bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling students' preferences and knowledge for improving educational achievements
Authors: Abu-Issa Abdallatif , Butmeh Hala , Tumar Iyad
Published: March 2024

Student modeling is a fundamental aspect in customized learning environments. It enables unified representation of students' characteristics that supports creating personalized learning experiences. This paper aims to build an effective student model by combining learning preferences with skill levels. A student profile is formulated upon detecting the user's learning styles and learning preferences, as well as their knowledge level and misconceptions. The pieces of information are collected through an interactive online platform, by completing personal and knowledge assessment quizzes. Moreover, a learner can make his/her profile open for other learners as a starting point for supporting collaborative learning. The results showed an improvement of students' educational achievements who used the platform, and the satisfaction level reported by non-neutral users was averaged as a score of 90%. The evaluation of this platform showed promising results regarding its ability in describing students in a comprehensive manner.
Climate adjusted projections of the distribution and frequency of poor air quality days for the contiguous United States
Authors: Wilson Bradley , Pope Mariah , Melecio-Vazquez David , Hsieh Ho , Alfaro Maximilian , Shu Evelyn , Porter Jeremy , Kearns Edward J.
Published: March 2024

Unhealthy air quality conditions can strongly affect long-term human health and wellbeing, yet many air quality data products focus on near real-time alerts or short-term forecasts. Understanding the full state of air quality also requires examining the longer term frequency and intensity of poor air quality at ground level, and how it might change over time. We present a new modeling framework to compute climate-adjusted estimates of air quality hazards for the contiguous United States (CONUS) at 10 km horizontal resolution. The framework blends results from statistical, machine-learning, and climate-chemistry models—including a bias-adjusted version of the EPA Community Multiscale Air Quality Model (CMAQ) time series as described in (Wilson et al., 2022)—for ground-level ozone, anthropogenic fine particulate matter (PM2.5), and wildfire smoke PM2.5 into consistent estimates of days exceeding the “unhealthy for sensitive groups” (orange colored) classification on the EPA Air Quality Index for 2023 and 2053. We find that joint PM2.5 and ozone orange+ days range from 1 day to 41 days across CONUS, with a median value of 2 days, across all years. Considering all properties across CONUS, we find that 63.5% percent are exposed to at least one orange or greater day in 2023, growing to 72.1% in 2053. For a 7-day threshold, 3.8% and 5.7% of properties are exposed in 2023 and 2053, respectively. Our results also support the identification of which parts of the country are most likely to be impacted by additional climate-related air quality risks. With growing evidence that even low levels of air pollution are harmful, these results are an important step forward in empowering individuals to understand their air quality risks both now and into the future.
Thyroid hormone action in adult neurogliogenic niches: the known and unknown
Authors: Valcárcel-Hernández Victor , Mayerl Steffen , Guadaño-Ferraz Ana , Remaud Sylvie
Published: March 2024

Over the last decades, thyroid hormones (THs) signaling has been established as a key signaling cue for the proper maintenance of brain functions in adult mammals, including humans. One of the most fascinating roles of THs in the mature mammalian brain is their ability to regulate adult neurogliogenic processes. In this respect, THs control the generation of new neuronal and glial progenitors from neural stem cells (NSCs) as well as their final differentiation and maturation programs. In this review, we summarize current knowledge on the cellular organization of adult rodent neurogliogenic niches encompassing well-established niches in the subventricular zone (SVZ) lining the lateral ventricles, the hippocampal subgranular zone (SGZ), and the hypothalamus, but also less characterized niches in the striatum and the cerebral cortex. We then discuss critical questions regarding how THs availability is regulated in the respective niches in rodents and larger mammals as well as how modulating THs availability in those niches interferes with lineage decision and progression at the molecular, cellular, and functional levels. Based on those alterations, we explore the novel therapeutic avenues aiming at harnessing THs regulatory influences on neurogliogenic output to stimulate repair processes by influencing the generation of either new neurons (i.e. Alzheimer’s, Parkinson’s diseases), oligodendrocytes (multiple sclerosis) or both (stroke). Finally, we point out future challenges, which will shape research in this exciting field in the upcoming years.
Causal association between mTOR-dependent circulating protein levels and central precocious puberty: a Mendelian randomization study
Authors: Ying Yuanxiao , Yu Ze , Wu Liping
Published: March 2024

Background

The mechanistic target of rapamycin (mTOR) signaling pathway has a significant effect on central precocious puberty (CPP). However, the causality between mTOR-dependent circulating protein levels and CPP is still unclear. Our aim is to assess the effects of seven mTOR-dependent circulating protein levels on CPP using Mendelian randomization (MR).

Methods

Instrumental variables (IVs) for mTOR-dependent circulating protein levels were retrieved from the proteomics-GWAS INTERVAL study and eQTLGen. The summary-level genetic datasets for CPP outcome were obtained from the FinnGen Consortium. Inverse-variance weighted (IVW) was used as the primary method and the pleiotropy, heterogeneity and robustness of the analyses were detected as sensitivity analysis. Positive exposures in the discovery cohort would be revalidated in the validation cohort.

Results

This two-sample MR study revealed a causal association between eIF4G level in plasma and CPP in both discovery cohort (IVW: OR = 0.45, 95% CI = 0.22–0.91, p = 0.026) and validation cohort (IVW: OR = 0.45, 95% CI = 0.24–0.85, p = 0.014).

Conclusions

There was a causal association between eIF4G level in plasma and CPP. Whether eIF4G can be used for the prevention or treatment of CPP needs to be explored in further studies.
Green technology: synthesis of iron-modified biochar derived from pine cones to remove azithromycin and ciprofloxacin from water
Authors: Aziz Sadia , Anbreen Sundus , Iftikhar Iqra , Fatima Tabassum , Iftikhar Aqsa , Ali Liaqat
Published: March 2024

The rise of antibiotic pollutants in water threatens ecosystems and human health. Iron-modified biochar (BC) exhibits adsorption properties and offers a promising approach for effective environmental remediation. The current study explored the potential of iron-loaded biochar synthesized from pine cones for antibiotic removal from water. In this study, pine cones, a sustainable and renewable source, were used to produce iron-modified biochar and employed to remove azithromycin, ciprofloxacin, and their mixture from aqueous solutions. Biochar was synthesized through pyrolysis and modified by the addition of iron salts. The analysis of iron-modified biochar by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) suggested a crystalline structure rich in minerals and functional groups (O–H, C=O, and C≡C) and loaded with iron, having plate-like roughness and distorted morphology along with sharp edges and corners. Antibiotic removal was evaluated by changing physical parameters, including biochar dose, pH, and temperature. The maximum removal percentages of azithromycin, ciprofloxacin, and their mixture were obtained as 87.8%, 91.3%, and 84%, respectively, at low pH, a low Fe-modified biochar dose, and higher temperature. Application of kinetic models suggested that the adsorption of antibiotics on iron-modified biochar is more inclined toward pseudo-second-order (R2 > 0.98) kinetics, indicating a chemisorption nature of the adsorption process. The findings highlight the potential of iron-modified biochar for removing antibiotics from aqueous solutions.
Seasonal and long-term climate drivers of tree species phenology and litterfall in a Nothofagus cool temperate rainforest of Australia
Authors: Vogado Nara O. , Liddell Michael J. , Peacock Ross J.
Published: March 2024

The cool temperate rainforests of eastern Australia are at risk from anthropogenic climate change with predicted changes in temperature, rainfall, severe weather, basal cloud layer, and droughts. Phenology and litter production are fundamental reproductive and growth processes to document in any ecosystem, yet very few long-term studies exist in Australian rainforests. In this study, long-term datasets are used to describe different phenological and litter production behaviours of tree species in a Nothofagus cool temperate rainforest in New South Wales (NSW), Australia, analysing seasonal and inter-annual climate drivers. Leaf fall at the community level was mostly influenced by Nothofagus moorei, driven by temperature and wind speed, and Ceratopetalum apetalum, driven by temperature, rainfall, and solar radiation. Mean dates of leaf fall at the community level were found to be advancing, correlated with an advance in solar radiation. We also analysed in detail the flowering behaviour of the dominant canopy tree species, N. moorei, which masts with a mean inter-flowering period of 3–4 years in 65% of flowering events. Three of the studied species presented mast flowering, C. apetalum, N. moorei, and Orites excelsus; however, they did not mast in the same years. All species presented strong seasonality in their phenological activity, but seasonality peaked in different months, and were driven by varied climate variables. Supra-annual peaks of flowering and fruiting did not occur at the same time for all species, and climate drivers of inter-annual phenological behaviour were different for each species. Our results show that projected changes in climate will affect species from cool temperate rainforests differently, affecting not only biomass production, but also species reproductive output and forest dynamics.
Bibliometric analysis of studies on threat assessment and prioritization of species for conservation
Authors: Wani Zishan Ahmad , Pant Shreekar , Bhat Jahangeer A. , Tariq Mohd , Siddiqui Sazada , Alshaharni Mohammed O.
Published: March 2024

The present study investigated the evolution and current situation of research on threat assessment and prioritization of species for conservation at a global level by analyzing bibliometrically the most relevant and productive authors, sources, and countries, most cited papers, country collaborations and most frequent keywords as reflected in the scientific literature using the Web of Science database. From 1989–2022, a total of 315 relevant documents were retrieved from 129 sources. Results revealed that since 1989, there has been an increase in the number of publications on threat assessment and prioritization of species for conservation. A total of 1,300 authors have contributed to the field through their research contributions. Among the 129 sources, the journals ‘Biodiversity and Conservation’ and ‘Biological Conservation’ are the most relevant and productive. Among countries, the USA has produced the highest number of publications, whereas Benin has the highest Multiple Country Production with a rate of 71.4%. Among the authors, ‘Keith DA’ has received the most citations, and among the sources, the journal ‘Biological Conservation’ received the highest number of citations. Conservation, biodiversity, conservation priorities, species richness, and threatened species are the most frequently used keywords and follow power-law distribution. The present study will be useful to the researchers in determining which journals to target and how to identify potential research partners in the concerned field. It is recommended that institutions in developed countries be encouraged to lead research programs in developing and underdeveloped countries so that such studies will be carried out at local, regional, and global scale, as biodiversity loss is a global issue.
Complex associations between cancer progression and immune gene expression reveals early influence of transmissible cancer on Tasmanian devils
Authors: Raven Nynke , Klaassen Marcel , Madsen Thomas , Jones Menna , Hamilton David G. , Ruiz-Aravena Manuel , Thomas Frederic , Hamede Rodrigo K. , Ujvari Beata
Published: March 2024

The world’s largest extant carnivorous marsupial, the Tasmanian devil, is challenged by Devil Facial Tumor Disease (DFTD), a fatal, clonally transmitted cancer. In two decades, DFTD has spread across 95% of the species distributional range. A previous study has shown that factors such as season, geographic location, and infection with DFTD can impact the expression of immune genes in Tasmanian devils. To date, no study has investigated within-individual immune gene expression changes prior to and throughout the course of DFTD infection. To explore possible changes in immune response, we investigated four locations across Tasmania that differed in DFTD exposure history, ranging between 2 and >30 years. Our study demonstrated considerable complexity in the immune responses to DFTD. The same factors (sex, age, season, location and DFTD infection) affected immune gene expression both across and within devils, although seasonal and location specific variations were diminished in DFTD affected devils. We also found that expression of both adaptive and innate immune genes starts to alter early in DFTD infection and continues to change as DFTD progresses. A novel finding was that the lower expression of immune genes MHC-II, NKG2D and CD8 may predict susceptibility to earlier DFTD infection. A case study of a single devil with regressed tumor showed opposite/contrasting immune gene expression patterns compared to the general trends observed across devils with DFTD infection. Our study highlights the complexity of DFTD’s interactions with the host immune system and the need for long-term studies to fully understand how DFTD alters the evolutionary trajectory of devil immunity.
VapC12 ribonuclease toxin modulates host immune response during Mycobacterium tuberculosis infection
Authors: Tyagi Shaifali , Sadhu Srikanth , Sharma Taruna , Paul Abhijit , Pandey Manitosh , Nain Vaibhav Kumar , Rathore Deepak Kumar , Chatterjee Samrat , Awasthi Amit , Pandey Amit Kumar
Published: March 2024

Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with ΔvapC12 induced a pro-inflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with ΔvapC12 succumbed early to the disease. Finally, we reported that the above phenotype of ΔvapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggests that failure of a timely resolution of the early inflammation by the ΔvapC12 infected mice led to hyperinflammation, altered T-cell response and high bacterial load. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the innate immune response of the host in ways that favor the long-term survival of the pathogen inside the host.
Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence
Authors: Barros Rafael dos Santos , Queiroz Luiz Adriano Damasceno , Assis Josiane Betim de , Pantoja Kamilla Costa , Bustia Sofia Xavier , Sousa Emanuella Sarmento Alho de , Rodrigues Stephen Fernandes , Akamine Eliana Hiromi , Sá-Nunes Anderson , Martins Joilson O.
Published: March 2024

Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism’s homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1β, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4+ and CD8+ T cell numbers were higher and lower, respectively, in SAM-P8 mice treated with RAPA, with the opposite observed in SAM-R1. Additionally, we found that the low dose of RAPA used did not trigger changes that could compromise the immune response of these mice and the administered dose may have contributed to changes in important lymphocyte populations in the adaptive immune response and the secretion of cytokines that directly collaborate with the maturation and proliferation of these cells.
Evolutionarily conserved mechanisms regulating stress-induced neutrophil redistribution in fish
Authors: Klak Katarzyna , Maciuszek Magdalena , Pijanowski Lukasz , Marcinkowska Magdalena , Homa Joanna , Verburg-van Kemenade B. M. Lidy , Rakus Krzysztof , Chadzinska Magdalena
Published: March 2024

Introduction

Stress may pose a serious challenge to immune homeostasis. Stress however also may prepare the immune system for challenges such as wounding or infection, which are likely to happen during a fight or flight stress response.

Methods

In common carp (Cyprinus carpio L.) we studied the stress-induced redistribution of neutrophils into circulation, and the expression of genes encoding CXC chemokines known to be involved in the regulation of neutrophil retention (CXCL12) and redistribution (CXCL8), and their receptors (CXCR4 and CXCR1-2, respectively) in blood leukocytes and in the fish hematopoietic organ – the head kidney. The potential involvement of CXC receptors and stress hormone receptors in stress-induced neutrophil redistribution was determined by an in vivo study with selective CXCR inhibitors and antagonists of the receptors involved in stress regulation: glucocorticoid/mineralocorticoid receptors (GRs/MRs), adrenergic receptors (ADRs) and the melanocortin 2 receptor (MC2R).

Results

The stress-induced increase of blood neutrophils was accompanied by a neutrophil decrease in the hematopoietic organs. This increase was cortisol-induced and GR-dependent. Moreover, stress upregulated the expression of genes encoding CXCL12 and CXCL8 chemokines, their receptors, and the receptor for granulocytes colony-stimulation factor (GCSFR) and matrix metalloproteinase 9 (MMP9). Blocking of the CXCR4 and CXCR1 and 2 receptors with selective inhibitors inhibited the stress-induced neutrophil redistribution and affected the expression of genes encoding CXC chemokines and CXCRs as well as GCSFR and MMP9.

Discussion

Our data demonstrate that acute stress leads to the mobilization of the immune system, characterized by neutrophilia. CXC chemokines and CXC receptors are involved in this stress-induced redistribution of neutrophils from the hematopoietic tissue into the peripheral blood. This phenomenon is directly regulated by interactions between cortisol and the GR/MR. Considering the pivotal importance of neutrophilic granulocytes in the first line of defense, this knowledge is important for aquaculture, but will also contribute to the mechanisms involved in the stress-induced perturbation in neutrophil redistribution as often observed in clinical practice.
DeepLION2: deep multi-instance contrastive learning framework enhancing the prediction of cancer-associated T cell receptors by attention strategy on motifs
Authors: Qian Xinyang , Yang Guang , Li Fan , Zhang Xuanping , Zhu Xiaoyan , Lai Xin , Xiao Xiao , Wang Tao , Wang Jiayin
Published: March 2024

Introduction

T cell receptor (TCR) repertoires provide valuable insights into complex human diseases, including cancers. Recent advancements in immune sequencing technology have significantly improved our understanding of TCR repertoire. Some computational methods have been devised to identify cancer-associated TCRs and enable cancer detection using TCR sequencing data. However, the existing methods are often limited by their inadequate consideration of the correlations among TCRs within a repertoire, hindering the identification of crucial TCRs. Additionally, the sparsity of cancer-associated TCR distribution presents a challenge in accurate prediction.

Methods

To address these issues, we presented DeepLION2, an innovative deep multi-instance contrastive learning framework specifically designed to enhance cancer-associated TCR prediction. DeepLION2 leveraged content-based sparse self-attention, focusing on the top k related TCRs for each TCR, to effectively model inter-TCR correlations. Furthermore, it adopted a contrastive learning strategy for bootstrapping parameter updates of the attention matrix, preventing the model from fixating on non-cancer-associated TCRs.

Results

Extensive experimentation on diverse patient cohorts, encompassing over ten cancer types, demonstrated that DeepLION2 significantly outperformed current state-of-the-art methods in terms of accuracy, sensitivity, specificity, Matthews correlation coefficient, and area under the curve (AUC). Notably, DeepLION2 achieved impressive AUC values of 0.933, 0.880, and 0.763 on thyroid, lung, and gastrointestinal cancer cohorts, respectively. Furthermore, it effectively identified cancer-associated TCRs along with their key motifs, highlighting the amino acids that play a crucial role in TCR-peptide binding.

Conclusion

These compelling results underscore DeepLION2's potential for enhancing cancer detection and facilitating personalized cancer immunotherapy. DeepLION2 is publicly available on GitHub, at https://github.com/Bioinformatics7181/DeepLION2, for academic use only.
Dysregulated FGFR3 signaling alters the immune landscape in bladder cancer and presents therapeutic possibilities in an agent-based model
Authors: Bergman Daniel R. , Wang Yixuan , Trujillo Erica , Fernald Anthony A. , Li Lie , Pearson Alexander T. , Sweis Randy F. , Jackson Trachette L.
Published: March 2024

Bladder cancer is an increasingly prevalent global disease that continues to cause morbidity and mortality despite recent advances in treatment. Immune checkpoint inhibitors (ICI) and fibroblast growth factor receptor (FGFR)-targeted therapeutics have had modest success in bladder cancer when used as monotherapy. Emerging data suggests that the combination of these two therapies could lead to improved clinical outcomes, but the optimal strategy for combining these agents remains uncertain. Mathematical models, specifically agent-based models (ABMs), have shown recent successes in uncovering the multiscale dynamics that shape the trajectory of cancer. They have enabled the optimization of treatment methods and the identification of novel therapeutic strategies. To assess the combined effects of anti-PD-1 and anti-FGFR3 small molecule inhibitors (SMI) on tumor growth and the immune response, we built an ABM that captures key facets of tumor heterogeneity and CD8+ T cell phenotypes, their spatial interactions, and their response to therapeutic pressures. Our model quantifies how tumor antigenicity and FGFR3 activating mutations impact disease trajectory and response to anti-PD-1 antibodies and anti-FGFR3 SMI. We find that even a small population of weakly antigenic tumor cells bearing an FGFR3 mutation can render the tumor resistant to combination therapy. However, highly antigenic tumors can overcome therapeutic resistance mediated by FGFR3 mutation. The optimal therapy depends on the strength of the FGFR3 signaling pathway. Under certain conditions, ICI alone is optimal; in others, ICI followed by anti-FGFR3 therapy is best. These results indicate the need to quantify FGFR3 signaling and the fitness advantage conferred on bladder cancer cells harboring this mutation. This ABM approach may enable rationally designed treatment plans to improve clinical outcomes.
Mycobacterium tuberculosis-dependent monocyte expression quantitative trait loci, cytokine production, and TB pathogenesis
Authors: Hong Hyejeong , Dill-McFarland Kimberly A. , Simmons Jason D. , Peterson Glenna J. , Benchek Penelope , Mayanja-Kizza Harriet , Boom W. Henry , Stein Catherine M. , Hawn Thomas R.
Published: March 2024

Introduction

The heterogeneity of outcomes after Mycobacterium tuberculosis (Mtb) exposure is a conundrum associated with millennia of host-pathogen co-evolution. We hypothesized that human myeloid cells contain genetically encoded, Mtb-specific responses that regulate critical steps in tuberculosis (TB) pathogenesis.

Methods

We mapped genome-wide expression quantitative trait loci (eQTLs) in Mtb-infected monocytes with RNAseq from 80 Ugandan household contacts of pulmonary TB cases to identify monocyte-specific, Mtb-dependent eQTLs and their association with cytokine expression and clinical resistance to tuberculin skin test (TST) and interferon-γ release assay (IGRA) conversion.

Results

cis-eQTLs (n=1,567) were identified in Mtb-infected monocytes (FDR<0.01), including 29 eQTLs in 16 genes which were Mtb-dependent (significant for Mtb:genotype interaction [FDR<0.1], but not classified as eQTL in uninfected condition [FDR≥0.01]). A subset of eQTLs were associated with Mtb-induced cytokine expression (n=8) and/or clinical resistance to TST/IGRA conversion (n=1). Expression of BMP6, an Mtb-dependent eQTL gene, was associated with IFNB1 induction in Mtb-infected and DNA ligand-induced cells. Network and enrichment analyses identified fatty acid metabolism as a pathway associated with eQTL genes.

Discussion

These findings suggest that monocyte genes contain Mtb-dependent eQTLs, including a subset associated with cytokine expression and/or clinical resistance to TST/IGRA conversion, providing insight into immunogenetic pathways regulating susceptibility to Mtb infection and TB pathogenesis.
Group A streptococcal collagen-like protein 1 restricts tumor growth in murine pancreatic adenocarcinoma and inhibits cancer-promoting neutrophil extracellular traps
Authors: Henderson Emily A. , Ivey Abby , Choi Soo Jeon , Santiago Stell , McNitt Dudley , Liu Tracy W. , Lukomski Slawomir , Boone Brian A.
Published: March 2024

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer associated with an immunosuppressive environment. Neutrophil extracellular traps (NETs) were initially described in the context of infection but have more recently been implicated in contributing to the tolerogenic immune response in PDAC. Thus, NETs are an attractive target for new therapeutic strategies. Group A Streptococcus (GAS) has developed defensive strategies to inhibit NETs.

Methods

In the present work, we propose utilizing intra-tumoral GAS injection to stimulate anti-tumor activity by inhibiting cancer-promoting NETs. Mice harboring Panc02 or KPC subcutaneous tumors injected with three different M-type GAS strains. Tumors and spleens were harvested at the endpoint of the experiments to assess bacterial colonization and systemic spread, while sera were analyzed for humoral responses toward the streptococcal antigens, especially the M1 and Scl1 proteins. Role of the streptococcal collagen-like protein 1 (Scl1) in anti-PDAC activity was assessed in vivo after intratumoral injection with M1 GAS wild-type, an isogenic mutant strain devoid of Scl1, or a complemented mutant strain with restored scl1 expression. In addition, recombinant Scl1 proteins were tested for NET inhibition using in vitro and ex vivo assays assessing NET production and myeloperoxidase activity.

Results

Injection of three different M-type GAS strains reduced subcutaneous pancreatic tumor volume compared to control in two different murine PDAC models. Limitation of tumor growth was dependent on Scl1, as isogenic mutant strain devoid of Scl1 did not reduce tumor size. We further show that Scl1 plays a role in localizing GAS to the tumor site, thereby limiting the systemic spread of bacteria and off-target effects. While mice did elicit a humoral immune response to GAS antigens, tested sera were weakly immunogenic toward Scl1 antigen following intra-tumoral treatment with Scl1-expressing GAS. M1 GAS inhibited NET formation when co-cultured with neutrophils while Scl1-devoid mutant strain did not. Recombinant Scl1 protein inhibited NETs ex vivo in a dose-dependent manner by suppressing myeloperoxidase activity.

Discussion

Altogether, we demonstrate that intra-tumoral GAS injections reduce PDAC growth, which is facilitated by Scl1, in part through inhibition of cancer promoting NETs. This work offers a novel strategy by which NETs can be targeted through Scl1 protein and potentiates its use as a cancer therapeutic.
Health-related quality of life in patients with inborn errors of immunity: a bibliometric analysis
Authors: Xiao Ningkun , Huang Xinlin , Zang Wanli , Kiselev Sergey , Bolkov Mikhail A. , Tuzankina Irina A. , Chereshnev Valery A.
Published: March 2024

Background

Inborn Errors of Immunity (IEI) are characterized by a heightened susceptibility to infections, allergies, and various other health complications. Health-Related Quality of Life (HRQOL) in patients with IEI is a critical area of research that demands attention due to the impact of IEI on patients’ lives. This study utilized bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of HRQOL in patients with IEI.

Methods

This bibliometric analysis utilized data from the Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) within the Web of Science core datasets up to January 1, 2024. The study focused on literature that addressed HRQOL in IEI patients, involving a total of 1,807 authors and 309 articles published across 112 journals. The analysis included publication volume and growth trends, country and institutional contributions, authorship, and journal analysis.

Results

The research found that despite the importance of HRQOL in IEI, the volume of publications in this field remains consistently low, with no significant increase in trend. The USA leads in publication and citation volumes, reflecting a geographical imbalance in research contributions. Key journals in this field include the Journal of Clinical Immunology, Frontiers in Immunology, and the Journal of Allergy and Clinical Immunology. The study highlights that while treatments like hematopoietic stem cell transplants and gene therapy have improved patient IEI survival rates, they still often come with significant side effects impacting HRQOL. The analysis underlines the need for comprehensive HRQOL assessments in IEI, considering the physical and psychological impacts of treatments.

Conclusions

This study represents a bibliometric analysis focusing on HRQOL in patients with. It underscores the need for more extensive and systematic research in this area, emphasizing the importance of a multidisciplinary approach. Despite advancements in medical treatments for IEI, there is a crucial need to focus on HRQOL to enhance patient satisfaction and overall well-being. The findings advocate for more personalized treatment plans and a better understanding of the psychosocial needs of patients with IEI to improve their quality of life.
Detection of the infective Plasmodium falciparum gametocytes by RT-qPCR assay from a malaria-endemic region of Northeastern India
Authors: Das Ram , Vashisht Kapil , Kori Lokesh , Singh Kuldeep , Kumar Gaurav , Hasan Izazul , Gam Jugal , Pandey Kailash C.
Published: March 2024

Introduction

The diagnosis of infectious reservoirs in malaria (gametocytes) is necessary, especially in low-density infections and asymptomatic malaria patients. The gametocyte stage is a surrogate marker for infection of P. falciparum malaria in healthy individuals. The early detection of infectious gametocytes and treatment will strengthen our efforts in curbing transmission. The nested PCR and real-time quantitative PCR (RT-qPCR) methods have been demonstrated for the diagnosis of infectious gametocyte reservoirs. In this study, RDT, blood smear microscopy, and nested-PCR were used for the detection of P. falciparum and P. vivax, and compared with RT-qPCR detection of Pfg27 gametocyte biomarker gene.

Methods

In the present cross-sectional study, 356 human blood samples were collected from endemic areas of Kokrajhar Assam (asymptomatic and symptomatic malaria patients) for malaria diagnosis.

Results

A total of 8.42%(30/356) incidence of malaria was observed. Malaria patients were observed to be both symptomatic, 80%(24/30; 13Pf+11Pv), and asymptomatic, 20%(6 (4Pf +2Pv)). More than 64%(11/17) of Pf and 92.3%(12/13) of Pv infections were observed in children and the adolescent population (age <20 years) by RDT, microscopy, nested PCR, and RT-qPCR methods. The prevalence of Pf infection was 4.77%(17/356) by RT-qPCR method. Of 16 the Pf positive samples 81.25%(13/16) were symptomatic and 18.75%(3/16) were asymptomatic. One asymptomatic individual was found positive for Pf infection by the RT-qPCR method.

Conclusion

The findings from this research study revealed that the routine microscopy and RDT methods are insufficient for detecting all asymptomatic malaria and gametocyte infectious reservoirs. The early detection of infectious P. falciparum gametocytes and the treatment of patients will be helpful in preventing the transmission of malaria.
Data model-based toolpath generation techniques for CNC milling machines
Authors: Liao Jianbin , Huang Zeng
Published: March 2024

Introduction: With the development of computer technology and data modeling, the use of point cloud models to generate tool paths is particularly important for improving productivity and accuracy.

Methods: This study proposes a new method that first preprocesses the point cloud data using four-point denoising and octree methods to improve processing efficiency. Subsequently, roughing tool paths were analyzed using the layer slicing method and finishing paths using the residual height method.

Results and Discussion: The experimental results show that the layer slicing method has a minimum error close to 10% on the roughing path generation and the computation time is reduced to 35 s, while the residual height method has an error rate of 10.17% on the finishing path and the computation time is only 11.82 s, which reflects a high trajectory smoothness and accuracy. The above results show that the study not only optimizes the tool path generation process and improves the machining efficiency and accuracy, but also demonstrates the potential application of point cloud models in the machining of complex parts.

Conclusion: The novel tool roughing and finishing methods provide more reliable path planning for actual machining operations, and future research will be devoted to further improving the performance of the data processing algorithms and exploring more efficient path planning strategies to facilitate automated production.
AGRAMP: machine learning models for predicting antimicrobial peptides against phytopathogenic bacteria
Authors: Shao Jonathan , Zhao Yan , Wei Wei , Vaisman Iosif I.
Published: March 2024

Introduction

Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics for combating plant pathogenic bacteria in agriculture and the environment. However, identifying potent AMPs through laborious experimental assays is resource-intensive and time-consuming. To address these limitations, this study presents a bioinformatics approach utilizing machine learning models for predicting and selecting AMPs active against plant pathogenic bacteria.

Methods

N-gram representations of peptide sequences with 3-letter and 9-letter reduced amino acid alphabets were used to capture the sequence patterns and motifs that contribute to the antimicrobial activity of AMPs. A 5-fold cross-validation technique was used to train the machine learning models and to evaluate their predictive accuracy and robustness.

Results

The models were applied to predict putative AMPs encoded by intergenic regions and small open reading frames (ORFs) of the citrus genome. Approximately 7% of the 10,000-peptide dataset from the intergenic region and 7% of the 685,924-peptide dataset from the whole genome were predicted as probable AMPs. The prediction accuracy of the reported models range from 0.72 to 0.91. A subset of the predicted AMPs was selected for experimental test against Spiroplasma citri, the causative agent of citrus stubborn disease. The experimental results confirm the antimicrobial activity of the selected AMPs against the target bacterium, demonstrating the predictive capability of the machine learning models.

Discussion

Hydrophobic amino acid residues and positively charged amino acid residues are among the key features in predicting AMPs by the Random Forest Algorithm. Aggregation propensity appears to be correlated with the effectiveness of the AMPs. The described models would contribute to the development of effective AMP-based strategies for plant disease management in agricultural and environmental settings. To facilitate broader accessibility, our model is publicly available on the AGRAMP (Agricultural Ngrams Antimicrobial Peptides) server.
Evaluation of cell disruption methods for protein and coenzyme Q10 quantification in purple non-sulfur bacteria
Authors: Wada Ojima Z. , Rashid Naim , Wijten Patrick , Thornalley Paul , Mckay Gordon , Mackey Hamish R.
Published: March 2024

A recent focus has been on the recovery of single-cell protein and other nutritionally valuable bioproducts, such as Coenzyme Q10 (CoQ10) from purple non-sulfur bacteria (PNSB) biomass following wastewater treatment. However, due to PNSB’s peculiar cell envelope (e.g., increased membrane cross-section for energy transduction) and relatively smaller cell size compared to well-studied microbial protein sources like yeast and microalgae, the effectiveness of common cell disruption methods for protein quantification from PNSB may differ. Thus, this study examines the efficiency of selected chemical (NaOH and EDTA), mechanical (homogenization and bead milling), physical (thermal and bath/probe sonication), and combined chemical–mechanical/physical treatment techniques on the PNSB cell lysis. PNSB biomass was recovered from the treatment of gas-to-liquid process water. Biomass protein and CoQ10 contents were quantified based on extraction efficiency. Considering single-treatment techniques, bead milling resulted in the best protein yields (p < 0.001), with the other techniques resulting in poor yields. However, the NaOH-assisted sonication (combined chemical/physical treatment technique) resulted in similar protein recovery (p = 1.00) with bead milling, with the former having a better amino acid profile. For example, close to 50% of the amino acids, such as sensitive ones like tryptophan, threonine, cystine, and methionine, were detected in higher concentrations in NaOH-assisted sonication (>10% relative difference) compared to bead-milling due to its less disruptive nature and improved solubility of amino acids in alkaline conditions. Overall, PNSB required more intensive protein extraction techniques than were reported to be effective on other single-cell organisms. NaOH was the preferred chemical for chemical-aided mechanical/physical extraction as EDTA was observed to interfere with the Lowry protein kit, resulting in significantly lower concentrations. However, EDTA was the preferred chemical agent for CoQ10 extraction and quantification. CoQ10 extraction efficiency was also suspected to be adversely influenced by pH and temperature.
A simplified version of rapid susceptibility testing of bacteria and yeasts using optical nanomotion detection
Authors: Villalba Maria I. , Gligorovski Vojislav , Rahi Sahand J. , Willaert Ronnie G. , Kasas Sandor
Published: March 2024

We present a novel optical nanomotion-based rapid antibiotic and antifungal susceptibility test. The technique consisted of studying the effects of antibiotics or antifungals on the nanometric scale displacements of bacteria or yeasts to assess their sensitivity or resistance to drugs. The technique relies on a traditional optical microscope, a video camera, and custom-made image analysis software. It provides reliable results in a time frame of 2–4 h and can be applied to motile, non-motile, fast, and slowly growing microorganisms. Due to its extreme simplicity and low cost, the technique can be easily implemented in laboratories and medical centers in developing countries.
Paracoccidioides spp.: the structural characterization of extracellular matrix, expression of glucan synthesis and associated genes and adhesins during biofilm formation
Authors: Oliveira Lariane Teodoro , Marcos Caroline Maria , Cabral Ana Karla Lima Freire , Medina-Alarcón Kaila Petronila , Pires Regina Helena , Fusco-Almeida Ana Marisa , Mendes-Giannini Maria José Soares
Published: March 2024

The genus Paracoccidioides includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which comprises four phylogenetic species. A key feature distinguishing planktonic growth from biofilm is the presence of a 3D extracellular matrix (ECM). Therefore, in this study, we analyzed biofilm formation in different species of Paracoccidioides yeast phase, characterized the structural elements of the matrix of P. brasiliensis (Pb18), P. lutzii (Pl01 and 8334) and P. restrepiensis (339 and 192) and evaluated the expression of glucan genes, according to the stage of biofilm evolution for P. brasiliensis. The strains were cultivated in planktonic and biofilm form for 24–144 h. The fungi biomass and metabolic activity were determined by crystal violet and tetrazolium salt reduction (XTT) tests and colony-forming unit (CFU) by plating. The biofilm structure was designed using scanning electron microscopy and confocal laser scanning microscopy techniques. The extracellular matrix of P. brasiliensis and P. lutzii biofilms was extracted by sonication, and polysaccharides, proteins, and extracellular DNA (eDNA) were quantified. The RNA was extracted with the Trizol® reagent and quantified; then, the cDNA was synthesized to analyze the enolase expression, 14-3-3, FKS1, AGS1, GEL3, and KRE6 genes by real-time PCR. All strains of Paracoccidioides studied form a biofilm with more significant metabolic activity and biomass values in 144 h. The extracellular matrix of P. brasiliensis and P. lutzii had a higher content of polysaccharides in their composition, followed by proteins and eDNA in smaller quantities. The P. brasiliensis biofilm kinetics of formation showed greater expression of genes related to glucan's synthesis and its delivery to the external environment in addition adhesins during the biofilm's adhesion, initiation, and maturation. The GEL3 and enolase genes increased in expression within 24 h and during the biofilm maturation period, there was an increase in 14-3-3, AGS1, and FKS1. Furthermore, at 144 h, there was a decrease in KRE6 expression and an increase in GEL3. This study highlights the potential for biofilm formation for three species of Paracoccidioides and the main components of the extracellular matrix that can contribute to a better understanding of biofilm organization.
MCSS: microbial community simulator based on structure
Authors: Hui Xingqi , Yang Jinbao , Sun Jinhuan , Liu Fang , Pan Weihua
Published: March 2024

De novo assembly plays a pivotal role in metagenomic analysis, and the incorporation of third-generation sequencing technology can significantly improve the integrity and accuracy of assembly results. Recently, with advancements in sequencing technology (Hi-Fi, ultra-long), several long-read-based bioinformatic tools have been developed. However, the validation of the performance and reliability of these tools is a crucial concern. To address this gap, we present MCSS (microbial community simulator based on structure), which has the capability to generate simulated microbial community and sequencing datasets based on the structure attributes of real microbiome communities. The evaluation results indicate that it can generate simulated communities that exhibit both diversity and similarity to actual community structures. Additionally, MCSS generates synthetic PacBio Hi-Fi and Oxford Nanopore Technologies (ONT) long reads for the species within the simulated community. This innovative tool provides a valuable resource for benchmarking and refining metagenomic analysis methods.

Code available at:https://github.com/panlab-bio/mcss
Structural insights into the C-terminus of the histone-lysine N-methyltransferase NSD3 by small-angle X-ray scattering
Authors: Belviso Benny Danilo , Shen Yunpeng , Carrozzini Benedetta , Morishita Masayo , di Luccio Eric , Caliandro Rocco
Published: March 2024

NSD3 is a member of six H3K36-specific histone lysine methyltransferases in metazoans. Its overexpression or mutation is implicated in developmental defects and oncogenesis. Aside from the well-characterized catalytic SET domain, NSD3 has multiple clinically relevant potential chromatin-binding motifs, such as the proline–tryptophan–tryptophan–proline (PWWP), the plant homeodomain (PHD), and the adjacent Cys-His-rich domain located at the C-terminus. The crystal structure of the individual domains is available, and this structural knowledge has allowed the designing of potential inhibitors, but the intrinsic flexibility of larger constructs has hindered the characterization of mutual domain conformations. Here, we report the first structural characterization of the NSD3 C-terminal region comprising the PWWP2, SET, and PHD4 domains, which has been achieved at a low resolution in solution by small-angle X-ray scattering (SAXS) data on two multiple-domain NSD3 constructs complemented with size-exclusion chromatography and advanced computational modeling. Structural models predicted by machine learning have been validated in direct space, by comparison with the SAXS-derived molecular envelope, and in reciprocal space, by reproducing the experimental SAXS profile. Selected models have been refined by SAXS-restrained molecular dynamics. This study shows how SAXS data can be used with advanced computational modeling techniques to achieve a detailed structural characterization and sheds light on how NSD3 domains are interconnected in the C-terminus.