bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phantom eye pain: a multicentric study in 100 patients
Authors: Martel Arnaud , Baillif Stephanie , Thomas Pierre , Almairac Fabien , Galatoire Olivier , Hamedani Mehrad , Fontaine Denys , Lanteri‐Minet Michel 
Published: October 2020

AbstractPurposePhantom eye syndrome (PES) is an underestimated complication of eye amputation (EA) characterized by phantom eye pain (PEP), phantom visions and/or phantom sensations. The aim of this study was to assess PEP prevalence, features, risk factors, social and psychological consequences and associated quality of life.MethodsA questionnaire study was conducted in three oculoplastic departments between April 2016 and July 2017. Patients >18 years who had undergone EA ≥3 months earlier were included and asked to complete a prestamped questionnaire. Patient's characteristics, preoperative, surgical and postoperative data were collected.ResultsOf the 185 questionnaires given, 115 (62%) were returned for analysis. Hundred patients with a mean age of 65.1 years (29–92; SD = 13.0) were included. Eye amputation (EA) indications were uveal melanoma (n = 24, 24%), trauma (n = 20, 20%), retinal detachment (n = 20, 20%), glaucoma (n = 14, 14%) and endophthalmitis (n = 12, 12%). Forty‐seven (47%), 30 (30%) and 38 (38%) patients experienced PEP, phantom visions and phantom sensations, respectively. Anxiety and depression [Hospital Anxiety Depression scale (HADS) score ≥8 for both] were diagnosed in 34 (34%) and 42 (42%) patients, respectively. The mean EQ‐5D‐3L and EQ‐5D visual analogue scale scores were 0.8 (0.06–1; SD = 0.2) and 68 (0–100; SD = 22), respectively. Preoperative eye pain (p = 0.031), glaucoma (p = 0.027), postoperative anxiety with HADS score ≥8 (p = 0.012) and ≥11 (p = 0.014), aesthetic discomfort (p = 0.002) and EQ‐5D‐3L score <0.8 (p < 0.001) were significantly associated with PEP in the univariate analysis. In the multivariate analysis, only anxiety (HADS score ≥8) was significantly associated with PEP (p = 0.009).ConclusionPhantom eye pain (PEP) is a common complication of EA strongly associated with postoperative anxiety.
Endothelial‐protective effects of a G‐protein‐biased sphingosine‐1 phosphate receptor‐1 agonist, SAR247799, in type‐2 diabetes rats and a randomized placebo‐controlled patient trial
Authors: Bergougnan Luc , Andersen Grit , Plum‐Mörschel Leona , Evaristi Maria Francesca , Poirier Bruno , Tardat Agnes , Ermer Marcel , Herbrand Theresa , Arrubla Jorge , Coester Hans Veit , Sansone Roberto , Heiss Christian , Vitse Olivier , Hurbin Fabrice , Boiron Rania , Benain Xavier , Radzik David , Janiak Philip , Muslin Anthony J. , Hovsepian Lionel , Kirkesseli Stephane , Deutsch Paul , Parkar Ashfaq A. 
Published: October 2020

AimsSAR247799 is a G‐protein‐biased sphingosine‐1 phosphate receptor‐1 (S1P1) agonist designed to activate endothelial S1P1 and provide endothelial‐protective properties, while limiting S1P1 desensitization and consequent lymphocyte‐count reduction associated with higher doses. The aim was to show whether S1P1 activation can promote endothelial effects in patients and, if so, select SAR247799 doses for further clinical investigation.MethodsType‐2 diabetes patients, enriched for endothelial dysfunction (flow‐mediated dilation, FMD <7%; n = 54), were randomized, in 2 sequential cohorts, to 28‐day once‐daily treatment with SAR247799 (1 or 5 mg in ascending cohorts), placebo or 50 mg sildenafil (positive control) in a 5:2:2 ratio per cohort. Endothelial function was assessed by brachial artery FMD. Renal function, biomarkers and lymphocytes were measured following 5‐week SAR247799 treatment (3 doses) to Zucker diabetic fatty rats and the data used to select the doses for human testing.ResultsThe maximum FMD change from baseline vs placebo for all treatments was reached on day 35; mean differences vs placebo were 0.60% (95% confidence interval [CI] −0.34 to 1.53%; P = .203) for 1 mg SAR247799, 1.07% (95% CI 0.13 to 2.01%; P = .026) for 5 mg SAR247799 and 0.88% (95% CI −0.15 to 1.91%; P = .093) for 50 mg sildenafil. Both doses of SAR247799 were well tolerated, did not affect blood pressure, and were associated with minimal‐to‐no lymphocyte reduction and small‐to‐moderate heart rate decrease.ConclusionThese data provide the first human evidence suggesting endothelial‐protective properties of S1P1 activation, with SAR247799 being as effective as the clinical benchmark, sildenafil. Further clinical testing of SAR247799, at sub‐lymphocyte‐reducing doses (≤5 mg), is warranted in vascular diseases associated with endothelial dysfunction.
Battleground midgut: The cost to the mosquito for hosting the malaria parasite
Authors: Hajkazemian Melika , Bossé Clément , Mozūraitis Raimondas , Emami S. Noushin 
Published: October 2020

AbstractIn eco‐evolutionary studies of parasite–host interactions, virulence is defined as a reduction in host fitness as a result of infection relative to an uninfected host. Pathogen virulence may either promote parasite transmission, when correlated with higher parasite replication rate, or decrease the transmission rate if the pathogen quickly kills the host. This evolutionary mechanism, referred to as ‘trade‐off’ theory, proposes that pathogen virulence evolves towards a level that most benefits the transmission. It has been generally predicted that pathogens evolve towards low virulence in their insect vectors, mainly due to the high dependence of parasite transmission on their vector survival. Therefore, the degree of virulence which malaria parasites impose on mosquito vectors may depend on several external and internal factors. Here, we review briefly (i) the role of mosquito in parasite development, with a particular focus on mosquito midgut as the battleground between Plasmodium and the mosquito host. We aim to point out (ii) the histology of the mosquito midgut epithelium and its role in host defence against parasite's countermeasures in the three main battle sites, namely (a) the lumen (microbiota and biochemical environment), (b) the peritrophic membrane (physical barrier) and (c) the tubular epithelium including the basal membrane (physical and biochemical barrier). Lastly, (iii) we describe the impact which malaria parasite and its virulence factors have on mosquito fitness.
A pharmacokinetic–pharmacodynamic model for the MET tyrosine kinase inhibitor, savolitinib, to explore target inhibition requirements for anti‐tumour activity
Authors: Jones Rhys D.O. , Grondine Mike , Borodovsky Alexandra , San Martin Maryann , DuPont Michelle , D'Cruz Celina , Schuller Alwin , Henry Ryan , Barry Evan , Castriotta Lillian , Anjum Rana , Petersson Klas , Sahota Tarjinder , Ahmed Ghada F. 
Published: October 2020

Background and PurposeSavolitinib (AZD6094, HMPL‐504, volitinib) is an oral, potent, and highly MET receptor TK inhibitor. This series of studies aimed to develop a pharmacokinetic–pharmacodynamic (PK/PD) model to link inhibition of MET phosphorylation (pMET) by savolitinib with anti‐tumour activity.Experimental ApproachCell line‐derived xenograft (CDX) experiments using human lung cancer (EBC‐1) and gastric cancer (MKN‐45) cells were conducted in athymic nude mice using a variety of doses and schedules of savolitinib. Tumour pMET changes and growth inhibition were calculated after 28 days. Population PK/PD techniques were used to construct a PK/PD model for savolitinib.Key ResultsSavolitinib showed dose‐ and dose frequency‐dependent anti‐tumour activity in the CDX models, with more frequent, lower dosing schedules (e.g., twice daily) being more effective than intermittent, higher dosing schedules (e.g., 4 days on/3 days off or 2 days on/5 days off). There was a clear exposure–response relationship, with maximal suppression of pMET of >90%. Data from additional CDX and patient‐derived xenograft (PDX) models overlapped, allowing calculation of a single EC50 of 0.38 ng·ml−1. Tumour growth modelling demonstrated that prolonged, high levels of pMET inhibition (>90%) were required for tumour stasis and regression in the models.Conclusion and ImplicationsHigh and persistent levels of MET inhibition by savolitinib were needed for optimal monotherapy anti‐tumour activity in preclinical models. The modelling framework developed here can be used to translate tumour growth inhibition from the mouse to human and thus guide choice of clinical dose and schedule.
Bridging the knowledge‐implementation gap between agency and academia: A case study of a graduate research experience
Authors: Karasov‐Olson Aviv , Bird Alicia K. , Collins Amy C. , Graves Emily E. , Shaw Julea A. , Tymstra Eric F. , Kelsey T. Rodd , Schwartz Mark W. 
Published: October 2020

AbstractConservation biology is particularly susceptible to the knowledge‐implementation gap where academic pursuits do not always meet the needs of practitioners. Providing future practitioners with relevant training and experiences as graduate students can help narrow this gap. An example of one such experience was a partnership between the University of California, Davis and The Nature Conservancy (TNC), established to conduct climate vulnerability assessments of wildlife in California. Here, we discuss the value of the experience for graduate students as both developing conservation professionals. Students were motivated to participate because of the opportunity to work on an applied project and valued collaborating with fellow graduate students. Overall, we felt the project successfully met objectives set out by TNC. In recognition of the value projects like these have, we provide a suite of recommendations based on our experience and lessons learned for academic faculty and conservation practitioners wishing to establish similar opportunities.
Left atrial structural and functional remodeling study in type 2 diabetic patients in sub‐Saharan Africa: Role of left atrial strain by 2D speckle tracking echocardiography
Authors: Menanga Alain Patrick , Nganou‐Gnindjio Chris Nadège , Ahinaga André Jules , Sadeu Wafeu Guy , Lade Viche , Nzokou Daryl , Boombhi Jérome , Kingue Samuel 
Published: October 2020

AbstractObjectiveTo evaluate the role of peak atrial longitudinal strain (PALS) through speckle tracking 2D echocardiography for the assessment of structural and functional left atrial (LA) remodeling in a type 2 diabetes mellitus (T2DM) population.MethodologyWe conducted a cross‐sectional study during a 9‐month period. T2DM adults aged 18 and above were included. The variables assessed during the study include age and gender of participants, diabetes characteristics, cardiovascular risk factors, clinical anthropometric and hemodynamic parameters, standard echocardiographic parameters, volume‐derived LA functions, and 2D PALS.ResultsWe included a total of 102 patients. The mean age was 58 ± 11.7 years, and the M/F sex ratio was 1:1.5. Coexistent arterial hypertension (HTN) was observed in more than half (59.8%) of the population sample. Mean 2D PALS was 29.2 ± 8.9% with 58.8% (95% CI: 50.0–68.6) of subjects having a reduced LA strain (ie,<32%). Reservoir and pump functions were the most altered LA volumetric phasic functions. Mean indexed LA maximal volume was 22.2 ± 6.8 mL/m2. There was a significant association between abnormal PALS and age, Body mass index (BMI), indexed LA volume, E/E’ ratio, LA active ejection fraction (pump function), and LA expansion index (reservoir function).ConclusionLeft atrial remodeling is a recurrent condition in adult T2DM Cameroonians. The reservoir and pump LA functions were the most affected. Assessment of LA global strain allows early detection of LA remodeling with comparison to LA size standard analyses. Age, BMI, indexed LA volume, E/E’ ratio, and reservoir and pump LA functions were associated to 2D LA global strain impairment.
Whole‐exome analyses of congenital muscular dystrophy and congenital myopathy patients from India reveal a wide spectrum of known and novel mutations
Authors: Sanga Shamita , Ghosh Arnab , Kumar Krishna , Polavarapu Kiran , Preethish‐Kumar Veeramani , Vengalil Seena , Nashi Saraswati , Bardhan Mainak , Arunachal Gautham , Raju Sanita , Gayathri Narayanappa , Biswas Nidhan K. , Chakrabarti Saikat , Nalini Atchayaram , Roy Sudipto , Acharya Moulinath 
Published: October 2020

Background and purposeCongenital muscular dystrophies (CMDs) and congenital myopathies (CMs) are a group of genetically and clinically heterogeneous degenerative primary muscle disorders with onset at birth or during infancy. Due to vast heterogeneity, clinical examination and protein‐based analyses often fail to identify the genetic causes of these diseases. The aim of this study was to genetically diagnose a cohort of 36 difficult‐to‐diagnose CMD and CM cases of Indian origin using next‐generation sequencing methods.MethodsWhole‐exome sequencing (WES) was performed to identify pathogenic mutations in previously reported CMD and CM‐related genes using variant calling and stringent variant filtration process. Subsequently, in silico homology modelling and molecular dynamics simulations (MDS) studies were undertaken for a number of novel and missense variants.ResultsA total of 33 and 21 rare and deleterious mutations were identified in 28 genes previously reported in CMD and CM based on OMIM, ClinVar and Orphanet, respectively. We could accurately diagnose 54% patients (n = 12/22) in the CMD group and 35% patients (n = 5/14) in the CM group. Furthermore, MDS studies for mutations located in LMNA, LAMA2 and RYR1 suggest that the wild‐type proteins are more stable than their mutant counterparts, implying a potential mechanism of pathogenesis.ConclusionThe WES findings led us to identify reported as well as novel variants for the first time in Indian patients with CMD and CM. This allowed us to achieve an accurate genetic diagnosis, which was difficult using conventional diagnostic tools. Transferring these WES findings to clinical practice will help guide clinical care of the affected patients and inform genetic counselling.
PRE‐driven protein NMR structures: an alternative approach in highly paramagnetic systems
Authors: Trindade Inês B. , Invernici Michele , Cantini Francesca , Louro Ricardo O. , Piccioli Mario 
Published: October 2020

Metalloproteins play key roles across biology, and knowledge of their structure is essential to understand their physiological role. For those metalloproteins containing paramagnetic states, the enhanced relaxation caused by the unpaired electrons often makes signal detection unfeasible near the metal center, precluding adequate structural characterization right where it is more biochemically relevant. Here, we report a protein structure determination by NMR where two different sets of restraints, one containing Nuclear Overhauser Enhancements (NOEs) and another containing Paramagnetic Relaxation Enhancements (PREs), are used separately and eventually together. The protein PioC from Rhodopseudomonas palustris TIE‐1 is a High Potential Iron‐Sulfur Protein (HiPIP) where the [4Fe‐4S] cluster is paramagnetic in both oxidation states at room temperature providing the source of PREs used as alternative distance restraints. Comparison of the family of structures obtained using NOEs only, PREs only, and the combination of both reveals that the pairwise root‐mean‐square deviation (RMSD) between them is similar and comparable with the precision within each family. This demonstrates that, under favorable conditions in terms of protein size and paramagnetic effects, PREs can efficiently complement and eventually replace NOEs for the structural characterization of small paramagnetic metalloproteins and de novo‐designed metalloproteins by NMR.DatabasesThe 20 conformers with the lowest target function constituting the final family obtained using the full set of NMR restraints were deposited to the Protein Data Bank (PDB ID: 6XYV). The 20 conformers with the lowest target function obtained using NOEs only (PDB ID: 7A58) and PREs only (PDB ID: 7A4L) were also deposited to the Protein Data Bank. The chemical shift assignments were deposited to the BMRB (code 34487).
Usage of compact compression specimens to determine non‐linear fracture parameters of concrete
Authors: Ince Ragip 
Published: October 2020

AbstractUp to now, the compact compression specimens (CCS) have only been used to estimate the fracture toughness parameter of cement‐based materials. In the study, the linear elastic fracture mechanics formulae of CCS, namely, the universal weight functions with four terms, KI (stress intensity factor), CMOD (crack mouth opening displacement), and COD (crack opening displacement) profile were, therefore, derived using the finite element method. To investigate the extent to which CCS tests could model the non‐linear fracture behaviour of concrete, 11 series of tests in the literature were subsequently examined for the effective crack models: the two‐parameter model, the size effect model, and the double‐K model. Two prediction formulae based on previous test data were proposed to estimate unstable fracture toughness and initiation fracture toughness of concrete. The results of CCS test‐based non‐linear fracture mechanics look viable and very promising.
Behaviour at short temporal scales drives dispersal dynamics and survival in a metapopulation of brook trout (Salvelinus fontinalis)
Authors: White Shannon L. , Wagner Tyler 
Published: October 2020

Abstract

Movement has been studied extensively in stream salmonids, and most data suggest that population‐level behaviour is best described by a leptokurtic distribution. This distribution emphasises the large proportion of sedentary individuals in a population, which can implicitly lead to assumptions of low population connectivity and overlook the ecological significance of rare individuals with more mobile phenotypes.

We report findings of a multi‐season radio telemetry study conducted on four adjacent populations of wild brook trout (Salvelinus fontinalis) connected by Loyalsock Creek in north‐central Pennsylvania. We used these data to investigate temporal and spatial patterns in movement and fitness trade‐offs associated with behavioural phenotype.

Similar to previous studies, we found that 59 of the 120 radio‐tagged individuals (49%) were sedentary and moved less than 200 m. Only 18% of individuals dispersed more than 1 km, but the maximum distance moved exceeded 13 km. We also found that mobile individuals had significantly higher summer and autumn survival than did sedentary fish, which could indicate that there are fitness benefits associated with vagility.

Most long‐distance movements were the result of fish migrating from small tributaries into a larger mainstem river in the days after spawning. Therefore, even though mobility was only expressed for a short duration and by relatively few individuals in the population, the behaviour appears to maintain metapopulation connectivity throughout the catchment.

Our study highlights the ecological significance of rare phenotypes for population demography across large spatial scales and the need to understand movement across multiple temporal and spatial scales to ensure adequate conservation of critical forms of cryptic life history diversity.
Countering fragmentation, taking back the state, or partisan agenda‐setting? Explaining policy integration and administrative coordination reforms
Authors: Trein Philipp , Ansell Christopher K. 
Published: October 2020

AbstractPolicies to integrate and coordinate across sectors have become important in recent years, but we know little about the drivers of these reforms. This article evaluates three explanations for differences in patterns of policy integration and administrative coordination reforms across countries and policy sectors over time. Reform activity could reflect: (a) the fragmenting effects of agencification; (b) a strategy of governments to regain policy control; or (c) partisan agendas. We test these explanatory scenarios using multilevel probit and structural equation models on an original dataset of policy integration and administrative coordination reforms. Our findings support the claim that reforms are a reaction to the institutional fragmentation produced by agencification and that agencies drive these reforms. Furthermore, we find that left parties are particularly likely to pursue policy integration reforms. We also find that policy integration and administrative coordination reform frequencies are linked but have different path dependencies.
Methods for Delivery and Distribution of Amendments for Subsurface Remediation: A Critical Review
Authors: Muller Katherine A. , Johnson Christian D. , Bagwell Christopher E. , Truex Michael J. 
Published: October 2020

AbstractThe ability to reliably deliver and widely distribute remedial amendments through the subsurface environment is of paramount importance to achieve cleanup objectives for contaminated sediments and groundwater for protection of sensitive environmental habitats and natural resources. A wide range of amendments, delivery techniques, and subsurface access methods are available. However, the applicability of these approaches is dependent on a multitude of site‐specific factors. In this review, an overview of amendments and access/distribution methods is provided, along with discussion of the maturity level, advantages, and limitations that relate to the potential effectiveness of each approach in the context of site‐specific factors. Each amendment and delivery approach are further evaluated for applicability to the following subsurface target zones: saturated, unsaturated, and perched water, with specific focus on high and low permeability regions in each zone. The review highlights a critical need for field‐tested approaches targeting unsaturated and perched water zones, as well as low‐permeability regions within all subsurface regions. The intent of this review is to provide critical information and insight into how amendments can be delivered, emplaced, and/or distributed effectively in the subsurface environment to effectively manage subsurface contamination.