bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protein kinase LKB1 promotes self‐renewal and blocks invasiveness in glioblastoma
Authors: Caja Laia , Dadras Mahsa Shahidi , Mezheyeuski Artur , Rodrigues‐Junior Dorival Mendes , Liu Sijia , Webb Anna Taylor , Gomez‐Puerto Maria Catalina , ten Dijke Peter , Heldin Carl‐Henrik , Moustakas Aristidis 
Published: August 2021

AbstractThe role of liver kinase B1 (LKB1) in glioblastoma (GBM) development remains poorly understood. LKB1 may regulate GBM cell metabolism and has been suggested to promote glioma invasiveness. After analyzing LKB1 expression in GBM patient mRNA databases and in tumor tissue via multiparametric immunohistochemistry, we observed that LKB1 was localized and enriched in GBM tumor cells that co‐expressed SOX2 and NESTIN stemness markers. Thus, LKB1‐specific immunohistochemistry can potentially reveal subpopulations of stem‐like cells, advancing GBM patient molecular pathology. We further analyzed the functions of LKB1 in patient‐derived GBM cultures under defined serum‐free conditions. Silencing of endogenous LKB1 impaired 3D‐gliomasphere frequency and promoted GBM cell invasion in vitro and in the zebrafish collagenous tail after extravasation of circulating GBM cells. Moreover, loss of LKB1 function revealed mitochondrial dysfunction resulting in decreased ATP levels. Treatment with the clinically used drug metformin impaired 3D‐gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. The IC50 of temozolomide in the GBM cultures was significantly decreased in the presence of metformin. This combinatorial effect was further enhanced after LKB1 silencing, which at least partially, was due to increased apoptosis. The expression of genes involved in the maintenance of tumor stemness, such as growth factors and their receptors, including members of the platelet‐derived growth factor (PDGF) family, was suppressed after LKB1 silencing. The defect in gliomasphere growth caused by LKB1 silencing was bypassed after supplementing the cells with exogenous PFDGF‐BB. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D‐gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread.
Phytochemical screening, green synthesis of gold nanoparticles, and antibacterial activity using seeds extract of Ricinus communis L
Authors: Rahman Taj Ur , Khan Hammad , Liaqat Wajiha , Zeb Muhammad Aurang 
Published: August 2021

AbstractIn the current research study, the phytochemical tests of the Ricinus communis L methanolic extract detected the presence of coumarin, reducing sugar, emodines, terpenoids, flavonoids, and steroids while water extract showed the presence of alkaloids, terpenoids, steroids, and soluble starch. The methanolic extract was further subjected to synthesize Au nanoparticles. The synthesized nanoparticles were confirmed by UV–Vis through the appearance of a peak at 550 nm which correspond to the existence of Au nanoparticles. The size and morphology of synthesized nanoparticle were further studied by the dynamic light scattering technique which shows that nanoparticles were in the range of 100 nm which were further confirmed by transmission electron microscopy. The synthesized nanoparticles and extracts were tested against different bacterial strains. The results revealed that methanolic extract showed maximum inhibition of 19.5 mm against Klebsiella pneumoniae and 20.33 mm against Bacillus cereus while water extract showed maximum inhibition of 18.16 mm against Pseudomonas aeruginosa and 19.33 mm against B. cereus. On the other hand, Au nanoparticles showed maximum inhibition of 18.5 mm against Escherichia coli.
Therapeutic interventions of remdesivir in diabetic and nondiabetic COVID‐19 patients: A prospective observational study conducted on Pakistani population
Authors: Qureshi Qiadat Hasnain , Ashraf Taimoor , Rehman Kanwal , Khosa Muhammad Kaleem , Akash Muhammad Sajid Hamid 
Published: August 2021

AbstractWe aimed to investigate the interventions of remdesivir in both diabetic and nondiabetic individuals who were suffering from a severe infection of novel coronavirus disease (COVID‐19). In this study, we aimed to explore the relationship between therapeutic effectiveness of remdesivir and complications of diabetes mellitus by observing the recovery period among diabetic and nondiabetic patients associated with COVID‐19 infection. A total of 850 COVID‐19 patients were recruited for this study, out of which 48% were diabetic and 52% were nondiabetics. The results of this study indicated that nondiabetic individuals administered with remdesivir recovered from COVID‐19 within 10 days showing a 95% confidence interval (p < 0.01), while the diabetic individuals recovered in 15 days. Nondiabetic patients administered with remdesivir exhibited higher chances of clinical improvement at 15th day than those who were associated with diabetes. Remdesivir administration improved the levels of various biochemical parameters, such as C‐reactive protein, lactate dehydrogenase, d‐Dimer, and ferritin both in diabetic and nondiabetic patients. However, a significant improvement (p < 0.01) was seen in the level of biochemical parameters among nondiabetic patients as compared to that of diabetic patients administered with remdesivir treatment. In the end, it was concluded that remdesivir could be considered as a possible therapeutic agent in the treatment of COVID‐19 both in diabetic and nondiabetic situations. However, diabetic patients showed a delayed recovery as compared with that of nondiabetic patients, in which the recovery rate was high.
Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum—Is TNT the solution?
Authors: Kazi Mufaddal , Jain Divakar , Padhy Amita Sekhar , Menon Munita , Desouza Ashwin , Sukumar Vivek , Gori Jayesh , Ostwal Vikas , Ankathi Suman Kumar , Saklani Avanish 
Published: August 2021

AbstractIntroductionThe results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet‐ring cell cancers (SRCC) that have an extremely aggressive biology.MethodsA retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high‐risk LARC. Primary endpoints were treatment failure and disease‐free survival (DFS)ResultsCTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down‐staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow‐up of 35 months, 56.5% had DFS events with a 3‐year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3‐year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS.ConclusionsSRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.
Mutations in circulating cell‐free tumour DNA: Predictors of survival in hepatocellular carcinoma
Authors: Howell Jessica , Atkinson Stephen R. , Pinato David J. , Khan Shahid A , Minisini Rosalba , Burlone Michela E. , Leutner Monica , Pirisi Mario , Büttner Reinhard , Odenthal Margarete , Sharma Rohini 
Published: August 2021

AbstractBackgroundHepatocellular carcinoma (HCC) incidence is increasing worldwide and prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Circulating cell‐free DNA of tumour origin (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We determined the utility of ctDNA as a prognostic biomarker of survival in HCC.MethodsPlasma cell‐free DNA and matched germline DNA were isolated from patients with HCC (n = 51) and cirrhosis (n = 10). Targeted, multiplex PCR ultra‐deep sequencing was performed using a liver cancer‐specific primer panel for genes ALB, AMPH, APC, ARID1A, ARID2, ATM, AXIN1, BAZ2B, BRAF, CSMD3, CTNNB1, DSE, ERBB2, HNF1A, IGFR2, IGSF10, KEAP1, MET, TP53, UBR3, USP25, ZIC3 and ZNF226. Associations between mutations in ctDNA and overall survival were analysed using Cox proportional hazards modelling.Results114 putative mutations (70 unique) in were detected in plasma ctDNA in 35 of 51 patients with HCC (69%). On univariable analysis, CSMD3 gene mutations were associated with shorter overall survival (Logrank HR 3.18, 95% CI 1.14‐8.86, P = .027). The median survival time was 15.5 months (IQR 7.77‐16.5 months) in patients with CSMD3 mutations compared with the median survival of 26.5 months (IQR 16.93‐46.07 months) in patients without CSMD3 mutations. Other factors associated with overall survival were advanced BCLC stage (HR 16.52, 95% CI 2.22‐122.94, P = .006) and Child‐Pugh Class (CPC HR 7.98, 95% CI 2.31‐27.61, P = .001). Cox proportional hazards modelling showed mutations in CSMD3 remained a significant independent risk for shorter overall survival in HCC when adjusted for age, BCLC stage and Child‐Pugh class (HR 4.91, 95% CI 1.60‐15.02, P = .005).ConclusionDetection of CSMD3 mutations in plasma ctDNA is associated with reduced overall survival in HCC patients, adjusted for potential confounding factors.
An empirical model to predict methane production in inland water sediment from particular organic matter supply and reactivity
Authors: Grasset Charlotte , Moras Simone , Isidorova Anastasija , Couture Raoul‐Marie , Linkhorst Annika , Sobek Sebastian 
Published: August 2021

AbstractThe highest CH4 production rates can be found in anoxic inland water surface sediments however no model quantifies CH4 production following fresh particular organic matter (POM) deposition on anoxic sediments. This limits our capability of modeling CH4 emissions from inland waters to the atmosphere. To generate such a model, we quantified how the POM supply rate and POM reactivity control CH4 production in anoxic surface sediment, by amending sediment at different frequencies with different quantities of aquatic and terrestrial POM. From the modeled CH4 production, we derived parameters related to the kinetics and the extent of CH4 production. We show that the extent of CH4 production can be well predicted by the quality (i.e., C/N ratio) and the quantity of POM supplied to an anoxic sediment. In particular, within the range of sedimentation rates that can be found in aquatic systems, we show that CH4 production increases linearly with the quantity of phytoplankton‐derived and terrestrially derived POM. A high frequency of POM addition, which is a common situation in natural systems, resulted in higher peaks in CH4 production rates. This suggests that relationships derived from earlier incubation experiments that added POM only once, may result in underestimation of sediment CH4 production. Our results quantitatively couple CH4 production in anoxic surface sediment to POM sedimentation flux, and are therefore useful for the further development of mechanistic models of inland water CH4 emission.
Building responsive governance for learning networks
Authors: Porcaro Keith 
Published: August 2021

AbstractIntroductionThis article describes a strategic governance review of Improve Care Now (ICN), a learning health network focused on improving clinical outcomes for adolescents with Crohn's disease and ulcerative colitis (IBD). ICN is organized around an “enhanced” patient registry and collaborative community of patients, parents, clinicians, and researchers.MethodsThe engagement included a review of ICN's governing documents, interviews and facilitated sessions with ICN stakeholders, and desk review to identify governance best practices that applied to ICN.ResultsThe review made recommendations to establish a plan to transition ICN's governance to its community, build pipelines for future network leaders, escalate uncommon data‐sharing decisions, and design safe online spaces for community members.ConclusionsGovernance can provide the scaffolding to help networks grow: organizing structures that support consistent, well documented, and inclusive decision‐making.
Biodegradable Porous Microneedles for an Electric Skin Patch
Authors: Abe Hiroya , Matsui Yuuya , Kimura Natsumi , Nishizawa Matsuhiko 
Published: August 2021

AbstractAn array of porous microneedles (PMNs) made of biodegradable poly(lactic‐co‐glycolic acid) (PLGA) is fabricated by a combination of molding and freeze‐drying methods. The optimized mixture of PLGA and 1,4‐dioxane is poured into a mold of a microneedle array, followed by the freezing and sublimation of the frozen particles of 1,4‐dioxane, a procedure that left an interconnecting porous structure in the PLGA with a porosity around 50%. The mechanical strength of the PMN made of PLGA (PLGA‐PMN) is reinforced by modification with carboxymethylcellulose (CMC), resulting in sufficient strength enough for insertion into an excised porcine skin. The transdermal resistance is significantly decreased by the CMC‐modified PLGA‐PMN, which would improve the efficiency and safety of DC current‐based transdermal techniques, including the electrical monitoring of the skin condition and iontophoresis for drug delivery and medical diagnosis.
Parametric reduced order models based on a Riemannian barycentric interpolation
Authors: Oulghelou Mourad , Allery Cyrille , Mosquera Rolando 
Published: August 2021

AbstractA new strategy for constructing parametric Galerkin reduced order models is presented in this article. This strategy is achieved thanks to the Riemannian manifold, quotient of the set of full‐rank matrices by the orthogonal group. Starting from a set of training parametrized subspaces of the same dimension, namely obtained by the proper orthogonal decomposition, the projection subspace for a new untrained parameter value is sought as the Karcher barycenter of the data points. The principal advantage of this strategy is that it leads to parametric reduced order models that are naturally flexible with respect to parameter variations. This property is a result of the simple expressions of the geodesic exponential and logarithmic mappings involved in the calculations of the approximated projection subspace. Confrontation with the usual interpolation in the tangent space to the Grassmann manifold is carried out for the flow problem past a circular cylinder and the flow in a lid‐driven cavity. Comparable results in terms of accuracy are obtained, while the proposed approach is shown to be computationally cheaper by allowing real‐time update of Galerkin projections.
Effect of mechanical treatments on orientation behavior and spectral properties of azoderivative dyes incorporated in poly(vinyl alcohol) films
Authors: Albu Raluca Marinica , Stoica Iuliana , Barzic Andreea Irina , Postolache Mihai , Angheluta Mihai‐Daniel , Dorohoi Dana Ortansa 
Published: August 2021

AbstractVarious azoderivative dyes were incorporated in uncolored poly(vinyl alcohol) (PVOH). One type of film was obtained by drying the layer of solution cast on glass plate. The other type was obtained by rubbing the PVOH layer before complete drying. Linear birefringence and dichroism of dyed polymer films were investigated as a function of stretching degree. An increase in the linear birefringence was found with increasing stretching degree for both uncolored and colored films. Dichroism of the PVOH films depends on the dye chemical structure and also on the stretching degree of both non‐rubbed and rubbed and dyed PVOH samples. Molecular modeling was used to examine interactions occurring between PVOH and the embedded dye molecule. These stretching degree dependencies were approximated mathematically, which was used to describe the behavior of some components of interference filters.
Organic Sonosensitizers for Sonodynamic Therapy: From Small Molecules and Nanoparticles toward Clinical Development
Authors: Li Dong , Yang Yang , Li Dengfeng , Pan Jie , Chu Chengchao , Liu Gang 
Published: August 2021

AbstractSonodynamic therapy (SDT) is a novel noninvasive therapeutic modality that combines low‐intensity ultrasound and sonosensitizers. Versus photo‐mediated therapy, SDT has the advantages of deeper tissue penetration, high accuracy, and less side effects. Sonosensitizers are critical for therapeutic efficacy during SDT and organic sonosensitizers are important because of their clear structure, easy monitoring, evaluation of drug metabolism, and clinical transformation. Notably, nanotechnology can be used in the field of sonosensitizers and SDT to overcome the inherent obstacles and achieve sustainable innovation. This review introduces organic small molecule sonosensitizers, nano organic sonosensitizers, and their clinical translation by providing ideas and references for the design of sonosensitizers and SDT so as to promote its transformation to clinical applications in the future.
Development of a Roadway‐Crossing Simulator for Actual Walking and Evaluation of Pedestrian Behavior
Authors: Uchibori Yuta , Handa Naoto , Fujiwara Katsuya , Mitobe Kazutaka 
Published: August 2021

AbstractPedestrians accounted for 36.6% of traffic accident fatalities in Japan (2019). Elderly pedestrians are often involved in such accidents while crossing a road. In order to investigate the characteristics of pedestrians who are prone to such accidents, we developed a ‘Roadway‐Crossing Simulator for actual walking’. The simulator projects a virtual traffic environment that is accurately reproduced in size and shape by eight projectors on 8.0‐m‐wide screens placed on both sides of a pedestrian. The simulator can motion‐capture the head, center of the scapula, and hips of a crossing pedestrian. In this study, we measured and analyzed the crossing behaviors of 10 young and 20 elderly people in a 7.5‐m section from a roadside zone before entering the road to the other end of the crosswalk. We report from this virtual traffic scenario the ‘Traffic accident incidence rate’, ‘Walking speed’, ‘Distance to pedestrians and vehicles’, ‘Inter‐vehicle selection ratio’ and ‘Elapsed time at roadside zone and roadway’. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Comparison between computed tomographic and ultrasonographic findings of the liver and spleen in dogs with confirmed hepatic or splenic lymphoma involvement
Authors: Mesquita Luis , Finotello Riccardo , Ferreira Amy , Maddox Thomas 
Published: August 2021

AbstractBackgroundComputed tomography (CT) and ultrasonography (US) may be used to assist staging in dogs with lymphoma. The imaging features of splenic and hepatic infiltration have never been directly compared in the same population of dogs.MethodsThe aim of this retrospective study was to describe and compare the CT and US findings of the liver and spleen in dogs with confirmed hepatic and/or splenic lymphoma and compare imaging and cytological diagnoses.ResultsCT and US studies of 18 dogs with multicentric lymphoma involving the liver and/or the spleen were retrospectively evaluated. US detected abnormalities more frequently than CT in the spleen with lymphoma, whereas CT detected abnormalities more frequently in the liver with lymphoma. The two diagnostic imaging modalities often disagreed in the findings, including the imaging classification of the organ as normal or abnormal.ConclusionUS and CT often disagree in the imaging findings present in hepatic and splenic lymphoma. The results of this study suggest that cytologic evaluation of both the liver and spleen is advisable regardless of their US or CT appearance for detection of lymphoma.
A methodology for simulating perched conditions in multilayer aquifer systems with 2D variably saturated flow
Authors: Aguilera Héctor , Heredia Díaz Javier , de la Losa Román Almudena 
Published: August 2021

AbstractSimulatingflow through multilayer aquifer systems is essential for groundwater management applications such evaluating natural recharge, assessing managed aquifer recharge (MAR), the characterization of surface water–groundwater interactions, and groundwater pollution risk analysis. However, dealing with flow through variably saturated porous media with perched water tables is a difficult task. Usual codes for groundwater flow modeling such as MODFLOW, TOUGH2, and FEFLOW require tedious procedures based on simplified assumptions and approximations. This paper presents a simple approach to simulate two‐dimensional flow through perched aquifers and aquitards in deep vadose zones by combining the Dirichlet and Neumann boundary conditions that may apply to any code simulating unsaturated flow. The proposed approach is illustrated with the unsaturated flow code VS2DTI. The main strengths of the proposed methodology are (a) variably saturated flow in the multilayer system is solved using Richards’ equation, taking into account the lateral flow that sustains observed water levels in perched aquifers and variations in recharge; (b) a Dirichlet‐type boundary condition at the top perched water table is substituted by a Neumann‐type boundary condition, allowing for the representation of any disturbance (e.g., infiltration from ponds, pumping from wells, etc.), regardless of duration and intensity; and (c) the impact of the disturbance is evaluated by comparing the responses of the undisturbed and the disturbed systems. The versatility of this methodology is applied to a MAR case study of a deep aquifer in a sedimentary basin where aquitards limit its feasibility.
Cover Image, Volume 8, Issue 5
Authors: Li Kexin , Hu Jinming , Li Ting , Liu Feng , Tao Juan , Liu Jiang , Zhang Zejin , Luo Xia , Li Linfeng , Deng Yongcui , Che Rongxiao 
Published: August 2021

The cover image is based on the Overview Microbial abundance and diversity investigations along rivers: Current knowledge and future directions by Kexin Li et al., https://doi.org/10.1002/wat2.1547.image
Assembly of multicomponent machines inRNAmetabolism: A common theme inmRNAdecay pathways
Authors: Machado de Amorim Alexandrina , Chakrabarti Sutapa 
Published: August 2021

AbstractMulticomponent protein–RNA complexes comprising a ribonuclease and partner RNA helicase facilitate the turnover of mRNA in all domains of life. While these higher‐order complexes provide an effective means of physically and functionally coupling the processes of RNA remodeling and decay, most ribonucleases and RNA helicases do not exhibit sequence specificity in RNA binding. This raises the question as to how these assemblies select substrates for processing and how the activities are orchestrated at the precise moment to ensure efficient decay. The answers to these apparent puzzles lie in the auxiliary components of the assemblies that might relay decay‐triggering signals. Given their function within the assemblies, these components may be viewed as “sensors.” The functions and mechanisms of action of the sensor components in various degradation complexes in bacteria and eukaryotes are highlighted here to discuss their roles in RNA decay processes.This article is categorized under:RNA Turnover and Surveillance > Regulation of RNA StabilityRNA Turnover and Surveillance > Turnover/Surveillance MechanismsRNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition