bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active Targeting Nanoparticle Self‐Assembled from Cisplatin‐Palbociclib Amphiphiles Ensures Optimal Drug Ratio for Combinatorial Chemotherapy
Authors: Xiang Yucheng , Liu Chendong , Chen Liqiang , Li Lian , Huang Yuan 
Published: March 2021

AbstractTriple negative breast cancer (TNBC) not only exhibits aggressive progression and metastasis, but also responds to neither hormone therapy nor checkpoint blockade therapy. Thus, combinatorial chemotherapy is indispensable for TNBC treatment. However, due to the different pharmacokinetics of individual drugs and weak synergistic effects caused by random drug molar ratio in tumor, direct coadministration is far from satisfactory. Constructing a nanoscale drug delivery system with fixed drug molar ratios and maximum drug content is an urgent problem. Herein, an active targeting nanoparticle self‐assembled from cisplatin‐palbociclib amphiphiles with optimal drug ratio is reported. The combination of cisplatin and palbociclib at a molar ratio of 1:2 is found to have the best synergistic effect and is selected for follow‐up studies. After conjugating two palbociclib molecules to one cisplatin molecule, a fixed cisplatin/palbociclib (1:2) molar ratio is enabled and this amphiphilic conjugate can self‐assemble into nanoparticles. A small amount of iRGD coupled 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐polyethylene glycol‐2000 (DSPE‐PEG‐iRGD) that further stabilizes the nanoparticle is introduced to fabricate the desired nanoparticle (iRGD‐PCN) and endow active tumor‐targeting ability. On an orthotopic TNBC mouse model, iRGD‐PCN efficiently accumulates in tumors and inhibits tumor growth. Additionally, the formation of lung metastasis nodes is also significantly suppressed. In general, the active targeting nanoparticles self‐assembled from cisplatin‐palbociclib amphiphiles provide options for combinatorial chemotherapy.
Recent Progress on Wear‐Resistant Materials: Designs, Properties, and Applications
Authors: Zhai Wenzheng , Bai Lichun , Zhou Runhua , Fan Xueling , Kang Guozheng , Liu Yong , Zhou Kun 
Published: March 2021

AbstractThere has been tremendous interest in the development of different innovative wear‐resistant materials, which can help to reduce energy losses resulted from friction and wear by ≈40% over the next 10–15 years. This paper provides a comprehensive review of the recent progress on designs, properties, and applications of wear‐resistant materials, starting with an introduction of various advanced technologies for the fabrication of wear‐resistant materials and anti‐wear structures with their wear mechanisms. Typical strategies of surface engineering and matrix strengthening for the development of wear‐resistant materials are then analyzed, focusing on the development of coatings, surface texturing, surface hardening, architecture, and the exploration of matrix compositions, microstructures, and reinforcements. Afterward, the relationship between the wear resistance of a material and its intrinsic properties including hardness, stiffness, strength, and cyclic plasticity is discussed with underlying mechanisms, such as the lattice distortion effect, bonding strength effect, grain size effect, precipitation effect, grain boundary effect, dislocation or twinning effect. A wide range of fundamental applications, specifically in aerospace components, automobile parts, wind turbines, micro‐/nano‐electromechanical systems, atomic force microscopes, and biomedical devices are highlighted. This review is concluded with prospects on challenges and future directions in this critical field.
Magnetic State Generation using Hamiltonian Guided Variational Autoencoder with Spin Structure Stabilization
Authors: Kwon Hee Young , Yoon Han Gyu , Park Sung Min , Lee Doo Bong , Choi Jun Woo , Won Changyeon 
Published: March 2021

AbstractNumerical generation of physical states is essential to all scientific research fields. The role of a numerical generator is not limited to understanding experimental results; it can also be employed to predict or investigate characteristics of uncharted systems. A variational autoencoder model is devised and applied to a magnetic system to generate energetically stable magnetic states with low local deformation. The spin structure stabilization is made possible by taking the explicit magnetic Hamiltonian into account to minimize energy in the training process. A significant advantage of the model is that the generator can create a long‐range ordered ground state of spin configuration by increasing the role of stabilization even if the ground states are not necessarily included in the training process. It is expected that the proposed Hamiltonian‐guided generative model can bring about great advances in numerical approaches used in various scientific research fields.
Metal‐Organic Fragments with Adhesive Excipient and Their Utilization to Stabilize Multimetallic Electrocatalysts for High Activity and Robust Durability in Oxygen Evolution Reaction
Authors: Choi Won Ho , Kim Keon‐Han , Lee Heebin , Choi Jae Won , Park Dong Gyu , Kim Gi Hwan , Choi Kyung Min , Kang Jeung Ku 
Published: March 2021

AbstractMultimetallic electrocatalysts have shown great potential to improve electrocatalytic performance, but their deteriorations in activity and durability are yet to be overcome. Here, metal‐organic fragments with adhesive excipient to realize high activity with good durability in oxygen evolution reaction (OER) are developed. First, a leaf‐like zeolitic–imidazolate framework (ZIF‐L) is synthesized. Then, ionized species in hydrogen plasma attack preferentially the organic linkers of ZIF‐L to derive cobalt–imidazole fragments (CIFs) as adhesive excipient, while they are designed to retain the coordinated cobalt nodes. Moreover, the vacant coordination sites at cobalt nodes and the unbound nitrogen at organic linkers induce high porosity and conductivity. The CIFs serve to stably impregnate trimetallic FeNiMo electrocatalysts (CIF:FeNiMo), and CIF:FeNiMo containing Fe contents of 22% and hexavalent Mo contents show to enable high activity with low overpotentials (203 mV at 10 mA cm−2 and 238 mV at 100 mA cm−2) in OER. The near O K‐edge extended X‐ray absorption fine structure proves further that high activity for OER originates from the partially filled eg orbitals. Additionally, CIF:FeNiMo exhibit good durability, as demonstrated by high activity retention during at least 45 days in OER.
Hematopoietic expression of a chimeric murine‐human CALR oncoprotein allows the assessment of anti‐CALR antibody immunotherapies in vivo
Authors: Achyutuni Sarada , Nivarthi Harini , Majoros Andrea , Hug Eva , Schueller Christina , Jia Ruochen , Varga Cecilia , Schuster Michael , Senekowitsch Martin , Tsiantoulas Dimitris , Kavirayani Anoop , Binder Christoph J , Bock Christoph , Zagrijtschuk Oleh , Kralovics Robert 
Published: March 2021

AbstractMyeloproliferative neoplasms (MPNs) are characterized by a pathologic expansion of myeloid lineages. Mutations in JAK2, CALR and MPL genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN. We generated a transgenic murine model with conditional expression of the human mutant exon 9 (del52) from the murine endogenous Calr locus. These mice develop essential thrombocythemia like phenotype with marked thrombocytosis and megakaryocytosis. The disease exacerbates with age showing prominent signs of splenomegaly and anemia. The disease is transplantable and mutCALR stem cells show proliferative advantage when compared to wild type stem cells. Transcriptome profiling of hematopoietic stem cells revealed oncogenic and inflammatory gene expression signatures. To demonstrate the applicability of the transgenic animals for immunotherapy, we treated mice with monoclonal antibody raised against the human mutCALR. The antibody treatment lowered platelet and stem cell counts in mutant mice. Secretion of mutCALR did not constitute a significant antibody sink. This animal model not only recapitulates human MPN but also serves as a relevant model for testing immunotherapeutic strategies targeting epitopes of the human mutCALR.
A rare case of postnatal mosaic trisomy 12 with severe congenital heart disease and literature review
Authors: Hu Xiaolin , Ayala Sofia Saenz , Dyer Lisa , Guan Qiaoning , Pena Loren 
Published: March 2021

AbstractTrisomy 12 is a rare autosomal aneuploidy. All postnatally diagnosed individuals with trisomy 12 have been mosaic for this chromosome abnormality. We herein report an infant girl presented at 2 weeks of age with severe congenital heart defect, tracheobronchomalacia, and dysmorphic features. All of the dysmorphic features of this patient fit into the known phenotype spectrum of mosaic trisomy 12, although this patient uniquely presented with macrocephaly. Tracheo‐bronchomalacia has been described once previously but had a significant impact on this patient's clinical course. The patient passed away at 2‐month‐old due to cardiac and respiratory complications. Chromosomal single nucleotide polymorphism (SNP) microarray analysis on a peripheral blood sample from the patient revealed trisomy 12 in approximately 50% of cells. Concurrent fluorescence in situ hybridization analysis of uncultured blood cells detected a comparable level of trisomy 12 mosaicism. Compared to conventional cytogenetics, SNP microarray examines all nucleated cells without sampling bias, has an increased power to estimate mosaicism level, and can provide a quick assessment of the underlying mechanism. Here we demonstrate the utilization of SNP microarray in the clinical diagnosis of those once considered rare disorders but might have been missed by conventional cytogenetic techniques.
The mystery of monozygotic twinning I: What can Amyoplasia tell us about monozygotic twinning and the possible role of twin–twin transfusion?
Authors: Hall Judith G. 
Published: March 2021

AbstractAmyoplasia is a very specific, nongenetic clinically recognizable form of arthrogryposis, representing about one‐third of individuals with arthrogryposis surviving the newborn period. There is a markedly increased number of individuals with Amyoplasia who are one of monozygotic (MZ) twins, with the other twin being normal. Thus, it would appear that Amyoplasia is definitely associated with and may be caused by an MZ twinning event. The twin–twin transfusion seen in MZ twins could play an etiologic role in producing Amyoplasia. In this article, Amyoplasia twinning is compared to twinning in other forms of arthrogryposis. The accompanying paper examines various types of MZ twinning (Hall, 2021). Amyoplasia is primarily associated with spontaneous MZ twinning.
Natural history study of adults with Wolf–Hirschhorn syndrome 1: Case series of personally observed 35 individuals
Authors: Battaglia Agatino , Lortz Amanda , Carey John C. 
Published: March 2021

AbstractWolf–Hirschhorn syndrome (WHS) is a contiguous gene disorder, clinically delineated by prenatal and postnatal growth deficiency, distinctive craniofacial features, intellectual disability, and seizures. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3). Although more than 300 persons with WHS have been reported in the literature, there is sparse, if any, long‐term follow‐up of these individuals and thus little knowledge about course and potential further complications and health risks during adulthood and advanced age. This study attempted to assess medical conditions and function of adult individuals with WHS. It was one component of a two‐part investigation on adults with WHS. The other part of the study is the patient‐reported outcomes study reported elsewhere. About 35 individuals with WHS (26 females; nine males), aged between 19 and 55 years were recruited. About 25 individuals were personally observed at the IRCCS Stella Maris Foundation by A.B. and followed up between 5 and 20 years; and 10 were recruited from the 4p‐Support Group, The United States. Of note, 23/35 (66%) are close to total care. About 11 out of 35 (31%) were partly self‐independent, requiring supervision on certain daily routines, and 1 out of 35 (3%) was fully independent. However, a positive perspective is given by the overall good health enjoyed by the 66% of our cohort of individuals. Overall, quality of life and level of function into adulthood appear to be less critical than anticipated from previous studies.
Design and synthesis of benzenesulfonamide‐linked imidazo[2,1‐b][1,3,4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors
Authors: Swain Baijayantimala , Aashritha Kamtam , Singh Priti , Angeli Andrea , Kothari Abhay , Sigalapalli Dilep K. , Yaddanapudi Venkata M. , Supuran Claudiu T. , Arifuddin Mohammed 
Published: March 2021

AbstractA novel series of imidazothiadiazole‐linked benzenesulfonamide derivatives (5a–t) was synthesized and subjected for screening against the four physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I, II, VA, and IX. The compounds selectively inhibited hCA I and II over hCA VA and IX. Furthermore, among the two cytosolic isoforms, hCA II was more effectively inhibited as compared with hCA I. The most active compounds were 5o with K
i = 0.246 µM and 5p with K
i = 0.376 µM against hCA II, whereas compound 5f showed good inhibition against both hCA I and II with K
i = 0.493 and 0.4 µM, respectively. This class of underexplored sulfonamides may be used to design isoform‐selective CA inhibitors targeting enzymes of medicinal chemistry interest.
Integrated geophysical study in the cemetery of Marquis of Haihun
Authors: Li Man , Zhang Zhiyong , Yang Jun , Xie Shangping 
Published: March 2021

AbstractA group of Han dynasty tombs were found in a small town in central eastern China. It is difficult to infer the underground structures of the cemetery based on surface information. Geophysical methods are nonintrusive technology that can be used in archaeological excavations to provide important underground information. Multiple geophysical methods including total magnetic field (TMF), self‐potential (SP), direct‐current resistivity (DCR) and ground‐penetrating radar (GPR) were used to investigate the structure of ancient tombs. Total magnetic anomaly (TMA) and SP data can be used to obtain the projections of anomalous bodies on earth surface. DCR and GPR data can be used to gauge and further determine the spatial locations and depths of the anomalies. The results of the integrated geophysical interpretation were used to optimize the excavation plans and were verified by the subsequent works, such as coffin chambers, dromoi, ancient building foundations and funeral pit. Integrated geophysical survey can effectively reduce the uncertainly of a single method and obtain the targets more accurately.
Ethical considerations for remote sensing and open data in relation to the endangered archaeology in the Middle East and North Africa project
Authors: Fisher Michael , Fradley Michael , Flohr Pascal , Rouhani Bijan , Simi Francesca 
Published: March 2021

AbstractThe UK‐based Endangered Archaeology in the Middle East and North Africa (EAMENA) project uses remote sensing techniques to rapidly record and evaluate the status of archaeological and cultural heritage sites in the MENA region. Applying remote sensing methods to the archaeological landscapes of 20 countries, EAMENA is one of the largest documentation projects of its kind. Such a scope raises important ethical questions fundamental to the practice of remote‐sensed archaeology, and this paper contributes to this discussion by reflecting on EAMENA's unique role in this subfield. We present ethical issues and possible solutions related to remote sensing and archaeology, drawing on models developed within the humanitarian aid sector and postcolonial archaeology. In addition, we consider issues of national sovereignty and their relationship to the engagement of local communities. Finally, this paper examines the roles of data openness and open access policies as ethical factors and how EAMENA has addressed these so far.
Serum Metabolomics Identifies Dysregulated Pathways and Potential Metabolic Biomarkers for Hyperuricemia and Gout
Authors: Shen Xia , Wang Can , Liang Ningning , Liu Zhen , Li Xinde , Zhu Zheng‐Jiang , Merriman Tony R. , Dalbeth Nicola , Terkeltaub Robert , Li Changgui , Yin Huiyong 
Published: March 2021

ObjectiveTo systematically profile metabolic alterations and dysregulated metabolic pathways in hyperuricemia and gout, and to identify potential metabolite biomarkers to discriminate gout from asymptomatic hyperuricemia.MethodsSerum samples from 330 participants, including 109 with gout, 102 with asymptomatic hyperuricemia, and 119 normouricemic controls, were analyzed by high‐resolution mass spectrometry–based metabolomics. Multivariate principal components analysis and orthogonal partial least squares discriminant analysis were performed to explore differential metabolites and pathways. A multivariate methods with Unbiased Variable selection in R (MUVR) algorithm was performed to identify potential biomarkers and build multivariate diagnostic models using 3 machine learning algorithms: random forest, support vector machine, and logistic regression.ResultsUnivariate analysis demonstrated that there was a greater difference between the metabolic profiles of patients with gout and normouricemic controls than between the metabolic profiles of individuals with hyperuricemia and normouricemic controls, while gout and hyperuricemia showed clear metabolomic differences. Pathway enrichment analysis found diverse significantly dysregulated pathways in individuals with hyperuricemia and patients with gout compared to normouricemic controls, among which arginine metabolism appeared to play a critical role. The multivariate diagnostic model using MUVR found 13 metabolites as potential biomarkers to differentiate hyperuricemia and gout from normouricemia. Two‐thirds of the samples were randomly selected as a training set, and the remainder were used as a validation set. Receiver operating characteristic analysis of 7 metabolites yielded an area under the curve of 0.83–0.87 in the training set and 0.78–0.84 in the validation set for distinguishing gout from asymptomatic hyperuricemia by 3 machine learning algorithms.ConclusionGout and hyperuricemia have distinct serum metabolomic signatures. This diagnostic model has the potential to improve current gout care through early detection or prediction of progression to gout from hyperuricemia.
Association of Machine Learning–Based Predictions of Medial Knee Contact Force With Cartilage Loss Over 2.5 Years in Knee Osteoarthritis
Authors: Brisson Nicholas M. , Gatti Anthony A. , Damm Philipp , Duda Georg N. , Maly Monica R. 
Published: March 2021

ObjectiveThe relationship between in vivo knee load predictions and longitudinal cartilage changes has not been investigated. We undertook this study to develop an equation to predict the medial tibiofemoral contact force (MCF) peak during walking in persons with instrumented knee implants, and to apply this equation to determine the relationship between the predicted MCF peak and cartilage loss in patients with knee osteoarthritis (OA).MethodsIn adults with knee OA (39 women, 8 men; mean ± SD age 61.1 ± 6.8 years), baseline biomechanical gait analyses were performed, and annualized change in medial tibial cartilage volume (mm3/year) over 2.5 years was determined using magnetic resonance imaging. In a separate sample of patients with force‐measuring tibial prostheses (3 women, 6 men; mean ± SD age 70.3 ± 5.2 years), gait data plus in vivo knee loads were used to develop an equation to predict the MCF peak using machine learning. This equation was then applied to the knee OA group, and the relationship between the predicted MCF peak and annualized cartilage volume change was determined.ResultsThe MCF peak was best predicted using gait speed, the knee adduction moment peak, and the vertical knee reaction force peak (root mean square error 132.88N; R2 = 0.81, P < 0.001). In participants with knee OA, the predicted MCF peak was related to cartilage volume change (R2 = 0.35, β = −0.119, P < 0.001).ConclusionMachine learning was used to develop a novel equation for predicting the MCF peak from external biomechanical parameters. The predicted MCF peak was positively related to medial tibial cartilage volume loss in patients with knee OA.
Scientific considerations to move towards biowaiver for biopharmaceutical classification system class III drugs: How modeling and simulation can help
Authors: Wu Fang , Cristofoletti Rodrigo , Zhao Liang , Rostami‐Hodjegan Amin 
Published: March 2021

AbstractThe 2017 Guidance by U.S. Food and Drug Administration (FDA) has recommended the criteria to qualify for a Biopharmaceutical Classification System (BCS)‐based biowaiver that includes high solubility of the drug across the physiological pH range as well as the formulation considerations, e.g., being qualitatively the same and quantitatively very similar to the reference product. These were ratified by the International Council for Harmonization (ICH) in 2018. The FDA has used the similar verbiage when referring to the BCS‐based biowaiver option for BCS class III drugs (highly soluble but poorly permeable). However, establishing in vitro‐in vivo correlations (IVIVC) using conventional mass balance deconvolution approaches, which assumes a single absorption compartment, is not likely for very rapidly dissolving dosage forms containing BCS III drugs. Unlike conventional mass balance deconvolution techniques, physiologically based pharmacokinetic models are able to disentangle different processes contributing to the input function, e.g., dissolution, gastrointestinal transit, and permeation and to establish IVIVC using variants of the compartmental absorption and transit model, supporting biowaiver for formulations containing BCS III drugs. However, there are knowledge gaps that need to be filled. This review provides a systematic assessment of the advancements in applications of physiologically based pharmacokinetic (PBPK) models for IVIVC and biowaiver for such cases with the aim of identifying the most important gaps and hurdles. It concludes by calling for research efforts on the impact of excipients on dissolution and permeation, alongside the development of PBPK modeling to link these in vitro characteristics to in vivo bioequivalence outcomes through simulations of virtual clinical studies