bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonpathogenic E. coli engineered to surface display cytokines as a new platform for immunotherapy
Authors: Romee Rizwan , Yang Shaobo , Sheffer Michal , Kaplan Isabel , Wang Zongqi , Tarannum Mubin , Dinh Khanhlinh , Abdulhamid Yasmin , Shapiro Roman , Porter Rebecca , Soiffer Robert , Ritz Jerome , Koreth John , Wei Yun , Chen Peiru , Zhang Ke , Márquez-Pellegrin Valeria , Bonanno Shanna , Joshi Neel , Guan Ming , Yang Mengdi , Li Deng , Bellini Chiara , Chen Jianzhu , Wu Catherine , Barbie David , Li Jiahe 
Published: March 2024

Abstract

Given the safety, tumor tropism, and ease of genetic manipulation in non-pathogenic Escherichia coli (E. coli), we designed a novel approach to deliver biologics to overcome poor trafficking and exhaustion of immune cells in the tumor microenvironment, via the surface display of key immune-activating cytokines on the outer membrane of E. coli K-12 DH5α. Bacteria expressing murine decoy-resistant IL18 mutein (DR18) induced robust CD8+ T and NK cell-dependent immune responses leading to dramatic tumor control, extending survival, and curing a significant proportion of immune-competent mice with colorectal carcinoma and melanoma. The engineered bacteria demonstrated tumor tropism, while the abscopal and recall responses suggested epitope spreading and induction of immunologic memory. E. coli K-12 DH5α engineered to display human DR18 potently activated mesothelin-targeting CAR NK cells and safely enhanced their trafficking into the tumors, leading to improved control and survival in xenograft mice bearing mesothelioma tumor cells, otherwise resistant to NK cells. Gene expression analysis of the bacteria-primed CAR NK cells showed enhanced TNFα signaling via NFκB and upregulation of multiple activation markers. Our novel live bacteria-based immunotherapeutic platform safely and effectively induces potent anti-tumor responses in otherwise hard-to-treat solid tumors, motivating further evaluation of this approach in the clinic.
Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals
Authors: Heinzel Sebastian , Jureczek Jenna , Kainulainen Veera , Nieminen Anni I. , Suenkel Ulrike , von Thaler Anna-Katharina , Kaleta Christoph , Eschweiler Gerhard W. , Brockmann Kathrin , Aho Velma T. E. , Auvinen Petri , Maetzler Walter , Berg Daniela , Scheperjan Filip 
Published: March 2024

Abstract

Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large cohort of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND study. Low (0–50 µg/g; n = 602), moderate (> 50–100 µg/g; n = 64) and high (> 100 µg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by gut microbiota. Moreover, the high calprotectin group showed increased BMI and more frequent disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.
Integrated Analysis of Single-Cell RNA Sequencing and Transcriptome Data Identifies a Pyroptosis-Associated Diagnostic Model for Parkinson’s Disease
Authors: Wang Lin , Qin Yidan , Song Jia , Xu Jing , Quan Wei , Su Hang , Zeng Huibin , Zhang Jian , Li Jia , Chen Jiajun 
Published: March 2024

Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by insidious onset. Despite the emphasis on motor symptom-based diagnosis, there remains an unmet clinical need for effective diagnostic approaches during the prodromal phase of PD. Recent advancements in single-cell RNA sequencing (scRNA-seq) and transcriptomic analyses of PD patients open avenues for identifying potential diagnostic biomarkers.
Methods: A comprehensive cell trajectory analysis was conducted using scRNA-seq datasets to pinpoint gene expressions associated with cellular transition from healthy to PD-affiliated state. Integrating the scRNA-seq datasets with Weighted Gene Co-expression Network Analysis (WGCNA) allowed the extraction of pyroptosis-associated differentially expressed genes (PDEGs). Leveraging LASSO logistic regression, Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and random forest methodologies, we devised a diagnostic model centered on PDEGs. Additionally, immunoinfiltration, inflammatory signaling pathways, and intercellular communication were discerned through scRNA-seq analyses.
Results: In PD patients, the number of cells including metencephalic-like cells, excitatory neurons, inhibitory neurons, and MHB-like cells were significantly reduced, whereas the proportion of astrocytes and microglia, the immunoinfiltration and inflammatory signaling pathways were upregulated as compared with healthy individuals. Using scRNA-seq and WGCNA analyses, two pyroptosis-related diagnostic genes POLR2K and TIMM8B were identified, and a diagnostic model based on them was constructed, which showed promising performance upon validation.
Conclusion: This study cleverly established a pyroptosis-related diagnostic model for PD through the analyses of scRNA-seq combined with transcriptome data, which improved the understanding of the role of PDEGs in PD and provided new insights into the diagnostic strategies for this neurodegenerative ailment.
Investigation of dynamic postural control in athletes with and without chronic ankle instability accompanied by high and low levels of kinesiophobia during jump landing: A cross-sectional study
Authors: Jafari Sarah , Naimi Sedigheh Sadat , Ebrahimabadi Zahra , Yousefi Mohammad , Mortezanejad Marzieh , Shanbehzadeh Sanaz 
Published: March 2024

Abstract
Background
Individuals with chronic ankle instability (CAI) commonly experience pain, swelling, giving way, and postural instability. It has been observed that they exhibit a certain level of fear of movement, which impacts their postural stability. The degree of fear of movement can be assessed using the Tampa Scale of Kinesiophobia (TSK), ranging from low to high levels. Dysfunction in postural control can be influenced by this fear of movement. In the present study, researchers compared the dynamic postural control characteristics during jump landing between CAI athletes with low and high levels of kinesiophobia and healthy controls.
Methods
Sixty participants with CAI were divided into three groups: CAI subjects with low kinesiophobia, CAI subjects with high kinesiophobia (determined by a cutoff of 38 in TSK score), and healthy controls. The participants performed a single-leg jump landing on a force plate, either on the side of the unstable ankle for CAI subjects or on the matching ankle for healthy controls. Time to stabilization (TTS), center of pressure displacement (COP), velocity of COP displacement in anterior-posterior (AP) and medial-lateral (ML) directions, as well as the total direction, were calculated for further analysis as outcome measures. Statistical analysis was conducted using one-way analysis of variance, with a significance level set at 0.05 for each analysis.
Results
The study's results revealed that the time to stability in the AP and total direction exhibited the most significant difference between the high kinesiophobia group and the healthy control groups (P = 0.019, P = 0.00 respectively). Additionally, CAI subjects with high kinesiophobia demonstrated a significant increase in the standard deviation of COP velocity in the AP direction (P = 0.002), a significant decrease in COP velocity variability in the ML direction (P = 0.002), and a significant increase in COP displacement variability in the ML direction compared to healthy controls (P = 0.006).
Conclusions
Individuals with high fear of re-injury may perceive the jumping landing task as threatening, requiring more time to land and regain stability. This fear can limit the variability of velocity in the ML direction, leading to reduced control over the AP direction due to constraints on controlling degrees of freedom.
The Single-cell Atlas of Short-chain Fatty Acid Receptors in Human and Mice Hearts
Authors: He Xiaojun , Long Qiang , Zhong Yiming , Qi Zhaoxi , Zhang Yecen , Qian Bei , Huang Shixing , Wang Xinming , Yang Xiaomei , Gao Wei Dong , Ye Xiaofeng , Zhao Qiang 
Published: March 2024

Abstract

The short-chain fatty acids (SCFAs), the product of dietary fiber fermentation by the gut microbiota, can protect against multiple cardiovascular diseases, while the molecular targets and underlying mechanisms need to be elucidated. One of the primary mechanisms of SCFA benefits was the direct activation of a group of G-protein-coupled receptors (GPCRs), termed free fatty acid receptors (FFARs), the FFAR2 (GPR43), and FFAR3 (GPR41). GPCRs serve as key regulators of a variety of intracellular responses and enable the design of highly selective novel drugs with reduced unwanted side effects. This needs an understanding of the heterogeneous distribution of GPCRs across multiple cell types and their overlapping signaling networks. At present, the distribution of FFAR2/3 in cardiac cells has not been entirely clarified. Using the public single-cell RNA-seq and single-nuclear RNA-seq data of human and mouse hearts, we illustrate the entire atlas of FFAR2/3 distribution in different regions and cell types in normal and infarcted hearts. These findings provide valuable information on the possible effect of SCFAs via FFAR2/3 in the heart and valuable references for future studies.
Anti-seasonal flooding drive substantial alterations in riparian plant diversity and niche characteristics in a unique hydro-fluctuation zone
Authors: Li Xiaoling , Yi Wenxiong , Duan Xiaodie , Chen Gong , Yang Jin , Deng Danli , Guo Xiaojuan , Yang Zhengjian , Huang Guiyun , Hu Meixiang , Ye Chen 
Published: March 2024

Abstract
Human-induced disturbances such as dam construction and regulation often alter the duration，frequency and seasonality of flooding and thus substantially influence plant characteristics in the hydro-fluctuation zones. However, the effect mechanism of anti-seasonal hydrological alterations on vegetation distribution patterns and niche characteristics in the water level fluctuation zones (WLFZs).is still unclear. In this study, 368 quadrats were selected to investigate the effects of the anti-seasonal hydrological regimes on the foristic composition, species diversity and niche characteristic in the hydro-fluctuation zone of the Three Gorges Reservoir (TGR), a unique riparian ecosystem, China. The results showed that the number of species per square meter (S), the Shannon-Wiener diversity index (H) and Simpson dominance index (D) of the plant guilds in the TGR increased significantly with elevation, which was inconsistent with humped diversity–disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index (E). The H, D, S and E from upstream to downstream firstly showed a significant increasing trend (p<0.05), reached the highest in the middle reaches, and then decreased in the lower reaches. The vegetation was classified into 12 guild types but the vegetation composition showed a significant variation with a transition from xerophytes to mesophytes and hygrophytes with the increasing flooding time. Cynodon dactylon was the most dominant species based on its highest important value and niche breadth. And high niche breadth had a high niche overlap between species. Therefore, anti-seasonal hydrological alterations precipitated substantial reduction of plant diversity, species competition and exclusion among species by expanding the niche in the guilds. The vegetation in the unique riparian ecosystems was still in the primary stage of plant community succession with low species diversity, high niche overlap, intense competition and obvious single-species dominant communities. Compared to total nitrogen, total phosphorus and soil organic matter factors, the hydrological alteration filtering was more important in explaining the plant guild patterns and niche characteristics. Therefore, there may be some differences in the governance strategies adopted in different areas of the novel riparian ecosystems for vegetation restoration efforts of the riparian forests.
Unraveling the Spatio-Temporal Dynamics of Soil and Root-Associated Microbiome in Texas Olive Orchards: A Comprehensive Analysis
Authors: Thenappan Dhivya P. , Thompson Dalton , Joshi Madhumita , Mishra Amit Kumar , Joshi Vijay 
Published: March 2024

Abstract

Understanding the structure and diversity of microbiomes is critical to establishing olives in non-traditional production areas. Limited studies have investigated soil and root-associated microbiota dynamics in olives across seasons or locations in the United States. We explored the composition and spatiotemporal patterns in two niches (roots and soils), seasons (spring, summer, and fall), and domains (bacteria and fungi) in the microbiome of the olive variety Arbequina across three olive orchards in Texas to investigate the structure of the olive-associated microbial communities and specificity to the root endosphere and soil rhizosphere zones. The bacterial populations in the rhizosphere (16.42%) and endosphere (15.49%) were dominated by Phylum Proteobacteria, followed by Actinobacteriota (RS, 12.63%; RE, 16.47%). Rubrobacter (5.27%) and Actinophytocola (3.49%) were dominant taxa in the rhizosphere and root endosphere at the genus level. Among fungal communities, phylum Ascomycota was prevalent in the rhizosphere (71.09%) and endosphere (41.37%). Members of the Chaetomiaceae taxon outnumbered (17.61%) another taxon in the root endosphere. As Per the alpha diversity indices, rhizosphere soil at Moulton showed much higher richness and diversity than other places, which predicted a significant difference in rhizosphere between locations for bacterial diversity and richness. There was no significant variation in the bacterial diversity in the niches and the fungal diversity within the root endosphere between locations. Beta diversity analysis confirmed the effect of compartments (Fungi: 12.3%; Bacteria: 45.1%) in influencing community differences. Microbial diversity was apparent within the endosphere (Bacteria:14.6%, Fungi:15.6%) and rhizosphere (30.5%, Fungi: 21.6%). The seasons influenced only the rhizosphere fungal diversity (8.5%), contrasting the bacterial diversity in either niche. The research provided a comprehensive overview of the microbial diversity present in both the rhizosphere and endosphere of olive trees. The abundance and composition of OTUs associated with the rhizosphere soil of Arbequina suggest its role as a source reservoir in defining the potential endophytes.
Second Order Numerical Technique for Singularly Perturbed Delay Differential Equations of Reaction Diffusion Type with Small Shift
Authors: Regal Akhila Mariya , S Dinesh Kumar 
Published: March 2024

Abstract

In this paper,we propose a finite difference scheme to solve singularly perturbed delay differential equation of reaction-diffusion type with small shift. The scheme derived is almost second order accurate. To evaluate its effectiveness, several test examples with varying perturbation and delay parameter are considered. The proposed scheme is compared with the results of other existing numerical schemes. Error estimate and the rate of convergence are shown in the tables for proposed numerical scheme.
The Use of Methylene Blue in Adult Patients with Septic Shock: A Systematic Review and Meta-analysis
Authors: Ng Ka Ting , Kwok Pei En , Lim Wei En , Teoh Wan Yi , Hasan Mohd Shahnaz , Abidin Mohd Fitry Zainal 
Published: March 2024

Abstract
Objectives
Methylene blue exerts its vasopressor effects by inhibiting nitric oxide-mediated vasodilation. Recent studies have suggested the use of methylene blue as a rescue therapy for patients with septic shock. The primary aim was to investigate the effect of methylene blue on the mean arterial pressure among adult patients with septic shock.
Methods
The MEDLINE, EMBASE, and CENTRAL databases were searched from their inception until October 2023. Randomized clinical trials (RCTs) comparing methylene blue and placebo in adults with septic shock were included.
Results
Our systematic review included 5 studies (n = 257) for data analysis. Our pooled analysis revealed that compared with the placebo, methylene blue significantly increased the mean arterial pressure (MD: 1.34 mmHg, 95% CI: 0.15 to 2.53, ρ = 0.03; level of evidence: very low). Methylene blue was associated with a significantly lower mortality rate (OR: 0.49, 95% CI: 0.27 to 0.88; ρ = 0.02; level of evidence: low), reduced serum lactate levels (MD: -0.76 mmol/L, 95% Cl: -1.22 to -0.31; ρ = 0.0009; level of evidence: low), reduced length of hospital stay (MD: -1.94 days, 95% Cl: -3.79 to -0.08; ρ = 0.04; level of evidence: low), and increased PaO2/FiO2 (MD: 34.78, 95% CI: 8.94 to 60.61; ρ = 0.008; level of evidence: low).
Conclusions
This meta-analysis showed that methylene blue administration was associated with increased mean arterial pressure and PaO2/FiO2 and was associated with a reduced mortality rate, serum lactate levels, and duration of hospitalization. However, a substantial degree of heterogeneity and an inadequate number of studies with a low level of evidence warrant future adequately powered RCTs to affirm our results.
Exploring Medical Students' Experience of the Learning Environment: A Mixed Methods Study in Saudi Medical College
Authors: Almansour Mohammed , Abouammoh Noura , Idris Reem Fahad Bin , Alsuliman Omar Abdullatif , Alhomaidi Renad Abdulrahman , Alhumud Mohammed Hamad , Alghamdi Hani A. 
Published: March 2024

Abstract
Background
In medical education, the learning environment (LE) significantly impacts students' professionalism and academic performance. Positive LE perceptions are linked to better academic outcomes. Our study, which was conducted 15 years after curriculum reform at King Saud University's College of Medicine, aimed to explore students' perspectives on their LE and identify areas for improvement. By understanding their experiences, we strive to enhance LE and promote academic success.
Methods
This mixed-method study employed an explanatory sequential approach in which a cross-sectional analytical survey phase was collected first using the Johns Hopkins Learning Environment Scale (JHLES), followed by qualitative focus groups. Findings from quantitative and qualitative methods were integrated using joint display.
Results
A total of 653 medical students completed the JHLES. The total average score was 81 out of 140 (16.8), and the average subscale scores ranged from 2.27 (0.95) for inclusion and safety to 3.37 (0.91) for community of peers. The qualitative approach encompasses both inductive and deductive analyses, identifying overarching themes comprising proudness, high expectations and competition, and views about the curriculum. The integration of results emphasizes the need for continued efforts to create a supportive and inclusive LE that positively influences students' experiences and academic success.
Conclusion
This research offers valuable insights for educational institutions seeking to enhance medical education quality and support systems. Recommendations include faculty development, the cultivation of supportive environments, curriculum revision, improved mentorship programs, and initiatives to promote inclusivity and gender equity. Future research should explore longitudinal and comparative studies, innovative mixed methods approaches, and interventions to further optimize medical education experiences. Overall, this study contributes to the ongoing dialog on medical education, offering a nuanced understanding of the complex factors influencing students' perceptions and suggesting actionable strategies for improvement.
Real-Time Detection and Discrimination of Radioactive Gas Mixtures Using Nanoporous Inorganic Scintillators
Authors: Dujardin Christophe , Luce Raphaël Marie , Mai Pavlo , Lerouge Frederic , Cheref Yannis , Pierre Sylvie , Sabot Benoît , Chaput frederic 
Published: March 2024

Abstract

The nuclear industry's expansion to encompass carbon-free electricity generation from small modular reactors and nuclear fuel reprocessing necessitates enhanced detection and monitoring of pure beta-emitting radioactive elements like 3H and 85Kr ; this endeavour is crucial for nuclear safety authorities tasked with environmental monitoring. However, the short range of electrons emitted by these gases makes detection challenging. Current methods, such as ionisation chambers and liquid scintillation do not offer at the same time good sensitivity, real-time analysis, and ease of implementation. We demonstrate an approach using a gas-solid mixture to overcome these limitations. We synthetized a transparent and scintillating nanoporous material, an aerogel of Y3Al5O12:Ce4+ and achieved real-time detection with an efficiency of 96% for 85Kr and 20\% for 85H. The method reaches a sensitivity bellow 100 mBq per cm3 over 100 s measurement time. Statistical analysis of the temporal responses allows measurement of gas mixtures containing both 3H and 85Kr . We are able to measure simultaneously pure beta emitters, a capability not possible previously. Our results demonstrate a compact and robust detection system for in-line measurement of strategic radioactive gases. This combination of concept and method enhances nuclear powerplant management and contributes to environmental safeguarding. Beyond the detection issues, this concept opens a wide field of new methods for radionuclide metrology.