bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells
Authors: Flood Michael D. , Eggers Erika D.
Published: October 2020

The adaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses covers only ∼3 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 and D2 families. D1Rs are expressed on horizontal cells and some bipolar, amacrine and ganglion cells. In the D2 family D2Rs are expressed on dopaminergic amacrine cells and D4Rs are primarily expressed on photoreceptors. However, the roles of activating these receptors to modulate the synaptic properties of the inputs to ganglion cells are not yet clear. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating D1Rs and D4Rs changed the light-evoked and spontaneous excitatory inputs to ON-sustained (ON-s) ganglion cells. We found that both D1R and D4R activation decrease the light-evoked excitatory inputs to ON-s ganglion cells, but that only the sum of the peak response decrease due to activating the two receptors was similar to the effect of light adaptation to a rod-saturating background. The largest effects on spontaneous excitatory activity of both D1R and D4R agonists was on the frequency of events, suggesting that both D1Rs and D4Rs are acting upstream of the ganglion cells.

New and Noteworthy

Dopamine by bright light conditions allows retinal neurons to reduce sensitivity to adapt to bright light conditions. It is not clear how and why dopamine receptors modulate retinal ganglion cell signaling. We found that both D1 and D4 dopamine receptors in photoreceptors and inner retinal neurons contribute significantly to the reduction in sensitivity of ganglion cells with light adaptation. However, light adaptation also requires dopamine independent mechanisms that could reflect inherent sensitivity changes in photoreceptors.
Forward variable selection improves the power of random forest for high- dimensional microbiome data
Authors: Dang Tung , Kishino Hirohisa
Published: October 2020

Background

Random forest (RF) captures complex feature patterns that differentiate groups of samples and is rapidly being adopted in microbiome studies. However, a major challenge is the high dimensionality of microbiome datasets. They include thousands of species or molecular functions of particular biological interest. This high dimensionality significantly reduces the power of random forest approaches for identifying true differences. The widely used Boruta algorithm iteratively removes features that are proved by a statistical test to be less relevant than random probes.

Result

We developed a massively parallel forward variable selection algorithm and coupled it with the RF classifier to maximize the predictive performance. The forward variable selection algorithm adds new variable to a set of selected variables as far as the prespecified criterion of predictive power is improved. At each step, the parameters of random forest are optimized. We demonstrated the performance of the proposed approach, which we named RF-FVS, by analyzing two published datasets from large-scale case-control studies: (i) 16S rRNA gene amplicon data forClostridioides difficileinfection (CDI) and (ii) shotgun metagenomics data for human colorectal cancer (CRC). The RF-FVS approach further screened the variables that the Boruta algorithm left and improved the accuracy of the random forest classifier from 81% to 99.01% for CDI and from 75.14% to 90.17% for CRC.

Conclusion

Valid variable selection is essential for the analysis of high-dimensional microbiota data. By adopting the Boruta algorithm for pre-screening of the variables, our proposed RF-FVS approach improves the accuracy of random forest significantly with minimum increase of computational burden. The procedure can be used to identify the functional profiles that differentiate samples between different conditions.
Visual neuroscience methods for marmosets: efficient receptive field mapping and head-free eye tracking
Authors: Jendritza Patrick , Klein Frederike J. , Rohenkohl Gustavo , Fries Pascal
Published: October 2020

The marmoset has emerged as a promising primate model system, in particular for visual neuroscience. Many common experimental paradigms rely on head fixation and an extended period of eye fixation during the presentation of salient visual stimuli. Both of these behavioral requirements can be challenging for marmosets. Here, we present two methodological developments, each addressing one of these difficulties. First, we show that it is possible to use a standard eye tracking system without head fixation to assess visual behavior in the marmoset. Eye tracking quality from head-free animals is sufficient to obtain precise psychometric functions from a visual acuity task. Secondly, we introduce a novel method for efficient receptive field mapping that does not rely on moving stimuli but uses fast flashing annuli and wedges. We present data recorded during head-fixation in areas V1 and V6 and show that receptive field locations are readily obtained within a short period of recording time. Thus, the methodological advancements presented in this work will contribute to establish the marmoset as a valuable model in neuroscience.
Ethyl 3,4-bis(acetyloxy)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate
Authors: Dallasta Pedroso Sofia , Caracelli Ignez , Zukerman-Schpector Julio , Soto-Monsalve Monica , De Almeida Santos Regina H. , Correia Carlos Roque D. , Llanes Garcia Ariel L. , Tiekink Edward R. T.
Published: October 2020

The title pyrrolidine compound, C18H23NO7, is a tetra-substituted species in which the five-membered ring has a twisted conformation with the twist occurring in the C—C bond bearing the adjacent acetyloxy substituents; the Cm—Ca—Ca—Cp torsion angle is −40.76 (18)° [m = methylene, a = acetyloxy and p = phenyl]. The N atom, which is sp
2-hybridized [sum of bond angles = 359.4°], bears an ethylcarboxylate substitutent and is connected to a methylene-C atom on one side and a carbon atom bearing a 4-methoxyphenyl group on the other side. Minor disorder is noted in the ethylcarboxylate substituent as well as in one of the acetyloxy groups; the major components of the disorder have site occupancies of 0.729 (9) and 0.62 (3), respectively. The most notable feature of the molecular packing is the formation of helical, supramolecular chains aligned along the b-axis direction whereby the carbonyl-O atom not involved in a disordered residue accepts C—H...O interactions from methylene-H and two-C atom separated methine-H atoms to form a six-membered {...HCCCH...O} synthon.
catena-Poly[[chloridotris(1,3-thiazolidine-2-thione-κS)cadmium(II)]-μ-chlorido]
Authors: Diop Aboubacar , Diop Tidiane , Kama Antoine Blaise , Diop Cheikh Abdou Khadre , Tumanov Nikolay
Published: October 2020

The synthesis and characterization of poly[dichloridotri(1,3-thiazolidine-2-thione)cadmium(II)], [CdCl2(C3H5NS2)3]
n
, prepared from CdCl2·H2O and C3H5NS2 (tzdSH) in a 1:3 ratio, are described. The CdII cation is coordinated by three 1,3-thiazolidine-2-thione molecules and three Cl− anions in a distorted octahedral environment. The Cd metal centres are connected via Cl− ligands, creating polymeric chains running along the a-axis direction. The conformation of the chains is stabilized by N—H...Cl hydrogen bonds.
The role of e-commerce in the urban food system under COVID-19: lessons from China
Authors: Guo Hongdong , Liu Yehong , Shi Xinjie , Chen Kevin Z.
Published: October 2020

Purpose

The purpose of this study is to investigate e-commerce as a new means to ensure that the urban demand for food can be met during the coronavirus disease 2019 (COVID-19) outbreak. Because a number of COVID-19 e-commerce models have emerged, this paper discusses whether and (if so) why and how e-commerce can ensure the food supply for urban residents if social distancing becomes a norm and the transport and logistics systems are hindered.

Design/methodology/approach

This study used qualitative research methods following the lack of empirical data. The authors referred to relevant literature, statistical data and official reports and comprehensively described the importance of e-commerce in ensuring the safety of food supply to Chinese urban residents under the impact of the epidemic. Corresponding to the traditional case study, this study presented a Chinese case on ensuring food supply through e-commerce during an epidemic.

Findings

The authors found that three e-commerce models played a substantial role in preventing the spread of the epidemic and ensuring the food supply for urban residents. The nationwide e-commerce platforms under market leadership played their roles by relying on the sound infrastructure of large cities and its logistics system was vulnerable to the epidemic. In the worst-affected areas, particularly in closed and isolated communities, the local e-commerce model was the primary model, supplemented by the unofficial e-commerce model based on social relations. Through online booking, centralized procurement and community distribution, the risk of cross infection could be effectively reduced and the food demand could be effectively satisfied. The theoretical explanation further verifies that, apart from e-commerce, a governance system that integrates the government, e-commerce platform, community streets and the unofficial guanxi also impels the success of these models.

Originality/value

Lessons from China are drawn for other countries struggling to deliver food to those in need under COVID-19. The study not only provides a solution that will ensure constant food supply to urban residents under the COVID-19 epidemic but also provides some reference for the maintenance of the food system of urban residents under the impact of a globalization-related crisis in future.
Location and economic resilience in rubber farming communities in southwest China
Authors: Jin Shaoze , Huang Jikun , Waibel Hermann
Published: October 2020

Purpose

In rural areas, geographic location is key to market access and labor mobility of farm households. This paper aims to investigate the opportunities and constraints of smallholder rubber farmers in southwest China to adjust to the changes in economic and institutional conditions, namely the declining rubber prices, emerging land rental markets and growing off-farm job opportunities.

Design/methodology/approach

The empirical basis is a dataset of some 600 rubber farmers in Xishuangbanna Dai Autonomous Prefecture, Yunnan Province, collected in March 2015. The study uses instrumental variable and recursive bivariate probit models to account for possible endogeneity and selection bias.

Findings

With rubber prices in decline, the elevation of rubber plantations is an essential factor for the costs of access to the local factor markets and influences farm households' possibilities to adopt coping strategies. Notably, we find a U-shape type of relationship between the location and renting-out land due to the decline in rubber profitability. Rubber producers in low elevations are better bestowed with access to local markets. Households in high elevations, where rubber planting came in later, can shift to new crops like tea. However, the economic resilience of farmers in middle elevations is low due to their higher adjustment costs.

Originality/value

The paper provides a constructive basis for designing more location-specific development policies and can help avoid the past often ineffective blanket measures. Its implications have significant relevance for areas with similar conditions, for example, the remote, ethnic minority–dominated and mountainous rural areas in China.
Staying in a hotel or peer-to-peer accommodation sharing? A discrete choice experiment with online reviews and discount strategies
Authors: Fu Shixuan , Cheng Xusen , Bao Ying , Bilgihan Anil , Okumus Fevzi
Published: October 2020

Purpose

This study aims to elicit the preferences of potential travelers for different property listings' attributes (online review number, positive valence rate of reviews and discount strategy) when selecting hotels and peer-to-peer (P2P) accommodation sharing on online booking platforms.

Design/methodology/approach

A discrete choice experiment (DCE) was conducted with 291 respondents with accommodation needs. They were asked to choose between pairs of listings.

Findings

The authors found that when booking accommodation online, complex discount strategies were not determinant both in selecting hotels and P2P accommodations. Positive valence rate of reviews has a higher impact on the selection of traditional hotels than P2P accommodations, while the number of online reviews has a higher impact on the selection of P2P accommodations than traditional hotels. The authors further discuss the effect of each attribute on online accommodation selection in terms of price ranges of the property listings.

Research limitations/implications

The findings provide suggestions for platform operators and product/service providers to improve their marketing strategies and optimize their management efforts.

Originality/value

To the best of the authors’ knowledge, this is one of the first studies that investigate the role of property listings' attributes on the selections between hotels and P2P accommodations. The findings from this research study could be generalized to other online platforms and electronic commerce-related transactions.
Psychological assessment in human resource management: discrepancies between theory and practice and two examples of integration
Authors: Sartori Riccardo , Costantini Arianna , Ceschi Andrea
Published: October 2020

Purpose

Psychological assessment refers to the process whereby different methods and techniques are used to test hypotheses about people and their psychological characteristics. Understanding employees' psychological makeup is key to allow effective human resource management, from hiring to retirement. However, the gap between scientific evidence and organizational practices dealing with psychological assessment is still great.

Design/methodology/approach

General review along with case study

Findings

This paper shows the differences between research and practice, i.e. between what scientific evidence suggests to assess people from a psychological point of view reliably and what practitioners do when they want to reach the same goal.

Originality/value

At the end of the article, two examples of integration between research and practice are presented. We discuss how methods and techniques of psychological assessment can be developed to both respect scientific criteria and meet specific organizational needs.
Consumer acceptance in context: Texture, melting, and sensory properties of fried ripened curd cheese
Authors: Cais‐Sokolińska Dorota , Kaczyński Łukasz K , Bierzuńska Paulina , Skotarczak Ewa , Dobek Anita
Published: October 2020

The aim of this study was not only to accurately characterise this cheese, but to check a consumer behaviour model using logistic regression models. Fried ripened curd cheese has a very specific sensory profile and colour, a uniform, plastic consistency and strong adhesive properties. Descriptive sensory analysis showed that the cheese is mostly characterised by old milk odour, stickiness, surface film and firmness. The aroma of this cheese is not accepted by young consumers. In this group, the level of education and employment affected the decision to eat the cheese. Only the oldest consumers consume the cheese because of its composition.
Comparative effectiveness of external vs blended facilitation on collaborative care model implementation in slow‐implementer community practices
Authors: Smith Shawna N. , Liebrecht Celeste M. , Bauer Mark S. , Kilbourne Amy M.
Published: October 2020

Objective

To evaluate the comparative effectiveness of external facilitation (EF) vs external + internal facilitation (EF/IF), on uptake of a collaborative chronic care model (CCM) in community practices that were slower to implement under low‐level implementation support.

Study Setting

Primary data were collected from 43 community practices in Michigan and Colorado at baseline and for 12 months following randomization.

Study Design

Sites that failed to meet a pre‐established implementation benchmark after six months of low‐level implementation support were randomized to add either EF or EF/IF support for up to 12 months. Key outcomes were change in number of patients receiving the CCM and number of patients receiving a clinically significant dose of the CCM. Moderators’ analyses further examined whether comparative effectiveness was dependent on prerandomization adoption, number of providers trained or practice size. Facilitation log data were used for exploratory follow‐up analyses.

Data Collection

Sites reported monthly on number of patients that had received the CCM. Facilitation logs were completed by study EF and site IFs and shared with the study team.

Principal Findings

N = 21 sites were randomized to EF and 22 to EF/IF. Overall, EF/IF practices saw more uptake than EF sites after 12 months (ΔEF/IF‐EF = 4.4 patients, 95% CI = 1.87‐6.87). Moderators' analyses, however, revealed that it was only sites with no prerandomization uptake of the CCM (nonadopter sites) that saw significantly more benefit from EF/IF (ΔEF/IF‐EF = 9.2 patients, 95% CI: 5.72, 12.63). For sites with prerandomization uptake (adopter sites), EF/IF offered no additional benefit (ΔEF/IF‐EF = −0.9; 95% CI: −4.40, 2.60). Number of providers trained and practice size were not significant moderators.

Conclusions

Although stepping up to the more intensive EF/IF did outperform EF overall, its benefit was limited to sites that failed to deliver any CCM under the low‐level strategy. Once one or more providers were delivering the CCM, additional on‐site personnel did not appear to add value to the implementation effort.
Rheology and tribology properties of cereal and legume flour paste from different botanical origins
Authors: Pang Zhihua , Cao Jinnuo , Li He , Chen Cunshe , Liu Xinqi
Published: October 2020

Paste made from eight types of cereal grains (low fiber containing grains [LF grains]: rice, sticky rice, black rice, and millet; and high fiber containing grains [HF grains]: wheat, buckwheat, oat, and barley), and four types of legumes (soybean, red bean, kidney bean, and mung bean), were studied in terms of particle size, rheological, and tribological properties. Sticky rice and soybean pastes showed lower yield stress, viscosity and consistency coefficient than other pastes. Most cereal pastes showed a major peak at approximately 160 µm except for oat and barley, while legume pastes showed mono modal profiles except for soybean. Tribological results showed that starch tended to develop type A friction profiles, showing a typical Stribeck curve; bran/fiber tended to develop type B profiles, showing an ascent curve with clear onset of hydrodynamic regime; protein and lipids promoted type C profiles, showing a flat plateau shaped curve. Water soluble polysaccharides in grains or legumes could improve the paste lubrication. In general, 5% of the black rice paste and sticky rice in the LF grain group, and the soybean paste in the legume group, showed a low friction coefficient (μ) in the entire entrainment speed range; barley paste and oat paste in the HF grain group showed relatively low μ at low entrainment speed (0.5 mm/s) and medium entrainment speed (5 and 10 mm/s), respectively.
New evidence for diplomacy between the Mediterranean and South Arabia
Authors: Bukharin Mikhail
Published: October 2020

Two inscriptions that shed more light on the history of contacts between Hellenistic Egypt, the Roman Empire and the South Arabian kingdoms between the second century BCE and the mid‐second century CE are in the focus of this research. One inscription mentions foreign gifts for King Ptolemy VIII Euergetes II Tryphon; the other ‒ a Greek inscription from Ẓafār ‒ seems to be the gift for either the king of Ḥimyar or the Roman colony in Ẓafār. The first inscription points to the existence of direct diplomatic contacts between these regions in the second century BCE. The second inscription is linked with the Latin text from the Farasān archipelago by viewing the reference in the first line to legio II Traiana.
Involvement of miR‐126 rs4636297 and miR‐146a rs2910164 polymorphisms in the susceptibility for diabetic retinopathy: a case–control study in a type 1 diabetes population
Authors: Massignam Eloísa Toscan , Dieter Cristine , Pellenz Felipe Mateus , Assmann Taís Silveira , Crispim Daisy
Published: October 2020

Background and purpose

MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression. MiRNA‐126 and miRNA‐146a have been described as having abnormal expressions in diabetic retinopathy (DR) patients. Polymorphisms in genes codifying miRNAs (miRSNPs) may alter the expression of the corresponding miRNA and, thus, interfere with susceptibility to DR. Therefore, miRSNPs in miR‐126 and miR‐146a genes could be associated with DR susceptibility. The purpose of this study was to investigate the association between miR‐126 rs4636297 (G/A) and miR‐146a rs2910164 (G/C) miRSNPs and DR.

Methods

This case–control study included 195 type 1 diabetes mellitus (T1DM) patients with DR (cases) and 215 patients without DR and with ≥10 years of T1DM (controls). MiRSNPs were genotyped by real‐time PCR.

Results

Genotype distributions of two analysed miRSNPs were in Hardy–Weinberg equilibrium in controls (p > 0.050). Frequencies of the miR‐126 rs4636297 miRSNP were not significantly different between case and control groups (p = 0.169). However, after adjustment for age, glycated haemoglobin, triglycerides, estimated glomerular filtration rate and ethnicity, the A allele of this miRSNP was associated with protection for DR under additive [OR: 0.444 (95% CI: 0.211–0.936), p = 0.033] and dominant [OR: 0.512 (95% CI: 0.303–0.865), p = 0.012] inheritance models. Genotype and allele frequencies of miR‐146a rs2910164 miRSNP did not differ between groups (p = 0.368 and p = 0.957), and this polymorphism was not associated with DR when assuming different inheritance models.

Conclusion

Our results suggest an association between the A allele of miR‐126 rs4636297 miRSNP and protection for DR in a Southern Brazilian population.
Single high‐dose peroral caffeine intake inhibits ultraviolet radiation‐induced apoptosis in human lens epithelial cells in vitro
Authors: Kronschläger Martin , Ruiß Manuel , Dechat Thomas , Findl Oliver
Published: October 2020

Purpose

The aim of the present study was to determine whether caffeine concentrations in human lens epithelial cells (LECs) achieved from acute peroral caffeine intake inhibit ultraviolet radiation‐induced apoptosis in vitro.

Methods

Patients were planned for cataract surgery of both eyes with a caffeine abstinence of 2 weeks in total, starting 1 week before surgery of the first eye. The second eye was scheduled 1 week after the first eye. At the day of the second eye surgery, patients were given coffee containing 180 mg caffeine shortly before surgery. Lens capsules including LEC, harvested after capsulorhexis, were transferred to a cell culture dish and immediately exposed to close to threshold ultraviolet radiation (UVR). At 24 hr after UVR exposure, apoptotic LECs were analysed by TdT‐mediated dUTP‐biotin nick end labeling (TUNEL) staining.

Results

TUNEL‐positive cells were detected in UVR‐exposed lens capsules both after caffeine intake and in controls. The mean difference in TUNEL‐positive cells between caffeine intake and contralateral controls (no caffeine) resulted in a 95% CI 15.3 ± 10.4% (degrees of freedom: 16).

Conclusion

Peroral caffeine consumption significantly decreased UVR‐induced apoptosis in LEC supporting epidemiological findings that caffeine delays the onset of cataract.
Associations between functional and structural measurements in non‐acute Vogt–Koyanagi–Harada disease
Authors: Souto Fernanda Maria Silveira , Missaka Ruy Felippe Brito Gonçalves , Lavezzo Marcelo Mendes , Mayumi Sakata Viviane , Oyamada Maria Kiyoko , Hirata Carlos Eduardo , Yamamoto Joyce Hisae
Published: October 2020

Purpose

To evaluate associations between functional and structural measurements in patients with non‐acute VKHD.

Methods

In this cross‐sectional study, 16 non‐acute VKHD patients (32 eyes; 14 female) were evaluated with multifocal electroretinogram (mfERG), standardized automated perimetry (SAP) and optical coherence tomography (OCT)examinations. All included patients had a minimum 12 months of follow‐up from acute onset and were participants of an ongoing prospective study since acute phase with systematic clinical imaging evaluations and electroretinogram examinations within a predefined treatment. Age‐ and gender‐matched controls were included. Main outcomes were functional and structural abnormalities and their correlation; secondary outcome was correlation of these findings with clinical characteristics, including fundus abnormalities.

Results

SAP and mfERG parameters were significantly worse in patients than in controls. Fourteen eyes (43.7%) had disrupted ellipsoid zone (EZ); visual acuity (VA) was similar between eyes with intact or disrupted EZ. Eyes with intact and disrupted EZ differed significantly concerning N1 and P1 amplitudes and N1 peak time values on mfERG and mean sensitivity (MS), central sensitivity (CS), foveal threshold, visual field index, mean deviation (MD) and pattern standard deviation values on SAP. The area under the curve on receiver operating curves for P1 amplitude was 0.81 (cut‐off value = 34.7 nV/deg2) and for MD value was 0.84 (cut‐off value = −5.2 dB). Central retinal thickness (CRT) significantly correlated with N1 and P1 amplitudes and P1 peak time values on mfERG (r = 0.354, r = 0.442 and r = −0.405, respectively) and MD, MS, CS and fovea threshold (log values) on SAP (r = 0.372, r = 0.406, r = 0.431 and r = 0.414, respectively). Statistically significant associations were found with the presence of peripapillary atrophy and recurrent anterior uveitis with a worse MD value (p = 0.004 and p < 0.001, respectively).

Conclusion

In non‐acute VKHD, disrupted EZ and reduced CRT were correlated with impaired mfERG and SAP parameters, even in patients with good VA.
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

Purpose

Phantom 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.

Methods

A 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.

Results

Of 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).

Conclusion

Phantom eye pain (PEP) is a common complication of EA strongly associated with postoperative anxiety.
Calcareous nannofossils in medieval mortar and mortar‐based materials: A powerful tool for provenance analysis
Authors: Falkenberg J. , Mutterlose J. , Kaplan U.
Published: October 2020

Calcareous nannofossils—very small‐scaled marine microfossils—occur in many archaeological materials. Foremost, these include limestones used in masonry, material which has not experienced significant modification by humans. Poorly documented are nannofossils in mortars, because the burning process of quicklime requires the heating of the raw material to > 800°C. Here we focus on calcareous nannofossils in mortar and mortar‐based samples of four medieval buildings in northern Germany. The study documents the presence of nannofossils in historic mortars. It supplies evidence for the provenance of the mortars used, thereby introducing a new tool for mortar provenance studies.
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

Aims

SAR247799 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.

Methods

Type‐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.

Results

The 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.

Conclusion

These 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

In 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 Purpose

Savolitinib (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 Approach

Cell 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 Results

Savolitinib 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 Implications

High 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

Conservation 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

Objective

To 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.

Methodology

We 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.

Results

We 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).

Conclusion

Left 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 purpose

Congenital 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.

Methods

Whole‐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.

Results

A 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.

Conclusion

The 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.

Databases

The 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

Up 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

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

Policies 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.