bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapidly accelerated development of neutralizing COVID‐19 antibodies by reducing cell line and CMC development timelines
Authors: Tan Kee Wee , Ji Pengfei , Qian Zichen , Gao Qiao , Wang Shuai , Li Qin , Gu Mingzhu , Zhang Qi , Hou Chengjian , Huang Yang , Lian Dujuan , Wang Junghao , Zhang Zheng , Zhang Sam , Wu Jiansheng , Zhou Weichang 
Published: December 2022

AbstractSince the Coronavirus Disease 2019 (COVID‐19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much‐shortened timeline of 3–6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS‐CoV‐2‐neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late‐stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next‐generation sequencing‐based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID‐19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic‐related biologics development may innovate typical biologics development timelines and become a new standard in the industry.
Identification of the metabolites of neocnidilide in rat, monkey and human liver microsomes by liquid chromatography coupled to benchtop Orbitrap mass spectrometry
Authors: Xie Tiantian , Huang Lihua , Wang Chengcheng 
Published: December 2022

AbstractNeocnidilide, a bioactive component isolated from Angelica sinensis (Oliv.) Diels, displayed anti‐inflammatory activity. The present work was performed to investigate in vitro metabolism of neocnidilide using liver microsomes. Neocnidilide (10 μM) was incubated with NADPH‐supplemented rat monkey and human liver microsomes. To identify the reactive metabolites, glutathione (GSH) was included in the incubations. Liquid chromatography coupled to an Orbitrap mass spectrometer was used to detect and identify the metabolites. The structures of the metabolites were characterized by accurate masses and fragmentation patterns. A total of six hydroxylation metabolites and nine GSH conjugates were tentatively identified characterized. The metabolic pathways included hydroxylation, dehydrogenation and GSH conjugation. M6 was the major metabolite in human liver microsomes. CYP1A2 (25%), 2B6 (31.6%), 2C9 (10.5%) and 3A4 (18%) were the predominant isoenzymes governing its formation. This study provides valuable information on the in vitro metabolism of neocnidilide, which is indispensable for the further safety assessment of this compound.
Determining the geographical origin of durum wheat samples by combining strontium isotope ratio and multielemental analyses
Authors: Monti Carlo , Cavanna Daniele , Rodushkin Ilia , Monti Arianna , Leporati Andrea , Suman Michele 
Published: December 2022

AbstractBackground and objectivesDetermining the geographical origin of durum wheat is an important and emerging challenge because consumers perceive added value of final products (e.g., pasta) depending on the origin. Declaration of geographical origin is also an emerging requirement of specific national regulations. Among analytical strategies for determining geographical origins of samples, isotopic techniques based on both light and radiogenic isotope targets stand out, despite limitations of applicability, validation and assessment of interyear variability.FindingsIn this study, 87Sr/86Sr isotopic analysis was successfully used to discriminate Italian (ITA) samples versus rest‐of‐the world (RoW) samples and subsequently integrated with an elemental analysis (ICP‒MS) on 75 elements. A tiered approach was finally adopted in which the results of the 87Sr/86Sr analysis were input to a second step of support vector machine classification modeling (SVMC) based on the Al, Mn, Mo, P, S, Ti, Y, and Zn percentages in each sample. This model was tested against a blind group of samples with overall satisfactory performance.ConclusionValuable information from multielemental and stable isotope ratio analyses was collected for authentic samples from different Italian, European, and non‐European regions harvested during different years.Significance and noveltyThis study demonstrates the potential and validity of an innovative combined multielemental and strontium isotope ratio approach for the geographic discrimination of durum wheat on a global scale: the developed predictive model has already been routinely employed to control industrial lots.
Was Menschen bewegt, die etwas bewegen
Authors: Stange Berit 
Published: December 2022

AbstractDr. Berit Stange ist Chemikerin und seit 2005 für Bayer, heute Covestro in Leverkusen tätig. 2019 wurde sie mit Dr. Christoph Gürtler und Prof. Dr. Walter Leitner* für ihre Arbeiten im Projekt “CO2 ‐ ein Rohstoff für nachhaltige Kunststoffe” für den deutschen Zukunftspreis nominiert. Das Team hat ein katalytisches Verfahren entwickelt, mit dem sich Kohlendioxid aus Abgasen zu marktfähigen Kosten als Ausgangsmaterial für die chemische Industrie nutzen lässt.
Unser wertvollstes Gut: der wissenschaftliche Nachwuchs
Authors: Beimdiek Franziska , Nagarajan Abhinav , Wachsmann Christian 
Published: December 2022

AbstractDie kreativen jungen Verfahrensingenieure und ‐ingenieurinnen (kjVI) liefern den wertvollsten Rohstoff für die Ingenieurswissenschaften: begeisterten Nachwuchs. Das Ziel der kjVI ist es, die Neugier in Schülern und Studierenden auf Verfahrenstechnik zu wecken sowie junge Verfahrenstechniker und ‐technikerinnen und Promovierende den lebendigen Austausch zwischen Industrie und Wissenschaft zu ermöglichen.
Wirtschaftlich und vielseitig
Authors: van Dorp Annette 
Published: December 2022

AbstractWie lassen sich die Vorteile einer Verdrängerpumpe auf eine kostengünstige Kolbenpumpe übertragen? Diese Fragen stellten sich die Entwickler beim Pumpenhersteller Bungartz. Das Ergebnis ist eine hermetisch dichte Rotationskolbenpumpe, die nicht nur energieeffizient arbeitet sondern auch weitere Vorteile verschiedener bereits bekannter Technologien kombiniert. Die neue Pumpe fördert pulsationsarm und erfordert durch ihre Konstruktion wenig Wartung.
Severe, life‐threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood
Authors: Holmqvist Anna Sällfors , Chen Yanjun , Hageman Lindsey , Landier Wendy , Wu Jessica , Francisco Liton F. , Ross Elizabeth Schlichting , Balas Nora A. , Bosworth Alysia , Te Hok Sreng , Goldman Frederick D. , Rosenthal Joseph , Wong F. Lennie , Weisdorf Daniel J. , Armenian Saro H. , Bhatia Smita 
Published: December 2022

AbstractBackgroundA comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied.MethodsSeven hundred eighty‐nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255‐item survey self‐reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life‐threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings.ResultsThe median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow‐up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft‐versus‐host disease (HR, 1.38; 95% CI, 1.09–1.74).ConclusionsTwo‐year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long‐term follow‐up.
A Single‐center, Open‐label, Parallel Control Study Comparing the Pharmacokinetics and Safety of a Single Oral Dose of Roflumilast and Its Active Metabolite Roflumilast N‐oxide in Healthy Chinese and Caucasian Volunteers
Authors: Han Mai , Lin Xiao‐yan , Cui Gang , Chen Shuai , Wu Wei , Mi Na , Wang Jing , Xiao Chun‐yan , Zhang Xin , Lu Xing , Li Jin‐tong 
Published: December 2022

AbstractRoflumilast is a phosphodiesterase‐4 inhibitor which treats chronic obstructive pulmonary disease (COPD). Roflumilast N‐oxide is the major metabolite of roflumilast with a similar mechanism of action to roflumilast. Although racial differences in roflumilast drug disposition have been observed, the necessity of dose adjustment is subject to debate. This study compares the pharmacokinetics of a single 500 μg dose of roflumilast in healthy Chinese and Caucasian subjects under uniform conditions. Chinese subjects were found to have longer t1/2 and higher AUC0‐t and Cmax than Caucasian subjects. The point estimates on the geometric mean of AUC0‐t in Chinese subjects were 22% higher for roflumilast and 46% higher for roflumilast N‐oxide. Point estimates on the geometric mean of Cmax were 9% and 24% higher for roflumilast and roflumilast N‐oxide, respectively. Total phosphodiesterase‐4 (PDE4) inhibitory (tPDE4i) activity, a theoretical parameter that describes the combined contribution to PDE4 inhibitory activity of roflumilast and roflumilast N‐oxide, was 44% higher in Chinese subjects than in Caucasian subjects. With about a 10‐fold higher plasma AUC compared to the parent roflumilast and a much longer observed half‐life, roflumilast N‐oxide has been estimated to contribute about 90% of tPDE4i, with 10% attributed to the parent compound roflumilast. Following body weight normalization, these figures were lower but remained significant. Safety analysis showed signs of reduced tolerance or different pharmacodynamic response to roflumilast in Chinese recipients than in Caucasians. Our results suggest that Chinese patients should receive a dose of roflumilast lower than 500 μg daily during future clinical trials.
Mega‐environment analysis and breeding for specific adaptation
Authors: Yan Weikai , Nilsen Kirby T. , Beattie Aaron 
Published: December 2022

AbstractMega‐environment (ME) analysis is analysis of multi‐year, multi‐location crop variety trial data conducted in a target region of a crop to understand the magnitude and nature of genotype‐by‐environment interaction (GE) of the crop in the region. If repeatable GE patterns are identified, then the target region must be divided into subregions or MEs. Breeding and utilizing ME‐specific cultivars will convert the repeatable GE into genotypic main effect (G) within ME, thereby improving heritability (selection reliability) and selection gain and maximize regional and overall productivity. If no repeatable GE is found, then the target region must be treated as a single ME and the GE must be accommodated by testing adequately, that is, at a sufficient number of locations in a sufficient number of years. This paper presents a theoretical framework of ME analysis, describes graphical tools to reveal the which‐won‐where patterns in a genotype‐by‐environment dataset, and demonstrates LG (location‐grouping) biplot analysis for revealing repeatable GE patterns and delineating MEs. The concept of G + GE or GGE, that is, GE relative to G, is emphasized. It is the relative GE that is the basis for ME analysis and breeding for specific adaptation; absolute magnitude of GE has little relevance for these purposes. Breeding ME‐specific oat cultivars in Canada is demonstrated with a real‐world example.
Migratory connectivity of North American waterfowl across administrative flyways
Authors: Roberts Anthony , Scarpignato Amy L. , Huysman Allison , Hostetler Jeffrey A. , Cohen Emily B. 
Published: December 2022

AbstractManagement of waterfowl that migrate seasonally across North America occurs within four flyways that were delineated in the early 1900s to include the annual movements of populations. Movements may have changed over the past century since the administrative flyways were established, and may do so while management plans are in use, so information about transitions among flyways through time can illustrate how management assumptions may change. Today there are more than 12 million records from 60 years of migratory waterfowl band recoveries to assess adaptive management approaches that will be most effective when they account for movements within and between flyways. We examined how much the movement of North American waterfowl occurs between flyways, whether those movements have changed through time, and whether movements of mallards are representative of multiple species, as suggested by current harvest management strategies. We estimated the probability a duck would transition from one flyway to another and the strength of migratory connectivity (MC) for each species within and among flyways. We used capture–mark–recovery models to estimate population‐specific movement within and among flyways (transition probabilities) for 15 migratory waterfowl species that were banded during breeding and recovered during winter. We developed new functionality in the R package MigConnectivity to estimate the species‐specific strength of MC using transition probability samples from the capture–mark–recovery models. We found the regular movement of duck populations among flyways, overall weak MC, and no consistent change in migratory movements through time. Mallard movements were median among all duck species, but significantly different from many species, particularly diving ducks. Despite the significant movement between flyways, our work suggests flyway management of waterfowl matches many of the seasonal movements of these species when considering mid‐continent flyway management. We recommend models accounting for all transition probabilities between populations and regularly estimating harvest derivations, transition probabilities, and MC metrics to verify that the current movements match model assumptions.
Multiscale relationships between humpback whales and forage species hotspots within a large marine ecosystem
Authors: Szesciorka Angela R. , Demer David A. , Santora Jarrod A. , Forney Karin A. , Moore Jeff E. 
Published: December 2022

AbstractFluctuations in prey abundance, composition, and distribution can impact predators, and when predators and fisheries target the same species, predators become essential to ecosystem‐based management. Because of the difficulty in collecting concomitant predator–prey data at appropriate scales in patchy environments, few studies have identified strong linkages between cetaceans and prey, especially across large geographic areas. During summer 2018, a line‐transect survey for cetaceans and coastal pelagic species was conducted over the continental shelf and slope of British Columbia, Canada, and the US West Coast, allowing for a large‐scale investigation of predator–prey spatial relationships. We report on a case study of humpback whales (Megaptera novaeangliae) and their primary prey—Pacific herring (Clupea pallasii), northern anchovy (Engraulis mordax), and krill—using generalized additive models to explore the relationships between whale abundance on 10‐km transect segments and prey metrics. Prey metrics included direct measures of biomass densities on segments and an original hotspot metric. For each prey species, segments in the upper fifth percentile for biomass density (across all segments) were designated hotspots, and whale counts on a segment were evaluated for their relationship to number of hotspot segments (species‐specific and multispecies) within 25, 50, or 100 km. Whale abundance was not strongly related to direct measures of biomass densities, whereas models using hotspot metrics were more effective at describing variation in whale abundance, underscoring that evaluating prey at relevant and measurable scales is critical in patchy, dynamic marine environments. Our analysis highlighted differences in the distribution and prey availability for three humpback whale distinct population segments (DPSs) as defined under the US Endangered Species Act, including threatened and endangered DPSs that forage within the California Current Large Marine Ecosystem. These linkages provide insights into which prey species whales may be targeting in different regions and across multiple scales and, consequently, how climatic variability and anthropogenic risks may differentially impact these distinct predator–prey assemblages. By identifying scale‐appropriate prey hotspots that co‐occur with humpback whale aggregations, and with targeted, consistent prey sampling and estimations of potential consumption rates by whales, these findings can help inform the conservation and management of humpback whales within an ecosystem‐based management framework.
Different proxies, different stories? Imperfect correlations and different determinants of fitness in bighorn sheep
Authors: Van de Walle Joanie , Larue Benjamin , Pigeon Gabriel , Pelletier Fanie 
Published: December 2022

AbstractMeasuring individual fitness empirically is required to assess selective pressures and predicts evolutionary changes in nature. There is, however, little consensus on how fitness should be empirically estimated. As fitness proxies vary in their underlying assumptions, their relative sensitivity to individual, environmental, and demographic factors may also vary. Here, using a long‐term study, we aimed at identifying the determinants of individual fitness in bighorn sheep (Ovis canadensis) using seven fitness proxies. Specifically, we compared four‐lifetime fitness proxies: lifetime breeding success, lifetime reproductive success, individual growth rate, individual contribution to population growth, and three multi‐generational proxies: number of granddaughters, individual descendance in the next generation, and relative genetic contribution to the next generation. We found that all proxies were positively correlated, but the magnitude of the correlations varied substantially. Longevity was the main determinant of most fitness proxies. Individual fitness calculated over more than one generation was also affected by population density and growth rate. Because they are affected by contrasting factors, our study suggests that different fitness proxies should not be used interchangeably as they may convey different information about selective pressures and lead to divergent evolutionary predictions. Uncovering the mechanisms underlying variation in individual fitness and improving our ability to predict evolutionary change might require the use of several, rather than one, the proxy of individual fitness.
Impacts of extreme climatic events on trophic network complexity and multidimensional stability
Authors: Polazzo Francesco , Hermann Markus , Crettaz‐Minaglia Melina , Rico Andreu 
Published: December 2022

AbstractUntangling the relationship between network complexity and ecological stability under climate change is an arduous challenge for theoretical and empirical ecology. Even more so, when considering extreme climatic events. Here, we studied the effects of extreme climatic events (heatwaves) on the complexity of realistic freshwater ecosystems using topological and quantitative trophic network metrics. Next, we linked changes in network complexity with the investigation of four stability components (temporal stability, resistance, resilience, and recovery) of community's functional, compositional, and energy flux stability. We found reduction in topological network complexity to be correlated with reduction of functional and compositional resistance. However, temperature‐driven increase in link‐weighted network complexity increased functional and energy flux recovery and resilience, but at the cost of increased compositional instability. Overall, we propose an overarching approach to elucidate the effects of climate change on multidimensional stability through the lens of network complexity, providing helpful insights for preserving ecosystems stability under climate change.
Pragmatic screening for heart failure in the general population using an electrocardiogram‐based neural network
Authors: Surendra Kishore , Nürnberg Sylvia , Bremer Jan P. , Knorr Marius S. , Ückert Frank , Wenzel Jan Per , Bei der Kellen Ramona , Westermann Dirk , Schnabel Renate B. , Twerenbold Raphael , Magnussen Christina , Kirchhof Paulus , Blankenberg Stefan , Neumann Johannes , Schrage Benedikt 
Published: December 2022

AbstractAimsWe aim to develop a pragmatic screening tool for heart failure at the general population level.Methods and resultsThis study was conducted within the Hamburg‐City‐Health‐Study, an ongoing, prospective, observational study enrolling randomly selected inhabitants of the city of Hamburg aged 45–75 years. Heart failure was diagnosed per current guidelines. Using only digital electrocardiograms (ECGs), a convolutional neural network (CNN) was built to discriminate participants with and without heart failure. As comparisons, known risk variables for heart failure were fitted into a logistic regression model and a random forest classifier. Of the 5299 individuals included into this study, 318 individuals (6.0%) had heart failure. Using only the digital ECGs instead of several risk variables as an input, the CNN provided a comparable predictive accuracy for heart failure versus the logistic regression model and the random forest classifier [area under the curve (AUC) of 0.75, a sensitivity of 0.67 and a specificity of 0.69 for the CNN; AUC 0.77, a sensitivity of 0.63 and a specificity of 0.76 for the logistic regression; AUC 0.79, a sensitivity of 0.67 and a specificity of 0.72 for the random forest classifier].ConclusionsUsing a CNN build on digital ECGs only and requiring no additional input, we derived a screening tool for heart failure in the general population. This could be perfectly embedded into clinical routine of general practitioners, as it builds on an already established diagnostic tool and does not require additional, time‐consuming input. This could help to alleviate the underdiagnosis of heart failure.