bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders
Authors: Seras‐Franzoso Joaquin , Díaz‐Riascos Zamira V. , Corchero José Luis , González Patricia , García‐Aranda Natalia , Mandaña Mònica , Riera Roger , Boullosa Ana , Mancilla Sandra , Grayston Alba , Moltó‐Abad Marc , Garcia‐Fruitós Elena , Mendoza Rosa , Pintos‐Morell Guillem , Albertazzi Lorenzo , Rosell Anna , Casas Josefina , Villaverde Antonio , Schwartz Simó , Abasolo Ibane 
Published: March 2021

AbstractIn the present study the use of extracellular vesicles (EVs) as vehicles for therapeutic enzymes in lysosomal storage disorders was explored. EVs were isolated from mammalian cells overexpressing alpha‐galactosidase A (GLA) or N‐sulfoglucosamine sulfohydrolase (SGSH) enzymes, defective in Fabry and Sanfilippo A diseases, respectively. Direct purification of EVs from cell supernatants was found to be a simple and efficient method to obtain highly active GLA and SGSH proteins, even after EV lyophilization. Likewise, EVs carrying GLA (EV‐GLA) were rapidly uptaken and reached the lysosomes in cellular models of Fabry disease, restoring lysosomal functionality much more efficiently than the recombinant enzyme in clinical use. In vivo, EVs were well tolerated and distributed among all main organs, including the brain. DiR‐labelled EVs were localized in brain parenchyma 1 h after intra‐arterial (internal carotid artery) or intravenous (tail vein) administrations. Moreover, a single intravenous administration of EV‐GLA was able to reduce globotriaosylceramide (Gb3) substrate levels in clinically relevant tissues, such kidneys and brain. Overall, our results demonstrate that EVs from cells overexpressing lysosomal enzymes act as natural protein delivery systems, improving the activity and the efficacy of the recombinant proteins and facilitating their access to organs neglected by conventional enzyme replacement therapies.
Bioorthogonally surface‐edited extracellular vesicles based on metabolic glycoengineering for CD44‐mediated targeting of inflammatory diseases
Authors: Lim Gyeong Taek , You Dong Gil , Han Hwa Seung , Lee Hansang , Shin Sol , Oh Byeong Hoon , Kumar E. K. Pramod , Um Wooram , Kim Chan Ho , Han Seungsu , Lee Sangho , Lim Seungho , Yoon Hong Yeol , Kim Kwangmeyung , Kwon Ick Chan , Jo Dong‐Gyu , Cho Yong Woo , Park Jae Hyung 
Published: March 2021

AbstractExtracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action. Herein, based on bioorthogonal copper‐free click chemistry (BCC), surface‐edited EVs were prepared by using metabolically glycoengineered cells. First, the exogenous azide group was generated on the cellular surface through metabolic glycoengineering (MGE) using the precursor. Next, PEGylated hyaluronic acid, capable of binding specifically to the CD44‐expressing cells, was labelled as the representative targeting moiety onto the cell surface by BCC. The surface‐edited EVs effectively accumulated into the target tissues of the animal models with rheumatoid arthritis and tumour, primarily owing to prolonged circulation in the bloodstream and the active targeting mechanism. Overall, these results suggest that BCC combined with MGE is highly useful as a simple and safe approach for the surface modification of EVs to modulate their in vivo fate.
Performance of Deep Learning and Genitourinary Radiologists in Detection of Prostate Cancer Using 3‐T Multiparametric Magnetic Resonance Imaging
Authors: Cao Ruiming , Zhong Xinran , Afshari Sohrab , Felker Ely , Suvannarerg Voraparee , Tubtawee Teeravut , Vangala Sitaram , Scalzo Fabien , Raman Steven , Sung Kyunghyun 
Published: March 2021

BackgroundSeveral deep learning‐based techniques have been developed for prostate cancer (PCa) detection using multiparametric magnetic resonance imaging (mpMRI), but few of them have been rigorously evaluated relative to radiologists' performance or whole‐mount histopathology (WMHP).PurposeTo compare the performance of a previously proposed deep learning algorithm, FocalNet, and expert radiologists in the detection of PCa on mpMRI with WMHP as the reference.Study TypeRetrospective, single‐center study.SubjectsA total of 553 patients (development cohort: 427 patients; evaluation cohort: 126 patients) who underwent 3‐T mpMRI prior to radical prostatectomy from October 2010 to February 2018.Field Strength/Sequence3‐T, T2‐weighted imaging and diffusion‐weighted imaging.AssessmentFocalNet was trained on the development cohort to predict PCa locations by detection points, with a confidence value for each point, on the evaluation cohort. Four fellowship‐trained genitourinary (GU) radiologists independently evaluated the evaluation cohort to detect suspicious PCa foci, annotate detection point locations, and assign a five‐point suspicion score (1: least suspicious, 5: most suspicious) for each annotated detection point. The PCa detection performance of FocalNet and radiologists were evaluated by the lesion detection sensitivity vs. the number of false‐positive detections at different thresholds on suspicion scores. Clinically significant lesions: Gleason Group (GG) ≥ 2 or pathological size ≥ 10 mm. Index lesions: the highest GG and the largest pathological size (secondary).Statistical TestsBootstrap hypothesis test for the detection sensitivity between radiologists and FocalNet.ResultsFor the overall differential detection sensitivity, FocalNet was 5.1% and 4.7% below the radiologists for clinically significant and index lesions, respectively; however, the differences were not statistically significant (P = 0.413 and P = 0.282, respectively).Data ConclusionFocalNet achieved slightly lower but not statistically significant PCa detection performance compared with GU radiologists. Compared with radiologists, FocalNet demonstrated similar detection performance for a highly sensitive setting (suspicion score ≥ 1) or a highly specific setting (suspicion score = 5), while lower performance in between.Level of Evidence3Technical Efficacy Stage2
Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome
Authors: López René , Pérez‐Araos Rodrigo , Salazar Álvaro , Espinoza Mauricio , Vial Cecilia , Cuiza Analia , Vial Pablo A. , Graf Jerónimo 
Published: March 2021

AbstractBackgroundHantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients.MethodsWe implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF‐responders if VA ECMO was avoided and HVHF‐nonresponders if VA ECMO support was needed despite HVHF. A targeted‐HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients.ResultsPatients had maximum serum lactate of 8.8 (8.7–12.8) mmol/L and a lowest cardiac index of 1.8 (1.8–1.9) L/min/m2. The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF‐responders who received targeted‐HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication.ConclusionHVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted‐HVHF may increase the chance of success.
Sparking Creativity in Science Education
Authors: Draper Jenna T. , Ryba Ren , Connell Sean D. 
Published: March 2021

AbstractWorld‐class science requires inspiration, so how can we spark creativity in the modern university environment? Creativity does not come automatically: in the modern age, factors from electronic devices to time pressure can stifle creative thought. Yet, to solve the major problems of the future, it will be essential to stimulate creativity in scientific research and teaching. Here, we bring together insights from the literature to offer ways to cultivate creativity in universities. We advocate for creativity at all levels of university culture within which students are embedded, from the students themselves, to teachers, to researchers, and to administrators. We found that, for students, creativity can involve accepting creative coursework and understanding failure; for teachers, it can involve being active mentors and designing creative courses; for researchers, it can involve conscious effort to make room for creative thought within pressured workloads, and researching across disciplines; and for administrators, it can involve relaxing restraints, allowing autonomy over courses, and encouraging cross‐disciplinary learning and research.
Intensive pulsed light pretreatment combined with controlled temperature and humidity for convection drying to reduce browning and improve quality of dried shiitake mushrooms
Authors: Zhang Jin , Yagoub Abu ElGasim A , Sun Yanhui , S Mujumdar Arun , Ma Haile , Wahia Hafida , Zhou Cunshan 
Published: March 2021

AbstractBACKGROUNDThe change of surface color caused by browning during the drying process of shiitake mushrooms seriously affects its market circulation. Intensive pulsed light (IPL) as a non‐heat‐treatment method can reduce enzyme activity by changing the enzyme structure. Therefore, in this study, the use of IPL pretreatment before drying was aimed to reduce the adverse reactions caused by the browning reaction during the drying processing of shiitake mushrooms.RESULTSShiitake mushrooms pretreated with 25 pulses of IPL energy of 400 J reduced the initial polyphenol oxidase enzyme activity, the browning index, and browning degree values by 42.83%, 43.02%, and 47.54% respectively. The IPL pretreatment enhanced the polysaccharides and reducing sugars contents and it reduced 5‐hydroxymethylfurfural generation in the dried shiitake mushrooms. The pretreatment also improved the surface color, the antioxidant activity, and retained the umami taste characteristics in the dried shiitake mushroom.CONCLUSIONThe IPL pretreatment combined with controlled temperature and humidity for convection drying could be a suitable method to improve the quality of dried shiitake mushrooms. Therefore, this study provides a new pretreatment method for materials that are prone to browning during drying. © 2021 Society of Chemical Industry.
Solid‐state NMR spectroscopy as a powerful tool to investigate the location of fluorinated lipids in highly porous hybrid organic–inorganic nanoparticles
Authors: Porcino Marianna , Li Xue , Gref Ruxandra , Martineau‐Corcos Charlotte 
Published: March 2021

AbstractNanosized metal–organic frameworks (nanoMOFs) have emerged as a new class of biodegradable and nontoxic nanomaterials of high interest for biomedical applications thanks to the possibility to load large amounts of a wide variety of therapeutic molecules in their porous structure. The surface of the highly porous nanoMOFs is usually engineered to increase their colloidal stability, to tune their interactions with the biological environment, and to allow targeting specific cells or organs. However, the atomic‐scale analysis of these complex core‐shell materials is highly challenging. In this study, we report the investigation of aluminum‐based nanoMOFs containing two fluorinated lipids by solid‐state NMR spectroscopy, including 27Al, 1H and 19F MAS NMR. The ensemble of NMR data provides a better understanding of the localization and conformation of the fluorinated lipids inside the pores or on the nanoMOF surface.
A scoping review protocol: Investigating the extent and legal process of cauda equina syndrome claims for UK physiotherapists
Authors: Leech Rachel L. , Selfe James , Ball Suzanne , Greenhalgh Susan , Hogan Gareth , Holway Janene , Willis Emma , Yeowell Gillian 
Published: March 2021

AbstractIntroductionCauda equina syndrome (CES) is a condition where early identification and treatment is crucial to avoid potentially devastating effects. There is a high number of litigation cases linked with CES given it is a relatively rare condition. This scoping review protocol proposes to explore the extent and process of CES litigation in UK healthcare context cases amongst UK physiotherapists.Methods and analysisThe methodological framework recommended by Arksey and O'Malley, Levac et al. and the Joanna Briggs Institute will be used throughout this review to aid reporting and transparency. A patient and public involvement (PPI) group meeting was convened at the beginning of the review process in order to provide knowledge exchange to inform the search strategy and propose resources to be used during the scoping review. Two reviewers will independently review the literature in order to apply the inclusion and exclusion criteria. Once the studies to be included have been identified, the data from these studies will be extracted and charted. Results will show quantitative data of the studies included in the review and a narrative synthesis of the literature.DisseminationThis scoping review will evaluate the existing knowledge relating to CES and litigation and will map the key concepts around this topic. Results will be disseminated to practitioners and policy‐makers through peer‐reviewed publications, conferences, reports and social media. This method may prove helpful to others who are investigating extent and processes relating to medicolegal cases involving healthcare practitioners.RegistrationThe current paper is registered with OSF registries (DOI 10.17605/OSF.IO/MP6Y3).
The residential contexts of Gravettian hunter‐gatherers from Arbreda Cave (Serinyà, Northeast Iberian Peninsula): Searching activity areas from archeozoological evidence
Authors: Rufí Isaac , Morera Núria , Lloveras Lluís , Soler Joaquim , Soler Narcís 
Published: March 2021

AbstractDuring the Gravettian, Arbreda Cave was frequently occupied by hunter‐gatherer communities. Within this period, the archeological levels E (Iberian Middle Gravettian) and D (Final Gravettian), dated to ca. 26–20 kyr 14C BP, are of particular interest, since fieldwork carried out during the 1980s revealed dense accumulations of archeological materials with remarkable concentrations of burnt remains. The archeozoological and taphonomic studies conducted with faunal remains recovered from both levels have provided essential information about subsistence activities; however, the concentrations of these remains have not been subjected to spatial distribution analysis. In recent decades, spatial analysis has become a key tool for deciphering the formation dynamics of archeological levels, as well as for offering valuable clues with which to understand the relation of the occupants with the morphology of the site cavities. The aims of this paper are to pinpoint the principal activity areas of both Gravettian levels of Arbreda Cave focusing on the location of main hearth‐related assemblages and to interpret these activity areas in terms of the use of the space by hunter‐gatherer groups. To achieve these goals, our research has been based on the processing of archeozoological and taphonomic data obtained in recent studies applying different spatial statistics methods, including techniques of density analysis and spatial correlation. Furthermore, for each level, the results obtained from the geostatistical approaches are supplemented by a detailed taphonomic analysis of the complete assemblage of remains recovered from the principal hearth‐related square. Finally, in each case, an accurate analysis of the burnt remain assemblage of each square provides further elucidation of the large amount of combusted remains in the area. The study reveals that hunter‐gatherer communities established themselves in particular areas of the cave, close to the north wall and beneath the existing roof of the rock shelter. The dense accumulations of different remains found in these areas has enabled us to hypothesize about its hearth‐related origin, where hearths would have been settled and marrow exploitation activities would have been carried out around them. Furthermore, the high rate of breakage and charred and calcined remains and a relatively high percentage of burnt spongy bones indicate that bones were used as fuel to supplement firewood. On the whole, the low level of space organization complexity of levels E and D main activity areas supports a seasonal pattern of occupation during the Iberian Middle Gravettian and Final Gravettian periods.
Harnessing artificial intelligence technology and social media data to support Cultural Ecosystem Service assessments
Authors: Egarter Vigl Lukas , Marsoner Thomas , Giombini Valentina , Pecher Caroline , Simion Heidi , Stemle Egon , Tasser Erich , Depellegrin Daniel 
Published: March 2021

Abstract

Cultural Ecosystem Services (CESs), such as aesthetic and recreational enjoyment, as well as sense of place and cultural heritage, play an outstanding role in the contribution of landscapes to human well‐being.

Scientists, however, still often struggle to understand how landscape characteristics contribute to deliver these intangible benefits, largely because it is hard to navigate how people value nature, and because there is a lack in methods that accommodate both comprehensive and time‐efficient evaluations.

Recent advances in technology and the proliferation of new data sources, such as social media data, open promising alternatives to traditional, resource‐intensive methods, facilitating the understanding of the multiple relationships between people and nature.

Here, we examine a user‐friendly artificial intelligence (AI)‐based approach for inferring visual‐sensory landscape values from Flickr data, combining computer vision with text mining. We show it is possible to automatically relate photographers' preferences in capturing landscape elements to a set of CESs (aesthetic value, outdoor recreation, cultural heritage, symbolic species) with reasonable accuracy, using the semantic content provided by approximately 640,000 artificially generated tags of photographs taken in the UNESCO world heritage site ‘The Dolomites’ (Italy). We used the geographic information in the data to demonstrate that these preferences can be further linked to different natural and human variables and be used to spatially predict CES patterns.

Over 90% of photograph tags could be linked to four CES categories with reasonable confidence (accuracy ration ∼ 80%). The Dolomites are highly appreciated for its aesthetic value (66% of images classified to that category) and vast cultural heritage (13%), followed by its outdoor recreation opportunities (11%) and symbolic species (10%). CES benefiting hotspots were found in areas with high tourism development and close to residential areas, and could largely be explained by a combination of environmental (e.g. landscape composition) and infrastructural (e.g. accessibility) variables.

We conclude that online available AI technology and social media data can effectively be used to support rapid, flexible and transferrable CES assessments. Our work can provide a reference for innovative adaptive management approaches that can harness emerging technologies to gain insights into human–nature relationships and to sustainably manage our environment.

A free Plain Language Summary can be found within the Supporting Information of this article.
Cell‐free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review
Authors: Familiari Alessandra , Boito Simona , Rembouskos Georgios , Ischia Benedetta , Accurti Veronica , Fabietti Isabella , Volpe Paolo , Persico Nicola 
Published: March 2021

AbstractBackground and aim of the studyScientific Societies do not recommend the use of cell‐free DNA (cfDNA) testing as a first‐tier screening for microdeletion and microduplication syndromes (MMs). The aim of this study was to review the current available literature on the performance of cell‐free DNA as a screening for MMs.MethodsMedline, Embase and the Cochrane Library were searched electronically from 2000 to January 2020 and articles reporting the diagnostic performance of cfDNA screening for MMs in large (>5000 cases) series were included. Between‐study heterogeneity and random effect model for screen positive rate (SPR), false positive rate (FPR) and positive predictive value (PPV) were calculated.ResultsWe identified 42 papers, seven included, for a total of 474,189 pregnancies and 210 cases of MMs. Diagnostic verification of positive cases was available overall in 486 (71.68 %) of 678 cases. The weighted pooled SPR, FPR and PPV were 0.19% (95% CI = 0.09–0.33), 0.07 (95% CI = 0.02–0.15) and 44.1 (95% CI = 31.49–63.07). In conclusion, the pooled PPV of cfDNA testing in screening for MMs was about 40%, ranging from 29% to 91%, for an overall FPR <0.1%.ConclusionsNo confirmatory analysis was available in cases that did not undergo invasive testing, which were the vast majority of cases with a negative test, and therefore, the DR and the negative predictive value cannot be determined.
Gizzard Shad Target Strength‐to‐Body Size Equations at Multiple Hydroacoustic Frequencies
Authors: Johnson Garret R. , Dillon Rebecca A. , Zweifel Richard D. , Ludsin Stuart A. , Conroy Joseph D. 
Published: March 2021

AbstractSpecies‐specific target strength (TS)‐to‐length (L) and TS‐to‐weight (W) equations can reduce bias in biomass estimates from hydroacoustic surveys, yet these equations do not exist for most fishes. Equations specific to the Gizzard Shad Dorosoma cepedianum, a wide‐ranging and often highly abundant prey fish in North American reservoirs and rivers, do not exist. Herein, we sought to develop TS–L and TS–W equations for Gizzard Shad by insonifying free‐swimming individuals of known sizes (36–209 mm TL) in a net cage at three transducer frequencies (70, 120, and 200 kHz). We derived TS–size relationships using major‐axis regression (MAR) and least‐squares regression (LSR), comparing our resultant TS–L equations to a commonly used multispecies equation (Love 1971). To determine how our Gizzard Shad‐specific equations affected estimates of prey fish biomass, we conducted mobile hydroacoustic surveys in four small, shallow Midwestern reservoirs and then estimated biomass using each equation. In general, for TS–L equations, MAR produced the highest estimates of biomass, followed by LSR and then the multispecies equation. Similarly, the TS–W equation derived using MAR produced greater biomass estimates than the equation using LSR. Our findings highlight the value of using species‐specific TS–size equations over multispecies equations in ecosystems dominated by a single fish species (e.g., Gizzard Shad in Midwestern reservoirs). They also demonstrate the value of using MAR to develop TS–size equations, owing to its ability to account for fish size measurement error. The use of species‐specific TS–size equations and MAR should lead to robust estimates of biomass in single‐species‐dominated ecosystems, thus benefiting fisheries assessment and decision making.