bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the association between neuroticism and adverse obstetric and neonatal outcomes
Authors: Axfors Cathrine , Eckerdal Patricia , Volgsten Helena , Wikström Anna-Karin , Ekselius Lisa , Ramklint Mia , Sundström Poromaa Inger , Skalkidou Alkistis 
Published: October 2019

AbstractNeuroticism is not only associated with affective disorders but also with certain somatic health problems. However, studies assessing whether neuroticism is associated with adverse obstetric or neonatal outcomes are scarce. This observational study comprises first-time mothers (n = 1969) with singleton pregnancies from several cohorts based in Uppsala, Sweden. To assess neuroticism-related personality, the Swedish universities Scales of Personality was used. Swedish national health registers were used to extract outcomes and confounders. In logistic regression models, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the outcomes by an increase of 63 units of neuroticism (equalling the interquartile range). Analyses were adjusted for maternal age, educational level, height, body mass index, year of delivery, smoking during pregnancy, involuntary childlessness, and psychiatric morbidity. Main outcomes were mode of delivery, gestational diabetes mellitus, gestational hypertension, preeclampsia, induction of delivery, prolonged delivery, severe lacerations, placental retention, postpartum haemorrhage, premature birth, infant born small or large for gestational age, and Apgar score. Neuroticism was not independently associated with adverse obstetric or neonatal outcomes besides gestational diabetes. For future studies, models examining sub-components of neuroticism or pregnancy-specific anxiety are encouraged.
A Dynamic Radiographic Imaging Study of Lumbar Intervertebral Disc Morphometry and Deformation In Vivo
Authors: Byrne Ryan M. , Aiyangar Ameet K. , Zhang Xudong 
Published: October 2019

AbstractIntervertebral discs are important structural components of the spine but also are significant sources of morbidity, especially for the “low back” lumbar region. Mechanical damage to, or degeneration of, the lumbar discs can diminish their structural integrity and elicit debilitating low back pain. Advancement of reparative or regenerative means to treat damaged or degenerated discs is hindered by a lack of basic understanding of the disc load-deformation characteristics in vivo. The current study presents an in vivo analysis of the morphometry and deformation of lumbar (L2-S1) intervertebral discs in 10 healthy participants while performing a common lifting act, using novel dynamic radiographic imaging of the lumbar vertebral body motion. Data analyses show uniquely different (p < 0.05) characteristics in morphometry, normal and shear strain patterns of the L5S1 discs, while the rest of lumbar discs exhibit great similarity. In particular shear strains in L2-L5 discs exhibited stronger linear correlations (R2 ≥ 0.80) between strain changes and amount of lumbar flexion-extension motion compared to L5S1 (R2 ≤ 0.5). The study therefore advances the state of knowledge on in vivo mechanical responses of the lumbar intervertebral discs during functional tasks.
Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences
Authors: Ye Meijun , Solarana Krystyna , Rafi Harmain , Patel Shyama , Nabili Marjan , Liu Yunbo , Huang Stanley , Fisher Jonathan A. N. , Krauthamer Victor , Myers Matthew , Welle Cristin 
Published: October 2019

AbstractExposure of the brain to high-intensity stress waves creates the potential for long-term functional deficits not related to thermal or cavitational damage. Possible sources of such exposure include overpressure from blast explosions or high-intensity focused ultrasound (HIFU). While current ultrasound clinical protocols do not normally produce long-term neurological deficits, the rapid expansion of potential therapeutic applications and ultrasound pulse-train protocols highlights the importance of establishing a safety envelope beyond which therapeutic ultrasound can cause neurological deficits not detectable by standard histological assessment for thermal and cavitational damage. In this study, we assessed the neuroinflammatory response, behavioral effects, and brain micro-electrocorticographic (µECoG) signals in mice following exposure to a train of transcranial pulses above normal clinical parameters. We found that the HIFU exposure induced a mild regional neuroinflammation not localized to the primary focal site, and impaired locomotor and exploratory behavior for up to 1 month post-exposure. In addition, low frequency (δ) and high frequency (β, γ) oscillations recorded by ECoG were altered at acute and chronic time points following HIFU application. ECoG signal changes on the hemisphere ipsilateral to HIFU exposure are of greater magnitude than the contralateral hemisphere, and persist for up to three months. These results are useful for describing the upper limit of transcranial ultrasound protocols, and the neurological sequelae of injury induced by high-intensity stress waves.
A unique olfactory bulb microcircuit driven by neurons expressing the precursor to glucagon-like peptide 1
Authors: Thiebaud Nicolas , Gribble Fiona , Reimann Frank , Trapp Stefan , Fadool Debra Ann 
Published: October 2019

AbstractThe presence of large numbers of local interneurons in the olfactory bulb has demonstrated an extensive local signaling process, yet the identification and purpose of olfactory microcircuits is poorly explored. Because the discrimination of odors in a complex environment is highly dependent on the tuning of information by local interneurons, we studied for the first time the role of preproglucagon (PPG) neurons in the granule cell layer of the olfactory bulb. Combining electrophysiological recordings and confocal microscopy, we discovered that the PPG neurons are a population of cells expressing the precursor of glucagon-like peptide 1 and are glutamatergic; able to modulate the firing pattern of the mitral cells (M/TCs). Optogenetic activation of PPG neurons resulted in a mixed excitation and inhibition that created a multiphasic response shaping the M/TCs firing pattern. This suggests that PPG neurons could drive neuromodulation of the olfactory output and change the synaptic map regulating olfactory coding.
Diversity of Mycobacterium tuberculosis in the Middle Fly District of Western Province, Papua New Guinea: microbead-based spoligotyping using DNA from Ziehl-Neelsen-stained microscopy preparations
Authors: Guernier-Cambert Vanina , Diefenbach-Elstob Tanya , Klotoe Bernice J. , Burgess Graham , Pelowa Daniel , Dowi Robert , Gula Bisato , McBryde Emma S. , Refrégier Guislaine , Rush Catherine , Sola Christophe , Warner Jeffrey 
Published: October 2019

AbstractTuberculosis remains the world’s leading cause of death from an infectious agent, and is a serious health problem in Papua New Guinea (PNG) with an estimated 36,000 new cases each year. This study describes the genetic diversity of Mycobacterium tuberculosis among tuberculosis patients in the Balimo/Bamu region in the Middle Fly District of Western Province in PNG, and investigates rifampicin resistance-associated mutations. Archived Ziehl-Neelsen-stained sputum smears were used to conduct microbead-based spoligotyping and assess genotypic resistance. Among the 162 samples included, 80 (49.4%) generated spoligotyping patterns (n = 23), belonging predominantly to the L2 Lineage (44%) and the L4 Lineage (30%). This is consistent with what has been found in other PNG regions geographically distant from Middle Fly District of Western Province, but is different from neighbouring South-East Asian countries. Rifampicin resistance was identified in 7.8% of the successfully sequenced samples, with all resistant samples belonging to the L2/Beijing Lineage. A high prevalence of mixed L2/L4 profiles was suggestive of polyclonal infection in the region, although this would need to be confirmed. The method described here could be a game-changer in resource-limited countries where large numbers of archived smear slides could be used for retrospective (and prospective) studies of M. tuberculosis genetic epidemiology.
Long term results of single high dose Stereotactic Body Radiotherapy in the treatment of primary lung tumors
Authors: Nicosia Luca , Reverberi Chiara , Agolli Linda , Marinelli Luca , De Sanctis Vitaliana , Valeriani Maurizio , Osti Mattia F. 
Published: October 2019

AbstractStereotactic body radiotherapy (SBRT) is a standard treatment for inoperable early-stage NSCLC, with local control rates comparable to surgical series. Promising results have been achieved utilizing a high single-dose schedule. The aim of our study was to evaluate long-term local control and toxicity in a series of patients treated with SBRT delivered in a single dose of 30 Gy. 44 patients affected by early stage NSCLC were treated with SBRT delivered in a single dose of 30 Gy. Survival and prognostic factors were retrospectively evaluated. Median follow-up was 34 months (range 3–81). Three- and 5-year local progression-free survival (LPFS) were 87.8% and 87.8% respectively (median 30 months; range 6–81 months), 3- and 5-year OS and CSS were 64.9% and 36.9%, 80.9% and 65.5%, respectively. Two (4.6%) cases of grade 3 pneumonitis occurred. At the univariate analysis lesion diameter ≤ 25 mm was predictive of better 5-year LPFS (95.8% versus 56.3%; p = 0.003) and 5-year PFS (69.8% versus 27.8%; p = 0.002). The results of our study indicated a high local control, survival and tolerability after a long-term follow-up with the use of SBRT 30 Gy single dose. Further prospective studies could better define the role of this regimen.
Differentiation of Induced Pluripotent Stem Cells towards Mesenchymal Stromal Cells is Hampered by Culture in 3D Hydrogels
Authors: Goetzke Roman , Keijdener Hans , Franzen Julia , Ostrowska Alina , Nüchtern Selina , Mela Petra , Wagner Wolfgang 
Published: October 2019

AbstractDirected differentiation of induced pluripotent stem cells (iPSCs) towards specific lineages remains a major challenge in regenerative medicine, while there is a growing perception that this process can be influenced by the three-dimensional environment. In this study, we investigated whether iPSCs can differentiate towards mesenchymal stromal cells (MSCs) when embedded into fibrin hydrogels to enable a one-step differentiation procedure within a scaffold. Differentiation of iPSCs on tissue culture plastic or on top of fibrin hydrogels resulted in a typical MSC-like phenotype. In contrast, iPSCs embedded into fibrin gel gave rise to much smaller cells with heterogeneous growth patterns, absence of fibronectin, faint expression of CD73 and CD105, and reduced differentiation potential towards osteogenic and adipogenic lineage. Transcriptomic analysis demonstrated that characteristic genes for MSCs and extracellular matrix were upregulated on flat substrates, whereas genes of neural development were upregulated in 3D culture. Furthermore, the 3D culture had major effects on DNA methylation profiles, particularly within genes for neuronal and cardiovascular development, while there was no evidence for epigenetic maturation towards MSCs. Taken together, iPSCs could be differentiated towards MSCs on tissue culture plastic or on a flat fibrin hydrogel. In contrast, the differentiation process was heterogeneous and not directed towards MSCs when iPSCs were embedded into the hydrogel.
Analysis of combined resistance to oxazolidinones and phenicols among bacteria from dogs fed with raw meat/vegetables and the respective food items
Authors: Wu Yifan , Fan Run , Wang Yinchao , Lei Lei , Feßler Andrea T. , Wang Zheng , Wu Congming , Schwarz Stefan , Wang Yang 
Published: October 2019

AbstractThe gene optrA is the first gene that confers resistance to the oxazolidinone tedizolid, a last resort antimicrobial agent in human medicine. In this study we investigated the presence of optrA and the multi-resistance genes poxtA and cfr in enterococci and staphylococci from (i) pet animals known to be fed raw meat and vegetables and (ii) the respective food items. We examined 341 bacterial isolates from cats and dogs, 195 bacterial isolates from supermarket food items and only one E. faecium collected from industrial food in Beijing during 2016. Thirty-five (6.5%) of the 537 isolates, including 31/376 (8.2%) enterococci and 4/161 (2.5%) staphylococci, were positive for optrA, while all isolates were negative for poxtA and cfr. S1-nuclease pulsed-field gel electrophoresis (PFGE) and Southern blotting confirmed that optrA was located in the chromosomal DNA of 19 isolates and on a plasmid in the remaining 16 isolates. Whole genome sequencing revealed several different genetic environments of optrA in plasmid- or chromosome-borne optrA genes. PFGE, multilocus sequence typing (MLST) and/or SNP analysis demonstrated that the optrA-carrying Staphylococcus and Enterococcus isolates were genetically heterogeneous. However, in single cases, groups of related isolates were identified which might suggest a transfer of closely related optrA-positive E. faecalis isolates between food items and dogs.
Downregulation of GRK5 hampers the migration of breast cancer cells
Authors: Sommer Ann-Katrin , Falcenberg Mathias , Ljepoja Bojan , Fröhlich Thomas , Arnold Georg J. , Wagner Ernst , Roidl Andreas 
Published: October 2019

AbstractSunitinib is a multispecific kinase inhibitor and one of its targets is the kinase GRK5, which is regulating a multitude of G protein-coupled receptors (GPCRs). In this study we demonstrate that a decreased GRK5 expression induced by knock-down experiments or sunitinib treatment hampers the migration of cancer cell lines. A proteomic analysis revealed many pathways related to cell migration which were down regulated upon the GRK5 knock-down. Furthermore, we found in MDA-MB-231 breast cancer cells that the inhibition of migration is mediated by the GPCR gastrin releasing peptide receptor (GRPR) leading to a reduced expression of migration regulating downstream targets like CDC42 and ROCK1. An in silico Kaplan Meier analysis revealed that GRK5 and GRPR overexpression reduces the distant metastasis free survival in triple-negative breast cancer (TNBC) patients. Thus, we suggest a novel anti-migratory effect of impaired GRK5 expression which induces a negative feedback loop on GRPR signalling.
A mid-Cretaceous enantiornithine foot and tail feather preserved in Burmese amber
Authors: Xing Lida , McKellar Ryan C. , O’Connor Jingmai K. , Niu Kecheng , Mai Huijuan 
Published: October 2019

AbstractSince the first skeletal remains of avians preserved in amber were described in 2016, new avian remains trapped in Cretaceous-age Burmese amber continue to be uncovered, revealing a diversity of skeletal and feather morphologies observed nowhere else in the Mesozoic fossil record. Here we describe a foot with digital proportions unlike any previously described enantiornithine or Mesozoic bird. No bones are preserved in the new specimen but the outline of the foot is recorded in a detailed skin surface, which is surrounded by feather inclusions including a partial rachis-dominated feather. Pedal proportions and plumage support identification as an enantiornithine, but unlike previous discoveries the toes are stout with transversely elongated digital pads, and the outer toe appears strongly thickened relative to the inner two digits. The new specimen increases the known diversity and morphological disparity among the Enantiornithes, hinting at a wider range of habitats and behaviours. It also suggests that the Burmese amber avifauna was distinct from other Mesozoic assemblages, with amber entrapment including representatives from unusual small forms.
FTIR, Raman and AFM characterization of the clinically valid biochemical parameters of the thrombi in acute ischemic stroke
Authors: Blat Aneta , Dybas Jakub , Chrabaszcz Karolina , Bulat Katarzyna , Jasztal Agnieszka , Kaczmarska Magdalena , Pulyk Roman , Popiela Tadeusz , Slowik Agnieszka , Malek Kamilla , Adamski Mateusz G. , Marzec Katarzyna M. 
Published: October 2019

AbstractThe significance and utility of innovative imaging techniques in arterial clot analysis, which enable far more detailed and automated analysis compared to standard methods, are presented. The examination of two types of human thrombi is shown, representing the main ischemic stroke etiologies: fibrin–predominant clot of large vessel origin and red blood cells–rich clot of cardioembolic origin. The synergy effect of Fourier–transform infrared spectroscopy (FTIR), Raman spectroscopy (RS) and atomic force microscopy (AFM) techniques supported by chemometrics in comparison with reference histological staining was presented. The main advantage of such approach refers to free–label and non–destructive quantitative imaging of clinically valid, biochemical parameters in whole sample (FTIR–low resolution) and selected regions (RS–ultra–high resolution). We may include here analysis of lipid content, its distribution and total degree of unsaturation as well as analysis of protein content (mainly fibrin and hemoproteins). The AFM studies enhanced the vibrational data, showed clearly shape and thickness of clot features as well as visualized the fibrin framework. The extraordinary sensitivity of FTIR and RS imaging toward detection and discrimination of clinically valid parameters in clot confirms its applicability in assessment of thrombi origin.
Nucleus pulposus primary cilia alter their length in response to changes in extracellular osmolarity but do not control TonEBP-mediated osmoregulation
Authors: Choi Hyowon , Madhu Vedavathi , Shapiro Irving M. , Risbud Makarand V. 
Published: October 2019

AbstractThe nucleus pulposus (NP) cells adapt to their physiologically hyperosmotic microenvironment through Tonicity-responsive enhancer binding protein (TonEBP/nuclear factor of activated T-cell5 [NFAT5])-mediated osmoregulation. Primary cilia in different organs serve diverse roles including osmosensing, but its contribution to NP cell osmoadaptive response is unknown. A high percentage of cultured primary NP cells possessed primary cilia that changed length in response to osmotic stimuli. Stable silencing ofIntraflagellar Transport 88 (Ift88)orKinesin Family Member 3 A (Kif3a)to inhibit the formation of primary cilia did not affect hyperosmotic upregulation of TonEBP. While ShKif3ablocked hyperosmotic increase of TonEBP-Transactivation Domain (TAD) activity, overall the knockdown of either gene did not alter the hyperosmotic status of proximal promoter activities and transcription of key TonEBP targets. On the other hand, a small decrease in TonEBP level under hypoosmotic condition was attenuated byIft88orKif3aknockdown. Noteworthy, none of the TonEBP target genes were responsive to hypoosmotic stimulus in control andIft88orKif3aknockdown cells, suggesting the primary role of TonEBP in the hyperosmotic adaptation of NP cells. Similarly, inKif3anull mouse embryonic fibroblasts (MEFs), the overall TonEBP-dependent hyperosmotic responses were preserved. Unlike NP cells, TonEBP targets were responsive to hypoosmolarity in wild-type MEFs, and these responses remained intact inKif3anull MEFs. Together, these results suggest that primary cilia are dispensable for TonEBP-dependent osmoadaptive response.
Dissecting the evolvability landscape of the CalB active site toward aromatic substrates
Authors: Santos Yossef López de los , Chew-Fajardo Ying Lian , Brault Guillaume , Doucet Nicolas 
Published: October 2019

AbstractA key event in the directed evolution of enzymes is the systematic use of mutagenesis and selection, a process that can give rise to mutant libraries containing millions of protein variants. To this day, the functional analysis and identification of active variants among such high numbers of mutational possibilities is not a trivial task. Here, we describe a combinatorial semi-rational approach to partly overcome this challenge and help design smaller and smarter mutant libraries. By adapting a liquid medium transesterification assay in organic solvent conditions with a combination of virtual docking, iterative saturation mutagenesis, and residue interaction network (RIN) analysis, we engineered lipase B from P. antarctica (CalB) to improve enzyme recognition and activity against the bulky aromatic substrates and flavoring agents methyl cinnamate and methyl salicylate. Substrate-imprinted docking was used to target active-site positions involved in enzyme-substrate and enzyme-product complexes, in addition to identifying ‘hot spots’ most likely to yield active variants. This iterative semi-rational design strategy allowed selection of CalB variants exhibiting increased activity in just two rounds of site-saturation mutagenesis. Beneficial replacements were observed by screening only 0.308% of the theoretical library size, illustrating how semi-rational approaches with targeted diversity can quickly facilitate the discovery of improved activity variants relevant to a number of biotechnological applications.
Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer
Authors: Suresh Voddu , Sundaram Rajivgandhi , Dash Pujarini , Sabat Surendra Chandra , Mohapatra Debasish , Mohanty Sneha , Vasudevan Dileep , Senapati Shantibhusan 
Published: October 2019

AbstractMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize the structure and function of Mesocricetus auratusMIF (MaMIF) and finally evaluate its effect on pancreatic tumor growthin vivo. Initially, the recombinant MaMIF was cloned, expressed and purified in a bacterial expression system. The MaMIF primary sequence, biochemical properties, and crystal structure analysis showed greater similarity with human MIF. The crystal structure of MaMIF illustrates that it forms a homotrimer as known in human and mouse. However, MaMIF exhibits some minor structural variations when compared to human and mouse MIF. Thein vitrofunctional studies show that MaMIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of MaMIF into HapT1 pancreatic tumor-bearing hamsters significantly enhanced the tumor growth and tumor-associated angiogenesis. Together, the current study shows a structural and functional similarity between the hamster and human MIF. Moreover, it has demonstrated that a high level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growthin vivo.