bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the impact of distributed snow water equivalent calibration and assimilation of Copernicus snow water equivalent on modelled snow and streamflow performance
Authors: Beaton Andy D. , Han Ming , Tolson Bryan A. , Buttle James M. , Metcalfe Robert A. 
Published: February 2024

AbstractAccuracy of the Copernicus snow water equivalent (SWE) product and the impact of SWE calibration and assimilation on modelled SWE and streamflow was evaluated. Daily snowpack measurements were made at 12 locations from 2016 to 2019 across a 4104 km2 mixed‐forest basin in the Great Lakes region of central Ontario, Canada. Sub‐basin daily SWE calculated from these sites, observed discharge, and lake levels were used to calibrate a hydrologic model developed using the Raven modelling framework. Copernicus SWE was bias corrected during the melt period using mean bias subtraction and was compared to daily basin average SWE calculated from the measured data. Bias corrected Copernicus SWE was assimilated into the models using a range of parameters and the parameterizations from the model calibration. The bias corrected Copernicus product agreed well with measured data and provided a good estimate of mean basin SWE demonstrating that the product shows promise for hydrology applications within the study region. Calibration to spatially distributed SWE substantially improved the basin scale SWE estimate while only slightly degrading the flow simulation demonstrating the value of including SWE in a multi‐objective calibration formulation. The particle filter experiments yielded the best SWE estimation but moderately degraded the flow simulation. The particle filter experiments constrained by the calibrated snow parameters produced similar results to the experiments using the upper and lower bounds indicating that, in this study, model calibration prior to assimilation was not valuable. The calibrated models exhibited varying levels of skill in estimating SWE but demonstrated similar streamflow performance. This indicates that basin outlet streamflow can be accurately estimated using a model with a poor representation of distributed SWE. This may be sufficient for applications where estimating flow is the primary water management objective. However, in applications where understanding the physical processes of snow accumulation, melt and streamflow generation are important, such as assessing the impact of climate change on water resources, accurate representations of SWE are required and can be improved via multi‐objective calibration or data assimilation, as demonstrated in this study.
Trim21 deficiency in mice increases HCC carcinogenesis in a NASH context and is associated with immune checkpoint upregulation
Authors: Kara‐Ali Ghania Hounana , Cano Luis , Dion Sarah , Imerzoukene Ghiles , Hamon Annaig , Simoes Eugénio Mélanie , Piquet‐Pellorce Claire , Ghukasyan Gevorg , Samson Michel , Le Seyec Jacques , Dimanche‐Boitrel Marie‐Thérèse 
Published: February 2024

AbstractThe global pandemic of metabolic diseases has increased the incidence of hepatocellular carcinoma (HCC) in the context of non‐alcoholic steatohepatitis (NASH). The downregulation of the E3 ubiquitin ligase TRIM21 has been linked to poor prognosis in different cancers including HCC. In order to investigate the role of TRIM21 in liver cancer progression on NASH, Trim21+/+ and Trim21−/− male mice were injected with streptozotocin at the neonatal stage. The hypoinsulinemic mice were then fed with a high‐fat high‐cholesterol diet (HFHCD) for 4, 8 or 12 weeks. All mice developed NASH which systematically resulted in HCC progression. Interestingly, compared to the Trim21+/+ control mice, liver damage was worsened in Trim21−/− mice, with more HCC nodules found after 12 weeks on HFHCD. Immune population analysis in the spleen and liver revealed a higher proportion of CD4+PD‐1+ and CD8+PD‐1+ T cells in Trim21−/− mice. The liver and HCC tumors of Trim21−/− mice also exhibited an increase in the number of PD‐L1+ and CD68+ PD‐L1+ cells. Thus, TRIM21 limits the emergence of HCC nodules in mice with NASH by potentially restricting the expression of PD‐1 in lymphocytes and PD‐L1 in tumors.
Successful treatment with low‐dose oral steroids for contracted bladder after intravesical instillation of Bacillus Calmette–Guérin
Authors: Katami Akinobu , Inoue Takamitsu , Sakurai Hiromichi , Onozawa Mizuki , Hisasue Shin‐ichi , Kawai Koji , Miyazaki Jun 
Published: February 2024

IntroductionContracted bladder is a rare adverse effect of intravesical Bacillus Calmette–Guérin instillation, with an incidence of 0.2–3.3%. This report aimed to present a case of contracted bladder successfully treated with a low‐dose oral steroid.Case presentationA 78‐year‐old man underwent a third transurethral resection of a bladder tumor. The pathological diagnosis was urothelial carcinoma in situ. After the fifth instillation of the second‐line induction therapy of Bacillus Calmette–Guérin, the patient discontinued treatment because of increased urinary frequency and a continuous mean voiding volume of 80 mL. The patient was diagnosed with a contracted bladder based on computed tomography findings and a urination chart. After initiating oral prednisolone (20 mg/day), the patient experienced significant recovery within 2 weeks for both urinary frequency and mean voiding volume of 226 mL.ConclusionA patient with a contracted bladder after Bacillus Calmette–Guérin instillation was successfully treated with low‐dose oral steroid therapy.
Nanoparticles derived from herbal preparations May represent a novel nucleic acid therapy
Authors: Feng Tingle , Ahmed Waqas , Ahmed Talha , Chen Lukui 
Published: February 2024

AbstractA significant number of nucleic acid therapies have been approved, highlighting the vast potential of nucleic acid therapeutics. Although numerous delivery strategies have been investigated, and progress has been made in nucleic acid delivery systems, the oral delivery route still presents a significant obstacle. Recently, a novel and promising force in oral nucleic acid delivery has emerged, namely Decoctosomes and Bencaosomes, obtained from the decoction of natural herbs, which refers to boiled Chinese herbal medicines. The active components of Decoctosomes include small molecules, peptides, and small RNAs (sRNAs). sRNAs were the first targets of extensive research. Additionally, Bencaosomes have been proven effective in several disease mouse models as artificially enhanced decoctosome products. This perspective summarizes the development and possible future directions of Decoctosomes and Bencaosomes, two varieties of nanoparticles that may open the door to new possibilities in nucleic acid therapy.
Wharton's jelly‐derived multifunctional hydrogels: New tools to promote intervertebral disc regeneration in vitro and ex vivo
Authors: Penolazzi Letizia , Chierici Anna , Notarangelo Maria Pina , Dallan Beatrice , Lisignoli Gina , Lambertini Elisabetta , Greco Pantaleo , Piva Roberta , Nastruzzi Claudio 
Published: February 2024

AbstractThe degeneration of intervertebral disc (IVD) is a disease of the entire joint between two vertebrae in the spine caused by loss of extracellular matrix (ECM) integrity, to date with no cure. The various regenerative approaches proposed so far have led to very limited successes. An emerging opportunity arises from the use of decellularized ECM as a scaffolding material that, directly or in combination with other materials, has greatly facilitated the advancement of tissue engineering. Here we focused on the decellularized matrix obtained from human umbilical cord Wharton's jelly (DWJ) which retains several structural and bioactive molecules very similar to those of the IVD ECM. However, being a viscous gel, DWJ has limited ability to retain ordered structural features when considered as architecture scaffold. To overcome this limitation, we produced DWJ‐based multifunctional hydrogels, in the form of 3D millicylinders containing different percentages of alginate, a seaweed‐derived polysaccharide, and gelatin, denatured collagen, which may impart mechanical integrity to the biologically active DWJ. The developed protocol, based on a freezing step, leads to the consolidation of the entire polymeric dispersion mixture, followed by an ionic gelation step and a freeze‐drying process. Finally, a porous, stable, easily storable, and suitable matrix for ex vivo experiments was obtained. The properties of the millicylinders (Wharton's jelly millicylinders [WJMs]) were then tested in culture of degenerated IVD cells isolated from disc tissues of patients undergoing surgical discectomy. We found that WJMs with the highest percentage of DWJ were effective in supporting cell migration, restoration of the IVD phenotype (increased expression of Collagen type 2, aggrecan, Sox9 and FOXO3a), anti‐inflammatory action, and stem cell activity of resident progenitor/notochordal cells (increased number of CD24 positive cells). We are confident that the DWJ‐based formulations proposed here can provide adequate stimuli to the cells present in the degenerated IVD to restart the anabolic machinery.
Nrf2 prevents diabetic cardiomyopathy via antioxidant effect and normalization of glucose and lipid metabolism in the heart
Authors: Yang Ge , Zhang Qihe , Dong Chao , Hou Guowen , Li Jinjie , Jiang Xin , Xin Ying 
Published: February 2024

AbstractMetabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. Here, we investigated in a cardiomyocyte‐restricted Nrf2 transgenic mice (Nrf2‐TG) the direct effect of Nrf2 on cardiomyocytes in DCM and its mechanism. In this study, cardiomyocyte‐restricted Nrf2 transgenic mice (Nrf2‐TG) were used to directly observe whether cardiomyocyte‐specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. Compared to wild‐type mice, Nrf2‐TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin‐induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. These results showed that Nrf2 can directly act on cardiomyocytes to exert a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by directly targeting lipid metabolic pathway of AMPK/Sirt1/PGC‐1α activation via upstream genes of sestrin2 and LKB1, and indirectly enabling AKT/GSK‐3β/HK‐Ⅱ activity via AMPK mediated p70S6K inhibition.
Dynamic changes of endothelial and stromal cilia are required for the maintenance of corneal homeostasis
Authors: Ni Hua , Li Lamei , Hu Die , Yang Mulin , Wang Difei , Ma Hongbo , Bu Weiwen , Yang Jia , Zhu Li‐E , Zhai Denghui , Song Ting , Yang Song , Lu Quanlong , Li Dengwen , Ran Jie , Liu Min 
Published: February 2024

AbstractPrimary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α‐smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.
Hydrogenolysis of biomass‐derived levulinic acid to produce 1,4‐pentanediol over Co/ZrO2 catalyst
Authors: Zhang Dingshuo , Zhang Heqian , Li Yue , Sun Daolai , Lv Jianhua 
Published: February 2024

AbstractBACKGROUNDLevulinic acid is an important platform chemical derivable from lignocellulosic biomass. In this work, the hydrogenolysis of levulinic acid to produce 1,4‐pentanediol was performed over some Co‐based non‐noble catalysts. The relationship between the catalyst properties and the catalytic activity was investigated, and the effects of the reaction conditions on the catalytic activity were studied.RESULTSThe Co/ZrO2 catalyst prepared by a coprecipitation method showed a high catalytic performance in the hydrogenolysis of levulinic acid to form 1,4‐pentanediol. The calcination of Co/ZrO2 significantly affected the catalytic activity, and a high calcination temperature of 750 °C could promote the formation of 1,4‐pentanediol. Meanwhile, the reduction of Co/ZrO2 at 400 °C in an H2 flow was beneficial for producing 1,4‐pentanediol, and the Co species after the reduction existed as the forms of Co2+ and Co0. A high H2 pressure and a moderate reaction temperature of 200 °C were beneficial for producing 1,4‐pentanediol, and a high 1,4‐pentanediol selectivity of 85.6% with a complete conversion of levulinic acid was obtained over the Co/ZrO2 catalyst at 200 °C under an H2 pressure of 7 MPa.CONCLUSIONThe Co species in the 400 °C‐reduced Co/ZrO2 catalyst existed as the forms of Co2+ and Co0. It was proposed that the synergistic effect of Co2+ and Co0 contributed to the effective formation of 1,4‐pentanediol from levulinic acid. © 2024 Society of Chemical Industry (SCI).
Metallurgical characteristics of AA6061 aluminium and AZ31B magnesium dissimilar joints by fusion welding technique
Authors: Ramaswamy Addanki , Nagasai Bellamkonda Prasanna , Dwivedy Maheshwar , Malarvizhi Sudersanan , Balasubramanian Visvalingam 
Published: February 2024

AbstractAluminium (Al) and magnesium (Mg) alloys are extensively used in the automobile sector because of their high strength‐to‐weight ratio, excellent castability low density and simplicity of recycling. Al‐Mg structures used in the automotive sector can potentially reduce their weight. Although there is a significant opportunity for substantial cost reduction, the use of magnesium in aluminium structures remains restricted. This study aims to weld 3 mm‐thick rolled sheets of AA6061 Al and AZ31B Mg alloy using the cold metal transfer (CMT) arc welding process. Three different filler wires (ER1100, ER4043, and ER5356) were used in the experiment. In this article, the mechanical and microstructure characteristics of Al/Mg dissimilar joints manufactured by CMT are evaluated and discussed in detail. Optical microscope (OM), scanning electron microscopy (SEM), energy dispersive x‐ray spectroscopy (EDX), and x‐ray diffraction (XRD) were used to analyze the CMT‐welded Al/Mg dissimilar joints. Of the three filler wires used, ER4043 (Al‐5%Si) filler wire yielded defect‐free sound joints due to the presence of Si, which improves the flow ability of molten filler during welding. The presence of Mg‐rich intermetallics‐Al12Mg17) and Al‐rich intermetallics‐Al3Mg2 were observed. The fractured area of the CMT‐welded Al/Mg dissimilar joints revealed the presence of the Mg‐rich intermetallics (Al12Mg17), which is responsible for the decrease in tensile strength. The reduction of intermetallics, particularly of Mg‐rich intermetallics (Al12Mg17) is important for improving joint strength.Research Highlights
Cold metal transfer (CMT) arc welding was used to control the Al‐Mg‐rich intermetallics in the Al/Mg dissimilar joints.
The microstructure, morphology and phase composition of the welded joints were studied by OM, SEM, TEM, EDS and XRD.
The weld metal and AL substrate bonded with a strong interface, while weld metal and Mg substrate were joined at the epitaxial solidification area where the intermetallic compounds of Mg2Al3, Mg17Al12 and Mg2Si are generated.
The weld metal on the Mg side experienced brittle fracture, with a continuous distribution of Mg2Al3, Mg17Al12 and Mg2Si.
Efficacy and safety of pantoprazole and itopride in patients with overlap of gastroesophageal reflux disease and dyspepsia: A prospective, open‐label, single‐arm pilot study
Authors: Lakhtakia Sundeep , Singh Aniruddha P , Singla Neeraj , Memon Sana F , Reddy Duvvur N 
Published: February 2024

AbstractBackground and AimCombining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping dyspepsia, but data regarding this is lacking.MethodsThis single‐center, prospective study evaluated the efficacy and safety of 6‐week treatment with fixed‐drug combination (FDC) of pantoprazole (PPI) and itopride (prokinetic) in 50 patients with ≥3 month history of GERD and overlapping dyspepsia refractory to pantoprazole. Efficacy was assessed as reduction in GERD symptom assessment scale (GSAS) distress score for 15 symptoms from baseline to week 6. Adverse events (AEs) were monitored up to week 6.ResultsAlthough heartburn was the most common symptom at week 6 (26.8%), its frequency significantly decreased from baseline (84.0%; P <0.01). A similar trend was observed for other symptoms: pressure/discomfort inside chest (19.5%), belching (14.6%), regurgitation (12.2%), bloating (9.8%), flatulence (9.8%), early satiety (7.3%), acidic/sour taste in mouth (7.3%), nausea (7.3%), frequent gurgling in stomach/belly (4.9%), and pressure/lump in throat (2.4%). Mean distress scores of all symptoms markedly decreased at week 6. Three AEs (n = 2) of moderate intensity were reported.ConclusionThe FDC of pantoprazole and itopride showed favorable efficacy and safety in patients with GERD and overlapping dyspepsia refractory to pantoprazole monotherapy. Nevertheless, further studies are warranted.
A novel composition of endogenous metabolic modulators improves red blood cell properties in sickle cell disease
Authors: van Dijk Myrthe J. , Traets Marissa J. M. , van Oirschot Brigitte A. , Ruiter Titine J. J. , de Wilde Jonathan R. A. , Bos Jennifer , van Solinge Wouter W. , Koziel Margaret J. , Jans Judith J. M. , Wani Revati , van Beers Eduard J. , van Wijk Richard , Rab Minke A. E. 
Published: February 2024

AbstractThe most common forms of sickle cell disease (SCD) are sickle cell anemia (SCA; HbSS) and HbSC disease. In both, especially the more dense, dehydrated and adherent red blood cells (RBCs) with reduced deformability are prone to hemolysis and sickling, and thereby vaso‐occlusion. Based on plasma amino acid profiling in SCD, a composition of 10 amino acids and derivatives (RCitNacQCarLKHVS; Axcella Therapeutics, USA), referred to as endogenous metabolic modulators (EMMs), was designed to target RBC metabolism. The effects of ex vivo treatment with the EMM composition on different RBC properties were studied in SCD (n = 9 SCA, n = 5 HbSC disease). Dose‐dependent improvements were observed in RBC hydration assessed by hemocytometry (MCV, MCHC, dense RBCs) and osmotic gradient ektacytometry (Ohyper). Median (interquartile range [IQR]) increase in Ohyper compared to vehicle was 4.9% (4.0%–5.5%), 7.5% (6.9%–9.4%), and 12.8% (11.5%–14.0%) with increasing 20×, 40×, and 80X concentrations, respectively (all p < 0.0001). RBC deformability (EImax using oxygen gradient ektacytometry) increased by 8.1% (2.2%–12.1%; p = 0.0012), 9.6% (2.9%–15.1%; p = 0.0013), and 13.3% (5.7%–25.5%; p = 0.0007), respectively. Besides, RBC adhesion to subendothelial laminin decreased by 43% (6%–68%; p = 0.4324), 58% (48%–72%; p = 0.0185), and 71% (49%–82%; p = 0.0016), respectively. Together, these results provide a rationale for further studies with the EMM composition targeting multiple RBC properties in SCD.
MR Susceptibility Separation for Quantifying Lesion Paramagnetic and Diamagnetic Evolution in Relapsing–Remitting Multiple Sclerosis
Authors: Zhu Ziyan , Naji Nashwan , Esfahani Javad Hamidi , Snyder Jeff , Seres Peter , Emery Derek J. , Noga Michelle , Blevins Gregg , Smyth Penelope , Wilman Alan H. 
Published: February 2024

BackgroundMultiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components.PurposeTo apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R2*/R2′/QSM.Study TypeLongitudinal, prospective.SubjectsTwenty relapsing–remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years).Field Strength/SequenceThree‐dimensional multiple echo gradient echo (QSM and R2* mapping), two‐dimensional dual echo fast spin echo (R2 mapping), T2‐weighted fluid attenuated inversion recovery, and T1‐weighted magnetization prepared gradient echo sequences at 3 T.AssessmentData were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid‐attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R2* or separated into positive/negative components from χ separation.Statistical TestsTwo‐sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R2*/R2′/QSM. Significant level: P < 0.005.ResultsA total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R2*/R2′. When lesions were grouped based on changes in QSM and R2*, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility‐sensitive MRI indices and χ separation.Data ConclusionSusceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R2* and QSM alone.Level of Evidence2Technical EfficacyStage 2