bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized‐induced neural stem cell therapy: Generation, transplant, and safety in a large animal model
Authors: Bomba Hunter N. , Sheets Kevin T. , Valdivia Alain , Khagi Simon , Ruterbories Laura , Mariani Christopher L. , Borst Luke B. , Tokarz Debra A. , Hingtgen Shawn D. 
Published: July 2020

AbstractIn this study, we take an important step toward clinical translation by generating the first canine‐induced neural stem cells (iNSCs). We explore key aspects of scale‐up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma. Created by direct transdifferentiation of fibroblasts, iNSCs are known to migrate through the brain, track down invasive cancer foci, and deliver anticancer payloads that significantly reduce tumor burden and extend survival of tumor‐bearing mice. Here, skin biopsies were collected from canines and converted into the first personalized canine iNSCs engineered to carry TNFα‐related apoptosis‐inducing ligand (TRAIL) and thymidine kinase (TK), as well as magnetic resonance imaging (MRI) contrast agents for in vivo tracking. Time‐lapse analysis showed canine iNSCs efficiently migrate to human tumor cells, and cell viability assays showed both TRAIL and TK monotherapy markedly reduced tumor growth. Using intraoperative navigation and two delivery methods to closely mimic human therapy, canines received autologous iNSCs either within postsurgical cavities in a biocompatible matrix or via a catheter placed in the lateral ventricle. Both strategies were well tolerated, and serial MRI showed hypointense regions at the implant sites that remained stable through 86 days postimplant. Serial fluid sample testing following iNSC delivery showed the bimodal personalized therapy was well tolerated, with no iNSC‐induced abnormal tissue pathology. Overall, this study lays an important foundation as this promising personalized cell therapy advances toward human patient testing.
Promising survival rate but high incidence of treatment‐related mortality after reduced‐dose craniospinal radiotherapy and tandem high‐dose chemotherapy in patients with high‐risk medulloblastoma
Authors: Lee Ji Won , Lim Do Hoon , Sung Ki Woong , Cho Hee Won , Ju Hee Young , Hyun Ju Kyung , Yoo Keon Hee , Koo Hong Hoe , Suh Yeon‐Lim , Joung Yoo‐Sook , Shin Hyung Jin 
Published: July 2020

AbstractBackgroundIn this study, we report the follow‐up results of reduced dose of craniospinal radiotherapy (CSRT) followed by tandem high‐dose chemotherapy (HDCT) in patients with high‐risk medulloblastoma (MB).MethodsNewly diagnosed high‐risk MB patients (metastatic disease, postoperative residual tumor >1.5 cm2, or large cell/anaplastic histology) over 3 years of age were enrolled in this study. Two cycles of pre‐RT chemotherapy, radiotherapy (RT) including reduced‐dose CSRT (23.4 or 30.6 Gy), four cycles of post‐RT chemotherapy, and tandem HDCT were administered. NanoString and DNA sequencing were performed using archival tissues.ResultsIn all, 40 patients were enrolled, and molecular subgrouping was possible in 21 patients (2 wingless, 3 sonic hedgehog, 8 Group 3, and 8 group 4). All patients including two patients who experienced progression during the induction chemotherapy underwent HDCT. Relapse/progression occurred only in four patients (5‐year cumulative incidence [CI] 10.4 ± 0.3%). However, six patients died from treatment‐related mortality (TRM) (four acute TRMs and two late TRMs) resulting in 18.5 ± 0.5% of 5‐year CI. Taken together, the 5‐year event‐free survival and overall survival were 71.1 ± 8.0% and 73.2 ± 7.9%, respectively. Late effects were evaluated in 25 patients and high‐tone hearing loss, endocrine dysfunction, dyslipidemia, and growth retardation were common.ConclusionsThe strategy using tandem HDCT following reduced‐dose CSRT showed promising results in terms of low relapse/progression rate; however, the high TRM rate indicates that modification of HDCT regimen and careful selection of patients who can benefit from HDCT will be needed in the future study.
Phase II trial of co‐administration of CD19‐ and CD20‐targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma
Authors: Sang Wei , Shi Ming , Yang Jingjing , Cao Jiang , Xu Linyan , Yan Dongmei , Yao Meixue , Liu Hui , Li Weidong , Zhang Bing , Sun Kemeng , Song Xuguang , Sun Cai , Jiao Jun , Qin Yuanyuan , Sang Tingting , Ma Yuanyuan , Wu Mei , Gao Xiang , Cheng Hai , Yan Zhiling , Li Depeng , Sun Haiying , Zhu Feng , Wang Ying , Zeng Lingyu , Li Zhenyu , Zheng Junnian , Xu Kailin 
Published: July 2020

AbstractPurposeAnti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 and anti‐CD20 CAR‐T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity.MethodsTotally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti‐CD19 and anti‐CD20 CAR‐T cells. Treatment response, toxicity, and persistence were monitored continuously.ResultsOf the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%‐94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%‐74.3%) had a complete response (CR). Peak levels of anti‐CD19 and anti‐CD20 CAR cells were associated with response (P = .007 and .002). Grade 3‐4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression‐free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level.ConclusionsCoadministration of anti‐CD19 and CD20 CAR‐T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178.
CACNA1S Arg528Cys mutation in a young Chinese man with thyrotoxic hypokalemic periodic paralysis
Authors: Rezkalla Nader , Imam Kamran , Marti Miriam , Ip Karen , Mashhadian Ardavan , Liu Antonio 
Published: July 2020

AbstractIt has long been believed that the patients with thyrotoxic hypokalemic periodic paralysis (THPP) may harbor genetic mutations commonly found in familial hypokalemic periodic paralysis. Despite extensive testing, such a mutation has escaped detection until now.
Cancer Cell Detection‐Based on Released Hydrogen Peroxide Using a Non‐Modified Closed Bipolar Electrochemical System
Authors: Shokouhi Maryam , Mehrgardi Masoud A. 
Published: July 2020

AbstractIn this study, a non‐modified closed bipolar electrochemical system for ultrasensitive cancer cell detection by quantitative measurement of released hydrogen peroxide in the presence of ascorbic acid has been developed. This system includes two separate chambers (reporting and sensing), a piece of a gold archival CD (compact disc) as a bipolar electrode, and two platinum driving electrodes. By following the ECL (electrochemiluminescence) intensities of luminol oxidation in the reporting chamber, the hydrogen peroxide released by cancer cells in the presence of ascorbic acid was monitored. Under the optimum conditions, the biosensor delivers a wide linear range from 2.5×10−9 to 1×10−6 M, and a detection limit for hydrogen peroxide as low as 1.8×10−9 M. Also, this system can detect cancer blood cell concentrations (CCRF‐CEM: T‐lymphoblastic leukemia cell line) as low as 12 cells in 300 μL of cell suspension. The present bipolar electrode‐electrochemiluminescence (BPE‐ECL) system demonstrates a simple and low‐cost device with excellent performance without any electrode surface modification for the detection of cancer cells based on different levels of released hydrogen peroxide by normal and cancer cells. The present biosensor can be applied as a promising alternative method for the detection of H2O2 in the field of pathology, cancer diagnosis, and environmental monitoring.
Nanogels with Selective Intracellular Reactivity for Intracellular Tracking and Delivery
Authors: Zu Guangyue , Mergel Olga , Ribovski Laís , Bron Reinier , Zuhorn Inge S. , van Rijn Patrick 
Published: July 2020

AbstractA multimodal approach for hydrogel‐based nanoparticles was developed to selectively allow molecular conjugated species to either be released inside the cell or remain connected to the polymer network. Using the intrinsic difference in reactivity between esters and amides, nanogels with an amide‐conjugated dye could be tracked intracellularly localizing next to the nucleus, while ester‐conjugation allowed for liberation of the molecular species from the hydrogel network inside the cell, enabling delivery throughout the cytoplasm. The release was a result of particle exposure to the intracellular environment. The conjugation approach and polymer network building rely on the same chemistry and provide a diverse range of possibilities to be used in nanomedicine and theranostic approaches.
Chemists around the World, Take Your Part in the Circular Economy!
Authors: Chatel Gregory 
Published: July 2020

AbstractBased on recent examples and initiatives reported in the literature, this concept article discusses how chemistry can contribute to the circular economy approach in order to improve our current and future economical, societal, and environmental system. Through five proposed levels of contribution, chemists can take a significant part in this global approach via the consideration of green chemistry principles, the simplification of syntheses, the limitation of complex products preparation, the efficient utilization of resources but also the novel ways of waste valorization. A more systematic and generalized environmental and economic assessment from the lab‐scale is also recommended. At last, chemists have to work even more collaboratively and in a multidisciplinary way, within chemistry and beyond.
Building [UIV70(OH)36(O)64]4− Oxocluster Frameworks with Sulfate, Transition Metals, and UV
Authors: Colliard Ian , Nyman May 
Published: July 2020

AbstractUranium(IV) oxide clusters, colloids, and materials are designed and studied for 1) nuclear materials applications, 2) understanding the environmental fate and transport of actinides, and 3) exploring the complex bonding behavior of open‐shell f‐elements. UIV‐oxyhydroxsulfate clusters are particularly relevant in industrial processes and in nature. Recent studies have shown that counter‐cations to these polynuclear anions differentiate rich structural topologies in the solid‐state. Herein, we present nine different structures with wheel‐shaped [U70(OH)36(O)64(SO4)60]4− (U70) linked into one‐ and two‐dimensional frameworks with sulfate, divalent transition metals (CrII, FeII, CoII, NiII) and UV. Small‐angle X‐ray scattering of these phases dissolved in butylamine reveals differing supramolecular assembly of U70 clusters, controlled primarily by sulfates. However, observed trends in transition metal linking guide future design of U70 materials with different topologies. Finally, U70 linking via UIV‐O‐UV‐O‐UIV bridges presents a rare example of mixed‐oxidation‐state uranium oxides without disorder.
SAR Studies of the Leupyrrins: Design and Total Synthesis of Highly Potent Simplified Leupylogs
Authors: Wosniok Paul R. , Knopf Christopher , Dreisigacker Sandra , Orozco‐Rodriguez J. Manuel , Hinkelmann Bettina , Mueller Peter P. , Brönstrup Mark , Menche Dirk 
Published: July 2020

AbstractLeupyrrins are highly potent antifungal agents. A structure–activity‐relationship study of natural and synthetic derivatives is reported which reveals important insights into the biological relevance of several structural subunits leading to the discovery of highly potent but drastically simplified leupylogs that incorporate a stable and readily available aromatic side chain. For their synthesis a concise strategy is described that enables a short and versatile access.
Adjoin: A causal consistency model based on the adjacency list in a distributed system
Authors: Tian Junfeng , Pang Yanan 
Published: July 2020

SummaryData consistency is a critical topic in distributed systems. In existing consistency models, causal consistency has attracted a significant amount of attention because it can satisfy high‐performance requirements even in the presence of network partitions. At present, most of the causal consistency models face a tradeoff between throughput and update visibility. Simultaneously, they cannot take full advantage of partial geo‐replication. To resolve the problems, this paper proposes a causal consistency model that supports partial replication using the adjacency list, called Adjoin. In Adjoin, each data center (DC) stores only a subset of the full data, by reading adjacency relationships, and the relevant nodes quickly reach synchronization. We also introduce the Adjacency Stable Vector and Adjacency Dependency Set to capture causality, which reduces the system storage overhead. We evaluate Adjoin with different workloads on a cloud platform using multiple sites. The results show that Adjoin has good performance in terms of throughput and update visibility compared with previous causal consistency models.
Farm Management Competition Provides Impact for Researchers, Producers, and Industry Partners
Authors: Ernst Matt 
Published: July 2020

AbstractAn interactive, real‐life farm management competition at the University of Nebraska–Lincoln is attracting committed participation from producers and industry all while generating a slew of data researchers can use to evaluate and compare impacts of multivariable crop management decisions. Earn 0.5 CEUs in Crop Management by reading this article and taking the quiz at www.certifiedcropadviser.org/education/classroom/classes/844.
Capacitor‐less induction heating system with self‐resonant bifilar coil
Authors: Vishnuram Pradeep , Ramachandiran Gunabalan 
Published: July 2020

SummaryIn this work, a capacitor‐less self‐resonating coil‐based induction heating (IH) system with magnetic resonant coupling has been proposed. In the conventional heating system, the inclusion of additional capacitor for creating the resonance results in poor efficiency of overall system. To overcome this issue, a bifilar coil system is implemented, which leads to series resonance at a particular frequency. The key mechanism is self‐resonance wireless power transfer concept to IH system; hence, no capacitor is needed in the system. The coil has a series association of the coil inductance and capacitance at the resonant operating condition. A mathematical modeling and steady state analysis is performed for the conventional (solenoidal) coil and bifilar coil to estimate the actual value of the capacitance and inductance of the coil. The performance of the bifilar coil system is tested through COMSOL multiphysics simulation tool and parameters like eddy current, magnetic flux, and temperature distribution in the work piece are analyzed. The experimental setup of the bifilar coil‐aided IH system is implemented with PIC16F877A microcontroller, and FLIR thermal imager is used to analyze the temperature distribution on the work piece. The experimental results are compared with the simulation results, and the bifilar coil system provides a promising solution.
Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials
Authors: Cozzi Nicholas V. , Daley Paul F. 
Published: July 2020

AbstractSince 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4‐phosphoryl ester of N,N‐dimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few studies of ayahuasca, a DMT‐containing water infusion, only one human study with pure DMT has been reported since the early 2000s. Newly planned clinical trials to assess the safety and efficacy of DMT in humans with major depressive disorders require high‐purity water‐soluble DMT for intravenous administration. Accordingly, we synthesized and characterized DMT hemifumarate for these upcoming studies. The synthetic approach of Speeter and Anthony was slightly modified to gain some efficiency in time. In particular, this is the first known report to use aluminum hydride, generated in situ from lithium aluminum hydride, to reduce the intermediate 2‐(1H‐indol‐3‐yl)‐N,N‐dimethyl‐2‐oxoacetamide to DMT. A quench protocol was developed to produce a good yield of exceptionally pure free base DMT upon workup, which was then converted to the hemifumarate salt. Analysis of the final product included differential scanning calorimetry, thermogravimetric analysis, gas chromatography–mass spectrometry (GC–MS), 1H and 13C nuclear magnetic resonance spectroscopy, high‐performance liquid chromatography, residual solvent analysis by GC headspace sampling, X‐ray powder diffraction analysis, and residual lithium analysis by inductively coupled plasma‐mass spectrometry. The DMT hemifumarate was minimally 99.9% pure, with no significant impurities or residual solvents, thus meeting regulatory standards for administration to humans.
Diet of a rare herbivore based on DNA metabarcoding of feces: Selection, seasonality, and survival
Authors: Goldberg Amanda R. , Conway Courtney J. , Tank David C. , Andrews Kimberly R. , Gour Digpal S. , Waits Lisette P. 
Published: July 2020

AbstractIn herbivores, survival and reproduction are influenced by quality and quantity of forage, and hence, diet and foraging behavior are the foundation of an herbivore's life history strategy. Given the importance of diet to most herbivores, it is imperative that we know the species of plants they prefer, especially for herbivorous species that are at risk for extinction. However, it is often difficult to identify the diet of small herbivores because: (a) They are difficult to observe, (b) collecting stomach contents requires sacrificing animals, and (c) microhistology requires accurately identifying taxa from partially digested plant fragments and likely overemphasizes less‐digestible taxa. The northern Idaho ground squirrel (Urocitellus brunneus) is federally threatened in the United States under the Endangered Species Act. We used DNA metabarcoding techniques to identify the diet of 188 squirrels at 11 study sites from fecal samples. We identified 42 families, 126 genera, and 120 species of plants in the squirrel's diet. Our use of three gene regions was beneficial because reliance on only one gene region (e.g., only trnL) would have caused us to miss >30% of the taxa in their diet. Northern Idaho ground squirrel diet differed between spring and summer, frequency of many plants in the diet differed from their frequency within their foraging areas (evidence of selective foraging), and several plant genera in their diet were associated with survival. Our results suggest that while these squirrels are generalists (they consume a wide variety of plant species), they are also selective and do not eat plants relative to availability. Consumption of particular genera such as Perideridia may be associated with higher overwinter survival.
Modeling transient fluid simulations with proper orthogonal decomposition and machine learning
Authors: Ooi Chinchun , Le Quang Tuyen , Dao My Ha , Nguyen Van Bo , Nguyen Hoang Huy , Ba Te 
Published: July 2020

SummaryIn this work, we present the results obtained from integrating several machine learning (ML) models with projection‐based reduced order model for modeling the canonical case of flow past a stationary cylinder. We demonstrate how ML models can be used to model the time‐varying characteristics of the proper orthogonal decomposition (POD) coefficients, and that the locally interpolating models such as regression trees and k‐nearest neighbors seem to be better for such models than other models like support vector regression or long‐short term memory networks. In addition, our numerical experiments also show that these POD coefficients are most effectively modeled by using their own previous time values, as opposed to the inclusion of high energy POD modes. Last but not least, we demonstrate that these models, although trained on inlet velocities of 0.8, 1.0, and 1.2 m/s, can still predict the POD coefficients of flow fields for inlet velocities of 0.9 and 1.25 m/s, with root mean squared error of under 10%.
Safety assessment of fermented jackfruit (Artocarpus heterophyllus) pulp and leaves in Sprague‐Dawley rats
Authors: Sabidi Sarah , Koh Soo Peng , Abd Shukor Shazwan , Adzni Sharifudin Shaiful , Sew Yun Shin 
Published: July 2020

AbstractFermented jackfruit (Artocarpus heterophyllus) extracts were produced using pure symbiotic culture of bacteria and yeast (SCOBY) under controlled fermentation process. Both female and male Sprague‐Dawley rats were orally administrated with 4,000 mg/kg of fermented jackfruit pulp and leaves extracts for 28 consecutive days. Body weight of rats was recorded at 1‐week interval until necropsy day. There was no mortality reported along the experiment with no significant differences (p > .05) record among organ histopathology and blood biochemical parameters in treated groups when compared to control group. Interestingly, there were significant differences (p < .05) in the lower body weight gained of treated rats groups as opposed to control group, indicating the potential anti‐obesity effect of fermented jackfruit extracts. In conclusion, no toxicity symptoms were observed in 28 days oral administration toxicity study of fermented jackfruit pulp and leaves extracts in Sprague‐Dawley rats for both sexes.
Evaluation of population stratification adjustment using genome‐wide or exonic variants
Authors: Chen Yuning , Peloso Gina M. , Liu Ching‐Ti , DeStefano Anita L. , Dupuis Josée 
Published: July 2020

AbstractPopulation stratification may cause an inflated type‐I error and spurious association when assessing the association between genetic variations with an outcome. Many genetic association studies are now using exonic variants, which captures only 1% of the genome, however, population stratification adjustments have not been evaluated in the context of exonic variants. We compare the performance of two established approaches: principal components analysis (PCA) and mixed‐effects models and assess the utility of genome‐wide (GW) and exonic variants, by simulation and using a data set from the Framingham Heart Study. Our results illustrate that although the PCs and genetic relationship matrices computed by GW and exonic markers are different, the type‐I error rate of association tests for common variants with additive effect appear to be properly controlled in the presence of population stratification. In addition, by considering single nucleotide variants (SNVs) that have different levels of confounding by population stratification, we also compare the power across multiple association approaches to account for population stratification such as PC‐based corrections and mixed‐effects models. We find that while these two methods achieve a similar power for SNVs that have a low or medium level of confounding by population stratification, mixed‐effects model can reach a higher power for SNVs highly confounded by population stratification.