bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boreal–Arctic wetland methane emissions modulated by warming and vegetation activity
Authors: Yuan Kunxiaojia , Li Fa , McNicol Gavin , Chen Min , Hoyt Alison , Knox Sara , Riley William J. , Jackson Robert , Zhu Qing 
Published: February 2024

AbstractWetland methane (CH4) emissions over the Boreal–Arctic region are vulnerable to climate change and linked to climate feedbacks, yet understanding of their long-term dynamics remains uncertain. Here, we upscaled and analysed two decades (2002–2021) of Boreal–Arctic wetland CH4 emissions, representing an unprecedented compilation of eddy covariance and chamber observations. We found a robust increasing trend of CH4 emissions (+8.9%) with strong inter-annual variability. The majority of emission increases occurred in early summer (June and July) and were mainly driven by warming (52.3%) and ecosystem productivity (40.7%). Moreover, a 2 °C temperature anomaly in 2016 led to the highest recorded annual CH4 emissions (22.3 Tg CH4 yr−1) over this region, driven primarily by high emissions over Western Siberian lowlands. However, current-generation models from the Global Carbon Project failed to capture the emission magnitude and trend, and may bias the estimates in future wetland CH4 emission driven by amplified Boreal–Arctic warming and greening.
1H NMR metabolomics insights into comparative diabesity in male and female zebrafish and the antidiabetic activity of DL-limonene
Authors: Benchoula Khaled , Serpell Christopher J. , Mediani Ahmed , Albogami Abdulaziz , Misnan Norazlan Mohmad , Ismail Nor Hadiani , Parhar Ishwar S. , Ogawa Satoshi , Hwa Wong Eng 
Published: February 2024

AbstractZebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene – a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity—and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.
Noval soliton solution, sensitivity and stability analysis to the fractional gKdV-ZK equation
Authors: Shakeel Muhammad , Zafar Asim , Alameri Abdu , Junaid U Rehman Muhammad , Awrejcewicz Jan , Umer Muhammad , Zahid Muhammad , Sooppy Nisar Kottakkaran 
Published: February 2024

AbstractThis work examines the fractional generalized Korteweg-de-Vries-Zakharov-Kuznetsov equation (gKdV-ZKe) by utilizing three well-known analytical methods, the modified $$\left( \frac{G^{'}}{G^2}\right)$$

G

′

G
2

-expansion method, $$\left( \frac{1}{G^{'}}\right)$$

1

G

′

-expansion method and the Kudryashov method. The gKdV-ZK equation is a nonlinear model describing the influence of magnetic field on weak ion-acoustic waves in plasma made up of cool and hot electrons. The kink, singular, anti-kink, periodic, and bright soliton solutions are observed. The effect of the fractional parameter on wave shapes have been analyzed by displaying various graphs for fractional-order values of $$\beta$$
β
. In addition, we utilize the Hamiltonian property to observe the stability of the attained solution and Galilean transformation for sensitivity analysis. The suggested methods can also be utilized to evaluate the nonlinear models that are being developed in a variety of scientific and technological fields, such as plasma physics. Findings show the effectiveness simplicity, and generalizability of the chosen computational approach, even when applied to complex models.
Dual anti-HER2/EGFR inhibition synergistically increases therapeutic effects and alters tumor oxygenation in HNSCC
Authors: Song Patrick N. , Lynch Shannon E. , DeMellier Chloe T. , Mansur Ameer , Gallegos Carlos A. , Wright Brian D. , Hartman Yolanda E. , Minton Laura E. , Lapi Suzanne E. , Warram Jason M. , Sorace Anna G. 
Published: February 2024

AbstractEpidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and hypoxia are associated with radioresistance. The goal of this study is to study the synergy of anti-HER2, trastuzumab, and anti-EGFR, cetuximab, and characterize the tumor microenvironment components that may lead to increased radiation sensitivity with dual anti-HER2/EGFR therapy in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography (PET) imaging ([89Zr]-panitumumab and [89Zr]-pertuzumab) was used to characterize EGFR and HER2 in HNSCC cell line tumors. HNSCC cells were treated with trastuzumab, cetuximab, or combination followed by radiation to assess for viability and radiosensitivity (colony forming assay, immunofluorescence, and flow cytometry). In vivo, [18F]-FMISO-PET imaging was used to quantify changes in oxygenation during treatment. Bliss Test of Synergy was used to identify combination treatment synergy. Quantifying EGFR and HER2 receptor expression revealed a 50% increase in heterogeneity of HER2 relative to EGFR. In vitro, dual trastuzumab-cetuximab therapy shows significant decreases in DNA damage response and increased response to radiation therapy (p < 0.05). In vivo, tumors treated with dual anti-HER2/EGFR demonstrated decreased tumor hypoxia, when compared to single agent therapies. Dual trastuzumab-cetuximab demonstrates synergy and can affect tumor oxygenation in HNSCC. Combination trastuzumab-cetuximab modulates the tumor microenvironment through reductions in tumor hypoxia and induces sustained treatment synergy.
Single-cell analysis reveals the spatial-temporal expression of genes associated with esophageal malformations
Authors: Maj Carlo , Eberts Antonia , Schumacher Johannes , Dasmeh Pouria 
Published: February 2024

AbstractUnderstanding the molecular mechanisms of congenital diseases is challenging due to their occurrence within specific developmental stages. Esophageal malformations are examples of such conditions, characterized by abnormalities in the development of esophagus during embryogenesis. These developmental malformations encompass a range of anomalies, including esophageal atresia, and tracheoesophageal fistula. Here, we investigated the preferential expression of 29 genes that are implicated in such malformations and their immediate interactome (a total of 67 genes). We conducted our analyses across several single-cell atlases of embryonic development, encompassing approximately 150,000 cells from the mouse foregut, 180,000 cells from human embryos, and 500,000 cells from 24 human organs. Our study, spanning diverse mesodermal and endodermal cell populations and early developmental stages, shows that the genes associated with esophageal malformations show their highest cell-type specific expression in lateral plate mesoderm cells and at the developmental stage of E8.75–E9.0 days. In human embryos, these genes show a significant cell-type specific expression among subpopulations of epithelial cells, fibroblasts and progenitor cells including basal cells. Notably, members of the forkhead-box family of transcription factors, namely FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor, SOX2, demonstrate the most significant preferential expression in both mouse and human embryos. Overall, our findings provide insights into the temporal and cellular contexts contributing to esophageal malformations.
The Temozolomide–Doxorubicin paradox in Glioblastoma in vitro–in silico preclinical drug-screening
Authors: Oraiopoulou Mariam-Eleni , Tzamali Eleftheria , Psycharakis Stylianos E. , Tzedakis Georgios , Makatounakis Takis , Manolitsi Katina , Drakos Elias , Vakis Antonis F. , Zacharakis Giannis , Papamatheakis Joseph , Sakkalis Vangelis 
Published: February 2024

AbstractAdjuvant Temozolomide is considered the front-line Glioblastoma chemotherapeutic treatment; yet not all patients respond. Latest trends in clinical trials usually refer to Doxorubicin; yet it can lead to severe side-effects if administered in high doses. While Glioblastoma prognosis remains poor, little is known about the combination of the two chemotherapeutics. Patient-derived spheroids were generated and treated with a range of Temozolomide/Doxorubicin concentrations either as monotherapy or in combination. Optical microscopy was used to monitor the growth pattern and cell death. Based on the monotherapy experiments, we developed a probabilistic mathematical framework in order to describe the drug-induced effect at the single-cell level and simulate drug doses in combination assuming probabilistic independence. Doxorubicin was found to be effective in doses even four orders of magnitude less than Temozolomide in monotherapy. The combination therapy doses tested in vitro were able to lead to irreversible growth inhibition at doses where monotherapy resulted in relapse. In our simulations, we assumed both drugs are anti-mitotic; Temozolomide has a growth-arrest effect, while Doxorubicin is able to cumulatively cause necrosis. Interestingly, under no mechanistic synergy assumption, the in silico predictions underestimate the in vitro results. In silico models allow the exploration of a variety of potential underlying hypotheses. The simulated-biological discrepancy at certain doses indicates a supra-additive response when both drugs are combined. Our results suggest a Temozolomide–Doxorubicin dual chemotherapeutic scheme to both disable proliferation and increase cytotoxicity against Glioblastoma.
Functional neuroplasticity of facilitation and interference effects on inhibitory control following 3-month physical exercise in aging
Authors: Wu Hong-Yi , Huang Chih-Mao , Hsu Ai-Ling , Chen Chiao-Nan , Wu Changwei W. , Chen Jyh-Horng 
Published: February 2024

AbstractPreservation of executive function, like inhibition, closely links to the quality of life in senior adults. Although neuroimaging literature has shown enhanced inhibitory function followed by aerobic exercise, current evidence implies inconsistent neuroplasticity patterns along different time durations of exercise. Hence, we conducted a 12-week exercise intervention on 12 young and 14 senior volunteers and repeatedly measured the inhibitory functionality of distinct aspects (facilitation and interference effects) using the numerical Stroop task and functional Magnetic Resonance Imaging. Results showcased improved accuracy and reduced reaction times (RT) after 12-week exercise, attributed to frontoparietal and default mode network effects. In young adults, the first phase (0 to six weeks) exercise increased the activation of the right superior medial frontal gyrus, associated with reduced RT in interference, but in the second intervention phase (six to twelve weeks), the decreased activation of the left superior medial frontal gyrus positively correlated with reduced RT in facilitation. In senior adults, the first six-week intervention led to reduced activations of the inferior frontal gyrus, inferior parietal gyrus, and default mode network regions, associated with the reduced RT in interference. Still, in the second intervention phase, only the visual area exhibited increased activity, associated with reduced RT in interference. Except for the distinctive brain plasticity between the two phases of exercise intervention, the between-group comparison also presented that the old group gained more cognitive benefits within the first six weeks of exercise intervention; however, the cognitive improvements in the young group occurred after six weeks of intervention. Limited by the sample size, these preliminary findings corroborated the benefits of aerobic exercise on the inhibitory functions, implying an age × exercise interaction on the brain plasticity for both facilitation and interference.
Standardization of the protocol for oral cavity examination and collecting of the biological samples for microbiome research using the next-generation sequencing (NGS): own experience with the COVID-19 patients
Authors: Brzychczy-Sroka Barbara , Talaga-Ćwiertnia Katarzyna , Sroka-Oleksiak Agnieszka , Gurgul Artur , Zarzecka-Francica Elżbieta , Ostrowski Wojciech , Kąkol Janusz , Drożdż Kamil , Brzychczy-Włoch Monika , Zarzecka Joanna 
Published: February 2024

AbstractTo date, publications have shown that compositions of oral microbiota differ depending on their habitats (e.g. tongue, tonsils, pharynx). The absence of set standards for the choice of the areas and conditions of material collection makes the oral microbiome one of the most difficult environments for a comparative analysis with other researchers, which is a meaningful limitation during an assessment of the potential effects of microorganisms as biomarkers in the courses of various human diseases. Therefore, standardisation of basic conditions of a dental examination and collection of material for the next generation sequencing (NGS) is worth attempting. The standardisation of the dental exam and collection of the clinical materials: saliva, swab from the tongue ridge, hard palate, palatine tonsils and oropharynx, supragingival plaque and subgingival plaque. Protocol involved the patients (n = 60), assigned to 3 groups: I—COVID-19 convalescents who received antibiotics, n = 17, II—COVID-19 convalescents, n = 23 and III—healthy individuals, n = 20. The collected biological samples were used to conduct NGS (16S rRNA). The conditions of patient preparation for collecting biological materials as well as the schedule of dental examination, were proposed. Based on the research conducted, we have indicated the dental indicators that best differentiate the group of COVID-19 patients (groups I and II) from healthy people (group III). These include the DMFT, D and BOP indices. The use of alpha and beta diversity analysis provided an overall insight into the diversity of microbial communities between specific niches and patient groups. The most different diversity between the studied group of patients (group II) and healthy people (group III) was noted in relation to the supragingival plaque. The order of activities during the dental exam as well as while collecting and securing clinical materials is particularly important to avoid technical errors and material contamination which may result in erroneous conclusions from the analyses of the results of sensitive tests such as the NGS. It has been shown that the dental indices: DMFT, D number, PI and BOP are the best prognostic parameters to assess the oral health. Based on beta diversity the most sensitive niche and susceptible to changes in the composition of the microbiota is the supragingival plaque. The procedures developed by our team can be applied as ready-to-use forms in studies conducted by other researchers.
A novel strategy for partial purification of alkane hydroxylase from P. chrysogenum SNP5 through reconstituting its native membrane into liposome
Authors: Das Satyapriy , Negi Sangeeta 
Published: February 2024

AbstractIntegral proteins or enzymes are still challenging to purify into their native state because of their need for an amphipathic environment and cofactors. Alkane hydroxylase (AlkB) is a membrane-bound enzyme that catalyzes the hydroxylation of a range of alkanes that have a broad spectrum of applications. In the current study, a novel approach has been explored for partial purification of alkane hydroxylase (AlkB) in its native state through restructuring the lipid bilayer of Penicilliumchrysogenum SNP5 into a liposome to extend the native and protective environment to AlkB enzyme. Three different methods i.e., reverse-phase evaporation method (RPEM), detergent-based method (DBM), and ethanol injection method (EIM) have been used for reconstituting its native membrane into liposome. On characterizing liposomes through fluorescence imaging, AFM, and particle size analysis, the reverse-phase evaporation method gave the best results based on the size distribution (i.e., 100–300 nm), the morphology of liposomes, and maximum AlkB specific activity (i.e., 140.68 U/mg). The maximum reconstitution efficiency of 29.48% was observed in RPEM followed by 17.3% in DBM and 12.3% in EIM. On the characterization of the purified AlkB, the molecular weight was measured of 44.6 KDa and the thermostability of liposomes synthesized with the RPEM method was obtained maximum at 55 °C. This approach may open a new strategy for the purification of integral enzymes/proteins in their native state in the field of protein purification and its applications in diversified industries.
scRNA-seq revealed high stemness epithelial malignant cell clusters and prognostic models of lung adenocarcinoma
Authors: Lin GuoYong , Gao ZhiSen , Wu Shun , Zheng JianPing , Guo XiangQiong , Zheng XiaoHong , Chen RunNan 
Published: February 2024

AbstractLung adenocarcinoma (LUAD) is one of the sole causes of death in lung cancer patients. This study combined with single-cell RNA-seq analysis to identify tumor stem-related prognostic models to predict the prognosis of lung adenocarcinoma, chemotherapy agents, and immunotherapy efficacy. mRNA expression-based stemness index (mRNAsi) was determined by One Class Linear Regression (OCLR). Differentially expressed genes (DEGs) were detected by limma package. Single-cell RNA-seq analysis in GSE123902 dataset was performed using Seurat package. Weighted Co-Expression Network Analysis (WGCNA) was built by rms package. Cell differentiation ability was determined by CytoTRACE. Cell communication analysis was performed by CellCall and CellChat package. Prognosis model was constructed by 10 machine learning and 101 combinations. Drug predictive analysis was conducted by pRRophetic package. Immune microenvironment landscape was determined by ESTIMATE, MCP-Counter, ssGSEA analysis. Tumor samples have higher mRNAsi, and the high mRNAsi group presents a worse prognosis. Turquoise module was highly correlated with mRNAsi in TCGA-LUAD dataset. scRNA analysis showed that 22 epithelial cell clusters were obtained, and higher CSCs malignant epithelial cells have more complex cellular communication with other cells and presented dedifferentiation phenomenon. Cellular senescence and Hippo signaling pathway are the major difference pathways between high- and low CSCs malignant epithelial cells. The pseudo-temporal analysis shows that cluster1, 2, high CSC epithelial cells, are concentrated at the end of the differentiation trajectory. Finally, 13 genes were obtained by intersecting genes in turquoise module, Top200 genes in hdWGCNA, DEGs in high- and low- mRNAsi group as well as DEGs in tumor samples vs. normal group. Among 101 prognostic models, average c-index (0.71) was highest in CoxBoost + RSF model. The high-risk group samples had immunosuppressive status, higher tumor malignancy and low benefit from immunotherapy. This work found that malignant tumors and malignant epithelial cells have high CSC characteristics, and identified a model that could predict the prognosis, immune microenvironment, and immunotherapy of LUAD, based on CSC-related genes. These results provided reference value for the clinical diagnosis and treatment of LUAD.
A pilot study for risk stratification of ventricular tachyarrhythmia in hypertrophic cardiomyopathy with routine echocardiography parameters
Authors: Derda Anselm A. , Abelmann Malin , Sieweke Jan-Thorben , Waleczek Florian J. G. , Weber Natalie , Zehrfeld Nadine , Bär Christian , Duncker David , Bavendiek Udo , Berliner Dominik , Bauersachs Johann , Sonnenschein Kristina , Thum Thomas 
Published: February 2024

AbstractVentricular tachyarrhythmia (VTA) are frequent arrhythmias in patients with hypertrophic cardiomyopathy (HCM). Representing a major risk factor for sudden cardiac death, Holter ECG at first clinical presentation appears insufficient. This study aims to investigate the ability of routinely obtained parameters associated with myocardial remodeling in stratifying for VTA in HCM. In this monocentric analysis, patients with HCM underwent 12-channel electrocardiography and echocardiography, including tissue doppler imaging. The study’s primary endpoint was the documentation of non-sustained and sustained ventricular tachycardia—summarized as ventricular tachyarrhythmias (VTA) on Holter ECG or active devices. The occurrence of VTA was exploratory. Based on our collective, we developed a risk model regarding VTA. Of 140 HCM patients, 38 (27.1%) had an episode of VTA. Patients with VTA were likelier to have a history of atrial fibrillation (p < 0.001), a thicker interventricular septum (p < 0.001) and lower peak systolic mitral annular velocity (p < 0.001). The parameters were independently associated with endpoint in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.80 (sensitivity, 63%; specificity, 88%). Our risk model including these widely available parameters is able to distinguish low and high-risk of VTA in patients with HCM.
Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial
Authors: Cobo-Ibáñez Tatiana , Mora Ortega Gemma , Sánchez-Piedra Carlos , Serralta-San Martín Gonzalo , Thuissard-Vasallo Israel J. , Lores Gutiérrez Vanesa , Soler Rangel Llanos , García Yubero Cristina , Esteban-Vázquez Ana , López-Aspiroz Elena , Andreu Vázquez Cristina , Toboso Inmaculada , Martínez Alonso de Armiño Blanca María , Olivares Alviso Rocío Alejandra , Calderón Nieto Rocío , Yañez Cecilia , Zakhour González Marlín Alejandra , Sainz Sánchez Tatiana , Arroyo de la Torre Silvia , Del Amo Del Arco Nazaret , Gómez-Cerezo Jorge Francisco , Ramírez Prieto Teresa , Martínez Hernández Alicia , Muñoz-Fernández Santiago 
Published: February 2024

AbstractPost-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908–8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).