bluuebunny/crossref_metadata_2025 huggingface dataset:
DSP-0509, a systemically available TLR7 agonist, exhibits combination effect with immune checkpoint blockade by activating anti-tumor immune effects
Authors: Ota Yosuke , Nagai Yasuhiro , Hirose Yuko , Hori Seiji , Koga-Yamakawa Erina , Eguchi Ken , Sumida Kentaro , Murata Masashi , Umehara Hiroki , Yamamoto Setsuko
Published: January 2023

TLR7 is an innate immune receptor that recognizes single-stranded RNAs, and its activation leads to anti-tumor immune effects. Although it is the only approved TLR7 agonist in cancer therapy, imiquimod is allowed to be administered with topical formulation. Thus, systemic administrative TLR7 agonist is expected in terms of expanding applicable cancer types. Here, we demonstrated the identification and characterization of DSP-0509 as a novel small-molecule TLR7 agonist. DSP-0509 is designed to have unique physicochemical features that could be administered systemically with a short half-life. DSP-0509 activated bone marrow-derived dendritic cells (BMDCs) and induced inflammatory cytokines including type I interferons. In the LM8 tumor-bearing mouse model, DSP-0509 reduced tumor growth not only in subcutaneous primary lesions but also in lung metastatic lesions. DSP-0509 inhibited tumor growth in several syngeneic tumor-bearing mouse models. We found that the CD8+ T cell infiltration of tumor before treatment tended to be positively correlated with anti-tumor efficacy in several mouse tumor models. The combination of DSP-0509 with anti-PD-1 antibody significantly enhanced the tumor growth inhibition compared to each monotherapy in CT26 model mice. In addition, the effector memory T cells were expanded in both the peripheral blood and tumor, and rejection of tumor re-challenge occurred in the combination group. Moreover, synergistic anti-tumor efficacy and effector memory T cell upregulation were also observed for the combination with anti-CTLA-4 antibody. The analysis of the tumor-immune microenvironment by using the nCounter assay revealed that the combination of DSP-0509 with anti-PD-1 antibody enhanced infiltration by multiple immune cells including cytotoxic T cells. In addition, the T cell function pathway and antigen presentation pathway were activated in the combination group. We confirmed that DSP-0509 enhanced the anti-tumor immune effects of anti-PD-1 antibody by inducing type I interferons via activation of dendritic cells and even CTLs. In conclusion, we expect that DSP-0509, a new TLR7 agonist that synergistically induces anti-tumor effector memory T cells with immune checkpoint blockers (ICBs) and can be administered systemically, will be used in the treatment of multiple cancers.
Emerging predictive biomarkers for novel therapeutics in peripheral T-cell and natural killer/T-cell lymphoma
Authors: Yap Daniel Ren Yi , Lim Jing Quan , Huang Dachuan , Ong Choon Kiat , Chan Jason Yongsheng
Published: January 2023

Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are rare subtypes of non-Hodgkin’s lymphoma that are typically associated with poor treatment outcomes. Contemporary first-line treatment strategies generally involve the use of combination chemoimmunotherapy, radiation and/or stem cell transplant. Salvage options incorporate a number of novel agents including epigenetic therapies (e.g. HDAC inhibitors, DNMT inhibitors) as well as immune checkpoint inhibitors. However, validated biomarkers to select patients for individualized precision therapy are presently lacking, resulting in high treatment failure rates, unnecessary exposure to drug toxicities, and missed treatment opportunities. Recent advances in research on the tumor and microenvironmental factors of PTCL and NKTCL, including alterations in specific molecular features and immune signatures, have improved our understanding of these diseases, though several issues continue to impede progress in clinical translation. In this Review, we summarize the progress and development of the current predictive biomarker landscape, highlight potential knowledge gaps, and discuss the implications on novel therapeutics development in PTCL and NKTCL.
A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss
Authors: Nørgaard-Pedersen Caroline , Steffensen Rudi , Kesmodel Ulrik Schiøler , Christiansen Ole Bjarne
Published: January 2023

Introduction

It is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL.

Methods

In 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, β2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLA-DRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l.

Results

Although slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination.

Discussion

In conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex.
RUNX1/CD44 axis regulates the proliferation, migration, and immunotherapy of gliomas: A single-cell sequencing analysis
Authors: Zhang Hao , Cao Hui , Luo Hong , Zhang Nan , Wang Zeyu , Dai Ziyu , Wu Wantao , Liu Guodong , Xie Zongyi , Cheng Quan , Cheng Yuan
Published: January 2023

Background

Glioma is one of the most common, primary, and lethal adult brain tumors because of its extreme aggressiveness and poor prognosis. Several recent studies relevant to the immune function of CD44, a transmembrane glycoprotein as a significant hyaluronic acid receptor, have achieved great success, revealing the critical role of CD44 in immune infiltration in gliomas. The overexpression of CD44 has been verified to correlate with cancer aggressiveness and migration, while the clinical and immune features of CD44 expression have not yet been thoroughly characterized in gliomas.

Methods

Molecular and clinical data of glioma collected from publicly available genomic databases were analyzed.

Results

CD44 was up-expressed in malignant gliomas, notably in the 1p/19q non-codeletion cases, isocitrate dehydrogenase (IDH) wild-type, and mesenchymal subtypes in GBM samples. CD44 expression level strongly correlates with stromal and immune cells, mainly infiltrating the glioma microenvironment by single-cell sequencing analysis. Meanwhile, CD44 can be a promising biomarker in predicting immunotherapy responses and mediating the expression of PD-L1. Finally, RUNX1/CD44 axis could promote the proliferation and migration of gliomas.

Conclusions

Therefore, CD44 was responsible for glioma growth and progression. It could potentially lead to a novel target for glioma immunotherapy or a prognostic biomarker.
Overlapping anti-NMDAR encephalitis and multiple sclerosis: A case report and literature review
Authors: Liu Pan , Yan Hui , Li Haizhe , Zhang Chunhua , Li Yanfang
Published: January 2023

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune-mediated disease characterized by complicated neuropsychiatric symptoms and the detection of cerebrospinal fluid antibodies against the GluN1 subunit of the NMDAR. With the proposed clinical method, more anti-NMDAR encephalitis patients have been discovered since its first report. However, anti-NMDAR encephalitis overlapping with multiple sclerosis (MS) is rare. Herein we report a male patient with anti-NMDAR encephalitis who developed MS in mainland China. Furthermore, we summarized the characteristics of patients who were diagnosed with overlapping MS and anti-NMDAR encephalitis in previous studies. Additionally, we pioneered the use of mycophenolate mofetil in immunosuppressive therapy, providing a novel therapeutic alternative for overlapping anti-NMDAR encephalitis and MS.
Sequencing to identify pathogens in Tenebrio molitor: Implications in insects farmed for food and feed
Authors: Leierer Dewey , Olmstead Morgan , Oppert Brenda
Published: January 2023

Introduction

The farmed insect industry is increasing in number and size to meet the demand for sustainably-produced protein. Larger insect farms are prone to losses due to pathogens, and more information is needed regarding the health of insects reared for food and feed.

Methods

In this study, high throughput sequencing was used to identify potential pathogens in a colony of Tenebrio molitor (yellow mealworm, Coleoptera: Tenebrionidae) that exhibited increased mortality in immature stages with eventual colony collapse. Sequences also were obtained from a healthy new colony of T. molitor, as well as a recovered individual from the collapsed colony.

Results

Screening of sequences obtained from the colonies and their rearing diet indicated that the collapsed colony had low diversity in microbial taxa, with predominantly sequences from the families Staphylococcaeceae and Streptococcaceae constituting from 53 to 88% of the total microbial reads. Conversely, in the new colony and their rearing diet, microbial sequences were from more than 15 different taxa, with Lactobacilleceae the most prevalent but representing only 21% of the total microbial reads. Evidence indicates that Bacillus thuringiensis may have been involved in the collapse of the colony, leading to sepsis and microbial dysbiosis, although the source of the bacteria was not identified. Sequences from the recovered individual reflected a microbial flora profile that was intermediate between those of the diseased collapsed and new colonies.

Discussion

These findings have implications for insects reared in confined environments and provide a rapid method to screen insect colonies by sequencing healthy and potentially diseased individuals.
Targeted surveillance detected novel beaked whale circovirus in ten new host cetacean species across the Pacific basin
Authors: Clifton Cody W. , Silva-Krott Ilse , Marsik Michael G. , West Kristi L.
Published: January 2023

The first cetacean circovirus, beaked whale circovirus (BWCV), was recently reported in a Longman’s beaked whale (Indopacetus pacificus) stranded in Hawai‘i and represents an emergent disease with unknown population impacts. In other species, circovirus infection may cause mortality or opportunistic co-infection by other pathogens. We report on a targeted surveillance of stranded cetaceans in the Pacific basin, including archived beaked whale species, strandings where pathological findings suggested disease presence, mass stranded animals, and additional individuals to represent a broad range of Hawaiian cetacean species. Archived tissues primarily from the brain, kidney, liver, lung, spleen, and lymph nodes of individuals stranded between 2000 and 2020 (n=30) were tested by PCR for the presence of BWCV. Suspect positive tissue amplicons were confirmed as BWCV through sequencing. Of the screened individuals, 15 animals tested positive in one or more tissues, with a single striped dolphin (Stenella coeruleoalba) testing positive in all six tissues. The highest rate of detection among positive cases was found in the brain (69%), followed by lymph (67%) and lung tissues (64%). Additionally, co-infections of cetacean morbillivirus (n=3), Brucella ceti (n=1), and Toxoplasma gondii (n=1) were found among the positive cases. These results expand the potential host range for BWCV into ten additional odontocete species. New host species include a dwarf sperm whale (Kogia sima) that stranded on O‘ahu in 2000, predating the initial case of BWCV. The results broaden the known geographic range of BWCV to Saipan in the Western Pacific, and American Samoa in the South Pacific, where stranded Cuvier’s beaked whales (Ziphius cavirostris) tested positive. Although the clinical significance is currently unknown, this study demonstrates that BWCV has a high prevalence within targeted cetacean screening efforts. Infectious diseases pose a major threat to cetaceans and BWCV may represent an important emerging disease within populations spanning the central, Western, and South Pacific.
Using a deep-learning approach to infer and forecast the Indonesian Throughflow transport from sea surface height
Authors: Xin Linchao , Hu Shijian , Wang Fan , Xie Wenhong , Hu Dunxin , Dong Changming
Published: January 2023

The Indonesian Throughflow (ITF) connects the tropical Pacific and Indian Oceans and is critical to the regional and global climate systems. Previous research indicates that the Indo-Pacific pressure gradient is a major driver of the ITF, implying the possibility of forecasting ITF transport by the sea surface height (SSH) of the Indo-Pacific Ocean. Here we used a deep-learning approach with the convolutional neural network (CNN) model to reproduce ITF transport. The CNN model was trained with a random selection of the Coupled Model Intercomparison Project Phase 6 (CMIP6) simulations and verified with residual components of the CMIP6 simulations. A test of the training results showed that the CNN model with SSH is able to reproduce approximately 90% of the total variance of ITF transport. The CNN model with CMIP6 was then transformed to the Simple Ocean Data Assimilation (SODA) dataset and this transformed model reproduced approximately 80% of the total variance of ITF transport in the SODA. A time series of ITF transport, verified by Monitoring the ITF (MITF) and International Nusantara Stratification and Transport (INSTANT) measurements of ITF, was then produced by the model using satellite observations from 1993 to 2021. We discovered that the CNN model can make a valid prediction with a lead time of 7 months, implying that the ITF transport can be predicted using the deep-learning approach with SSH data.
Pathways of methane removal in the sediment and water column of a seasonally anoxic eutrophic marine basin
Authors: Żygadłowska Olga M. , Venetz Jessica , Klomp Robin , Lenstra Wytze K. , van Helmond Niels A. G. M. , Röckmann Thomas , Wallenius Anna J. , Martins Paula Dalcin , Veraart Annelies J. , Jetten Mike S. M. , Slomp Caroline P.
Published: January 2023

Methane (CH4) is a key greenhouse gas. Coastal areas account for a major proportion of marine CH4 emissions. Eutrophication and associated bottom water hypoxia enhance CH4 production in coastal sediments. Here, we assess the fate of CH4 produced in sediments at a site in a seasonally anoxic eutrophic coastal marine basin (Scharendijke, Lake Grevelingen, the Netherlands) in spring (March) and late summer (September) in 2020. Removal of CH4 in the sediment through anaerobic oxidation with sulfate (SO42-) is known to be incomplete in this system, as confirmed here by only slightly higher values of δ13C-CH4 and δD-CH4 in the porewater in the shallow sulfate-methane-transition zone (~5-15 cm sediment depth) when compared to deeper sediment layers. In March 2020, when the water column was fully oxygenated, CH4 that escaped from the sediment was at least partially removed in the bottom water through aerobic oxidation. In September 2020, when the water column was anoxic below ~35 m water depth, CH4 accumulated to high concentrations (up to 73 µmol L-1) in the waters below the oxycline. The sharp counter gradient in oxygen and CH4 concentrations at ~35 m depth and increase in δ13C-CH4 and δD-CH4 above the oxycline indicate mostly aerobic water column removal of CH4. Water column profiles of particulate and dissolved Fe and Mn suggest redox cycling of both metals at the oxycline, pointing towards a potential role of metal oxides in CH4 removal. Water column profiles of NH4+ and NO3- indicate removal of both solutes near the oxycline. Analyses of 16S rRNA gene sequences retrieved from the water column reveal the presence of aerobic CH4 oxidizing bacteria (Methylomonadaceae) and anaerobic methanotrophic archaea (Methanoperedenaceae), with the latter potentially capable of NO3- and/or metal-oxide dependent CH4 oxidation, near the oxycline. Overall, our results indicate sediment and water column removal of CH4 through a combination of aerobic and anaerobic pathways, which vary seasonally. Some of the CH4 appears to escape from the surface waters to the atmosphere, however. We conclude that eutrophication may make coastal waters a more important source of CH4 to the atmosphere than commonly assumed.
Divergence of epibacterial community assemblage correlates with malformation disease severity in Saccharina japonica seedlings
Authors: Yan Yongwei , Wang Shanshan , Liu Kuimei , Mo Zhaolan , Yang Huichao , Rong Xiaojun , Li Jie
Published: January 2023

Malformation disease (MD) is one of the major constraints in the mariculture of the commercially important seaweed Saccharina japonica, which can cause severe losses of the kelp seedlings in the production process. However, the pathogenesis of MD remains largely undetermined. In this study, using cultivation experiments under laboratory conditions, MD severity was estimated for the young sporophytes of S. japonica, which were separately cultivated under different treatment conditions, including light intensity, duration of light exposure, and maturity level of the parent kelp. The associations between MD severity and epibacterial community divergence and assembly patterns were characterized. Higher MD severity significantly correlated with longer light exposure, and with both unmatured and overmatured parent kelp. The bacterial classes γ-Proteobacteria and α-Proteobacteria dominated all samples, but different MD severities were associated with different epibacterial communities. Comparisons of predicted functions for epibacterial communities revealed that longer light exposure led to a depletion in development and regeneration, while overmatured parent kelp resulted in a depletion in glycan biosynthesis and metabolism. Functional comparisons of the epibacterial communities between normal and unmatured parent kelp-generated seedlings revealed significantly different categories related to metabolism, environmental information processing, cellular processes, drug resistance, and bacterial infection. The significantly different pathways between groups, notably those related to bacterial infection and cellular processes, were partly consistent with the differences in bacterial compositions. The assembly of epiphytic bacterial communities was predominately governed by deterministic processes, and less impact was determined when there was significantly higher MD severity except when using overmatured parent kelp. Co-occurrence networks of the epibacterial communities associated with higher MD severity contained fewer nodes and exhibited lower modularity, but had higher graph density and degrees compared with those of seedlings with lower MD severity, indicating more complicated interactions. Nesterenkonia, Glycocaulis, Halomonas, Pseudoalteromonas, Pseudomonas, Loktanella, and Cobetia were frequently determined keystone taxa in communities associated with higher MD severity. The present study enhances our understanding of the factors significantly associated with MD severity and the potential roles of epimicrobiome in determining the disease severity, which will be useful for disease management in the future.
Coral disease outbreak at the remote Flower Garden Banks, Gulf of Mexico
Authors: Johnston Michelle A. , Studivan Michael S. , Enochs Ian C. , Correa Adrienne M. S. , Besemer Nicole , Eckert Ryan J. , Edwards Kimberly , Hannum Ryan , Hu Xinping , Nuttall Marissa , O’Connell Kelly , Palacio-Castro Ana M. , Schmahl George P. , Sturm Alexis B. , Ushijima Blake , Voss Joshua D.
Published: January 2023

East and West Flower Garden Bank (FGB) are part of Flower Garden Banks National Marine Sanctuary (FGBNMS) in the northwest Gulf of Mexico. This geographically-isolated reef system contains extensive coral communities with the highest coral cover (>50%) in the continental United States due, in part, to their remoteness and depth, and have historically exhibited low incidence of coral disease and bleaching despite ocean warming. Yet in late August 2022, disease-like lesions on seven coral species were reported during routine monitoring surveys on East and West FGB (2.1–2.6% prevalence). A series of rapid response cruises were conducted in September and October 2022 focused on 1) characterizing signs and epidemiological aspects of the disease across FGB and within long-term monitoring sites, 2) treating affected coral colonies with Base 2B plus amoxicillin, and 3) collecting baseline images through photostations and photomosaics. Marginal and/or multi-focal lesions and tissue loss were observed, often associated with substantial fish and invertebrate predation, affecting the dominant coral species Pseudodiploria strigosa (7–8% lesion prevalence), Colpophyllia natans (11–18%), and Orbicella spp. (1%). Characterizing this disease event during its early epidemic phase at East and West FGB provides a critical opportunity to observe how coral disease functions in a relatively healthy coral ecosystem versus on reefs chronically affected by various stressors (e.g., Caribbean reefs adjacent to urban centers). Insights into the etiology, spread, and impacts of the disease can ultimately inform efforts to mitigate its effects on coral communities.
Design and advanced computational approaches based comprehensive structural parametric investigations of rotary-wing UAV imposed with conventional and hybrid computational composite materials: A validated investigation
Authors: Raja Vijayanandh , AL-bonsrulah Hussein A. Z. , Gnanasekaran Raj Kumar , Eldin Sayed M. , Rajendran Parvathy , Baskaran Balamurali , Sakthivel Pradesh
Published: January 2023

This work aims to design a rotary-wing unmanned aerial system (RUAS) that monitors the pollutants and minimizes their concentration in the atmosphere. This RUAS could be well suited for implementation in cities such as New Delhi and Ghaziabad, where air pollution is a major concern. This RUAV’s well-thought-out design and use would be good for the environment also a step forward in the technology of UASs. Therefore, an advanced approach in design as well as innovative computational composite materials development based on structural analysis of this RUAS has been made. The major components involved in this comprehensive investigation are the fuselage, main rotor and tail rotor of RUAS. The aerodynamic parameters on RUAS have been estimated through the advanced technique adopted computational fluid dynamics approach using ANSYS Fluent 17.2. The finite element analysis (FEA) of the RUAS imposed under two different approaches enforced on lightweight composite materials has been estimated through ANSYS Structural 17.2. Firstly, the advanced computational platform for the development of composite materials has been created through the ANSYS Composite Preprocessor tool 17.2, wherein computational moldings of the fuselages of RUAV are framed. The computational moldings are greatly supported and so the conventional polymer matrix composites, metal matrix based composites, and advanced hybrid composites are well prepared. A ll of these uniquely framed materials have undergone computational structural investigations, and the material suitable for RUAVs has thus been selected. The computational tests are validated with advanced experimental outcomes, which furthermore enhanced the reliability of this proposed work. Additionally, the main rotor and entire RUAV are also computationally investigated under aerodynamic loading conditions through fluid structure interaction (FSI) approach. At last, the suitable lightweight material for all the parts of RUAS is shortlisted through innovative integrated computational engineering analyses.
A review on BCC-structured high-entropy alloys for hydrogen storage
Authors: Kong Lingjie , Cheng Bo , Wan Di , Xue Yunfei
Published: January 2023

Recently, high entropy alloys (HEAs) with body-centred cubic (BCC) single phase structures have attracted wide attention in many fields including hydrogen storage, due to their unique structural characteristics and excellent performance. Its novel design concept provides more possibilities for the investigation of advanced hydrogen storage materials, in which several remarkable research works have been published, providing opportunities for the design of hydrogen storage materials with unprecedented properties. In this review, we combed through the definition and criteria of high entropy alloys, and summarized the current research status of body-centred cubic-structured high entropy alloys for hydrogen storage from multiple perspectives of composition designs, synthesis processes, and hydrogen storage properties. Moreover, the possible application scenarios and future research directions are analysed.
SARS-CoV-2 epidemiology, antibody dynamics, and neutralisation capacity in Irish healthcare workers in the era of booster COVID-19 vaccinations
Authors: McGrath Jonathan , Kenny Claire , Nielsen Charlotte Salgaard , Domegan Lisa , Walsh Cathal , Rooney Peadar , Walsh Shane , Conlon Niall , Brady Gareth , Ibrahim Aya , Dunne Jean , McCormack William , Corcoran Niamh , Allen Niamh , Fleming Catherine , Bergin Colm
Published: January 2023

Background

The PRECISE Study, a multi-phase cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers (HCW) investigated: (1) risk factors for SARS-CoV-2 seropositivity, (2) the durability of antibody responses in a highly vaccinated HCW cohort, and (3) the neutralisation capacity of detected antibodies, prior to booster COVID-19 vaccination.

Materials and methods

Serology samples were collected across two hospital sites in November 2021 and analysed using the Roche Elecsys Anti-SARS-CoV-2/Elecsys-S Anti-SARS-CoV-2 assays to detect anti-nucleocapsid (N) and anti-spike (S) antibodies respectively. Paired serology results from prior study phases were used to analyse changes in individual HCW serostatus over time. Risk-factors for SARS-CoV-2 infection were assessed for demographic and work-related factors. Antibody neutralisation capacity was assessed in a subset of samples via an in vitro ACE2 binding enzyme-linked immunosorbent assay.

Results

2,344 HCW samples were analysed. Median age was 43 years (IQR 33–50) with 80.5% (n = 1,886) female participants. Irish (78.9%, n = 1,850) and Asian (12.3%, n = 288) were the most commonly reported ethnicities. Nursing/midwifery (39.3%, n = 922) was the most common job role. 97.7% of participants were fully vaccinated, with Pfizer (81.1%, n = 1,902) and AstraZeneca (16.1%, n = 377) the most common vaccines received. Seroprevalence for anti-SARS-CoV-2 antibodies indicating prior infection was 23.4%, of these 33.6% represented previously undiagnosed infections. All vaccinated participants demonstrated positive anti-S antibodies and in those with paired serology, no individual demonstrated loss of previously positive anti-S status below assay threshold for positivity. Interval loss of anti-N antibody positivity was demonstrated in 8.8% of previously positive participants with paired results. Risk factors for SARS-CoV-2 seropositivity suggestive of previous infection included age 18–29 years (aRR 1.50, 95% CI 1.19–1.90, p < 0.001), India as country of birth (aRR 1.35, 95% CI 1.01–1.73, p = 0.036), lower education level (aRR 1.35, 95% CI 1.11–1.66, p = 0.004) and HCA job role (aRR 2.12, 95% CI 1.51–2.95, p < 0.001). Antibody neutralisation varied significantly by anti-SARS-CoV-2 antibody status, with highest levels noted in those anti-N positive, in particular those with vaccination plus previous SARS-CoV-2 infection.

Conclusion

All vaccinated HCWs maintained anti-S positivity prior to COVID-19 booster vaccination, however anti-N positivity was more dynamic over time. Antibody neutralisation capacity was highest in participants with COVID-19 vaccination plus prior SARS-CoV-2 infection.
Association between endocrine therapy and cognitive decline in breast cancer based on propensity score matching
Authors: Yin Yulian , Jin Lan , Chu Meiling , Zhou Yue , Tu Siyuan , Cheng Yifan , Ye Meina , Wu Jingjing , Chen Hongfeng
Published: January 2023

Purpose

To study the status quo of the cognitive function of the breast cancer patients with (who went through) the endocrine therapy by the epidemiological investigation, analyze the key factor of the cognition impairment and explore the impact of the endocrine therapy time on the cognition decline after using Propensity Score Matching to balance the covariates.

Methods

In this study, the epidemiological questionnaire information was collected from 226 female breast cancer endocrine treatment patients who visited the Breast Clinic of Longhua Hospital Affiliated to Shanghai University of Chinese Medicine from November 2020 to February 2022, and the results of the overall cognitive function, the function test of each cognitive domain, the patient’s self-cognition, quality of life, and emotional status evaluation of the patients. In this study, according to the principle of random matching, the nearest matching method with a matching tolerance of 0.2 and a matching ratio of 1:2 was used for orientation score matching. After the covariant such as age, BMI, and duration of education were balanced, the effects of the duration of endocrine therapy on the overall cognitive function and the functions of each cognitive domain were analyzed.

Results

In 226 cases of female breast cancer patients (who went through) the endocrine therapy, the propensity score matching was performed, ultimately, 99 were ruled out, successful matched ones were 49 of the cognition-decline group and 78 of the standard group. With age, education time, BMI and other covariates balanced, the endocrine therapy duration was the risk factor of the cognition impairment (P < 0.05, OR = 1.296, 95% CI = 1.008−1.665), with the extension of endocrine treatment time, there was a rising risk of the cognition impairment (LLA statistic = 5.872, P < 0.05). The cognitive domain scores in the cognition-decline group were lower than the standard group (P < 0.05), but there was a difference in self-report cognition.

Conclusion

The endocrine therapy duration was the risk factor for the cognition impairment of the breast cancer patients, and with prolonged endocrine treatment, there was a rising (an increasing) risk for the cognition impairment.
Regulation of autophagy and lipid accumulation under phosphate limitation in Rhodotorula toruloides
Authors: Wang Ya-nan , Liu Fang-jie , Liu Hong-di , Zhang Yue , Jiao Xiang , Ye Ming-liang , Zhao Zong-bao Kent , Zhang Su-fang
Published: January 2023

Background

It is known that autophagy is essential for cell survival under stress conditions. Inorganic phosphate (Pi) is an essential nutrient for cell growth and Pi-limitation can trigger autophagy and lipid accumulation in oleaginous yeasts, yet protein (de)-phosphorylation and related signaling events in response to Pi limitation and the molecular basis linking Pi-limitation to autophagy and lipid accumulation remain elusive.

Results

Here, we compared the proteome and phosphoproteome of Rhodotorula toruloides CGMCC 2.1389 under Pi-limitation and Pi-repletion. In total, proteome analysis identified 3,556 proteins and the phosphoproteome analysis identified 1,649 phosphoproteins contained 5,659 phosphosites including 4,499 pSer, 978 pThr, and 182 pTyr. We found Pi-starvation-induced autophagy was regulated by autophagy-related proteins, but not the PHO pathway. When ATG9 was knocked down, the engineered strains produced significantly less lipids under Pi-limitation, suggesting that autophagy required Atg9 in R. toruloides and that was conducive to lipid accumulation.

Conclusion

Our results provide new insights into autophagy regulation under Pi-limitation and lipid accumulation in oleaginous yeast, which should be valuable to guide further mechanistic study of oleaginicity and genetic engineering for advanced lipid producing cell factory.
Aeromonas hydrophila ST251 and Aeromonas dhakensis are major emerging pathogens of striped catfish in Vietnam
Authors: Bartie Kerry L. , Ngô Thao P. H. , Bekaert Michaël , Hoang Oanh Dang Thi , Hoare Rowena , Adams Alexandra , Desbois Andrew P.
Published: January 2023

Introduction

Aeromonads are ubiquitous in aquatic environments and several species are opportunistic pathogens of fish. Disease losses caused by motile Aeromonas species, particularly Aeromonas hydrophila, can be challenging in intensive aquaculture, such as at striped catfish (Pangasianodon hypophthalmus) farms in Vietnam. Outbreaks require antibiotic treatments, but their application is undesirable due to risks posed by resistance. Vaccines are an attractive prophylactic and they must protect against the prevalent strains responsible for ongoing outbreaks.

Methods

This present study aimed to characterize A. hydrophila strains associated with mortalities in striped catfish culture in the Mekong Delta by a polyphasic genotyping approach, with a view to developing more effective vaccines.

Results

During 2013–2019, 345 presumptive Aeromonas spp. isolates were collected at farms in eight provinces. Repetitive element sequence-based PCR, multi-locus sequence typing and whole-genome sequencing revealed most of the suspected 202 A. hydrophila isolates to belong to ST656 (n = 151), which corresponds to the closely-related species Aeromonas dhakensis, with a lesser proportion belonging to ST251 (n = 51), a hypervirulent lineage (vAh) of A. hydrophila already causing concern in global aquaculture. The A. dhakensis ST656 and vAh ST251 isolates from outbreaks possessed unique gene sets compared to published A. dhakensis and vAh ST251 genomes, including antibiotic-resistance genes. The sharing of resistance determinants to sulphonamides (sul1) and trimethoprim (dfrA1) suggests similar selection pressures acting on A. dhakensis ST656 and vAh ST251 lineages. The earliest isolate (a vAh ST251 from 2013) lacked most resistance genes, suggesting relatively recent acquisition and selection, and this underscores the need to reduce antibiotics use where possible to prolong their effectiveness. A novel PCR assay was designed and validated to distinguish A. dhakensis and vAh ST251 strains.

Discussion

This present study highlights for the first time A. dhakensis, a zoonotic species that can cause fatal human infection, to be an emerging pathogen in aquaculture in Vietnam, with widespread distribution in recent outbreaks of motile Aeromonas septicaemia in striped catfish. It also confirms vAh ST251 to have been present in the Mekong Delta since at least 2013. Appropriate isolates of A. dhakensis and vAh should be included in vaccines to prevent outbreaks and reduce the threat posed by antibiotic resistance.
Observations supporting hypothetical commensalism and competition between two Campylobacter jejuni strains colonizing the broiler chicken gut
Authors: Chagneau Sophie , Gaucher Marie-Lou , Thériault William P. , Fravalo Philippe , Thibodeau Alexandre
Published: January 2023

Campylobacter jejuni is the most prevalent bacterial foodborne pathogen in humans. Given the wide genetic diversity of C. jejuni strains found in poultry production, a better understanding of the relationships between these strains within chickens could lead to better control of this pathogen on farms. In this study, 14-day old broiler chickens were inoculated with two C. jejuni strains (103 or 107 CFU of D2008b and 103 CFU of G2008b, alone or together) that were previously characterized in vitro and that showed an opposite potential to compete for gut colonization in broilers. Liver samples and ileal and cecal contents were collected and used to count total C. jejuni and to quantify the presence of each strain using a strain specific qPCR or PCR approach. Ileal tissue samples were also collected to analyze the relative expression level of tight junction proteins. While a 103 CFU inoculum of D2008b alone was not sufficient to induce intestinal colonization, this strain benefited from the G2008b colonization for its establishment in the gut and its extraintestinal spread. When the inoculum of D2008b was increased to 107 CFU – leading to its intestinal and hepatic colonization – a dominance of G2008b was measured in the gut and D2008b was found earlier in the liver for birds inoculated by both strains. In addition, a transcript level decrease of JAM2, CLDN5 and CLDN10 at 7 dpi and a transcript level increase of ZO1, JAM2, OCLN, CLDN10 were observed at 21 dpi for groups of birds having livers contaminated by C. jejuni. These discoveries suggest that C. jejuni would alter the intestinal barrier function probably to facilitate the hepatic dissemination. By in vitro co-culture assay, a growth arrest of D2008b was observed in the presence of G2008b after 48 h of culture. Based on these results, commensalism and competition seem to occur between both C. jejuni strains, and the dynamics of C. jejuni intestinal colonization and liver spread in broilers appear to be strain dependent. Further in vivo experimentations should be conducted to elucidate the mechanisms of commensalism and competition between strains in order to develop adequate on-farm control strategies.
Combined transcriptome and proteome analysis of Bcfrp1 involved in regulating the biosynthesis of abscisic acid and growth in Botrytis cinerea TB-31
Authors: Chen Dongbo , Shu Dan , Wei Zhao , Luo Di , Yang Jie , Li Zhemin , Tan Hong
Published: January 2023

Introduction

Abscisic acid (ABA) is an important sesquiterpene compound that regulates the stress resistance of plants. Botrytis cinerea can synthesize ABA via the mevalonic acid pathway. To identify the functional genes that are involved in the biosynthesis of ABA, we performed insertion mutagenesis into B. cinerea TB-31.

Methods

We obtained the ABA-reduced mutant E154 by insertion mutagenesis, and we identified the insertion site was located upstream of the gene bcfrp1 by Thermal asymmetric interlaced PCR. We performed a detailed phenotypic characterization of the bcfrp1 knockout and complementation mutants in TB-31. Furthermore, transcriptome and proteome analyses were conducted to explore how bcfrp1 affects the level of the ABA biosynthesis.

Results

The bcfrp1 gene encodes an F-box protein. The phenotypic results confirmed the positive contribution of bcfrp1 to the biosynthesis of ABA and growth. Between TB-31 and ΔBcfrp1, we obtained 4,128 and 1,073 differentially expressed genes and proteins, respectively. The impaired ABA biosynthesis in the ΔBcfrp1 mutants was primarily affected by the different levels of expression of the ABA biosynthetic gene cluster and the genes involved in the mevalonic acid pathway. In addition, we further characterized the differentially expressed genes and proteins that participated in the growth, secondary metabolism, and signal transduction in B. cinerea based on the transcriptome and proteome data.

Discussion

This research based on the transcriptome and proteome analyses to display the changes after the deletion of bcfrp1 in B. cinerea TB-31, will help us to explore the molecular mechanism of ABA biosynthesis in B. cinerea.
Dynamics of community-acquired meningitis syndrome outbreaks in southern France
Authors: Morsli Madjid , Salipante Florian , Kerharo Quentin , Boudet Agathe , Stephan Robin , Dunyach-Remy Catherine , Zandotti Christine , Lavigne Jean-Philippe , Drancourt Michel
Published: January 2023

In southern France, cases of community-acquired meningitis syndrome (CAM) are typically clustered as outbreaks with determinants which remain unknown. This 61-month retrospective investigation in Nîmes and Marseille university hospital laboratories, yielded 2,209/20,779 (10.63%) documented CAM cases caused by 62 different micro-organisms, represented by seasonal viral etiologies (78.8%), including Enterovirus, Herpes Simplex Virus (HSV), and Varicella-Zoster Virus (VZV; 1,620/2,209 = 73.4%). Multi correspondence analysis revealed an association of infection with age and sex, with the risk of infection being relatively higher in young men, as confirmed by Fisher’s exact test (p < 10−3). Bacterial meningitis accounted for 20% of cases, mostly caused by Streptococcus pneumoniae (27.4% of cases), Neisseria meningitidis (12.5%), and Haemophilus influenzae (9.5%) with bacteria/virus coinfection (0.9%), and only six cases of documented fungal meningitis. In total, 62.6% of cases, of which 88.7% were undocumented, arose from 10 outbreaks. 33.2% of undocumented cases were aged >60 years compared to 19.2% of documented cases (p < 0.001), and viral infection was more common in the summer (87.5%) compared to other seasons (72.3%; p < 0.001). Outbreaks most often started in Nîmes and moved eastward toward Marseille at a speed of ~9 km/day, and these dynamics significantly correlated with atmospheric temperature, especially during summer outbreaks. In particular, the incidence of Enterovirus-driven outbreaks correlated with temperature, revealing correlation coefficients of 0.64 in Nîmes and 0.72 in Marseille, and its occurrence in Marseille lagged that in Nîmes by 1–2 weeks. Tracing the dynamics of CAM outbreak during this retrospective investigation in southern France yielded a speed of displacement that correlated with the variation in temperature between both cities, and these results provide clues for the next occurrence of undocumented outbreaks.
Method for estimating disease risk from microbiome data using structural equation modeling
Authors: Tokuno Hidetaka , Itoga Tatsuya , Kasuga Jumpei , Okuma Kana , Hasuko Kazumi , Masuyama Hiroaki , Benno Yoshimi
Published: January 2023

The relationship between the human gut microbiota and disease is of increasing scientific interest. Previous investigations have focused on the differences in intestinal bacterial abundance between control and affected groups to identify disease biomarkers. However, different types of intestinal bacteria may have interacting effects and thus be considered biomarker complexes for disease. To investigate this, we aimed to identify a new kind of biomarker for atopic dermatitis using structural equation modeling (SEM). The biomarkers identified were latent variables, which are complex and derived from the abundance data for bacterial marker candidates. Groups of females and males classified as healthy participants [normal control (NC) (female: 321 participants, male: 99 participants)], and patients afflicted with atopic dermatitis only [AS (female: 45 participants, male: 13 participants)], with atopic dermatitis and other diseases [AM (female: 75 participants, male: 34 participants)], and with other diseases but without atopic dermatitis [OD (female: 1,669 participants, male: 866 participants)] were used in this investigation. The candidate bacterial markers were identified by comparing the intestinal microbial community compositions between the NC and AS groups. In females, two latent variables (lv) were identified; for lv1, the associated components (bacterial genera) were Alistipes, Butyricimonas, and Coprobacter, while for lv2, the associated components were Agathobacter, Fusicatenibacter, and Streptococcus. There was a significant difference in the lv2 scores between the groups with atopic dermatitis (AS, AM) and those without (NC, OD), and the genera identified for lv2 are associated with the suppression of inflammatory responses in the body. A logistic regression model to estimate the probability of atopic dermatitis morbidity with lv2 as an explanatory variable had an area under the curve (AUC) score of 0.66 when assessed using receiver operating characteristic (ROC) analysis, and this was higher than that using other logistic regression models. The results indicate that the latent variables, especially lv2, could represent the effects of atopic dermatitis on the intestinal microbiome in females. The latent variables in the SEM could thus be utilized as a new type of biomarker. The advantages identified for the SEM are as follows: (1) it enables the extraction of more sophisticated information when compared with models focused on individual bacteria and (2) it can improve the accuracy of the latent variables used as biomarkers, as the SEM can be expanded.
The bidirectional relationship between periodontal disease and pregnancy via the interaction of oral microorganisms, hormone and immune response
Authors: Wen Xingyue , Fu Xiangqing , Zhao Chongjun , Yang Lei , Huang Ruijie
Published: January 2023

Periodontal disease has been suggested to be linked to adverse pregnancy outcomes such as preterm birth, low birth weight, and preeclampsia. Adverse pregnancy outcomes are a significant public health issue with important clinical and societal repercussions. This article systematically reviews the available epidemiological studies involving the relationship between periodontal disease and adverse pregnancy outcomes over the past 15 years, and finds a weak but independent association between adverse pregnancy outcomes and periodontal disease. The bidirectional association and the potential mechanisms are then explored, focusing on three possible mechanisms: inflammatory reaction, oral microorganisms and immune response. Specifically, elevated systemic inflammation and increased periodontal pathogens with their toxic products, along with a relatively suppressed immune system may lead to the disruption of homeostasis within fetal-placental unit and thus induce adverse pregnancy outcomes. This review also explains the possible mechanisms around why women are more susceptible to periodontal disease. In conclusion, pregnant women are more likely to develop periodontal disease due to hormonal changes, and periodontal disease has also been suspected to increase the incidence of adverse pregnancy outcomes. Therefore, in order to lessen the risk of adverse pregnancy outcomes, both obstetricians and dentists should pay attention to the development of periodontal diseases among women during pregnancy.