bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra- and inter-specific density dependence of body condition, growth, and habitat temperature in chub mackerel (Scomber japonicus)
Authors: Kamimura Yasuhiro , Taga Makoto , Yukami Ryuji , Watanabe Chikako , Furuichi Sho
Published: March 2021

The density dependence of growth and body condition have important impacts on fish population dynamics and fisheries management. Although population density is known to affect the temperature of the habitat selected, how this affects the density dependence of growth and body condition remains unclear. Here, we investigated annual changes in body condition, habitat temperature, and cohort-specific growth of chub mackerel (Scomber japonicus) in the western North Pacific and examined quarterly changes in the density dependence of body condition. We hypothesized that chub mackerel body condition is affected both directly (e.g., through competition for food) and indirectly (through changes in habitat temperature) by the abundance of both conspecifics (i.e., chub mackerel) and heterospecifics (the Japanese sardineSardinops melanostictus). Indeed, chub mackerel body condition, habitat temperature, and growth all decreased with increasing conspecific and heterospecific abundance. Mean annual growth rates in chub mackerel were positively corelated with body condition. The best model showed that conspecific and/or heterospecific abundance had strong negative effects on chub mackerel body condition in all seasons, and influenced habitat temperature in some seasons. By contrast, temperature effects on body condition were weak. Therefore, direct effects likely have more impact than indirect effects on density-dependent body condition and growth.
Pyrethroid and metal residues in different coffee bean preparing processes and their human health risk assessments via consumption
Authors: Khunlert Paphatsara , Tanhan Phanwimol , Poapolathep Amnart , Poapolathep Saranya , Imsilp Kanjana
Published: March 2021

The study was conducted on 50 samples of coffee beans from various origins. The samples included green coffee beans, roasted beans, brew coffee drinks and coffee sludge. Three processes were used to prepare these samples: dried, semi-washed, and washed. Three synthetic pyrethroid insecticides and nine heavy metals were subsequently analyzed using modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) and acid digestion methods, respectively. The quantification of pyrethroids was performed by GC-μECD whereas those of metals were determined using flame atomic absorption spectrophotometer. According to the results, concentrations of both pyrethroids and heavy metals were predominantly found in green coffee beans except for Cr. Pyrethroid insecticides were not detectable in brew coffee drink and heavy metal concentrations were below the acceptable daily intake (ADI) level. Risk estimations for daily coffee intake using the health risk indices (HRIs) and target hazard quotients (THQs) of normal and the 97.5 percentile Thai consumers were less than 1. This indicated that the coffee drinks from studied samples could not cause potential health risk.
Cooperation amongc-subunits of FoF1-ATP synthase in rotation-coupled proton translocation
Authors: Mitome Noriyo , Kubo Shintaroh , Ohta Sumie , Takashima Hikaru , Shigefuji Yuto , Niina Toru , Takada Shoji
Published: March 2021

In FoF1-ATP synthase, proton translocation through Fodrives rotation of thec-subunit oligomeric ring relative to thea-subunit. Recent studies suggest that in each step of the rotation, key glutamic acid residues in differentc-subunits contribute to proton release to and proton uptake from thea-subunit. However, no studies have demonstrated cooperativity amongc-subunits toward FoF1-ATP synthase activity. Here, we addressed this usingBacillusPS3 ATP synthase harboringc-ring with various combinations of wild-type andcE56D, enabled by genetically fused single-chainc-ring. ATP synthesis and proton pump activities were decreased by a singlecE56D mutation and further decreased by doublecE56D mutations. Moreover, activity further decreased as the two mutation sites were separated, indicating cooperation amongc-subunits. Similar results were obtained for proton transfer-coupled molecular simulations. Simulations revealed that prolonged proton uptake in mutatedc-subunits is shared between twoc-subunits, explaining the cooperation observed in biochemical assays.
Ovalbumin antigen-specific activation of T cell receptor closely resembles soluble antibody stimulation as revealed by BOOST phosphotyrosine proteomics
Authors: Chua Xien Yu , Salomon Arthur
Published: March 2021

Activation of T cell receptors (TCR) leads to a network of early signaling predominantly orchestrated by tyrosine phosphorylation in T cells. TCR are commonly activated using soluble anti-TCR antibodies, but this approach is not antigen-specific. Alternatively, activating the TCR using specific antigens of a range of binding affinities in the form of peptide-major histocompatibility complex (pMHC) is presumed to be more physiological. However, due to the lack of wide-scale phosphotyrosine (pTyr) proteomic studies directly comparing anti-TCR antibodies and pMHC, a comprehensive definition of these activated states remains enigmatic. Elucidation of the tyrosine phosphoproteome using quantitative pTyr proteomics enables a better understanding of the unique features of these activating agents and the role of ligand binding affinity on signaling. Here, we apply the recently established Broad-spectrum Optimization Of Selective Triggering (BOOST) to examine perturbations in tyrosine phosphorylation of TCR triggered by anti-TCR antibodies and pMHC. Our data reveals that high-affinity ovalbumin (OVA) pMHC activation of the TCR triggers a largely similar, albeit potentially stronger, pTyr-mediated signaling regulatory axis compared to anti-TCR antibody. Signaling output resulting from OVA pMHC variants correlates well with their weaker affinities, enabling affinity-tunable control of signaling strength. Collectively, we provide a framework for applying BOOST to compare pTyr-mediated signaling pathways of T cells activated in an antigen-independent and antigen-specific manner.

Abstract Graphic
Mathematical Models of Retinitis Pigmentosa: The Trophic Factor Hypothesis
Authors: Roberts Paul A.
Published: March 2021

Retinitis pigmentosa (RP) is the term used to denote a group of inherited retinal-degenerative conditions that cause progressive sight loss. Individuals with this condition lose their light-sensitive photoreceptor cells, known as rods and cones, over a period of years to decades; degeneration starting in the retinal periphery, and spreading peripherally and centrally over time. RP is a rod-cone dystrophy, meaning that rod health and function are affected earlier and more severely than that of cones. Rods degenerate due to an underlying mutation, whereas the reasons for cone degeneration are unknown. A number of mechanisms have been proposed to explain secondary cone loss and the spatio-temporal patterns of retinal degeneration in RP. One of the most promising is the trophic factor hypothesis, which suggests that rods produce a factor necessary for cone survival, such that, when rods degenerate, cone degeneration follows. In this paper we formulate and analyse mathematical models of RP under the trophic factor hypothesis. These models are constructed as systems of reaction-diffusion partial differential equations in one spatial dimension, and are solved and analysed using a combination of numerical and analytical methods. We predict the conditions under which cones will degenerate following the loss of a patch of rods from the retina, the critical trophic factor treatment rate required to prevent cone degeneration following rod loss and the spatio-temporal patterns of cone loss that would result if the trophic factor mechanism alone were responsible for retinal degeneration.
Mining signaling flow to interpret mechanisms of synergy of drug combinations using deep graph neural networks
Authors: Zhang Heming , Chen Yixin , Payne Philip , Li Fuhai
Published: March 2021

Complex signaling pathways/networks are believed to be responsible for drug resistance in cancer therapy. Drug combinations inhibiting multiple signaling targets within cancer-related signaling networks have the potential to reduce drug resistance. Deep learning models have been reported to predict drug combinations. However, these models are hard to be interpreted in terms of mechanism of synergy (MoS), and thus cannot well support the human-AI based clinical decision making. Herein, we proposed a novel computational model,DeepSignalingFlow, which seeks to address the preceding two challenges. Specifically, a graph convolutional network (GCN) was developed based on a core cancer signaling network consisting of 1584 genes, with gene expression and copy number data derived from 46 core cancer signaling pathways. The novel up-stream signaling-flow (from up-stream signaling to drug targets), and the down-stream signaling-flow (from drug targets to down-stream signaling), were designed using trainable weights of network edges. The numerical features (accumulated information due to the signaling-flows of the signaling network) of drug nodes that link to drug targets were then used to predict the synergy scores of such drug combinations. The model was evaluated using the NCI ALMANAC drug combination screening data. The evaluation results showed that the proposedDeepSignalingFlowmodel can not only predict drug combination synergy score, but also interpret potentially interpretable MoS of drug combinations.
Massively parallel, computationally-guided design of a pro-enzyme
Authors: Yachnin Brahm J. , Azouz Laura R. , White Ralph E. , Minetti Conceição A. S. A. , Remeta David P. , Tan Victor M. , Drake Justin M. , Khare Sagar D.
Published: March 2021

Confining the activity of a designed protein to a specific microenvironment would have broad-ranging applications, such as enabling cell type-specific therapeutic action by enzymes while avoiding off-target effects. While many natural enzymes are synthesized as inactive zymogens that can be activated by proteolysis, it has been challenging to re-design any chosen enzyme to be similarly stimulus-responsive. Here, we develop a massively parallel computational design, screening, and next-generation sequencing-based approach for pro-enzyme design. As a model system, we employ carboxypeptidase G2 (CPG2), a clinically approved enzyme that has applications in both the treatment of cancer and controlling drug toxicity. Detailed kinetic characterization of the most effective designed variants shows that they are inhibited by approximately 80% compared to the unmodified protein, and their activity is fully restored following incubation with site-specific proteases. Introducing disulfide bonds between the pro-and catalytic domains based on the design models increases the degree of inhibition to 98%, but decreases the degree of restoration of activity by proteolysis. A selected disulfide-containing pro-enzyme exhibits significantly lower activity relative to the fully activated enzyme when evaluated in cell culture. Structural and thermodynamic characterization provides detailed insights into the pro-domain binding and inhibition mechanisms. The described methodology is general and could enable the design of a variety of pro-proteins with precise spatial regulation.

Significance

Proteins have shown promise as therapeutics and diagnostics, but their effectiveness is limited by our inability to spatially target their activity. To overcome this limitation, we developed a computationally-guided method to design inactive “pro-enzymes” or “zymogens,” which are activated through cleavage by a protease. Since proteases are differentially expressed in various tissues and disease states, including cancer, these pro-enzymes could be targeted to the desired microenvironment. We tested our method on the therapeutically-relevant protein, carboxypeptidase G2 (CPG2). We designed Pro-CPG2s that are inhibited by 80-98% and are partially to fully re-activatable following protease treatment. The developed methodology, with further refinements, could pave the way for routinely designing protease-activated protein-based therapeutics and diagnostics that act in a spatially controlled manner.
Shank3mutations impair electrical synapse scaffolding and transmission in mouse brain
Authors: Lautz Jonathan , Zhu Zhiyi , Speed Haley E. , Smith Stephen E. P. , Welsh John P.
Published: March 2021

Shank3mutations contribute to intellectual disability. Because SHANK3 is a protein scaffold that helps organize the multiprotein network of the glutamatergic postsynaptic density (PSD), alterations in chemical synaptic transmission are implicated. Electrical synaptic transmission is a second form of synaptic transmission, enabled by intercellular channels comprised of connexin36 that support direct electrical communication among neurons, electrical brain rhythms, and neurocognitive states. Using multiplex proteomics, we report that two autism-related mutations of mouseShank3disrupt the glutamatergic PSD differently, but have in common the disruption of an association between NMDA-type glutamate-receptors (NMDARs) and connexin36. Mutation ofShank3exons 13-16 most robustly dissociated connexin36 from NMDARs while impairing electrical synaptic transmission and the synchrony of an electrical rhythm in mouse inferior olive. We suggest that electrical synapses are a component of an “extended PSD” sensitive toShank3mutations that produce intellectual disability, at least in part, by impairing electrical synaptic transmission.
Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism
Authors: Konno Yuki , Maruyama Ami , Tomita Masaru , Makinoshima Hideki , Nakayama Joji
Published: March 2021

Metastasis, a leading contributor to the morbidity of cancer patients, occurs through multiple steps. As each of these steps is promoted by different molecular mechanisms, blocking metastasis needs to target each of these steps. Here we report that cinnamon bark extract (CBE) has a suppressor effect on metastatic dissemination of cancer cells. Though a zebrafish embryo screen which utilizes conserved mechanisms between metastasis and zebrafish gastrulation for identifying anti-metastasis drugs, CBE was identified to interfere with gastrulation progression of zebrafish. A zebrafish xenotransplantation model of metastasis validated that CBE suppressed metastatic dissemination of human cancer cells (MDA-MB-231). Interestingly, quantitative metabolome analyses revealed that CBE-treated MDA-MB-231 cells disrupted the production of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which are intermediate metabolites of glycolytic metabolism. CBE decreased the expression of hexokinase 2 (HK2), which catalyzes G6P production, and pharmacological inhibition of HK2 suppressed cell invasion and migration of MDA-MB-231 cells. Taken together, CBE suppressed metastatic dissemination of human cancer cells by inhibiting glycolytic metabolism.
Evolutionary differences in the ACE2 reveals the molecular origins of
COVID-19 susceptibility
Authors: Cheng Ryan R. , Dodero-Rojas Esteban , Di Pierro Michele , Onuchic José N.
Published: March 2021

We explore the energetic frustration patterns associated with the binding
between the SARS-CoV-2 spike protein and the ACE2 receptor protein in a broad
selection of animals. Using energy landscape theory and the concept of energy
frustration—theoretical tools originally developed to study protein folding—we
are able to identify interactions among residues of the spike protein and ACE2
that result in COVID-19 resistance. This allows us to identify whether or not a
particular animal is susceptible to COVID-19 from the protein sequence of ACE2
alone. Our analysis predicts a number of experimental observations regarding
COVID-19 susceptibility, demonstrating that this feature can be explained, at
least partially, on the basis of theoretical means.
Crystal chemistry of lamprophyllite-group minerals from the Murun alkaline complex (Russia) and pegmatites of Rocky Boy and Gordon Butte (USA): single crystal X-ray diffraction and Raman spectroscopy study
Authors: Aksenov Sergey M. , Ryanskaya Anastasia D. , Shchapova Yuliya V. , Chukanov Nikita V. , Vladykin Nikolay V. , Votyakov Sergey L. , Rastsvetaeva Ramiza K.
Published: March 2021

Specific features of the crystal chemistry of lamprophyllite-group minerals (LGMs) are discussed using the available literature data and the results of the single-crystal X-ray diffraction and a Raman spectroscopic studies of several samples taken from the Murun alkaline complex (Russia), and Rocky Boy and Gordon Butte pegmatites (USA) presented here. The studied samples are unique in their chemical features and the distribution of cations over structural sites. In particular, the sample from the Gordon Butte pegmatite is a member of the barytolamprophyllite–emmerichite solid solution series, whereas the samples from the Murun alkaline complex and from the Rocky Boy pegmatite are intermediate members of the solid solution series formed by lamprophyllite and a hypothetical Sr analogue of emmerichite. The predominance of O2−over OH−and F−at theXsite is a specific feature of sample Cha-192 from the Murun alkaline complex. New data on the Raman spectra of LGMs obtained in this work show that the wavenumbers of the O—H stretching vibrations depend on the occupancies of theM2 andM3 sites coordinating with (OH)−groups. Cations other than Na+and Ti4+(mainly, Mg and Fe3+) can play a significant role in the coordination of theXsite occupied by (OH)−. Data on polarized Raman spectra of an oriented sample indicate that the OH groups having different local coordinations have similar orientations with respect to the crystal. The calculated measures of similarity (Δ) for lamprophyllite and ericssonite are identical (0.157 and 0.077 for the 2M- and 2O-polytypes, respectively), which indicates that these minerals are crystal-chemically isotypic and probably should be considered within the same mineral group by analogy to the other mineralogical groups which combine isotypic minerals.
Maleate salts of bedaquiline
Authors: Zeller Matthias , Bogdanowich-Knipp Susan , Smith Pamela , Purcell Dale K. , Okezue Mercy , Smith Daniel T. , Byrn Stephen R. , Clase Kari L.
Published: March 2021

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-methoxyquinolin-3-yl)-3-hydroxy-3-(naphthalen-1-yl)-4-phenylbutyl]dimethylazanium 3-carboxyprop-2-enoate}, C32H32BrN2O2
+·C4H3O4
−, namely, a hemihydrate, a tetrahydrofuran (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydromaleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intramolecular hydrogen bond typical for cis-dicarboxylic acid anions. The conformations of the cations and packing interactions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.
Severely burned wood from wildfires has low functional potential in streams
Authors: Vaz Pedro Gonçalves , Merten Eric C. , Robinson Christopher T. , Pinto Paulo
Published: March 2021

More frequent and more severe forest fires mean more severely burned wood in streams. Instream wood provides habitat complexity, alters geomorphology, retains organic and inorganic material, promotes hyporheic flow and acts as substrate for biofilm and invertebrates. However, little is known about instream wood functions in fire‐prone biomes and how they combine with wood burning levels to guide postfire management efforts.

Over 3 years, we tracked instream wood following forest fires in central Portugal. We examined for the first time the influence of burning level, season and a large suite of driving factors on the likelihood of four different functions having primary ecological consequences—retention of organic matter, serving as substrate for aquatic biota, being key pieces forming wood jams and deflecting flow including pool habitat formation.

One of the main ecological functions of wood in rivers is to provide substrate for vegetation, periphyton, biofilm and oviposition. Our results show that this can be negatively affected when the wood is severely burned.

Except for jam formation, the probability of each stream wood function changed markedly with season and the probability of non‐function was nearly twice as high in the Euro‐Mediterranean dry season than in the wet season.

More anchored and decayed wood increased the probability of all functions, whereas the effect of submergence depended on the function. Challenging the ‘size paradigm’ that larger sized pieces provide more function, our data suggest that the effect of size is function‐specific.

Synthesis and applications. We show how postfire stream restoration success can be maximized by selecting the most appropriate wood and taking advantage of attribute‐function relationships. We urge managers to refrain from removing wood or to selectively remove the most severely carbonized only, allowing the persistence of great potential to provide substrate for stream biota. The non‐attraction of severely burned wood as substrate can be compensated for by other wood with attributes enhancing this function, such as wood deeper within the bankfull area, and with large diameters. These results will help to inform successful management, as is increasingly asked from restoration ecology.
What is better for animal conservation translocation programmes: Soft‐ or hard‐release? A phylogenetic meta‐analytical approach
Authors: Resende Paloma S. , Viana‐Junior Arleu B. , Young Robert John , Azevedo Cristiano S.
Published: March 2021

Animal conservation translocation is an important tool available to conservation biologists to address problems of isolated, declining or endangered populations. This approach includes both captive‐bred and free‐ranging origin animals, which are used to rescue genetically limited populations and re‐establish extirpated populations. Both soft‐ and hard‐release protocols (the release of animals with or without acclimatization, respectively) are used in animal conservation translocation programmes; however, there is no consensus on whether one has better conservation outcomes than the other.

Here, we analysed data from 17 studies to measure the efficiency of both techniques for fauna conservation. Using phylogenetic meta‐analysis, we compared results from articles that used soft‐ and hard‐release protocols to determine the overall effect size. In addition, we examined if the success metrics, type of environment, taxonomic group and animal's origin affected the outcomes of each type of translocation programmes.

We calculated 61 effect sizes for 17 species. We found that the soft‐release protocol is approximate 40% better than the hard‐release protocol (Estimates = 0.44, CI 95: 0.11–0.76). Soft‐release programme increased success by 77% (Estimates = 0.78, CI 95: 0.37–1.19) when movement metrics were used (as compared to hard‐release) and were 41% more successful with terrestrial species.

In general, soft‐releases showed better outcomes by reducing movements away from the release site, but this was driven mostly by terrestrial reptile translocations (77% chance of success); when birds and mammals or the other success metrics were evaluated, both release techniques had similar effects. Lastly, the origin (i.e. captive or wild) of the released animals did not influence the success rate of soft‐ versus hard‐releases.

Synthesis and applications. We conducted a meta‐analysis to evaluate which is the best release protocol for success in animal conservation: soft‐ or hard‐release. Our results showed that soft‐releases are in general better than hard‐releases, especially for reptiles. Protocol outcomes were similar for birds and mammals and were not linked to the origin of the released animals. We recommend that the decision of which protocol to use needs also to consider the financial costs of the used protocol.
Low‐cost tools mitigate climate change during reproduction in an endangered marine ectotherm
Authors: Clarke Leo J. , Elliot Rebecca L. , Abella‐Perez Elena , Jenkins Stuart R. , Marco Adolfo , Martins Samir , Hawkes Lucy A.
Published: March 2021

The impacts of anthropogenic climate change will be most dramatic for species that live in narrow thermal niches, such as reptiles. Given the imminent threat to biodiversity, and that actions to reduce carbon emissions are not yet sufficient, it is important that a sound evidence base of potential mitigation options is available for conservation managers.

Successful incubation and production of male sea turtle hatchlings is threatened by increased global temperatures (sex is determined by the temperature at which eggs incubate). Here we test two conservation tools to reduce incubation temperatures: clutch splitting and clutch shading, on a nesting loggerhead turtle Caretta caretta population in the Eastern Atlantic Ocean.

During the thermosensitive period of incubation, split and shaded clutches were both 1.00°C cooler than control nests. Clutch splitting (mean: 45 eggs) reduced nest temperatures by reducing metabolic heating during incubation compared to controls (mean: 92 eggs). Modelled primary sex ratios differed between nest treatments, with 1.50% (±6% SE) females produced in shaded nests, 45.00% (±7% SE) females in split nests and 69.00% (±6% SE) females in controls. Neither treatment affected hatchling size, success, mass or vigour. When clutch splitting was repeated 2 years later, hatch success was higher in split clutches compared to controls.

Synthesis and applications. Clutch splitting and clutch shading successfully altered the thermal profile of incubating turtle nests. When there is sufficient knowledge to better understand the effects of intervention on fundamental population demographics, they will be useful for reducing incubation temperatures in sea turtle nests, potentially increasing nest survival and male hatchling production. The effect of clutch splitting in reducing nest temperature was lower relative to clutch shading, but requires significantly less funding, materials and specialist skill, key factors for management of turtle rookeries that are often in remote, resource‐limited areas.
Walking the Dark Side: Evading Parliamentary Scrutiny
Authors: Judge David
Published: March 2021

Parliamentary scrutiny assumes a dual willingness—a willingness of government to be scrutinised and a willingness of Parliament to scrutinise, alongside a singular capacity: the ability of Parliament to scrutinise. In the official Westminster view of scrutiny these principles and practicalities are aligned and serve to illuminate the processes and actions of government. There is, however, also a ‘dark side’: where the principles and practicalities of scrutiny are not aligned. While an aversion to parliamentary scrutiny has been hard‐wired into the ‘executive mentality’, the ‘ministerial mindset’, and the ‘instincts of secrecy’ shared by all contemporary UK governments, an examination of the first eighteen months of Boris Johnson's premiership—in the exceptionally turbulent times of ‘getting Brexit done’ and ‘beating coronavirus’—reveals a distinct propensity of his Conservative government to walk on the dark side of parliamentary scrutiny in this period.
The effect of sample hemolysis on blood ethanol analysis using headspace gas chromatography
Authors: Kosecki Patrick Allan , Brooke Phillip , Abbott Lori , Canonico Erika
Published: March 2021

Hemolysis, a common occurrence in blood collected for chemical analysis, has been reported to affect analytical test results for some analytes depending upon the material tested and the analytical technique employed. The potential for hemolysis to impact blood ethanol determinations using headspace gas chromatography of samples diluted with an internal standard was investigated. A sample of non‐hemolyzed blood and a matched sample of hemolyzed blood were both analyzed thirty times for ethanol concentration using headspace gas chromatography. The mean ethanol concentration measured for the non‐hemolyzed samples was 0.0639 g/dl. The mean ethanol concentration measured for the hemolyzed samples was 0.0642 g/dl. The calculated t value, 1.897, was less than the critical t value, 2.002, at a 0.05 level of significance. There was no measured statistical difference detected between the mean blood ethanol concentration determined for a hemolyzed whole blood sample and a non‐hemolyzed whole blood sample.
Impact of patient race/ethnicity on emergency department management of pediatric gastroenteritis in the setting of a clinical pathway
Authors: Congdon Morgan , Schnell Stephanie A. , Londoño Gentile Tatiana , Faerber Jennifer A. , Bonafide Christopher P. , Blackstone Mercedes M. , Johnson Tiffani J.
Published: March 2021

Background

Acute gastroenteritis (AGE) is a common pediatric diagnosis in emergency medicine, accounting for 1.7 million visits annually. Little is known about racial/ethnic differences in care in the setting of standardized care models.

Methods

We used quality improvement data for children 6 months to 18 years presenting to a large, urban pediatric emergency department (ED) treated via a clinical pathway for AGE/dehydration between 2011 and 2018. Race/ethnicity was evaluated as a single variable (non‐Hispanic [NH]‐White, NH‐Black, Hispanic, and NH‐other) related to ondansetron and intravenous fluid (IVF) administration, ED length of stay (LOS), hospital admission, and ED revisits using multivariable regression.

Results

Of 30,849 ED visits for AGE/dehydration, 18.0% were NH‐White, 57.2% NH‐Black, 12.5% Hispanic, and 12.3% NH‐other. Multivariable mixed‐effects generalized linear regression controlling for age, sex, triage acuity, payer, and language revealed that, compared to NH‐White patients, NH‐other patients were more likely to receive ondansetron (adjusted odds ratio [95% CI] = 1.30 [1.17 to 1.43]). NH‐Black, Hispanic, and NH‐other patients were significantly less likely to receive IVF (0.59 [0.53 to 0.65]; 0.74 [0.64 to 0.84]; 0.74 [0.65 to 0.85]) or be admitted to the hospital (0.54 [0.45 to 0.64]; 0.62 [0.49 to 0.78]; 0.76 [0.61 to 0.94]), respectively. NH‐Black and Hispanic patients had shorter LOS (median = 245 minutes for NH‐White, 176 NH‐Black, 199 Hispanic, and 203 NH‐other patients) without significant differences in ED revisits.

Conclusions

Despite the presence of a clinical pathway to guide care, NH‐Black, Hispanic, and NH‐other children presenting to the ED with AGE/dehydration were less likely to receive IVF or hospital admission and had shorter LOS compared to NH‐White counterparts. There was no difference in patient revisits, which suggests discretionary overtreatment of NH‐White patients, even with clinical guidelines in place. Further research is needed to understand the drivers of differences in care to develop interventions promoting equity in pediatric emergency care.
Microclimate Engineering for Climate Change Adaptation in Agriculture: The Case of California Pistachios
Authors: Trilnick Itai , Zilberman David
Published: March 2021

Can farmers adapt to climate change by altering effective weather conditions on their fields? Existing technologies allow farmers to cool down plants by a few degrees during critical periods, reducing the damage from excess heat. With nonlinear effects of high temperatures on yields, slight cooling can bring significant gains in many crops. We call this approach “microclimate engineering” (MCE) and note that it could be useful as a climate change adaptation concept. Our case study deals with California pistachios, threatened by warming daytime temperatures in the winter. A new solution for sunlight reflection, based on products already used in other contexts and crops, could potentially help deal with this challenge. We develop a model to analyze grower choice and market outcomes with MCE for California pistachios. The expected increase in welfare for the period of 2020–2040 is assessed at 0.49–1.42 billion dollars under several scenarios. Simulation results show increases in consumer surplus and total welfare when MCE is available but decreases in aggregate grower profits. We also introduce market power to test its potential effects on the gains from MCE, finding mixed effects.
Impact of early life geohelminths on wheeze, asthma and atopy in Ecuadorian children at 8 years
Authors: Cooper Philip J. , Chis Ster Irina , Chico Martha E. , Vaca Maritza , Oviedo Yisela , Maldonado Augusto , Barreto Mauricio L. , Platts‐Mills Thomas A. E. , Strachan David P.
Published: March 2021

Background

Early‐life exposures to geohelminths may protect against development of wheeze/asthma and atopy.

Objective

To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years.

Methods

Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy.

Results

1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite‐specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non‐atopic children.

Conclusions

Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).
Biallelic RFC1 pentanucleotide repeat expansions in Greek patients with late‐onset ataxia
Authors: Kontogeorgiou Zoi , Kartanou Chrisoula , Tsirligkani Chrysanthi , Anagnostou Evangelos , Rentzos Michail , Stefanis Leonidas , Karadima Georgia , Koutsis Georgios
Published: March 2021

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) has been recently linked to biallelic expansions of a pentanucleotide repeat in the replication factor C subunit 1 (RFC1) gene. Herein, we sought to investigate the presence of pathological RFC1 expansions in selected Greek patients with late‐onset ataxia and delineate the phenotypic spectrum of genetically confirmed CANVAS in the Greek population. We screened genetically a total of 77 selected index patients, 67 originating from a cerebellar ataxia cohort and 10 from a hereditary neuropathy cohort. We identified five index cases (6.5%) with biallelic pathological RFC1 expansions, two in the cerebellar ataxia cohort (3%) and three in the neuropathy cohort (30%). Overall, four out of five of cases with full‐blown CANVAS and one case with sensory ataxic neuropathy had biallelic pathological expansions. The phenotypic spectrum of positive cases (including two affected siblings) was consistent with previous reports and implied that the sensory neuropathy may be the earliest feature in genetically confirmed CANVAS. Screening for biallelic RFC1 expansions is recommended in all cases with late‐onset ataxia of unknown cause, particularly when a sensory neuropathy is present.
Renal function outcomes and kidney biopsy features of living kidney donors with hypertension
Authors: Merzkani Massini A. , Mullan Aidan , Denic Aleksandar , D'Costa Matthew , Iverson Ryan , Kremers Walter , Alexander Mariam P. , Textor Stephen C. , Taler Sandra J. , Stegall Mark D. , Augustine Joshua , Issa Naim , Rule Andrew D.
Published: March 2021

Background

The medium‐ to long‐term outcomes of living kidney donors with hypertension compared to normotensive donors are not well understood, especially with the recent changes in hypertension guidelines.

Methods

We studied a cohort of 950 living kidney donors using different definitions of hypertension based on either ≥140/90 or ≥130/80 mmHg thresholds and based on either office or ambulatory blood pressure readings. Microstructural features on kidney biopsy at the time of donation were compared using different definitions of hypertension.

Results

After adjusting for years of follow‐up, age, sex, and baseline eGFR, hypertension (by any definition) did not significantly predict an eGFR < 45 ml/min/1.73 m2 at a median follow‐up of 10 years postdonation, though there was a borderline association with ambulatory blood pressure ≥ 130/80 mmHg predicting a 40% decline in eGFR (OR = 1.53, 1.00–2.36; p = .051). Proteinuria was predicted by office blood pressure ≥ 140/90 mmHg and by nondipper profile on nocturnal ambulatory blood pressure measurements. At the time of donation, larger glomeruli and arterial hyalinosis on biopsy were associated with hypertension defined by either ≥140/90 or ≥130/80 mmHg (by office or ambulatory measurements). Nocturnal nondipper status was associated with larger glomeruli size but not arteriolar hyalinosis when compared to dippers.

Conclusions

In programs that accept donors with controlled hypertension, various definitions of hypertension are associated with histological findings in the donated kidney, but none predict a clinically significant decline in kidney function 10 years after donation. These data support allowing healthy individuals with controlled hypertension to donate a kidney. However, donors with office hypertension (≥140/90 mmHg) and nondippers (regardless of hypertension status) are at greater long‐term risk for proteinuria, and particularly for these donors, longer follow‐up is warranted.
High‐risk human papillomavirus and ZEB1 in ocular adnexal sebaceous carcinoma
Authors: Moore Robert F. , Zhang Xinhai R. , Allison Derek B. , Rooper Lisa M. , Campbell Ashley A. , Eberhart Charles G.
Published: March 2021

Background

Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy. Oncologic drivers of ocular sebaceous carcinoma are incompletely understood.

Methods

A retrospective search of our pathology archives for OA sebaceous carcinoma identified 18 primary resection specimens. Immunohistochemistry for p16 and ZEB1 and RNA in situ hybridization for high‐risk human papillomavirus (HPV) subtypes were performed.

Results

High‐risk HPV was demonstrated in 2/11 (18%) cases. p16 overexpression was observed in 10/11 (91%). No association between gender, age at presentation, tumor location, intraepithelial spread, tumor size, and T stage was observed between HPV‐driven and nonviral cases. High expression of ZEB1 was observed in the intraepithelial component of 4/14 (28%) cases and in the subepithelial component of 1/13 (7%) cases. ZEB1 overexpression was not associated with HPV status, T stage, or tumor size.

Conclusion

As previously described by others, our findings suggest that a subset of OA sebaceous carcinomas may arise via an HPV‐dependent pathway. However, unlike high‐risk HPV‐driven carcinomas of the oropharynx, we did not identify an association between HPV‐status and prognostic features. Furthermore, p16 expression was not a useful surrogate marker for HPV‐driven disease. ZEB1 overexpression is not associated with HPV in our cohort of ocular sebaceous carcinoma.
Perineuriomatous nevi: A series of eight cases highlighting unifying pathologic features to avoid misdiagnosis
Authors: McAfee John L. , Dermawan Josephine K. , Billings Steven D. , Ko Jennifer S.
Published: March 2021

Background

Perineuriomatous nevi are rare and diagnostically problematic. We report a series of eight perineuriomatous nevi to highlight the diagnostic features.

Methods

Cases were retrospectively reviewed and characterized.

Results

Median age was 42.5 years (range 25‐64), with equal sex distribution. Lesions occurred on the arm (n = 4), trunk (n = 2), and head/neck (n = 2). Median size was 7.5 mm (range 5‐12 mm). Clinical differential diagnoses included atypical nevus (3), blue nevus (1), neurofibroma (1), and dermatofibroma (1). Lesions were circumscribed, dome‐shaped (5/8), and biphasic (8/8) with nested epithelioid cells and wavy spindled cells arranged in whorled fascicles in a myxocollagenous stroma. When present, junctional growth was lentiginous (4/8). No cases displayed pleomorphism or mitotic figures. The perineuriomatous component stained positively for epithelial membrane antigen (8/8 focal to diffuse) and CD34 (4/5 focal to diffuse). SOX10 and S100 protein stained all nevoid cells and in some cases a subset of intermingled spindled cells in perineuriomatous areas, where other melanocytic markers were negative. p16 protein expression was uniformly retained (3/3), and p53 negative (0/2). Nevoid cells in most lesions were positive for BRAFV600E (5/7). Ki67 was mildly elevated (~5%) in 3/3 cases.

Conclusions

Recognizing the histopathologic and immunophenotypic features in these unusual nevi helps avoid overdiagnosis.
Abolition of the obligation to cease an occupation for acknowledgment of an occupational skin disease: Backgrounds and perspectives
Authors: Elsner Peter
Published: March 2021

The occupational disease skin No. 5101 (“severe or recurrent skin diseases that have forced the patient to refrain from all activities that were or could be the cause of the development, aggravation or resurgence of the disease”) is the most frequently notified occupational disease in Germany. Since 1936, the medical‐objective obligation to refrain from risky work activities, which has been necessary for the recognition of this occupational disease, was intended to delimit trivial diseases, facilitate the determination of occupational causality and promote prevention.

The abolition of the legal obligation to refrain from risky work activities as a criterion for the recognition of the occupational disease 5101 as of 01.01.2021 has significant effects on the occupational dermatological care and expert assessment of this occupational disease. For less severe occupational skin diseases, however, the preventive dermatologist’s procedure established since 1972 will continue to apply.
“Summer sowing”: A successful innovation to increase the adoption of key species of annual forage legumes for agriculture in Mediterranean and temperate environments
Authors: Nutt Brad J. , Loi Angelo , Hackney Belinda , Yates Ron J. , D’Antuono Mario , Harrison Robert J. , Howieson John G.
Published: March 2021

This paper reports on the evaluation of “summer sowing,” an innovative approach to increase the adoption of recently domesticated species of hard seeded annual legumes in Mediterranean and temperate Agriculture. The research revealed that several species of annual legumes whose seed can be readily harvested on‐farm and which possess natural hard seed dormancy, may be sown into dry soil in late summer without additional processing. These studies proved that the hard seed dormancy was broken down sufficiently in the soil over 4–6 weeks to produce robust legume pastures with more than 150 seedlings per m2 following the first winter rains, in replicated field sites established across wide agro‐ecological zones in Western Australia (WA) and New South Wales (NSW). Ornithopus sativus Brot., O. compressus L. and Trifolium spumosum L. were suitable for summer sowing based on both hard seed breakdown patterns and subsequent seedling survival in WA. While in NSW, in addition to these legumes, Biserrula pelecinus L., T. vesiculosum Savi. and T. glanduliferum Boiss. were also suitable for summer sowing. A 1.5‐ to 10‐fold increase in herbage production was achieved relative to conventionally sown T. subterraneum L. This development represents a step change in forage legume development for renovated pastures in these environments. Importantly, the experiments revealed differences in G x E effects on seedling establishment, total herbage production and seed yield in different climatic zones. The summer sowing approach is presented as a revolutionary method for pasture renovation that overcomes significant barriers to adoption.
Optimizing the growth of forage and grain legumes on low pH soils through the application of superior Rhizobium leguminosarum biovar viciae strains
Authors: Yates Ron J. , Steel Emma J. , Poole Chris M. , Harrison Robert J. , Edwards Tom J. , Hackney Belinda F. , Stagg Georgina R. , Howieson John G.
Published: March 2021

Climate variability and current farming practices have led to declining soil fertility and pH, with a heavy reliance on fertilizers and herbicides. The addition of forage and grain legumes to farming systems not only improves soil health but also increases farm profitability through nitrogen (N) fertilizer cost offsets. However, the formation of effective symbioses between legumes and rhizobia can be unreliable and is considered at risk when combined with dry sowing practices such as those that have been designed to obviate effects of climate change. This research was initiated to improve the robustness of the legume/rhizobia symbiosis in low pH, infertile and dry soils. Production from two cultivars of field pea (Pisum sativum) and two species of vetch (Vicia spp.), and symbiotic outcomes when inoculated with a range of experimental rhizobial strains (Rhizobium leguminosarum biovar viciae), was assessed in broad acre field trials which simulated farmer practice. New rhizobia strains increased nodulation, N fixation, produced more biomass and higher seed yield than comparator commercial strains. Strain WSM4643 also demonstrated superior survival when desiccated compared to current commercial strains in the laboratory and on seed when delivered as inoculant in peat carriers. WSM4643 is a suitable prospect for a commercial inoculant in Australia and other agricultural areas of the world where growing peas and vetch on soils generally considered problematic for this legume/rhizobia symbiosis. A particular advantage of WSM4643 may be that it potentiates sowing inoculated legumes into dry soil, which is a contemporary response by farmers to climate variation.