bluuebunny/crossref_metadata_2025_split huggingface dataset:
GMP‐compliant manufacturing of biologically active cell‐derived vesicles produced by extrusion technology
Authors: Lau Hui‐Chong , Han Dong Woo , Park Jinhee , Lehner Edwine , Kals Carina , Arzt Claudia , Bayer Elisabeth , Auer Daniela , Schally Tanja , Grasmann Eva , Fang Han , Lee Jae‐Young , Lee Hyun Soo , Han Jinah , Gimona Mario , Rohde Eva , Bae Shingyu , Oh Seung Wook 
Published: December 2022

AbstractExtracellular vesicles (EVs) released by a variety of cell types have been shown to act as a natural delivery system for bioactive molecules such as RNAs and proteins. EV therapy holds great promise as a safe and cell‐free therapy for many immunological and degenerative diseases. However, translation to clinical application is limited by several factors, including insufficient large‐scale manufacturing technologies and low yield. We have developed a novel drug delivery platform technology, BioDrone™, based on cell‐derived vesicles (CDVs) produced from diverse cell sources by using a proprietary extrusion process. This extrusion technology generates nanosized vesicles in far greater numbers than naturally obtained EVs. We demonstrate that the CDVs are surrounded by a lipid bilayer membrane with a correct membrane topology. Physical, biochemical and functional characterisation results demonstrate the potential of CDVs to act as effective therapeutics. Umbilical cord mesenchymal stem cell (UCMSC)‐derived CDVs exhibit a biological activity that is similar to UCMSCs or UCMSC‐derived EVs. Lastly, we present the establishment of a GMP‐compliant process to allow the production of a large number of UCMSC‐CDVs in a reproducible manner. GMP‐compliant manufacturing of CDVs will facilitate the preclinical and clinical evaluation of these emerging therapeutics in anti‐inflammatory or regenerative medicine. This study also represents a crucial step in the development of this novel drug delivery platform based on CDVs.
Isolation of native EVs from primary biofluids—Free‐flow electrophoresis as a novel approach to purify ascites‐derived EVs
Authors: Preußer Christian , Stelter Kathrin , Tertel Tobias , Linder Manuel , Helmprobst Frederik , Szymanski Witold , Graumann Johannes , Giebel Bernd , Reinartz Silke , Müller Rolf , Weber Gerhard , von Strandmann Elke Pogge 
Published: December 2022

AbstractAlthough extracellular vesicles (EVs) have been extensively characterized, efficient purification methods, especially from primary biofluids, remain challenging. Here we introduce free‐flow electrophoresis (FFE) as a novel approach for purifying EVs from primary biofluids, in particular from the peritoneal fluid (ascites) of ovarian cancer patients. FFE represents a versatile, fast, matrix‐free approach for separating different analytes with inherent differences in charge density and/or isoelectric point (pI). Using a series of buffered media with different pH values allowed us to collect 96 fractions of ascites samples. To characterize the composition of the individual fractions, we used state‐of‐the‐art methods such as nanoflow and imaging flow cytometry (nFCM and iFCM) in addition to classical approaches. Of note, tetraspanin‐positive events measured using nFCM were enriched in a small number of distinct fractions. This observation was corroborated by Western blot analysis and electron microscopy, demonstrating only minor contamination with soluble proteins and lipid particles. In addition, these gently purified EVs remain functional. Thus, FFE represents a new, efficient and fast method for separating native and highly purified EVs from complicated primary samples.
Material properties of skin in the flying snakeChrysopelea ornata
Authors: Dellinger Sarah B. , De Vita Raffaella , Vlachos Pavlos P. , Muñoz Martha M. , Socha John J. 
Published: December 2022

AbstractIn snakes, the skin serves for protection, camouflage, visual signaling, locomotion, and its ability to stretch facilitates large prey ingestion. The flying snakes of the genusChrysopeleaare capable of jumping and gliding through the air, requiring additional functional demands: its skin must accommodate stretch in multiple directions during gliding and, perhaps more importantly, during high‐speed, direct‐impact landing. Is the skin of flying snakes specialized for gliding? Here, we characterized the material properties of the skin ofChrysopelea ornataand compared them with two nongliding species of colubrid snakes,Thamnophis sirtalisandPantherophis guttatus, as well as with previously published values. The skin was examined using uniaxial tensile testing to measure stresses, and digital image correlation methods to determine strains, yielding metrics of strength, elastic modulus, strain energy, and extensibility. To test for loading orientation effects, specimens were tested from three orientations relative to the snake's long axis: lateral, circumferential, and ventral. Specimens were taken from two regions of the body, pre‐ and pos‐tpyloric, to test for regional effects related to the ingestion of large prey. In comparison withT. sirtalisandP. guttatus,C. ornataexhibited higher post‐pyloric and lower pre‐pyloric extensibility in circumferential specimens. However, overall there were few differences in skin material properties ofC. ornatacompared to other species, both within and across studies, suggesting that the skin of flying snakes is not specialized for gliding locomotion. Surprisingly, circumferential specimens demonstrated lower strength and extensibility in pre‐pyloric skin, suggesting less regional specialization related to large prey.
Ramsey numbers of the quadrilateral versus books
Authors: Li Tianyu , Lin Qizhong , Peng Xing 
Published: December 2022

AbstractA book is a graph which consists of triangles sharing a common edge. In this paper, we study Ramsey numbers of quadrilateral versus books. Previous results give the exact value of for . We aim to determine the exact value of for infinitely many . To achieve this, we first prove that for and . This improves upon a result by Faudree, Rousseau, and Sheehan which states that
Combining the new upper bound and constructions of ‐free graphs, we are able to determine the exact value of for infinitely many . As a special case, we show for all prime powers .
Tell‐a provider about tele: Reducing overuse of telemetry across 10 hospitals in a safety net system
Authors: Krouss Mona , Israilov Sigal , Alaiev Daniel , Seferi Arta , Kansara Tikal , Brandeis Gary , Saladini‐Aponte Carla , Wat Monica , Talledo Joseph , Tsega Surafel , Chandra Komal , Zaurova Milana , Manchego Peter A. , Najafi Nader , Cho Hyung J. 
Published: December 2022

AbstractBackgroundTelemetry is often a scarce resource at hospitals and is important for arrhythmia and myocardial ischemia detection. Overuse of telemetry monitoring leads to alarm fatigue resulting in failure to respond to arrhythmias, patient harm, and possible unnecessary testing.MethodsThis quality improvement initiative was implemented across NYC Health and Hospitals, an 11‐hospital urban safety net system. The electronic health record intervention involved the addition of a mandatory indication in the telemetry order and a best practice advisory (BPA) that would fire after the recommended time period for reassessment had passed.ResultsThe average telemetry hours per patient encounter went from 60.1 preintervention to 48.4 postintervention, a 19.5% reduction (p < .001). When stratified by the 11 hospitals, decreases ranged from 9% to 30%. The BPA had a 53% accept rate and fired 52,682 times, with 27,938 “discontinue telemetry” orders placed. The true accept rate was 50.4%, as there was a 2.6% 24‐h reorder rate. There was variation based on clinician specialty and clinician type (attending, fellow, resident, physician associate, nurse practitioner).ConclusionWe successfully reduced telemetry monitoring across a multisite safety net system using solely an electronic health record (EHR) intervention. This expands on previous telemetry monitoring reduction initiatives using EHR interventions at single academic sites. Further study is needed to investigate variation across clinician type, specialty, and post‐acute sites.
Zero Echo Time vs. T1‐Weighted MRI for Assessment of Cortical and Medullary Bone Morphology Abnormalities Using CT as the Reference Standard
Authors: Xu Jun , Hu Yawen , Zhou Ruizhi , Sun Shiqing , Chen Haisong 
Published: December 2022

BackgroundConventional MR pulse sequences result in poor signal from low T2 cortical bone because the minimum achievable echo time is limited. A sequence resulting in improved bone contrast is desirable.PurposeTo evaluate the image quality and diagnostic performance of grayscale inversion zero echo time imaging (GI‐ZTE) and grayscale inversion T1‐weighted imaging (GI‐T1WI) compared with computed tomography (CT).Study TypeProspective.SubjectsA total of 50 patients with musculoskeletal tumors or tumor‐like diseases of the lower extremities having MRI and CT studies.Field Strength/SequenceGI‐T1WI and GI‐ZTE sequences at 1.5 T.AssessmentAssessed cortical and medullary bone morphology abnormalities using CT as the reference standard. Three radiologists scored the images quality and recorded nine metrics to assess the diagnostic performance.Statistical TestsDifferences in image quality were calculated using the Wilcoxon signed‐rank test. The intraclass correlation coefficient (ICC) was used to analyze the agreement of quantitative lesion parameters between CT and MR sequences, as well as the interobserver reliability. A P value <0.05 was considered statistically significant.ResultsImage quality score was significantly higher for CT images than GI‐TIWI images. Except for radiologist 3 [4(0) vs 4 (1)], there was no significant difference in scores between CT and GI‐ZTE [radiologist 1: 4 (0) vs 4 (0), P = 0.133; radiologist 2: 4 (0) vs 4 (0), P = 0.085]. There was good–excellent agreement between both MR sequences and CT for size, lesion number, location, sclerotic rim, expanded shell, destruction pattern, and matrix mineralization for all radiologists (ICC: 0.636–1.000). The consistency of periosteal reaction and penetration of the cortex was fair to good (0.481–0.729) between GI‐T1WI and CT and good to excellent between GI‐ZTE and CT (0.682–0.852).Data ConclusionsGI‐ZTE images had superior intermodality agreement with CT images and allowed visualization of more cortical bone detail than GI‐T1WI images.Evidence Level1.Technical EfficacyStage 2.
Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment
Authors: Lai Chih‐Cheng , Hsueh Po‐Ren 
Published: December 2022

AbstractNirmatrelvir/ritonavir (NMV‐r) is an effective anti‐SARS‐CoV‐2 agent and has been recommended in the treatment of nonhospitalized patients with COVID‐19. In rare occasions, some patients experience virologic and symptomatic rebound after initial resolution, which we call COVID‐19 rebound after NMV‐r. Although COVID rebound can also occur after molnupiravir treatment or even no antiviral treatment, we have more serious concern about the rebound after NMV‐r, which remains the most effective antiviral. Due to a lack of information about its frequency, mechanism, outcomes, and management, we conducted this review to provide comprehensive and updated information to address these questions. Based on the limited evidence, the incidence of COVID‐19 rebound after NMV‐r was less than 2%, and most cases developed 5–15 days after initiating NMV‐r treatment. Almost all reported cases had mild symptoms, and the clinical condition gradually subsided without additional treatment. Overall, the clinical outcome was favorable, and only a small number of patients required emergency department visits or hospitalization. Regarding virologic rebound, culturable SARS‐CoV‐2 with possible transmission was observed, so re‐isolation may be needed.
Evaluating satellite‐ and reanalysis‐based precipitation products over the Qinghai‐Tibetan Plateau in the perspective of a new error‐index system
Authors: Liu Jianwei , Zhou Yuyan , Lu Fan , Yu Yuanhui , Yan Denghua , Hu Yingying , Xue Wei 
Published: December 2022

AbstractThe necessity of evaluating satellite‐ and reanalysis‐based precipitation products as optional proxies of precipitation observations is widely understood. Four typical satellite‐ or reanalysis‐based precipitation products from TRMM, CPC, CMFD and ERA5‐Land datasets were evaluated at temporal and spatial scales using a new error‐index system method across the Qinghai‐Tibetan Plateau (QTP) from 1979 to 2018. The error‐index system consisted of 10 indices, which were classified into two categories, that is, the comprehensive error indices and error component indices. A local error decomposition scheme suitable for the QTP was built according to the simulation test. Results showed the datasets except ERA5‐Land performed better at monthly scale than that at daily scale generally, though significant differences were found among the products. Particularly, CMFD achieved the highest accuracy in estimating monthly and daily precipitation, followed by CPC, while TRMM performed similarly to ERA5‐Land. It was estimated that over one fifth of the precipitation were falsely recorded in the four products. Approximately over 15% of daily precipitation were overestimated or underestimated with an accumulated extent reaching up to 60 mm per month in summer. Spatial results indicated that large deviations were found in the southeast QTP, which were derived from a significant underestimation. Besides, a large proportion of false and missing estimation of precipitation events were witnessed in the northeast river basins. Through the comparison, CMFD and CPC had reduced all error components except HNB in both magnitude and the ratio. And the datasets tended to overestimate the slight precipitation and underestimate the heavy rainfall. And the products did not eliminate the large deviations in the southeast and north QTP. The assessment results reported here will provide some valuable feedbacks for the improvement of these products.
Comparing two weather generator‐based downscaling tools for simulating storm intensification and its impacts on soil erosion under climate change
Authors: Zhang Xunchang (John) , Busteed Phillip R. , Chen Jie , Yuan Lifeng 
Published: December 2022

AbstractStorm intensification is projected to increase under climate change; however, it is quite challenging to statistically downscale storm intensification for climatic impact assessment. The objectives of this study are to compare two weather generator‐based tools in simulating daily precipitation extremes at a point scale, both with and without storm intensification options, and to further evaluate the responses of simulated surface runoff and soil loss to generated precipitation extremes under various cropping and tillage systems at a station in central Oklahoma, U.S.A. Results show that all data sources including raw GCM, raw RCM, and statistically downscaled GCM datasets are capable of providing information on future storm intensification, depending on particular ensemble members or models in each source. Thus, it is recommended that all data sources including as many members as possible should be used in model screening. Compared with the SYNthetic weather generaTOR (SYNTOR), the Generator for Point Climate Change (GPCC) tool tends to generate a stronger storm intensification, partially because GPCC takes into consideration the increased variance of monthly precipitation as projected by GCMs in adjusting daily precipitation variance for future climate generation. However, there are no discernable differences between storm intensification options with each tool because weaker signals of storm intensification are projected for the study site coupled with a projected decline in future annual precipitation. Simulated soil loss and surface runoff rates with GPCC were significantly greater than those with SYNTOR due to GPCC generating more frequent and heavier storms. Given the sizable differences in extreme precipitation generation, both tools could be used to generate a range of the potential impacts of storm intensification under climate change on soil erosion and surface hydrology.
Effects of altitude and varieties on overwintering adaptability and cold resistance mechanism of alfalfa roots in the Qinghai–Tibet Plateau
Authors: Yao Xixi , Qian Li , Changhui Li , Yi Sun 
Published: December 2022

AbstractBACKGROUNDThe roots are the main functional organs involved in the overwintering adaptability of alfalfa (Medicago sativa). However, it is still unclear how the roots are involved in the cold resistance in the high‐altitude area of the Qinghai–Tibet Plateau (QTP). In this study, three winter‐surviving 2‐year‐old alfalfa varieties (M. sativa Zhongmeng No.1, M. sativa Chiza No.1, and M. sativa Gongnong No.1) planted at two different altitudes (2812 m and 3109 m) in the northeast edge of the QTP were used to explore the cold‐resistance mechanism.RESULTSAt low altitudes (2812 m), the overwintering rate, taproot length, root area, root surface area, and root average diameter, plant height, fresh yield and hay yield of M. sativa Zhongmeng No.1 were significantly higher (P < 0.01) than for the other two varieties. At high altitude (3109 m), lateral root length, number of lateral roots, main root dry weight, and lateral root dry weight of M. sativa Chiza No.1 were higher (P < 0.01) than the other two varieties. At low and high altitudes, the activities of peroxidase and catalase were higher (P < 0.05) in M. sativa Chiza No.1 during post‐winter and pre‐winter respectively. At low altitude, higher soluble sugar (P < 0.05) and proline (P < 0.01) contents were recorded during the pre‑ and post‐winter periods. Membership function analysis showed that M. sativa Zhongmeng No.1 has the strongest cold resistance. The structural equation model showed that the overwintering rate of alfalfa was mainly affected by the morphological characteristics of roots and the physiological characteristics of roots, with contribution rates of 0.54 and 0.75 respectively, and the physiological characteristics of roots had the greatest effect on the overwintering rate.CONCLUSIONSThis study is of great significance to effectively solve the overwintering of alfalfa, the lack of high‐quality legume forage resources, and promote the development of animal husbandry in the alpine areas of the QTP. © 2022 Society of Chemical Industry.
Construction of benzyl isothiocyanate‐loaded fish skin gelatin‐luteolin compound emulsion delivery system, and its digestion and absorption characteristics
Authors: Liu Zhiyu , Lin Songyi , Liu Wenwen , Nakamura Yoshimasa , Tang Yue 
Published: December 2022

AbstractBACKGROUNDFish skin gelatin (FSG) and luteolin (LUT) were used as composite emulsifiers, and benzyl isothiocyanate (BITC) was used as a model of nutrient delivery to construct a stable emulsion. The storage stability of the FSG–LUT emulsion and its effect on BITC release were investigated both in vitro and ex vivo.RESULTSLUT can quench FSG fluorophores statically and form a stable complex through hydrogen bonding and hydrophobic interactions. The FSG–LUT emulsion storage stability and embedding rate were higher than those of the FSG emulsion. The FSG–LUT emulsion microstructure was resistant to oral and gastric digestion, and the BITC retention rate and bioaccessibility were much higher than those of the FSG emulsion. Lastly, the ex vivo everted gut sac of rat intestine study demonstrated that BITC showed the highest absorption in the ileum, and the FSG–LUT emulsion absorbed BITC and sustained a controlled release in a specific position.CONCLUSIONLUT could form stable complexes with FSG, which improved the stability and bioavailability of BITC in the FSG–LUT emulsion delivery system, and promoted further intestinal BITC absorption. © 2022 Society of Chemical Industry.
Genotypic variation in carbon and nitrogen metabolism in the cotton subtending leaves and seed cotton yield under various nitrogen levels
Authors: Iqbal Asif , Jing Niu , Qiang Dong , Kayoumu Mirezhatijiang , Wang Xiangru , Gui Huiping , Zhang Hengheng , Xiling Zhang , Meizhen Song 
Published: December 2022

AbstractBACKGROUNDNitrogen (N) is the key nutrient required for high cotton production; however, its excessive use can increase the cost of production and environmental problems. Reducing the application of N while sustaining the yield is an important issue to be solved. Therefore, this study was designed to investigate the genotypic variations in subtending leaf physiology and its contribution to seed cotton yield of contrasting N‐efficient cotton genotypes under various N levels in pot and field conditions.RESULTSThe results showed that the application of N increased the enzymatic activities related to carbon (C) and N metabolisms. Under the same N level, the C/N metabolisms of the N‐efficient genotypes were significantly higher than N‐inefficient genotypes, indicating a strong N assimilation and photoassimilation ability in N‐efficient genotypes, especially under low N level. Moreover, the antioxidant enzymatic activities were significantly higher, whereas malondialdehyde content was lower in N‐efficient cotton genotypes than in N‐inefficient ones. Therefore, N‐efficient cotton genotypes showed strong resistance, higher C/N metabolisms, and provided sufficient dry matter for boll development. As a result, the yield, N use efficiency, and value cost ratio of the N‐efficient cotton genotypes were higher than in the N‐inefficient genotypes.CONCLUSIONIt was confirmed that the higher C/N metabolisms in the cotton subtending leaves of N‐efficient cotton genotypes could support higher seed cotton yield under relatively low N application. © 2022 Society of Chemical Industry.
Hypertrophic lichen planus of the vulva
Authors: Korbi Mouna , Ben Ammou Syrine , Ouni Nour el Imene , Bellalah Ahlem , Bel Hadj Ali Hichem , Zili J. 
Published: December 2022

AbstractVulvovaginal lichen planus is a type of chronic inflammatory dermatosis of the vulva, usually seen as a part of widespread lichen planus. The common clinical types of vulval lichen planus include papulosquamous, erosive, and pigmented types. Hypertrophic lichen planus of the vulva is a rare entity. We report a case of hypertrophic lichen planus of the vulva