bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-EGFR antibody 528 binds to domain III of EGFR at a site shifted from the cetuximab epitope
Authors: Makabe Koki , Yokoyama Takeshi , Uehara Shiro , Uchikubo-Kamo Tomomi , Shirouzu Mikako , Kimura Kouki , Tsumoto Kouhei , Asano Ryutaro , Tanaka Yoshikazu , Kumagai Izumi 
Published: March 2021

AbstractAntibodies have been widely used for cancer therapy owing to their ability to distinguish cancer cells by recognizing cancer-specific antigens. Epidermal growth factor receptor (EGFR) is a promising target for the cancer therapeutics, against which several antibody clones have been developed and brought into therapeutic use. Another antibody clone, 528, is an antagonistic anti-EGFR antibody, which has been the focus of our antibody engineering studies to develop cancer drugs. In this study, we explored the interaction of 528 with the extracellular region of EGFR (sEGFR) via binding analyses and structural studies. Dot blotting experiments with heat treated sEGFR and surface plasmon resonance binding experiments revealed that 528 recognizes the tertiary structure of sEGFR and exhibits competitive binding to sEGFR with EGF and cetuximab. Single particle analysis of the sEGFR–528 Fab complex via electron microscopy clearly showed the binding of 528 to domain III of sEGFR, the domain to which EGF and cetuximab bind, explaining its antagonistic activity. Comparison between the two-dimensional class average and the cetuximab/sEGFR crystal structure revealed that 528 binds to a site that is shifted from, rather than identical to, the cetuximab epitope, and may exclude known drug-resistant EGFR mutations.
Chlorite oxidized oxyamylose differentially influences the microstructure of fibrin and self assembling peptide hydrogels as well as dental pulp stem cell behavior
Authors: EzEldeen Mostafa , Toprakhisar Burak , Murgia Denise , Smisdom Nick , Deschaume Olivier , Bartic Carmen , Van Oosterwyck Hans , Pereira Rafaela Vaz Sousa , Opdenakker Ghislain , Lambrichts Ivo , Bronckaers Annelies , Jacobs Reinhilde , Patterson Jennifer 
Published: March 2021

AbstractTailored hydrogels mimicking the native extracellular environment could help overcome the high variability in outcomes within regenerative endodontics. This study aimed to evaluate the effect of the chemokine-binding and antimicrobial polymer, chlorite-oxidized oxyamylose (COAM), on the microstructural properties of fibrin and self-assembling peptide (SAP) hydrogels. A further goal was to assess the influence of the microstructural differences between the hydrogels on the in vitro behavior of human dental pulp stem cells (hDPSCs). Structural and mechanical characterization of the hydrogels with and without COAM was performed by atomic force microscopy and scanning electron microscopy to characterize their microstructure (roughness and fiber length, diameter, straightness, and alignment) and by nanoindentation to measure their stiffness (elastic modulus). Then, hDPSCs were encapsulated in hydrogels with and without COAM. Cell viability and circularity were determined using confocal microscopy, and proliferation was determined using DNA quantification. Inclusion of COAM did not alter the microstructure of the fibrin hydrogels at the fiber level while affecting the SAP hydrogel microstructure (homogeneity), leading to fiber aggregation. The stiffness of the SAP hydrogels was sevenfold higher than the fibrin hydrogels. The viability and attachment of hDPSCs were significantly higher in fibrin hydrogels than in SAP hydrogels. The DNA content was significantly affected by the hydrogel type and the presence of COAM. The microstructural stability after COAM inclusion and the favorable hDPSCs' response observed in fibrin hydrogels suggest this system as a promising carrier for COAM and application in endodontic regeneration.
Market instability and the size-variance relationship
Authors: Buldyrev Sergey V. , Flori Andrea , Pammolli Fabio 
Published: March 2021

AbstractWe show that some key features of the behavior of mutual funds is accounted for by a stochastic model of proportional growth. We find that the negative dependence of the variance of funds’ growth rates on size is well described by an approximate power law. We discover that during periods of crisis the volatility of the largest funds’ growth rates increases with respect to mid-sized funds. Our result reveals that a lower and flatter slope provides relevant information on the structure of the system. We find that growth rates volatility poorly depends on the size of the funds, thus questioning the benefits of diversification achieved by larger funds. Our findings show that the slope of the size-variance relationship can be used as a synthetic indicator to monitor the intensity of instabilities and systemic risk in financial markets.
Decratonization by rifting enables orogenic reworking and transcurrent dispersal of old terranes in NE Brazil
Authors: Ganade Carlos E. , Weinberg Roberto F. , Caxito Fabricio A. , Lopes Leonardo B. L. , Tesser Lucas R. , Costa Iago S. 
Published: March 2021

AbstractDispersion and deformation of cratonic fragments within orogens require weakening of the craton margins in a process of decratonization. The orogenic Borborema Province, in NE Brazil, is one of several Brasiliano/Pan-African late Neoproterozoic orogens that led to the amalgamation of Gondwana. A common feature of these orogens is that a period of extension and opening of narrow oceans preceded inversion and collision. For the case of the Borborema Province, the São Francisco Craton was pulled away from its other half, the Benino-Nigerian Shield, during an intermittent extension event between 1.0–0.92 and 0.9–0.82 Ga. This was followed by inversion of an embryonic and confined oceanic basin at ca. 0.60 Ga and transpressional orogeny from ca. 0.59 Ga onwards. Here we investigate the boundary region between the north São Francisco Craton and the Borborema Province and demonstrate how cratonic blocks became physically involved in the orogeny. We combine these results with a wide compilation of U–Pb and Nd-isotopic model ages to show that the Borborema Province consists of up to 65% of strongly sheared ancient rocks affiliated with the São Francisco/Benino-Nigerian Craton, separated by major transcurrent shear zones, with only ≈ 15% addition of juvenile material during the Neoproterozoic orogeny. This evolution is repeated across a number of Brasiliano/Pan-African orogens, with significant local variations, and indicate that extension weakened cratonic regions in a process of decratonization that prepared them for involvement in the orogenies, that led to the amalgamation of Gondwana.
Admission serum potassium levels and prognosis of vasospastic angina
Authors: Seo Won-Woo , Jo Sang-Ho , Kim Sung Eun , Kim Hyun-Jin , Han Seung Hwan , Lee Kwan Yong , Her Sung Ho , Lee Min-Ho , Cho Seong-Sik , Kim Hack-Lyoung , Baek Sang Hong 
Published: March 2021

AbstractHypokalemia is a common electrolyte disturbance and is related to poor prognosis in patients with cardiovascular disease. However, the role of hypokalemia in patients with vasospastic angina (VSA) has not yet been studied. The present study enrolled 1454 patients diagnosed with VSA according to ergonovine provocation test results and available admission serum potassium data. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia. Based on a hypokalemia definition as serum potassium concentration ≤ 3.5 mEq/L, the hypokalaemia group included 70 patients (4.8%). The median potassium levels were 3.4 mEq/L [interquartile range (IQR) 3.3–3.5] in the hypokalemia group and 4.1 mEq/L (IQR 3.9–4.3) in the no-hypokalemia group. The median follow-up duration was 764 days. Primary outcomes occurred in seven patients (10.0%) in the hypokalemia group and 51 patients (3.7%) in the no-hypokalemia group. The Kaplan–Meier analysis showed a higher cumulative incidence of primary outcomes in the hypokalemia group compared to that in the no-hypokalemia group (log-rank P = 0.014). Multivariate Cox regression analysis also showed that hypokalemia was an independent predictor of primary outcomes. In conclusion, hypokalemia at admission was associated with adverse clinical outcomes in VSA.
On the modulation and maintenance of hibernation in captive dwarf lemurs
Authors: Blanco Marina B. , Greene Lydia K. , Schopler Robert , Williams Cathy V. , Lynch Danielle , Browning Jenna , Welser Kay , Simmons Melanie , Klopfer Peter H. , Ehmke Erin E. 
Published: March 2021

AbstractIn nature, photoperiod signals environmental seasonality and is a strong selective “zeitgeber” that synchronizes biological rhythms. For animals facing seasonal environmental challenges and energetic bottlenecks, daily torpor and hibernation are two metabolic strategies that can save energy. In the wild, the dwarf lemurs of Madagascar are obligate hibernators, hibernating between 3 and 7 months a year. In captivity, however, dwarf lemurs generally express torpor for periods far shorter than the hibernation season in Madagascar. We investigated whether fat-tailed dwarf lemurs (Cheirogaleus medius) housed at the Duke Lemur Center (DLC) could hibernate, by subjecting 8 individuals to husbandry conditions more in accord with those in Madagascar, including alternating photoperiods, low ambient temperatures, and food restriction. All dwarf lemurs displayed daily and multiday torpor bouts, including bouts lasting ~ 11 days. Ambient temperature was the greatest predictor of torpor bout duration, and food ingestion and night length also played a role. Unlike their wild counterparts, who rarely leave their hibernacula and do not feed during hibernation, DLC dwarf lemurs sporadically moved and ate. While demonstrating that captive dwarf lemurs are physiologically capable of hibernation, we argue that facilitating their hibernation serves both husbandry and research goals: first, it enables lemurs to express the biphasic phenotypes (fattening and fat depletion) that are characteristic of their wild conspecifics; second, by “renaturalizing” dwarf lemurs in captivity, they will emerge a better model for understanding both metabolic extremes in primates generally and metabolic disorders in humans specifically.
A parameter adaptive method for state of charge estimation of lithium-ion batteries with an improved extended Kalman filter
Authors: Yang Shichun , Zhou Sida , Hua Yang , Zhou Xinan , Liu Xinhua , Pan Yuwei , Ling Heping , Wu Billy 
Published: March 2021

AbstractAn accurate state of charge (SOC) estimation in battery management systems (BMS) is of crucial importance to guarantee the safe and effective operation of automotive batteries. However, the BMS consistently suffers from inaccuracy of SOC estimation. Herein, we propose a SOC estimation approach with both high accuracy and robustness based on an improved extended Kalman filter (IEKF). An equivalent circuit model is established, and the simulated annealing-particle swarm optimization (SA-PSO) algorithm is used for offline parameter identification. Furthermore, improvements have been made with noise adaptation, a fading filter and a linear-nonlinear filtering based on the traditional EKF method, and rigorous mathematical proof has been carried out accordingly. To deal with model mismatch, online parameter identification is achieved by a dual Kalman filter. Finally, various experiments are performed to validate the proposed IEKF. Experimental results show that the IEKF algorithm can reduce the error to 2.94% under dynamic stress test conditions, and robustness analysis is verified with noise interference, hence demonstrating its practicability for extending to state estimation of battery packs applied in real-world operating conditions.
APTES monolayer coverage on self-assembled magnetic nanospheres for controlled release of anticancer drug Nintedanib
Authors: Karade V. C. , Sharma A. , Dhavale R. P. , Dhavale R. P. , Shingte S. R. , Patil P. S. , Kim J. H. , Zahn D. R. T. , Chougale A. D. , Salvan G. , Patil P. B. 
Published: March 2021

AbstractThe use of an appropriate delivery system capable of protecting, translocating, and selectively releasing therapeutic moieties to desired sites can promote the efficacy of an active compound. In this work, we have developed a nanoformulation which preserves its magnetization to load a model anticancerous drug and to explore the controlled release of the drug in a cancerous environment. For the preparation of the nanoformulation, self-assembled magnetic nanospheres (MNS) made of superparamagnetic iron oxide nanoparticles were grafted with a monolayer of (3-aminopropyl)triethoxysilane (APTES). A direct functionalization strategy was used to avoid the loss of the MNS magnetization. The successful preparation of the nanoformulation was validated by structural, microstructural, and magnetic investigations. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were used to establish the presence of APTES on the MNS surface. The amine content quantified by a ninhydrin assay revealed the monolayer coverage of APTES over MNS. The monolayer coverage of APTES reduced only negligibly the saturation magnetization from 77 emu/g (for MNS) to 74 emu/g (for MNS-APTES). Detailed investigations of the thermoremanent magnetization were carried out to assess the superparamagnetism in the MNS. To make the nanoformulation pH-responsive, the anticancerous drug Nintedanib (NTD) was conjugated with MNS-APTES through the acid liable imine bond. At pH 5.5, which mimics a cancerous environment, a controlled release of 85% in 48 h was observed. On the other hand, prolonged release of NTD was found at physiological conditions (i.e., pH 7.4). In vitro cytotoxicity study showed dose-dependent activity of MNS-APTES-NTD for human lung cancer cells L-132. About 75% reduction in cellular viability for a 100 μg/mL concentration of nanoformulation was observed. The nanoformulation designed using MNS and monolayer coverage of APTES has potential in cancer therapy as well as in other nanobiological applications.
Many-impurity scattering on the surface of a topological insulator
Authors: Hernando José Luis , Baba Yuriko , Díaz Elena , Domínguez-Adame Francisco 
Published: March 2021

AbstractWe theoretically address the impact of a random distribution of non-magnetic impurities on the electron states formed at the surface of a topological insulator. The interaction of electrons with the impurities is accounted for by a separable pseudo-potential method that allows us to obtain closed expressions for the density of states. Spectral properties of surface states are assessed by means of the Green’s function averaged over disorder realisations. For comparison purposes, the configurationally averaged Green’s function is calculated by means of two different self-consistent methods, namely the self-consistent Born approximation (SCBA) and the coherent potential approximation (CPA). The latter is often regarded as the best single-site theory for the study of the spectral properties of disordered systems. However, although a large number of works employ the SCBA for the analysis of many-impurity scattering on the surface of a topological insulator, CPA studies of the same problem are scarce in the literature. In this work, we find that the SCBA overestimates the impact of the random distribution of impurities on the spectral properties of surface states compared to the CPA predictions. The difference is more pronounced when increasing the magnitude of the disorder.
The effect of ABO blood group and antibody class on the risk of COVID-19 infection and severity of clinical outcomes
Authors: Almadhi Marwa Ali , Abdulrahman Abdulkarim , Alawadhi Abdulla , Rabaan Ali A. , Atkin Stephen , AlQahtani Manaf 
Published: March 2021

AbstractThe COVID-19 pandemic has affected more than 100 million cases and caused immense burdens on governments and healthcare systems worldwide. Since its emergence in December 2019, research has been focused on treating the infected, identifying those at risk and preventing spread. There is currently no known biological biomarker that predicts the risk of infection. Several studies emerged suggesting an association between ABO blood group and the risk of COVID-19 infection. In this study, we used retrospective observational data in Bahrain to investigate the association between ABO blood group and risk of infection, as well as susceptibility to severe ICU-requiring infection. We found a higher risk associated with blood group B, and a lower risk with blood group AB. No association was observed between blood group and the risk of a severe ICU-requiring infection. We extended the analysis to study the association by antibodies; anti-a (blood groups B and O) and anti-b (blood groups A and O). No association between antibodies and both risk of infection or susceptibility to severe infection was found. The current study, along with the variation in blood group association results, indicates that blood group may not be an ideal biomarker to predict risk of COVID-19 infection.
A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury
Authors: Okano Junko , Nakae Yuki , Nakagawa Takahiko , Katagi Miwako , Terashima Tomoya , Nagakubo Daisuke , Nakayama Takashi , Yoshie Osamu , Suzuki Yoshihisa , Kojima Hideto 
Published: March 2021

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.
Oscillatory pattern of glycemic control in patients with diabetes mellitus
Authors: Vasquez-Muñoz Manuel , Arce-Alvarez Alexis , von Igel Magdalena , Veliz Carlos , Ruiz-Esquide Gonzalo , Ramirez-Campillo Rodrigo , Alvarez Cristian , Ramirez-Velez Robinson , Crespo Fernando A. , Izquierdo Mikel , Del Rio Rodrigo , Andrade David C. 
Published: March 2021

AbstractDaily glucose variability is higher in diabetic mellitus (DM) patients which has been related to the severity of the disease. However, it is unclear whether glycemic variability displays a specific pattern oscillation or if it is completely random. Thus, to determine glycemic variability pattern, we measured and analyzed continuous glucose monitoring (CGM) data, in control subjects and patients with DM type-1 (T1D). CGM data was assessed for 6 days (day: 08:00–20:00-h; and night: 20:00–08:00-h). Participants (n = 172; age = 18–80 years) were assigned to T1D (n = 144, females = 65) and Control (i.e., healthy; n = 28, females = 22) groups. Anthropometry, pharmacologic treatments, glycosylated hemoglobin (HbA1c) and years of evolution were determined. T1D females displayed a higher glycemia at 10:00–14:00-h vs. T1D males and Control females. DM patients displays mainly stationary oscillations (deterministic), with circadian rhythm characteristics. The glycemia oscillated between 2 and 6 days. The predictive model of glycemia showed that it is possible to predict hyper and hypoglycemia (R2 = 0.94 and 0.98, respectively) in DM patients independent of their etiology. Our data showed that glycemic variability had a specific oscillation pattern with circadian characteristics, with episodes of hypoglycemia and hyperglycemia at day phases, which could help therapeutic action for this population.
An ex vivo model of medical device-mediated bacterial skin translocation
Authors: Wang Hao , Agrawal Anant , Wang Yi , Crawford David W. , Siler Zachary D. , Peterson Marnie L. , Woofter Ricky T. , Labib Mohamed , Shin Hainsworth Y. , Baumann Andrew P. , Phillips K. Scott 
Published: March 2021

AbstractThe skin is a barrier and part of the immune system that protects us from harmful bacteria. Because indwelling medical devices break this barrier, they greatly increase the risk of infection by microbial pathogens. To study how these infections can be prevented through improved clinical practices and medical device technology, it is important to have preclinical models that replicate the early stages of microbial contamination, ingress, and colonization leading up to infection. At present, there are no preclinical ex vivo models specifically developed to simulate conditions for indwelling medical devices. Translocation of pathogens from outside the body across broken skin to normally sterile internal compartments is a rate-limiting step in infectious pathogenesis. In this work, we report a sensitive and reproducible ex vivo porcine skin–catheter model to test how long antimicrobial interventions can delay translocation. Skin preparation was first optimized to minimize tissue damage. The presence of skin dramatically decreased bacterial migration time across the polyurethane catheter interface from > 96 h to 12 h. Using visual colony detection, fluorescence, a luminescent in vitro imaging system, and confocal microscopy, the model was used to quantify time-dependent differences in translocation for eluting and non-eluting antimicrobial catheters. The results show the importance of including tissue in preclinical biofilm models and help to explain current gaps between in vitro testing and clinical outcomes for antimicrobial devices.
A multi-scale pipeline linking drug transcriptomics with pharmacokinetics predicts in vivo interactions of tuberculosis drugs
Authors: Cicchese Joseph M. , Sambarey Awanti , Kirschner Denise , Linderman Jennifer J. , Chandrasekaran Sriram 
Published: March 2021

AbstractTuberculosis (TB) is the deadliest infectious disease worldwide. The design of new treatments for TB is hindered by the large number of candidate drugs, drug combinations, dosing choices, and complex pharmaco-kinetics/dynamics (PK/PD). Here we study the interplay of these factors in designing combination therapies by linking a machine-learning model, INDIGO-MTB, which predicts in vitro drug interactions using drug transcriptomics, with a multi-scale model of drug PK/PD and pathogen-immune interactions called GranSim. We calculate an in vivo drug interaction score (iDIS) from dynamics of drug diffusion, spatial distribution, and activity within lesions against various pathogen sub-populations. The iDIS of drug regimens evaluated against non-replicating bacteria significantly correlates with efficacy metrics from clinical trials. Our approach identifies mechanisms that can amplify synergistic or mitigate antagonistic drug interactions in vivo by modulating the relative distribution of drugs. Our mechanistic framework enables efficient evaluation of in vivo drug interactions and optimization of combination therapies.