bluuebunny/crossref_metadata_2025 huggingface dataset:
STRICT POSTURING WITH OR WITHOUT BILATERAL PATCHING FOR POSTERIOR VITREOUS DETACHMENT–RELATED VITREOUS HEMORRHAGE
Authors: van Etten Peter G. , van Overdam Koen A. , Reyniers Rudolf , Veckeneer Marc , Faridpooya Koorosh , Wubbels René J. , Manning Sonia , La Heij Ellen C. , van Meurs Jan C.
Published: May 2019

Purpose:

To determine whether bilateral patching with posturing is superior to posturing alone in visualizing the superior retina in suspected posterior vitreous detachment (PVD)–related vitreous hemorrhage (VH).

Methods:

Prospective randomized controlled trial: 80 patients with fundus-obscuring VH due to suspected retinal tear were randomized to strict posturing and bilateral patching overnight (Treatment A, 40 patients) or posturing (Treatment B, 40 patients).

Primary outcome:

Visualization of ≥4 clock hours superior retina. Secondary outcome measures: laser treatment, vitrectomy rate, and retinal detachment within 12 months.

Results:

Intention-to-treat analysis: In 38/40 (95%) with Treatment A and 32/40 (80%) with Treatment B, the confirmed diagnosis was PVD-related VH. Visibility of the superior retina for all patients: 29/40 (73%) after Treatment A and 21/40 (53%) after Treatment B (P = 0.07). Subgroup analysis for confirmed PVD-related VH; visibility of the superior retina: 29/38 (76%) after Treatment A and 15/32 (47%) after Treatment B (P = 0.01). In subgroup analysis, vitrectomy rate within 12 months was 61% (Treatment A) and 53% (Treatment B) (P = 0.63). Retinal detachment: eight patients after each treatment.

Conclusion:

In patients with suspected PVD-related VH, overnight bilateral patching was not superior to posturing alone in superior retina visualization, but in a post-hoc analysis of patients with confirmed PVD-related VH, bilateral patching was superior.
EN FACE IMAGE–BASED ANALYSIS OF RETINAL TRACTION CAUSED BY EPIRETINAL MEMBRANE AND ITS RELATIONSHIP WITH VISUAL FUNCTIONS
Authors: Hirano Masayuki , Morizane Yuki , Kanzaki Yuki , Kimura Shuhei , Hosokawa Mio , Shiode Yusuke , Doi Shinichiro , Toshima Shinji , Takahashi Kosuke , Hosogi Mika , Fujiwara Atsushi , Takasu Ippei , Shiraga Fumio
Published: May 2019

Purpose:

To evaluate the relationship between retinal traction caused by epiretinal membrane and visual functions.

Methods:

In this institutional study, en face swept-source optical coherence tomography images of 141 eyes of 130 patients with epiretinal membrane were analyzed to investigate maximum depth of retinal folds, which represents retinal traction strength and the distribution pattern of retinal folds. We investigated the relationships between the maximum depth and distribution pattern of retinal folds and visual functions as well as the effects of membrane peeling.

Results:

Maximum retinal fold depth was significantly correlated with the metamorphopsia score (P < 0.001). Fifteen eyes showed retinal folds radially extending from the macular epiretinal membrane (radiating folds group), whereas 126 eyes showed a multidirectional pattern of retinal folds (multidirectional folds group). The radiating folds group showed a significantly lower metamorphopsia score (P = 0.014). Multiple regression analysis revealed that the metamorphopsia score was significantly related to maximum retinal fold depth (P = 0.003), distribution pattern (P = 0.015), and central retinal thickness (P < 0.001). One month after membrane peeling, parafoveal retinal folds resolved completely in all cases, and both visual acuity (P < 0.001) and average metamorphopsia score (P = 0.036) were significantly improved.

Conclusion:

Both the strength and the distribution pattern of retinal traction are significantly related to metamorphopsia in epiretinal membrane patients.
Confronting the Post—ACA American Health Crisis
Authors: Fiscella Kevin
Published: May 2019

The United States is in the midst of a health crisis marked by unprecedented 3-year declines in life expectancy. Addressing this national crisis requires alignment of public policies, public health policies, and health care policies, with the overarching aim of improving national health and health equity. Aligning national polices to support human needs provides a foundation for implementing post–Affordable Care Act national health care reform. Reform should start with the twin goals of improving health care value and equity. A focus on value, that is, outcomes and processes desired by patients, is critical to ensuring that resources are judiciously deployed to optimize individual and population health. A focus on health care equity ensures that the health care system is intentionally designed to minimize inequities in health care processes and outcomes, particularly for member of socially disadvantaged groups. All sectors related to the health care system—from policies and payment mechanisms to delivery design, measurement, patient engagement/democratization, training, and research—should be tightly aligned with improving health care value and equity during this next era of health care reform.
An American Path to Universal Coverage
Authors: Kirsch Richard
Published: May 2019

The politics of health care policy create opportunities driven by public demands for lowering costs and providing health security, constrained by fear of loss of what people have now, fears that will be inflamed by opponents. The best course toward reform will provide people a choice of improved public coverage and the ability to keep improved employer coverage. There are a variety of ways to design these proposals, some of which can be characterized as Medicare for All. Inclusion of a Medicare/public plan in the Affordable Care Act marketplaces is a policy option but one of relatively low significance.
Portopulmonary Hypertension: A Survey of Practice Patterns and Provider Attitudes
Authors: DuBrock Hilary M. , Salgia Reena J. , Sussman Norman L. , Bartolome Sonja D. , Kadry Zakiyah , Mulligan David C. , Jenkins Sarah , Lackore Kandace , Channick Richard N. , Kawut Steven M. , Krowka Michael J.
Published: May 2019

Background.

The role of liver transplantation (LT) in the management of portopulmonary hypertension (POPH) is poorly understood. The aim of this study was to better understand provider attitudes and practice patterns regarding the management of patients with POPH and to assess the concordance between clinical practice and current guidelines.

Methods.

We performed a multicenter survey study of hepatologists and pulmonary hypertension (PH) physicians at US LT centers that performed >50 transplants per year. Survey responses are summarized as number (%). Associations were assessed using a Wilcoxon-rank sum, chi-square, or Fisher exact test, as appropriate.

Results.

Seventy-four providers from 35 centers were included. There was marked variability regarding screening practices, management, and attitudes. Forty-two percent responded that POPH nearly always or often improves with LT, and 15.5% reported that POPH rarely or never improves. In contrast to current guidelines, 50.7% agreed that treated POPH should be an indication for LT in patients with compensated cirrhosis. Hepatologists were more likely than PH physicians to agree that POPH should be an indication for LT (P = 0.02). Forty-nine percent of respondents thought that the current POPH Model for End-stage Liver Disease exception criteria should be modified, and management of patients with an elevated mean pulmonary arterial pressure and normal pulmonary vascular resistance differed from current policies.

Conclusions.

There is marked variability in provider attitudes and practice patterns regarding the management of POPH. This study highlights the need for prospective studies to inform practice and for improved implementation of practice guidelines in order to standardize care.
Strong magnetic exchange and frustrated ferrimagnetic order in a weberite-type inorganic–organic hybrid fluoride
Authors: Clark L. , Albino M. , Pimenta V. , Lhoste J. , da Silva I. , Payen C. , Grenèche J.-M. , Maisonneuve V. , Lightfoot P. , Leblanc M.
Published: May 2019

We combine powder neutron diffraction, magnetometry and
57
Fe Mössbauer spectrometry to determine the nuclear and magnetic structures of a strongly interacting weberite-type inorganic–organic hybrid fluoride, Fe
2
F
5
(H
taz
). In this structure, Fe
2+
and Fe
3+
cations form magnetically frustrated hexagonal tungsten bronze layers of corner-sharing octahedra. Our powder neutron diffraction data reveal that, unlike its purely inorganic fluoride weberite counterparts which adopt a centrosymmetric
Imma
structure, the room-temperature nuclear structure of Fe
2
F
5
(H
taz
) is best described by a non-centrosymmetric
Ima
2 model with refined lattice parameters
a
 = 9.1467(2) Å,
b
 = 9.4641(2) Å and
c
 = 7.4829(2) Å. Magnetic susceptibility and magnetization measurements reveal that strong antiferromagnetic exchange interactions prevail in Fe
2
F
5
(H
taz
) leading to a magnetic ordering transition at
T
N
 = 93 K. Analysis of low-temperature powder neutron diffraction data indicates that below
T
N
, the Fe
2+
sublattice is ferromagnetic, with a moment of 4.1(1)

µ
B

per Fe
2+
at 2 K, but that an antiferromagnetic component of 0.6(3)

µ
B

cants the main ferromagnetic component of Fe
3+
, which aligns antiferromagnetically to the Fe
2+
sublattice. The zero-field and in-field Mössbauer spectra give clear evidence of an excess of high-spin Fe
3+
species within the structure and a non-collinear magnetic structure.

This article is part of the theme issue ‘Mineralomimesis: natural and synthetic frameworks in science and technology’.
Prospects for electroactive and conducting framework materials
Authors: Murase Ryuichi , Ding Bowen , Gu Qinyi , D'Alessandro Deanna M.
Published: May 2019

Electroactive and conducting framework materials, encompassing coordination polymers and metal–organic frameworks, have captured the imagination of the scientific community owing to their highly designable nanoporous structures and their potential applications in electrochromic devices, electrocatalysts, porous conductors, batteries and solar energy harvesting systems, among many others. While they are now considered integral members of the broader field of inorganic materials, it is timely to reflect upon their strengths and challenges compared with ‘traditional’ solid-state materials such as minerals, pigments and zeolites. Indeed, the latter have been known since ancient times and have been prized for centuries in fields as diverse as art, archaeology and industrial catalysis. This opinion piece considers a brief historical perspective of traditional electroactive and conducting inorganic materials, with a view towards very recent experimental progress and new directions for future progress in the burgeoning area of coordination polymers and metal–organic frameworks. Overall, this article bears testament to the rich history of electroactive solids and looks at the challenges inspiring a new generation of scientists.

This article is part of the theme issue ‘Mineralomimesis: natural and synthetic frameworks in science and technology’.
Hydrogen-bond-mediated structural variation of metal guanidinium formate hybrid perovskites under pressure
Authors: Yang Zhengqiang , Cai Guanqun , Bull Craig L. , Tucker Matthew G. , Dove Martin T. , Friedrich Alexandra , Phillips Anthony E.
Published: May 2019

The hybrid perovskites are coordination frameworks with the same topology as the inorganic perovskites, but with properties driven by different chemistry, including host-framework hydrogen bonding. Like the inorganic perovskites, these materials exhibit many different phases, including structures with potentially exploitable functionality. However, their phase transformations under pressure are more complex and less well understood. We have studied the structures of manganese and cobalt guanidinium formate under pressure using single-crystal X-ray and powder neutron diffraction. Under pressure, these materials transform to a rhombohedral phase isostructural to cadmium guanidinium formate. This transformation accommodates the reduced cell volume while preserving the perovskite topology of the framework. Using density-functional theory calculations, we show that this behaviour is a consequence of the hydrogen-bonded network of guanidinium ions, which act as struts protecting the metal formate framework against compression within their plane. Our results demonstrate more generally that identifying suitable host–guest hydrogen-bonding geometries may provide a route to engineering hybrid perovskite phases with desirable crystal structures.

This article is part of the theme issue ‘Mineralomimesis: natural and synthetic frameworks in science and technology’.
The olfactory basis of orchid pollination by mosquitoes
Authors: Lahondère Chloé , Vinauger Clément , Okubo Ryo P. , Wolff Gabriella H. , Chan Jeremy K. , Akbari Omar S. , Riffell Jeffrey A.
Published: May 2019

Mosquitoes are important vectors of disease and require sources of carbohydrates for reproduction and survival. Unlike host-related behaviors of mosquitoes, comparatively less is understood about the mechanisms involved in nectar-feeding decisions, or how this sensory information is processed in the mosquito brain. Here we show that Aedes spp. mosquitoes, including Aedes aegypti, are effective pollinators of the Platanthera obtusata orchid, and demonstrate this mutualism is mediated by the orchid’s scent and the balance of excitation and inhibition in the mosquito’s antennal lobe (AL). The P. obtusata orchid emits an attractive, nonanal-rich scent, whereas related Platanthera species – not visited by mosquitoes – emit scents dominated by lilac aldehyde. Calcium imaging experiments in the mosquito AL revealed that nonanal and lilac aldehyde each respectively activate the LC2 and AM2 glomerulus, and remarkably, the AM2 glomerulus is also sensitive to DEET, a mosquito repellent. Lateral inhibition between these two glomeruli reflects the level of attraction to the orchid scents: whereas the enriched nonanal scent of P. obtusata activates the LC2 and suppresses AM2, the high level of lilac aldehyde in the other orchid scents inverts this pattern of glomerular activity, and behavioral attraction is lost. These results demonstrate the ecological importance of mosquitoes beyond operating as disease vectors and open the door towards understanding the neural basis of mosquito nectar-seeking behaviors.

Significance Statement

Nectar-feeding by mosquitoes is important for survival and reproduction, and hence disease transmission. However, we know little about the sensory mechanisms that mediate mosquito attraction to sources of nectar, like those of flowers, or how this information is processed in the mosquito brain. Using a unique mutualism between Aedes mosquitoes and Platanthera obtusata orchids, we reveal that this mutualism is mediated by the orchid’s scent. Furthermore, lateral inhibition in the mosquito’s antennal (olfactory) lobe – via the neurotransmitter GABA – is critical for the representation of the scent. These results have implications toward understanding the olfactory basis of mosquito-nectar-seeking behaviors.
Spatial control of viscoelasticity in phototunable hyaluronic acid hydrogels
Authors: Hui Erica , Gimeno Kathryn I. , Guan Grant , Caliari Steven R.
Published: May 2019

Viscoelasticity has emerged as a critical regulator of cell behavior. However, there is an unmet need to develop biomaterials where viscoelasticity can be spatiotemporally tuned to mimic the dynamic and heterogeneous nature of tissue microenvironments. Toward this objective, we developed a modular hyaluronic acid hydrogel system combining light-mediated covalent and supramolecular crosslinking to afford spatiotemporal control of network viscoelastic properties. Covalently crosslinked elastic hydrogels or viscoelastic hydrogels combining covalent and supramolecular interactions were fabricated to match healthy and fibrotic liver stiffness. LX-2 human hepatic stellate cells cultured on viscoelastic substrates displayed reduced spreading, less actin stress fiber organization, and lower myocardin-related transcription factor A (MRTF-A) nuclear localization compared to cells on elastic hydrogels. We further demonstrated the dynamic capabilities of our hydrogel system through photomediated secondary incorporation of either covalent or supramolecular crosslinks to modulate viscoelastic properties. We used photopatterning to create hydrogel models with well-controlled patterned regions of stiff elastic mechanics representing fibrotic tissue nodules surrounded by regions of soft viscoelastic hydrogel mimicking healthy tissue. Cells responded to the local mechanics of the patterned substrate with increased spreading in fibrosis-mimicking regions. Together, this work represents an important step forward toward the creation of hydrogel models with spatiotemporal control of both stiffness and viscoelastic cell-instructive cues.
An adult brain atlas reveals broad neuroanatomical changes in independently evolved populations of Mexican cavefish
Authors: Loomis Cody , Peuß Robert , Jaggard James , Wang Yongfu , McKinney Sean , Raftopoulos Stephen , Raftopoulos Austin , Whu Daniel , Green Matthew , McGaugh Suzanne E. , Rohner Nicolas , Keene Alex C. , Duboue Erik R.
Published: May 2019

A shift in environmental conditions impacts the evolution of complex developmental and behavioral traits. The Mexican cavefish, Astyanax mexicanus, is a powerful model for examining the evolution of development, physiology, and behavior because multiple cavefish populations can be compared to an extant and ancestral-like surface population of the same species. Many behaviors have diverged in cave populations of A. mexicanus, and previous studies have shown that cavefish have a loss of sleep, reduced stress, an absence of social behaviors, and hyperphagia. Despite these findings, surprisingly little is known about the changes in neuroanatomy that underlie these behavioral phenotypes. Here, we use serial sectioning to generate a brain atlas of surface fish and three independent cavefish populations. Volumetric reconstruction of serial-sectioned brains confirms convergent evolution on reduced optic tectum volume in all cavefish populations tested. In addition, we quantified volumes of specific neuroanatomical loci within several brain regions, which have previously been implicated in behavioral regulation, including the hypothalamus, thalamus, and habenula. These analyses reveal an expansion of the hypothalamus across all three cavefish populations relative to surface fish, as well as subnuclei-specific differences within the thalamus and habenulae. Taken together, these analyses support the notion that changes in environmental conditions are accompanied by neuroanatomical changes in brain structures associated with behavior. This atlas provides a resource for comparative neuroanatomy of additional brain regions and the opportunity to associate brain anatomy with evolved changes in behavior.
A stress-induced block in dicarboxylate uptake and utilization in Salmonella
Authors: Hersch Steven J. , Radan Bojana , Ilyas Bushra , Lavoie Patrick , Navarre William Wiley
Published: May 2019

Bacteria have evolved to sense and respond to their environment by altering gene expression and metabolism to promote growth and survival. In this work we demonstrate that Salmonella displays an extensive (>30 hour) lag in growth when subcultured into media where dicarboxylates such as succinate are the sole carbon source. This growth lag is regulated in part by RpoS, the RssB anti-adaptor IraP, translation elongation factor P, and to a lesser degree the stringent response. We also show that small amounts of proline or citrate can trigger early growth in succinate media and that, at least for proline, this effect requires the multifunctional enzyme/regulator PutA. We demonstrate that activation of RpoS results in the repression of dctA, encoding the primary dicarboxylate importer, and that constitutive expression of dctA induced growth. This dicarboxylate growth lag phenotype is far more severe across multiple Salmonella isolates than in its close relative E. coli. Replacing 200 nt of the Salmonella dctA promoter region with that of E. coli was sufficient to eliminate the observed lag in growth. We hypothesize that this cis-regulatory divergence might be an adaptation to Salmonella’s virulent lifestyle where levels of phagocyte-produced succinate increase in response to bacterial LPS. We found that impairing dctA repression had no effect on Salmonella’s survival in acidified succinate or in macrophage but propose alternate hypotheses of fitness advantages acquired by repressing dicarboxylate uptake.

Importance

Bacteria have evolved to sense and respond to their environment to maximize their chance of survival. By studying differences in the responses of pathogenic bacteria and closely related non-pathogens, we can gain insight into what environments they encounter inside of an infected host. Here we demonstrate that Salmonella diverges from its close relative E. coli in its response to dicarboxylates such as the metabolite succinate. We show that this is regulated by stress response proteins and ultimately can be attributed to Salmonella repressing its import of dicarboxylates. Understanding this phenomenon may reveal a novel aspect of the Salmonella virulence cycle, and our characterization of its regulation yields a number of mutant strains that can be used to further study it.
Evoregions: Mapping Shifts in Phylogenetic Turnover Across Biogeographic Regions
Authors: Maestri Renan , Duarte Leandro
Published: May 2019

Biogeographic regionalization offers context to the geographical evolution of clades. The positions of bioregions inform both the spatial location of clusters in species distribution and where their most important boundaries are. Nevertheless, defining bioregions based on species distribution alone only incidentally recovers regions that are important during the evolution of the focal group. The extent to which bioregions correspond to centers of independent diversification depends on how clusters of species composition naturally reflect the radiation of single clades, which is not the case when mixed colonization occurred. Here, we showed that using phylogenetic turnover based on fuzzy sets, instead of species composition, led to more adequate detection of evolutionary important bioregions, that is, regions that truly account for the independent diversification of lineages. Mapping those evoregions in the phylogenetic tree quickly reveals the timing and location of major shifts of biogeographic regions. Moreover, evolutionary transition zones are easily mapped, and permits the recognition of regions with high phylogenetic overlap. Our results using the global radiation of rats and mice (Muroidea) recovered four evoregions—three major evolutionary arenas corresponding to the Neotropics, a Nearctic-Siberian, and a Paleotropical-Australian evoregion, and a fourth and fuzzy Afro-Palearctic evoregion. In comparison, an analysis with a method considering species distribution alone found 52 bioregions. Evoregions is a useful framework whenever the question is related to the identification of the most important centers of a group’s diversification history and its evolutionary transitions zones.
Aberrant striatal oscillations after dopamine loss in parkinsonian non-human primates
Authors: Singh Arun , Papa Stella M.
Published: May 2019

Dopamine depletion in Parkinson’s disease (PD) is associated with abnormal oscillatory activity in the cortico-basal ganglia network. However, the oscillatory pattern of striatal neurons in PD remains poorly defined. Here, we analyzed the local field potentials in one untreated and five MPTP-treated non-human primates (NHP) to model advanced PD. Augmented oscillatory activity in the alpha (8-13 Hz) and low-beta (13-20 Hz) frequency bands was found in the striatum in parallel to the motor cortex and globus pallidus of the NHP-PD model. The coherence analysis showed increased connectivity in the cortico-striatal and striato-pallidal pathways at alpha and low-beta frequency bands, confirming the presence of abnormal 8-20 Hz activity in the cortico-basal ganglia network. The acute L-Dopa injection that induced a clear motor response normalized the amplified 8-20 Hz oscillations. These findings indicate that pathological striatal oscillations at alpha and low-beta bands are concordant with the basal ganglia network changes after dopamine depletion, and thereby support a key role of the striatum in the generation of parkinsonian motor abnormalities.
The advantages and disadvantages of short- and long-read metagenomics to infer bacterial and eukaryotic community composition
Authors: Pearman William S. , Freed Nikki E. , Silander Olin K.
Published: May 2019

Background

The first step in understanding ecological community diversity and dynamics is quantifying community membership. An increasingly common method for doing so is through metagenomics. Because of the rapidly increasing popularity of this approach, a large number of computational tools and pipelines are available for analysing metagenomic data. However, the majority of these tools have been designed and benchmarked using highly accurate short read data (i.e. illumina), with few studies benchmarking classification accuracy for long error-prone reads (PacBio or Oxford Nanopore). In addition, few tools have been benchmarked for non-microbial communities.

Results

Here we use simulated error prone Oxford Nanopore and high accuracy Illumina read sets to systematically investigate the effects of sequence length and taxon type on classification accuracy for metagenomic data from both microbial and non-microbial communities. We show that very generally, classification accuracy is far lower for non-microbial communities, even at low taxonomic resolution (e.g. family rather than genus).

Conclusions

We then show that for two popular taxonomic classifiers, long error-prone reads can significantly increase classification accuracy, and this is most pronounced for non-microbial communities. This work provides insight on the expected accuracy for metagenomic analyses for different taxonomic groups, and establishes the point at which read length becomes more important than error rate for assigning the correct taxon.
Transposable element dynamics are consistent across theDrosophilaphylogeny, despite drastically differing content
Authors: Hill Tom
Published: May 2019

Background

The evolutionary dynamics of transposable elements (TEs) vary across the tree of life and even between closely related species with similar ecologies. InDrosophila, most of the focus on TE dynamics has been completed inDrosophila melanogasterand the overall pattern indicates that TEs show an excess of low frequency insertions, consistent with their frequent turn over and high fitness cost in the genome. Outside ofD. melanogaster, insertions in the speciesDrosophila algonquin, suggests that this situation may not be universal, even withinDrosophila. Here we test whether the pattern observed inD. melanogasteris similar across fiveDrosophilaspecies that share a common ancestor more than fifty million years ago.

Results

For the most part, TE family and order insertion frequency patterns are broadly conserved between species, supporting the idea that TEs have invaded species recently, are mostly costly and dynamics are conserved in orthologous regions of the host genome

Conclusions

Most TEs retain similar activities and fitness costs across theDrosophilaphylogeny, suggesting little evidence of drift in the dynamics of TEs across the phylogeny, and that most TEs have invaded species recently.
SolXplain: An Explainable Sequence-Based Protein Solubility Predictor
Authors: Mall Raghvendra
Published: May 2019

Motivation

Protein solubility is a property associated with protein expression and is a critical determinant of the manufacturability of therapeutic proteins. It is thus imperative to design accurate in-silico sequence-based solubility predictors.

Methods

In this study, we propose SolXplain, an extreme gradient boosting machine based protein solubility predictor which achieves state-of-the-art performance using physio-chemical, sequence and novel structure derived features from protein sequences. Moreover, SolXplain has a unique attribute that it can provide explanation for the predicted class label for each test protein based on its corresponding feature values using SHapley Additive exPlanations (SHAP) method.

Results

Based on an independent test set, SolXplain outperformed other sequence-based methods by at least 2% in accuracy and 2% in Matthew’s correlation coefficient, with an overall accuracy of 78% and Matthew’s correlation coefficient of 0.56. Additionally, for fractions of exposed residues (FER) at various residual solvent accessibility (RSA) cutoffs, we observed higher fractions to associate positively with protein solubility, and tripeptide stretches that contain one isoleucine and one or more histidines, to associate negatively with solubility. The improved prediction accuracy of SolXplain enables it to predict protein solubility with greater consistency and screen for sequences with enhanced manufacturability.
Terminal neuron localization to the upper cortical plate is controlled by the transcription factor NEUROD2
Authors: Guzelsoy Gizem , Akkaya Cansu , Atak Dila , Dunn Cory D. , Kabakcioglu Alkan , Ozlu Nurhan , Ince-Dunn Gulayse
Published: May 2019

Excitatory neurons of the mammalian cerebral cortex are organized into six functional layers characterized by unique patterns of connectivity, as well as distinctive physiological and morphological properties. Cortical layers appear after a highly regulated migration process in which cells move from the deeper, proliferative zone toward the superficial layers. Importantly, defects in this radial migration process have been implicated in neurodevelopmental and psychiatric diseases. Here we report that during the final stages of migration, transcription factor Neurogenic Differentiation 2 (Neurod2) contributes to terminal cellular localization within the cortical plate. In mice, in utero knockdown of Neurod2 results in reduced numbers of neurons localized to the uppermost region of the developing cortex, also termed the primitive cortical zone. Our ChIP-Seq and RNA-Seq analyses of genes regulated by NEUROD2 in the developing cortex identify a number of key target genes with known roles in Reelin signaling, a critical regulator of neuronal migration. Our focused analysis of regulation of the Reln gene, encoding the extracellular ligand REELIN, uncovers NEUROD2 binding to conserved E-box elements in multiple introns. Furthermore, we demonstrate that knockdown of NEUROD2 in primary cortical neurons results in a strong increase in Reln gene expression at the mRNA level, as well as a slight upregulation at the protein level. These data reveal a new role for NEUROD2 during the late stages of neuronal migration, and our analysis of its genomic targets offer new genes with potential roles in cortical lamination.
The Early Sociocognitive Battery: a clinical tool for early identification of children at risk for social communication difficulties and ASD?
Authors: Roy Penny , Chiat Shula
Published: May 2019

Background

A substantial proportion of preschool children referred to speech and language therapy (SLT) services have social communication difficulties and/or autistic spectrum disorders (SC&/ASD) that are not identified until late childhood. These ‘late’ diagnosed children miss opportunities to benefit from earlier targeted interventions. Prior evidence from a follow‐up clinical sample showed that preschool performance on the Early Sociocognitive Battery (ESB) was a good predictor of children with social communication difficulties 7–8 years later.

Aims

The aims were three‐fold: (1) to determine the impact of child/demographic factors on ESB performance in a community sample of young children; (2) to assess the ESB's concurrent validity and test–retest reliability; and (3) to use cut‐offs for ‘low’ ESB performance derived from the community sample data to evaluate in a clinical sample the predictiveness of the ESB at 2–4 years for outcomes at 9–11 years, including parent‐reported SC&/ASD diagnosis.

Methods & Procedures

A community sample of 205 children aged 2–4 years was assessed on the ESB and a receptive vocabulary test. A subsample (n = 20) was retested on the ESB within 2 weeks. Parents completed a questionnaire providing background child/demographic information. The clinical sample from our previous study comprised 93 children assessed on the ESB at 2;6 to < 4;0 whose parents completed the Social Responsiveness Scale (SRS), our measure of social communication, when the children were 9–11 years. Cut‐offs for ‘low’ ESB performance derived from the community sample were used to determine the predictive validity of ‘low’ ESB scores for social communication outcomes and parent‐reported SC&/ASD diagnosis according to age of ESB assessment.

Outcome & Results

Findings from the community sample confirmed the ESB as psychometrically robust, sensitive to age and language delay, and, in contrast to the receptive vocabulary measure, unaffected by bilingualism. While overall associations between ESB performance and later social communication difficulties in the clinical sample were particularly strong for the youngest age group (2;6 to < 3;0; r = .71, p < .001), ‘low’ ESB performance was equally predictive across age groups and overall identified 89% of children with ‘late’ SC&/ASD diagnoses (sensitivity), and 75% of those without (specificity).

Conclusions & Implications

Results indicate that the ESB is a valid preschool assessment suitable for use with children from diverse language backgrounds. It identifies deficits in key sociocognitive skills and is predictive of social communication difficulties in school‐age children that had not been identified in preschool clinical assessment, supporting earlier targeted interventions for these children.
In Vitro Digestibility and Quality of an Emulsified Meat Product Formulated With Animal Fat Encapsulated With Pectin
Authors: Santiaguín‐Padilla Aarón Jonary , Peña‐Ramos Etna Aida , Pérez‐Gallardo Alfonso , Rascón‐Chu Agustin , González‐Ávila Marisela , González‐Ríos Humberto , González‐Noriega Julio A , Islava‐Lagarda Thalia
Published: May 2019

Animal fat plays a key role in the structure, quality, and acceptability of emulsified meat products. However, a high consumption of saturated fat has been related to several health problems. Fat encapsulation with a nondigestible carbohydrate, such as pectin, may offer a promising alternative to reduce fat intake from a meat product, by preventing its digestion and absorption. The objective of this study was to develop a meat sausage with pectin‐encapsulated‐fat (PEF) to decrease its lipid digestibility, without compromising its acceptability. Pork fat particles encapsulation by emulsification with a 4% pectin solution, and also stability during meat processing and cooking, was confirmed by confocal microscopy. No changes (P > 0.05) compared to Control (C) were found on thermal stability and composition of sausages formulated with direct addition of pectin (T1) and with incorporation of PEF (T2). However, in comparison with C, pH, color, and texture of T1 and T2 samples were affected (P < 0.05). Nevertheless, these changes had no influence (P > 0.05) on sensory acceptability of treated samples, and actually improved (P < 0.05) their texture acceptance. In vitro digestive degradation of triacylglycerols was decreased (P < 0.05) by 20% on T2 samples compared to control and it was superior (P < 0.05) to T1 (8%). Confocal images confirmed lipid digestibility reduction of T2 samples. Incorporation of PEF in a meat sausage offers a better protection against the hydrolytic action of lipases over triaclyglycerides, than a direct addition of pectin, without affecting its sensory acceptability. Therefore, it can be a potential strategy to reduce fat intake from meat products.

Practical Application

Reduction or replacement strategies tested to modify or decrease fat content in meat products usually leads to nondesirable sensory attributes. However, decreasing lipid digestibility by encapsulating animal fat with nondigestible pectin offers a new approach to reduce fat intake from full‐animal‐fat meat products, without affecting their sensory acceptability.
Change in Chemical Composition of Simmental Crossbred Cattle Milk Improved its Physicochemical, Nutritional, and Processed Properties
Authors: Li Xin , Ma Xin , Xiao Na , Long Wei , Wu Yong , Tong Ping , Chen Hongbing
Published: May 2019

This study aimed to evaluate a new milk resource from Simmental crossbred cattle, which could be an alternative raw milk for dairy products. In the experiment, physicochemical characterization of raw milk was evaluated according to the Standards. In addition, Simmental crossbred cattle milk (SHCM) samples had the higher contents of total amino acid than those of Chinese Holstein cow milk (HCM) samples, especially for Leu, Lys, Met, and Phe. We also observed the contents of protein, fat, and lactose in SHCM samples changed during 12 months, where in milk fat content was mostly affected by the season, followed by the lactose and protein contents. Moreover, texture profile analysis showed that yoghurt made from SHCM had stronger structures, which especially reflected in hardness and chewiness. The G’ of yoghurt made from SHCM during storage time was always higher than that made from HCM, indicating that SHCM yoghurt showed higher apparent viscosity values. Logically, the milk from Simmental crossbred cattle has desirable physicochemical characteristics and nutritional value, which could be a new better resource of dairy products.

Practical Application

Compared with Chinese Holstein cattle, Simmental crossbred cattle have strong resistance to moist weather and better performance in disease resistance, which are particularly important for lactating cows persisting in south of China. We evaluated the nutritional values of SHCM and HCM, and compared the seasonal variation on chemical composition of SHCM sample. All the data could be used to produce different dairy products using raw milk from different seasons. In addition, textural properties of yoghurt made from two milks were also determined, and we suggested that SHCM could be used as a new resource candidate for developing dairy product in the future.
Retrogradation and Digestibility of Rice Starch Gels: The Joint Effect of Degree of Gelatinization and Storage
Authors: Denchai Naree , Suwannaporn Prisana , Lin Jenshinn , Soontaranon Siriwat , Kiatponglarp Worawikunya , Huang Tzou‐Chi
Published: May 2019

Retrogradation affects acceptability of starchy foods; however, it is preferred in some products such as rice noodles. Amylose content, gelatinization temperature, and storage condition were reported to affect retrogradation but with disputed data. The joint effects of these parameters were interested in this study. Rice starch was gelatinized using different temperatures (77, 81, 95, and 121 °C) and stored isothermally with temperature cycles for 10 days. Results showed that the most important parameter that affected retrogradation was storage time followed by storage condition and gelatinization temperature. The recrystallization rate constant (k) and Avrami exponent (n) of retrograded starches stored under temperature cycle were higher than isothermal storage. All samples showed similar polymorphs of a mixture of B and V types. High‐temperature gelatinized starch gel stored under temperature cycle condition produced higher yield of resistant starch. The study provided useful information on how to apply these parameters to control the retrogradation of starchy foods, especially rice noodle.

Practical Application

Retrogradation is found to be more prominent at higher gelatinization temperature and longer storage time. Resistant starch produced from retrograded starch depended largely on storage time than storage condition. This finding can be applied to improve rice noodle qualities (by increasing retrogradation) with lower digestibility (by producing higher resistant starch).
A Natural Peanut Edible Coating Enhances the Chemical and Sensory Stability of Roasted Peanuts
Authors: Martín María Paula , Riveros Cecilia Gabriela , Paredes Alejandro Javier , Allemandi Daniel Alberto , Nepote Valeria , Grosso Nelson Rubén
Published: May 2019

This study aims to assess the enhancement of the chemical and sensory properties of roasted peanuts during storage, through the application of high‐protein defatted peanut flour (DPF) coatings incorporated with and without antioxidants. The control sample without coating, packed in normal atmosphere (control), showed the highest conjugated dienes (CD) increment (from 1.17 on day 0 to 3.60 on day 180). Roasted peanuts without coating, packed in high barrier bags under vacuum, reached the lowest CD at day 180 (1.92). Conjugated trienes and peroxide values were analogous to CD. The control exhibited the greatest decrease in α‐tocopherol (from 27.65 mg/100 g on day 0 to 21.32 mg/100 g on day 180) and γ‐tocopherol (from 21.91 mg/100 g on day 0 to 14.99 mg/100 g on day 180). 3‐Methylpyridine and 2,5‐dimethylpyrazine decreased with storage time only for the control, which had the highest increase in oxidized flavor (from 0 on day 0 to 13.30 on day 180), cardboard (from 7.67 on day 0 to 15.23 on day 180), and astringency. The lowest decreases in roasted peanutty scores were seen in coated samples. DPF coatings delayed roasted peanuts oxidation, enhancing their sensory properties and shelf life compared with the control sample.

Practical Application

Defatted peanut flour (DPF) is a byproduct obtained during peanut oil extraction and is a possible material for edible film preparation. This strategy adds value to the peanut industry by transforming a by‐product into a material with the potential to develop biodegradable and economical films. The application of this DPF‐based edible coating on the surface of roasted peanuts may have contributed to extent product's shelf life, allowing for coated products to be packaged in lower barrier and less expensive materials. Use of peanut material to coat peanuts avoids the risk of allergen protein cross contamination, which would be highly valuable for the food industry.
Managing Regional Conflict: The Gulf Cooperation Council and the Embargo of Qatar
Authors: Miller Rory
Published: May 2019

This article will explore the arrangement of and relations between states inside ROs as they move from conflict to negotiation, as well as the different types of negotiations that they choose – bilateral, mediated, multiparty, or hybrid. In doing so, it will illuminate the opportunities that exist at the regional level to develop inclusive regional frameworks for mediation and negotiation and, in the right circumstances, effective security communities. Broadly defined, a security community exists when sovereign states can overcome a lack of mutual trust and difficult regional environments to develop new forms of cooperative security that prioritize self‐restraint and the peaceful resolution of differences and reduce the expectation of the need to resort to organized violence to settle interstate disputes (Adler and Barnett, 1988; Adler and Greve, 2009).
Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model
Authors: Lee Ji Yeon , Song Haengseok , Dash Oyunbileg , Park Mira , Shin Na E. , McLane Michael W. , Lei Jun , Hwang Jong Yun , Burd Irina
Published: May 2019

Problem

Maternal inflammation leads to preterm birth and perinatal brain injury. Melatonin, through its anti‐inflammatory effects, has been shown to be protective against inflammation‐induced perinatal adverse effects. However, the immunomodulatory effects of melatonin on preterm birth and prematurity‐related morbidity remain unknown. We wanted to investigate the effects of maternally administered melatonin on preterm birth and perinatal brain injury in a mouse model of maternal inflammation.

Method of study

A model of maternal inflammation employing lipopolysaccharide (LPS) was used to mimic the most common clinical scenario of preterm birth, that of maternal inflammation. Mice were randomly divided into the following groups: control, LPS, and LPS with melatonin pre‐treatment. Doppler ultrasonography was used to obtain fetal and maternal hemodynamic measurements in utero. Placenta and fetal brains were harvested and analyzed for proinflammatory markers and signs of perinatal brain injury, respectively. Surviving offspring were assessed for neuromotor outcomes.

Results

Melatonin pre‐treatment lowered the level of proinflammatory cytokines in the uterus and the placenta, significantly improved LPS‐induced acute fetal neuroinflammation and perinatal brain injury, as well as significantly upregulated the SIRT1/Nrf2 signaling pathway to reduce LPS‐induced inflammation. Melatonin also prevented adverse neuromotor outcomes in offspring exposed to maternal inflammation.

Conclusion

Maternally administered melatonin modulated immune responses to maternal inflammation and decreased preterm birth and perinatal brain injury. These results suggest that melatonin, a safe treatment during pregnancy, may be used as an experimental therapeutic in clinical trials.
Food allergy endotype with high risk of severe anaphylaxis in children—Monosensitization to cashew 2S albumin Ana o 3
Authors: Blazowski Lukasz , Majak Pawel , Kurzawa Ryszard , Kuna Piotr , Jerzynska Joanna
Published: May 2019

Background

Food allergy in children can be life‐threatening. Component‐resolved diagnostics approach to food anaphylaxis is rarely assessed in children.

The aim of the study was to identify the food allergen components as the triggers responsible for severe anaphylaxis, with regard to characteristics and associated risks, among children in a large, population‐based setting.

Methods

Two hundred and seventy‐one children who were hospitalized due to systemic allergic reaction (SAR) and food anaphylaxis were recruited. Medical history was assessed, and culprit allergen source and anaphylaxis severity grade were established. Specific IgE to 112 allergen components using multiplex ImmunoCAP ISAC immunoassay and specific IgE to hazelnut, Cor a 14, and cashew, Ana o 3, using singleplex ImmunoCAP immunoassay were determined.

Results

We analyzed data from 237 SAR/anaphylaxis in 237 children. Trigger at allergen component level was defined for every episode. The most common triggers of SAR/anaphylaxis were seeds (50.6%), among them, the storage proteins. Anaphylaxis triggered by Ana o 3, 2S albumin from cashews (aOR = 15.0; 95% CI: 3.27 to 73.47); Tri a 19 from wheat (aOR = 9.93; 95% CI: 1.73 to 56.97); and Cor a 9 from hazelnut (aOR = 6.53; 95% CI: 1.16 to 36.72) had the worst clinical presentation including cardiovascular and severe respiratory symptoms (grade IV‐V vs I‐III in Cox scale). Thirteen out of 237 (5.5%) SAR/anaphylaxis patients were triggered by Ana o 3. Almost 82% of patients with severe Ana o 3 anaphylaxis were sensitized only to this component and had no concomitant food sensitization.

Conclusion

Monosensitization to Ana o 3 is, irrespective of other parameters, connected with high risk of severe anaphylaxis.