased in female ones, thus abolishing the sexual dimorphism observed in the control groups. Reduced contractile response to U46619 was observed in the IUGR vein of both sexes. No difference between groups was observed in response to 5HT in arteries. In conclusion, the change in parameters of the umbilical cord blood vessels in response to a mild insult seems to show adaptation that favors better exchange of deoxygenated and wasted blood from the fetus to the placenta with increased myogenic tone.
Asymmetry and Heterogeneity: Part and Parcel in Cardiac Autonomic Innervation and Function
Authors: Zandstra Tjitske E. , Notenboom Robbert G. E. , Wink Jeroen , Kiès Philippine , Vliegen Hubert W. , Egorova Anastasia D. , Schalij Martin J. , De Ruiter Marco C. , Jongbloed Monique R. M.
Published: September 2021

The cardiac autonomic nervous system (cANS) regulates cardiac adaptation to different demands. The heart is an asymmetrical organ, and in the selection of adequate treatment of cardiac diseases it may be relevant to take into account that the cANS also has sidedness as well as regional differences in anatomical, functional, and molecular characteristics. The left and right ventricles respond differently to adrenergic stimulation. Isoforms of nitric oxide synthase, which plays an important role in parasympathetic function, are also distributed asymmetrically across the heart. Treatment of cardiac disease heavily relies on affecting left-sided heart targets which are thought to apply to the right ventricle as well. Functional studies of the right ventricle have often been neglected. In addition, many principles have only been investigated in animals and not in humans. Anatomical and functional heterogeneity of the cANS in human tissue or subjects is highly valuable for understanding left- and right-sided cardiac pathology and for identifying novel treatment targets and modalities. Within this perspective, we aim to provide an overview and synthesis of anatomical and functional heterogeneity of the cANS in tissue or subjects, focusing on the human heart.
A-Lipoic Acid Alleviates Folic Acid-Induced Renal Damage Through Inhibition of Ferroptosis
Authors: Li Xue , Zou Yu , Fu Yuan-Yuan , Xing Jia , Wang Kai-Yue , Wan Peng-Zhi , Zhai Xiao-Yue
Published: September 2021

Folic acid (FA)-induced acute kidney injury (AKI) is characterized by the disturbance of redox homeostasis, resulting in massive tubular necrosis and inflammation. Α-lipoic acid (LA), as an antioxidant, has been reported to play an important role in renal protection, but the underlying mechanism remains poorly explored. The aim of this study is to investigate the protective effect of LA on FA-induced renal damage. Our findings showed that LA could ameliorate renal dysfunction and histopathologic damage induced by FA overdose injection. Moreover, FA injection induced severe inflammation, indicated by increased release of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-1β, as well as infiltration of macrophage, which can be alleviated by LA supplementation. In addition, LA not only reduced the cellular iron overload by upregulating the expressions of Ferritin and ferroportin (FPN), but also mitigated reactive oxygen species (ROS) accumulation and lipid peroxidation by increasing the levels of antioxidant glutathione (GSH) and glutathione peroxidase-4 (GPX4). More importantly, we found that LA supplementation could reduce the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive tubular cells caused by FA, indicating that the tubular cell death mediated by ferroptosis may be inhibited. Further study demonstrated that LA supplementation could reverse the decreased expression of cystine/glutamate antiporter xCT (SLC7A11), which mediated GSH synthesis. What is more, mechanistic study indicated that p53 activation was involved in the inhibitory effect of SLC7A11 induced by FA administration, which could be suppressed by LA supplementation. Taken together, our findings indicated that LA played the protective effect on FA-induced renal damage mainly by inhibiting ferroptosis.