bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase
Authors: van Rumund Anouke , Pavelka Lukas , Esselink Rianne A. J. , Geurtz Ben P. M. , Wevers Ron A. , Mollenhauer Brit , Krüger Rejko , Bloem Bastiaan R. , Verbeek Marcel M. 
Published: March 2021

AbstractPeripheral decarboxylase inhibitors (PDIs) prevent conversion of levodopa to dopamine in the blood by the enzyme aromatic L-amino acid decarboxylase (AADC). Alterations in enzyme activity may contribute to the required higher dosages of levodopa observed in many patients with Parkinson’s disease. We evaluated the effect of levodopa/PDI use on serum AADC enzyme activity. Serum AADC enzyme activity was evaluated in three independent cohorts of patients with Parkinson’s disease or parkinsonism (n = 301) and compared between patients on levodopa/PDI vs. patients not on this medication. AADC enzyme activity was elevated in 62% of patients on levodopa/PDI treatment, compared to 19% of patients not on levodopa/PDI (median 90 mU/L vs. 50 mU/L, p < 0.001). Patients with elevated AADC activity had longer disease duration and higher doses of levodopa/PDI. These findings may implicate that peripheral AADC induction could underlie a waning effect of levodopa, necessitating dose increases to maintain a sustained therapeutic effect.
Electronic reconstruction forming a C2-symmetric Dirac semimetal in Ca3Ru2O7
Authors: Horio M. , Wang Q. , Granata V. , Kramer K. P. , Sassa Y. , Jöhr S. , Sutter D. , Bold A. , Das L. , Xu Y. , Frison R. , Fittipaldi R. , Kim T. K. , Cacho C. , Rault J. E. , Fèvre P. Le , Bertran F. , Plumb N. C. , Shi M. , Vecchione A. , Fischer M. H. , Chang J. 
Published: March 2021

AbstractElectronic band structures in solids stem from a periodic potential reflecting the structure of either the crystal lattice or electronic order. In the stoichiometric ruthenate Ca3Ru2O7, numerous Fermi surface-sensitive probes indicate a low-temperature electronic reconstruction. Yet, the causality and the reconstructed band structure remain unsolved. Here, we show by angle-resolved photoemission spectroscopy, how in Ca3Ru2O7 a C2-symmetric massive Dirac semimetal is realized through a Brillouin-zone preserving electronic reconstruction. This Dirac semimetal emerges in a two-stage transition upon cooling. The Dirac point and band velocities are consistent with constraints set by quantum oscillation, thermodynamic, and transport experiments, suggesting that the complete Fermi surface is resolved. The reconstructed structure—incompatible with translational-symmetry-breaking density waves—serves as an important test for band structure calculations of correlated electron systems.
Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application
Authors: Zha Kangkang , Li Xu , Yang Zhen , Tian Guangzhao , Sun Zhiqiang , Sui Xiang , Dai Yongjing , Liu Shuyun , Guo Quanyi 
Published: March 2021

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.
AS03-adjuvanted H7N9 inactivated split virion vaccines induce cross-reactive and protective responses in ferrets
Authors: Stadlbauer Daniel , Waal Leon de , Beaulieu Edith , Strohmeier Shirin , Kroeze Edwin J. B. Veldhuis , Boutet Philippe , Osterhaus Albert D. M. E. , Krammer Florian , Innis Bruce L. , Nachbagauer Raffael , Stittelaar Koert J. , Mallett Corey P. 
Published: March 2021

AbstractHuman infections with avian H7N9 subtype influenza viruses are a major public health concern and vaccines against H7N9 are urgently needed for pandemic preparedness. In early 2013, novel H7N9 influenza viruses emerged in China that caused about 1600 human cases of infection with a high associated case fatality rate. In this study, two H7N9 split virion vaccines with or without AS03 adjuvant were tested in the naive ferret model. Serological analyses demonstrated that homologous hemagglutination inhibition and microneutralization antibody titers were detectable in the ferrets after the first immunization with the AS03-adjuvanted vaccines that were further boosted by the second immunization. In addition, heterologous antibody titers against older H7 subtype viruses of the North American lineage (H7N7, H7N3) and newer H7 subtype viruses of the Eurasian lineage (H7N9) were detected in the animals receiving the AS03-adjuvanted vaccines. Animals receiving two immunizations of the AS03-adjuvanted vaccines were protected from weight loss and fever in the homologous challenge study and had no detectable virus in throat or lung samples. In addition, microscopic examination post-challenge showed animals immunized with the AS03-adjuvanted vaccines had the least signs of lung injury and inflammation, consistent with the greater relative efficacy of the adjuvanted vaccines. In conclusion, this study demonstrated that the AS03-adjuvanted H7N9 vaccines elicited high levels of homologous and heterologous antibodies and protected against H7N9 virus damage post-challenge.
Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
Authors: Ved R. , Sharouf F. , Harari B. , Muzaffar M. , Manivannan S. , Ormonde C. , Gray W. P. , Zaben M. 
Published: March 2021

AbstractTraumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.
The dear enemy effect drives conspecific aggressiveness in an Azteca-Cecropia system
Authors: Zorzal Gabriela , Camarota Flávio , Dias Marcondes , Vidal Diogo M. , Lima Eraldo , Fregonezi Aline , Campos Ricardo I. 
Published: March 2021

AbstractTerritoriality is costly, and the accurate identification of intruders and the decision to perform aggressive responses are key behavioral traits in social animals. We studied aggression among individuals belonging to close and distant nests of the plant-antAzteca muelleri, which lives in stems of the pioneer treeCecropia glaziovii. More specifically, we aim to investigate if the DE (dear-enemy effect—less aggression towards neighbors than strangers) or NN (nasty-neighbor effect—less aggression to strangers than neighbors) effects or even none of them apply for this iconic Azteca-Cecropia system. We further checked if ant aggression towards conspecifics is related to cuticular hydrocarbon profiles (CHCs), which provide chemical cues for nestmate recognition. Therefore, we sampled 46 nests ofA.muelleriin three Brazilian Atlantic forest fragments and performed behavioral trials within and between sites. Consistently with the DE effect, we found higher aggression levels in ‘between sites’ versus ‘within sites’ treatments as well as a positive effect of spatial distance on ant aggressiveness. We found no effect of the overall dissimilarities on CHC blend on ant aggressiveness, but of one CHC class, the methylated alkanes. Overall, we provide key insights on nest-mate recognition in obligatory ant-plant mutualisms.
Development of a rapid scabies immunodiagnostic assay based on transcriptomic analysis of Sarcoptes scabiei var. nyctereutis
Authors: Akuta Teruo , Minegishi Daisuke , Kido Nobuhide , Imaizumi Keitaro , Nakaoka Shinji , Tachibana Shin-Ichiro , Hikosaka Kenji , Hori Fumi , Masataka  , Nakagawa  , Sakuma Chiaki , Oouchi Yuki , Nakajima Yu , Tanaka Sohei , Omiya Tomoko , Morikaku Kouki , Kawahara Minori , Tada Yoshifumi , Tarui Hiroshi , Ueda Takafumi , Kikuchi-Ueda Takane , Ono Yasuo 
Published: March 2021

AbstractScabies is a highly contagious skin disease caused by the mite Sarcoptes scabiei that affects many mammals. However, the sensitivity of traditional tests for scabies diagnosis in humans is less than 50%. To simplify the diagnosis of scabies, methods that are simple, sensitive, specific, and cost-effective are required. We developed an immunodiagnostic test based on S. scabiei var. nyctereutis RNA-seq data collected from Japanese raccoon dogs with sarcoptic mange. Three candidate antigens—a highly expressed hypothetical protein “QR98_0091190,” another mite allergen known as “SMIPP-Cc,” and an abundant “vitellogenin-like protein”—were evaluated by western-blot analysis. A lateral flow immunoassay, using specific antibodies against the vitellogenin-like protein, successfully detected scabies in the skin flakes of S. scabiei-infected raccoon dogs. This assay can potentially diagnose scabies more accurately in wildlife, as well as in humans.
Discontinuous phase transitions in the multi-state noisy q-voter model: quenched vs. annealed disorder
Authors: Nowak Bartłomiej , Stoń Bartosz , Sznajd-Weron Katarzyna 
Published: March 2021

AbstractWe introduce a generalized version of the noisy q-voter model, one of the most popular opinion dynamics models, in which voters can be in one of $$s \ge 2$$

s
≥
2

states. As in the original binary q-voter model, which corresponds to $$s=2$$

s
=
2

, at each update randomly selected voter can conform to its q randomly chosen neighbors only if they are all in the same state. Additionally, a voter can act independently, taking a randomly chosen state, which introduces disorder to the system. We consider two types of disorder: (1) annealed, which means that each voter can act independently with probability p and with complementary probability $$1-p$$

1
-
p

conform to others, and (2) quenched, which means that there is a fraction p of all voters, which are permanently independent and the rest of them are conformists. We analyze the model on the complete graph analytically and via Monte Carlo simulations. We show that for the number of states $$s>2$$

s
>
2

the model displays discontinuous phase transitions for any $$q>1$$

q
>
1

, on contrary to the model with binary opinions, in which discontinuous phase transitions are observed only for $$q>5$$

q
>
5

. Moreover, unlike the case of $$s=2$$

s
=
2

, for $$s>2$$

s
>
2

discontinuous phase transitions survive under the quenched disorder, although they are less sharp than under the annealed one.
Vaginal microbiome and serum metabolite differences in late gestation commercial sows at risk for pelvic organ prolapse
Authors: Kiefer Zoë E. , Koester Lucas R. , Showman Lucas , Studer Jamie M. , Chipman Amanda L. , Keating Aileen F. , Schmitz-Esser Stephan , Ross Jason W. 
Published: March 2021

AbstractSow mortality attributable to pelvic organ prolapse (POP) has increased in the U.S. swine industry and continues to worsen. Two main objectives of this study were, (1) to develop a perineal scoring system that can be correlated with POP risk, and (2) identify POP risk-associated biological factors. To assess POP risk during late gestation, sows (n = 213) were scored using a newly developed perineal scoring (PS) system. Sows scored as PS1 (low), PS2 (moderate), or PS3 (high) based on POP risk. Subsequently, 1.5, 0.8, and 23.1% of sows scored PS1, PS2, or PS3, respectively, experienced POP. To identify biomarkers, serum and vaginal swabs were collected from late gestation sows differing in PS. Using GC–MS, 82 serum metabolite differences between PS1 and PS3 animals (P < 0.05) were identified. Vaginal swabs were utilized for 16S rRNA gene sequencing and differences in vaginal microbiomes between PS1 and PS3 animals were detected on a community level (P < 0.01) along with differences in abundances of 89 operational taxonomic units (P < 0.05). Collectively, these data demonstrate that sows with greater POP risk have differential serum metabolites and vaginal microflora. Additionally, an initial and novel characterization of the sow vaginal microbiome was determined.
Initial cell density encodes proliferative potential in cancer cell populations
Authors: Enrico Bena Chiara , Del Giudice Marco , Grob Alice , Gueudré Thomas , Miotto Mattia , Gialama Dimitra , Osella Matteo , Turco Emilia , Ceroni Francesca , De Martino Andrea , Bosia Carla 
Published: March 2021

AbstractIndividual cells exhibit specific proliferative responses to changes in microenvironmental conditions. Whether such potential is constrained by the cell density throughout the growth process is however unclear. Here, we identify a theoretical framework that captures how the information encoded in the initial density of cancer cell populations impacts their growth profile. By following the growth of hundreds of populations of cancer cells, we found that the time they need to adapt to the environment decreases as the initial cell density increases. Moreover, the population growth rate shows a maximum at intermediate initial densities. With the support of a mathematical model, we show that the observed interdependence of adaptation time and growth rate is significantly at odds both with standard logistic growth models and with the Monod-like function that governs the dependence of the growth rate on nutrient levels. Our results (i) uncover and quantify a previously unnoticed heterogeneity in the growth dynamics of cancer cell populations; (ii) unveil how population growth may be affected by single-cell adaptation times; (iii) contribute to our understanding of the clinically-observed dependence of the primary and metastatic tumor take rates on the initial density of implanted cancer cells.
Potential benefits of L. acidophilus in dyslipidemic rats
Authors: Reamtong Onrapak , Thiangtrongjit Tipparat , Kosoltanapiwat Nathamon , Panbangred Watanalai , Prangthip Pattaneeya 
Published: March 2021

AbstractSeveral studies have shown that probiotics and synbiotics ameliorate dyslipidemia. However, the molecular mechanisms mediating their effects remain to be determined. Therefore, we aimed to compare the effects of a probiotic, a prebiotic, and a synbiotic in dyslipidemic Sprague–Dawley rats, and explore the mechanisms involved using a proteomic approach. The rats were allocated to five groups: a control group that was fed normal chow, and four high-fat diet-fed groups, three of which were administered a probiotic (Lactobacillus acidophilus), a prebiotic (inulin), or a combination of the two (a synbiotic) for 30 days. We showed that the administration of inulin, and especially L. acidophilus, improved the lipid profile and reduced the serum concentrations of inflammatory markers in high-fat diet-fed rats. Proteomic analysis showed changes in lipid elongation, glycerolipid metabolism, activation of antioxidants, and a reduction in the activation of the mitogen-activated protein kinase signaling pathway in the livers of rats administered L. acidophilus, which likely mediate its beneficial effects on inflammation and dyslipidemia by reduced the levels of 18.56% CRP, 35.71% TNF-α 25.6% LDL-C and 28.57% LDL-C/HDL-C ratio when compared to HF group. L. acidophilus and inulin may represent effective natural means of maintaining inflammation and dyslipidemia.
Nitrocellulose-bound achromopeptidase for point-of-care nucleic acid tests
Authors: Chondrogiannis Georgios , Khaliliazar Shirin , Toldrà Anna , Réu Pedro , Hamedi Mahiar M. 
Published: March 2021

AbstractEnzymes are the cornerstone of modern biotechnology. Achromopeptidase (ACP) is a well-known enzyme that hydrolyzes a number of proteins, notably proteins on the surface of Gram-positive bacteria. It is therefore used for sample preparation in nucleic acid tests. However, ACP inhibits DNA amplification which makes its integration difficult. Heat is commonly used to inactivate ACP, but it can be challenging to integrate heating into point-of-care devices. Here, we use recombinase polymerase amplification (RPA) together with ACP, and show that when ACP is immobilized on nitrocellulose paper, it retains its enzymatic function and can easily and rapidly be activated using agitation. The nitrocellulose-bound ACP does, however, not leak into the solution, preventing the need for deactivation through heat or by other means. Nitrocellulose-bound ACP thus opens new possibilities for paper-based Point-of-Care (POC) devices.
The medium-chain fatty acid decanoic acid reduces oxidative stress levels in neuroblastoma cells
Authors: Mett Janine , Müller Uli 
Published: March 2021

AbstractEnhanced oxidative stress is a contributing factor in the pathogenesis of several neurodegenerative disorders such as Alzheimer´s disease. Beneficial effects have been demonstrated for medium-chain fatty acids (MCFAs) nutritionally administered as medium-chain triglycerides (MCTs) or coconut oil (CO). The observed effects on cognitive impairment are generally attributed to the hepatic metabolism of MCFAs, where resulting ketone bodies serve as an alternate energy source to compensate for the impaired glucose utilisation in the human brain. Here we show that the saturated MCFA decanoic acid (10:0) reduces the oxidative stress level in two different neuroblastoma cell lines. Phosphatidylcholine (PC) containing decanoic acid (10:0) (PC10:0/10:0) reduced the cellular H2O2 release in comparison to solvent, L-α-Glycerophosphorylcholine and PC containing the long-chain fatty acid (LCFA) arachidic acid (20:0). This effect seems to be at least partially based on an upregulation of catalase activity, independent of alterations in catalase gene expression. Further, PC10:0/10:0 decreased the intracellular oxidative stress level and attenuated the H2O2-induced cell death. It did not affect the level of the ketone body β-hydroxybutyrate (βHB). These results indicate that decanoic acid (10:0) and possibly MCFAs in general directly reduce oxidative stress levels independent of ketone levels and thus may promote neuronal health.
Population pharmacokinetics and dose optimization of vancomycin in neonates
Authors: Lee Soon Min , Yang Seungwon , Kang Soyoung , Chang Min Jung 
Published: March 2021

AbstractThe pharmacokinetics of vancomycin vary among neonates, and we aimed to conduct population pharmacokinetic analysis to determine the optimal dosage of vancomycin in Korean neonates. From a retrospective chart review, neonates treated with vancomycin from 2008 to 2017 in a neonatal intensive care unit (NICU) were included. Vancomycin concentrations were collected based on therapeutic drug monitoring, and other patient characteristics were gathered through electronic medical records. We applied nonlinear mixed-effect modeling to build the population pharmacokinetic model. One- and two-compartment models with first-order elimination were evaluated as potential structural pharmacokinetic models. Allometric and isometric scaling was applied to standardize pharmacokinetic parameters for clearance and volume of distribution, respectively, using fixed powers (0.75 and 1, respectively, for clearance and volume). The predictive performance of the final model was developed, and dosing strategies were explored using Monte Carlo simulations with AUC0–24 targets 400–600. The patient cohort included 207 neonates, and 900 vancomycin concentrations were analyzed. Only 37.4% of the analyzed concentrations were within trough concentrations 5–15 µg/mL. A one-compartment model with first-order elimination best described the vancomycin pharmacokinetics in neonates. Postmenstrual age (PMA) and creatinine clearance (CLcr) affected the clearance of vancomycin, and model evaluation confirmed the robustness of the final model. Population pharmacokinetic modeling and dose optimization of vancomycin in Korean neonates showed that vancomycin clearance was related to PMA and CLcr, as well as body weight. A higher dosage regimen than the typical recommendation is suggested.
Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys
Authors: de Alcantara Bianca Nascimento , Imbeloni Aline Amaral , de Brito Simith Durans Darlene , de Araújo Marialva Tereza Ferreira , do Rosário Moutinho da Cruz Ermelinda , de Carvalho Carlos Alberto Marques , de Mendonça Maria Helena Rodrigues , de Sousa Jorge Rodrigues , Moraes Adriana Freitas , Filho Arnaldo Jorge Martins , de Lourdes Gomes Lima Maria , Neto Orlando Pereira Amador , Chiang Jannifer Oliveira , de Azevedo Scalercio Sarah Raphaella Rocha , Carneiro Liliane Almeida , Quaresma Juarez Antônio Simões , da Costa Vasconcelos Pedro Fernando , de Almeida Medeiros Daniele Barbosa 
Published: March 2021

AbstractThe absence of an adequate animal model for studies has limited the understanding of congenital Zika syndrome (CZS) in humans during the outbreak in America. In this study, we used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a model of Zika virus (ZIKV) infection. Seven pregnant female squirrel monkeys were experimentally infected at three different gestational stages, and we were able reproduce a broad range of clinical manifestations of ZIKV lesions observed in newborn humans. Histopathological and immunohistochemical analyses of early-infected newborns (2/4) revealed damage to various areas of the brain and ZIKV antigens in the cytoplasm of neurons and glial cells, indicative of CZS. The changes caused by ZIKV infection were intrauterine developmental delay, ventriculomegaly, simplified brain gyri, vascular impairment and neuroprogenitor cell dysfunction. Our data show that the ZIKV infection outcome in squirrel monkeys is similar to that in humans, indicating that this model can be used to help answer questions about the effect of ZIKV infection on neuroembryonic development and the morphological changes induced by CZS.