bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Subacute Thyroiditis Recurrence: A Systematic Review and Meta-Analysis of Cohort Studies
Authors: Zhang Jing , Ding Guoyong , Li Jingru , Li Xiao , Ding Lin , Li Xiangyun , Yang Shuxiang , Tang Fang
Published: December 2021

Background

Subacute thyroiditis (SAT) is a self-limited inflammatory thyroid disease with recurring episodes. However, the results regarding the recurrence rate and risk factors for SAT are inconsistent. This meta-analysis aimed to summarize the evidence of the recurrence rate and the risk factors for SAT.

Methods

The present study involved the performance of a systematic literature search of all English studies published in PubMed, Embase, Web of Science, and The Cochrane Library from inception to August 20, 2021. Cohort studies that reported the SAT recurrence rate and risk factors for recurrence were included. Two independent investigators extracted relevant information. Fixed- and random-effects models were used to pool effect sizes based on study heterogeneity.

Results

Eighteen cohort studies were identified. The pooled findings showed that the recurrence rate was 12.0% (95% CI: 8.2%, 17.1%). The risk of recurrence in the glucocorticoids group was higher than that in the NSAIDs group (RR = 1.84, 95% CI: 1.04, 3.24). However, there was no significant difference in age or sex between the recurrence group and the non-recurrence group. Findings from one or two cohort studies also indicated that the copresence of HLA-B*18:01 and -B*35, the number of days required to taper prednisolone (PSL) to 5 mg/day, the duration of disease before treatment less than 30 days, the sialic acid level, or the TSH level at the termination of treatment and further extension of the hypoechoic area and increase in thyroid volume were related to the recurrence of SAT.

Conclusion

Recurrence was common in SAT patients. The present study indicated that glucocorticoid treatment was associated with a higher recurrence rate of SAT than NSAIDs treatment. The clinical implications of this association should be interpreted with caution, and further clinical trials on the long-term effects of different treatment strategies are needed.
Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency
Authors: Jiang Lingling , Fei Haiyi , Tong Jinfei , Zhou Jiena , Zhu Jiajuan , Jin Xiaoying , Shi Zhan , Zhou Yan , Ma Xudong , Yu Hailan , Yang Jianhua , Zhang Songying
Published: December 2021

Objective

We explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.

Methods

Fecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman’s rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.

Results

The abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.

Conclusions

The interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.
Genetic Drift Versus Climate Region Spreading Dynamics of COVID-19
Authors: Di Pietro R. , Basile M. , Antolini L. , Alberti S.
Published: December 2021

Background: The current propagation models of COVID-19 are poorly consistent with existing epidemiological data and with evidence that the SARS-CoV-2 genome is mutating, for potential aggressive evolution of the disease.

Objectives: We looked for fundamental variables that were missing from current analyses. Among them were regional climate heterogeneity, viral evolution processes versus founder effects, and large-scale virus containment measures.

Methods: We challenged regional versus genetic evolution models of COVID-19 at a whole-population level, over 168,089 laboratory-confirmed SARS-CoV-2 infection cases in Italy, Spain, and Scandinavia at early time-points of the pandemic. Diffusion data in Germany, France, and the United Kingdom provided a validation dataset of 210,239 additional cases.

Results: Mean doubling time of COVID-19 cases was 6.63 days in Northern versus 5.38 days in Southern Italy. Spain extended this trend of faster diffusion in Southern Europe, with a doubling time of 4.2 days. Slower doubling times were observed in Sweden (9.4 days), Finland (10.8 days), and Norway (12.95 days). COVID-19 doubling time in Germany (7.0 days), France (7.5 days), and the United Kingdom (7.2 days) supported the North/South gradient model. Clusters of SARS-CoV-2 mutations upon sequential diffusion were not found to clearly correlate with regional distribution dynamics.

Conclusion: Acquisition of mutations upon SARS-CoV-2 spreading failed to explain regional diffusion heterogeneity at early pandemic times. Our findings indicate that COVID-19 transmission rates are rather associated with a sharp North/South climate gradient, with faster spreading in Southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 infectivity. Very cold regions may be better spared by recurrent courses of SARS-CoV-2 infection.
VaAPRT3 Gene is Associated With Sex Determination in Vitis amurensis
Authors: Men Yan , Li Ji-Rui , Shen Hai-Lin , Yang Yi-Ming , Fan Shu-Tian , Li Kun , Guo Yin-Shan , Lin Hong , Liu Zhen-Dong , Guo Xiu-Wu
Published: December 2021

In the past decade, progress has been made in sex determination mechanism in Vitis. However, genes responsible for sexual differentiation and its mechanism in V. amurensis remain unknown. Here, we identify a sex determination candidate gene coding adenine phosphoribosyl transferase 3 (VaAPRT3) in V. amurensis. Cloning and sequencing of the VaAPRT3 gene allowed us to develop a molecular marker able to discriminate female individuals from males or hermaphrodites based on a 22-bp InDel. Gene expression and endogenous cytokinin content analysis revealed that the VaAPRT3 gene is involved in sex determination or, to be precise, in female organ differentiation, through regulating cytokinin metabolism in V. amurensis. This study enlarged the understanding of sex determination mechanism in the genus Vitis, and the sex marker could be used as a helpful tool for sexual identification in breeding programs as well as in investigation and collection of V. amurensis germplasms.
Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers
Authors: Nyanhete Tinashe E. , Edwards Robert J. , LaBranche Celia C. , Mansouri Katayoun , Eaton Amanda , Dennison S. Moses , Saunders Kevin O. , Goodman Derrick , Janowska Katarzyna , Spreng Rachel L. , Zhang Lu , Mudrak Sarah V. , Hope Thomas J. , Hora Bhavna , Bradley Todd , Georgiev Ivelin S. , Montefiori David C. , Acharya Priyamvada , Tomaras Georgia D.
Published: December 2021

Broadly neutralizing antibodies (bNAbs), known to mediate immune control of HIV-1 infection, only develop in a small subset of HIV-1 infected individuals. Despite being traditionally associated with patients with high viral loads, bNAbs have also been observed in therapy naïve HIV-1+ patients naturally controlling virus replication [Virus Controllers (VCs)]. Thus, dissecting the bNAb response in VCs will provide key information about what constitutes an effective humoral response to natural HIV-1 infection. In this study, we identified a polyclonal bNAb response to natural HIV-1 infection targeting CD4 binding site (CD4bs), V3-glycan, gp120-gp41 interface and membrane-proximal external region (MPER) epitopes on the HIV-1 envelope (Env). The polyclonal antiviral antibody (Ab) response also included antibody-dependent cellular phagocytosis of clade AE, B and C viruses, consistent with both the Fv and Fc domain contributing to function. Sequence analysis of envs from one of the VCs revealed features consistent with potential immune pressure and virus escape from V3-glycan targeting bNAbs. Epitope mapping of the polyclonal bNAb response in VCs with bNAb activity highlighted the presence of gp120-gp41 interface and CD4bs antibody classes with similar binding profiles to known potent bNAbs. Thus, these findings reveal the induction of a broad and polyfunctional humoral response in VCs in response to natural HIV-1 infection.
Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System
Authors: Kraus Richard Felix , Gruber Michael Andreas
Published: December 2021

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.
LncRNA Expression Profiles in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets
Authors: Wu Han , Chen Shuxian , Li Aifen , Shen Kangyuan , Wang Shuting , Wang Sijie , Wu Ping , Luo Wenying , Pan Qingjun
Published: December 2021

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common multisystem autoimmune diseases that share, among others, many clinical manifestations and serological features. The role of long non-coding RNAs (lncRNAs) has been of particular interest in the pathogenesis of autoimmune diseases. Here, we aimed to summarize the roles of lncRNAs as emerging novel biomarkers and therapeutic targets in SLE and RA. We conducted a narrative review summarizing original articles on lncRNAs associated with SLE and RA, published until November 1, 2021. Based on the studies on lncRNA expression profiles in samples (including PBMCs, serum, and exosomes), it was noted that most of the current research is focused on investigating the regulatory mechanisms of these lncRNAs in SLE and/or RA. Several lncRNAs have been hypothesized to play key roles in these diseases. In SLE, lncRNAs such as GAS5, NEAT1, TUG1, linc0949, and linc0597 are dysregulated and may serve as emerging novel biomarkers and therapeutic targets. In RA, many validated lncRNAs, such as HOTAIR, GAS5, and HIX003209, have been identified as promising novel biomarkers for both diagnosis and treatment. The shared lncRNAs, for example, GAS5, may participate in SLE pathogenesis through the mitogen-activated protein kinase pathway and trigger the AMP-activated protein kinase pathway in RA. Here, we summarize the data on key lncRNAs that may drive the pathogenesis of SLE and RA and could potentially serve as emerging novel biomarkers and therapeutic targets in the coming future.
Prenatal and Postnatal Cigarette Smoke Exposure Is Associated With Increased Risk of Exacerbated Allergic Airway Immune Responses: A Preclinical Mouse Model
Authors: Janbazacyabar Hamed , van Bergenhenegouwen Jeroen , Garssen Johan , Leusink-Muis Thea , Ark Ingrid van , van Daal Marthe T. , Folkerts Gert , Braber Saskia
Published: December 2021

Increased exposure to household air pollution and ambient air pollution has become one of the world’s major environmental health threats. In developing and developed countries, environmental cigarette smoke (CS) exposure is one of the main sources of household air pollution (HAP). Moreover, results from different epidemiological and experimental studies indicate that there is a strong association between HAP, specifically CS exposure, and the development of allergic diseases that often persists into later life. Here, we investigated the impact of prenatal and postnatal CS exposure on offspring susceptibility to the development of allergic airway responses by using a preclinical mouse model. Pregnant BALB/c mice were exposed to either CS or air during pregnancy and lactation and in order to induce allergic asthma the offspring were sensitized and challenged with house dust mite (HDM). Decreased lung function parameters, like dynamic compliance and pleural pressure, were observed in PBS-treated offspring born to CS-exposed mothers compared to offspring from air-exposed mothers. Maternal CS exposure significantly increased the HDM-induced airway eosinophilia and neutrophilia in the offspring. Prenatal and postnatal CS exposure increased the frequency of Th2 cells in the lungs of HDM-treated offspring compared to offspring born to air-exposed mothers. Offspring born to CS-exposed mothers showed increased levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared to offspring from air-exposed mothers. Ex-vivo restimulation of lung cells isolated from HDM-treated offspring born to CS-exposed mothers also resulted in increased IL-4 production. Finally, serum immunoglobulins levels of HDM-specific IgE and HDM-specific IgG1 were significantly increased upon a HDM challenge in offspring born to CS-exposed mothers compared to offspring from air-exposed mothers. In summary, our results reveal a biological plausibility for the epidemiological studies indicating that prenatal and postnatal CS exposure increases the susceptibility of offspring to allergic immune responses.
Spatial Distribution of Different Age Groups of Herring in Norwegian Sea, May 1996–2020
Authors: Eliasen Sólvá Káradóttir , Homrum Eydna Í. , Jacobsen Jan Arge , Kristiansen Inga , Óskarsson Guðmundur J. , Salthaug Are , Stenevik Erling Kåre
Published: December 2021

The commercially important Norwegian spring spawning herring is characterized by its extensive annual migrations and, on a decadal timescale, large shifts in migration patterns. These changes are not well understood, but have previously been linked to temperature, food availability, and size and age composition of the stock. Acoustic and trawl data from the International Ecosystem Surveys in the Nordic Seas, carried out annually in May since 1996, were used to analyze the spatial distribution of herring in the period 1996–2020. The dataset was disaggregated into age classes, and information about where the different age classes feed in May was derived. The analysis of herring feeding patterns in May confirms that the youngest age classes are generally found close to the Norwegian shelf, whereas the older age classes display larger variations in where they are distributed. During the period 1996–1998, the oldest age classes were found in the central and western Norwegian Sea. During the period 1999–2004, the whole stock migrated north after spawning, leaving the regions in the southern Norwegian Sea void of herring. Since 2005 the oldest herring has again congregated in the south-western Norwegian Sea, in the frontal zone between the cooler East Icelandic water and the warmer Atlantic water. There was a significant positive relationship both between stock size and distribution area and between stock size and density. Moreover, it is likely that the strong year classes 1991/1992 and 1998/1999, which were relatively old when the respective changes in migration patterns occurred, were important contributors to the changes observed in 1999 and 2005, respectively.
Measuring the Concentration of Serum Syndecan-1 to Assess Vascular Endothelial Glycocalyx Injury During Hemodialysis
Authors: Kusuzawa Keigo , Suzuki Keiko , Okada Hideshi , Suzuki Kodai , Takada Chihiro , Nagaya Soichiro , Yasuda Ryu , Okamoto Haruka , Ishihara Takuma , Tomita Hiroyuki , Kawasaki Yuki , Minamiyama Toru , Nishio Ayane , Fukuda Hirotsugu , Shimada Takuto , Tamaoki Yuto , Yoshida Tomoki , Nakashima Yusuke , Chiba Naokazu , Yoshimura Genki , Kamidani Ryo , Miura Tomotaka , Oiwa Hideaki , Yamaji Fuminori , Mizuno Yosuke , Miyake Takahito , Kitagawa Yuichiro , Fukuta Tetsuya , Doi Tomoaki , Suzuki Akio , Yoshida Takahiro , Tetsuka Nobuyuki , Yoshida Shozo , Ogura Shinji
Published: December 2021

Glycocalyx is present on the surface of healthy endothelium, and the concentration of serum syndecan-1 can serve as an injury marker. This study aimed to assess endothelial injury using serum syndecan-1 as a marker of endothelial glycocalyx injury in patients who underwent hemodialysis. In this single-center, retrospective, observational study, 145 patients who underwent hemodialysis at the Gifu University Hospital between March 2017 and December 2019 were enrolled. The median dialysis period and time were 63 months and 3.7 h, respectively. The serum syndecan-1 concentration significantly increased from 124.6 ± 107.8 ng/ml before hemodialysis to 229.0 ± 138.1 ng/ml after hemodialysis (P < 0.001). Treatment with anticoagulant nafamostat mesylate inhibited hemodialysis-induced increase in the levels of serum syndecan-1 in comparison to unfractionated heparin. Dialysis time and the change in the syndecan-1 concentration were positively correlated. Conversely, the amount of body fluid removed and the changes in the syndecan-1 concentration were not significantly correlated. The reduction in the amount of body fluid removed and dialysis time inhibited the change in the syndecan-1 levels before and after hemodialysis. In conclusion, quantitative assessment of the endothelial glycocalyx injury during hemodialysis can be performed by measuring the serum syndecan-1 concentration, which may aid in the selection of appropriate anticoagulants, reduction of hemodialysis time, and the amount of body fluid removed.
The Role of EUPATI CH in Promoting Patient Involvement in Clinical Research: A Multi-Stakeholder Research Project
Authors: Sessa Cristiana , Schmid Caecilia , Tolotti Angela , Magnin Annette , Haerry David , Bonetti Loris , Klingmann Ingrid
Published: December 2021

Background: The European Patients' Academy on Therapeutic Innovation Switzerland (EUPATI CH) was established as an association in 2016 with the mission to improve patient empowerment in Switzerland, raise public awareness of EUPATI's education material, and foster multi-stakeholder partnerships in order to promote public involvement in all aspects of medicines research and development (R&D). In order to achieve its goal of improving patient involvement (PI) in all processes of medicines R&D in Switzerland and to obtain guidance and recommendations for future activities, EUPATI CH initiated a multi-stakeholder survey on PI experiences, hurdles, and best practices. The survey enabled EUPATI CH to obtain and analyze the views of various stakeholders and shape its workplan.

Methods: Data collection occurred between January and July 2019 using a survey and semi-structured interviews with individual stakeholders from different groups. The online survey responses were analyzed using quantitative methods and the interviews were analyzed using qualitative methods.

Results: The online survey was completed by 55 respondents (10%), and the semi-structured interviews were conducted with 14 stakeholders. Respondents to the online survey were patient representatives (45%), researchers from academia (25%), individuals from the pharmaceutical industry (9%), healthcare professionals (23%), and representatives from government agencies (6%). Some respondents were also members of EUPATI CH. Thirty-eight percent of respondents consider PI in Switzerland to be limited or absent. They identified the main barriers to PI as, first and foremost, a lack of funds and human resources (65%), followed by a lack of information and a lack of education on how to become a patient advocate (21%), a lack of collaboration with other stakeholders (16%), and a lack of adequate resources. Respondents' expectations of EUPATI CH's role in supporting PI were to provide education for active PI and improve networking and collaboration among stakeholders.

Conclusions: EUPATI CH's multi-stakeholder research identified some of the difficulties in promoting PI in medicines R&D in Switzerland, in particular the complex collaboration among stakeholders and a lack of funds, human resources, and knowledge. To respond to these difficulties, EUPATI CH has begun preparing a basic training course for patients that is adapted to Switzerland.
Zoledronic Acid for Periprosthetic Bone Mineral Density Changes in Patients With Osteoporosis After Hip Arthroplasty—An Updated Meta-Analysis of Six Randomized Controlled Trials
Authors: Liu Yuan , Xu Jia-Wen , Li Ming-Yang , Wu Li-Min , Zeng Yi , Shen Bin
Published: December 2021

Introduction:Periprosthetic bone mineral density (BMD) loss following total hip arthroplasty (THA) may threaten the survival of the implant, especially in patients with osteoporosis. Zoledronic acid (ZA) is the representative of the third generation of bisphosphonates, which were effective in reducing bone loss in conditions associated with accelerated bone turnover. The aim of this study was to evaluate the efficacy and safety of ZA in patients with osteoporosis after THA.

Methods:Randomized controlled trials (RCTs) associated with ZA and THA were searched from the MEDLINE, PubMed, EMBASE, Wanfang database, and the Web of Science (August 2021). Other methods, such as hand search and email request were also tried. The methodological quality was assessed by the Risk of Bias (RoB) 2.0. Relevant data were abstracted from the included RCTs and authors were contacted when necessary.

Results:In this study, six RCTs involving a total of 307 patients were finally included and analyzed. The pooled data demonstrated that significantly less periprosthetic BMD loss in Gruen zone seven had occurred in the ZA-treated patients than in the control patients at 3 months (mean difference [MD] = 4.03%; 95%CI: 0.29–7.76%;P= 0.03), 6 months (MD = 7.04%; 95%CI: 2.12–11.96%;P= 0.005), and 12 months (MD = 7.12%; 95%CI: 0.33–13.92%;P= 0.04). The Harris Hip Score (HHS) was also significantly increased in ZA group at 6 and 12 months after operation (P= 0.03 andP= 0.02, respectively). Influenza-like symptom was found related to the usage of ZA [relative risk (RR) = 7.03,P< 0.0001].

Conclusion:A meta-analysis of six RCTs suggested that ZA was beneficial in maintaining the periprosthetic BMD in patients with osteoporosis at 6 and 12 months after THA. In addition, the HHS was significantly improved in patients treated with ZA. However, the short length of follow-up of the available studies resulted in the lack of analyses regarding the survival of implants including the rate of aseptic loosing, periprosthetic fracture, and revision. It still needs to be determined in research with longer follow-up period.

Clinical Trial Registration:Researchregistry.com, identifier: reviewregistry1087.
Exacerbation of Psoriasis Following COVID-19 Vaccination: Report From a Single Center
Authors: Huang Yi-Wei , Tsai Tsen-Fang
Published: December 2021

The temporal association had been reported between vaccination and exacerbation of psoriasis, and episodes of psoriasis flare-up have recently been attributed to COVID-19 vaccines. We recruited 32 unimmunized controls and 51 vaccinated psoriasis patients, 49 of whom were under biological therapy, with regular clinic visits receiving a total of 63 shots of vaccines, including 30 doses of Moderna mRNA-1273 and 33 doses of AstraZeneca-Oxford AZD1222. Fifteen episodes of exacerbation attacked within 9.3 ± 4.3 days, which is higher than two episodes in the control group (p = 0.047). The mean post-vaccination severity of the worsening episodes increased from PASI 3.1 to 8.0 (p < 0.001). Three patients showed morphologic change from chronic plaque-type to guttate psoriasis. Deterioration of psoriasis following COVID-19 vaccination was not associated with age, sex, disease duration, psoriatic arthritis, family history of psoriasis, history of erythroderma, current biologics use, comorbidities, vaccine types, human leukocyte antigen (HLA)-C genotypes, baseline PASI nor pre-vaccination PASI. For those who received two doses of vaccination, all but one patient aggravated after the first shot but not the second. The mechanism of psoriasis exacerbation in immunized individuals is unclear, but Th17 cells induced by COVID-19 vaccines may play a role. In the pandemic era, psoriasis patients and physicians should acknowledge the possibility of fluctuation of disease activity when vaccinated against COVID-19. Nevertheless, compared to a treatable dermatologic disease with rapid resolution of exacerbation, psoriasis patients who do not have contraindications to vaccination should benefit from COVID-19 vaccines in the prevention of severe COVID-19 infection and fatality.
Added Value of Genomic Surveillance of Virulence Factors in Shiga Toxin-Producing Escherichia coli in New South Wales, Australia
Authors: Sim Eby M. , Kim Ryan , Gall Mailie , Arnott Alicia , Howard Peter , Valcanis Mary , Howden Benjamin P. , Sintchenko Vitali
Published: December 2021

The disease caused by Shiga toxin-producing Escherichia coli (STEC) remains a significant public health challenge globally, but the incidence of human STEC infections in Australia remains relatively low. This study examined the virulence characteristics and diversity of STEC isolates in the state of New South Wales between December 2017 and May 2020. Utilisation of both whole and core genome multi-locus sequence typing (MLST) allowed for the inference of genomic diversity and detection of isolates that were likely to be epidemiologically linked. The most common STEC serotype and stx subtype detected in this study were O157:H7 and stx1a, respectively. A genomic scan of other virulence factors present in STEC suggested interplay between iron uptake system and virulence factors that mediate either iron release or countermeasures against host defence that could result in a reduction of stx1a expression. This reduced expression of the dominant stx genotype could contribute to the reduced incidence of STEC-related illness in Australia. Genomic surveillance of STEC becomes an important part of public health response and ongoing interrogation of virulence factors in STEC offers additional insights for the public health risk assessment.
Involvement of Small Colony Variant-Related Heme Biosynthesis Genes in Staphylococcus aureus Persister Formation in vitro
Authors: Wang Xuyang , Li Weizheng , Wang Wenjie , Wang Shiyong , Xu Tao , Chen Jiazhen , Zhang Wenhong
Published: December 2021

Background: Persisters are important reasons for persistent infections, and they can lead to antibiotic treatment failure in patients and consequently chronic infection. Staphylococcus aureus small colony variants (SCVs) have been shown to be related to persistent infection. Mutations in the genes of the heme biosynthesis pathway lead to the formation of SCVs. However, the relationship between heme production genes and persister has not been tested.

Methods:HemA and hemB were knocked out by allelic replacement from S. aureus strain USA500 separately, and then, the heme deficiency was complemented by overexpression of related genes and the addition of hemin. The stress-related persister assay was conducted. RNA-sequencing was performed to find genes and pathways involved in heme-related persister formation, and relative genes and operons were further knocked out and overexpressed to confirm their role in each process.

Results: We found that heme biosynthesis deficiency can lead to decreased persister. After complementing the corresponding genes or hemin, the persister levels could be restored. RNA-seq on knockout strains showed that various metabolic pathways were influenced, such as energy metabolism, amino acid metabolism, carbohydrate metabolism, and membrane transport. Overexpression of epiF and operon asp23 could restore USA500∆hemA persister formation under acid stress. Knocking out operon arc in USA500∆hemA could further reduce USA500∆hemA persister formation under acid and oxidative stress.

Conclusion: Heme synthesis has a role in S. aureus persister formation.
Modulation of the Wheat Seed-Borne Bacterial Community by Herbaspirillum seropedicae RAM10 and Its Potential Effects for Tryptophan Metabolism in the Root Endosphere
Authors: Carril Pablo , Cruz Joana , di Serio Claudia , Pieraccini Giuseppe , Ait Bessai Sylia , Tenreiro Rogério , Cruz Cristina
Published: December 2021

Plants and their associated microbiota share ecological and evolutionary traits that are considered to be inseparably woven. Their coexistence foresees the use of similar metabolic pathways, leading to the generation of molecules that can cross-regulate each other’s metabolism and ultimately influence plant phenotype. However, the extent to which the microbiota contributes to the overall plant metabolic landscape remains largely unexplored. Due to their early presence in the seed, seed-borne endophytic bacteria can intimately colonize the plant’s endosphere while conferring a series of phytobeneficial services to their host. Understanding the dynamics of these endophytic communities is a crucial step toward the formulation of microbial inoculants that can modulate the functionality of the plant-associated microbiota for improved plant fitness. In this work, wheat (Triticum aestivum) roots non-inoculated and inoculated with the bacterium Herbaspirillum seropedicae strain RAM10 were analyzed to explore the impact of inoculant–endophyte–wheat interrelationships on the regulation of tryptophan (Trp) metabolism in the endosphere environment. Root inoculation with H. seropedicae led to phylum-specific changes in the cultivable seed-borne endophytic community. This modulation shifted the metabolic potential of the community in light of its capacity to modulate the levels of key Trp-related metabolites involved in both indole-3-acetic acid (IAA) biosynthesis and in the kynurenine pathway. Our results support a mode of action of H. seropedicae relying on a shift in both the composition and functionality of the seed-borne endophytic community, which may govern important processes such as root growth. We finally provide a conceptual framework illustrating that interactions among roots, inoculants, and seed-borne endophytes are critical to fine-tuning the levels of IAA in the endosphere. Understanding the outcomes of these interactions is a crucial step toward the formulation of microbial inoculants based on their joint action with seed-borne endophytic communities to promote crop growth and health in a sustainable manner.
Duck Plague Virus pUL48 Protein Activates the Immediate-Early Gene to Initiate the Transcription of the Virus Gene
Authors: Zhou Tong , Fan Dengjian , Wang Mingshu , Cheng Anchun , Wu Ying , Yang Qiao , Tian Bin , Jia Renyong , Ou Xumin , Mao Sai , Sun Di , Zhang Shaqiu , Zhu Dekang , Chen Shun , Liu Mafeng , Zhao Xin-Xin , Huang Juan , Gao Qun , Yu Yanling , Zhang Ling
Published: December 2021

Duck plague caused by the duck plague virus (DPV) is an infectious disease that seriously harms the waterfowl breeding industry. The VP16 protein of α herpesvirus can bind to specific cis-acting elements upstream of the promoter of the immediate-early (IE, α) gene to promote the transcription of the IE gene, so it is also called the trans-inducer of IE gene (α-TIF). However, no studies on DPV α-TIF have been reported. This study investigated the DPV pUL48, a homolog of HSV-1 VP16, transcriptional activation region, target sequence, and viral protein affecting its transcriptional activation using a dual-luciferase reporter gene detection system, and pUL48 was identified as the α-TIF of DPV. (1) The regulation of pUL48 on DPV different gene promoters showed that pUL48 could activate all the promoters of IE genes (ICP4, ICP22, and ICP27) but not the promoters of early and late genes. (2) The activity of pUL48 to ICP4 and ICP22 promoters with different upstream lengths showed that pUL48 activated ICP4 and ICP22 promoters by acting on TAATGA (T) TAT element upstream of ICP4 promoter and TAATTATAT element upstream of ICP22 promoter, respectively. (3) Transcriptional activation of IE gene by truncated proteins of different lengths at the N-terminal of pUL48 was detected. The results showed that the transcriptional activation domain of pUL48 was amino acids 1–60 at the N-terminal, and amino acids 1–20 was its core region. In addition, it was found that pUL14, pUL46, and pUL47 significantly promoted the transcriptional activation of pUL48. The effects of loss of pUL47 and its nuclear localization signal on the nuclear entry and transcriptional activation function of pUL48 were further examined. The results showed that pUL47 could promote the nuclear entry of pUL48 through its nuclear localization signal at positions 40–50 and 768–777 amino acids, thus, enhancing the transcriptional activation function of pUL48 and synergistic promotion of viral gene transcription.
Dynamic and Assembly of Benthic Bacterial Community in an Industrial-Scale In-Pond Raceway Recirculating Culture System
Authors: Hou Yiran , Li Bing , Xu Gangchun , Li Da , Zhang Chengfeng , Jia Rui , Li Quanjie , Zhu Jian
Published: December 2021

To reduce water utilization, limit environmental pollution, and guarantee aquatic production and quality, the in-pond raceway recirculating culture system (IPRS) has been developed and is widely used. The effectiveness and sustainability of IPRSs rely on a good understanding of the ecological processes related to bacterial communities in the purification area. In this study, we investigated the dynamics and assembly mechanisms of benthic bacterial communities in the purification area of an industrial-scale IRPS. We found significant temporal and spatial variations in the sediment characteristics and benthic bacterial communities of the IPRS, although correlation analyses revealed a very limited relationship between them. Among the different culture stages, we identified numerous benthic bacteria with different abundances. Abundances of the phyla Bacteroidota and Desulfobacterota decreased whereas those of Myxococcota and Gemmatimonadota increased as the culture cycle progressed. Co-occurrence networks revealed that the bacterial community was less complex but more stable in the IPRS at the final stage compared with the initial stage. The neutral community model (NCM) showed that stochastic processes were the dominant ecological processes shaping the assembly of the benthic bacterial community. The null model suggested that homogenizing dispersal was more powerful than dispersal limitation and drift in regulating the assembly of the community. These findings indicate that the benthic microbial communities in purification areas of the IPRS may not be affected by the deposited wastes, and a more stable benthic microbial communities were formed and mainly driven by stochastic processes. However, the benthic microbial communities in the purification area at the end of the culturing stage was characterized by potentially inhibited organic matter degradation and carbon and sulfur cycling abilities, which was not corresponding to the purification area’s function. From this point on, the IPRS, especially the purification area was needed to be further optimized and improved.
MAP3K8 Is a Prognostic Biomarker and Correlated With Immune Response in Glioma
Authors: Ren Jing , Xu Yixin , Liu Jia , Wu Sicheng , Zhang Ruihan , Cao Haowei , Sun Jinmin
Published: December 2021

MAP3K8 is a serine/threonine kinase that is widely expressed in immune cells, non-immune cells, and many tumor types. The expression, clinical significance, biological role, and the underlying molecular mechanisms of MAP3K8 in glioma have not been investigated yet. Here, we discovered that MAP3K8 was aberrantly overexpressed in glioma and correlated with poor clinicopathological features of glioma by analysis on different datasets and immunohistochemistry staining. MAP3K8 is an independent prognostic indicator and significantly correlates with the progression of glioma. We also performed the function and pathway enrichment analysis of MAP3K8 in glioma to explore its biological functions and underlying molecular mechanisms in glioma. MAP3K8 co-expressed genes were mainly enriched in immune-related biological processes such as neutrophil activation, leukocyte migration, neutrophil-mediated immunity, lymphocyte-mediated immunity, T-cell activation, leukocyte cell–cell adhesion, regulation of leukocyte cell–cell adhesion, B-cell-mediated immunity, myeloid cell differentiation, and regulation of cell–cell adhesion. Single-cell RNA sequencing data and immunohistochemistry analysis demonstrated that MAP3K8 is expressed in malignant and immune cells and mainly enriched in the microglia/macrophage cells of glioma. The expression of MAP3K8 was positively correlated with immune infiltration, including effector memory CD4+ T cells, plasmacytoid dendritic cells, neutrophils, myeloid dendritic cells, mast cells, and macrophage in glioma. Further correlation analysis demonstrated that a series of inhibitory immune checkpoint molecules, chemokines, and chemokine receptors was positively correlated with the expression of MAP3K8. MAP3K8 might play an essential role in tumor immunity, and inhibition of MPA3K8 is a plausible strategy for glioma immunotherapy.
Progress in the Research and Targeted Therapy of ErbB/HER Receptors in Urothelial Bladder Cancer
Authors: Chen Dong , Ye Yunlin , Guo Shengjie , Yao Kao
Published: December 2021

Bladder cancer is a lethal malignancy and a majority of bladder cancer arise from urothelial cells. Infiltration and metastasis are barriers for the radical cystectomy to achieve favored outcome and are the main cause of death. Systemic therapy, including chemotherapy, targeted therapy, and immunotherapy, is fundamental for these patients. erbB/HER receptors are found to be overexpressed in a subgroup of urothelial carcinoma, targeting erbB/HER receptors in these patients was found to be an efficient way in the era of genetic testing. To evaluate the role of erbB/HER receptors in bladder cancer, we reviewed the literature and ongoing clinical trials as regards to this topic to unveil the context of erbB/HER receptors in bladder cancer, which probably help to solidate the theoretical basis and might instruct further research.
The Role of the Diaphragm in Postural Stability and Visceral Function in Parkinson’s Disease
Authors: Yu Xin , Jiang Hong-ying , Zhang Chen-xi , Jin Zhao-hui , Gao Lei , Wang Rui-dan , Fang Jin-ping , Su Yuan , Xi Jia-ning , Fang Bo-yan
Published: December 2021

Background: In normal subjects, the diaphragm plays a key functional role in postural stability, articulation, respiration, defecation, and urination.

Objectives: The aim of this study was to investigate the role of the diaphragm in postural stability and visceral function in patients with Parkinson’s disease (PD) and to compare the diaphragm function by gender, Hoehn and Yahr (H&Y) staging, and motor subtypes.

Methods: In total, 79 patients were enrolled in this cross-sectional study. The severity of the disease was assessed by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III and by H&Y staging. Postural stability was quantitatively recorded, and respiratory function was evaluated by spirometry. Several scales were used to evaluate visceral function in patients with PD. In addition, diaphragm ultrasound was used to measure the excursion, contraction velocity, and thickness of the diaphragm during quiet breathing, deep breathing, and the sniff test. Significant features were selected by the least absolute shrinkage and selection operator (LASSO) regression and fitted in the multivariate linear regression and Pearson’s correlation analysis.

Results: Diaphragm thickness and excursion during quiet breathing were significantly different between men and women and between H&Y stage 1–2 and stage 2.5–3, whereas the diaphragm function was not influenced by motor subtypes. It was shown that the diaphragmatic function was significantly correlated with postural stability, voice function, respiratory function, constipation, and urological function to varying degrees in patients with PD.

Conclusion: The diaphragmatic function is associated with dysfunction in PD although it remains unclear as to whether the observed changes in the diaphragm are primary or secondary.
China Registry Study on Cognitive Impairment in the Elderly: Protocol of a Prospective Cohort Study
Authors: Zhu Yingying , Pan Dong , He Lei , Rong Xiaoming , Li Honghong , Li Yi , Pi Yaxuan , Xu Yongteng , Tang Yamei
Published: December 2021

Introduction: To develop appropriate strategies for early diagnosis and intervention of cognitive impairment, the identification of minimally invasive and cost-effective biomarkers for the early diagnosis of cognitive impairment is crucial and desirable. Therefore, the CHina registry study on cOgnitive imPairment in the Elderly (HOPE) study is designed to investigate the natural course of cognitive decline and explore the clinical, imaging, and biochemical markers for the detection and diagnosis of cognitive impairment on its earliest stage.

Methods: Approximately 5,000 Chinese elderly aged more than 50 years were recruited from Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China by the year 2024. All subjects were invited to complete the clinical assessment, neuropsychological assessment, the biological samples collection (blood and cerebrospinal fluid (CSF)], magnetic resonance imaging (MRI) examination, and optional amyloid and tau PET. The follow-up survey was conducted every 1 year to repeat these assessments for 20 years. To better clarify the relationship between potential risk factors and endpoint events [changes in cognitive score or incidence of mild cognitive impairment (MCI) and/or dementia], appropriate statistical methods were used to analyze the data, including but not limited to, such as linear mixed-effect model, competing risk model, or the least absolute shrinkage and selection operator model.

Significance: The CHina registry study on cOgnitive imPairment in the Elderly study is designed to explore the longitudinal changes in characteristics of participants with cognitive decline and to identify potential plasma and imaging biomarkers with cost-benefit and scalability advantages. The results will enable broader clinical access and efficient population screening and then improve the development of treatment and the quality of life for cognitive impairment at the early stage.

Trial registration number: NCT04360200.
The Individual Ictal Fingerprint: Combining Movement Measures With Ultra Long-Term Subcutaneous EEG in People With Epilepsy
Authors: Kjaer Troels W. , Remvig Line S. , Helge Asbjoern W. , Duun-Henriksen Jonas
Published: December 2021

Background: Epileptic seizures are caused by abnormal brain wave hypersynchronization leading to a range of signs and symptoms. Tools for detecting seizures in everyday life typically focus on cardiac rhythm, electrodermal activity, or movement (EMG, accelerometry); however, these modalities are not very effective for non-motor seizures. Ultra long-term subcutaneous EEG-devices can detect the electrographic changes that do not depend on clinical changes. Nonetheless, this also means that it is not possible to assess whether a seizure is clinical or subclinical based on an EEG signal alone. Therefore, we combine EEG and movement-related modalities in this work. We focus on whether it is possible to define an individual “multimodal ictal fingerprint” which can be exploited in different epilepsy management purposes.

Methods: This study used ultra long-term data from an outpatient monitoring trial of persons with temporal lobe epilepsy obtained with a subcutaneous EEG recording system. Subcutaneous EEG, an EMG estimate and chest-mounted accelerometry were extracted from four persons showing more than 10 well-defined electrographic seizures each. Numerous features were computed from all three modalities. Based on these, the Gini impurity measure of a Random Forest classifier was used to select the most discriminative features for the ictal fingerprint. A total of 74 electrographic seizures were analyzed.

Results: The optimal individual ictal fingerprints included features extracted from all three tested modalities: an acceleration component; the power of the estimated EMG activity; and the relative power in the delta (0.5–4 Hz), low theta (4–6 Hz), and high theta (6–8 Hz) bands of the subcutaneous EEG. Multimodal ictal fingerprints were established for all persons, clustering seizures within persons, while separating seizures across persons.

Conclusion: The existence of multimodal ictal fingerprints illustrates the benefits of combining multiple modalities such as EEG, EMG, and accelerometry in future epilepsy management. Multimodal ictal fingerprints could be used by doctors to get a better understanding of the individual seizure semiology of people with epilepsy. Furthermore, the multimodal ictal fingerprint gives a better understanding of how seizures manifest simultaneously in different modalities. A knowledge that could be used to improve seizure acknowledgment when reviewing EEG without video.