bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha‐Synuclein Dopaminylation Presented in Plasma of Both Healthy Subjects and Parkinson's Disease Patients
Authors: Zhao Huiyuan , Huang Shuai , Palanisamy Sivakumar , Wang Cui , Rainer Gregor , Zhang Xiaozhe 
Published: June 2020

PurposeAlpha‐synuclein (α‐syn) dopaminylation can lead to the death of dopaminergic neurons in the brain and is a risk factor of Parkinson's disease (PD). This study aims to examine whether such a posttranslational modification (PTM) is presented in human blood plasma.Experimental DesignIn vitro reaction simulation between α‐syn and dopamine (DA) is conducted to study the biochemical mechanism. Then α‐syn from human blood plasma samples is detected by using immunoprecipitation‐mass spectrometry (IP‐MS). Lastly the levels of endogenous α‐syn and α‐syn dopaminylation in 88 blood plasma samples from patients with PD, major depressive disorder (MDD), and healthy control (HC) are compared.ResultsDA modifies α‐syn with the addition of dopamine‐quinone (DAQ) into lysine sites of α‐syn in vitro and the addition of DAQ and 3,4‐dihydroxyphenylacetaldehyde (DOPAL) in plasma samples. The unmodified α‐syn between the PD and HC groups showed similar levels. The levels of two peptides, one with lysine 34 (34K) DAQ modification and the other with lysine 23 (23K) ubiquitination, are significantly higher in PD and MDD compared with HC.Conclusions and Clinical RelevanceThus, α‐syn dopaminylation is measurable and might be used to indicatethe presence and progression of neurological disorders.
Conformational changes in a Vernier zone region: Implications for antibody dual specificity
Authors: Arslan Merve , Karadag Dilara , Kalyoncu Sibel 
Published: June 2020

AbstractUnderstanding the determinants of antibody specificity is one of the challenging tasks in antibody development. Monospecific antibodies are still dominant in approved antibody therapeutics but there is a significant body of work to show that multispecific antibodies can increase the overall therapeutic effect. Dual‐specific or “Two‐in‐One” antibodies can bind to two different antigens separately with the same antigen‐binding site as opposed to bispecifics, which simultaneously bind to two different antigens through separate antigen‐binding units. These nonstandard dual‐specific antibodies were recently shown to be promising for new antibody‐based therapeutics. Here, we physicochemically and structurally analyzed six different antibodies of which two are monospecific and four are dual‐specific antibodies derived from monospecific templates to gain insight about dual‐specificity determinants. These dual‐specific antibodies can target both human epidermal growth factor receptor 2 and vascular endothelial growth factor at different binding affinities. We showed that a particular region of clustered Vernier zone residues might play key roles in gaining dual specificity. While there are minimal intramolecular interactions between a certain Vernier zone region, namely LV4 and LCDR1 of monospecific template, there is a significant structural change and consequently close contact formation between LV4‐LCDR1 loops of derived dual‐specific antibodies. Although Vernier zone residues were previously shown to be important for humanization applications, they are mostly underestimated in the literature. Here, we also aim to resurrect Vernier zone residues for antibody engineering efforts.
Relative fitness and stability of resistance in a near‐isogenic strain of indoxacarb resistant Helicoverpa armigera (Lepidoptera: Noctuidae)
Authors: Bird Lisa J , Drynan Linda J , Walker Paul W 
Published: June 2020

AbstractBACKGROUNDA strain of Helicoverpa armigera with 171‐fold resistance to indoxacarb was introgressed with a susceptible strain by serial backcrossing and reselection with indoxacarb resulting in the creation of the near‐isogenic GY7‐39BC4 strain. Fitness was compared on artificial diet under diapause and non‐diapause conditions in resistant, susceptible and F1 progeny from a reciprocal backcross of the two strains using life history trait analyses. Selection experiments were used to determine stability of resistance.RESULTSThere were no significant differences between strains in survival, female fertility or realized fecundity. A comparison of the intrinsic rate of population increase showed similar relative fitness between strains. Lower male fertility and male longevity in the resistant strain and one of the F1 strains compared with the susceptible strain suggests small non‐recessive costs may be associated with male reproductive capacity in individuals with indoxacarb resistance alleles. However, there was no significant decline in resistance in the GY7‐39 strain when reared in the absence of insecticide for five generations. Following an artificially induced diapause, survival was reduced by 52% and pupal weights were significantly lower in the resistant strain compared with the susceptible strain.CONCLUSIONSThese results suggest indoxacarb resistance does not confer a major fitness cost under standard laboratory conditions. However, a survival cost associated with overwintering highlights the imperative for adoption of management strategies in northern regions of Australia where a winter diapause does not occur. © 2020 Society of Chemical Industry
Use of median‐based estimator to construct Phase II exponential chart
Authors: Kumar Nirpeksh , Jaiswal Sonam 
Published: June 2020

AbstractThe Shewhart‐type exponential control chart is a popular and extensively used among all time‐between‐events control charts for its simplicity. When the parameter is unknown, Phase II control limits are constructed, and the success of its implementation depends to an extent on the estimated value of the parameter, obtained from Phase I dataset. However, when the Phase I data are contaminated with spurious observations/outliers, the performance of the chart is suspected to deviate from what is normally expected. Traditionally, maximum likelihood estimator (MLE) and minimum variance unbiased estimator (MVUE) are used to estimate the unknown process parameter. Both of estimators are the functions of sample mean. In this paper, the median‐based estimator (MBE) that is a function of sample median is used to construct Phase II control limits. Moreover, performance of the proposed chart is examined when Phase I sample consists of contaminated observations/outliers. It is found that the proposed chart outperforms the existing charts whether the sample is contaminated or not.
Isotopic and elemental corroborates for wild bearded capuchin (Sapajus libidinosus) omnivorous dietary adaptation at Fazenda Boa Vista, Brazil
Authors: Reitsema Laurie J. , Jones Caroline E. , Gilbert Hannah R. , Fragaszy Dorothy , Izar Patrícia 
Published: June 2020

RationaleThis study analyzes variability in the diets of wild bearded capuchin monkeys, Sapajus libidinosus, by analyzing stable carbon (δ13C) and nitrogen (δ15N) isotope ratios and elemental concentrations (%C and %N) of fecal samples and food items. Developing isotopic and elemental correlates for diets of habituated subjects is a necessary step towards applying similar methods to interpret diets of unhabituated or cryptic subjects.MethodsFecal samples from wild capuchins and their foods were collected at Fazenda Boa Vista, Brazil. Fecal samples from laboratory‐housed Sapajus spp. and their foods were analyzed to establish diet‐feces offsets for δ13C, δ15N, %C, and %N. Samples were dried, powdered, and measured for isotopic and elemental values. A Bayesian mixing model commutes isotopic and elemental data from wild capuchins into likely proportions of different food categories.ResultsThe captive study shows small diet‐feces spaces for Sapajus spp. of −0.8 ± 0.7‰ for δ13C, −0.2 ± 0.4‰ for δ15N, −6.1 ± 1.7% for %C, and −1.0 ± 0.6% for %N. The wild study shows omnivorous diets based on C3, C4, and CAM plants, and fauna. Subject diets are highly varied within and between days. Fecal data show age‐related differences in diet and crop‐raiding. There is no consistent isotopic or elemental difference between mothers and infants.ConclusionsFecal stable isotope and elemental evidence employed in a Bayesian mixing model reflects the highly varied diets of capuchin monkeys in an isotopically heterogeneous environment. The isotopic and elemental variability reported here will aid similar diet reconstructions among unhabituated subjects in the future, but precludes tracking weaning isotopically among capuchins in this environment.
Gas diffusion characteristics of agricultural soils from South Greenland
Authors: Weber Peter L. , de Jonge Lis Wollesen , Greve Mogens H. , Norgaard Trine , Moldrup Per 
Published: June 2020

AbstractThe Arctic is warming at twice the global average, which may impact agricultural production in Greenland. Therefore knowledge of the functional properties of Greenlandic soil resources is necessary. The relative soil gas diffusivity [the soil gas diffusion coefficient (Dp)–free‐air diffusion coefficient (Do) ratio] is the chief parameter controlling gas transport in soils. Predictions of Dp/Do are needed to estimate root zone aeration and terrestrial greenhouse gas fluxes. We used existing models to analyze the Dp/Do of soils from Greenlandic fields and a pore connectivity index (Cip) to infer their degree of structural development and identify the main parameters controlling Dp/Do. In total, 201 × 3 intact 100‐cm3 soil samples were sampled across six fields with clay and organic C contents of 0.016 to 0.089 and 0.016 to 0.105 kg kg−1, respectively. The Dp/Do was measured with the one‐chamber nonsteady‐state method at soil water potentials between –10 and –1,000 cm H2O. Accurate determination of total porosity (Φ) was ensured by calibrating a particle density model on 129 samples. The soils exhibited a less developed structure and highly tortuous pore networks, resulting in low Dp/Do as a function of air‐filled porosity (ε). Density‐corrected models with air saturation (ε/Φ) reduced the RMSE. Furthermore, Cip at –1,000 cm H2O soil water potential increased linearly with dry bulk density (ρb), suggesting that ρb is a key controller of Dp/Do, which is important for planning cultivation practices for Southern Greenlandic soils. Lastly, we found that an air saturation >35% is required for adequate soil aeration.
Current status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: Gleaning insights for possible use in COVID-19
Authors: Yen B. Linju , Yen Men-Luh , Wang Li-Tzu , Liu Ko-Jiunn , Sytwu Huey-Kang 
Published: June 2020

Abstract
The broad immunomodulatory properties of human mesenchymal stem cells (MSCs) have allowed for wide application in regenerative medicine as well as immune/inflammatory diseases, including unmatched allogeneic use. The novel coronavirus disease COVID-19 has unleashed a pandemic in record time accompanied by an alarming mortality rate mainly due to pulmonary injury and acute respiratory distress syndrome. Because there are no effective preventive or curative therapies currently, MSC therapy (MSCT) has emerged as a possible candidate despite the lack of preclinical data of MSCs for COVID-19. Interestingly, MSCT preclinical data specifically on immune/inflammatory disorders of the lungs were among the earliest to be reported in 2003, with the first clinical use of MSCT for graft-vs-host disease reported in 2004. Since these first reports, preclinical data showing beneficial effects of MSC immunomodulation have accumulated substantially, and as a consequence, over a third of MSCT clinical trials now target immune/inflammatory diseases. There is much preclinical evidence for MSCT in noninfectious—including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis—as well as infectious bacterial immune/inflammatory lung disorders, with data generally demonstrating therapeutic effects; however, for infectious viral pulmonary conditions, the preclinical evidence is more scarce with some inconsistent outcomes. In this article, we review the mechanistic evidence for clinical use of MSCs in pulmonary immune/inflammatory disorders, and survey the ongoing clinical trials—including for COVID-19—of MSCT for these diseases, with some perspectives and comment on MSCT for COVID-19.
Post‐embryonic development of Fritzolenellus suggests the ancestral morphology of the early developmental stages in Trilobita
Authors: Laibl Lukáš , Maletz Jörg , Olschewski Pascal 
Published: June 2020

AbstractTrilobite development has been intensively explored during the past decades, but information on ancestral character combinations in the early developmental stages of trilobites remains unknown. Trilobites of the superfamily Olenelloidea are one of the earliest diverging groups. Study of their development coupled with the development of other early diverging trilobite groups can provide information on the ancestral morphology of trilobite early stages. Herein we describe numerous well‐preserved specimens of the olenelloid trilobite Fritzolenellus lapworthi. The earliest stages have circular cephala bearing intergenal spines and lacking genal spines. During subsequent development, morphological changes involve the modification of the cephalic shape from circular to semicircular, expansion of the frontal glabellar lobe, gradual shortening of intergenal spines and origin and prolongation of genal spines. Trunk development of Fritzolenellus suggests that macropleurae and macrospine development are two independent processes and that the origin of the opisthotrunk is linked with the onset of phase 5 of cephalic development. The morphology of the early developmental stages of Fritzolenellus and of some related taxa differs in many aspects from the morphology of equivalent stages of some other members of Olenelloidea. Consequently, two basic morphotypes are recognized during the early development of Olenelloidea: the Fritzolenellus and the Olenellus morphotypes. Comparison with Fallotaspidoidea and Redlichiina indicates that early developmental stages of these taxa share character combinations that are typical for the Fritzolenellus morphotype. Such a comparison suggests that characters defining the Fritzolenellus morphotype are ancestral for Trilobita. The Olenellus morphotype is probably a derived condition within Olenelloidea and might be related to predator deterrence.
Cover Image, Volume 12, Issue 4
Authors: Zezina Ekaterina , Sercan‐Alp Oezen , Herrmann Matthias , Biesemann Nadine 
Published: June 2020

The cover image is based on the Advanced Review Glucose transporter 1 in rheumatoid arthritis and autoimmunity by Ekaterina Zezina et al., https://doi.org/10.1002/wsbm.1483.image
HIF-1α is involved in blood–brain barrier dysfunction and paracellular migration of bacteria in pneumococcal meningitis
Authors: Devraj Gayatri , Guérit Sylvaine , Seele Jana , Spitzer Daniel , Macas Jadranka , Khel Maryam I. , Heidemann Roxana , Braczynski Anne K. , Ballhorn Wibke , Günther Stefan , Ogunshola Omolara O. , Mittelbronn Michel , Ködel Uwe , Monoranu Camelia M. , Plate Karl H. , Hammerschmidt Sven , Nau Roland , Devraj Kavi , Kempf Volkhard A. J. 
Published: June 2020

AbstractBacterial meningitis is a deadly disease most commonly caused by Streptococcus pneumoniae, leading to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer of S. pneumoniae from blood to the brain across the blood–cerebrospinal fluid barrier or the blood–brain barrier (BBB). The underlying mechanisms are still poorly understood. Current treatment strategies include adjuvant dexamethasone for inflammation and cerebral edema, followed by antibiotics. The success of dexamethasone is however inconclusive, necessitating new therapies for controlling edema, the primary reason for neurological complications. Since we have previously shown a general activation of hypoxia inducible factor (HIF-1α) in bacterial infections, we hypothesized that HIF-1α, via induction of vascular endothelial growth factor (VEGF) is involved in transmigration of pathogens across the BBB. In human, murine meningitis brain samples, HIF-1α activation was observed by immunohistochemistry. S. pneumoniae infection in brain endothelial cells (EC) resulted in in vitro upregulation of HIF-1α/VEGF (Western blotting/qRT-PCR) associated with increased paracellular permeability (fluorometry, impedance measurements). This was supported by bacterial localization at cell–cell junctions in vitro and in vivo in brain ECs from mouse and humans (confocal, super-resolution, electron microscopy, live-cell imaging). Hematogenously infected mice showed increased permeability, S. pneumoniae deposition in the brain, along with upregulation of genes in the HIF-1α/VEGF pathway (RNA sequencing of brain microvessels). Inhibition of HIF-1α with echinomycin, siRNA in bEnd5 cells or using primary brain ECs from HIF-1α knock-out mice revealed reduced endothelial permeability and transmigration of S. pneumoniae. Therapeutic rescue using the HIF-1α inhibitor echinomycin resulted in increased survival and improvement of BBB function in S. pneumoniae-infected mice. We thus demonstrate paracellular migration of bacteria across BBB and a critical role for HIF-1α/VEGF therein and hence propose targeting this pathway to prevent BBB dysfunction and ensuing brain damage in infections.
Reversed shoulder arthroplasty leads to significant histological changes of the deltoid muscle: a prospective intervention trial
Authors: Koch Matthias , Schmidt Christian , Kerschbaum Maximilian , Winkler Tobias , Pfeifer Christian G. , Greiner Stefan 
Published: June 2020

AbstractIntroductionReverse shoulder arthroplasty (RSA) shows promising short- and mid-term results in cuff tear arthropathy. However, functional impairments are described in long-term findings. Micromorphological changes in the periarticular musculature could be in part responsible for this, but have not yet been analysed. Thus, histological changes of the deltoid muscle and their association to the functional outcome were evaluated in this study.Material and methodsA total of 15 patients treated with RSA were included in this prospective study. Functional outcome was assessed using the Constant Score (CS) and the DASH (disabilities of the arm, shoulder and hand) Score before RSA and after a mean follow-up of 12 months. Deltoid muscle biopsies were harvested intraoperatively and 12 months postoperatively. Mean deltoid muscle fibre area (MMFA) was calculated histologically after haematoxylin–eosin staining.ResultsPostoperative shoulder function significantly improved within 12 months (CS: Δ 37.4 ± 22.6,p = 0.001; DASH: Δ 27.1 ± 29.1,p = 0.006). The MMFA significantly decreased (p = 0.02), comparing the results from the intraoperative biopsy (MMFA: 8435.8 µm2, SD ± 5995.9 µm2) to the 12 months biopsy (MMFA: 5792. µm2, SD ± 3223.6 µm2). No correlation could be found between the functional score results and MMFA.ConclusionSigns of deltoid muscle changes in terms of a reduced MMFA can be detected 1 year after RSA and thus already a long time before long-term functional impairments become apparent. Further studies with larger patient series and longer follow-up periods as well as extended histological assessments and simultaneous radiological examinations are required.
Towards eHealth to support the health journey of headache patients: a scoping review
Authors: van de Graaf Daniëlle L. , Schoonman Guus G. , Habibović Mirela , Pauws Steffen C. 
Published: June 2020

AbstractObjectiveThe aim of this study is to (1) review the digital health tools that have been used in headache studies, and (2) discuss the effectivity and reliability of these tools.BackgroundMany headache patients travel a long and troublesome journey from first symptoms until a meaningful care plan. eHealth, mHealth, and digital therapeutic modalities have been advocated as the way forward to improve patient care.MethodOnline databases PubMed, Cinahl, and PsycINFO were searched using a predefined search query. A data extraction form was used to gather relevant data elements from the selected papers.ResultsA total of 39 studies were selected. The studies included 94,127 participants. The majority of studies focused on diaries (N = 27 out of 39). Digital (cognitive) behavioral therapy were also quite common (N = 7 out of 39). Other digital health tool categories were tele-consultations, telemonitoring and patient portals.ConclusionMany digital health tools for headache patients regarding diaries and behavioral/therapeutical treatment are described in scientific research with limited information on effectivity and reliability. Scientific knowledge with regard to other categories such as tele-consultations, patient portals, telemonitoring including medication adherence, online information resources, wearable, symptom checkers, digital peer support is still scarce or missing.
Count outcome meta-analysis for comparing treatments by fusing mixed data sources: comparing interventions using across report information
Authors: Böhning Dankmar , Sangnawakij Patarawan 
Published: June 2020

AbstractAssessing interventions applied to target populations is a matter of prime interest. Studies are usually undertaken to see whether an alternative intervention is superior (or at least equivalent) to a comparable standard intervention. This is typically achieved by comparing alternative and standard intervention within a given study, and the developed meta-analytic methodology is building on this assumption. Very little work has been delivered when studies only report results on one of the interventions only, but not on both. This is the situation we consider here, and it is motivated by study reports on two surgeries for treatment of asymptomatic antenatally diagnosed congenital lung malformations in young children. Reports are often only available for one of the two, and restricting analysis on those with results on both surgeries will restrict data to 33% of the potential sources. We show in this paper how data sources can be fused and under which condition this fusion will provide valid results. Application to the case study shows the potential gain of the suggested approach in reaching a more conclusive analysis. We argue that studies should best allow within-study comparison, but if only one intervention information is available (for example, as the required surgery expertise for the comparative intervention is not deliverable at the respective site), harnessing one-group information can provide additional insights.
Longitudinal patterns of fish assemblages in European boreal streams
Authors: Sutela Tapio , Vehanen Teppo , Jounela Pekka 
Published: June 2020

AbstractFish assemblages are known to change from headwaters to river outlets. Still, our knowledge of this change is often approximate or sporadic. In this study, we quantified the average longitudinal change from a large electrofishing data set of boreal streams in Northern Europe. The average species richness increased from headwaters to medium-sized rivers but levelled off when reaching large rivers. Existence of some headwater specialist fish species, e.g. brook trout (Salvelinus fontinalis), was interpreted to support the fish zonation concept over the concept of accumulative addition of species downstream. The traditional fish zonation concept developed in Western Europe suggests four zones from headwaters to river outlets, the trout zone, the grayling zone, the barbel zone and the bream zone. Of these, only the trout zone was clearly present with a high dominance in the headwaters of the streams studied. For the North European boreal streams, we suggest a zonation concept with three dominating fish species from headwaters downstream, brown trout (Salmo trutta), bullhead (Cottus gobio) and Atlantic salmon (Salmo salar). Discovered longitudinal shifts in fish guild compositions offered an opportunity for an ecological interpretation of the data and a promising basis for bioassessment.