bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional in vitro, in silico and DFT analyses on antimicrobial BagremycinA biosynthesized by Micromonospora chokoriensis CR3 from Hieracium canadense
Authors: Tanvir Rabia , Ijaz Saadia , Sajid Imran , Hasnain Shahida 
Published: May 2024

AbstractAmong the actinomycetes in the rare genera, Micromonospora is of great interest since it has been shown to produce novel therapeutic compounds. Particular emphasis is now on its isolation from plants since its population from soil has been extensively explored. The strain CR3 was isolated as an endophyte from the roots of Hieracium canadense, and it was identified as Micromonospora chokoriensis through 16S gene sequencing and phylogenetic analysis. The in-vitro analysis of its extract revealed it to be active against the clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Candida tropicalis (15 mm). No bioactivity was observed against Gram-negative bacteria, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 706003. The Micromonospora chokoriensis CR3 extract was also analyzed through the HPLC-DAD-UV–VIS resident database, and it gave a maximum match factor of 997.334 with the specialized metabolite BagremycinA (BagA). The in-silico analysis indicated that BagA strongly interacted with the active site residues of the sterol 14-α demethylase and thymidylate kinase enzymes, with the lowest binding energies of − 9.7 and − 8.3 kcal/mol, respectively. Furthermore, the normal mode analysis indicated that the interaction between these proteins and BagA was stable. The DFT quantum chemical properties depicted BagA to be reasonably reactive with a HOMO-LUMO gap of (ΔE) of 4.390 eV. BagA also passed the drug-likeness test with a synthetic accessibility score of 2.06, whereas Protox-II classified it as a class V toxicity compound with high LD50 of 2644 mg/kg. The current study reports an endophytic actinomycete, M. chokoriensis, associated with H. canadense producing the bioactive metabolite BagA with promising antimicrobial activity, which can be further modified and developed into a safe antimicrobial drug.
A simple and highly sensitive LC–MS workflow for characterization and quantification of ADC cleavable payloads
Authors: Mak Shi Ya , Chen Shuwen , Fong Wey Jia , Choo Andre , Ho Ying Swan 
Published: May 2024

AbstractAntibody–drug conjugates (ADC) payloads are cleavable drugs that act as the warhead to exert an ADC’s cytotoxic effects on cancer cells intracellularly. A simple and highly sensitive workflow is developed and validated for the simultaneous quantification of six ADC payloads, namely SN-38, MTX, DXd, MMAE, MMAF and Calicheamicin (CM). The workflow consists of a short and simple sample extraction using a methanol-ethanol mixture, followed by a fast liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis. The results showed that well-validated linear response ranges of 0.4–100 nM for SN38, MTX and DXd, 0.04–100 nM for MMAE and MMAF, 0.4–1000 nM for CM were achieved in mouse serum. Recoveries for all six payloads at three different concentrations (low, medium and high) were more than 85%. An ultra-low sample volume of only 5 µL of serum is required due to the high sensitivity of the method. This validated method was successfully applied to a pharmacokinetic study to quantify MMAE in mouse serum samples.
Weight loss treatment for COVID-19 in patients with NCDs: a pilot prospective clinical trial
Authors: Oshakbayev Kuat , Durmanova Aigul , Zhankalova Zulfiya , Idrisov Alisher , Bedelbayeva Gulnara , Gazaliyeva Meruyert , Nabiyev Altay , Tordai Attila , Dukenbayeva Bibazhar 
Published: May 2024

AbstractCOVID-19 comorbid with noncommunicable chronic diseases (NCDs) complicates the diagnosis, treatment, and prognosis, and increases the mortality rate. The aim is to evaluate the effects of a restricted diet on clinical/laboratory inflammation and metabolic profile, reactive oxygen species (ROS), and body composition in patients with COVID-19 comorbid with NCDs. We conducted a 6-week open, pilot prospective controlled clinical trial. The study included 70 adult patients with COVID-19 comorbid with type 2 diabetes (T2D), hypertension, or nonalcoholic steatohepatitis (NASH). Interventions: a restricted diet including calorie restriction, hot water drinking, walking, and sexual self-restraint. Primary endpoints: COVID-19 diagnosis by detecting SARS-CoV-2 genome by RT-PCR; weight loss in Main group; body temperature; C-reactive protein. Secondary endpoints: the number of white blood cells; erythrocyte sedimentation rate; adverse effects during treatment; fasting blood glucose, glycosylated hemoglobin A1c (HbA1c), systolic/diastolic blood pressure (BP); blood lipids; ALT/AST, chest CT-scan. In Main group, patients with overweight lost weight from baseline (− 12.4%; P < 0.0001); 2.9% in Main group and 7.2% in Controls were positive for COVID-19 (RR: 0.41, CI: 0.04–4.31; P = 0.22) on the 14th day of treatment. Body temperature and C-reactive protein decreased significantly in Main group compared to Controls on day 14th of treatment (P < 0.025). Systolic/diastolic BP normalized (P < 0.025), glucose/lipids metabolism (P < 0.025); ALT/AST normalized (P < 0.025), platelets increased from baseline (P < 0.025), chest CT (P < 0.025) in Main group at 14 day of treatment. The previous antidiabetic, antihypertensive, anti-inflammatory, hepatoprotective, and other symptomatic medications were adequately decreased to completely stop during the weight loss treatment. Thus, the fast weight loss treatment may be beneficial for the COVID-19 patients with comorbid T2D, hypertension, and NASH over traditional medical treatment because, it improved clinical and laboratory/instrumental data on inflammation; glucose/lipid metabolism, systolic/diastolic BPs, and NASH biochemical outcomes, reactive oxygen species; and allowed patients to stop taking medications.Trial Registration: ClinicalTrials.gov NCT05635539 (02/12/2022): https://clinicaltrials.gov/ct2/show/NCT05635539?term=NCT05635539&draw=2&rank=1.
Synthesis and anti-inflammatory activities of two new N-acetyl glucosamine derivatives
Authors: Zhang Zhichang , Wang Weicheng , Xu Peng , Cui Quanjun , Yang Xinlin , Hassan Ameer E. 
Published: May 2024

AbstractN-acetyl glucosamine (NAG) is a natural amino sugar found in various human tissues with previously described anti-inflammatory effects. Various chemical modifications of NAG have been made to promote its biomedical applications. In this study, we synthesized two bi-deoxygenated NAG, BNAG1 and BNAG2 and investigated their anti-inflammatory properties, using an in vivo and in vitro inflammation mouse model induced by lipopolysaccharide (LPS). Among the parent molecule NAG, BNAG1 and BNAG2, BNAG1 showed the highest inhibition against serum levels of IL-6 and TNF α and the leukocyte migration to lungs and peritoneal cavity in LPS challenged mice, as well as IL-6 and TNF α production in LPS-stimulated primary peritoneal macrophages. BNAG2 displayed an anti-inflammatory effect which was comparable to NAG. These findings implied potential application of these novel NAG derivatives, especially BNAG1, in treatment of certain inflammation-related diseases.
Influence of biochar on the removal of Microcystin-LR and Saxitoxin from aqueous solutions
Authors: Chambers Cadianne , Grimes Savannah , Fire Spencer , Reza M. Toufiq 
Published: May 2024

AbstractThe present study assessed the effective use of biochar for the adsorption of two potent HAB toxins namely, Microcystin-LR (MCLR) and Saxitoxin (STX) through a combination of dosage, kinetic, equilibrium, initial pH, and competitive adsorption experiments. The adsorption results suggest that biochar has excellent capabilities for removing MCLR and STX, with STX reporting higher adsorption capacities (622.53–3507.46 µg/g). STX removal required a minimal dosage of 0.02 g/L, while MCLR removal needed 0.4 g/L for > 90%. Similarly, a shorter contact time was required for STX removal compared to MCLR for > 90% of toxin removed from water. Initial pH study revealed that for MCLR acidic conditions favored higher uptake while STX favored basic conditions. Kinetic studies revealed that the Elovich model to be most suitable for both toxins, while STX also showed suitable fittings for Pseudo-First Order and Pseudo-Second Order in individual toxin systems. Similarly, for the Elovich model the most suited kinetic model for both toxins in presence of each other. Isotherm studies confirmed the Langmuir–Freundlich model as the best fit for both toxins. These results suggest adsorption mechanisms including pore filling, hydrogen bonding, π–π interactions, hydrophobic interactions, electrostatic attraction, and dispersive interactions.
Experimental study on the punching failure model of soft red rock subgrade by BPT-BVM methods and it’s assessment of the load bearing capacity
Authors: Chen Jibin , Pan Qiang , Wei Yao , Luo Yibin , Zhao Zhuangfu , Zhao Li , Bai Yu 
Published: May 2024

AbstractThe recommended bearing capacity of medium weathering mudstone foundation is less than the capacity of the rock structure to withstand loads in Southwest China. A comprehensive failure characterization of medium weathering mudstone in Chengdu has been performed including bearing plate test (BPT), binocular vision measurement (BVM) test, uniaxial compressive strength test, trial trench test of shallow rock surface and 3D imaging in this paper. Failure behavior of rock has been modeled with 3D imaging algorithm that utilizes Zhang’s calibration method in BVM system combination with trial trench test of shallow rock surface. The bearing capacity of medium weathering mudstone foundation were extracted from uniaxial experiments and BPT-BVM test by fitting relevant material properties to the data. The results revealed that: Bearing capacity of medium weathering mudstone of layered isotropic in Chengdu is undervalued. Specifically, the characteristic load carrying value is in the range 1500–2500 kP, that is 50% higher than in the local standard system. Failure process is different from Hoek–Brown Failure Criterion, presenting a wave peak transfer phenomenon of the increment displacement into the distance. Thus, it can be reduced to that of punching failures for thin bedded structures of Moudstone foundations. Compressive strength of soft rock proves to be main factor limiting the bearing capacity, a clear correlation between the uniaxial compressive strength reduction coefficient and the bearing capacity has been used to establish, leading to the proposal of a load bearing capacity prediction model.
Identifying potential (re)hemorrhage among sporadic cerebral cavernous malformations using machine learning
Authors: Li Xiaopeng , Jones Peng , Zhao Mei 
Published: May 2024

AbstractThe (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.
Validating reference-based algorithms to determine cell-type heterogeneity in ovarian cancer DNA methylation studies
Authors: Biskup Edyta , Lopacinska-Jørgensen Joanna , Vestergaard Lau Kræsing , Høgdall Estrid 
Published: May 2024

AbstractInformation about cell composition in tissue samples is crucial for biomarker discovery and prognosis. Specifically, cancer tissue samples present challenges in deconvolution studies due to mutations and genetic rearrangements. Here, we optimized a robust, DNA methylation-based protocol, to be used for deconvolution of ovarian cancer samples. We compared several state-of-the-art methods (HEpiDISH, MethylCIBERSORT and ARIC) and validated the proposed protocol in an in-silico mixture and in an external dataset containing samples from ovarian cancer patients and controls. The deconvolution protocol we eventually implemented is based on MethylCIBERSORT. Comparing deconvolution methods, we paid close attention to the role of a reference panel. We postulate that a possibly high number of samples (in our case: 247) should be used when building a reference panel to ensure robustness and to compensate for biological and technical variation between samples. Subsequently, we tested the performance of the validated protocol in our own study cohort, consisting of 72 patients with malignant and benign ovarian disease as well as in five external cohorts. In conclusion, we refined and validated a reference-based algorithm to determine cell type composition of ovarian cancer tissue samples to be used in cancer biology studies in larger cohorts.
Composition and fatty acid profile of milk from cows fed diets supplemented with raw and n-3 PUFA-enriched fish oil
Authors: Bodkowski Robert , Wierzbicki Heliodor , Mucha Anna , Cholewińska Paulina , Wojnarowski Konrad , Patkowska-Sokoła Bożena 
Published: May 2024

AbstractDietary supplementation of ruminants with fish oil is a strategy for favorably modifying the fatty acid composition of milk fat. This study investigated the effect of supplementing cows’ diet with fish oil after low-temperature crystallisation (LTC-FO) compared to its raw form (FO) on milk yield, milk components (fat, protein, and lactose), and milk fatty acid profile. Twenty-four mid-lactating multiparous Polish Holstein–Friesian cows fed a total-mix ration were randomly assigned to two homogeneous groups (n = 12 cows each) and supplemented with LTC-FO or FO at 1% of dry matter. Milk samples were collected on days 14 and 30 of the 30-day experiment. No significant differences between the groups in terms of milk yield, milk protein, and lactose content were found, however, the fat yield and content decreased in the LTC-FO group. Milk fat from cows in the LTC-FO group contained significantly higher levels of C18:1 trans-11, C18:2 cis-9, trans-11, C18:3n − 3, C20:5, and C22:6, and lower levels of saturated fatty acids compared to the FO group (p < 0.05). Therefore, LTC-FO may be a more efficient feed additive than FO and may serve as a practical way to modify the fatty acid composition of milk fat.
Enhancing stress measurements accuracy control in the construction of long-span bridges
Authors: Gaute-Alonso Alvaro , Garcia-Sanchez David , Ramos-Gutierrez Óscar Ramón , Ntertimanis Vasileios 
Published: May 2024

AbstractThis paper introduces new contributions for construction procedures designed to enhance the robustness and precision of stress control in active anchorage and short presetressing units for long-span bridges, particularly addressing potential technical risks. The primary focus is on optimizing stress management for bridge stays, suspension cables, and short prestressing units by emphasizing a unified parameter: stress. The contributions of this research encompass (1) the introduction of advanced load cells for stress control in active anchorages and (2) the implementation of a novel synchronized multi-strain gage load cell network for short prestressing units, crucial in situations where prestressing losses can attain significant magnitudes. To validate these advancements, the authors present (3) a practical experience and results obtained from applying these methodologies in monitoring the structural response during the construction of the Tajo Bridge using the cable-stayed cantilever technique.
Anti-inflammatory properties and characterization of water extracts obtained from Callicarpa kwangtungensis Chun using in vitro and in vivo rat models
Authors: Li Jun-Jian , Li Li , Su Shan-Shan , Liao Mei-Lan , Gong Qiu-Zi , Liu Mei , Jiang Shan , Zhang Zai-Qi , Zhou Hua , Liu Jian-Xin 
Published: May 2024

AbstractCallicarpa kwangtungensis Chun (CK) is a common remedy exhibits anti-inflammatory properties and has been used in Chinese herbal formulations, such as KangGongYan tablets. It is the main component of KangGongYan tablets, which has been used to treat chronic cervicitis caused by damp heat, red and white bands, cervical erosion, and bleeding. However, the anti-inflammatory effects of CK water extract remains unknown. This study assessed the anti-inflammatory effects of CK in vivo and in vitro, characterized its main components in the serum of rats and verified the anti-inflammatory effects of serum containing CK. Nitric oxide (NO), tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) release by RAW264.7 cells was examined by ELISA and Griess reagents. Inflammation-related protein expression in LPS-stimulated RAW264.7 cells was measured by western blotting. Furthermore, rat model of foot swelling induced by λ-carrageenan and a collagen-induced arthritis (CIA) rat model were used to explore the anti-inflammatory effects of CK. The components of CK were characterized by LC–MS, and the effects of CK-containing serum on proinflammatory factors levels and the expression of inflammation-related proteins were examined by ELISA, Griess reagents and Western blotting. CK suppressed IL-6, TNF-α, and NO production, and iNOS protein expression in LPS-stimulated RAW264.7 cells. Mechanistic studies showed that CK inhibited the phosphorylation of ERK, P38 and JNK in the MAPK signaling pathway, promoted the expression of IκBα in the NF-κB signaling pathway, and subsequently inhibited the expression of iNOS, thereby exerting anti-inflammatory effects. Moreover, CK reduced the swelling rates with λ-carrageenan induced foot swelling, and reduced the arthritis score and incidence in the collagen-induced arthritis (CIA) rat model. A total of 68 compounds in CK water extract and 31 components in rat serum after intragastric administration of CK were characterized. Serum pharmacological analysis showed that CK-containing serum suppressed iNOS protein expression and NO, TNF-α, and IL-6 release. CK may be an anti-inflammatory agent with therapeutic potential for acute and chronic inflammatory diseases, especially inflammatory diseases associated with MAPK activation.
Prognostic relevance of radiological findings on early postoperative MRI for 187 consecutive glioblastoma patients receiving standard therapy
Authors: Rykkje Alexander Malcolm , Carlsen Jonathan Frederik , Larsen Vibeke Andrée , Skjøth-Rasmussen Jane , Christensen Ib Jarle , Nielsen Michael Bachmann , Poulsen Hans Skovgaard , Urup Thomas Haargaard , Hansen Adam Espe 
Published: May 2024

AbstractSeveral prognostic factors are known to influence survival for patients treated with IDH-wildtype glioblastoma, but unknown factors may remain. We aimed to investigate the prognostic implications of early postoperative MRI findings. A total of 187 glioblastoma patients treated with standard therapy were consecutively included. Patients either underwent a biopsy or surgery followed by an early postoperative MRI. Progression-free survival (PFS) and overall survival (OS) were analysed for known prognostic factors and MRI-derived candidate factors: resection status as defined by the response assessment in neuro-oncology (RANO)-working group (no contrast-enhancing residual tumour, non-measurable contrast-enhancing residual tumour, or measurable contrast-enhancing residual tumour) with biopsy as reference, contrast enhancement patterns (no enhancement, thin linear, thick linear, diffuse, nodular), and the presence of distant tumours. In the multivariate analysis, patients with no contrast-enhancing residual tumour or non-measurable contrast-enhancing residual tumour on the early postoperative MRI displayed a significantly improved progression-free survival compared with patients receiving only a biopsy. Only patients with non-measurable contrast-enhancing residual tumour showed improved overall survival in the multivariate analysis. Contrast enhancement patterns were not associated with survival. The presence of distant tumours was significantly associated with both poor progression-free survival and overall survival and should be considered incorporated into prognostic models.
Loci cg06256735 and cg15815843 in the MFAP5 gene regulatory regions are hypomethylated in varicose veins apparently due to active demethylation
Authors: Smetanina Mariya A. , Korolenya Valeria A. , Sipin Fedor A. , Oscorbin Igor P. , Sevostyanova Kseniya S. , Gavrilov Konstantin A. , Shevela Andrey I. , Filipenko Maxim L. 
Published: May 2024

Abstract
Varicose vein disease (VVD) is a common health problem worldwide. Microfibril-associated protein 5 (MFAP5) is one of the potential key players in its pathogenesis. Our previous microarray analysis revealed the cg06256735 and cg15815843 loci in the regulatory regions of the MFAP5 gene as hypomethylated in varicose veins which correlated with its up-regulation. The aim of this work was to validate preliminary microarray data, estimate the level of 5-hydroxymethylcytosine (5hmC) at these loci, and determine the methylation status of one of them in different layers of the venous wall. For this, methyl- and hydroxymethyl-sensitive restriction techniques were used followed by real-time PCR and droplet digital PCR, correspondingly, as well as bisulfite pyrosequencing of +/- oxidized DNA. Our microarray data on hypomethylation at the cg06256735 and cg15815843 loci in whole varicose vein segments were confirmed and it was also demonstrated that the level of 5hmC at these loci is increased in VVD. Specifically, among other layers of the venous wall, tunica (t.) intima is the main contributor to hypomethylation at the cg06256735 locus in varicose veins. Thus, it was shown that hypomethylation at the cg06256735 and cg15815843 loci takes place in VVD, with evidence to suggest that it happens through their active demethylation leading to up-regulation of the MFAP5 gene, and t. intima is most involved in this biochemical process.