bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia
Authors: Rautenberg Christina , Stölzel Friedrich , Röllig Christoph , Stelljes Matthias , Gaidzik Verena , Lauseker Michael , Kriege Oliver , Verbeek Mareike , Unglaub Julia Marie , Thol Felicitas , Krause Stefan W. , Hänel Mathias , Neuerburg Charlotte , Vucinic Vladan , Jehn Christian-Friedrich , Severmann Julia , Wass Maxi , Fransecky Lars , Chemnitz Jens , Holtick Udo , Schäfer-Eckart Kerstin , Schröder Josephine , Kraus Sabrina , Krüger William , Kaiser Ulrich , Scholl Sebastian , Koch Kathrin , Henning Lea , Kobbe Guido , Haas Rainer , Alakel Nael , Röhnert Maximilian-Alexander , Sockel Katja , Hanoun Maher , Platzbecker Uwe , Holderried Tobias A. W. , Morgner Anke , Heuser Michael , Sauer Tim , Götze Katharina S. , Wagner-Drouet Eva , Döhner Konstanze , Döhner Hartmut , Schliemann Christoph , Schetelig Johannes , Bornhäuser Martin , Germing Ulrich , Schroeder Thomas , Middeke Jan Moritz 
Published: October 2021

AbstractTo investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10−3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation.
LHPP suppresses colorectal cancer cell migration and invasion in vitro and in vivo by inhibiting Smad3 phosphorylation in the TGF-β pathway
Authors: Hou Bin , Li Wenhan , Xia Peng , Zhao Fengyu , Liu Zhao , Zeng Qingnuo , Wang Shilong , Chang Dongmin 
Published: October 2021

AbstractThe roles of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) in tumorigenesis have been recently proven in hepatocellular carcinoma (HCC), cervical, pancreatic, bladder, and thyroid cancers. Previous research demonstrated thatLHPPrepressed cell proliferation and growth by inactivating the phosphatidylinositol 3-kinase/AKTsignaling pathway in vitro and in vivo. However, the functions and potential mechanisms ofLHPPas a tumor suppressor in colorectal cancer (CRC) metastasis are still unknown. Consequently, the Transwell assay and xenograft nude model showed thatLHPPinhibited migration and invasion of CRC cells in vitro and in vivo, respectively. The expression of total and nuclear epithelial-to-mesenchymal transition (EMT)-related proteins were significantly reduced afterLHPPupregulation. Human Gene Expression Array and IPA (Ingenuity Pathway Analysis) commercial software were applied to identify differentially expressed genes (DEGs) and potential cell signaling pathways. A total of 330 different genes were observed, including 177 upregulated genes and 153 downregulated genes. Bioinformatics analysis suggested that the transforming growth factor-β (TGF-β) signaling pathway was highly inactivated in this study. Then, Smad3 phosphorylation was apparently decreased, whereas Smad7 expression was markedly enhanced after upregulatingLHPPexpression. These results were proven once again after TGF-β1 stimulation. Furthermore, a specific inhibitor of Smad3 phosphorylation (SIS3) was applied to verify thatLHPPrepressed EMT of cancer cells by attenuating TGF-β/Smad signaling. The results suggested that suppression of the TGF-β/Smad signaling pathway byLHPPoverexpression could be abolished by SIS3.
AI-based design of a nuclear reactor core
Authors: Sobes Vladimir , Hiscox Briana , Popov Emilian , Archibald Rick , Hauck Cory , Betzler Ben , Terrani Kurt 
Published: October 2021

AbstractThe authors developed an artificial intelligence (AI)-based algorithm for the design and optimization of a nuclear reactor core based on a flexible geometry and demonstrated a 3× improvement in the selected performance metric: temperature peaking factor. The rapid development of advanced, and specifically, additive manufacturing (3-D printing) and its introduction into advanced nuclear core design through the Transformational Challenge Reactor program have presented the opportunity to explore the arbitrary geometry design of nuclear-heated structures. The primary challenge is that the arbitrary geometry design space is vast and requires the computational evaluation of many candidate designs, and the multiphysics simulation of nuclear systems is very time-intensive. Therefore, the authors developed a machine learning-based multiphysics emulator and evaluated thousands of candidate geometries on Summit, Oak Ridge National Laboratory’s leadership class supercomputer. The results presented in this work demonstrate temperature distribution smoothing in a nuclear reactor core through the manipulation of the geometry, which is traditionally achieved in light water reactors through variable assembly loading in the axial direction and fuel shuffling during refueling in the radial direction. The conclusions discuss the future implications for nuclear systems design with arbitrary geometry and the potential for AI-based autonomous design algorithms.
Irreversibility effects in peristaltic transport of hybrid nanomaterial in the presence of heat absorption
Authors: Sheriff Samreen , Ahmad S. , Mir N. A. 
Published: October 2021

AbstractThe nano heat transport has gained much significance in recent era. The micro-level devices are enganged succssfully in diverse fields like electronics, biomedical, navel structures, manufacturing, transportation, and automotive industries in order to improve the heat transfer for cooling and heating. Owing to this fact, the current article illustrates the features of irreversibility and thermal jump in peristaltic transport of hybrid nanoliquid. Here, water is used as base liquid while nanoparticles include polystyrene and graphene oxide. The flow is carried out in a non-uniform channel where the walls of channel flexible nature. Additionally, magnetic field impacts on flow and Joule heating analysis are examined. The aspect featuring heat absorption is introduced. Nanoparticle's shapes effect is also incorporated in flow analysis. Under the consideration of small Rynold number and long wavelength, the relevent equations are reduced by implementing non-dimensional variables. Involved pertinent parameters influence the peristaltic flow characteristics are displayed graphically and discussed concisely. The result indicates that temperature curves are dominant for pure water as compared to P/water nanofluid and P-GO/water hybrid nanofluid. Moreover, the convergent channel shows least entropy effects and extreme effects are noted for divergent case whereas uniform channel stays behind the divergent one.
Determining the immune environment of cutaneous T-cell lymphoma lesions through the assessment of lesional blood drops
Authors: Torii Kan , Okada Yukinori , Morita Akimichi 
Published: October 2021

AbstractDetailed analysis of the cells that infiltrate lesional skin cannot be performed in skin biopsy specimens using immunohistochemistry or cell separation techniques because enzyme treatments applied during the isolation step can destroy small amounts of protein and minor cell populations in the biopsy specimen. Here, we describe a method for isolating T cells from drops of whole blood obtained from lesions during skin biopsy in patients with cutaneous T-cell lymphoma. Lesional blood is assumed to contain lesional resident cells, cells from capillary vessels, and blood overflowing from capillary vessels into the lesion area. The lesional blood showed substantial increases in distinct cell populations, chemokines, and the expression of various genes. The proportion of CD8+CD45RO+T cells in the lesional blood negatively correlated with the modified severity-weighted assessment tool scores. CD4+CD45RO+T cells in the lesional blood expressed genes associated with the development of cancer and progression of cutaneous T-cell lymphoma. In addition, CD8+CD45RO+T cells in lesional blood had unique T-cell receptor repertoires in lesions of each stage. Assessment of lesional blood drops might provide new insight into the pathogenesis of mycosis fungoides and facilitate evaluation of the treatment efficacy for mycosis fungoides as well as other skin inflammatory diseases.
Barriers to cognitive screening in acute stroke units
Authors: Abzhandadze Tamar , Buvarp Dongni , Lundgren-Nilsson Åsa , Sunnerhagen Katharina S. 
Published: October 2021

AbstractCognitive impairment is common after stroke. However, not all patients with stroke undergo cognitive screening, despite recommendations. The aim of this retrospective, explorative study was to examine the barriers to cognitive screening in acute stroke units. Data were retrieved from two Swedish Stroke registries. The outcome variable was cognitive screening during the stay at acute stroke units. Forty-three candidate explanatory variables were considered for analysis, encompassing sociodemographic factors and stroke-related outcomes during the stay at acute stroke units. The Least Absolute Shrinkage and Selection Operator and decision-tree methods were used. Of the 1120 patients (56% male, mean age: 72 years, 50% with mild stroke), 44% did not undergo cognitive screening. Walking 10 m post-stroke was the most important attribute for decisions regarding cognitive screening. The classification accuracy, sensitivity, and specificity of the model were 70% (95% CI 63–75%), 71% (63–78%), and 67% (55–77%), respectively. Patient-related parameters that influenced cognitive screening with a valid and reliable screening instrument in acute stroke units included new stroke during the hospitalisation, aphasia at admission, mobility problems, impaired verbal output skills, and planned discharge to another care facility. The barriers to cognitive screening were both patient- and organisation-related, suggesting the need for patient-tailored cognitive screening tools as well as the implementation and systematic adherence to guidelines.
Myricetin ameliorates ox-LDL-induced HUVECs apoptosis and inflammation via lncRNA GAS5 upregulating the expression of miR-29a-3p
Authors: Bai Yunpeng , Liu Xiankun , Chen Qingliang , Chen Tongyun , Jiang Nan , Guo Zhigang 
Published: October 2021

AbstractOxidized low-density lipoprotein (ox-LDL)-induced endothelial cell dysfunction is a significant event in the progression of atherosclerosis. Even Myricetin (Myr) has been exhibited strong antioxidant potency, the effect on atherosclerosis is still elusive. HUVECs were subjected to ox-LDL, before which cells were preconditioned with Myr. Cell Counting Kit-8 assay, flow cytometry, quantitative real-time polymerase chain reaction and Western blot were carried out to assess the impacts of ox-LDL and Myr on HUVECs. The expression of EndMT markers was determined by Western blot analysis and immunocytochemistry. In addition, the relationship of GAS5 and miR-29a-3p was evaluated by RNA Fluorescent in Situ Hybridization and RNA immunoprecipitation assay. Myr preconditioning prevented ox-LDL-induced apoptosis, inflammatory response, and EndMT. GAS5 was upregulated in response to ox-LDL while it was down-regulated by Myr preconditioning. GAS5 over-expression attenuates Myr protective effects against ox-LDL–mediated HUVEC injury. Besides, miR-29a-3p is a target of GAS5 and down-regulated miR-29a-3p could further reduce the effects of GAS5 in ox-LDL–mediated HUVEC. Furthermore, Myr inactivated the TLR4/NF-κB signalling pathway in ox-LDL-treated HUVEC by down-regulating GAS5 or upregulating miR-26a-5p. Myr possessed an anti-inflammatory and anti-EndMT function against ox-LDL-induced HUVEC injury by regulating the GAS5/miR-29a-3p, indicating that Myr may have an important therapeutic function for atherosclerosis.
Factors associated with assisted ventilation use in amyotrophic lateral sclerosis: a nationwide population-based study in Korea
Authors: Yoon Seo Yeon , Kim Han-Kyoul , Kim Mi Ji , Suh Jee Hyun , Leigh Ja-Ho 
Published: October 2021

AbstractFew studies have investigated the factors associated with assisted ventilation use in amyotrophic lateral sclerosis (ALS) in western countries with a relatively small number of participants. This study aimed to evaluate the factors associated with assisted ventilation use using a large nationwide cohort covering the entire Korean population. We selected patients with primary or secondary diagnoses of ALS (ICD-10 code: G12.21) and a registration code for ALS (V123) in the rare intractable disease registration program. Covariates included in the analyses were age, sex, socioeconomic status and medical condition. Factors associated with non-invasive ventilation (NIV) and tracheostomy invasive ventilation (TIV) were evaluated. Logistic regression analyses were performed using odds ratios and 95% confidence intervals. In total, 3057 patients with ALS were enrolled. During the 6-year follow-up period, 1228 (40%) patients started using assisted ventilation: 956 with NIV and 272 with TIV. There was no significant difference in the assisted ventilation use according to sex, whereas different patterns of discrepancies were noted between the sexes: Females living in non-metropolitan areas showed decreased use of assisted ventilation, whereas high income levels showed a positive relationship with assisted ventilation use only in males. Patients aged ≥ 70 years showed decreased use of NIV. NIV use was more affected by socioeconomic status than TIV, whereas TIV showed a significant relationship with medical conditions such as nasogastric tube insertion and gastrostomy. We found that various factors, including age, socioeconomic status, and medical condition, were related with assisted ventilation use. Understanding the pattern of assisted ventilation use would help set optimal management strategies in patients with ALS.
Improving heat and mass transfer rates through continuous drop-wise condensation
Authors: Alshehri Ali , Rothstein Jonathan P. , Kavehpour H. Pirouz 
Published: October 2021

AbstractDrop-wise condensation (DWC) has been the focus of scientific research in vapor condensation technologies since the 20th century. Improvement of condensation rate in DWC is limited by the maximum droplet a condensation surface could sustain and the frequency of droplet shedding. Furthermore, The presence of non-condensable gases (NCG) reduces the condensation rate significantly. Here, we present continuous drop-wise condensation to overcome the need of hydrophobic surfaces while yet maintaining micron-sized droplets. By shifting focus from surface treatment to the force required to sweep off a droplet, we were able to utilize stagnation pressure of jet impingement to tune the shed droplet size. The results show that droplet size being shed can be tuned effectively by tuning the jet parameters. our experimental observations showed that the effect of NCG is greatly alleviated by utilizing this technique. An improvement by multiple folds in mass transfer compactness factor compared to state-of-the-art dehumidification technology was possible.
Early crack detection using modified spectral clustering method assisted with FE analysis for distress anticipation in cement-based composites
Authors: Vedrtnam Ajitanshu , Kumar Santosh , Barluenga Gonzalo , Chaturvedi Shashikant 
Published: October 2021

AbstractThe present work reports an efficient way of capturing real-time crack propagation in concrete structures. The modified spectral analysis based algorithm and finite element modeling (FEM) were utilised for crack detection and quantitative analysis of crack propagation. Crack propagation was captured in cement-based composite (CBC) containing saw dust and M20 grade concrete under compressive loading using a simple and inexpensive 8-megapixel mobile phone camera. The randomly selected images showing crack initiation and propagation in CBCs demonstrated the crack capturing capability of developed algorithm. A measure of oriented energy was provided at crack edges to develop a similarity spatial relationship among the pairwise pixels. FE modelling was used for distress anticipation, by analysing stresses during the compressive test in constituents of CBCs. FE modeling jointly with the developed algorithm, can provide real-time inputs from the crack-prone areas and useful in early crack detection of concrete structures for preventive support and management.
BMP7 reduces the fibrocartilage chondrocyte phenotype
Authors: Ripmeester Ellen G. J. , Caron Marjolein M. J. , van den Akker Guus G. H. , Steijns Jessica , Surtel Don A. M. , Cremers Andy , Peeters Laura C. W. , van Rhijn Lodewijk W. , Welting Tim J. M. 
Published: October 2021

AbstractThe fibrocartilage chondrocyte phenotype has been recognized to attribute to osteoarthritis (OA) development. These chondrocytes express genes related to unfavorable OA outcomes, emphasizing its importance in OA pathology. BMP7 is being explored as a potential disease-modifying molecule and attenuates the chondrocyte hypertrophic phenotype. On the other hand, BMP7 has been demonstrated to relieve organ fibrosis by counteracting the pro-fibrotic TGFβ-Smad3-PAI1 axis and increasing MMP2-mediated Collagen type I turnover. Whether BMP7 has anti-fibrotic properties in chondrocytes is unknown. Human OA articular chondrocytes (HACs) were isolated from end-stage OA femoral cartilage (total knee arthroplasty; n = 18 individual donors). SW1353 cells and OA HACs were exposed to 1 nM BMP7 for 24 h, after which gene expression of fibrosis-related genes and fibrosis-mediating factors was determined by RT-qPCR. In SW1353, Collagen type I protein levels were determined by immunocytochemistry and western blotting. PAI1 and MMP2 protein levels and activity were measured with an ELISA and activity assays, respectively. MMP2 activity was inhibited with the selective MMP-2 inhibitor OA-Hy. SMAD3 activity was determined by a (CAGA)12-reporter assay, and pSMAD2 levels by western blotting. Following BMP7 exposure, the expression of fibrosis-related genes was reduced in SW1353 cells and OA HACs. BMP7 reduced Collagen type I protein levels in SW1353 cells. Gene expression of MMP2 was increased in SW1353 cells following BMP7 treatment. BMP7 reduced PAI1 protein levels and -activity, while MMP2 protein levels and -activity were increased by BMP7. BMP7-dependent inhibition of Collagen type I protein levels in SW1353 cells was abrogated when MMP2 activity was inhibited. Finally, BMP7 reduced pSMAD2 levels determined by western blotting and reduced SMAD3 transcriptional activity as demonstrated by decreased (CAGA)12 luciferase reporter activity. Our data demonstrate that short-term exposure to BMP7 decreases the fibrocartilage chondrocyte phenotype. The BMP7-dependent reduction of Collagen type I protein expression seems MMP2-dependent and inhibition of Smad2/3-PAI1 activity was identified as a potential pathway via which BMP7 exerts its anti-fibrotic action. This indicates that in chondrocytes BMP7 may have a double mode-of-action by targeting both the hypertrophic as well as the fibrotic chondrocyte phenotype, potentially adding to the clinical relevance of using BMP7 as an OA disease-modifying molecule.
Brain microvasculature endothelial cell orientation on micropatterned hydrogels is affected by glucose level variations
Authors: Porras Hernández Ana María , Barbe Laurent , Pohlit Hannah , Tenje Maria , Antfolk Maria 
Published: October 2021

AbstractThis work reports on an effort to decipher the alignment of brain microvasculature endothelial cells to physical constrains generated via adhesion control on hydrogel surfaces and explore the corresponding responses upon glucose level variations emulating the hypo- and hyperglycaemic effects in diabetes. We prepared hydrogels of hyaluronic acid a natural biomaterial that does not naturally support endothelial cell adhesion, and specifically functionalised RGD peptides into lines using UV-mediated linkage. The width of the lines was varied from 10 to 100 µm. We evaluated cell alignment by measuring the nuclei, cell, and F-actin orientations, and the nuclei and cell eccentricity via immunofluorescent staining and image analysis. We found that the brain microvascular endothelial cells aligned and elongated to these physical constraints for all line widths. In addition, we also observed that varying the cell medium glucose levels affected the cell alignment along the patterns. We believe our results may provide a platform for further studies on the impact of altered glucose levels in cardiovascular disease.
Pre-concentration of microRNAs by LNA-modified magnetic beads for enhancement of electrochemical detection
Authors: Ustuner Serife , Lindsay Mark A. , Estrela Pedro 
Published: October 2021

AbstractMicroRNAs are extremely promising candidates for early cancer diagnosis and prognosis. The levels of circulating microRNAs provide valuable information about cancer disease at its early stages. However, the levels of microRNAs that need to be detected are extremely low and difficult to discriminate from a large pool of oligonucleotides. There is the need for accurate, rapid and sensitive detection methodologies for detection of microRNAs. We developed electrochemical impedance spectroscopy peptide nucleic acid (PNA)-based sensors that can detect miRNAs in diluted serum with a limit of detection of 0.38 fM. In order to further improve the accuracy and reliability of the sensors, we developed an assay using magnetic beads for simple and rapid fishing of target microRNAs from solution and its pre-concentration prior to electrochemical detection. Our methodology utilizes magnetic beads for the capture of the target microRNA from solution and brings the concentrated sample to the sensor surface. We modify the magnetic beads with locked nucleic acids (LNA), which have high affinity and specificity to their complementary microRNA sequence. The separated and concentrated microRNA is then detected using the PNA-based sensors. By exposing the sensing electrodes only to the captured microRNAs, interferences from other nucleotides or biomolecules from the sample are eliminated.