bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal prediction and possible causes of sudden losses of sea-ice in the Weddell Sea in recent years based on potential oceanic and atmospheric factors
Authors: Zhao Hui-Jun , Xiao Dong , Bian Lin-Gen , Wu Wei , Yang Hai-Wei , Chen Qi , Liang Tian , Sun Lan-Dong
Published: February 2023

The seasonal prediction of sea-ice concentration (SIC), especially sudden loss events, is always challenging. Weddell Sea SIC experienced two unprecedented decline events, falling from 2.21% in the austral winter of 2015 to 0.02% in the austral summer of 2016 and then falling to −2.32% in the austral spring of 2017. This study proposes several statistical prediction models for Weddell Sea SIC and performs them for a period that includes the sudden decline events. We identified six potential oceanic and atmospheric factors at different leading times that relate to the variability of the Weddell Sea SIC, including the Pacific Decadal Oscillation (PDO), Atlantic Multidecadal Oscillation (AMO), Niño12 sea surface temperature (SST), Southeastern Indian Ocean (SEIO) SST, Antarctic sea level pressure (SLP), and Weddell Sea surface air temperature (SAT). Multiple linear regression models were employed to establish equations to simulate the variation of Weddell Sea SIC under three groups of climate factors for 1979–2012. These models could effectively reproduce the low-frequency variation of SIC in the Weddell Sea during the simulation period and the high-frequency values through two kinds of error-correction methods developed in this study. After applying these error correction methods, the correlation coefficients (absolute errors) of these models were enhanced (decreased) during the simulation period. In the prediction period of 2013–2018, the corrected models generally predicted well the sudden losses of Weddell Sea SIC. The possible primary factors influencing these sudden losses were the PDO, Niño12 SST, Southern Annular Mode (SAM), and SAT during 2015–2016 and the AMO, PDO, Niño12 SST, SAM, and SAT during 2016–2017.
Analytical validation and implementation of a pan cancer next-generation sequencing panel, CANSeqTMKids for molecular profiling of childhood malignancies
Authors: Schilter Kala F. , Smith Brandon A. , Nie Qian , Stoll Kathryn , Felix Juan C. , Jarzembowski Jason A. , Reddi Honey V.
Published: February 2023

Next-Generation Sequencing (NGS) allows rapid analysis of multiple genes for the detection of clinically actionable variants. This study reports the analytical validation of a targeted pan cancer NGS panel CANSeqTMKids for molecular profiling of childhood malignancies. Analytical validation included DNA and RNA extracted from de-identified clinical specimens including formalin fixed paraffin embedded (FFPE) tissue, bone marrow and whole blood as well as commercially available reference materials. The DNA component of the panel evaluates 130 genes for the detection of single nucleotide variants (SNVs), Insertion and Deletions (INDELs), and 91 genes for fusion variants associated with childhood malignancies. Conditions were optimized to use as low as 20% neoplastic content with 5 ng of nucleic acid input. Evaluation of the data determined greater than 99% accuracy, sensitivity, repeatability, and reproducibility. The limit of detection was established to be 5% allele fraction for SNVs and INDELs, 5 copies for gene amplifications and 1,100 reads for gene fusions. Assay efficiency was improved by automation of library preparation. In conclusion, the CANSeqTMKids allows for the comprehensive molecular profiling of childhood malignancies from different specimen sources with high quality and fast turnaround time.
Inbreeding evaluation using microsatellite confirmed inbreeding depression in growth in the Fenneropenaeus chinensis natural population
Authors: Lyu Ding , Sun Song , Shan Xiujuan , Wang Weiji
Published: February 2023

Understanding inbreeding depressions (IBDs), the effect on the phenotypic performance of inbreeding, is of major importance for evolution and conservation genetics. Inbreeding depressions in aquatic animals were well documented in a domestic or captive population, while there is less evidence of inbreeding depression in natural populations. Chinese shrimp, Fenneropenaeus chinensis, is an important species in both aquaculture and fishery activities in China. To investigate inbreeding depression in natural populations, four Fenneropenaeus chinensis natural populations (Huanghua, Qinhuangdao, Qingdao, and Haiyang) were collected from the Bohai and Yellow seas. Microsatellite markers were used to evaluate individual inbreeding coefficients (F) of all samples. Furthermore, the effects of inbreeding on growth traits were investigated. The results showed marker-based F was continuous and ranged from 0 to 0.585, with an average of 0.191 ± 0.127, and there was no significant difference among the average F of the four populations. Regression analysis using the four populations showed inbreeding had a very significant (p < 0.01) effect on body weight. When analyzing a single population, regression coefficients were also all negative and those in Huanghua and in Qingdao were significant at the level of p < 0.05 and < 0.01, respectively. Inbreeding depressions, expressed as the percent change in body weight per 10% increase in F, were 2.75% in Huanghua, 2.22% in Qingdao, and 3.69% in all samples. This study provided a piece of rare evidence of inbreeding depression in natural populations and also guidance toward the conservation of wild Fenneropenaeus chinensis resources.
Prognostic roles of a novel basement membranes-related gene signature in lung adenocarcinoma
Authors: Zhu Xingzhuang , Liu Xiaoyan , Qiu Xiaowen , Niu Zihao , Dong Wei , Song Yipeng
Published: February 2023

Background: The basement membranes (BMs) are involved in tumor progression, while few comprehensive analyses to date are performed on the role of BM-related gene signatures in lung adenocarcinoma (LUAD). Thus, we aimed to develop a novel prognostic model in LUAD based on BMs-related gene profiling.

Methods: The LUAD BMs-related gene profiling and corresponding clinicopathological data were obtained from the basement membrane BASE, The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) databases. The Cox regression and least absolute shrinkage and selection operator (LASSO) methods were used to construct a BMs-based risk signature. The concordance index (C-index), receiver operating characteristic (ROC), and calibration curves were generated to evaluate the nomogram. The GSE72094 dataset was used to validate prediction of the signature. The differences in functional enrichment, immune infiltration, and drug sensitivity analyses were compared based on risk score.

Results: In TCGA training cohort, 10 BMs-related genes were found, (e.g., ACAN, ADAMTS15, ADAMTS8, BCAN, etc). The signal signature based on these 10 genes was categorized into high- and low-risk groups regarding survival differences (p < 0.001). Multivariable analysis showed that the signature of combined 10 BMs-related genes was an independent prognostic predictor. Such a prognostic value of BMs-based signature in validation cohort of the GSE72094 were further verified. The GEO verification, C-index, and ROC curve showed that the nomogram had accurate prediction performance. The functional analysis suggested that BMs were mainly enriched in extracellular matrix-receptor (ECM-receptor) interaction. Moreover, the BMs-based model was correlated with immune checkpoint.

Conclusion: This study identified BMs-based risk signature genes and demonstrated their ability to predict prognosis and guide personalized treatment of patients with LUAD.
COVID-19 vaccine uptake, hesitancy and clinical effects on patients with Takayasu’s arteritis: A web-based questionnaire survey from a large cohort
Authors: Kong Xiufang , Dai Xiaojuan , Ma Lingying , Wang Jinghua , Sun Ying , Jiang Lindi
Published: February 2023

Objective

This study aimed to investigate the Coronavirus disease 2019 (COVID-19) vaccination rate, reasons for vaccine hesitancy and clinical effects on patients with Takayasu’s arteritis (TAK).

Methods

A web-based survey was administered to a TAK cohort established by the Department of Rheumatology, Zhongshan Hospital through WeChat in April, 2022. Responses from a total of 302 patients were received. The Sinovac or Sinopharm inactivated vaccination rate, side effects, and vaccine hesitancy reasons were analyzed. In addition, disease flare, new disease onset, and changes of immune-related parameters after vaccination were analyzed in vaccinated patients.

Results

Among 302 patients, 93 (30.79%) received the inactivated COVID-19 vaccination. Among the 209 unvaccinated patients, the most common reason for hesitancy were concern about side effects (136, 65.07%). Vaccinated patients had a longer disease duration (p = 0.08) and lower use of biologic agents (p < 0.001); 16 (17.20%) of the 93 vaccinated patients developed side effects, and most of them were mild; 8 (8.60%) developed disease flares or new-onset disease 12-128 days post-vaccination and 2 (2.15%) developed serious adverse effects (vision defect and cranial infarction). Immune-related parameters of 17 patients indicated decreases in IgA and IgM after vaccination (p < 0.05). Eighteen (19.35%) of the 93 vaccinated patients were diagnosed post-vaccination.These patients had a significantly higher percentage of CD19+ B cells at disease onset (p < 0.05) than the unvaccinated patients diagnosed at the same time.

Conclusion

The vaccination rate was low in TAK, which was mainly caused by concerns about negative effects of vaccination on their disease. An acceptable safety profile was observed in vaccinated patients. The risk of disease flare associated with COVID-19 vaccination warrants further investigation.
Role of immune cell infiltration and small molecule drugs in adhesive capsulitis: Novel exploration based on bioinformatics analyses
Authors: Liu Hailong , Yu Baoxi , Deng Zengfa , Zhao Hang , Zeng Anyu , Li Ruiyun , Fu Ming
Published: February 2023

Background

Adhesive capsulitis (AC) is a type of arthritis that causes shoulder joint pain, stiffness, and limited mobility. The pathogenesis of AC is still controversial. This study aims to explore the role of immune related factors in the occurrence and development of AC.

Methods

The AC dataset was downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed immune-related genes (DEIRGs) were obtained based on R package “DESeq2” and Immport database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore the functional correlation of DEIRGs. MCC method and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the hub genes. The immune cell infiltration in shoulder joint capsule between AC and control was evaluated by CIBERSORTx, and the relationship between hub genes and infiltrating immune cells was analyzed by Spearman’s rank correlation. Finally, potential small molecule drugs for AC were screened by the Connectivity Map database (CMap) and further verified by molecular docking.

Results

A total of 137 DEIRGs and eight significantly different types of infiltrating immune cells (M0 macrophages, M1 macrophages, regulatory T cells, Tfh cells, monocytes, activated NK cells, memory resting CD4+T cells and resting dendritic cells) were screened between AC and control tissues. MMP9, FOS, SOCS3, and EGF were identified as potential targets for AC. MMP9 was negatively correlated with memory resting CD4+T cells and activated NK cells, but positively correlated with M0 macrophages. SOCS3 was positively correlated with M1 macrophages. FOS was positively correlated with M1 macrophages. EGF was positively correlated with monocytes. Additionally, dactolisib (ranked first) was identified as a potential small-molecule drug for the targeted therapy of AC.

Conclusions

This is the first study on immune cell infiltration analysis in AC, and these findings may provide a new idea for the diagnosis and treatment of AC.
Urinary exosome tsRNAs as novel markers for diagnosis and prediction of lupus nephritis
Authors: Chen Shanshan , Zhang Xiaoshan , Meng Kaifang , Sun Yifan , Shu Ruilu , Han Yan , Feng Qingxiu , Li Zhiyang , Yang Ping , Liang Jun
Published: February 2023

Objective

Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Early identification of renal disease in SLE is important. Renal biopsy is currently recognized as the gold standard for diagnosing LN, however, it is invasive and inconvenient for dynamic monitoring. Urine has been considered more promising and valuable than blood in identifying inflamed kidney tissue. Here, we determine whether the signatures of tRNA-derived small noncoding RNA (tsRNA) in urinary exosomes can serve as novel biomarkers for the diagnosis of LN.

Methods

tsRNA sequencing was performed in exosome extracted from pooled urine of 20 LN patients and 20 SLE without LN, and the top 10 upregulated tsRNAs were screened as candidate markers of LN. The candidate urinary exosomal tsRNAs were primarily elected by TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) in 40 samples (20 LN and 20 SLE without LN) in the training phase. In the validation phase, selected tsRNAs from the training phase were further confirmed in a larger cohort (54 LN patients and 39 SLE without LN). Receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic efficacy.

Results

Upregulated levels of tRF3-Ile-AAT-1 and tiRNA5-Lys-CTT-1 in the urinary exosomes were observed in LN compared with SLE without LN (P < 0.0001 and P < 0.001) and healthy controls (P < 0.01 and P < 0.01), with the area under the curve (AUC) of 0.777 (95% CI: 0.681-0.874, sensitivity 79.63%, specificity 66.69%) and 0.715 (95% CI: 0.610-0.820, sensitivity 66.96%, specificity 76.92%) for discriminating LN from SLE without LN patients. SLE patients with mild activity and moderate to severe activity had higher levels of urinary exosome derived tRF3-Ile AAT-1 (P = 0.035 and P < 0.001) and tiRNA5-Lys-CTT-1 (P = 0.021 and P < 0.001) compared with patients with no activity. Moreover, bioinformatics analysis revealed that both of the tsRNAs regulate the immune process by modulating metabolism and signal pathway.

Conclusion

In this study, we demonstrated that urinary exosome tsRNAs can be served as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.
Advances in mechanism and regulation of PANoptosis: Prospects in disease treatment
Authors: Zhu Peng , Ke Zhuo-Ran , Chen Jing-Xian , Li Shi-Jin , Ma Tian-Liang , Fan Xiao-Lei
Published: February 2023

PANoptosis, a new research hotspot at the moment, is a cell death pattern in which pyroptosis, apoptosis, and necroptosis all occur in the same cell population. In essence, PANoptosis is a highly coordinated and dynamically balanced programmed inflammatory cell death pathway that combines the main features of pyroptosis, apoptosis, and necroptosis. Many variables, such as infection, injury, or self-defect, may be involved in the occurrence of PANoptosis, with the assembly and activation of the PANoptosome being the most critical. PANoptosis has been linked to the development of multiple systemic diseases in the human body, including infectious diseases, cancer, neurodegenerative diseases, and inflammatory diseases. Therefore, it is necessary to clarify the process of occurrence, the regulatory mechanism of PANoptosis, and its relation to diseases. In this paper, we summarized the differences and relations between PANoptosis and the three types of programmed cell death, and emphatically expounded molecular mechanism and regulatory patterns of PANoptosis, with the expectation of facilitating the application of PANoptosis regulation in disease treatment.
Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects
Authors: Couvidou Adèle , Rojas-Jiménez Gabriel , Dupuis Arnaud , Maître Blandine
Published: February 2023

Patients with hematological disorders and severe thrombocytopenia require extensive and iterative platelet transfusion support. In these patients, platelet transfusion refractoriness represents a serious adverse transfusion event with major outcomes for patient care. Recipient alloantibodies against the donor HLA Class I antigens expressed at the cell surface of platelets result in a rapid removal of transfused platelets from the circulation and thus, therapeutic and prophylactic transfusion failure leading to a major bleeding risk. In this case, the only way to support the patient relies on the selection of HLA Class I compatible platelets, an approach restricted by the limited number of HLA-typed donors available and the difficulty of meeting the demand in an emergency. However, not all patients with anti-HLA Class I antibodies develop refractoriness to platelet transfusions, raising the question of the intrinsic characteristics of the antibodies and the immune-mediated mechanisms of platelet clearance associated with a refractory state. In this review, we examine the current challenges in platelet transfusion refractoriness and detail the key features of the antibodies involved that should be considered. Finally, we also provide an overview of future therapeutic strategies.
Immunoregulation by antigen-presenting cells in human intestinal lamina propria
Authors: Ogino Takayuki , Takeda Kiyoshi
Published: February 2023

Antigen-presenting cells, including macrophages and dendritic cells, are a type of innate immune cells that can induce the differentiation of T cells and activate the adaptive immune response. In recent years, diverse subsets of macrophages and dendritic cells have been identified in the intestinal lamina propria of mice and humans. These subsets contribute to the maintenance of intestinal tissue homeostasis by regulating the adaptive immune system and epithelial barrier function through interaction with intestinal bacteria. Further investigation of the roles of antigen-presenting cells localized in the intestinal tract may lead to the elucidation of inflammatory bowel disease pathology and the development of novel treatment approaches.
Regionally disparate ecological responses to microplastic slowing of faecal pellets yields coherent carbon cycle response
Authors: Kvale Karin , Hunt Claire , James Aidan , Koeve Wolfgang
Published: February 2023

Microplastic is a ubiquitous marine pollutant whose small dimensions make it biologically available to phytoplankton and zooplankton. These organisms are crucial as the basis of the marine food web and for the export of organic material in the form of faecal pellets from the surface to deeper in the water column, forming a long-term carbon sink. Previous laboratory studies have demonstrated empirically that ingestion of low density microplastics reduces the sinking rates of zooplankton faecal pellets. This study uses a complex earth system model to analyse this effect and assess its wider impacts in a changing climate. Results show that the slowing of faecal pellet sinking stimulates changes to ecosystems regionally and reduces ocean carbon uptake by about 4.4 Pg C between the years 1950-2100, 0.24% of anthropogenic emissions over this time. However, perturbation of organic particle fluxes is significant, especially in gyres, and of the order of climate change impacts over the same time period. We calculate that plastics carbon has a 3 orders of magnitude greater impact on marine ecosystems than atmospheric carbon over our centennial timescale. Large uncertainties in model parameters and simplistic model structure suggest our results should be interpreted as motivation to further investigate parameter estimation, calcification responses to pollution, and the combined effects of multiple impact mechanisms on ecosystems.
Depth and temperature profiles reflect individual differences in the daytime diving behaviours of pelagic thresher sharks
Authors: Oliver Simon P. , Grothues Thomas M. , Mayo Zoe J. , Williams Amie L. , Silvosa Medel , Cases Gary
Published: February 2023

We used acoustic telemetry to investigate the roles of depth and temperature in the daytime foraging behaviours of 13 tagged pelagic thresher sharks by monitoring their fine scale vertical movements in the Philippines. Cumulatively, pelagic thresher shark dives traversed the entire water column where they encountered temperatures that ranged from 33°C at the surface to 12°C at 250 m depths throughout the day, but the movements of individuals varied in the extent of both their deep and shallow water limits. Dives were not synchronized to diurnal cycles, and periodicity reflected cycles of similar dives, the dives themselves, deviations, cruising, and individuality. Pelagic thresher shark movements between the warm surface layer and cooler waters below the thermocline (155 – 175 m) may reflect a common Alopiid strategy that balances maintaining tolerable ambient water temperatures with opportunities to search for and forage on spatially patchy distributions of prey.
Impact of the COVID-19 pandemic on imaging case volumes in King Abdullah University Hospitals (KAUH)
Authors: Gharaibeh Maha , El-Obeid Eyhab , Khasawneh Ruba , Karrar Musaab , Salman Mohamed , Farah Ahmad , Ahmmed Sammah , Al-Omari Mamoon , Elheis Mwaffaq , Abualigah Laith
Published: February 2023

Objective

COVID-19 has an increased burden on the delivery of services because the measures taken by the governments forced hospitals to cancel most of their elective procedures and led to the shutting down of outpatient clinics. This study aimed to evaluate the impact COVID-19 pandemic on the volume of radiology exams based on patient service locations and imaging modality in the North of Jordan.

Methods

The imaging case volumes that were performed at the King Abdullah University Hospital (KAUH), Jordan, from 1 January 2020 to 8 May 2020, were retrospectively collected and compared to those from 1 January 2019 to 28 May 2019, to determine the impact of the pandemic of COVID-19 on the volume of radiological examinations. The 2020 study period was chosen to cover the peak of COVID-19 cases and to record the effects on imaging case volumes.

Results

A total of 46,194 imaging case volumes were performed at our tertiary center in 2020 compared to 65,441 imaging cases in 2019. Overall, the imaging case volume in 2020 decreased by 29.4% relative to the same period in 2019. The imaging case volumes decreased for all imaging modalities relative to 2019. The number of nuclear images showed the highest decline (41.0%) in 2020, followed by the number of ultrasounds (33.2%). Interventional radiology was the least affected imaging modality by this decline, with about a 22.9% decline.

Conclusion

The number of imaging case volumes decreased significantly during the COVID-19 pandemic and its associated lockdown. The outpatient service location was the most affected by this decline. Effective strategies must be adopted to avoid the aforementioned effect on the healthcare system in future pandemics.
The effect comparison of ILM flap and traditional ILM peeling in iMH
Authors: Chen Yiqi , Xu Yijun , Ye Xin , Yu Jiafeng , Wang Chenxi , Zhang Zhengxi , Mao Jianbo , Shen Lijun
Published: February 2023

Purpose

To compare the changes in anatomical structure and visual function after idiopathic macular hole (iMH) treatment with internal limiting membrane (ILM) peeling and inverted ILM flap and determine the value of the inverted ILM flap for the treatment of iMH.

Methods

Forty-nine patients with iMH (49 eyes) were included in this study and followed up for 1 year (12 months) after treatment with inverted ILM flap and ILM peeling respectively. The main foveal parameters assessed included the preoperative minimum diameter (MD), intraoperative residual fragments, and postoperative ELM reconstruction. Visual function was assessed using best-corrected visual acuity.

Results

The hole closure rate was 100% for 49 patients; 15 patients were treated with the inverted ILM flap, and 34 patients underwent ILM peeling. There were no differences between the postoperative best-corrected visual acuities and the rates of ELM reconstruction for the flap and peeling groups with different MDs. In the flap group, ELM reconstruction was associated with the preoperative MD, presence of an ILM flap, and hyperreflective changes in the inner retina 1 month after surgery. In the peeling group, ELM reconstruction was associated with the preoperative MD, intraoperative residual fragments at the hole edge, and hyperreflective changes in the inner retina.

Conclusion

The inverted ILM flap and the ILM Peeling were both able to obtain high closure rate. However, the inverted ILM flap showed no obvious advantages related to anatomical morphology and visual function over ILM peeling.
The DETAIL questionnaire is a useful and effective tool to assess spondyloarthritis in patients with inflammatory bowel disease
Authors: Keskin Onur , Farisogullari Bayram , Yardimci Gozde Kubra , Gurbuz Burcu , Kole Melike , Parlak Erkan , Karadag Omer , Kav Taylan , Kalyoncu Umut
Published: February 2023

Introduction

This study aimed to determine the effectiveness of adding a simple questionnaire related to musculoskeletal system to routine outpatient examination to detect undiagnosed axial and peripheral arthropathy in patients with inflammatory bowel disease (IBD).

Materials and methods

A musculoskeletal symptom questionnaire was given to all patients with IBD during their follow-up examinations between January 2020 and November 2021. The DETAIL questionnaire consisting of six questions about the musculoskeletal system was administered by asking the patients with IBD. All patients who answered yes to at least one of these questions were directed to specialists in the rheumatology department to undergo a detailed examination. The patients who were diagnosed with rheumatological disease after further investigation were recorded. Patients with a known diagnosis of rheumatological disease were excluded from the study.

Findings

There were 333 patients with IBD included in the study. Of these patients, 41 (12.3%) had a previously diagnosed rheumatological disease and were excluded from the evaluation. Of the remaining 292 patients (147 with ulcerative colitis, 139 with Crohn’s disease and six with indeterminate colitis; mean age 42 years), 67 (23%) answered yes to at least one of the questions and were referred to a rheumatology consultation. Rheumatological examination was completed in 52 patients. As a result of the evaluations, 24 patients (8.2%) were diagnosed with enteropathic arthritis (14 axial, 9 peripheral, and 1 axial plus peripheral). Patients with newly diagnosed enteropathy had a lower median disease age than patients without enteropathy.

Conclusion

The DETAIL questionnaire is an effective and easy tool for identifying missed cases of SpA in patients with IBD.
Responses of carbapenemase-producing and non-producing carbapenem-resistant Pseudomonas aeruginosa strains to meropenem revealed by quantitative tandem mass spectrometry proteomics
Authors: Salvà-Serra Francisco , Jaén-Luchoro Daniel , Marathe Nachiket P. , Adlerberth Ingegerd , Moore Edward R. B. , Karlsson Roger
Published: February 2023

Pseudomonas aeruginosa is an opportunistic pathogen with increasing incidence of multidrug-resistant strains, including resistance to last-resort antibiotics, such as carbapenems. Resistances are often due to complex interplays of natural and acquired resistance mechanisms that are enhanced by its large regulatory network. This study describes the proteomic responses of two carbapenem-resistant P. aeruginosa strains of high-risk clones ST235 and ST395 to subminimal inhibitory concentrations (sub-MICs) of meropenem by identifying differentially regulated proteins and pathways. Strain CCUG 51971 carries a VIM-4 metallo-β-lactamase or ‘classical’ carbapenemase; strain CCUG 70744 carries no known acquired carbapenem-resistance genes and exhibits ‘non-classical’ carbapenem-resistance. Strains were cultivated with different sub-MICs of meropenem and analyzed, using quantitative shotgun proteomics based on tandem mass tag (TMT) isobaric labeling, nano-liquid chromatography tandem-mass spectrometry and complete genome sequences. Exposure of strains to sub-MICs of meropenem resulted in hundreds of differentially regulated proteins, including β-lactamases, proteins associated with transport, peptidoglycan metabolism, cell wall organization, and regulatory proteins. Strain CCUG 51971 showed upregulation of intrinsic β-lactamases and VIM-4 carbapenemase, while CCUG 70744 exhibited a combination of upregulated intrinsic β-lactamases, efflux pumps, penicillin-binding proteins and downregulation of porins. All components of the H1 type VI secretion system were upregulated in strain CCUG 51971. Multiple metabolic pathways were affected in both strains. Sub-MICs of meropenem cause marked changes in the proteomes of carbapenem-resistant strains of P. aeruginosa exhibiting different resistance mechanisms, involving a wide range of proteins, many uncharacterized, which might play a role in the susceptibility of P. aeruginosa to meropenem.
Oral microbiota dysbiosis accelerates the development and onset of mucositis and oral ulcers
Authors: Min Ziyang , Yang Lei , Hu Yu , Huang Ruijie
Published: February 2023

With the rapid development of metagenomic high-throughput sequencing technology, more and more oral mucosal diseases have been proven to be associated with oral microbiota shifts or dysbiosis. The commensal oral microbiota can greatly influence the colonization and resistance of pathogenic microorganisms and induce primary immunity. Once dysbiosis occurs, it can lead to damage to oral mucosal epithelial defense, thus accelerating the pathological process. As common oral mucosal diseases, oral mucositis and ulcers seriously affect patients’ prognosis and quality of life. However, from the microbiota perspective, the etiologies, specific alterations of oral flora, pathogenic changes, and therapy for microbiota are still lacking in a comprehensive overview. This review makes a retrospective summary of the above problems, dialectically based on oral microecology, to provide a new perspective on oral mucosal lesions management and aims at improving patients’ quality of life.
Evaluation of IR Biotyper for carbapenem-resistant Pseudomonas aeruginosa typing and its application potential for the investigation of nosocomial infection
Authors: Hu Yanyan , Zhu Kun , Jin Dingping , Shen Weiyi , Liu Congcong , Zhou Hongwei , Zhang Rong
Published: February 2023

Pseudomonas aeruginosa is one of the most common opportunistic pathogens causing severe nosocomial infections for its patterns of multidrug resistance, particularly for carbapenems. Timely epidemiological surveillance could greatly facilitate infection control of P. aeruginosa and many deadly pathogens alike. IR Biotyper (IRBT), is a novel real-time typing tool, based on a Fourier-transform infrared (FTIR) spectroscopy system. It is critical to comprehensively establish and evaluate the feasibility of IRBT in P. aeruginosa strain typing. In the current study, we first established standards and schemes for its routine laboratory application, and we found that Mueller–Hinton agar plates give better discriminatory power than blood agar plates. Data showed that the cut-off value of 0.15 with an additional 0.025 range was optimal. Secondly, 27 clinically isolated carbapenem-resistant P. aeruginosa (CRPA) strains collected from October 2010 to September 2011 were evaluated for typing effectiveness by comparing IRBT to the other commonly used typing methods, such as multi-locus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS)-based typing. When using WGS-based typing as the reference method, the typing method of FTIR spectroscopy (AR = 0.757, SID = 0.749) could better cluster P. aeruginosa strains than MLST and in silico serotyping (AR = 0.544, SID = 0.470). Though PFGE showed the highest discriminatory power, low concordance was observed between PFGE and the other methods. Above all, this study demonstrates the utility of the IRBT as a quick, low-cost, real-time typing tool for the detection of CRPA strains.
Amoxicillin-docosahexaenoic acid encapsulated chitosan-alginate nanoparticles as a delivery system with enhanced biocidal activities against Helicobacter pylori and improved ulcer healing
Authors: Khoshnood Saeed , Negahdari Babak , Kaviar Vahab Hassan , Sadeghifard Nourkhoda , Abdullah Mohd Azmuddin , El-Shazly Mohamed , Haddadi Mohammad Hossein
Published: February 2023

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat’s stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.
An adenine/thymidine-rich region is integral to RepL-mediated DNA replication
Authors: Huan Yang Wei , Brown Russell , Wang Baojun
Published: February 2023

The lytic replication of bacteriophage P1 requires RepL expression and the lytic stage origin, oriL, which is postulated to be located within repL gene sequence. The exact sequence of P1 oriL and the mechanism(s) of RepL-mediated DNA replication, however, are not fully understood. By using repL gene expression to induce DNA replication of a gfp and a rfp reporter plasmids, we demonstrated that synonymous base substitution in an adenine/thymidine-rich region of repL gene sequence, termed AT2, significantly inhibited the RepL-mediated signal amplification. Contrastingly, mutations in an IHF and two DnaA binding sites did not affect the RepL-mediated signal amplification significantly. A truncated repL sequence with the AT2 region allowed RepL-mediated signal amplification in trans therefore verifying a significant role of the AT2 region in RepL-mediated DNA replication. A combination of repL gene expression and a non-protein-coding copy of repL gene sequence (termed nc-repL) was able to amplify the output of an arsenic biosensor. Furthermore, mutation(s) at single or multiple positions within the AT2 region produced varying levels of RepL-mediated signal amplification. Overall, our results provide novel insights into the identity and location of P1 oriL as well as demonstrating the potential of using repL constructs to amplify and modulate the output of genetic biosensors.
Environmental factors contributing to the convergence of bacterial community structure during indigo reduction
Authors: Farjana Nowshin , Tu Zhihao , Furukawa Hiromitsu , Yumoto Isao
Published: February 2023

Indigo is solubilized through the reducing action of the microbiota that occurs during alkaline fermentation of composted leaves of Polygonum tinctorium L. (sukumo). However, the environmental effects on the microbiota during this treatment, as well as the mechanisms underlying the microbial succession toward stable state remain unknown. In this study, physicochemical analyses and Illumina metagenomic sequencing was used to determine the impact pretreatment conditions on the subsequent initiation of bacterial community transition and their convergence, dyeing capacity and the environmental factors critical for indigo reducing state during aging of sukumo. The initial pretreatment conditions analyzed included 60°C tap water (heat treatment: batch 1), 25°C tap water (control; batch 2), 25°C wood ash extract (high pH; batch 3) and hot wood ash extract (heat and high pH; batch 4), coupled with successive addition of wheat bran from days 5 to 194. High pH had larger impact than heat treatment on the microbiota, producing more rapid transitional changes from days 1 to 2. Although the initial bacterial community composition and dyeing intensity differed during days 2–5, the microbiota appropriately converged to facilitate indigo reduction from day 7 in all the batches, with Alkaliphilus oremalandii, Amphibacillus, Alkalicella caledoniensis, Atopostipes suicloalis and Tissierellaceae core taxa contributing to the improvement of when the dyeing intensity. This convergence is attributed to the continuous maintenance of high pH (day 1 ~) and low redox potential (day 2~), along with the introduction of wheat bran at day 5 (day 5~). PICRUSt2 predictive function profiling revealed the enrichment of phosphotransferease system (PTS) and starch and sucrose metabolism subpathways key toward indigo reduction. Seven NAD(P)-dependent oxidoreductases KEGG orthologs correlating to the dyeing intensity was also identified, with Alkalihalobacillus macyae, Alkalicella caledoniensis, and Atopostipes suicloalis contributing significantly toward the initiation of indigo reduction in batch 3. During the ripening period, the staining intensity was maintained by continuous addition of wheat bran and the successive emergence of indigo-reducing bacteria that also contributed to material circulation in the system. The above results provide insight into the interaction of microbial system and environmental factors in sukumo fermentation.
Co-inoculation of antagonistic Bacillus velezensis FH-1 and Brevundimonas diminuta NYM3 promotes rice growth by regulating the structure and nitrification function of rhizosphere microbiome
Authors: Wang Jingjing , Zhao Siqi , Xu Song , Zhao Wei , Zhang Xiaoxia , Lei Yu , Zhai Huanhuan , Huang Zhiyong
Published: February 2023

Microbial inoculation with plant growth-promoting microorganisms (PGPMs) is one of the most promising technologies to solve the current global challenges. Co-inoculants is more efficient and stable than mono-inoculants. However, the growth promoting mechanism of co-inoculants in complex soil system is still poorly understood. In this study, the effects on rice, soil and the microbiome of the mono-inoculant Bacillus velezensis FH-1 (F) and Brevundimonas diminuta NYM3 (N) and the co-inoculant FN obtained in previous works were compared. Correlation analysis and PLS-PM were used to explore the primary mechanism of different inoculants promoting rice growth. We hypothesized that inoculants promoted plant growth (i) by themselves, (ii) by improving soil nutrient availability or (iii) by regulating the rhizosphere microbiome in complex soil system. We also assumed that different inoculants had different ways of promoting plant growth. The results showed that FN significantly promoted rice growth and nitrogen absorption and slightly increased soil total nitrogen and microbial network complexity compared with F, N and the control (CK). B. velezensis FH-1 and B. diminuta NYM3 interfered with each other’s colonization in FN. FN increased the complexity of the microbial network compared to F and N. The bacterial community of FN was quite different from CK and N, while the fungal community was not significantly different from other treatments. The species and functions enriched or inhibited by FN are part of F. The correlation analysis and PLS-PM results showed that inoculants (F/N/FN) promoted the growth of rice mainly by regulating the rhizosphere microbiome rather than by themselves or by improving soil nutrient availability. Co-inoculant FN promotes rice growth specifically by enhancing microbial nitrification function through enriching related species compared with F or N. This may provide theoretical guidance for the construction and application of co-inoculants in the future.
Brewing potential of strains of the boreal wild yeast Mrakia gelida
Authors: Linnakoski Riikka , Jyske Tuula , Eerikäinen Ronja , Veteli Pyry , Cortina-Escribano Marta , Magalhães Frederico , Järvenpää Eila , Heikkilä Lotta , Hutzler Mathias , Gibson Brian
Published: February 2023

Demand for low- or non-alcoholic beers has been growing in recent years. Thus, research is increasingly focusing on non-Saccharomyces species that typically are only able to consume the simple sugars in wort, and therefore have a limited production of alcohol. In this project, new species and strains of non-conventional yeasts were sampled and identified from Finnish forest environments. From this wild yeast collection, a number of Mrakia gelida strains were selected for small-scale fermentation tests and compared with a reference strain, the low-alcohol brewing yeast Saccharomycodes ludwigii. All the M. gelida strains were able to produce beer with an average of 0.7% alcohol, similar to the control strain. One M. gelida strain showing the most promising combination of good fermentation profile and production of desirable flavor active compounds was selected for pilot-scale (40 L) fermentation. The beers produced were matured, filtered, carbonated, and bottled. The bottled beers were then directed for in-house evaluation, and further analyzed for sensory profiles. The beers produced contained 0.6% Alcohol by volume (ABV). According to the sensory analysis, the beers were comparable to those produced by S. ludwigii, and contained detectable fruit notes (banana and plum). No distinct off-flavors were noted. A comprehensive analysis of M. gelida’s resistance to temperature extremes, disinfectant, common preservatives, and antifungal agents would suggest that the strains pose little risk to either process hygiene or occupational safety.
The role of Epstein–Barr virus in nasopharyngeal carcinoma
Authors: Su Zhi Yi , Siak Pui Yan , Leong Chee-Onn , Cheah Shiau-Chuen
Published: February 2023

Nasopharyngeal carcinoma (NPC) is a metastasis-prone malignancy closely associated with the Epstein–Barr virus (EBV). Despite ubiquitous infection of EBV worldwide, NPC incidences displayed predominance in certain ethnic groups and endemic regions. The majority of NPC patients are diagnosed with advanced-stage disease, as a result of anatomical isolation and non-specific clinical manifestation. Over the decades, researchers have gained insights into the molecular mechanisms underlying NPC pathogenesis as a result of the interplay of EBV infection with several environmental and genetic factors. EBV-associated biomarkers were also used for mass population screening for the early detection of NPC. EBV and its encoded products also serve as potential targets for the development of therapeutic strategies and tumour-specific drug delivery. This review will discuss the pathogenic role of EBV in NPC and efforts in exploiting the potential of EBV-associated molecules as biomarkers and therapeutic targets. The current knowledge on the role of EBV and its associated products in NPC tumorigenesis, development and progression will offer a new outlook and potential intervention strategy against this EBV-associated malignancy.
SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge
Authors: Hosaka Yoshie , Yan Yan , Naito Toshio , Oyama Rieko , Tsuchiya Koji , Yamamoto Norio , Nojiri Shuko , Hori Satoshi , Takahashi Kazuhisa , Tabe Yoko
Published: February 2023

Background

Previous studies have shown that patients with immunosuppression tend to have longer-lasting SARS-CoV-2 infections and a number of mutations were observed during the infection period. However, these studies were, in general, conducted longitudinally. Mutation evolution among groups of patients with immunosuppression have not been well studied, especially among Asian populations.

Methods

Our study targeted a nosocomial cluster of SARS-CoV-2 infection in a Japanese medical center during Delta surge (AY.29 sublineage), involving ward nurses and inpatients. Whole-genome sequencing analyses were performed to examine mutation changes. Haplotype and minor variant analyses were furtherly performed to detect the mutations on the viral genomes in detail. In addition, sequences of the first wild-type strain hCoV-19/Wuhan/WIV04/2019 and AY.29 wild-type strain hCoV-19/Japan/TKYK15779/2021 were used as references to assess the phylogenetical development of this cluster.

Results

A total of 6 nurses and 14 inpatients were identified as a nosocomial cluster from September 14 through 28, 2021. All were Delta variant (AY.29 sublineage) positive. 92.9% of infected patients (13 out of 14) were either cancer patients and/or receiving immunosuppressive or steroid treatments. Compared to AY.29 wild type, a total of 12 mutations were found in the 20 cases. Haplotype analysis found one index group of eight cases with F274F (N) mutation and 10 other haplotypes with one to three additional mutations. Furthermore, we found that cases with more than three minor variants were all cancer patients under immunosuppressive treatments. The phylogenetical tree analysis, including 20 nosocomial cluster-associated viral genomes, the first wild-type strain and the AY.29 wild-type strain as references, indicated the mutation development of the AY.29 virus in this cluster.

Conclusion

Our study of a nosocomial SARS-CoV-2 cluster highlights mutation acquisition during transmission. More importantly, it provided new evidence emphasizing the need to further improve infection control measures to prevent nosocomial infection among immunosuppressed patients.
Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity
Authors: Morais K. L. P. , Ciccone L. , Stura E. , Alvarez-Flores M. P. , Mourier G. , Driessche M. Vanden , Sciani J. M. , Iqbal A. , Kalil S. P. , Pereira G. J. , Marques-Porto R. , Cunegundes P. , Juliano L. , Servent D. , Chudzinski-Tavassi A. M.
Published: February 2023

Amblyomin-X is a Kunitz-type FXa inhibitor identified through the transcriptome analysis of the salivary gland from Amblyomma sculptum tick. This protein consists of two domains of equivalent size, triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth, and reduction of metastasis. To study the structural properties and functional roles of the N-terminal (N-ter) and C-terminal (C-ter) domains of Amblyomin-X, we synthesized them by solid-phase peptide synthesis, solved the X-Ray crystallographic structure of the N-ter domain, confirming its Kunitz-type signature, and studied their biological properties. We show here that the C-ter domain is responsible for the uptake of Amblyomin-X by tumor cells and highlight the ability of this domain to deliver intracellular cargo by the strong enhancement of the intracellular detection of molecules with low cellular-uptake efficiency (p15) after their coupling with the C-ter domain. In contrast, the N-ter Kunitz domain of Amblyomin-X is not capable of crossing through the cell membrane but is associated with tumor cell cytotoxicity when it is microinjected into the cells or fused to TAT cell-penetrating peptide. Additionally, we identify the minimum length C-terminal domain named F2C able to enter in the SK-MEL-28 cells and induces dynein chains gene expression modulation, a molecular motor that plays a role in the uptake and intracellular trafficking of Amblyomin-X.