bluuebunny/crossref_metadata_2025 huggingface dataset:
La asociación entre la Leucopenia y la gravedad de la Sepsis: Un Análisis Sistemático
Authors: Núñez Pérez María
Published: May 2024

Este estudio se centra en la sepsis, una condición médica grave que puede resultar de una respuesta inflamatoria descontrolada a una infección, y su asociación con la leucopenia, una reducción en el número de leucocitos en la sangre. La investigación se justifica por la necesidad de comprender mejor cómo la leucopenia afecta la gravedad de la sepsis, potencialmente empeorando el pronóstico de los pacientes. Mediante un análisis sistemático de la literatura existente, se busca evaluar y confirmar esta asociación, resaltando la relevancia de la leucopenia como un indicador pronóstico en la gestión clínica de la sepsis. El estudio se desarrolló siguiendo un diseño sistemático riguroso, con criterios específicos de inclusión y exclusión para seleccionar estudios relevantes y asegurar la validez de los hallazgos. Los resultados indican una asociación significativa entre la leucopenia y la severidad de la sepsis, sugiriendo que la presencia de leucopenia puede servir como un marcador de mal pronóstico, lo cual es crucial para la estratificación del riesgo y la toma de decisiones terapéuticas en pacientes sépticos. A pesar de algunas limitaciones, como la heterogeneidad de los estudios y posibles sesgos, los hallazgos subrayan la necesidad de monitorizar los niveles de leucocitos en pacientes con sepsis y promover investigaciones futuras para explorar mecanismos subyacentes y evaluar intervenciones que mejoren los resultados clínicos.
Determining value in the treatment of activated PI3Kδ syndrome in Spain: a multicriteria decision analysis from the perspective of key stakeholders
Authors: Gil Alicia , Reyes Abad María , Alerany Carmen , Alsina Laia , López Granados Eduardo , Neth Olaf , Poveda José Luis , Rivière Jacques G. , Rodríguez-Gallego Carlos , Tutein Nolthenius Joanne B. , Figueiredo Raquel , Subías Labazuy Silvia
Published: May 2024

Introduction: Activated phosphoinositide 3-kinase (PI3K)δ syndrome (APDS) is an ultra-rare inborn error of immunity (IEI) combining immunodeficiency and immune dysregulation. This study determined what represents value in APDS in Spain from a multidisciplinary perspective applying multicriteria decision analysis (MCDA) methodology.
Methods: A multidisciplinary committee of nine experts scored the evidence matrix. A specific framework for orphan drug evaluation in Spain and the weights assigned by a panel of 98 evaluators and decision-makers was used. Re-evaluation of scores was performed.
Results: APDS is considered a very severe disease with important unmet needs, including misdiagnosis and diagnostic delay. Current management is limited to treatment of symptoms with off-label use of therapies supported by limited evidence. Therapeutic benefit is partial, resulting in limited disease control. Haematopoietic stem cell transplantation (HSCT), the only potential curative alternative, is restricted to a reduced patient population and without evidence of long-term efficacy or safety. All options present a limited safety profile. Data on patients’ quality of life are lacking. APDS is associated with high pharmacological, medical and indirect costs.
Conclusions: APDS is considered a severe disease, with limited understanding by key stakeholders of how treatment success is assessed in clinical practice, the serious impact that has on patients and the associated high economic burden. This study brings to light how MCDA methodology could represent a useful tool to complement current clinical and decision-making methods used by APDS experts and evaluators.
The omega-3 postbiotic trans-10-cis-15-octadecadienoic acid attenuates contact hypersensitivity in mice through downregulation of vascular endothelial growth factor A
Authors: Saika Azusa , Nagatake Takahiro , Kishino Shigenobu , Kitamura Nahoko , Honda Tetsuya , Hosomi Koji , Tiwari Prabha , Node Eri , Kawai Soichiro , Kondo Saki , Ishida Kei , Kabashima Kenji , Ogawa Jun , Kunisawa Jun
Published: May 2024

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid–derived metabolites: trans-10-cis-15-octadecadienoic acid (t10,c15-18:2) and cis-9-cis-15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2—but not c9,c15-18:2—attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid–derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis–induced inflammation.
Cryptococcus neoformans trehalose-6-phosphate synthase (tps1) promotes organ-specific virulence and fungal protection against multiple lines of host defenses
Authors: Goughenour Kristie , Creech Arianna , Xu Jintao , He Xiumiao , Hissong Rylan , Giamberardino Charles , Tenor Jennifer , Toffaletti Dena , Perfect John , Olszewski Michal
Published: May 2024

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted (tps1Δ) Cryptococci are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (tps1Δ:TPS1) strains expand in the lungs and disseminate, causing 100% mortality. Rapid pulmonary clearance of tps1Δ mutant is T-cell independent and relies on its susceptibility to lung resident factors and innate immune factors, exemplified by tps1Δ but not H99 inhibition in a coculture with dispersed lung cells and its rapid clearance coinciding with innate leukocyte infiltration. In the disseminated model of infection, which bypasses initial lung–fungus interactions, tps1Δ strain remains highly attenuated. Specifically, tps1Δ mutant is unable to colonize the lungs from the bloodstream or expand in spleens but is capable of crossing into the brain, where it remains controlled even in the absence of T cells. In contrast, strains H99 and tps1Δ:TPS1 rapidly expand in all studied organs, leading to rapid death of the infected mice. Since the rapid pulmonary clearance of tps1Δ mutant resembles a response to acapsular strains, the effect of tps1 deletion on capsule formation in vitro and in vivo was examined. Tps1Δ cryptococci form capsules but with a substantially reduced size. In conclusion, TPS1 is an important virulence factor, allowing C. neoformans evasion of resident pulmonary and innate defense mechanisms, most likely via its role in cryptococcal capsule formation.
Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects
Authors: Zhang Yu , Chen Shihan , Tian Yan , Fu Xianghui
Published: May 2024

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.
Animal models of Takotsubo syndrome: bridging the gap to the human condition
Authors: Zulfaj Ermir , Nejat AmirAli , Haamid Abdulhussain , Elmahdy Ahmed , Espinosa Aaron , Redfors Björn , Omerovic Elmir
Published: May 2024

Modelling human diseases serves as a crucial tool to unveil underlying mechanisms and pathophysiology. Takotsubo syndrome (TS), an acute form of heart failure resembling myocardial infarction, manifests with reversible regional wall motion abnormalities (RWMA) of the ventricles. Despite its mortality and clinical similarity to myocardial infarction, TS aetiology remains elusive, with stress and catecholamines playing central roles. This review delves into current animal models of TS, aiming to assess their ability to replicate key clinical traits and identifying limitations. An in-depth evaluation of published animal models reveals a variation in the definition of TS among studies. We notice a substantial prevalence of catecholamine-induced models, particularly in rodents. While these models shed light on TS, there remains potential for refinement. Translational success in TS research hinges on models that align with human TS features and exhibit the key features, including transient RWMA. Animal models should be comprehensively evaluated regarding the various systemic changes of the applied trigger(s) for a proper interpretation. This review acts as a guide for researchers, advocating for stringent TS model standards and enhancing translational validity.
Formation mechanism of the small-angle X-type strike-slip faults in deep basin and its controlling on hydrocarbon accumulation: a case study from the Tabei Uplift, Tarim Basin, NW China
Authors: Song Xingguo , Chen Shi , Zhang Yintao , Xie Zhou , Liang Xinxin , Yang Minghui , Zheng Mingjun , Shi Xukai
Published: May 2024

In the central Tarim Basin, numerous hydrocarbon deposits were found along ultra-deep strike-slip faults, and its evolving progress and formation mechanism are research hotspots. The Paleozoic small-angle X-type strike-slip fault in the Tabei Uplift is the research subject in this article. Based on high-precision three-dimensional seismic data, three structural deformation layers were revealed: the rift system, weak strike-slip deformation and salt tectonics in the deep structural layer (Sinian–Middle Cambrian), the strong strike-slip deformation and karst-dissolution structure in the middle structural layer (Upper Cambrian–Middle Ordovician), and echelon normal faults in the shallow structural layer (Upper Ordovician–Carboniferous). The formation and evolution of strike-slip faults is jointly controlled by the distribution pattern of basement rift and the activities of surrounding orogenic belts, which can be divided into three stages. In the Middle to Late Cambrian, the initial subduction of the Paleo-Asian and Proto-Tethyan oceans precipitated the emergence of two sets of small-angle X-type strike-slip faults, striking NW and NE above the grooves of Precambrian rifts, influenced by local weak compressive stress. Affected by the closure of peripheral paleo-ocean, strike-slip faults deformed considerably in the Middle–Late Ordovician and were reactivated in the Silurian–Carboniferous, forming en-echelon normal faults in the shallow layer. The layered deformation structure of the strike-slip faults significantly affects the accumulation of hydrocarbons. The differential hydrocarbon enrichment of faults in the Tabei Uplift is collectively influenced by the distribution of source rocks and the migration of oil and gas. The topographical features of the Tabei Uplift, along with the distribution of strike-slip faults across tectonic units, have rendered the NE direction the preferential pathway for hydrocarbon migration. Additionally, impacted by the development of en echelon faults, the NE-trending faults offer superior conditions for hydrocarbon preservation and charging condition, compared to the NW-trending faults.
Production characteristics and influencing factors of coalbed methane wells: a case study of the high-ranking coal seam in the southeastern Qinshui Basin, China
Authors: Chen Xiaolong , Gao Yufei , Wang Yaqing
Published: May 2024

This study focuses on coalbed methane (CBM) wells in high-ranking coal seam as the research subject. Considering the influence of effective stress and matrix shrinkage, a comprehensive permeability calculation model for CBM reservoirs is established. Based on this model, the variations in pressure and permeability during well production are quantified. By integrating static geological parameters, a finely classified classification of CBM wells is achieved using self-organizing map (SOM) neural network. Subsequently, an analysis of production dynamic characteristics and productivity differences among different types of CBM wells is performed, followed by providing drainage optimization suggestions. The results of SOM analysis show that 7,000 m3/d and 1,500 m3/d can be used as the production boundaries for the wells with different productivity in Block P. The daily gas production of exceptional well exceeds 7,000 m3/d, and the permeability remains relatively stable throughout the drainage process of this well. The daily gas production of the potential well ranges from 1,500 to 7,000 m3/d, and the permeability exhibits a significant decrease during the drainage process. The daily gas production of Inefficient well is consistently below 1,500 m3/d with moderate permeability variation. In addition to well location and structural geology, production variability is also influenced by the matching of reservoir conditions and drainage systems. This is primarily manifested in discontinuous drainage systems and rapid decline in bottom hole pressure (BHP) during early production. The analysis of drainage parameters indicates that in order to achieve optimal production from CBM wells, the BHP should exhibit an initial rapid decline followed by a slowly decrease during the early production period, with an average pressure drop ranging from 0.005 to 0.02 MPa/d. The research findings can offer technical guidance for the future advancement of CBM in the P Block.
The more, the better? A multivariate longitudinal study on L2 motivation and anxiety in EFL oral presentations
Authors: Wu Hao
Published: May 2024

Introduction

For decades, oral presentations have become a common method of assessment in language learning classrooms. Nonetheless, anxiety is a persistent negative feeling pervasive in EFL learners. Although applied linguistic research suggests that there is a relationship between motivation and anxiety, the nature and direction of this relationship remain inconsistent.

Methods

To tackle this concern, this mixed-methods longitudinal study aimed to investigate the growth trajectories of Chinese EFL learners’ L2 motivation and anxiety in oral presentations. The participants were 171 second-year undergraduate medical students who attended an English for Academic Purposes (EAP) course. They delivered four oral presentations and reported their L2 motivation and anxiety levels in questionnaire surveys.

Results

(1) As the number of EFL learners giving oral presentations increased, the L2 motivation levels increased, and the anxiety levels decreased. (2) Those who were initially more anxious about giving oral presentations had higher decrease rates during the four oral presentations. (3) There was co-development but inverse relationships between ideal L2 self and anxiety and between ought-to L2 self and anxiety, although a complete parallel process model was not established.

Discussion

These findings suggest that students’ perceptions of L2 motivation interact with anxiety levels over time but in a sophisticated fashion. Finally, pedagogical implications for EFL oral presentation instruction are provided.
Differences in IDO1+ dendritic cells and soluble CTLA-4 are associated with differential clinical responses to methotrexate treatment in rheumatoid arthritis
Authors: Malik Anikó E. , Slauenwhite Drew , McAlpine Sarah M. , Hanly John G. , Marshall Jean S. , Issekutz Thomas B.
Published: May 2024

Objective

Antigen-presenting dendritic cells (DCs) and monocytes play an essential role in rheumatoid arthritis (RA) pathogenesis, however, their tolerogenic potential remains unclear. Herein, the tolerogenic profiles of DCs are characterized in treatment-naïve RA patients to determine their role to inflammatory arthritis management.

Methods

Thirty-six treatment-naïve RA patients were enrolled, of which 62% were non-responders to methotrexate (MTX) monotherapy based on disease activity score (DAS) after 6-months of therapy. DC and monocyte subset frequencies, activation (CD40, CD86, CD209 expression), and tolerogenic profile (intracellular indoleamine-2,3-dioxygenase [IDO1] and cytotoxic T lymphocyte antigen 4 [CTLA-4] expression) were examined in the baseline peripheral blood by multicolor flow-cytometry. Soluble CTLA-4 (sCTLA-4) levels in plasma were measured.

Results

DC subsets were decreased in RA compared to healthy controls (HC), and the frequency of conventional DCs (cDC) inversely correlated with inflammatory markers and improvement in disease activity. CD141+ cDC1s were the major IDO1-expressing cells. IDO1+cDC1s were reduced in RA patients compared to HC. The baseline frequency of IDO1+cDC1s inversely correlated with improvement in disease activity. CTLA-4 expression in CD1c+ cDC2s and monocytes was lower in RA patients compared to HC. Moreover, MTX-responders had a significantly lower frequency of IDO1+cDC1 cells and higher level of sCTLA-4 in the plasma compared to MTX non-responders. There was a strong predictive association of low IDO1+cDC1 cells, low sCTLA-4 and non-response to MTX.

Conclusions

Our findings reveal altered DC and monocytes immunophenotypes that are associated with RA pathology and treatment response. The frequencies of tolerogenic IDO1+cDC1s and the low level of sCTLA-4 are strongly associated with MTX non-responsiveness and therapeutic outcome. These results suggest that investigation of the association IDO1+cDC1 and sCTLA-4 with response to treatment may be more generalizable to other autoimmune diseases.
Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes
Authors: Ma Boyi , Ren Chenlu , Yin Yadong , Zhao Shuhua , Li Jia , Yang Hong
Published: May 2024

Background

Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women’s lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism.

Methods

Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively.

Results

A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors.

Conclusion

The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients’ prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.
Application of a biofilm-enhanced A2O system in the treatment of wastewater from mariculture
Authors: Ma Xiaona , Yin Rui , Yang Chen , Cai Chen , Zhao Jufan , Lv Chuxiu , Wang Xinchen , Chen Shiyu , Ren Jilong , Zhang Bingzhi
Published: May 2024

Development of environment-friendly and efficient aquaculture effluent treatment system is crucial for sustainable intensification of aquaculture, in the face of the rapidly increasing environmental pressure in the mariculture industry. In this study, mariculture wastewater was treated by the anoxic-anaerobic-oxic biochemical treatment system (A2O system) with traditional activated sludge replaced by nitrifying bacteria, denitrification bacteria and phosphorus accumulating bacteria absorbed on PBS carrier biofilms suitable for saline/brackish water. The results showed that biofilm-enhanced A2O system can effectively remove pollutants from aquaculture wastewater. The removal efficiencies of CODMn, NH4+-N, TN and TP in A2O system were approximately 86.3%-90.8%, 97.7%-99.5%, 94.6%-95.2% and 97.0%-98.1%. The results further showed that CODMn, NH4+-N, and TN were mainly removed in anaerobic tank and anoxic tank, while TP was mainly removed in the anoxic tank and oxic tank. The biofilm-enhanced A2O system by adding nitrifying bacteria and phosphorus accumulating bacteria biofilms using PBS as carriers instead of conventional activated sludge could be applied to the treatment of circulating aquaculture wastewater. This study provides a feasible scheme for enhancing the efficiency of A2O system in the treatment of aquaculture tail water, and provides a reference for the immobilization of microorganisms.
Metal in biological samples from electronic cigarette users and those exposed to their second-hand aerosol: a narrative review
Authors: Batista Diane Rezende , Coelho Liana Sousa , Tanni Suzana Erico , de Godoy Irma
Published: May 2024

Introduction

Electronic nicotine delivery systems (ENDS) are gradually becoming more popular, particularly, among today’s youth. Despite being marketed as safe by the tobacco industry, the notable absence of regulation in their composition is evident. Both the generated fluids and aerosol exhibit a wide variety of substances that are not yet fully identified. In addition to additives, the aerosol contains metals, the presence of which can be attributed to the excessive heating of metallic filaments used in vaporizing the liquid.

Objective

This review aimed to identify and describe studies that have assessed metal levels in biological samples obtained from electronic cigarette users and those exposed to their second-hand aerosol. This involved detailing the types and concentrations of metals identified and the biological samples in which the metals were detected.

Methods

Two independent researchers conducted searches in the MEDLINE and EMBASE databases to identify studies that measured the metal levels in human non-invasive biological samples from electronic cigarette users and second-hand exposure. Data were presented as a narrative review.

Results

In total, 18 articles were included in this review. Overall active and passive exposure to ENDS was related to higher levels of many metals, including lead and cadmium, in biological samples. ENDS users, in general, have lower metal concentrations in biological samples compared to the users of combustible cigarettes.

Conclusion

The exposure to primary and second-hand e-cigarette aerosol is related to higher metal concentrations in the biological samples. The adverse effects of this exposure on long-term users are yet to be determined.
Feature elimination and stacking framework for accurate heart disease detection in IoT healthcare systems using clinical data
Authors: Jian Wang , Li Jian Ping , Haq Amin Ul , Khan Shakir , Alotaibi Reemiah Muneer , Alajlan Saad Abdullah , Heyat Md Belal Bin
Published: May 2024

Introduction

Heart disease remains a complex and critical health issue, necessitating accurate and timely detection methods.

Methods

In this research, we present an advanced machine learning system designed for efficient and precise diagnosis of cardiac disease. Our approach integrates the power of Random Forest and Ada Boost classifiers, along with incorporating data pre-processing techniques such as standard scaling and Recursive Feature Elimination (RFE) for feature selection. By leveraging the ensemble learning technique of stacking, we enhance the model's predictive performance by combining the strengths of multiple classifiers.

Results

The evaluation metrics results demonstrate the superior accuracy and obtained the higher performance in terms of accuracy, 99.25%. The effectiveness of our proposed system compared to baseline models.

Discussion

Furthermore, the utilization of this system within IoT-enabled healthcare systems shows promising potential for improving heart disease diagnosis and ultimately enhancing patient outcomes.
Liposomal mitoxantrone-based multidrug chemotherapy as a bridge to allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute lymphoblastic leukemia (ALL) after immunotherapy failure: a case report
Authors: Deng Jin , Chen Hongxia , Yang Yi , Ji Hua , Liu Hui
Published: May 2024

Acute lymphoblastic leukemia (ALL) represents a malignancy involving early-stage differentiated lymphoid cells that invade the bone marrow, blood, and extramedullary sites. First-line treatment spans 2–3 years with induction, consolidation, intensification, and long-term maintenance phases. Relapsed/refractory (R/R) ALL typically carries an adverse prognosis, and there is currently no standard of care for this disease. Here, we present a case of R/R ALL that responded effectively to liposomal mitoxantrone-based multidrug chemotherapy, resulting in a rapid complete response after 35 days of therapy. Subsequently, the patient was successfully treated with allo-HSCT. At 5 months follow-up, the patient was alive and leukemia-free. Additionally, no severe adverse events were recorded during liposomal mitoxantrone treatment or hospitalization for allo-HSCT. Given the encouraging efficacy and the manageable adverse events observed in our case, liposomal mitoxantrone-based multidrug chemotherapy should be further explored as a bridge to allo-HSCT in patients with R/R ALL.
Theoretical investigations on modeling blood flow through vessel for understanding effectiveness of magnetic nanocarrier drug delivery systems
Authors: Alzhrani Rami M. , Aldawsari Mohammed F. , Alamoudi Jawaher Abdullah
Published: May 2024

For cancer therapy, the focus is now on targeting the chemotherapy drugs to cancer cells without damaging other normal cells. The new materials based on bio-compatible magnetic carriers would be useful for targeted cancer therapy, however understanding their effectiveness should be done. This paper presents a comprehensive analysis of a dataset containing variables x(m), y(m), and U(m/s), where U represents velocity of blood through vessel containing ferrofluid. The effect of external magnetic field on the fluid flow is investigated using a hybrid modeling. The primary aim of this research endeavor was to construct precise and dependable predictive models for velocity, utilizing the provided input variables. Several base models, including K-nearest neighbors (KNN), decision tree (DT), and multilayer perceptron (MLP), were trained and evaluated. Additionally, an ensemble model called AdaBoost was implemented to further enhance the predictive performance. The hyper-parameter optimization technique, specifically the BAT optimization algorithm, was employed to fine-tune the models. The results obtained from the experiments demonstrated the effectiveness of the proposed approach. The combination of the AdaBoost algorithm and the decision tree model yielded a highly impressive score of 0.99783 in terms of R2, indicating a strong predictive performance. Additionally, the model exhibited a low error rate, as evidenced by the root mean square error (RMSE) of 5.2893 × 10−3. Similarly, the AdaBoost-KNN model exhibited a high score of 0.98524 using R2 metric, with an RMSE of 1.3291 × 10−2. Furthermore, the AdaBoost-MLP model obtained a satisfactory R2 score of 0.99603, accompanied by an RMSE of 7.1369 × 10−3.
A decade of insight: bibliometric analysis of gut microbiota’s role in osteoporosis (2014–2024)
Authors: Luo Zhi Qiang , Huang Ya Jing , Chen Ze Hua , Lu Chen Yin , Zhou Biao , Gong Xiang Hao , Shen Zhen , Wang Tao
Published: May 2024

Purpose

Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota’s contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods.

Methods

Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package “Bibliometrix” for bibliometric analysis.

Results

A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. “Probiotics” and “inflammation” are the keywords in the research.

Conclusion

This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.
Assessment of the relationship between gut microbiota and bone mineral density: a two-sample Mendelian randomization study
Authors: Xue Yuan , Wang Xuan , Liu Honglin , Kang Junfeng , Liang Xiaohong , Yao Aina , Dou Zhifang
Published: May 2024

Background

Emerging evidence from observational studies and clinical trials suggests a connection between the gut microbiota and variations in bone mineral density (BMD). Nonetheless, the specific association between gut microbiota and BMD alterations at different skeletal sites has not been comprehensively explored. To address this, we employed Genome-Wide Association Study (GWAS) summary statistics from a publicly accessible database, conducting a two-sample Mendelian Randomization analysis to elucidate the potential causal relationship between gut microbiota composition and BMD.

Methods

This study utilized two distinct thresholds for screening instrumental variables (IVs), followed by an extensive series of quality control procedures to identify IVs that were significantly related to exposure. Gut microbiota were classified into two sets based on hierarchical levels: phylum, class, order, family, and genus. Bone mineral density (BMD) data were systematically collected from four skeletal sites: femoral neck, lumbar spine, forearm, and heel. For Mendelian Randomization (MR) analysis, robust methods including Inverse-Variance Weighting (IVW) and the Wald Ratio Test were employed. Additional analytical tests such as the Outlier Test, Heterogeneity Test, ‘Leave-One-Out’ Test, and Pleiotropy Test were conducted to assess the impact of horizontal pleiotropy, heterogeneities, and the genetic variation stability of gut microbiota on BMD causal associations. The MR Steiger Directionality Test was applied to exclude studies with potential directional biases.

Results

In this two-sample Mendelian randomization analysis, we utilized five sets of exposure GWAS (Genome-Wide Association Studies) summary statistics and four sets of outcome GWAS summary statistics. The initial analysis, applying a threshold of p < 5 × 10−6, identified 48 significant causal relationships between genetic liability in the gut microbiome and bone mineral density (BMD). A subsequent analysis with a more stringent threshold of p < 5 × 10−8 uncovered 14 additional causal relationships. Upon applying the Bonferroni correction, 9 results from the first analysis and 10 from the second remained statistically significant.

Conclusion

Our MR analysis revealed a causal relationship between gut microbiota and bone mineral density at all sites, which could lead to discoveries in future mechanistic and clinical studies of microbiota-associated osteoporosis.
Effect of Lentinus sajor-caju on the chemical composition and antioxidant activity of highland barley straw under solid-state fermentation
Authors: Wang Yuqiong , Liao Yangci , Gou Changlong , Zhang Hang , Chen Liming , Bao Yuhong
Published: May 2024

Introduction

The efficient utilization of straw resources as animal feed has gained considerable attention. The objective of this study was to evaluate whether Lentinus sajor-caju treatment alters the chemical composition and antioxidant activity of highland barley straw and enhances its functional value as a ruminant feed.

Methods

The chemical composition, antioxidant capacity, and metabolomic profile of highland barley straw were determined after 21 days of solid-state fermentation with L. sajor-caju at 25°C. The differential metabolites between fermented and unfermented highland barley straw were identified by LC–MS and the relationship between the identified metabolites and antioxidant capacity was elucidated.

Results

The results showed that, compared with untreated highland barley straw, the crude protein and ether extract contents were higher (51.55 and 76.43%, respectively) in highland barley straw after 21 days of incubation with L. sajor-caju, whereas the hemicellulose, cellulose, and acid detergent lignin contents were lower (2.48, 25.08, and 45%, respectively). The total antioxidant capacity was significantly higher in L. sajor-caju-treated than in untreated highland barley straw. In total, 600 differential metabolites (301 upregulated and 299 downregulated) were identified between L. sajor-caju-fermented and unfermented highland barley straw. Correlation analysis results showed that Fe2+ scavenging and total phenolic content were strongly correlated with total antioxidant capacity. Meanwhile, the differential flavonoid metabolites between fermented and unfermented highland barley straw were primarily associated with antioxidant activity, with kaempferol 3-xylosylglucoside, isoginkgetin, and rhoifolin being the most representative.

Conclusion

Thus, this study demonstrates that L. sajor-caju could enhance the functional value of highland barley straw, showing the potential of L. sajor-caju for improving the utilization of agricultural straws in ruminants.
Next generation sequencing-aided screening, isolation, molecular identification, and antimicrobial potential for bacterial endophytes from the medicinal plant, Elephantorrhiza elephantina
Authors: Tlou Matsobane , Ndou Benedict , Mabona Nokufa , Khwathisi Adivhaho , Ateba Collins , Madala Ntakadzeni , Serepa-Dlamini Mahloro Hope
Published: May 2024

Elephantorrhiza elephantina, a wild plant in southern Africa, is utilized in traditional medicine for various ailments, leading to its endangerment and listing on the Red List of South African Plants. To date, there have been no reports on bacterial endophytes from this plant, their classes of secondary metabolites, and potential medicinal properties. This study presents (i) taxonomic characterization of bacterial endophytes in leaf and root tissues using 16S rRNA, (ii) bacterial isolation, morphological, and phylogenetic characterization, (iii) bacterial growth, metabolite extraction, and LC–MS-based metabolite fingerprinting, and (iv) antimicrobial testing of bacterial crude extracts. Next-generation sequencing yielded 693 and 2,459 DNA read counts for the rhizomes and leaves, respectively, detecting phyla including Proteobacteria, Bacteroidota, Gemmatimonadota, Actinobacteriota, Verrucomicrobiota, Dependentiae, Firmicutes, and Armatimonodata. At the genus level, Novosphingobium, Mesorhizobium, Methylobacterium, and Ralstonia were the most dominant in both leaves and rhizomes. From root tissues, four bacterial isolates were selected, and 16S rRNA-based phylogenetic characterization identified two closely related Pseudomonas sp. (strain BNWU4 and 5), Microbacterium oxydans BNWU2, and Stenotrophomonas maltophilia BNWU1. The ethyl acetate:chloroform (1:1 v/v) organic extract from each isolate exhibited antimicrobial activity against all selected bacterial pathogens. Strain BNWU5 displayed the highest activity, with minimum inhibitory concentrations ranging from 62.5 μg/mL to 250 μg/mL against diarrhoeagenic Escherichia coli, Escherichia coli O157:H7, Salmonella enterica, antibiotic-resistant Vibrio cholerae, Staphylococcus aureus, Bacillus cereus, and Enterococcus durans. LC–MS analysis of the crude extract revealed common antimicrobial metabolites produced by all isolates, including Phenoxomethylpenicilloyl (penicilloyl V), cis-11-Eicosenamide, 3-Hydroxy-3-phenacyloxindole, and 9-Octadecenamide.
Enhancement on migration and biodegradation of Diaphorobacter sp. LW2 mediated by Pythium ultimum in soil with different particle sizes
Authors: Li Jialu , Hong Mei , Lv Jing , Tang Rui , Wang Ruofan , Yang Yadong , Liu Na
Published: May 2024

Introduction

The composition and structure of natural soil are very complex, leading to the difficult contact between hydrophobic organic compounds and degrading-bacteria in contaminated soil, making pollutants hard to be removed from the soil. Several researches have reported the bacterial migration in unsaturated soil mediated by fungal hyphae, but bacterial movement in soil of different particle sizes or in heterogeneous soil was unclear. The remediation of contaminated soil enhanced by hyphae still needs further research.

Methods

In this case, the migration and biodegradation of Diaphorobacter sp. LW2 in soil was investigated in presence of Pythium ultimum.

Results

Hyphae could promote the growth and migration of LW2 in culture medium. It was also confirmed that LW2 was able to migrate in the growth direction and against the growth direction along hyphae. Mediated by hyphae, motile strain LW2 translocated over 3 cm in soil with different particle size (CS1, 1.0–2.0 mm; CS2, 0.5–1.0mm; MS, 0.25–0.5 mm and FS, <0.25 mm), and it need shorter time in bigger particle soils. In inhomogeneous soil, hyphae participated in the distribution of introduced bacteria, and the total number of bacteria increased. Pythium ultimum enhanced the migration and survival of LW2 in soil, improving the bioremediation of polluted soil.

Discussion

The results of this study indicate that the mobilization of degrading bacteria mediated by Pythium ultimum in soil has great potential for application in bioremediation of contaminated soil.
Potential SLA Hp-4.0 haplotype-restricted CTL epitopes identified from the membrane protein of PRRSV induce cell immune responses
Authors: Luo Tingyu , Xin Chang , Liu Hongyi , Li Changwen , Chen Hongyan , Xia Changyou , Gao Caixia
Published: May 2024

Swine leukocyte antigen (SLA) class I molecule-restricted T-cell epitopes, which induce cytotoxic T lymphocyte (CTL) responses, play a critical role in the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) and the development of efficient protective vaccines. The SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01 alleles, assigned the Hp-4.0 haplotype, are highly prevalent and usually present in all pig breeds. However, the SLA Hp-4.0 haplotype-restricted CTL epitopes in the structural membrane (M) protein of PRRSV are still unknown. In this study, we predicted 27 possible 9-mer epitope peptides in M protein with high binding scores for SLA-1*04:01:01 using CTL epitope prediction tools. In total, 45 SLA class I complexes, comprising the predicted peptide, extracellular region of the SLA-I molecules, and β2-microglobulin, were constructed in vitro to detect the specific binding of these peptides to SLA-1*04:01:01 (27 complexes), SLA-2*04:01 (9 complexes), and SLA-3*04:01 (9 complexes), respectively. Our results showed that the M27 (T91WKFITSRC), M39 (N130HAFVVRRP), and M49 (G158RKAVKQGV) peptides bind specifically to SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01, respectively. Subsequently, using peripheral blood mononuclear cells (PBMCs) isolated from the homozygous Hp-4.0 and Hp-26.0 haplotype piglets vaccinated with commercial PRRSV HuN4-F112 strain, we determined the capacities of these 27 potential peptides to stimulate their proliferation with a Cell Counting Kit-8 and their secretion and expression of interferon gamma (IFN-γ) with an ELISpot assay and real-time qPCR, respectively. The immunological activities of M27, M39, and M49 were therefore confirmed when they efficiently induced PBMC proliferation and IFN-γ secretion in PBMCs from piglets with the prevalent SLA Hp-4.0 haplotype. The amino acid sequence alignment revealed that M27, M39, and M49 are highly conserved among 248 genotype II PRRSV strains collected between 1998 and 2019. These findings contribute to the understanding of the mechanisms of cell-mediated immune responses to PRRSV. Our study also provides a novel strategy for identifying and confirming potential SLA haplotype-restricted CTL epitopes that could be used to develop novel peptide-based vaccines against swine diseases.
Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes
Authors: Pastor Florentin , Charles Emilie , Belmudes Lucid , Chabrolles Hélène , Cescato Marion , Rivoire Michel , Burger Thomas , Passot Guillaume , Durantel David , Lucifora Julie , Couté Yohann , Salvetti Anna
Published: May 2024

Phosphorylation is a major post-translation modification (PTM) of proteins which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either promote or counteract viral replication. Among more than 500 kinases constituting the human kinome only few have been described as important for the hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core (HBc) protein. In addition, little is known on the consequences of HBV infection on the activity of cellular kinases. The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape early after infection. For this, primary human hepatocytes (PHHs) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phosphoproteomic analysis was conducted 2- and 7-days post-infection. The results indicated that while, as expected, HBV infection only minimally modified the cell proteome, significant changes were observed in the phosphorylation state of several host proteins at both time points. Gene enrichment and ontology analyses of up- and down-phosphorylated proteins revealed common and distinct signatures induced by infection. In particular, HBV infection resulted in up-phosphorylation of proteins involved in DNA damage signaling and repair, RNA metabolism, in particular splicing, and cytoplasmic cell-signaling. Down-phosphorylated proteins were mostly involved in cell signaling and communication. Validation studies carried out on selected up-phosphorylated proteins, revealed that HBV infection induced a DNA damage response characterized by the appearance of 53BP1 foci, the inactivation of which by siRNA increased cccDNA levels. In addition, among up-phosphorylated RNA binding proteins (RBPs), SRRM2, a major scaffold of nuclear speckles behaved as an antiviral factor. In accordance with these findings, kinase prediction analysis indicated that HBV infection upregulates the activity of major kinases involved in DNA repair. These results strongly suggest that HBV infection triggers an intrinsic anti-viral response involving DNA repair factors and RBPs that contribute to reduce HBV replication in cell culture models.