bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico design of an epitope-based vaccine ensemble for fasliolopsiasis
Authors: Konhar Ruchishree , Das Kanhu Charan , Nongrum Aiboklang , Samal Rohan Raj , Sarangi Shailesh Kumar , Biswal Devendra Kumar
Published: January 2025

Introduction

Fasciolopsiasis, a food-borne intestinal disease is most common in Asia and the Indian subcontinent. Pigs are the reservoir host, and fasciolopsiasis is most widespread in locations where pigs are reared and aquatic plants are widely consumed. Human infection has been most commonly documented in China, Bangladesh, Southeast Asia, and parts of India. It predominates in school-age children, and significant worm burdens are not uncommon. The causal organism is Fasciolopsis buski, a giant intestinal fluke that infects humans and causes diarrhoea, fever, ascites, and intestinal blockage. The increasing prevalence of medication resistance and the necessity for an effective vaccination make controlling these diseases challenging.

Methods

Over the last decade, we have achieved major advances in our understanding of intestinal fluke biology by in-depth interrogation and analysis of evolving F. buski omics datasets. The creation of large omics datasets for F. buski by our group has accelerated the discovery of key molecules involved in intestinal fluke biology, toxicity, and virulence that can be targeted for vaccine development. Finding successful vaccination antigen combinations from these huge number of genes/proteins in the available omics datasets is the key in combating these neglected tropical diseases. In the present study, we developed an in silico workflow to select antigens for composing a chimeric vaccine, which could be a significant technique for developing a fasciolopsiasis vaccine that prevents the parasite from causing serious harm.

Results and discussion

This chimeric vaccine can now be tested experimentally and compared to other vaccine candidates to determine its potential influence on human health. Although the results are encouraging, additional validation is needed both in vivo and in vitro. Considering the extensive genetic data available for intestinal flukes that has expanded with technological advancements, we may need to reassess our methods and suggest a more sophisticated technique in the future for identifying vaccine molecules.
Motivations regarding continuing or terminating pregnancy in women with high-risk pregnancies: a scoping review
Authors: Antunes Mónica , Galhanas Ana , Vitorino Ana Lúcia , Palma Sara , Frias Ana
Published: January 2025

Background

The decisions of women with high-risk pregnancies to continue or terminate a pregnancy are complex and influenced by various factors. This scoping review synthesises the qualitative literature on the underlying motivations influencing these decisions.

Aim

This analysis explores the underlying motivations that influence women's decisions regarding the continuation or termination of pregnancy, considering the challenges and dilemmas this population faces.

Methods

This review was conducted following the Joanna Briggs Institute's methodology. No date restrictions were applied to the search. Titles and abstracts were screened to select original studies, and cross-checking was performed to avoid case overlap. We included studies that focused on the factors influencing women's decisions to either continue or terminate pregnancies when complications arose.

Results

Eighteen studies involving women from different countries and cultural contexts were included. The review identifies four main themes driving these decisions: health considerations, religious convictions, social and political factors and ethical and moral dilemmas. Each theme interlinks to form a complex web of influences that significantly shape women's choices, illustrating how deeply personal, societal, and ethical contexts converge in these critical decisions. Significant emotional and cognitive factors, particularly hope, also play a crucial role. The findings highlight the complexity of the decision-making process and provide a deeper understanding of the personal, social, and spiritual dimensions involved.

Conclusions

Multiple factors shape the complex decisions of women with high-risk pregnancies. Understanding these motivations is crucial to providing appropriate support and counselling. This review underscores the need for healthcare professionals to be aware of the diversity of factors involved and to adopt an individualized and context-sensitive approach in their practice, guiding their future actions.
Immune regulatory genes impact the hot/cold tumor microenvironment, affecting cancer treatment and patient outcomes
Authors: Sang Mengmeng , Ge Jia , Ge Juan , Tang Gu , Wang Qiwen , Wu Jiarun , Mao Liming , Ding Xiaoling , Zhou Xiaorong
Published: January 2025

Background and aims

Immunologically hot tumors, characterized by an inflamed tumor microenvironment (TME), contrast significantly with immunologically cold tumors. The identification of these tumor immune subtypes holds clinical significance, as hot tumors may exhibit improved prognoses and heightened responsiveness to checkpoint blockade therapy. Nevertheless, as yet there is no consensus regarding the clinically relevant definition of hot/cold tumors, and the influence of immune genes on the formation of hot/cold tumors remains poorly understood.

Methods

Data for 33 different types of cancer were obtained from The Cancer Genome Atlas database, and their immune composition was assessed using the CIBERSORT algorithm. Tumors were categorized as either hot or cold based on their distinct immune composition, ongoing immune response, and overall survival. A customized immunogram was created to identify important immunological characteristics. Kyoto Encyclopedia of Genes and Genomes and Hallmark pathway enrichment were evaluated through gene set variation analysis. Additionally, hub genes that regulate the tumor microenvironment were identified, and their expression patterns were analyzed using single-cell RNA sequencing. Furthermore, drug sensitivity and molecular docking analyses were performed to identify potential drug candidates capable of transforming cold tumors into hot tumors. For validation, a clinical cohort of patients diagnosed with pancreatic adenocarcinoma was examined using multiplex immunohistochemistry.

Results

We were able to differentiate between hot and cold tumors in various types of cancer (bladder urothelial carcinoma, pancreatic adenocarcinoma, and cervical squamous cell carcinoma) by analyzing the presence of CD8+ T cells, activated natural killer cells, and M2-type macrophages, as well as the cytolytic activity and T cell proliferation. Hub genes that regulate the TME, including PDCD1, CD276, and NT5E, were discovered. The increased expression of NT5E and its prognostic significance were confirmed through multiplex immunohistochemistry in pancreatic adenocarcinoma. Finally, dasatinib and tozasertib were identified as drug candidates capable of converting cold pancreatic adenocarcinoma tumors into hot tumors.

Conclusion

In this study, we developed a framework for discerning clinically significant immune subtypes across various cancer types, further identifying several potential targets for converting cold tumors into hot tumors to enhance anticancer treatment efficacy.
Discordance between humoral and cellular immune responses to cytomegalovirus infection in CMV seropositive patients awaiting lung transplantation
Authors: Boada-Pérez Meritxell , Berastegui Cristina , Erro Marta , Ussetti Piedad , Crespo Elena , Donadeu Laura , Bestard Oriol , Anguera Gabriel , Solé Amparo , Ponz Mir Ricardo , Molloy Brian , Revilla-López Eva , Monforte Víctor , Gómez-Ollés Susana
Published: January 2025

Introduction

Risk stratification for CMV infection in lung transplantation (LT) currently relies on determining donor and recipient CMV IgG before transplantation. However, it has been observed that some patients who test positive for CMV-specific humoral response before kidney transplantation (KT) exhibit a weak or absent CMV-specific cellular response. The significance of this observation in LT is still unknown.

Methods

This prospective, multicenter, observational study evaluated the agreement between CMV IgG serology and specific cell-mediated response (specific T cell Enzyme-Linked ImmunoSpot Assay, ELISPOT, against CMV pp65 and IE-1 antigens) in 121 patients on the waiting list for LT.

Results

One hundred and four (86%) patients were seropositive for CMV. Discordant humoral and cellular immunologic responses were observed, 29% of seropositive patients had a weak ELISPOT response to IE-1 and 39% to pp65. In 22% of seropositive patients, there was a weak or no response to both antigens. All seronegative patients did not respond to either antigen.

Conclusions

Therefore, over 20% of CMV seropositive LT candidates showed weak CMV-specific cellular immune responses despite detectable serological memory against CMV. This may be important in assessing the risk of developing a CMV infection after transplantation.
Nanoparticles containing intracellular proteins modulate neutrophil functional and phenotypic heterogeneity
Authors: Raudszus Leonore , Bahreini Farbod , Allan Susanne , Kalies Kai-Uwe , Caldwell Charles C. , Kalies Kathrin
Published: January 2025

Neutrophils are rapidly recruited to sites of infection, injury, or to immune complexes. Upon arrival, they initiate degranulation, release reactive oxygen species (ROS), and/or nuclear extracellular traps (NETs) to eliminate invading microorganisms, clear debris, or remove abnormal immunoglobulins. While these processes ideally trigger healing and a return to balance, overshooting neutrophil function can lead to life-threatening infections such as sepsis or persistent inflammation observed in various autoimmune diseases. However, recent evidence highlights a phenotypic and functional heterogeneity of neutrophils that extends well beyond their traditional - potentially harmful- role as first responders. For example, neutrophils regulate ongoing inflammation by modulating macrophage function through efferocytosis, T cell responses by antigen presentation and the release of cytokines. The factors that induce neutrophil differentiation into activating or regulatory phenotypes remain poorly defined. Here, we hypothesize that intracellular components that have been released into the extracellular space could contribute to the phenotypic heterogeneity of neutrophils. To find out, we used nanoparticles composed of intracellular proteins (cell-derived nanoparticles, CDNPs) and analyzed their effects on cultured murine bone marrow neutrophils (BMN). We observed that CDNPs activate BMN transiently with an increase in the expression of CD11b without triggering classical effector functions. Additionally, CDNPs induce the secretion of IL-10, shift PMA-induced cell death toward apoptosis, and increase the expression of CD80. Mechanistically, our findings indicate that 26% of BMNs ingest CDNPs. These BMNs preferentially express CD54+, fail to migrate toward CXCL12, exhibit diminished responses to LPS, and undergo apoptosis. These data identify CDNPs as biomaterials that modulate neutrophil behavior by fine-tuning the expression of CD11b and CD80.
Tumor cells escape immunosurveillance by hampering LFA-1
Authors: Upadhyay Shishir , Murugu Lewis , Svensson Lena
Published: January 2025

During tumor immunosurveillance, leukocytes play a crucial role in the cellular defense system, working collaboratively with other immune components to recognize and eliminate aberrant cells. Integral to this process is the integrin Lymphocyte Function-Associated Antigen 1 (LFA-1). LFA-1 facilitates adhesion during leukocyte migration and helps establish stable cell-to-cell contacts between leukocytes and their targets. Additionally, as a receptor, LFA-1 signaling activates leukocytes, promoting their differentiation and effector functions against cancer. However, tumors can develop mechanisms to evade immune clearance by disrupting LFA-1 functions or hijacking its pathways. In this review, we first detail how leukocytes utilize LFA-1 during immunosurveillance and then explore how tumors counteract this process in the tumor microenvironment (TME) by either altering LFA-1 functions or exploiting it to drive tumorigenesis. Moreover, we discuss therapeutic strategies targeting LFA-1, including inhibitors tested in laboratory studies and animal models, highlighting their potential as anticancer interventions and the need for further research to evaluate their clinical utility.
Epithelial-mesenchymal transition in asthma: its role and underlying regulatory mechanisms
Authors: Zhang Bingxi , Feng Xinru , Tian Lincha , Xiao Bo , Hou Lixia , Mo Biwen , Yao Dong
Published: January 2025

Bronchial asthma (asthma) is a respiratory disease characterized by chronic inflammation, airway hyperresponsiveness, and airway remodeling. Numerous studies have delved into asthma’s pathogenesis, among which epithelial mesenchymal transition (EMT) is considered one of the important mechanisms in the pathogenesis of asthma. EMT refers to the transformation of epithelial cells, which lose their original features and acquire a migratory and invasive stromal phenotype. EMT contributes to normal physiological functions like growth, development, and wound healing. However, EMT is also involved in the occurrence and development of many diseases. Currently, the precise regulatory mechanism linking EMT and asthma remain obscure. Increasing evidence suggests that airway EMT contributes to asthma pathogenesis via dysregulation of associated control mechanisms. This review explores EMT’s significance in asthma and the regulatory networks associated with EMT in this context.
Overcoming immune evasion with innovative multi-target approaches for glioblastoma
Authors: Su Hai , Peng Yin , Wu Yilong , Zeng Xiaoli
Published: January 2025

Glioblastoma (GBM) cells leverage complex endogenous and environmental regulatory mechanisms to drive proliferation, invasion, and metastasis. Tumor immune evasion, facilitated by a multifactorial network, poses a significant challenge to effective therapy, as evidenced by the limited clinical benefits of monotherapies, highlighting the adaptive nature of immune evasion. This review explores glioblastoma’s immune evasion mechanisms, the role of ICIs in the tumor microenvironment, and recent clinical advancements, offering theoretical insights and directions for monotherapy and combination therapy in glioblastoma management.
Planning for success but facing uncertainty: lessons learned from a native oyster, Ostrea lurida, restoration project in the Salish Sea
Authors: McArdle James T. , Barber Julie S. , Grossman Sarah K. , Hunter Lindy L.
Published: January 2025

Overexploitation and degradation of water quality nearly depleted Olympia oyster stocks in Puget Sound, Washington, USA by the early 1900s. With an intended goal of creating self-sustaining Olympia oyster populations in a target region in Puget Sound, the Swinomish Indian Tribal Community began reestablishing Olympia oysters at two different sites, Kiket and Lone Tree, from 2015-2017. One of our primary objectives was to quantify the biological successes or failures of our reestablished populations. Our results provide a guide for the evolution of project-specific, evidence-based restoration plans that could allow for further use of adaptive management and conservation aquaculture. Following the creation of experimental plots and restoration beds across two sites using 735 m² of shell habitat, including 245 m² of seeded cultch, we measured temporal change in oyster length and density as proxies for growth, recruitment, and survival. Significant growth was observed each year in each lagoon. Despite the known presence of brooding oysters and competent larvae in the region, we found no evidence of recruitment at either site through six years of monitoring. Survival decreased significantly each year and at each site. Thus, while we quantify evidence of growth and reproduction, we are not meeting the success metrics of recruitment or survival therefore hindering the chances of long-term success. We hypothesize that our restoration efforts are hampered by the relatively small population size within our restored areas, insufficient amounts of appropriate surrounding habitat, and lower water residence time. Our study suggests managers need to consistently monitor restoration projects due to site-specific differences and to determine if local failure is a possibility. Low survival and recruitment do not necessitate termination of projects. However, these measurements do suggest that projects like ours need to consider expanding use of conservation aquaculture as a tool or employing adaptive management by developing and implementing novel strategies to increase naturally-occurring adult populations and available habitat.
Concentration-dependent effect of norfloxacin on iron toxicity in the intestine of large yellow croaker Larimichthys crocea (Richardson, 1846)
Authors: Zeng Lin , Wang Yong-Hong , Ai Chun-Xiang , Liu Bin , Yu Min-Hui , Zhang Hui , Li Fei
Published: January 2025

This study explores the effects of norfloxacin (NOR) on oxidative damage, iron (Fe) transport, energy metabolism, and immunotoxicity in the intestine of large yellow croaker under Fe stress. The fish were subjected to Fe (180 μg/L), low-dose NOR (1.8 μg/L, LNOR), high-dose NOR (180 μg/L, HNOR), Fe plus LNOR, and Fe plus HNOR for 60 days. These results demonstrated that Fe alone exposure increased malondialdehyde (MDA), protein carboxylation (PC), and mortality rate, and impaired intestinal tissue, which was related to the increment of Fe accumulation. Compared to Fe alone exposure, Fe plus LNOR exposure decreased MDA, PC, and mortality rate, and alleviated intestinal malformations by improving Fe transport, energy metabolism, anti-inflammatory response, and protein folding protective effect, and reducing pro-inflammatory response, indicating that LNOR had an antagonistic effect on Fe toxicity. Compared to Fe alone exposure, Fe plus HNOR exposure elevated MDA, PC, and mortality rate, and deteriorated intestinal malformations by inhibiting Fe excretion, energy metabolism, anti-inflammatory response, and protein folding protective effect, and enhancing pro-inflammatory response, indicating a synergetic effect between HNOR and Fe stress. These findings suggested that NOR had a dose-dependent effect on Fe-toxicity to large yellow croaker, which contributes to revealing the molecular mechanisms behind their interaction and its ecological implications.
Baricitinib treatment for hospitalized patients with severe COVID-19 on invasive mechanical ventilation: a propensity score-matched and retrospective analysis
Authors: Mao Yanxiong , Guo Anyi , Zhang Ying , Lai Jianxing , Yuan Dian , Zhang Hao , Diao Wenqi , Chen Weisong , Yan Fugui
Published: January 2025

Introduction

Baricitinib is a selective inhibitor of Janus kinase (JAK)1 and JAK2, which is associated with clinical improvement in non-severe COVID-19 patients. But in severe COVID-19 patients, the effectiveness of baricitinib is still controversial.

Methods

A propensity score-matched and retrospective study was conducted to evaluate the effectiveness of baricitinib in severe COVID-19 patients requiring invasive mechanical ventilation (IMV).

Results

A total number of 48 patients treated with baricitinib were included, and 48 patients were assigned to control group by propensity score matching. The mean ages were high in both group (baricitinib group vs. control group: 78.80 ± 9.04 vs. 82.57 ± 9.27), and most were unvaccinated (62.5% vs. 66.7%. Baricitinib group had a higher proportion of patients with hypertension (73.9% vs. 45.5%, p = 0.006). Control group had higher level of creatine kinase-myocardial band (247.50 vs. 104.50, p = 0.021). Patients in the baricitinib group were more likely to receive nirmatrelvir/ritonavir (39.6% vs. 16.7%, p = 0.017) and intravenous immunoglobin (14.6% vs. 0, p = 0.007). Baricitinib group had significantly lower all-cause 28-days mortality than control group (72.9% vs. 89.6%, p = 0.004).

Conclusion

The present study revealed baricitinib reduced 28-days mortality in severe COVID-19 patients on IMV. The effectiveness of baricitinib in treating patients with severe COVID-19 on IMV needs to be further investigated through future studies.
Hypomagnesemia, insulin secretion and action in patients without diabetes, 1 year after kidney transplantation
Authors: Carlsen Rasmus K. , Åsberg Anders , Svensson My , Birkeland Kåre I. , Jørgensen Hanne S. , Bressendorff Iain , Gulseth Hanne L. , Midtvedt Karsten , Nordheim Espen , Jenssen Trond G.
Published: January 2025

Introduction

Hypomagnesemia after kidney transplantation has been reported as a potential risk factor for development of post-transplant diabetes mellitus.

Methods

In kidney transplant recipients undergoing an oral glucose tolerance test during one-year surveillance follow-up we estimated insulin sensitivity with the Matsuda index, a modified Stumvoll index, and HOMA-2IR. First and second phase insulin secretion was assessed using the Stumvoll equation. Participants were categorized into tertiles by plasma magnesium levels, (<0.7, 07–0.78,>0.78 mmol/L).

Results

We included 208 patients (62% men, median age 51 years). Patients in the lowest compared to the highest magnesium tertile had higher measured GFR (mean 59 vs. 49 mL/min, p = 0.002), tacrolimus trough concentration (mean 6.7 vs. 5.5 μg/L, p < 0.001), and fasting plasma glucose (mean 5.5 vs. 5.3 mmol/L, p = 0.03). There was no significant difference in the Matsuda index between magnesium tertiles, nor in insulin sensitivity assessed by modified Stumvoll index, HOMA-2IR, first or second phase insulin. Results indicate a non-significant trend toward lower disposition index in the lowest vs. highest tertile (p = 0.052).

Conclusion

In kidney transplant recipients with lower compared to normal plasma magnesium levels we found a higher fasting plasma glucose but no differences in insulin sensitivity indexes nor dynamic insulin measurements.
Comparison of the conceive-design-implement-operate model and lecture-based learning in teaching the “healthcare-associated infections” course
Authors: Chen Yu , Zhang Rui , Zhou Zhenke , Hong Min , Huang Zheng , Wen Heling , Peng Lei
Published: January 2025

Background

Healthcare-associated infections (HAI) are infections acquired by patients during treatment in various healthcare institutions. These infections significantly increase morbidity, mortality, and healthcare costs. Enhancing HAI education for nurses can improve patient safety and medical quality.

Aim

The study aimed to assess the effectiveness of the new conceive-design-implement-operate (CDIO) teaching model on nursing students’ HAI learning outcomes and compare it with the traditional LBL model, providing valuable insights for future HAI education in nursing.

Methods

A total of 110 nursing students were randomly assigned to one of two groups for HAI training during the 2022–2023 academic year: a group that engaged in the CDIO model and another that received traditional lecture-based learning (LBL). The effectiveness of these pedagogical approaches was evaluated by comparing pre-and post-training test scores, and we used the Course Experience Questionnaire (CEQ) to collect students’ feedback on the course and teaching.

Results

Compared to traditional LBL method, the CDIO model significantly improved the overall scores and practical application scores of nursing students in the HAI course, with these advantages still retained after 24 weeks. Additionally, preliminary results show that students in the CDIO model scored higher on CEQ categories such as good teaching, clear goals and standards, appropriate assessment, generic skills, and independence, but they also reported an increased workload.

Conclusion

Our research is the first to apply the CDIO framework to nursing education in HAI courses, enhancing nursing students’ practical application skills, particularly in the sustained retention in this area. Our study indicates that the CDIO teaching model has significant advantages in enhancing course experience and teaching effectiveness.
Detection of macular and peripheral ocular microvascular changes after carotid artery revascularization using widefield SS-OCTA
Authors: Luo Ting , Wang Lu , Zhang Li
Published: January 2025

Purpose

This study aims to investigate microvascular changes in the macular and peripheral regions, as well as alterations in the foveal avascular zone (FAZ) of the ipsilateral eye using widefield swept-source optical coherence tomography angiography (SS-OCTA) in patients with severe carotid artery stenosis (SCAS) after carotid artery revascularization (CAR).

Design

This study employed a prospective study design.

Methods

SCAS patients were examined using widefield SS-OCTA, which covered an area of 16 × 16 mm centered on the fovea. These examinations were conducted both before and after CAR to assess changes in retinal and choroidal blood flow in the macular and peripheral regions, as well as alterations in the characteristics of the FAZ.

Results

A total of 56 patients and their corresponding 56 ipsilateral eyes were included in this study. In the macular area, a significant increase in the vessel density of the retinal superficial vascular complex (VDRSVC) was found, while a significant decrease was noted in the vessel density of the retinal deep vascular complex (VDRDVC) after CAR. Additionally, both the area and circumference of the FAZ decreased significantly after CAR. In the peripheral regions, significant increases were detected in both VDRSVC and the three-dimensional choroidal vascularity index (3D-CVI) post-CAR.

Conclusion

The findings of this study demonstrated that CAR can improve perfusion in both the macular and peripheral fundus and lead to a decreased area and circumference of the FAZ in the ipsilateral eye. The observed decrease in the VDRDVC after CAR may be attributed to microvascular embolization and ischemia within the deep capillary plexus (DCP).
Clinical outcomes of a hydrophobic trifocal diffractive intraocular lens: a literature review
Authors: Ristvedt Deborah , Bosc Camille , Thompson Vance
Published: January 2025

The aim of this review is to summarize the clinical outcomes reported in patients following the implantation of the hydrophobic diffractive trifocal FineVision HP intraocular lens (IOL). A literature search in PubMed (U.S. National Library of Medicine) was performed to identify publications, both prospective and retrospective, which have reported the clinical outcomes of patients who were implanted with this IOL model after cataract or refractive lens exchange surgeries. A total of 18 clinical studies published between 2019 and 2024 were included in this review. The available data reported in the different clinical publications was analyzed in detail, focusing mainly on refraction, visual acuity, the defocus curve, optical quality, contrast sensitivity, and patient-reported outcome questionnaires. In addition, the adverse events and other measurements reported in some studies were also analyzed. Our review encompassed a total of 1,028 eyes analyzed at different follow-up periods up to a maximum of 24 months. The analysis carried out in this review leads us to conclude that the FineVision HP IOL provides good refractive outcomes and excellent visual performance when implanted.
Bibliometrics of the current state of application of teletechnology in the rehabilitation of patients with heart and large blood vessel disease
Authors: Wang Sican , Yu Ping , Zhou Xuemei , Yuan Yuan , Chen Jian , Chen Dongmei , Liang Jingyan , Xu Li
Published: January 2025

The first publication on the use of teletechnology in heart and large blood vessels dates back to 1961. Since then, the study of teletechnology in heart and large blood vessels has become popular, and the number of publications has drastically increased. Hence, it is imperative to establish a comprehensive research framework that enables researchers and other stakeholders to understand the use of remote technologies in heart and large blood vessels. To bridge this gap, bibliometrics was used, a novel approach to determine the most prolific countries, institutions, journals, authors, source topics, funding agencies, and the most popular category of remote technologies and solutions for disease rehabilitation. The corpus was extracted from the WOS core database and analyzed using CiteSpace 6.2R7 and VOS Viewer 1.6.18 versions. The number of publications has grown since the start of the 21st century, with the United States, the United Kingdom, and Italy being the most productive nations. The most commonly used remote technology was a 24 h dynamic electrocardiogram (ECG) and ambulatory blood pressure monitoring. The most researched objective indicators were heart rate, blood pressure, and cardiac output. The primary research focused on daily life, physical activity, exercise endurance, and quality of life. Moreover, heart failure and coronary artery disease were the most extensively researched diseases.
Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil
Authors: Marcon Davi Josué , Sharma Abhinav , Souza Alex Brito , Barros Rafaella Bonfim , Andrade Valnete das Graças Dantas , Guimarães Ricardo José de Paula Souza , Lima Luana Nepomuceno Gondim , Monteiro Lúcia Helena Martins Tavares , Quaresma Ana Judith Pires Garcia , Ribeiro Layana Rufino , Suffys Philip Noel , Warren Robin Mark , Alberio Carlos Augusto Abreu , Lima Karla Valéria Batista , Conceição Emilyn Costa
Published: January 2025

Bedaquiline, an antimicrobial used to treat drug-resistant tuberculosis (DR-TB), was introduced in Brazil in October 2021. Monitoring the emergence and transmission of DR-TB is crucial for implementing public health to control the spread of DR strains of Mycobacterium tuberculosis. To measure its impact on the multi-drug treatment scheme in the state of Pará, we aimed to conduct genomic surveillance of DR-TB after bedaquiline was introduced in Brazil. Individuals treated for DR-TB between October 2021 and December 2022, in the reference hospital to treat DR-TB cases from the state of Pará, were included in the study. Clinical and bacteriological information was obtained from the National Laboratory Management Environment and the Special TB Treatment Information System. Genomic DNA was extracted from bacterial cultures performed at the Pará Central Laboratory (LACEN-PA). Whole-genome sequencing (WGS) was obtained using Illumina Nextera-XT and NextSeq 550 and genomes were analyzed using the MAGMA and TB-Profiler pipelines interpreted according to the World Health Organization (WHO) mutations catalog 2nd edition. Geoprocessing was performed based on the patient’s residences. Cutoffs of 5–12 single nucleotide polymorphisms (SNPs) were used for transmission analysis. From the 103 patients reported as DR-TB, viable cultures were obtained from 67. Forty isolates were selected randomly for WGS. Among these, a mixed infection of M. tuberculosis L1 and L4 and a co-infection of M. tuberculosis and Mycobacterium chelonae were observed. The genotypic drug susceptibility profile of TB stains (39/40) was as follows: sensitive (1/2, 5%), rifampicin mono-resistant (RR) (4/10%), isoniazid mono-resistant (1/2%), multidrug-resistant (MDR) (21/52%), extensively drug-resistant (XDR) (3/7%), pre-XDR (8/20%), and other (1/2%). Among the 38 isolates of M. tuberculosis strains without mixed infection, using a cutoff of 12 SNPs and suggestive of recent TB transmission, 14 (37%) were grouped into five clusters (C1–C5) and included RR (C5), MDR (C3, C4, C5), pre-XDR, and XDR (C2) strains. We recommend greater attention from the regional public health authorities to detect and track resistance to new drugs, especially in areas with pre-XDR and XDR cases. This is the first report on the detection and transmission of XDR-TB in Pará, Brazil, after the recent re-definition of XDR-TB by the WHO in 2021.
Human papillomavirus, vaginal microbiota and metagenomics: the interplay between development and progression of cervical cancer
Authors: Leon-Gomez Paul , Romero Vanessa I.
Published: January 2025

Persistent infection with oncogenic human papillomavirus (HPV) types, such as HPV 16 or 18, is a major factor in cervical cancer development. However, only a small percentage of infected women develop cancer, indicating that other factors are involved. Emerging evidence links vaginal microbiota with HPV persistence and cancer progression. Alterations in microbial composition, function, and metabolic pathways may contribute to this process. Despite the potential of metagenomics to explore these interactions, studies on the vaginal microbiota’s role in cervical cancer are limited. This review systematically examines the relationship between cervical microbiota, HPV, and cervical cancer by analyzing studies from PubMed, EBSCO, and Scopus. We highlight how microbial diversity influences HPV persistence and cancer progression, noting that healthy women typically have lower microbiota diversity and higher Lactobacillus abundance compared to HPV-infected women, who exhibit increased Gardenella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., associated with dysbiosis. We discuss how microbial diversity is associated with HPV persistence and cancer progression, noting that studies suggest healthy women typically have lower microbiota diversity and higher Lactobacillus abundance, while HPV-infected women exhibit increased Gardnerella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., indicative of dysbiosis. Potential markers such as Gardnerella and Prevotella have been identified as potential microbiome biomarkers associated with HPV infection and cervical cancer progression. The review also discusses microbiome-related gene expression changes in cervical cancer patients. However, further research is needed to validate these findings and explore additional microbiome alterations in cancer progression.
Novel cycloviruses identified by mining human blood metagenomic data show close relationship to those from animals
Authors: Wang Yuanqing , Jiang Xiaojie , Xi Yuan , Wei Siqi , Ning Songyi , Zhang Wen
Published: January 2025

The family Circoviridae includes the genera Circovirus and Cyclovirus. Cycloviruses have been found in serum samples from chronic HBV, HCV, or HIV-infected individuals as well as asymptomatic blood donors. However, research on cycloviruses is relatively limited. We used viral metagenomics to mine, analyze, and visualize the human blood virome, successfully identifying three new genomes, each encoding Rep and Capsid proteins. These proteins are crucial for viral replication and host-cell interaction: the Rep protein is involved in initiating viral genome replication, while the Capsid protein plays a key role in the assembly of new virions and the virus's ability to interact with host immune systems. Distance matrix and phylogenetic analyses show that these cycloviruses share high sequence similarity with viruses found in both humans and animals across different regions of Africa. This finding not only confirms the presence of previously uncharacterized cycloviruses in human blood, but also provides insight into their potential role in host transmission and their ecological significance. Further research is needed to explore the functional roles of these cycloviruses in viral pathogenesis, particularly how they may influence host immunity and contribute to chronic infections. Additionally, studies investigating the host range and mechanisms of cross-species transmission will be essential to understanding the broader implications of cycloviruses in human and animal health.
Insight into the phylogeny and antibiotic resistance of Pseudomonas spp. originating from soil of the Białowieża National Park in Northeastern Poland
Authors: Lewandowska Wioleta , Mahillon Jacques , Drewnowska Justyna Małgorzata , Swiecicka Izabela
Published: January 2025

The Pseudomonas genus includes species present in various environments and known for antibiotic resistance. However, only hospital-associated Pseudomonas aeruginosa have been extensively studied regarding antibiotic resistance. Thus, to fill the gap in knowledge on antibiotic resistance among other Pseudomonas spp., we investigated 41 isolates from soil samples taken in the Białowieża National Park in Northeastern Poland. This unique forest without notable anthropogenic influence, provides excellent conditions for research of antibiotic resistance from the perspective of natural environments. The phylogeny trees obtained based on the nucleotide sequence of the 16S rRNA gene and gyrB gene grouped the isolates into clusters belonging to the Pseudomonas fluorescens, Pseudomonas koreensis, and Pseudomonas putida groups, originating from the P. fluorescens lineage. All isolates under study demonstrated resistance to at least 12 out of the 24 antibiotics tested. Resistance to colistin, cefotaxime, and imipenem was detected in 73, 73, and 17% of the isolates, respectively. Most isolates showing resistance to imipenem and colistin clustered within the P. fluorescens group. Seven isolates were highly multi-resistant, to up to 18 of the 24 antibiotics tested. The presence of resistance genes related to intrinsic resistance of P. aeruginosa has been confirmed in environmental isolates.
Intercropping of Saccharum spp. with Dictyophora indusiata: effects on microbial communities and metabolite profiles during bagasse degradation
Authors: Duan Mingzheng , Wu Xiaojian , Long Shengfeng , Huang Hairong , Li Xiang , Li Yijie , Li Changning , Feng Bin , Chen Jiafu , Zhong Defa , Chen Zhendong , Wang Zeping
Published: January 2025

Background

Intercropping Saccharum spp. (sugarcane) with the fungus Dictyophora indusiata together with bagasse amendment represents an innovative circular agriculture method that can enhance soil health, boost sugarcane yields, and increase farm profitability. Understanding the process by which D. indusiata degrades bagasse is key to optimizing this method.

Aims

This study aims to clarify the microbial and metabolic processes involved in bagasse degradation by D. indusiata in the sugarcane intercropping system.

Methods

Chemical composition analysis, metabarcoding sequencing, and metabolomic profiling were conducted on D. indusiata-degraded bagasse (DIBA) and naturally degraded bagasse (BA).

Results

Analysis of chemical composition revealed that only acid detergent fiber (ADF) and crude protein content differed significantly between the DIBA and BA treatments. Metabarcoding sequencing showed that DIBA significantly altered the bacterial and fungal communities, reducing microbial diversity. Metabolomic analysis indicated an enhancement of biological metabolism, particularly carbohydrate breakdown, in the DIBA treatment. Key metabolites, such as glucose, cellobiose, and D-mannose, were more abundant in DIBA samples. In addition, unique metabolites such as L-alanine, serine, and oxaloacetate were detected in the DIBA treatment, suggesting more efficient bagasse degradation compared with natural processes.

Conclusion

The use of macrofungi such as D. indusiata can play a pivotal role in circular agriculture by transforming agricultural waste into valuable soil amendments. Future research should focus on the long-term impact of this system on soil quality and crop yield, as well as the underlying mechanisms, to further optimize intercropping systems and the use of fungi in agricultural waste management.
Characterization of microbial communities in flavors and fragrances during storage
Authors: Feng Yingjie , Zhang Tingting , Yang Jinchu , Liu Wenzhao , Yang Yongfeng , Huang Jihong , Huang Shen , Yang Zongcan , Liu Qianjin , Zheng Wenchao , Zhou Qing
Published: January 2025

Flavors and fragrances are essential for product quality, yet they are highly susceptible to contamination due to high moisture content and rich nutrients. This study investigates microbial growth, pH changes, volatile compound dynamics, and microbial community changes during the storage of flavors and fragrances. Results indicate that total viable counts (TVC) remained stable for the first three days but increased rapidly afterward, exceeding the acceptable limit of 5 log CFU/mL by day 7. The pH levels initially rose slightly, followed by a steady decline, which indicates spoilage progression. Gas chromatography–mass spectrometry (GC–MS) analysis revealed significant degradation of key aromatic compounds, such as 5-hydroxymethylfurfural (5-HMF), vanillin, and its derivative ethyl vanillin. Whole genome shotgun (WGS) sequencing demonstrated a marked increase in microbial community richness and diversity as storage progressed, with a notable shift in composition. Early storage stages were dominated by fungal species from the Ascomycota phylum, while later stages saw a rise in spoilage-associated bacteria, particularly from the Firmicutes and Proteobacteria phyla. Throughout the storage process, Zygosaccharomyces and its dominant species, Zygosaccharomyces bailii, remained prevalent, though their average relative abundance decreased from 81.26 to 32.29%. In addition, the bacterial species Oceanobacillus sojae and Niallia nealsonii showed significant increases in relative abundance, suggesting that bacteria were one of the key contributors to the spoilage of flavors and fragrances. Functional analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database indicated a shift in metabolic pathways within the microbial community, with heightened metabolic activity correlating with spoilage. These findings provide valuable insights for improving storage methods and quality control of flavors and fragrances.
Mesalazine: a novel therapeutic agent for periodontitis via regulation of periodontal microbiota and inhibiting Porphyromonas gingivalis
Authors: Wang Yuqi , Ma Jun , Wang Haoyu , Yi Jingzheng , Bai Yuxin , Hu Min , Yan Jiaqing
Published: January 2025

Introduction

Periodontitis and inflammatory bowel disease are chronic inflammatory diseases with shared epidemiological, biological, and therapeutic associations. Given the similarities in their pathogenic factors, this study hypothesized that mesalazine, a key treatment agent for inflammatory bowel disease, could also be effective in managing periodontitis.

Methods

The antimicrobial effect of mesalazine on Porphyromonas gingivalis was investigated in vitro, including observations of morphological changes on the surface of P. gingivalis. Additionally, the impact of mesalazine on both the formation and established plaque biofilms was examined. The antimicrobial mechanism was elucidated by assessing the expression of P. gingivalis virulence genes and by determining the disruptive effect on P. gingivalis cell membranes. An in vivo rat model of periodontitis was constructed to evaluate mesalazine’s efficacy and its influence on the periodontal bacterial flora in the context of periodontitis.

Results and discussion

Our results demonstrated that mesalazine concentrations ranging from 0.5 to 2 mg/mL significantly inhibited P. gingivalis proliferation over 72 h. Flow cytometry revealed a marked reduction in the number of viable cells following mesalazine treatment. At the nanometer scale, mesalazine induced crumpling and rupture of the P. gingivalis surface, compromising cell membrane integrity. Mesalazine not only suppressed the formation of plaque biofilms by P. gingivalis and polymicrobial communities but also disrupted pre-existing biofilms. The data also suggested that mesalazine could disrupt the integrity of the P. gingivalis cell membrane and inhibit the expression of virulence factors. An animal model of periodontitis in rats was successfully constructed in vivo. Mesalazine treatment inhibited alveolar bone resorption, alleviated inflammation of periodontal tissues, and improved the composition of the periodontal flora to a healthier state. This study establishes that mesalazine can treat periodontitis through modulation of the periodontal flora and its anti-inflammatory properties, thus broadening its classical therapeutic applications.
Dual EMCV-IRES-integrated dengue virus can express an exogenous gene and cellular Mdm2 integration suppresses the dengue viral replication
Authors: Teramoto Tadahisa
Published: January 2025

Flaviviruses transmit through a wide range of vertebrate and arthropod hosts, while the other genera in Flaviviridae replicate in a limited set of vertebrate hosts. Flaviviruses possess a 5′ cap in their genome RNA for translation, while the other genera utilize their internal ribosome entry site (IRES) sequences instead of a 5′ cap. In this study, the translational modification to add an IRES sequence was examined. An IRES sequence derived from encephalomyocarditis (EMCV) was inserted into dengue virus serotype 2 (DENV2); a non-structural (NS) polyprotein was translated by IRES separately from 5′ cap-induced structural polyprotein translation. It was revealed that the IRES-integrated DENV2 is prevented from replicating in C6/36 mosquito cells, suggesting that the 5′ cap is an advantageous mechanism for flavivirus translation in invertebrate species. I further created dual IRES-integrated DENV2, in which a non-viral gene can be expressed by the flanking IRESs. The insertion of eGFP fluorescently visualized the virus spread. The renilla luciferase (Rluc) integration enabled the viral replication quantification. It was also revealed that a cellular gene, Mdm2, which antagonizes tumor suppressor protein p53 (TP53), could terminate the viral replication in BHK21 cells. Thus, the modifications of the DENV genome with IRES and the subsequent foreign gene could be utilized for controlling viral replications.
Labeling tumor-associated extracellular vesicles with antibody-DNA conjugates for quantitative analysis
Authors: Du Xiao , Li Hongxiu , Shen Shiyi , Tian Chao , Cao Xiaohuan , Xu Xingang , Xu Nan , Wang Shuling , Tian Qingchang
Published: January 2025

Introduction

Extracellular vesicles (EVs) shed from tumor cells into peripheral circulation or other body fluids are promising biomarkers for cancer diagnosis with enormously long circulation. Consequently, precise methods for differentiating normal and tumor-associated EVs (TAEs) are required.

Methods

This study used quantifiable antibody-DNA conjugate-assisted quantitative methods combined with proximity ligation technology to detect TAEs. The antibody-DNA conjugate contained one antibody associated with three oligonucleotides for signal amplification. The antibody in the conjugate can recognize the surface tumor antigens of TAEs. Simultaneously, DNA in the conjugate is attached to the surfaces of TAEs and holds the signal amplification post, converting protein identities to DNA amplification for protein detection, even at the molecular level.

Results

These findings revealed that TAEs can be quantitatively detected using DNA-mediated quantitative polymerase chain reaction (qPCR). Antibody-DNA conjugates were used to recognize the epithelial cell adhesion molecule (EpCAM) antigen on the TAE surface and quantify the antigen using qPCR for cancer analysis.

Discussion

This method proposed a new quantitative detection approach for TAEs, which aim to identify specific EV-associated markers for diagnostic or therapeutic, this method could inspire a new idea for tumor diagnosis and detection of other diseases.