bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised Machine Learning‐Based Clustering of Nanosized Fluorescent Extracellular Vesicles
Authors: Kuypers Sören , Smisdom Nick , Pintelon Isabel , Timmermans Jean‐Pierre , Ameloot Marcel , Michiels Luc , Hendrix Jelle , Hosseinkhani Baharak 
Published: January 2021

AbstractExtracellular vesicles (EV) are biological nanoparticles that play an important role in cell‐to‐cell communication. The phenotypic profile of EV populations is a promising reporter of disease, with direct clinical diagnostic relevance. Yet, robust methods for quantifying the biomarker content of EV have been critically lacking, and require a single‐particle approach due to their inherent heterogeneous nature. Here, multicolor single‐molecule burst analysis microscopy is used to detect multiple biomarkers present on single EV. The authors classify the recorded signals and apply the machine learning‐based t‐distributed stochastic neighbor embedding algorithm to cluster the resulting multidimensional data. As a proof of principle, the authors use the method to assess both the purity and the inflammatory status of EV, and compare cell culture and plasma‐derived EV isolated via different purification methods. This methodology is then applied to identify intercellular adhesion molecule‐1 specific EV subgroups released by inflamed endothelial cells, and to prove that apolipoprotein‐a1 is an excellent marker to identify the typical lipoprotein contamination in plasma. This methodology can be widely applied on standard confocal microscopes, thereby allowing both standardized quality assessment of patient plasma EV preparations, and diagnostic profiling of multiple EV biomarkers in health and disease.
Metabolic and immune dysfunction of glia in neurodegenerative disorders: Focus on iPSC models
Authors: Rõlova Taisia , Lehtonen Šárka , Goldsteins Gundars , Kettunen Pinja , Koistinaho Jari 
Published: January 2021

Abstract
The research on neurodegenerative disorders has long focused on neuronal pathology and used transgenic mice as disease models. However, our understanding of the chronic neurodegenerative process in the human brain is still very limited. It is increasingly recognized that neuronal loss is not caused solely by intrinsic degenerative processes but rather via impaired interactions with surrounding glia and other brain cells. Dysfunctional astrocytes do not provide sufficient nutrients and antioxidants to the neurons, while dysfunctional microglia cannot efficiently clear pathogens and cell debris from extracellular space, thus resulting in chronic inflammatory processes in the brain. Importantly, human glia, especially the astrocytes, differ significantly in morphology and function from their mouse counterparts, and therefore more human-based disease models are needed. Recent advances in stem cell technology make it possible to reprogram human patients' somatic cells to induced pluripotent stem cells (iPSC) and differentiate them further into patient-specific glia and neurons, thus providing a virtually unlimited source of human brain cells. This review summarizes the recent studies using iPSC-derived glial models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis and discusses the applicability of these models to drug testing. This line of research has shown that targeting glial metabolism can improve the survival and function of cocultured neurons and thus provide a basis for future neuroprotective treatments.
Fetal neurosonography detects differences in cortical development and corpus callosum in late‐onset small fetuses
Authors: Paules C. , Miranda J. , Policiano C. , Crovetto F. , Youssef L. , Hahner N. , Nakaki A. , Crispi F. , Gratacós E. , Eixarch E. 
Published: January 2021

ABSTRACTObjectiveTo explore whether neurosonography can detect differences in cortical development and corpus callosal length in late‐onset small fetuses subclassified into small‐for‐gestational age (SGA) or growth restricted (FGR).MethodsThis was a prospective cohort study in singleton pregnancies, including normally grown fetuses (birth weight between the 10th and 90th centiles) and late‐onset small fetuses (estimated fetal weight < 10th centile, diagnosed after 32 weeks of gestation and confirmed by birth weight < 10th centile). Small fetuses were subclassified into SGA (birth weight between the 3rd and 9th centiles and normal fetoplacental Doppler) and FGR (birth weight < 3rd centile and/or abnormal cerebroplacental ratio and/or abnormal uterine artery Doppler). Neurosonography was performed at 33 ± 1 weeks of gestation to assess the depth of the insula, Sylvian fissure and parieto‐occipital sulcus in the axial views and corpus callosal length in the midsagittal plane. Measurements were performed offline using Alma Workstation software and were adjusted by biparietal diameter or cephalic index. Linear regression analysis was used to assess the association between the neurosonographic variables and study group, adjusting for confounding factors such as gender, gestational age at neurosonography, nulliparity and pre‐eclampsia.ResultsIn total, 318 fetuses were included, of which 97 were normally grown and 221 were late‐onset small fetuses that were further subdivided into late‐onset SGA (n = 67) or late‐onset FGR (n = 154). Compared to controls, both SGA and FGR cases showed significantly increased insular depth adjusted for biparietal diameter (median (interquartile range), controls 0.329 (0.312–0.342) vs SGA 0.339 (0.321–0.347) vs FGR 0.336 (0.325–0.349); P = 0.006). A linear tendency to reduced Sylvian fissure depth adjusted for biparietal diameter was also observed across the study groups (mean ± SD, controls 0.148 ± 0.021 vs SGA 0.142 ± 0.025 vs FGR 0.139 ± 0.022; P = 0.003). However, differences were significant only between the FGR and control groups. Corpus callosal length adjusted for cephalic index was significantly reduced in FGR cases compared with both controls and SGA cases, while there was no difference between SGA cases and controls (median (interquartile range), controls 0.500 (0.478–0.531) vs SGA 0.502 (0.487–0.526) vs FGR 0.475 (0.447–0.508); P = 0.005). No differences were found in parieto‐occipital sulcus depth between the three study groups.ConclusionNeurosonography seems to be a sensitive tool to detect subtle structural differences in brain development in late‐onset small fetuses. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Measuring nitrate leaching across the critical zone at the field to farm scale
Authors: Gurevich Hanna , Baram Shahar , Harter Thomas 
Published: January 2021

AbstractResearch is lacking monitoring beyond the root zone for programmatic or regulatory assessment and for onsite monitoring of field‐ or farm scale agricultural nitrate leaching to groundwater. Here, we investigate the relationship between measurements of N at the sediment core scale, the groundwater monitoring well scale, and the field or farm management scale. Importantly, we monitor across the vertical continuum of root zone (RZ, to 3 m), deep vadose zone (DVZ, to 7 m), and upper saturated zone (SZ, to 14 m) in a highly heterogeneous alluvial sediment system, common to many agricultural groundwater basins. Twenty 14‐m‐deep sediment cores collected across a 56‐ha commercial almond orchard were characterized for texture, water content, nitrate, and ammonium. Groundwater nitrate samples (GW) were also obtained from monitoring wells installed and screened across the SZ at the coring sites. Measured parameters were found highly variable at the 0.05‐m core sample scale. Monitoring well nitrate concentrations also span over a half order of magnitude despite the uniform agronomic practices across the orchard. Laterally aggregated, orchard‐scale parameter means exhibited significant vertical trends and differed in variability between RZ, DVZ, and SZ. Within the SZ, coarse texture facies nitrate concentrations were most closely correlated to GW nitrate, confirming the significance of preferential flow paths within the SZ. The data also indicate significant correlation between DVZ and GW nitrate concentrations. Our findings have important implications to developing appropriate onsite monitoring tools of field‐ or farm‐scale N emissions to groundwater.
Postzygotic reproductive isolation among three Saccharomyces yeast species
Authors: Toyomura Kousuke , Hisatomi Taisuke 
Published: January 2021

AbstractWe have previously isolated heterothallic haploid strains from original homothallic diploids of two yeast species in the family Saccharomycetaceae. In this study, heterothallic haploid strains were isolated from an original homothallic diploid of Saccharomyces kudriavzevii type strain, followed by investigation of sexual interactions among these yeast strains, in addition to S. cerevisiae laboratory strains. It has been shown that prezygotic reproductive isolation was observed between Kazachstania naganishii and S. cerevisiae with α‐factor mating pheromones representing crossaction with each other beyond the genus boundary. Using heterothallic strains, postzygotic reproductive isolation system was shown to reside in the genus Saccharomyces by mass mating and cell–cell contact experiments. In mass mating experiments, crossaction of α‐factor and a‐factor mating pheromones and sexual agglutination effectively occurred beyond species boundaries among S. kudriavzevii, S. paradoxus, and S. cerevisiae. When the fates of cell–cell pairs from these Saccharomyces yeast species were systematically chased one by one, interspecific F1 hybrids were effectively produced, while sporulations were partially prohibited, with spore germination perfectly blocked in the hybrids. These results indicated that postzygotic reproductive isolation definitively resides among these Saccharomyces yeast species and that disorder of chromosome organization had to some extent occurred in interspecific F1 hybrids.
Crystal Structure and Physical Properties of the Lanthanum Chalcoantimonate TlLa2Sb3Se9
Authors: Menezes Luke T. , Richter‐Bisson Zoltan W. , Assoud Abdeljalil , Kuropatwa Bryan A. , Kleinke Holger 
Published: January 2021

AbstractThe new lanthanum chalcoantimonate TlLa2Sb3Se9 has been synthesized and its crystal structure determined. TlLa2Sb3Se9 crystallizes in an ordered variant of the KLa2Sb3S9 type, space group P212121 with the lattice parameters a=4.2621(2) Å, b=15.155(5) Å, c=25.505(9) Å. The band gap of TlLa2Sb3Se9 was calculated to be 0.47 eV, and experimentally determined to be 0.68 eV. Its thermoelectric properties were optimized via doping with Ca2+; samples with the compositions TlLa2‐xCaxSb3Se9 (x=0.01, 0.03, 0.05) were synthesized. Despite ultralow thermal conductivity, the maximum thermoelectric figure‐of‐merit of the undoped sample was only zT=0.031 at 623 K, which was increased to 0.078 for the sample with the nominal composition of TlLa1.95Ca0.05Sb3Se9. These low values are a consequence of the uncompetitively low electrical conductivity.
Hydrazone‐Based Ligand with Pyrrolidine Donor and Its Molybdenum(VI) Complex: Synthesis, Structure, and Reactivity
Authors: Nica Simona , Buchholz Axel , Görls Helmar , Plass Winfried 
Published: January 2021

AbstractThe Schiff‐base condensation of salicylaldehyde and 4‐aminobutanehydrazide hydrochloride leads to the hydrazone‐based ligand H2salhyab containing an amino side chain. The reaction of H2salhyab ⋅ HCl with bis(acetylacetonato)dioxidomolybdenum leads to the formation of [MoO2(salhycab)(MeOH)] (H2salhycab=2‐((pyrrolidine‐2‐ylidenehydrazineylidene)methyl)phenol), whereby the amino side chain reacted with the hydrazide carbonyl group to form a cyclic amidine with a pyrrolidine ring leading a new type of tridentate hydrazone ligand with [NNO] donor set. X‐ray crystallography revealed the additional coordination of a methanol molecule at the molybdenum(VI) center which leads to the formation of hydrogen‐bonded dimers of the neutral complex in the crystal structure. The complex [MoO2(salhycab)(MeOH)] was found to be an efficient catalyst for the peroxidic oxidation of phenyl methyl sulfide.
BMI and BMI change following incident type 2 diabetes and risk of microvascular and macrovascular complications: the EPIC-Potsdam study
Authors: Polemiti Elli , Baudry Julia , Kuxhaus Olga , Jäger Susanne , Bergmann Manuela M. , Weikert Cornelia , Schulze Matthias B. 
Published: January 2021

Abstract
Aims/hypothesis
Studies suggest decreased mortality risk among people who are overweight or obese compared with individuals with normal weight in type 2 diabetes (obesity paradox). However, the relationship between body weight or weight change and microvascular vs macrovascular complications of type 2 diabetes remains unresolved. We investigated the association between BMI and BMI change with long-term risk of microvascular and macrovascular complications in type 2 diabetes in a prospective cohort study.

Methods
We studied participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, who were free of cancer, cardiovascular disease and microvascular disease at diagnosis (n = 1083). Pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI were evaluated in multivariable-adjusted Cox models.

Results
There were 85 macrovascular (myocardial infarction and stroke) and 347 microvascular events (kidney disease, neuropathy and retinopathy) over a median follow-up of 10.8 years. Median pre-diagnosis BMI was 29.9 kg/m2 (IQR 27.4–33.2), and the median relative annual BMI change was −0.4% (IQR −2.1 to 0.9). Higher pre-diagnosis BMI was positively associated with total microvascular complications (multivariable-adjusted HR per 5 kg/m2 [95% CI]: 1.21 [1.07, 1.36], kidney disease 1.39 [1.21, 1.60] and neuropathy 1.12 [0.96, 1.31]) but not with macrovascular complications (HR 1.05 [95% CI 0.81, 1.36]). Analyses according to BMI categories corroborated these findings. Effect modification was not evident by sex, smoking status or age groups. In analyses according to BMI change categories, BMI loss of more than 1% indicated a decreased risk of total microvascular complications (HR 0.62 [95% CI 0.47, 0.80]), kidney disease (HR 0.57 [95% CI 0.40, 0.81]) and neuropathy (HR 0.73 [95% CI 0.52, 1.03]), compared with participants with a stable BMI; no clear association was observed for macrovascular complications (HR 1.04 [95% CI 0.62, 1.74]). The associations between BMI gain compared with stable BMI and diabetes-related vascular complications were less apparent. Associations were consistent across strata of sex, age, pre-diagnosis BMI or medication but appeared to be stronger among never-smokers compared with current or former smokers.

Conclusions/interpretation
Among people with incident type 2 diabetes, pre-diagnosis BMI was positively associated with microvascular complications, while a reduced risk was observed with weight loss when compared with stable weight. The relationships with macrovascular disease were less clear.

Graphical abstract
Association between newly initiated thiazide diuretics and hospitalization due to hyponatremia
Authors: Mannheimer Buster , Bergh Cecilia Fahlén , Falhammar Henrik , Calissendorff Jan , Skov Jakob , Lindh Jonatan D. 
Published: January 2021

Abstract
Purpose
Thiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden.

Methods
Population-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides.

Results
Individuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28–89). The associations gradually declined reaching an aOR of 2.9 (2.7–3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia.

Conclusions
Thiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest.
Retinal venous pressure is decreased after anti-VEGF therapy in patients with retinal vein occlusion–related macular edema
Authors: Kida Teruyo , Flammer Josef , Konieczka Katarzyna , Ikeda Tsunehiko 
Published: January 2021

Abstract
Purpose
The pathomechanism leading to retinal vein occlusion (RVO) is unclear. Mechanical compression, thrombosis, and functional contractions of veins are discussed as the reasons for the increased resistance of venous outflow. We evaluated changes in the retinal venous pressure (RVP) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent to determine the effect on RVO-related macular edema.

Methods
Twenty-six patients with RVO-related macular edema (16 branch RVOs [BRVOs] and 10 central RVOs [CRVOs], age 72.5 ± 8.8 years) who visited our hospital were included in this prospective study. Visual acuity (VA), intraocular pressure (IOP), central retinal thickness (CRT) determined by macular optical coherence tomography, and RVP measured using an ophthalmodynamometer were obtained before intravitreal injection of ranibizumab (IVR) and 1 month later.

Results
Comparison of the BRVOs and CRVOs showed that VA was significantly improved by a single injection in BRVOs (P < 0.0001; P = 0.1087 for CRVOs), but CRT and RVP were significantly decreased without significant difference in IOP after the treatment in both groups (P < 0.0001).

Conclusion
The anti-VEGF treatment resulted in a significant decrease in the RVP, but the RVP remained significantly higher than the IOP. An increased RVP plays a decisive role in the formation of macula edema, and reducing it is desirable.
Rigid commutators and a normalizer chain
Authors: Aragona Riccardo , Civino Roberto , Gavioli Norberto , Scoppola Carlo Maria 
Published: January 2021

AbstractThe notion of rigid commutators is introduced to determine the sequence of the logarithms of the indices of a certain normalizer chain in the Sylow 2-subgroup of the symmetric group on$$2^n$$2nletters. The terms of this sequence are proved to be those of the partial sums of the partitions of an integer into at least two distinct parts, that relates to a famous Euler’s partition theorem.
Model-driven development platform selection: four industry case studies
Authors: Farshidi Siamak , Jansen Slinger , Fortuin Sven 
Published: January 2021

AbstractModel-driven development platforms shift the focus of software development activity from coding to modeling for enterprises. A significant number of such platforms are available in the market. Selecting the best fitting platform is challenging, as domain experts are not typically model-driven deployment platform experts and have limited time for acquiring the needed knowledge. We model the problem as a multi-criteria decision-making problem and capture knowledge systematically about the features and qualities of 30 alternative platforms. Through four industry case studies, we confirm that the model supports decision-makers with the selection problem by reducing the time and cost of the decision-making process and by providing a richer list of options than the enterprises considered initially. We show that having decision knowledge readily available supports decision-makers in making more rational, efficient, and effective decisions. The study’s theoretical contribution is the observation that the decision framework provides a reliable approach for creating decision models in software production.
FTIR Spectroscopy Detects Intermolecular β-Sheet Formation Above the High Temperature Tm for Two Monoclonal Antibodies
Authors: Baird Garrett , Farrell Chris , Cheung Jason , Semple Andrew , Blue Jeffery , Ahl Patrick L. 
Published: January 2021

Abstract
The temperature-dependent secondary structure of two monoclonal IgG antibodies, anti-IGF1R and anti-TSLP, were examined by transmission mode Fourier Transform Infrared (FTIR) spectroscopy. Anti-IGF1R and anti-TSLP are IgG monoclonal antibodies (mAbs) directed against human Insulin-like Growth Factor 1 Receptor for anti-tumor activity and Thymic Stromal Lymphopoietin cytokine for anti-asthma activity, respectively. Differential scanning calorimetry (DSC) clearly indicates both antibodies in their base formulations have a lower temperature protein conformational change near 70 °C (Tm1) and a higher temperature protein conformational change near 85 °C (Tm2). Thermal scanning dynamic light scatting (TS-DLS) indicates a significant particle size increase for both antibodies near Tm2 suggesting a high level of protein aggregation. The nature of these protein conformational changes associated with increasing the formulation temperature and decreasing sucrose concentration were identified by transmission mode FTIR and second derivative FTIR spectroscopy of temperature controlled aqueous solutions of both monoclonal antibodies. The transition from intra-molecular β sheets to inter-molecular β sheets was clearly captured for both monoclonal antibodies using FTIR spectroscopy. Finally, FTIR Spectroscopy was able to show the impact of a common excipient such as sucrose on the stability of each monoclonal antibody, further demonstrating the usefulness of FTIR spectroscopy for studying protein aggregation and formulation effects.
Heterologous Expression of the Barley (Hordeum vulgare L.) Xantha-f, -g and -h Genes that Encode Magnesium Chelatase Subunits
Authors: Mahdi Rabab , Stuart David , Hansson Mats , Youssef Helmy M. 
Published: January 2021

Abstract
Biosynthesis of chlorophyll involves several enzymatic reactions of which many are shared with the heme biosynthesis pathway. Magnesium chelatase is the first specific enzyme in the chlorophyll pathway. It catalyzes the formation of Mg-protoporphyrin IX from the insertion of Mg2+ into protoporphyrin IX. The enzyme consists of three subunits encoded by three genes. The three genes are named Xantha-h, Xantha-g and Xantha-f in barley (Hordeum vulgare L.). The products of the genes have a molecular weight of 38, 78 and 148 kDa, respectively, as mature proteins in the chloroplast. Most studies on magnesium chelatase enzymes have been performed using recombinant proteins of Rhodobacter capsulatus, Synechocystis sp. PCC6803 and Thermosynechococcus elongatus, which are photosynthetic bacteria. In the present study we established a recombinant expression system for barley magnesium chelatase with the long-term goal to obtain structural information of this enigmatic enzyme complex from a higher plant. The genes Xantha-h, -g and -f were cloned in plasmid pET15b, which allowed the production of the three subunits as His-tagged proteins in Escherichia coli BL21(DE3)pLysS. The purified subunits stimulated magnesium chelatase activity of barley plastid extracts and produced activity in assays with only recombinant proteins. In preparation for future structural analyses of the barley magnesium chelatase, stability tests were performed on the subunits and activity assays were screened to find an optimal buffer system and pH.