bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal transition and increased therapy resistance of glioblastoma cells is related to astrocyte reactivity
Authors: Niklasson Mia , Bergström Tobias , Jarvius Malin , Sundström Anders , Nyberg Frida , Haglund Caroline , Larsson Rolf , Westermark Bengt , Segerman Bo , Segerman Anna 
Published: July 2019

AbstractGrade IV astrocytoma/glioblastoma multiforme (GBM) is essentially incurable, partly due to its heterogenous nature, demonstrated even within the glioma‐initiating cell (GIC) population. Increased therapy resistance of GICs is coupled to transition into a mesenchymal (MES) cell state. The GBM MES molecular signature displays a pronounced inflammatory character and its expression vary within and between tumors. Herein, we investigate how MES transition of GBM cells relates to inflammatory responses of normal astroglia. In response to CNS insults astrocytes enter a reactive cell state and participate in directing neuroinflammation and subsequent healing processes. We found that the MES signature show strong resemblance to gene programs induced in reactive astrocytes. Likewise, astrocyte reactivity gene signatures were enriched in therapy‐resistant MES‐like GIC clones. Variable expression of astrocyte reactivity related genes also largely defined intratumoral GBM cell heterogeneity at the single‐cell level and strongly correlated with our previously defined therapy‐resistance signature (based on linked molecular and functional characterization of GIC clones). In line with this, therapy‐resistant MES‐like GIC secreted immunoregulatory and tissue repair related proteins characteristic of astrocyte reactivity. Moreover, sensitive GIC clones could be made reactive through long‐term exposure to the proinflammatory cytokine interleukin 1 beta (IL1β). IL1β induced a slow MES transition, increased therapy resistance, and a shift in DNA methylation profile towards that of resistant clones, which confirmed a slow reprogramming process. In summary, GICs enter through MES transition a reactive‐astrocyte‐like cell state, connected to therapy resistance. Thus, from a biological point of view, MES GICs would preferably be called ‘reactive GICs’. The ability of GBM cells to mimic astroglial reactivity contextualizes the immunomodulatory and microenvironment reshaping abilities of GBM cells that generate a tumor‐promoting milieu. This insight will be important to guide the development of future sensitizing therapies targeting treatment‐resistant relapse‐driving cell populations as well as enhancing the efficiency of immunotherapies in GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Blood‐based biomarkers in the maternal circulation associated with fetal growth restriction
Authors: Tong Stephen , Joy Kaitu'u‐Lino Tu'uhevaha , Walker Susan Philippa , MacDonald Teresa Mary 
Published: July 2019

AbstractFetal growth restriction (FGR) is associated with threefold to fourfold increased risk of stillbirth. Identifying FGR, through its commonly used surrogate—the small‐for‐gestational‐age (SGA, estimated fetal weight and/or abdominal circumference <10th centile) fetus—and instituting fetal surveillance and timely delivery decrease stillbirth risk. Methods available to clinicians for antenatal identification of SGA fetuses have surprisingly poor sensitivity. About 80% of cases remain undetected. Measuring the symphysis‐fundal height detects only 20% of SGA fetuses, and even universal third trimester ultrasound detects, at best, 57% of those born SGA. There is an urgent need to find better ways to identify this at‐risk cohort. This review summarises efforts to identify molecular biomarkers (proteins, metabolites, or ribonucleic acids) that could be used to better predict FGR. Most studies examining potential biomarkers to date have utilised case‐control study designs without proceeding to validation in independent cohorts. To develop a robust test for FGR, large prospective studies are required with a priori validation plans and cohorts. Given that current clinical care detects 20% of SGA fetuses, even a screening test with ≥60% sensitivity at 90% specificity could be clinically useful, if developed. This may be an achievable aspiration. If discovered, such a test may decrease stillbirth.
Antidepressant continuation in pregnancy and risk of gestational diabetes
Authors: Wartko Paige D. , Weiss Noel S. , Enquobahrie Daniel A. , Chan K.C. Gary , Stephenson‐Famy Alyssa , Mueller Beth A. , Dublin Sascha 
Published: July 2019

AbstractPurposePrevious studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding.MethodsWe conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as “continuers” (n = 1634); those without a fill were “discontinuers” (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity.ResultsCompared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84‐1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, −1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90‐1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87‐2.68), but neither association was statistically significant.ConclusionsOur study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.
Methodologic considerations for noninterventional studies of switching from reference biologic to biosimilars
Authors: Desai Rishi J. , Kim Seoyoung C. , Curtis Jeffrey R. , Bosco Jaclyn L.F. , Eichelberger Bernadette , Barr Charles E. , Lockhart Catherine M. , Bradbury Brian D. , Clewell Jerry , Cohen Hillel P. , Gagne Joshua J. ,   the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Switching Workgroup
Published: July 2019

AbstractPurposeAs more biosimilars become available in the United States, postapproval noninterventional studies describing biosimilar switching and comparing effectiveness and/or safety between switchers and nonswitchers will play a key role in generating real‐world evidence to inform clinical practices and policy decisions. Ensuring sound methodology is critical for making valid inferences from these studies.MethodsThe Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) convened a workgroup consisting of academic researchers, industry scientists, and practicing clinicians to establish best practice recommendations for the conduct of noninterventional studies of biosimilar and reference biologic switching. The workgroup members participated in eight teleconferences between August 2017 and February 2018 to discuss specific topics and build consensus.ResultsThis report provides workgroup recommendations covering five main considerations relating to noninterventional studies describing reference biologic to biosimilar switching and comparing reference biologic to biosimilars for safety and effectiveness in the presence of switching at treatment initiation and during follow‐up: (a) selecting appropriate data sources from a range of available options including insurance claims, electronic health records, and registries; (b) study designs; (c) outcomes of interest including health care utilization and clinical endpoints; (d) analytic approaches including propensity scores, disease risk scores, and instrumental variables; and (e) special considerations including avoiding designs that ignore history of biologic use, avoiding immortal time bias, exposure misclassification, and accounting for postindex switching.ConclusionRecommendations provided in this report provide a framework that may be helpful in designing and critically evaluating postapproval noninterventional studies involving reference biologic to biosimilar switching.
Spasticity and Pain after Spinal Cord Injury: Impact on Daily Life and the Influence of Psychological Factors
Authors: Tibbett Jacqueline A. , Field‐Fote Edelle C. , Thomas Christine K. , Widerström‐Noga Eva G. 
Published: July 2019

BackgroundSpasticity and pain frequently co‐occur in persons with spinal cord injury (SCI), yet, how these sequelae interact in daily life is unclear. Additionally, little is known about how psychological factors relate to the perception of spasticity and its impacts on daily life.Objectives(1) Characterize relationships between spasticity and chronic pain with regard to perceived severity, difficulty dealing, and life interference. (2) Determine the extent to which perceived spasticity severity and physiological, psychological, and pain‐related factors contribute to impacts of spasticity on daily life (difficulty in dealing, life interference). (3) Determine the effects of painful spasticity on aspects of chronic pain and spasticity (severity, life interference, interference with sleep, and spasm duration).DesignObservational study.SettingUniversity laboratory.ParticipantsTwenty participants with SCI and lower extremity spasticity.MethodsMeasures included International SCI Pain Basic Data Set, Pain and Spasticity Inventories, Difficulty Dealing with Pain/Spasticity, SCI‐Spasticity Evaluation Tool, Connor‐Davidson Resilience and Moorong Self‐Efficacy Scales, Spinal Cord Assessment Tool for Spastic Reflexes, spasm duration, and injury‐related and demographic factors. Bivariate correlations, multiple regression analyses, and pairwise comparisons were performed.ResultsSpasticity and chronic pain were directly related, with respect to perceived severity, difficulty dealing, and life interference (rho = 0.514‐0.673, P < .05). Shorter injury duration, greater perceived spasticity severity, and greater difficulty dealing with pain explained 61% of variance in difficulty dealing with spasticity. Greater perceived spasticity severity and lower resilience explained 72% of variance in life interference of spasticity. Spasm duration was not significantly associated with perceived spasticity severity. Participants with painful spasticity had significantly greater chronic pain severity (P = .02) and sleep‐related impact of spasticity (P = .03) than participants without painful spasticity.ConclusionsPerceived severity of spasticity, injury duration, ability to deal with chronic pain, resilience, and painful spasms appear to play important roles in the negative impacts of spasticity on life after SCI.Level of EvidenceIII.
Lack of resonance assistance in a classical intramolecular hydrogen bond: An exploration from quantum theory of atoms‐in‐molecules perspective
Authors: Paul Bijan K. 
Published: July 2019

AbstractA computational investigation has been performed to characterize the intramolecular hydrogen bond (IMHB) interaction in 7‐hydroxy‐2,3‐dihydro‐1H‐inden‐1‐one (7H1I). The results of natural bond orbital (NBO) analysis describe the formation of the IMHB in 7H1I in terms of hyperconjugative charge transfer from the lone electron pair of the acceptor oxygen atom (Oa) to the σ* antibonding orbital of the Od―H1proton donating bond. However, the key motivation of the present work rests on characterization of the IMHB interaction by calculation of electron density (ρc), its Laplacian (∇2ρc), and electron energy density parameters at the bond critical point (BCP) based on the quantum theory of atoms‐in‐molecules (QTAIM). The topological parameters reveal the intriguing result of the lack of resonance assistance in the IMHB of 7H1I despite the presence of an apparently suitable route for the same, contrary to its aromatic (salicylic acid) and nonaromatic ((Z)‐3‐hydroxyacrylaldehyde) analogues. This inference is further supported by an analysis of the aromaticity of the conjoined benzene nucleus. The predominance of hyperconjugation as compared with rehybridization underlying the formation of IMHB in 7H1I is also argued in this context.
The predominant roles of the sequence periodicity in the self‐assembly of collagen‐mimetic mini‐fibrils
Authors: Chen Fangfang , Strawn Rebecca , Xu Yujia 
Published: July 2019

AbstractCollagen fibrils represent a unique case of protein folding and self‐association. We have recently successfully developed triple‐helical peptides that can further self‐assemble into collagen‐mimetic mini‐fibrils. The 35 nm axially repeating structure of the mini‐fibrils, which is designated the d‐period, is highly reminiscent of the well‐known 67 nm D‐period of native collagens when examined using TEM and atomic force spectroscopy. We postulate that it is the pseudo‐identical repeating sequence units in the primary structure of the designed peptides that give rise to the d‐period of the quaternary structure of the mini‐fibrils. In this work, we characterize the self‐assembly of two additional designed peptides: peptide Col877 and peptide Col108rr. The triple‐helix domain of Col877 consists of three pseudo‐identical amino acid sequence units arranged in tandem, whereas that of Col108rr consists of three sequence units identical in amino acid composition but different in sequence. Both peptides form stable collagen triple helices, but only triple helices Col877 self‐associate laterally under fibril forming conditions to form mini‐fibrils having the predicted d‐period. The Co108rr triple helices, however, only form nonspecific aggregates having no identifiable structural features. These results further accentuate the critical involvement of the repeating sequence units in the self‐assembly of collagen mini‐fibrils; the actual amino acid sequence of each unit has only secondary effects. Collagen is essential for tissue development and function. This novel approach to creating collagen‐mimetic fibrils can potentially impact fundamental research and have a wide range of biomedical and industrial applications.
Intrinsically disordered domains: Sequence ➔ disorder ➔ function relationships
Authors: Zhou Jianhong , Oldfield Christopher J. , Yan Wenying , Shen Bairong , Dunker A. Keith 
Published: July 2019

AbstractDisordered domains are long regions of intrinsic disorder that ideally have conserved sequences, conserved disorder, and conserved functions. These domains were first noticed in protein–protein interactions that are distinct from the interactions between two structured domains and the interactions between structured domains and linear motifs or molecular recognition features (MoRFs). So far, disordered domains have not been systematically characterized. Here, we present a bioinformatics investigation of the sequence–disorder–function relationships for a set of probable disordered domains (PDDs) identified from the Pfam database. All the Pfam seed proteins from those domains with at least one PDD sequence were collected. Most often, if a set contains one PDD sequence, then all members of the set are PDDs or nearly so. However, many seed sets have sequence collections that exhibit diverse proportions of predicted disorder and structure, thus giving the completely unexpected result that conserved sequences can vary substantially in predicted disorder and structure. In addition to the induction of structure by binding to protein partners, disordered domains are also induced to form structure by disulfide bond formation, by ion binding, and by complex formation with RNA or DNA. The two new findings, (a) that conserved sequences can vary substantially in their predicted disorder content and (b) that homologues from a single domain can evolve from structure to disorder (or vice versa), enrich our understanding of the sequence ➔ disorder ensemble ➔ function paradigm.
The structure of the extended E2 DNA‐binding domain of the bovine papillomavirus‐1
Authors: Leroy Ludmila , Barbosa João Alexandre Ribeiro Gonçalves , de Prat‐Gay Gonzalo , Polikarpov Igor , Pinheiro Carlos Basílio 
Published: July 2019

AbstractBovine papillomavirus proteins were extensively studied as a prototype for the human papillomavirus. Here, the crystal structure of the extended E2 DNA‐binding domain of the dominant transcription regulator from the bovine papillomavirus strain 1 is described in the space group P3121. We found two protein functional dimers packed in the asymmetric unit. This new protein arrangement inside the crystal led to the reduction of the mobility of a previously unobserved loop directly involved in the protein‐DNA interaction, which was then modeled for the first time.
Brain histamine H1 receptor occupancy after oral administration of desloratadine and loratadine
Authors: Nakamura Tadaho , Hiraoka Kotaro , Harada Ryuichi , Matsuzawa Takuro , Ishikawa Yoichi , Funaki Yoshihito , Yoshikawa Takeo , Tashiro Manabu , Yanai Kazuhiko , Okamura Nobuyuki 
Published: July 2019

AbstractSome histamine H1 receptor (H1R) antagonists induce adverse sedative reactions caused by blockade of histamine transmission in the brain. Desloratadine is a second‐generation antihistamine for treatment of allergic disorders. Its binding to brain H1Rs, which is the basis of sedative property of antihistamines, has not been examined previously in the human brain by positron emission tomography (PET). We examined brain H1R binding potential ratio (BPR), H1R occupancy (H1RO), and subjective sleepiness after oral desloratadine administration in comparison to loratadine. Eight healthy male volunteers underwent PET imaging with [11C]‐doxepin, a PET tracer for H1Rs, after a single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double‐blind crossover study. BPR and H1RO in the cerebral cortex were calculated, and plasma concentrations of loratadine and desloratadine were measured. Subjective sleepiness was quantified by the Line Analogue Rating Scale (LARS) and the Stanford Sleepiness Scale (SSS). BPR was significantly lower after loratadine administration than after placebo (0.504 ± 0.074 vs 0.584 ± 0.059 [mean ± SD], P < 0.05), but BPR after desloratadine administration was not significantly different from BPR after placebo (0.546 ± 0.084 vs 0.584 ± 0.059, P = 0.250). The plasma concentration of loratadine was negatively correlated with BPR in subjects receiving loratadine, but that of desloratadine was not correlated with BPR. Brain H1ROs after desloratadine and loratadine administration were 6.47 ± 10.5% and 13.8 ± 7.00%, respectively (P = 0.103). Subjective sleepiness did not significantly differ among subjects receiving the two antihistamines and placebo. At therapeutic doses, desloratadine did not bind significantly to brain H1Rs and did not induce any significant sedation.
Machine learning and signed particles, an alternative and efficient way to simulate quantum systems
Authors: Sellier Jean Michel , Kapanova Kristina G. , Leygonie Jacob , Caron Gaetan Marceau 
Published: July 2019

AbstractRecently neural networks have been applied in the context of the signed particle formulation of quantum mechanics to rapidly and reliably compute the Wigner kernel of any provided potential. Important advantages were introduced, such as the reduction of the amount of memory required for the simulation of a quantum system by avoiding the storage of the kernel in a multi‐dimensional array, as well as attainment of consistent speedup by the ability to realize the computation only on the cells occupied by signed particles. An inherent limitation was the number of hidden neurons to be equal to the number of cells of the discretized real space. In this work, anew network architecture is presented, decreasing the number of neurons in its hidden layer, thereby reducing the complexity of the network and achieving an additional speedup. The approach is validated on a onedimensional quantum system consisting of a Gaussian wave packet interacting with a potential barrier.
A high‐resolution, multimodal data set for agricultural robotics: A Ladybird's‐eye view of Brassica
Authors: Bender Asher , Whelan Brett , Sukkarieh Salah 
Published: July 2019

AbstractThis article presents an agricultural data set collected by Ladybird, an autonomous field robot designed at the Australian Centre for Field Robotics. The data set contains weekly scans of cauliflower and broccoli (Brassica oleracea) covering a 10 week growth cycle from transplant to harvest. The data set includes ground truth; physical characteristics of the crop; environmental data collected by a weather station and a soil sensor network; and scans of the crop performed by Ladybird, which include stereo color, thermal and hyperspectral imagery. The layout of the farm and data collection methodology are described. A description of Ladybird's capabilities and sensors are provided. Benchmark results are provided to illustrate the contents of the data set and how it can be processed. The hyperspectral data are compiled into hypercubes and the pixels are classified into crop, weed, or soil. An object detector is applied to the color imagery to locate the crop. Our intention in releasing the data set is to facilitate robotics and machine learning research activity in agriculture. The data set can be downloaded from https://doi.org/10.25910/5c941d0c8bccb.
Animal‐borne wireless network: Remote imaging of community ecology
Authors: Park Shinkyu , Aschenbach Konrad H. , Ahmed Manjur , Scott William L. , Leonard Naomi E. , Abernathy Kyler , Marshall Greg , Shepard Mike , Martins Nuno C. 
Published: July 2019

AbstractThis article describes the design, construction, and field‐testing of a standalone networked animal‐borne monitoring system conceived to study community ecology remotely. The system consists of an assemblage of identical battery‐powered sensing devices with wireless communication capabilities that are each collar‐mounted on a study animal and together form a mobile ad hoc network. The sensing modalities of each device include high‐definition video, inertial accelerometry, and location resolved via a global positioning system module. Our system is conceived to use information exchange across the network to enable the devices to jointly decide without supervision when and how to use each sensing modality. The ultimate goal is to extend battery life while making sure that important events are appropriately documented. This requires judicious use of highly informative but power‐hungry sensing modalities, such as video, because battery capacity is constrained by stringent weight and dimension restrictions. We have proposed algorithms to regulate sensing rates, data transmission among devices, and triggering for video recording based on location and animal group movements and configuration. We have also developed the hardware and firmware of our devices to reliably execute these algorithms in the exacting conditions of real‐life deployments. We describe validation of the performance and reliability of our system using deployment results for a mission in Gorongosa National Park (Mozambique) to monitor two species in their natural habitat: the waterbuck and the African buffalo. We present movement data and snapshots of animal point‐of‐view videos collected by 14 fully operational devices collared on 10 waterbucks and 4 buffaloes.