bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases
Authors: Huang Richard S.P. , Haberberger James , McGregor Kimberly , Mata Douglas A. , Decker Brennan , Hiemenz Matthew C. , Lechpammer Mirna , Danziger Natalie , Schiavone Kelsie , Creeden James , Graf Ryon P. , Strowd Roy , Lesser Glenn J. , Razis Evangelia D. , Bartsch Rupert , Giannoudis Athina , Bhogal Talvinder , Lin Nancy U. , Pusztai Lajos , Ross Jeffrey S. , Palmieri Carlo , Ramkissoon Shakti H. 
Published: June 2021

AbstractBackgroundAmong patients with breast carcinoma who have metastatic disease, 15%–30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of patients with breast carcinoma brain metastases (BCBMs) and compared it with a cohort of patients with primary breast carcinomas (BCs).Material and MethodsWe retrospectively analyzed 733 BCBMs tested with comprehensive genomic profiling (CGP) and compared them with 10,772 primary breast carcinomas (not-paired) specimens. For a subset of 16 triple-negative breast carcinoma (TNBC)–brain metastasis samples, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) was performed concurrently.ResultsA total of 733 consecutive BCBMs were analyzed. Compared with primary BCs, BCBMs were enriched for genomic alterations in TP53 (72.0%, 528/733), ERBB2 (25.6%, 188/733), RAD21 (14.1%, 103/733), NF1 (9.0%, 66/733), BRCA1 (7.8%, 57/733), and ESR1 (6.3%,46/733) (p &lt; .05 for all comparisons). Immune checkpoint inhibitor biomarkers such as high tumor mutational burden (TMB-high; 16.2%, 119/733); high microsatellite instability (1.9%, 14/733); CD274 amplification (3.6%, 27/733); and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like mutational signature (5.9%, 43/733) were significantly higher in the BCBM cohort compared with the primary BC cohort (p &lt; .05 for all comparisons). When using both CGP and PD-L1 IHC, 37.5% (6/16) of patients with TNBC brain metastasis were eligible for atezolizumab based on PD-L1 IHC, and 18.8% (3/16) were eligible for pembrolizumab based on TMB-high status.ConclusionWe found a high prevalence of clinically relevant genomic alterations in patients with BCBM, suggesting that tissue acquisition (surgery) and/or cerebrospinal fluid for CGP in addition to CGP of the primary tumor may be clinically warranted.Implications for PracticeThis study found a high prevalence of clinically relevant genomic alterations in patients with breast carcinoma brain metastasis (BCBM), suggesting that tissue acquisition (surgery) and/or cerebrospinal fluid for comprehensive genomic profiling (CGP) in addition to CGP of the primary tumor may be clinically warranted. In addition, this study identified higher positive rates for FDA-approved immunotherapy biomarkers detected by CGP in patients with BCBM, opening a possibility of new on-label treatments. Last, this study noted limited correlation between tumor mutational burden and PD-L1 immunohistochemistry (IHC), which shows the importance of testing patients with triple-negative BCBM for immune checkpoint inhibitor eligibility with both PD-L1 IHC and CGP.
Liquid Biopsy in Glioblastoma Management: From Current Research to Future Perspectives
Authors: Gatto Lidia , Franceschi Enrico , Di Nunno Vincenzo , Tosoni Alicia , Lodi Raffaele , Brandes Alba Ariela 
Published: June 2021

AbstractGlioblastoma (GBM) is the most common primary tumor of the central nervous system. Arising from neuroepithelial glial cells, GBM is characterized by invasive behavior, extensive angiogenesis, and genetic heterogeneity that contributes to poor prognosis and treatment failure. Currently, there are several molecular biomarkers available to aid in diagnosis, prognosis, and predicting treatment outcomes; however, all require the biopsy of tumor tissue. Nevertheless, a tissue sample from a single location has its own limitations, including the risk related to the procedure and the difficulty of obtaining longitudinal samples to monitor treatment response and to fully capture the intratumoral heterogeneity of GBM. To date, there are no biomarkers in blood or cerebrospinal fluid for detection, follow-up, or prognostication of GBM. Liquid biopsy offers an attractive and minimally invasive solution to support different stages of GBM management, assess the molecular biology of the tumor, identify early recurrence and longitudinal genomic evolution, predict both prognosis and potential resistance to chemotherapy or radiotherapy, and allow patient selection for targeted therapies. The aim of this review is to describe the current knowledge regarding the application of liquid biopsy in glioblastoma, highlighting both benefits and obstacles to translation into clinical care.Implications for PracticeTo translate liquid biopsy into clinical practice, further prospective studies are required with larger cohorts to increase specificity and sensitivity. With the ever-growing interest in RNA nanotechnology, microRNAs may have a therapeutic role in brain tumors.
Regional air transportation of ovarian tissue for cryopreservation in a prepubertal female with cancer
Authors: Schermerhorn Sophia M. V. , Rosen Mitchell P. , Blevins Erin M. , Byrd Kevin A. , Rabban Joseph T. , Marsh Philip , Lucas Donald J. 
Published: June 2021

AbstractOvarian tissue cryopreservation is the only fertility preservation (FP) option available to prepubescent females receiving gonadotoxic therapy, but it has limited availability. A 6‐year‐old female was diagnosed with high‐risk rhabdomyosarcoma, and the planned treatment carried an 80% risk of ovarian failure. Her parents desired FP, but the nearest center was 500 miles away. The patient underwent oophorectomy at the cancer center with air transport of the tissue to the oncofertility center, where it was successfully cryopreserved. Formation of networks between full‐service and limited oncofertility centers in a hub‐and‐spoke model would increase access to FP services, particularly in children.
A green approach for the development of functionalized graphene and cardanol‐based polybenzoxazine nanocomposite
Authors: Sambandam Sahila , Nallamuthu Prabhu , Lakshmanan Saraswathi Jayakumari 
Published: June 2021

AbstractA new facile synthesis of functionalized graphene (fg‐p) reinforced bio‐based polybenzoxazine nanocomposite (pbf2%–pbf10%) was developed in this work. Cardanol, formaldehyde, and furfuryl amine were used to make a bio‐based benzoxazine monomer (bf). bf and benzoxazine polymer (pbf) were characterized by Fourier transform infrared (FT‐IR) and nuclear magnetic resonance spectroscopies, and fg‐p was characterized by FT‐IR spectroscopy, X‐ray diffraction, and scanning electron microscopy. The electrochemical properties of the fg‐p sheets and their nanocomposites (pbf2%–pbf10%) were examined using cyclic voltammetry and electrochemical impedance spectroscopy. The results of electrochemical measurements showed that pbf4% has the largest specific capacitance of 78.2 F/g when compared to pbf (36.98 F/g), which shows that fg‐p reinforced pbf nanocomposites have potential application as the high‐performance capacitor electrode material.
Preparation of poly(acrylamide‐co‐2‐acrylamido‐2‐methylpropan sulfonic acid)‐g‐Carboxymethyl cellulose/Titanium dioxide hydrogels and modeling of their swelling capacity and mechanic strength behaviors by response surface method technique
Authors: Boztepe Cihangir , Daskin Mahmut , Erdogan Ahmet , Sarici Talha 
Published: June 2021

AbstractIt is very important that new generation, unique, high mechanical strength, and biocompatible hydrogel composites are developed due to their potential to be used as biomaterials in the biomedical field. Modeling of the swelling capacity and mechanical strength behavior of hydrogels is a domain of steadily increasing academic and industrial importance. These behaviors are difficult to model accurately due to hydrogels show very complex behavior depending on the content. In this study, a series of poly(acrylamide‐co‐2‐acrylamido‐2‐methylpropan sulfonic acid)‐g‐carboxymethyl cellulose/TiO2 (poly(AAm‐co‐AMPS)‐g‐CMC/TiO2) superabsorbent hydrogel composites were prepared by free‐radical graft copolymerization in aqueous solution. Structural and surface morphology characterizations were conducted by using Fourier‐transform infrared spectroscopy and scanning electron microscope analysis techniques. For modeling the equilibrium swelling capacity and fracture strength behaviors of hydrogels, the composition parameters (such as mole ratio of AMPS/AAm, wt% of CMC, and wt% of TiO2) was proposed by response surface method (RSM) Design Expert‐10 software. Statistical parameters showed that the RSM model has good performance in modeling the swelling capacity and mechanic fracture strength behaviors of poly(AAm‐co‐AMPS)‐g‐CMC/TiO2 hydrogel composites. According to the RSM model results, the maximum swelling capacity and fracture strength values were calculated as 270.39 g water/g polymer and 159.23 kPa, respectively.
Fabrication and applications of stimuli‐responsive micro/nanopillar arrays
Authors: Park Jeong Eun , Won Sukyoung , Cho Woongbi , Kim Jae Gwang , Jhang Saebohm , Lee Jae Gyeong , Wie Jeong Jae 
Published: June 2021

AbstractThe functional surface features of living creatures are driven by the complex morphology of periodically arranged micro/nanoscale structures. Various fabrication processes have been devised mimic the performance of natural features; these methods morph hierarchical and multi‐leveled pillar arrays, such as top‐down, bottom‐up, and a hybrid of top‐down and bottom‐up processes. Different methodologies are employed depending on the materials, such as polymeric composites, metal oxides, metals, and carbon nanotubes. In this review, we discuss the shape‐reconfiguration of stimuli‐responsive micro/nanopillar arrays achieved by capillary force, light, magnetic field, and heat. In particular, photo‐ and magnetic actuation of pillar arrays revealed programmability according to the arrangement of the liquid crystal molecules or magnetic particles by remote control. Furthermore, applications of micro/nanopillar arrays, such as adhesives, omniphobicity, optics, and biomedical technologies, are also discussed.
Role of montelukast in multitrigger wheezers attending chest clinic in Punjab, India
Authors: Kahlon Gursavreen K. , Pooni Puneet A. , Bhat Deepak , Dhooria Gurdeep S. , Bhargava Siddharth , Arora Kamal , Gill Karambir S. 
Published: June 2021

AbstractBackgroundWheeze is seen in 40% of preschool children, one‐third of these may develop recurrent wheeze. Montelukast is an oral, once a day, easy to give therapy but there is no definite evidence to support its use in a recent meta‐analysis. Present study was done to evaluate role of daily montelukast and various factors affecting the outcome after therapy in multitrigger wheeze (MTW).MethodsA prospective study conducted in Pediatric chest clinic over 18 months at DMCH, Ludhiana. Children from 6 months to 5 years, diagnosed cases of MTW were started on montelukast. Diagnosis based on symptoms of recurrent wheeze triggered by various allergens/precipitants was made by pediatrician in charge of chest clinic. Children were followed up at 1 and 3 months. They were labeled as controlled, partially controlled, or uncontrolled as per global initiative for asthma guidelines. Data were used to compare the outcome related to various factors.ResultsTotal 139 out of 150 children came for regular follow‐up. At the end of 3 months, 94 (67.7%) were controlled, 8 (5.7%) partially controlled, and 37 (26.6%) children remained uncontrolled on montelukast. Factors associated with poor control were onset of symptoms at younger age (<6 months of age), family history of allergies, prior multiple visits or hospitalizations due to MTW, use of MDI in the past. No significant side effects were reported by parents.ConclusionSymptomatically two‐third of children became better after starting montelukast. There were few factors which resulted in poorer control in subset of patients.
Proteomic analysis of a murine model of lung hypoplasia induced by oligohydramnios
Authors: Najrana Tanbir , Ahsan Nagib , Abu‐Eid Rasha , Uzun Alper , Noble Lelia , Tollefson George , Sanchez‐Esteban Juan 
Published: June 2021

AbstractSevere oligohydramnios (OH) due to prolonged loss of amniotic fluid can cause pulmonary hypoplasia. Animal model of pulmonary hypoplasia induced by amniotic fluid drainage is partly attributed to changes in mechanical compression of the lung. Although numerous studies on OH‐model have demonstrated changes in several individual proteins, however, the underlying mechanisms for interrupting normal lung development in response to a decrease of amniotic fluid volume are not fully understood. In this study, we used a proteomic approach to explore differences in the expression of a wide range of proteins after induction of OH in a mouse model of pulmonary hypoplasia to find out the signaling/molecular pathways involved in fetal lung development. Liquid chromatography‐massspectromery/mass spectrometry analysis found 474 proteins that were differentially expressed in OH‐induced hypoplastic lungs in comparison to untouched (UnT) control. Among these proteins, we confirmed the downregulation of AKT1, SP‐D, and CD200, and provided proof‐of‐concept for the first time about the potential role that these proteins could play in fetal lung development.
Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB
Authors: Michalska Karolina , Wellington Samantha , Maltseva Natalia , Jedrzejczak Robert , Selem‐Mojica Nelly , Rosas‐Becerra L. Rodrigo , Barona‐Gómez Francisco , Hung Deborah T. , Joachimiak Andrzej 
Published: June 2021

AbstractIntracellular growth and pathogenesis of Chlamydia species is controlled by the availability of tryptophan, yet the complete biosynthetic pathway for l‐Trp is absent among members of the genus. Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB – a bifunctional enzyme catalyzing the last two steps in l‐Trp synthesis. TrpA (subunit α) converts indole‐3‐glycerol phosphate into indole and glyceraldehyde‐3‐phosphate (α reaction). The former compound is subsequently used by TrpB (subunit β) to produce l‐Trp in the presence of l‐Ser and a pyridoxal 5′‐phosphate cofactor (β reaction). Previous studies have indicated that in Chlamydia, TrpA has lost its catalytic activity yet remains associated with TrpB to support the β reaction. Here, we provide detailed analysis of the TrpAB from C. trachomatis D/UW‐3/CX, confirming that accumulation of mutations in the active site of TrpA renders it enzymatically inactive, despite the conservation of the catalytic residues. We also show that TrpA remains a functional component of the TrpAB complex, increasing the activity of TrpB by four‐fold. The side chain of non‐conserved βArg267 functions as cation effector, potentially rendering the enzyme less susceptible to the solvent ion composition. The observed structural and functional changes detected herein were placed in a broader evolutionary and genomic context, allowing identification of these mutations in relation to their trp gene contexts in which they occur. Moreover, in agreement with the in vitro data, partial relaxation of purifying selection for TrpA, but not for TrpB, was detected, reinforcing a partial loss of TrpA functions during the course of evolution.
Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
Authors: McFeely Savannah J. , Yu Jingjing , Wang Yan , Wu Cheryl , Ragueneau‐Majlessi Isabelle 
Published: June 2021

AbstractAlthough the use of excipients is widespread, a thorough understanding of the drug interaction potential of these compounds remains a frequent topic of current research. Not only can excipients alter the disposition of coformulated drugs, but it is likely that these effects on co‐administered drugs can reach to clinical significance leading to potential adverse effects or loss of efficacy. These risks can be evaluated through use of in silico methods of mechanistic modeling, including approaches, such as population pharmacokinetic (PK) and physiologically‐based PK modeling, which require a comprehensive understanding of the compounds to ensure accurate predictions. We established a knowledgebase of the available compound (or substance) and interaction‐specific parameters with the goal of providing a single source of physiochemical, in vitro, and clinical PK and interaction data of commonly used excipients. To illustrate the utility of this knowledgebase, a model for cremophor EL was developed and used to hypothesize the potential for CYP3A‐ and P‐gp‐based interactions as a proof of concept.
Preparation and characterization of whey protein isolate/chitosan/microcrystalline cellulose composite films
Authors: Zhai Xinyu , Zhang Xia , Ao Huanping , Yin Yuxi , Li Xue , Ren Difeng 
Published: June 2021

AbstractA bio‐based composite film was prepared using whey protein isolate (WPI), chitosan (CS) and microcrystalline cellulose (MCC). The effects of film‐forming material concentration ratio, pH value and glycerin addition on the mechanical properties, water vapour permeability and transmittance of the composite film were investigated using response surface methodology. Optimum film‐forming process conditions were obtained, including a CS/MCC concentration ratio of 1.5:1, pH 3.6 and 30% glycerin addition. Scanning electron microscopy and atomic force microscopy images showed that the surface of the WPI/CS/MCC composite films was flat, uniform and smooth. Fourier‐transform infrared spectroscopy analysis indicated that hydrogen bonds occurred between the film‐forming materials. The film‐forming materials were concluded to have good compatibility, while the WPI/CS/MCC composite film showed better mechanical properties and moisture barrier properties, which will provide a good application prospect and foundation for the food packaging industry.
First‐principles study on the plutonium ions interaction with diamide molecules in acid solutions
Authors: Ryzhkov Mikhail V. , Enyashin Andrei N. , Delley Bernard 
Published: June 2021

AbstractTheoretical study of the formation of PuZ+ (Z = 3, 4, 5, 6) complexes with the two types of diamide molecules C8N2H10O2(CH3)2 (dimethylbicyclicdiamide—DMDA) with bicyclic structure and C3N2H2O2(CH3)4 (tetramethylmalonamide—TMMA) with acyclic structure was carried out using ab initio DFT based DMol3 and relativistic discrete variational methods. The results of gas phase modeling showed that the appropriate positions of the oxygen atoms in DMDA in comparison with TMMA cannot explain the considerable difference in sorption affinity of these molecules. For the modeling of solutions, the implicit (COSMO) and explicit methods were used. In the latter approach, we included 40 water molecules, 16NO3− or 16Cl− and 16H+ ions into the systems under investigation. The obtained results showed the principle role of solution in the weakening of actinide bonding with TMMA and DMDA molecules due to interaction with H2O and NO3− or Cl− ions.
Voltage‐Tunable Ultra‐Steep Slope Atomic Switch with Selectivity over 1010
Authors: Kim Kwang‐Hyun , Park Youngjun , Kim Min‐Kyu , Lee Jang‐Sik 
Published: June 2021

AbstractAtomic switch‐based selectors, which utilize the formation of conductive filaments by the migration of ions, are researched for cross‐point array architecture due to their simple structure and high selectivity. However, the difficulty in controlling the formation of filaments causes uniformity and reliability issues. Here, a multilayer selector with Pt/Ag‐doped ZnO/ZnO/Ag‐doped ZnO/Pt structure by the sputtering process is presented. A multilayer structure enables control of the filament formation by preventing excessive influx of Ag ions. The multilayer selector device exhibits a high on‐current density of 2 MA cm−2, which can provide sufficient current for the operation with the memory device. Also, the device exhibits high selectivity of 1010 and a low off‐current of 10−13 A. The threshold voltage of selector devices can be controlled by modulating the thickness of the ZnO layer. By connecting a multilayer selector device to a resistive switching memory, the leakage current of the memory device can be reduced. These results demonstrate that a multilayer structure can be used in a selector device to improve selectivity and reliability for use in high‐density memory devices.
Supramolecular Nanosubstrate‐Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion
Authors: Ban Qian , Yang Peng , Chou Shih‐Jie , Qiao Li , Xia Haidong , Xue Jingjing , Wang Fang , Xu Xiaobin , Sun Na , Zhang Ryan Y. , Zhang Ceng , Lee Athena , Liu Wenfei , Lin Ting‐Yi , Ko Yu‐Ling , Antovski Petar , Zhang Xinyue , Chiou Shih‐Hwa , Lee Chin‐Fa , Hui Wenqiao , Liu Dahai , Jonas Steven J. , Weiss Paul S. , Tseng Hsian‐Rong 
Published: June 2021

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein 9 (CRISPR/Cas9) is an efficient and precise gene‐editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9•sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP⊂SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate‐mediated delivery. Utilizing the U87 glioblastoma cell line as a model system, a variety of parameters for cellular‐uptake of the RNP‐laden nanoparticles are examined. Dose‐ and time‐dependent CRISPR/Cas9‐mediated gene disruption is further examined in a green fluorescent protein (GFP)‐expressing U87 cell line (GFP‐U87). The utility of an optimized SMNP formulation in co‐delivering Cas9 protein and two sgRNAs that target deletion of exons 45–55 (708 kb) of the dystrophin gene is demonstrated. Mutations in this region lead to Duchenne muscular dystrophy, a severe genetic muscle wasting disease. Efficient delivery of these gene deletion cargoes is observed in a human cardiomyocyte cell line (AC16), induced pluripotent stem cells, and mesenchymal stem cells.
Bond strength degradation in concrete cracked by expansion agent filled pipes
Authors: Syll Amadou Sakhir , Aburano Togo , Kanakubo Toshiyuki 
Published: June 2021

AbstractIn this study, the bond behavior of corroded reinforced concrete was investigated by conducting pull‐out tests on concrete specimens with variable induced crack widths and different splitting modes. To simulate cracks due to corrosion and focus on their effect on bond strength degradation, a novel method using expansion agent filled pipes is proposed. With the increase of the crack width over elapsed time from filling the aluminum pipe with an expansion agent, a target crack width was obtained. The results confirm that the type of splitting greatly influences the reduction in bond strength with deterioration of bond strength more severe in “Side‐split” than in “Single‐split.” Furthermore, using the surface crack width as a variable, empirical formulas to predict bond strength degradation due to corrosion of rebar are proposed. These prediction models give a good correlation when compared to the available literature.