bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Voevodsky motive of the moduli space of Higgs bundles on a curve
Authors: Hoskins Victoria , Lehalleur Simon Pepin 
Published: February 2021

AbstractWe study the motive of the moduli space of semistable Higgs bundles of coprime rank and degree on a smooth projective curveCover a fieldkunder the assumption thatChas a rational point. We show this motive is contained in the thick tensor subcategory of Voevodsky’s triangulated category of motives with rational coefficients generated by the motive ofC. Moreover, over a field of characteristic zero, we prove a motivic non-abelian Hodge correspondence: the integral motives of the Higgs and de Rham moduli spaces are isomorphic.
Beat the stress: breeding for climate resilience in maize for the tropical rainfed environments
Authors: Prasanna Boddupalli M. , Cairns Jill E. , Zaidi P. H. , Beyene Yoseph , Makumbi Dan , Gowda Manje , Magorokosho Cosmos , Zaman-Allah Mainassara , Olsen Mike , Das Aparna , Worku Mosisa , Gethi James , Vivek B. S. , Nair Sudha K. , Rashid Zerka , Vinayan M. T. , Issa AbduRahman Beshir , San Vicente Felix , Dhliwayo Thanda , Zhang Xuecai 
Published: February 2021

Abstract
Key message

Intensive public sector breeding efforts and public-private partnerships have led to the increase in genetic gains, and deployment of elite climate-resilient maize cultivars for the stress-prone environments in the tropics.

Abstract
Maize (Zea mays L.) plays a critical role in ensuring food and nutritional security, and livelihoods of millions of resource-constrained smallholders. However, maize yields in the tropical rainfed environments are now increasingly vulnerable to various climate-induced stresses, especially drought, heat, waterlogging, salinity, cold, diseases, and insect pests, which often come in combinations to severely impact maize crops. The International Maize and Wheat Improvement Center (CIMMYT), in partnership with several public and private sector institutions, has been intensively engaged over the last four decades in breeding elite tropical maize germplasm with tolerance to key abiotic and biotic stresses, using an extensive managed stress screening network and on-farm testing system. This has led to the successful development and deployment of an array of elite stress-tolerant maize cultivars across sub-Saharan Africa, Asia, and Latin America. Further increasing genetic gains in the tropical maize breeding programs demands judicious integration of doubled haploidy, high-throughput and precise phenotyping, genomics-assisted breeding, breeding data management, and more effective decision support tools. Multi-institutional efforts, especially public–private alliances, are key to ensure that the improved maize varieties effectively reach the climate-vulnerable farming communities in the tropics, including accelerated replacement of old/obsolete varieties.
Current and future therapies for type 1 diabetes
Authors: von Scholten Bernt Johan , Kreiner Frederik F. , Gough Stephen C. L. , von Herrath Matthias 
Published: February 2021

AbstractIn type 1 diabetes, insulin remains the mature therapeutic cornerstone; yet, the increasing number of individuals developing type 1 diabetes (predominantly children and adolescents) still face severe complications. Fortunately, our understanding of type 1 diabetes is continuously being refined, allowing for refocused development of novel prevention and management strategies. Hitherto, attempts based on immune suppression and modulation have been only partly successful in preventing the key pathophysiological feature in type 1 diabetes: the immune-mediated derangement or destruction of beta cells in the pancreatic islets of Langerhans, leading to low or absent insulin secretion and chronic hyperglycaemia. Evidence now warrants a focus on the beta cell itself and how to avoid its dysfunction, which is putatively caused by cytokine-driven inflammation and other stress factors, leading to low insulin-secretory capacity, autoantigen presentation and immune-mediated destruction. Correspondingly, beta cell rescue strategies are being pursued, which include antigen vaccination using, for example, oral insulin or peptides, as well as agents with suggested benefits on beta cell stress, such as verapamil and glucagon-like peptide-1 receptor agonists. Whilst autoimmune-focused prevention approaches are central in type 1 diabetes and will be a requirement in the advent of stem cell-based replacement therapies, managing the primarily cardiometabolic complications of established type 1 diabetes is equally essential. In this review, we outline selected recent and suggested future attempts to address the evolving profile of the person with type 1 diabetes.
Graphical abstract
Endowing Artificial Intelligence with legal subjectivity
Authors: Wojtczak Sylwia 
Published: February 2021

AbstractThis paper reflects on the problem of endowing Artificial Intelligence (AI) with legal subjectivity, especially with regard to civil law. It is necessary to reject the myth that the criteria of legal subjectivity are sentience and reason. Arguing that AI may have potential legal subjectivity based on an analogy to animals or juristic persons suggests the existence of a single hierarchy or sequence of entities, organized according to their degree of similarity to human beings; also, that the place of an entity in this hierarchy determines the scope of subjectivity attributed to it. Rather, it is participation or presence in social life, whatever the role, that is the true criterion of subjectivity. In addition, it is clear that even if AI is not currently a significant participant in social life, it will be in the nearest future. Despite the potential dangers associated with endowing AI with some kind of subjectivity, such a course is inescapable, and should be considered sooner rather than later.
Analysis of mono-, di-, triacylglycerols, and fatty acids in food emulsifiers by high-performance liquid chromatography–mass spectrometry
Authors: Schick Dinah , Link Katharina , Schwack Wolfgang , Granvogl Michael , Oellig Claudia 
Published: February 2021

AbstractMono- and diacylglycerols (MG/DG) of fatty acids (FA), known as emulsifiers of the type E 471, are food additives used to adjust techno-functional properties of various foodstuffs. These emulsifiers, however, are not defined single compounds but comprise, in addition to MG and DG, other constituents such as FA, triacylglycerols (TG), and glycerol. Although the emulsifiers’ compositions affect techno-functional properties of the food, knowledge of the composition is scarcely available, and the emulsifiers and their dosage are generally chosen empirically. Thus, a simple and rather inexpensive method for the simultaneous determination of FA, 1-MG, 2-MG, 1,2-DG, 1,3-DG, and TG by high-performance liquid chromatography–mass spectrometry including a straightforward quantitation strategy has been developed. Reversed-phase chromatography with gradient elution offered adequate separation of 29 considered analytes within 21 peaks, while mass-selective detection provided their unequivocal identification. The quantitation strategy based on calibration just with the C16:0 representatives of each lipid class and a corresponding response factor system has proven to provide reliable results. The determined concentrations of different mixtures comprising varying compositions and concentrations of C16:0, C18:0, and C18:1 components of each lipid class deviated < 20% (n = 351) from the respective target concentrations. Limits of decision were determined to 0.3–0.8 mg/L and limits of quantitation to 0.8–1.7 mg/L, expressed as C16:0 representatives. Application of the method to various E 471 emulsifiers provided detailed data on their chemical compositions, and calculated FA compositions matched very well those determined by common methods such as gas chromatography with flame ionization detection.
Pressure Function and Limit Theorems for Almost Anosov Flows
Authors: Bruin Henk , Terhesiu Dalia , Todd Mike 
Published: February 2021

AbstractWe obtain limit theorems (Stable Laws and Central Limit Theorems, both standard and non-standard) and thermodynamic properties for a class of non-uniformly hyperbolic flows: almost Anosov flows, constructed here. The link between the pressure function and limit theorems is studied in an abstract functional analytic framework, which may be applicable to other classes of non-uniformly hyperbolic flows.
Warming mediates intraspecific multiple predator effects from an invasive crustacean
Authors: Cuthbert Ross N. , Wasserman Ryan J. , Dalu Tatenda , Briski Elizabeta 
Published: February 2021

AbstractInvasive alien species impacts might be mediated by environmental factors such as climatic warming. For invasive predators, multiple predator interactions could also exacerbate or dampen ecological impacts. These effects may be especially pronounced in highly diverse coastal ecosystems that are prone to profound and rapid regime shifts. We examine emergent effects of warming on the strength of intraspecific multiple predator effects from a highly successful invasive gammarid Gammarus tigrinus, using a functional response approach towards larval chironomids (feeding rates under different prey densities). Single predator maximum feeding rates were three-times higher at 24 °C compared to 18 °C overall, with potentially prey destabilising type II functional responses exhibited. However, pairs of gammarids exhibited intraspecific multiple predator effects that were in turn mediated by temperature regime, whereby synergisms were found at the lower temperature (i.e. positive non-trophic interactions) and antagonisms detected at the higher temperature (i.e. negative non-trophic interactions) under high prey densities. Accordingly, warming scenarios may worsen the impact of this invasive alien species, yet implications of temperature change are dependent on predator–predator interactions. Emergent effects between abiotic and biotic factors should be considered in ecological impact predictions across habitat types for invasive alien species.
Effects of age and sex on the distribution and symmetry of lumbar spinal and neural foraminal stenosis: a natural language processing analysis of 43,255 lumbar MRI reports
Authors: Travis Caton Michael , Wiggins Walter F. , Pomerantz Stuart R. , Andriole Katherine P. 
Published: February 2021

AbstractPurposeThe purpose of this study is to investigate relationship of patient age and sex to patterns of degenerative spinal stenosis on lumbar MRI (LMRI), rated as moderate or greater by a spine radiologist, using natural language processing (NLP) tools.MethodsIn this retrospective, IRB-approved study, LMRI reports acquired from 2007 to 2017 at a single institution were parsed with a rules-based natural language processing (NLP) algorithm for free-text descriptors of spinal canal stenosis (SCS) and neural foraminal stenosis (NFS) at each of six spinal levels (T12-S1) and categorized according to a 6-point grading scale. Demographic differences in the anatomic distribution of moderate (grade 3) or greater SCS and NFS were calculated by sex, and age and within-group differences for NFS symmetry (left vs. right) were calculated as odds ratios.ResultsForty-three thousand two hundred fifty-five LMRI reports (34,947 unique patients, mean age = 54.7; sex = 54.9% women) interpreted by 152 radiologists were studied. Prevalence of significant SCS and NFS increased caudally from T12-L1 to L4-5 though less at L5-S1. NFS was asymmetrically more prevalent on the left at L2-L3 and L5-S1 (p< 0.001). SCS and NFS were more prevalent in men and SCS increased with age at all levels, but the effect size of age was largest at T12-L3. Younger patients (< 50 years) had relatively higher NFS prevalence at L5-S1.ConclusionNLP can identify patterns of lumbar spine degeneration through analysis of a large corpus of radiologist interpretations. Demographic differences in stenosis prevalence shed light on the natural history and pathogenesis of LSDD.
Advances in monitoring and control of refolding kinetics combining PAT and modeling
Authors: Pauk Jan Niklas , Raju Palanisamy Janani , Kager Julian , Koczka Krisztina , Berghammer Gerald , Herwig Christoph , Veiter Lukas 
Published: February 2021

Abstract
Overexpression of recombinant proteins in Escherichia coli results in misfolded and non-active protein aggregates in the cytoplasm, so-called inclusion bodies (IB). In recent years, a change in the mindset regarding IBs could be observed: IBs are no longer considered an unwanted waste product, but a valid alternative to produce a product with high yield, purity, and stability in short process times. However, solubilization of IBs and subsequent refolding is necessary to obtain a correctly folded and active product. This protein refolding process is a crucial downstream unit operation—commonly done as a dilution in batch or fed-batch mode. Drawbacks of the state-of-the-art include the following: the large volume of buffers and capacities of refolding tanks, issues with uniform mixing, challenging analytics at low protein concentrations, reaction kinetics in non-usable aggregates, and generally low re-folding yields. There is no generic platform procedure available and a lack of robust control strategies. The introduction of Quality by Design (QbD) is the method-of-choice to provide a controlled and reproducible refolding environment. However, reliable online monitoring techniques to describe the refolding kinetics in real-time are scarce. In our view, only monitoring and control of re-folding kinetics can ensure a productive, scalable, and versatile platform technology for re-folding processes. For this review, we screened the current literature for a combination of online process analytical technology (PAT) and modeling techniques to ensure a controlled refolding process. Based on our research, we propose an integrated approach based on the idea that all aspects that cannot be monitored directly are estimated via digital twins and used in real-time for process control.

Key points
• Monitoring and a thorough understanding of refolding kinetics are essential for model-based control of refolding processes.
• The introduction of Quality by Design combining Process Analytical Technology and modeling ensures a robust platform for inclusion body refolding.
Clinical validity of second-generation tau PET tracers as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework
Authors: Bischof Gérard N , Dodich Alessandra , Boccardi Marina , van Eimeren Thilo , Festari Cristina , Barthel Henryk , Hansson Oskar , Nordberg Agneta , Ossenkoppele Rik , Sabri Osama , Giovanni B Frisoni G , Garibotto Valentina , Drzezga Alexander 
Published: February 2021

Abstract
Purpose
In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into the clinical context.

Methods
All available literature was systematically searched based on a set of search terms that related independently to analytic validity (phases 1–2), clinical validity (phase 3–4), and clinical utility (phase 5). The progress on each of the phases was determined based on scientific criteria applied for each phase and coded as fully, partially, preliminary achieved or not achieved at all.

Results
The validation of the second-generation tau PET tracers has successfully passed the analytical phase 1 of the strategic biomarker roadmap. Assay definition studies showed evidence on the superiority over first-generation tau PET tracers in terms of off-target binding. Studies have partially achieved the primary aim of the analytical validity stage (phase 2), and preliminary evidence has been provided for the assessment of covariates on PET signal retention. Studies investigating of the clinical validity in phases 3, 4, and 5 are still underway.

Conclusion
The current literature provides overall preliminary evidence on the establishment of the second-generation tau PET tracers into the clinical context, thereby successfully addressing some methodological issues from the tau PET tracer of the first generation. Nevertheless, bigger cohort studies, longitudinal follow-up, and examination of diverse disease population are still needed to gauge their clinical validity.
Baseline PET/CT imaging parameters for prediction of treatment outcome in Hodgkin and diffuse large B cell lymphoma: a systematic review
Authors: Frood R. , Burton C. , Tsoumpas C. , Frangi A. F. , Gleeson F. , Patel C. , Scarsbrook A. 
Published: February 2021

Abstract
Purpose
To systematically review the literature evaluating clinical utility of imaging metrics derived from baseline fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for prediction of progression-free (PFS) and overall survival (OS) in patients with classical Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL).

Methods
A search of MEDLINE/PubMed, Web of Science, Cochrane, Scopus and clinicaltrials.gov databases was undertaken for articles evaluating PET/CT imaging metrics as outcome predictors in HL and DLBCL. PRISMA guidelines were followed. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.

Results
Forty-one articles were included (31 DLBCL, 10 HL). Significant predictive ability was reported in 5/20 DLBCL studies assessing SUVmax (PFS: HR 0.13–7.35, OS: HR 0.83–11.23), 17/19 assessing metabolic tumour volume (MTV) (PFS: HR 2.09–11.20, OS: HR 2.40–10.32) and 10/13 assessing total lesion glycolysis (TLG) (PFS: HR 1.078–11.21, OS: HR 2.40–4.82). Significant predictive ability was reported in 1/4 HL studies assessing SUVmax (HR not reported), 6/8 assessing MTV (PFS: HR 1.2–10.71, OS: HR 1.00–13.20) and 2/3 assessing TLG (HR not reported). There are 7/41 studies assessing the use of radiomics (4 DLBCL, 2 HL); 5/41 studies had internal validation and 2/41 included external validation. All studies had overall moderate or high risk of bias.

Conclusion
Most studies are retrospective, underpowered, heterogenous in their methodology and lack external validation of described models. Further work in protocol harmonisation, automated segmentation techniques and optimum performance cut-off is required to develop robust methodologies amenable for clinical utility.
Prognostic value of coronary vascular dysfunction assessed by rubidium-82 PET/CT imaging in patients with resistant hypertension without overt coronary artery disease
Authors: Gaudieri Valeria , Mannarino Teresa , Zampella Emilia , Assante Roberta , D’Antonio Adriana , Nappi Carmela , Cantoni Valeria , Green Roberta , Petretta Mario , Arumugam Parthiban , Cuocolo Alberto , Acampa Wanda 
Published: February 2021

Abstract
Purpose
The identification of coronary vascular dysfunction may enhance risk stratification in patients with resistant hypertension (RH). We evaluated if impaired coronary vascular function, assessed by rubidium-82 (82Rb) positron emission tomography/computed tomography (PET/CT) imaging, is associated with increased cardiovascular risk in patients with hypertension without overt coronary artery disease (CAD).

Methods
We studied 517 hypertensive subjects, 26% with RH, without overt CAD, and with normal stress-rest myocardial perfusion imaging at 82Rb PET/CT. The outcome end points were cardiac death, nonfatal myocardial infarction, coronary revascularization, and admission for heart failure.

Results
Over a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (p < 0.05) and had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF), and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR (all p < 0.05) were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time.

Conclusion
The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension.
A New Preoperative Risk Score for Predicting Postoperative Complications in Elderly Patients Undergoing Hepatectomy
Authors: Tomita Koichi , Koganezawa Itsuki , Nakagawa Masashi , Ochiai Shigeto , Gunji Takahiro , Yokozuka Kei , Ozawa Yosuke , Hikita Kosuke , Kobayashi Toshimichi , Sano Toru , Chiba Naokazu , Kawachi Shigeyuki 
Published: February 2021

AbstractBackgroundPostoperative complications are not rare in the elderly population after hepatectomy. However, predicting postoperative risk in elderly patients undergoing hepatectomy is not easy. We aimed to develop a new preoperative evaluation method to predict postoperative complications in patients above 65 years of age using biological impedance analysis (BIA).MethodsClinical data of 59 consecutive patients (aged 65 years or older) who underwent hepatectomy at our institution between 2017 and 2020 were retrospectively analyzed. Risk factors for postoperative complications (Clavien‐Dindo ≥ III) were evaluated using multivariate regression analysis. Additionally, a new preoperative risk score was developed for predicting postoperative complications.ResultsFifteen patients (25.4%) had postoperative complications, with biliary fistula being the most common complication. Abnormal skeletal muscle mass index from BIA and type of surgical procedure were found to be independent risk factors in the multivariate analysis. These two variables and preoperative serum albumin levels were used for developing the risk score. The postoperative complication rate was 0.0% with a risk score of ≤ 1 and 57.1% with a risk score of ≥ 4. The area under the receiver operating characteristic curve of the risk score was 0.810 (p = 0.001), which was better than that of other known surgical risk indexes.ConclusionDecreased skeletal muscle and the type of surgical procedure for hepatectomy were independent risk factors for postoperative complications after elective hepatectomy in elderly patients. The new preoperative risk score is simple, easy to perform, and will help in the detection of high‐risk elderly patients undergoing elective hepatectomy.