bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase IIa Study Evaluating Safety, Pharmacokinetics, and Antiviral Activity of GSK2838232, a Novel, Second-generation Maturation Inhibitor, in Participants With Human Immunodeficiency Virus Type 1 Infection
Authors: DeJesus Edwin , Harward Sara , Jewell Roxanne C , Johnson Mark , Dumont Etienne , Wilches Viviana , Halliday Fiona , Talarico Christine L , Jeffrey Jerry , Gan Jianjun , Xu Jianfeng , Felizarta Franco , Scribner Anita , Ramgopal Moti , Benson Paul , Johns Brian A 
Published: October 2019

Abstract

Background
GSK2838232 is a second-generation, potent, small-molecule, oral human immunodeficiency virus type 1 (HIV-1) maturation inhibitor for once-daily administration boosted with a pharmacoenhancer.

Methods
The phase 2a, proof-of-concept study was an open-label, adaptive dose-ranging design. Safety, pharmacokinetics, and efficacy of GSK2838232 boosted by cobicistat were evaluated in individuals with HIV-1 infection. The study participants (N = 33) received GSK2838232 once daily across a range of doses (20–200 mg) with cobicistat 150 mg for 10 days.

Results
GSK2838232 was safe and well tolerated with no clinically meaningful changes in safety parameters or adverse events. Exposure (maximum concentration and area under the concentration-time curve from time zero to the concentration at 24 hours postdose) increased 2- to 3-fold with repeated dosing in an approximately dose-proportional manner, reaching steady-state by day 8 with a half-life (t½) from 16.3 to 19.2 hours. Clearance and t½ values were not dependent on dose. Viral load declined from baseline with all GSK2838232 doses. Mean maximum declines from baseline to day 11 in HIV-1 RNA log10 copies/mL with the 20-mg, 50-mg, 100-mg, and 200-mg cohorts were −0.67, −1.56, −1.32, and −1.70, respectively. CD4+ cell counts increased at doses ≥50 mg.

Conclusions
GSK2838232 with cobicistat was well tolerated and exhibited efficacy as a short-term monotherapy in participants with HIV-1. This positive proof-of-concept study supports the continued development of GSK2838232 for the treatment of HIV as part of combination antiretroviral therapy.

Clinical Trials Registration
NCT03045861.
Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy
Authors: Marks Michael , Bell Lucy C K , Jones Imogen , Rampling Tommy , Kranzer Katharina , Morris-Jones Stephen , Logan Sarah , Pollara Gabriele 
Published: October 2019

AbstractThe OVIVA study demonstrated noninferiority for managing bone and joint infections (BJIs) with oral antibiotics. We report that 79.7% of OPAT patients being treated for BJIs at our center would be eligible for oral antibiotics, saving a median (IQR) 19.5 IV-antibiotic days (8.5–37) and GBP 1234 (569–2594) per patient.
Ultrasound Image Despeckling and Enhancement using Modified Multiscale Anisotropic Diffusion Model in Non-Subsampled Shearlet Domain
Authors: Bedi Anterpreet Kaur , Sunkaria Ramesh Kumar , Mittal Deepti 
Published: October 2019

Abstract
Ultrasound imaging is undoubtedly the most used imaging modality for diagnostic purposes. Unfortunately, it is accompanied by speckle which can degrade texture information by obscuring fine details like boundaries and edges. This work presents a method for despeckling ultrasound images by treating them with multiscale modified speckle reduction anisotropic diffusion model and Non-Subsampled shearlet transform (NSST). The method involves division of images using a non-subsampled Laplacian pyramid. This results in low and high frequency image components. Modified anisotropic diffusion is used on the low frequency part. The high frequency component, as subjected to shearlet function, generates noisy coefficients in various directions. These coefficients are further subjected to NSST thresholding. The denoised low and high frequency image components are then recombined to obtain the enhanced image. This multidimensional and multidirectional method improves the qualitative characteristics of ultrasound images by not just removing speckle noise but also by preserving edges, thus resulting in effective image enhancement. Performance of the method is analysed on synthetic and real medical ultrasound images. Results reveal that the proposed method exceeds the state-of-the-art methods in the context of edge preservation and structural similarities, and thus, it is an effective aid to radiologists in their clinical diagnosis by providing an enhanced denoised image.
Monarch-EWA: Monarch-Earthworm-Based Secure Routing Protocol in IoT
Authors: Sugave Shounak , Jagdale Balaso 
Published: October 2019

AbstractRouting in the Internet of Things (IoT) renders the protection against various network attacks as any attacker intrudes the routing mechanism for establishing the destructive mechanisms against the network, which insists the essentiality of the security protocols in IoT. Thus, the paper proposes a secure protocol based on an optimization algorithm, Monarch-Earthworm Algorithm (Monarch-EWA), which is the modification of the Monarch Butterfly algorithm using the Earthworm Optimization Algorithm (EWA) in order to render effective security to the network. Initially, the effective nodes are selected using the Deep Convolutional Neural Network (deep CNN) classifier based on the factors, trust and energy of the node, and stochastic gradient descent algorithm trains the deep CNN classifier. The secure nodes are involved in routing for which the secure multipath is chosen optimally using the proposed Monarch-EWA, which chooses the secure multipath based on the factors, energy and trust. The analysis of the proposed method in the presence of attacks, such as black hole, message replicate and distributed denial of service, reveals that the proposed method outperformed the existing methods. The proposed Monarch-EWA protocol acquired the maximal energy, throughput and detection rate of 0.2268 J, 48.2759% and 82.6231%, respectively, with the minimal delay of 0.0959 ms.
Classes of preferential attachment and triangle preferential attachment models with power-law spectra
Authors: Eikmeier Nicole , Gleich David F 
Published: October 2019

AbstractPreferential attachment (PA) models are a common class of graph models which have been used to explain why power-law distributions appear in the degree sequences of real network data. Among other properties of real-world networks, they commonly have non-trivial clustering coefficients due to an abundance of triangles as well as power laws in the eigenvalue spectra. Although there are triangle PA models and eigenvalue power laws in specific PA constructions, there are no results that existing constructions have both. In this article, we present a specific Triangle Generalized Preferential Attachment Model that, by construction, has non-trivial clustering. We further prove that this model has a power law in both the degree distribution and eigenvalue spectra.
The Monseigneur and the grands seigneurs: Questions of Priority in Early Modern France
Authors: Sternberg G 
Published: October 2019

Abstract
This article investigates a series of epistolary contestations among the French high command in the seventeenth and eighteenth centuries in order to unlock their far-reaching military, political, cultural and social ramifications. Remarkably, disagreements over the use of the term Monseigneur and other epistolary status-markers took priority over military expediency, disrupting French armed operations in the midst of external war or internal rebellion. Such priority of traditional values over new ideals of royal service qualifies the thesis of a reconfiguration of noble Mentalités under the Bourbon monarchy. What is more, close analysis of these conflicts and tensions reveals their impact on everyday communication, sociability and friendship, and uncovers a rich spectrum of coping strategies, from open confrontation to subtler forms of evasion or accommodation. Drawing on new archival findings as well as on a reinterpretation of celebrated literary texts, this analysis also serves to recontextualise these writings as part of information networks that played an active role in the conflicts themselves. Finally, the underlying contestations over social priority newly illuminate the changing landscape of the French aristocracy during this period, revealing points of fissure, collective identities and moments of transformation. In particular, the article brings into relief the changing fortunes of those who remained part of the aristocratic system but did not obtain the positions that increasingly became emblematic of the highest rank. These contestations thus powerfully illustrate how epistolary ceremonial, and cultural practices more generally, can advance our understanding of social structures and dynamics.
Dental and craniofacial features associated with GNAS loss of function mutations
Authors: Le Norcy Elvire , Reggio-Paquet Camille , de Kerdanet Marc , Mignot Brigitte , Rothenbuhler Anya , Chaussain Catherine , Linglart Agnès 
Published: October 2019

Summary

Background
Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3–1/100,000). Heterozygous inactivating mutations involving the maternal GNAS exons 1–13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone). To date, little information is available on craniofacial features in patients with PHP. The small number of patients studied in previous reports as well as the lack of molecular characterization of the patients may have precluded the detection of specific orofacial manifestations in the different PHP subtypes.

Materials/Methods
We conducted a systematic analysis of dental and craniofacial features in 19 patients with iPPSD2 and maternal GNAS inactivating mutations to assess the frequency and specificity of the anomalies.

Results
Facial examinations showed reduced vertical, sagittal, and transverse development of the mid-facial structures. Intraoral and radiographic examinations revealed that 89 per cent of the patients had at least one dental anomaly, including tooth submergence leading to severe infraocclusion in 83 per cent of cases. Craniofacial analysis of lateral cephalometric radiographs also showed a significant alteration in the development of the cranial base and maxillary and mandibular structures in these patients.

Conclusions
Patients with iPPSD2 and maternal GNAS mutations had specific craniofacial alterations and dental abnormalities. These specific defects should be assessed in order to provide appropriate dental and orthodontic care to these patients. (clinical trial registration: 1920371 v 0, French Nationale Data Processing and Liberties Commission - CNIL).
The ‘Plan de Paris’: who made this viol?
Authors: Mackey Shem 
Published: October 2019

Abstract
The ‘Plan de Paris’ viol, so called because of the map of Paris that comprises part of the incredible marquetry on the back, has long had a question mark over its origins. There are connections to one of France’s most famous luthiers, Jean-Baptiste Vuillaume, and other French musical notaries of the 17th and 18th centuries. The instrument has been attributed to the Füssen-born maker Gaspard Duiffoprugcar and was once thought to have been made in the 16th century. However, it is now widely and correctly considered to be a product of the late 17th century. The shape and construction details of this viol place it firmly in the second half of the 1600s and within the French/English style of making.
The instrument has undergone a number of substantial adjustments since its original incarnation and the identity of the original maker has consequently been obscured. These later adjustments and their origins are not the main subject of this article, but their nature and quality do make them deserving of study. Is it now possible to prove who really did make this viol? This article presents the evidence that reveals that this instrument displays many characteristics that are typical of the workmanship of the French maker Michel Collichon, who worked in Paris between c.1683 and 1693.
Systematic collection of patient-reported outcomes in atrial fibrillation: feasibility and initial results of the Utah mEVAL AF programme
Authors: Steinberg Benjamin A , Turner Jeffrey , Lyons Ann , Biber Joshua , Chelu Mihail G , Fang James C , Freedman Roger A , Han Frederick T , Hardisty Benjamin , Marrouche Nassir F , Ranjan Ravi , Shah Rashmee U , Spertus John A , Stehlik Josef , Zenger Brian , Piccini Jonathan P , Hess Rachel 
Published: October 2019

Abstract

Aims
Incorporating patient-reported outcomes (PROs) into routine care of atrial fibrillation (AF) enables direct integration of symptoms, function, and health-related quality of life (HRQoL) into practice. We report our initial experience with a system-wide PRO initiative among AF patients.

Methods and results
All patients with AF in our practice undergo PRO assessment with the Toronto AF Severity Scale (AFSS), and generic PROs, prior to electrophysiology clinic visits. We describe the implementation, feasibility, and results of clinic-based, electronic AF PRO collection, and compare AF-specific and generic HRQoL assessments. From October 2016 to February 2019, 1586 unique AF patients initiated 2379 PRO assessments, 2145 of which had all PRO measures completed (90%). The median completion time for all PRO measures per visit was 7.3 min (1st, 3rd quartiles: 6, 10). Overall, 38% of patients were female (n = 589), mean age was 68 (SD 12) years, and mean CHA2DS2-VASc score was 3.8 (SD 2.0). The mean AFSS symptom score was 8.6 (SD 6.6, 1st, 3rd quartiles: 3, 13), and the full range of values was observed (0, 35). Generic PROs of physical function, general health, and depression were impacted at the most severe quartiles of AF symptom score (P &lt; 0.0001 for each vs. AFSS quartile).

Conclusion
Routine clinic-based, PRO collection for AF is feasible in clinical practice and patient time investment was acceptable. Disease-specific AF PROs add value to generic HRQoL instruments. Further research into the relationship between PROs, heart rhythm, and AF burden, as well as PRO-guided management, is necessary to optimize PRO utilization.
Surviving onshore soil microbial communities differ among the Qing-Tibetan lakes with different salinity
Authors: Huang Jianrong , Yang Jian , Jiang Hongchen , Wu Geng , Xie Zhanling , Dong Hailiang 
Published: October 2019

ABSTRACTLittle is known about the onshore microbial contribution to the microbial communities in nearby lakes and its response to salinity. In this study, transplanting experiments were established by caging onshore soils with dialysis bags followed by in situ 50-day incubation in nearby lakes with different salinity on the Qinghai-Tibetan Plateau. At the end of the experiment, geochemical and microbial analyses were performed on the original soils, caged soils and lake waters and sediments at the incubation sites. The results showed that the salinity increased significantly (P < 0.05) in the caged soils and such salinity increases showed significant (P < 0.05) positive correlation with the salinity of the studied lakes. The microbial community composition and predicted functions in the caged soils were significantly (P < 0.05) changed in comparison with their corresponding original soils, and such variation could be mainly explained by the succession of members of the Proteobacteria, Bacteroidetes and Actinobacteria from the original soils to their corresponding caged soils. The onshore microbial contribution appeared to be limited (up to 11.2% for sediment and negligible for water, respectively) to nearby lake microbial communities. Nevertheless, the survival of onshore soil microbial communities was mainly limited by the salinity of the receiving lakes.
Compound Dynamics and Combinatorial Patterns of Amino Acid Repeats Encode a System of Evolutionary and Developmental Markers
Authors: Pelassa Ilaria , Cibelli Marica , Villeri Veronica , Lilliu Elena , Vaglietti Serena , Olocco Federica , Ghirardi Mirella , Montarolo Pier Giorgio , Corà Davide , Fiumara Ferdinando 
Published: October 2019

AbstractHomopolymeric amino acid repeats (AARs) like polyalanine (polyA) and polyglutamine (polyQ) in some developmental proteins (DPs) regulate certain aspects of organismal morphology and behavior, suggesting an evolutionary role for AARs as developmental “tuning knobs.” It is still unclear, however, whether these are occasional protein-specific phenomena or hints at the existence of a whole AAR-based regulatory system in DPs. Using novel approaches to trace their functional and evolutionary history, we find quantitative evidence supporting a generalized, combinatorial role of AARs in developmental processes with evolutionary implications. We observe nonrandom AAR distributions and combinations in HOX and other DPs, as well as in their interactomes, defining elements of a proteome-wide combinatorial functional code whereby different AARs and their combinations appear preferentially in proteins involved in the development of specific organs/systems. Such functional associations can be either static or display detectable evolutionary dynamics. These findings suggest that progressive changes in AAR occurrence/combination, by altering embryonic development, may have contributed to taxonomic divergence, leaving detectable traces in the evolutionary history of proteomes. Consistent with this hypothesis, we find that the evolutionary trajectories of the 20 AARs in eukaryotic proteomes are highly interrelated and their individual or compound dynamics can sharply mark taxonomic boundaries, or display clock-like trends, carrying overall a strong phylogenetic signal. These findings provide quantitative evidence and an interpretive framework outlining a combinatorial system of AARs whose compound dynamics mark at the same time DP functions and evolutionary transitions.
The Social Relationship Context of Elder Mistreatment
Authors: Wong Jaclyn S , Breslau Hannah , McSorley V Eloesa , Wroblewski Kristen E , Howe Melissa J K , Waite Linda J 
Published: October 2019

Abstract

Background and Objectives
Elder mistreatment victims at risk of poor physical and psychological health may benefit from increased social support. This article identifies mistreatment victims among community-dwelling older Americans and maps their social networks to guide the design of social support interventions.

Research Design and Methods
Using nationally representative survey data from Wave 3 (2015–2016) of the National Social Life, Health, and Aging Project (N = 2,334) and descriptive, latent class, and regression analyses, we estimate the prevalence of mistreatment since age 60, identify the alleged perpetrators’ relationships to the victims, and examine victims’ social networks.

Results
Self-reported lifetime prevalence of elder mistreatment is as high as 21%, depending on the mistreatment behavior measured. Latent class analysis reveals two mistreatment classes: 12% of older adults experienced multiple types of mistreatment (polyvictimization), and 6% experienced primarily financial mistreatment. Although alleged perpetrators are unlikely to appear in older adults’ core social networks, the most commonly reported perpetrators are children and relatives. Regression analyses show that experiencing mistreatment since age 60 is associated with having less current social support, more social strain, and fewer kin in the core social network. Older adults reporting polyvictimization also have less-dense core networks.

Discussion and Implications
Increasing family support should be done cautiously because children and relatives are frequently named as mistreatment perpetrators. Increasing communication across polyvictimization victims’ network members may support their well-being. Providing outside assistance with financial management could benefit financial mistreatment victims.
Towards assessing the influence of sediment loading on Last Interglacial sea level
Authors: Pico T 
Published: October 2019

SUMMARY
Locally, the elevation of last interglacial (LIG; ∼122 ka) sea level markers is modulated by processes of vertical displacement, such as tectonic uplift or glacial isostatic adjustment, and these processes must be accounted for in deriving estimates of global ice volumes from geological sea level records. The impact of sediment loading on LIG sea level markers is generally not accounted for in these corrections, as it is assumed that the impact is negligible except in extremely high depositional settings, such as the world's largest river deltas. Here we perform a generalized test to assess the extent to which sediment loading may impact global variability in the present-day elevation of LIG sea level markers. We numerically simulate river sediment deposition using a diffusive model that incorporates a migrating shoreline to construct a global history of sedimentation over the last glacial cycle. We then calculate sea level changes due to this sediment loading using a gravitationally self-consistent model of glacial isostatic adjustment, and compare these predictions to a global compilation of LIG sea level data. We perform a statistical analysis, which accounts for spatial autocorrelation, across a global compilation of 1287 LIG sea level markers. Though limited by uncertainties in the LIG sea level database and the precise history of river deposition, this analysis suggests there is not a statistically significant global signal of sediment loading in LIG sea level markers. Nevertheless, at sites where LIG sea level markers have been measured, local sea level predicted using our simulated sediment loading history is perturbed up to 16 m. More generally, these predictions establish the relative sensitivity of different regions to sediment loading. Finally, we consider the implications of our results for estimates of tectonic uplift rates derived from LIG marine terraces; we predict that sediment loading causes 5–10 m of subsidence over the last glacial cycle at specific locations along active margin regions such as California and Barbados, where deriving long-term tectonic uplift rates from LIG shorelines is a common practice.
Ricci Iteration for Coupled Kähler–Einstein Metrics
Authors: Takahashi Ryosuke 
Published: October 2019

AbstractIn this paper, we introduce the “coupled Ricci iteration”, a dynamical system related to the Ricci operator and twisted Kähler–Einstein metrics as an approach to the study of coupled Kähler–Einstein (CKE) metrics. For negative 1st Chern class, we prove the smooth convergence of the iteration. For positive 1st Chern class, we also provide a notion of coercivity of the Ding functional and show its equivalence to the existence of CKE metrics. As an application, we prove the smooth convergence of the iteration on CKE Fano manifolds assuming that the automorphism group is discrete.
The Differences Between Consecutive Primes, V
Authors: Heath-Brown Roger 
Published: October 2019

AbstractWe show that $$\begin{equation*}\sum_{\substack{p_n\le x\\ p_{n+1}-p_n\ge\sqrt{p_n}}}(p_{n+1}-p_n) \ll_{\varepsilon} x^{3/5+\varepsilon}\end{equation*}$$or any fixed $\varepsilon&gt;0$. This improves a result of Matomäki, in which the exponent was $2/3$.