Towards DNA Nanomachines for Cancer Treatment: Achieving Selective and Efficient Cleavage of Folded RNA

A mean machine: A deoxyribozyme‐based DNA nanomachine (DNA machine) was developed to bind a fragment of a housekeeping gene mRNA using arms 1–4 and cleave it only in the presence of the cancer marker N‐Myc (see picture). The DNA machine was equipped with RNA‐binding functions for efficient unwinding of folded RNA and can be seen as an initial step towards the development of anticancer gene‐therapy agents based on multifunctional DNA associations.

Abstract

Despite decades of effort, gene therapy (GT) has failed to deliver clinically significant anticancer treatment, owing in part to low selectivity, low efficiency, and poor accessibility of folded RNA targets. Herein, we propose to solve these common problems of GT agents by using a DNA nanotechnology approach. We designed a deoxyribozyme‐based DNA machine that can i) recognize the sequence of a cancer biomarker with high selectivity, ii) tightly bind a structured fragment of a housekeeping gene mRNA, and iii) cleave it with efficiency greater than that of a traditional DZ‐based cleaving agent. An important advantage of the DNA nanomachine over other gene therapy approaches (antisense, siRNA, and CRISPR/cas) is its ability to cleave a housekeeping gene mRNA after being activated by a cancer marker RNA, which can potentially increase the efficiency of anticancer gene therapy. The DNA machine could become a prototype platform for a new type of anticancer GT agent.

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Reactive Amphiphilic Conjugated Polymers for Inhibiting Amyloid β Assembly

Protein misfolding and aberrant aggregations are associated with multiple prevalent and intractable diseases. Inhibition of the amyloid assembly is a promising strategy for the treatment of amyloidoses. However, present effective inhibitors binding to target proteins are based on non‐covalent interactions, which are intrinsically weak and susceptible. Here, we designed and synthesized a reactive conjugated polymer, poly (p‐phenylene vinylene) derivative functionalized with p‐nitrophenyl active ester (PPV‐NP) that could inhibit the assembly of amyloid proteins, degrade preformed fibrils and cut down the cytotoxicity of amyloid aggregations in living cells through combining hydrophobic interactions with irreversible covalent linkage. PPV‐NP also exhibited excellent capacity to eliminate Aβ plaques in brain slices in ex vivo assays. This work represents an innovative attempt to inhibit protein pathogenic aggregates, which may offer insights into the development of therapeutic strategies for amyloidosis.

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Synthesis and characterization of three multi‐shell metalloid gold clusters of the form Au32(R3P)12Cl8

Three multi‐shell metalloid gold clusters of the composition Au32(R3P)12Cl8 (R = Et, nPr, nBu) could be obtained in a straightforward synthesis by reducing R3PAuCl with NaBH4 in ethanol. The Au32 core is comprised of two shells, whereas the inner one shows a tilted icosahedron and the outer one a distorted dodecahedral arrangement. The outer shell is completed by eight chloride atoms and twelve R3P groups. The inner icosahedron shows bond lengths typical for elemental gold while the distances of the gold atoms in the dodecahedral arrangement are in the region of aurophilic interactions. Quantum chemical calculations illustrate the Jahn‐Teller effect observed within the cluster core is attributed to the electronic shell filling. The easy reproducibility, good solubility and yield of those clusters qualify them as perfect starting points for further research.

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Selective Decrosslinking in Liquid Crystal Polymer Actuator for Optical Reconfiguration of Origami and Light‐fueled Locomotion

The ability to optically reconfigure an existing actuator of liquid crystal polymer network (LCN) so that it can display a new actuation behavior or function is highly desired in developing materials for soft robotics application. Herein we demonstrate a powerful approach relying on selective polymer chain decrosslinking in LCN actuator with uniaxial LC alignment. Using an anthracene‐containing LCN, spatially controlled optical decrosslinking can be realized through photocleavage of anthracene dimers under 254 nm UV light, which alters the distribution of actuation (crosslinked) and non‐actuation (decrosslinked) domains and thus determines the actuation behavior upon order‐disorder phase transition. Based on this mechanism, a single actuator of flat shape can be reconfigured in an on‐demand manner to exhibit reversible shape transformation such as self‐folding into origami 3D structures. Moreover, using dye‐doped LCN actuator, light‐fueled micro‐walker can be optically reconfigured to adopt different locomotion behaviors, changing from moving in the laser scanning direction to moving in the opposite direction.

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Template‐Free Synthesis and Selective Filling of Janus Nanocups

Filled to the brim: Two types of Janus nanocups were prepared from ABC triblock terpolymers through cross‐linking and disassembly of shape‐anisotropic "tulip‐bulb" microparticles. Both nanocups feature mirrored Janus properties that allow selective filling of the cup interior or the exterior with compatible materials.

Abstract

We report on the formation of shape‐ and surface‐anisotropic Janus nanocups (JNCs) by evaporation‐induced confinement assembly (EICA) of ABC triblock terpolymers. During microphase separation in spherical confinement, the triblock terpolymer spontaneously adopted a hemispherical shape with an inner concentric lamella–lamella (ll) morphology. Cross‐linking and disassembly of the microparticles resulted in well‐defined JNCs with different chemistry on the inside and outside. By synthesizing polymers with increasing length of the cross‐linkable block, we tuned the mechanical stability of the nanocups, which is relevant to control opening and closing of the cup cavity. We utilize the Janus properties for selective uptake of cargo exemplified by the filling of JNCs with polymer or gold nanoparticles. The directional properties of JNCs suggest applications in locomotion, oil‐spill recovery, storage and release, templating, and as nanoreactors with attoliter volume.

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Direct Production of Higher Oxygenates by Syngas Conversion over a Multifunctional Catalyst

A stable multifunctional catalyst composed of CoMn oxides and CuZnAlZr oxides was developed for direct conversion of syngas to higher oxygenates and olefins with total selectivity of 80.6 wt % at CO conversion of 29.0 %. The interaction manner of the two components plays a crucial role in suppressing C1 products formation and enhancing the selectivity to higher oxygenates.

Abstract

Selective synthesis of higher oxygenates (linear α‐alcohols and α‐aldehydes, C OH) from syngas is highly attractive but remains challenging owing to the low C OH selectivity and low catalytic stability. Herein we introduce a multifunctional catalyst composed of CoMn and CuZnAlZr oxides that dramatically increased the oxygenates selectivity to 58.1 wt %, where more than 92.0 wt % of the produced oxygenates are C OH. Notably, the total selectivity to value‐added chemicals including oxygenates and olefins reached 80.6 wt % at CO conversion of 29.0 % with high stability. The appropriate component proximity can effectively suppress the formation of the undesired C1 products, and the selectively propulsion of reaction network by synergetic effect of different components contributes to the enhanced selectivity to higher oxygenates. This work provides an alternative strategy for the rational design of new catalysts for direct conversion of syngas into higher oxygenates with co‐production of olefins.

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Organelle‐Targeted BODIPY Photocages: Visible‐Light‐Mediated Subcellular Photorelease

Organelle‐specific BODIPY photocages: A general platform for the synthesis of BODIPY photocages suitable for the visible‐light‐mediated release of bioactive molecules in specific pre‐designated organelles is presented.

Abstract

Photocaging facilitates non‐invasive and precise spatio‐temporal control over the release of biologically relevant small‐ and macro‐molecules using light. However, sub‐cellular organelles are dispersed in cells in a manner that renders selective light‐irradiation of a complete organelle impractical. Organelle‐specific photocages could provide a powerful method for releasing bioactive molecules in sub‐cellular locations. Herein, we report a general post‐synthetic method for the chemical functionalization and further conjugation of meso‐methyl BODIPY photocages and the synthesis of endoplasmic reticulum (ER)‐, lysosome‐, and mitochondria‐targeted derivatives. We also demonstrate that 2,4‐dinitrophenol, a mitochondrial uncoupler, and puromycin, a protein biosynthesis inhibitor, can be selectively photoreleased in mitochondria and ER, respectively, in live cells by using visible light. Additionally, photocaging is shown to lead to higher efficacy of the released molecules, probably owing to a localized and abrupt release.

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Stacking‐Layer‐Number Dependence of Water Adsorption in 3D Ordered Close‐Packed g‐C3N4 Nanosphere Arrays for Photocatalytic Hydrogen Evolution

Finding the right number: 3D ordered close‐packed g‐C₃N₄ nanosphere arrays are constructed by a two‐step nanocasting method. Through a precise control of the average nanosphere stacking layer number in the arrays, a stacking‐layer‐number dependence of water adsorption is revealed, which subsequently leads to a remarkably improved photocatalytic hydrogen evolution on the optimized sample.

Abstract

Water adsorption capacity is a key factor to influence the photocatalytic H₂ evolution activity of polymeric g‐C₃N₄ . Herein, we report the synthesis of 3D ordered close‐packed g‐C₃N₄ nanosphere arrays (CNAs) that significantly enhance the water adsorption capacity. Through precisely controlling the average stacking‐layer number (ASLN) of the nanospheres in CNAs, we reveal an interesting stacking‐layer‐number dependence of water adsorption in the newly designed CNAs for accelerating the H₂ evolution reaction, which can be attributed to the differences in adsorption surface areas and adsorption sites endowed by the point‐defect cavities in sample CNAs.

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Assessment of a Large Enzyme–Drug Complex by Proton‐Detected Solid‐State NMR Spectroscopy without Deuteration

The faster, the better? Fast magic angle spinning (MAS) makes solid‐state NMR characterization of complex proteins possible even in the absence of deuteration. It is shown for a 29 kDa complex of hCAII:acetazolamide that structure, dynamics, as well as sidechain proton characteristics become accessible despite a large facilitation of sample production.

Abstract

Solid‐state NMR spectroscopy has recently enabled structural biology with small amounts of non‐deuterated proteins, largely alleviating the classical sample production demands. Still, despite the benefits for sample preparation, successful and comprehensive characterization of complex spin systems in the few cases of higher‐molecular‐weight proteins has thus far relied on traditional ¹³C‐detected methodology or sample deuteration. Herein we show for a 29 kDa carbonic anhydrase:acetazolamide complex that different aspects of solid‐state NMR assessment of a complex spin system can be successfully accessed using a non‐deuterated, 500 μg sample in combination with adequate spectroscopic tools. The shown access to protein structure, protein dynamics, as well as biochemical parameters in amino acid sidechains, such as histidine protonation states, will be transferable to proteins that are not expressible in E. coli.

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Spontaneous and Fast Molecular Motion at Room Temperature in the Solid State

Beacons lit by molecular motion: Intermolecular forces drive the formation of π‐π interactions even in the solid state. Shear forces/scratching disrupt the interactions, turning on emission. The quenched π‐π‐interactions quickly reform even in a film, allowing the visualization of the molecular motions. Theoretical calculations show that the formation of π‐interactions is highly favorable and driving this motion.

Abstract

The development of molecular machines requires new building blocks which are easy to characterize and visualize to realize a complexity comparable to their natural counterparts such as biological enzymes. Furthermore, with the desire to build functional nanobots capable of navigating living organisms, it is necessary that the building blocks show mobility even in the solid state. Herein we report a system which is emissive in the amorphous state but is non‐fluorescent in the crystalline state due to the formation of extensive π‐π interactions. This dual nature could be exploited for easy visualization of its solid‐state molecular rearrangement. The emission of the amorphous film was quenched as the molecules spontaneously formed π‐π interactions even in the solid state. Scratching the non‐emissive film destroyed the interactions and restored the emission of the film. The emission quickly disappeared with an average lifetime of 20 s as the compound reformed the π‐network even at room temperature.

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Blinking Beats Bleaching: The Control of Superoxide Generation by Photo‐ionized Perovskite Nanocrystals

Blink: Single‐molecule studies reveal the mechanism of superoxide‐mediated oxidative disintegration of methylammonium lead iodide perovskite nanocrystals. The generation of superoxide occurs in the excited neutral state of a nanocrystal and ultrafast non‐radiative relaxation hinders electron transfer in the ionized state, allowing for the recovery of photoluminescence intensity after long‐living OFF states.

Abstract

Moisture‐ or oxidation‐induced degradation is a major challenge in the advancement of perovskites‐based technology. The oxidation is caused by electron transfer from a photo‐excited perovskite nanocrystal to oxygen and the formation of superoxide that disintegrates the perovskite structure. In air, the emission intensity of a methylammonium lead iodide (MAPbI₃) perovskite nanocrystal continuously decreases, whereas a nanocrystal in argon or a polymer shows exceptionally stable emission intensity. Surprisingly, in air, the emission intensity of a nanocrystal with long‐lived OFF states completely recovers after the OFF state. This property, along with the rate of non‐radiative relaxation that exceeds the rate of electron transfer suggest that the perovskite nanocrystals produce and react with superoxide in the excited neutral state, but not in the ionized state. In other words, the ultrafast non‐radiative relaxation in the ionized state hinders electron transfer to oxygen and prevents oxidation of perovskites.

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Mechanism‐Dependent Modulation of Ultrafast Interfacial Water Dynamics in Intrinsically Disordered Protein Complexes

The dance of water: Water dynamics at the interface of intrinsically disordered proteins was studied on the femto‐ to nanosecond timescale by using a combination of advanced site‐specific spectroscopic tools. The results offer new insight into the relationship between solvation dynamics and the binding mechanism of proteins of central relevance to nuclear transport.

Abstract

The recognition of intrinsically disordered proteins (IDPs) is highly dependent on dynamics owing to the lack of structure. Here we studied the interplay between dynamics and molecular recognition in IDPs with a combination of time‐resolving tools on timescales ranging from femtoseconds to nanoseconds. We interrogated conformational dynamics and surface water dynamics and its attenuation upon partner binding using two IDPs, IBB and Nup153FG, both of central relevance to the nucleocytoplasmic transport machinery. These proteins bind the same nuclear transport receptor (Importinβ) with drastically different binding mechanisms, coupled folding–binding and fuzzy complex formation, respectively. Solvent fluctuations in the dynamic interface of the Nup153FG‐Importinβ fuzzy complex were largely unperturbed and slightly accelerated relative to the unbound state. In the IBB‐Importinβ complex, on the other hand, substantial relative slowdown of water dynamics was seen in a more rigid interface. These results show a correlation between interfacial water dynamics and the plasticity of IDP complexes, implicating functional relevance for such differential modulation in cellular processes, including nuclear transport.

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Comment on “Predictive value of 18F-FDG PET/CT on survival in locally advanced rectal cancer after neoadjuvant chemoradiation”

L'articolo Comment on "Predictive value of 18F-FDG PET/CT on survival in locally advanced rectal cancer after neoadjuvant chemoradiation" sembra essere il primo su European Review.

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Contributions of innate lymphocytes to allergic responses

Purpose of review Allergic diseases represent a growing global health concern, especially among pediatric populations. Current strategies for the treatment of allergies and asthma focus on limiting the severity of the symptoms; however, additional research investigating the mechanisms promoting inflammation in the context of allergic reactions may lead to the development of more effective therapeutic strategies. Recent findings Novel studies have highlighted the contributions of innate lymphocytes to the induction of inflammatory responses to allergens. Remarkably, neuron-derived signals, hormones, and even vitamins have been suggested to modulate the activity of innate lymphocytes, opening new windows of opportunity for the treatment of allergic inflammation. Summary These studies highlight the complex interactions of the nervous, endocrine, and immune system that promote pathology in the context of allergic inflammation. Further studies are required to understand these interactions in order to aid in the development of novel and much-needed therapies to treat allergic conditions.

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Phenotypes of wheezing and asthma in preschool children

Purpose of review The purpose of this review is to provide an overview of the identified phenotypes of preschool wheezing. Recent findings Early life wheezing patterns have been described in multiple populations, with several commonalities found between cohorts. Early life environmental exposures have been found to be differentially associated with preschool wheezing phenotypes and their future trajectories. These include allergen and microbe exposure, environmental tobacco smoke exposure, and maternal stress and depression. Elevated IgE in early life may also influence future asthma risk. Summary Preschool wheezing phenotypes are heterogeneous and complex, with trajectories that are related to factors including environmental exposures. More research is needed to characterize these relationships, hopefully leading to targeted prevention strategies.

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Impact of occupational exposure on human microbiota

Purpose of review Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome. Recent findings Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome. Summary An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment.

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Severe asthma in children: therapeutic considerations

Purpose of review Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed. Recent findings Adherence monitoring using electronic devices has shown that only 20–30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6–11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain. Summary Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.

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Basophil activation testing in occupational respiratory allergy to low molecular weight compounds

Purpose of review There is an unmet need for better immunological tests in cases of suspected occupational asthma to many workplace chemicals; here we consider the basophil activation test (BAT), a potential alternative to the detection of specific IgE antibodies. Recent findings BAT is fairly widely used in general allergy services; and there is increasing experience of its use in the diagnosis of occupational allergy to low molecular weight agents and chemicals including wood dusts, persulphates, antibiotics and latex. Summary There is potential for BAT to become a useful tool in the clinical consideration of occupational asthma and of its mechanisms, and even to take a place in a Bayesian-based diagnostic algorithm. Further development will only occur if specialist centres with appropriate facilities, and preferably in collaboration, contemplate its use.

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Use of population data for assessing trends in work-related asthma mortality

Purpose of review Work-related asthma has been associated with poorer asthma control and frequent unscheduled healthcare visits, and can be fatal. Case reports of work-related asthma deaths are rare, but can initiate efforts to prevent additional cases. We reviewed relevant literature and data sources to evaluate whether analyzing mortality data at the population level can help identify potential sources of exposures that contribute to work-related asthma. Recent findings A limited number of population-based studies have addressed work-related asthma mortality. Data on asthma mortality are derived from death certificates using the International Classification of Diseases (ICD) as a standard for coding cause. However, no discrete code for work-related asthma is available. Analysis of asthma mortality relative to industries and occupations appears to identify high-risk jobs that were not identified by analyzing asthma morbidity data. Summary Beyond recognized work-related asthma deaths, it is possible that occupational exposures have contributed to other asthma deaths that have gone unnoticed and could potentially be identified by the analysis of mortality data at the population level. Such analyses in the United States appear to assist in recognizing high-risk occupations and industries. Additional analyses would be possible if a work-related asthma ICD code were available.

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Editorial introductions

No abstract available

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Diagnosis of occupational hypersensitivity pneumonitis

Purpose of review To discuss the diagnostic methods currently used in the study of patients with hypersensitivity pneumonitis, with special emphasis on the most recent contributions published in the medical literature regarding the diagnosis of occupational hypersensitivity pneumonitis (OHP). This review presents an update of the use of these diagnostic tests, a controversial issue among experts. Recent findings In spite of the multiple attempts at systematization and the publication of expert consensus statements, standardizing and diagnostic methods and criteria remain particularly difficult. As a result, centers tend to rely on their own experience and establish diagnosis by consensus among their multidisciplinary teams. Though recommendable in many ways, this method presents significant limitations. Summary Diagnosis of OHP should be made with a thorough clinical history of the symptoms and clinical signs as well as a meticulous review, if possible by an expert, of possible exposures in the working environment; a meticulous physical examination; high-resolution computed tomography of the thorax; serum determination of specific immunoglobuline Gs; bronchoalveolar lavage and possibly cryobiopsy; fungal culture; and, when appropriate, a specific inhalation challenge test with the suspected antigen.

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Precision medicine in childhood asthma

Purpose of review Childhood asthma is a heterogeneous disease and many children have uncontrolled disease. Therefore an individualized approach is needed to improve asthma outcomes in children. Precision medicine using clinical characteristics, biomarkers, and the rapidly involving field of genomics and pharmacogenomics aims to achieve asthma control and reduce future risks with less side-effects in individual children with asthma. Recent findings It is not yet possible to select treatment options on clinical characteristics. Novel monoclonal antibodies are efficacious in patients with severe, eosinophilic asthma. Reduced lung function growth and early decline is a prevalent finding in children with persistent asthma. Pharmacogenetic studies have identified children at risk for cortisol suppression when using inhaled corticosteroids. Summary Clinical characteristics and simple biomarkers like eosinophils, IgE, and the fraction of exhaled nitric oxide may be used in clinical practice for a basic precision medicine approach, deciding which children will have the best chance to respond to inhaled corticosteroids and to the biologicals omalizumab and mepolizumab. Further application of pharmacogenomics and breathomics needs additional studies before they can be applied as tools for precision medicine in individual children with asthma.

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Single inhaler maintenance and reliever therapy in pediatric asthma

Purpose of review Asthma affects more than 25 million people worldwide and continues to grow in prevalence. According to a center for disease control and prevention (CDC) report, the total annual cost of asthma in the United States between 2008 and 2013, including medical care, absenteeism, and mortality, was $81.9 billion. Although the National Institute of Health guidelines recommend fixed inhaled corticosteroid (ICS) dosing, the 2008–2010 Medical Expenditure Panel Survey showed that asthma is still poorly controlled. Single inhaler maintenance and reliever therapy (SMART) offers a possible alternative management plan. This is a review of SMART vs. current treatment guidelines. Recent findings SMART addresses variable inflammation with symptom-driven dosing of ICS. It relies on a combination inhaler that has a long-acting β-agonist, which has an immediate onset of action to provide quick relief, in combination with an ICS. Recent studies show that SMART decreases the frequency and severity of asthma exacerbations when compared to fixed ICS dosing. In addition, intermittent use of ICS gave a reduced effect on growth and permitted a lower total amount of ICS to be delivered. Summary SMART appears to outperform treatment that is based on current guidelines in the United States. As inhalers capable of being used for SMART are already approved, what is needed is Food and Drug Administration approval of the SMART strategy.

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Management of acute loss of asthma control: yellow zone strategies

Purpose of review Asthma exacerbations are associated with a significant burden to both the individual patient and to the healthcare system. Patients often step-up home therapies in response to increased asthma symptoms, and the asthma action plan was created to empower patients to self-manage their asthma care. The yellow (intermediate) zone of the asthma action plan is frequently poorly defined, and current Expert Panel Report 3 guideline recommendations are not effective for all patients. This article reviews the evidence behind various recommended yellow zone intervention strategies. Recent findings There are many potential methods of delivering yellow zone therapy, and recent studies have assessed preventive efficacy of a scheduled increase in controller medication(s), reliever medication(s), or a symptom-driven combination of both. The literature suggests that, in certain asthma subpopulations, some methods may be more efficacious than others. Summary Multiple yellow zone approaches may be beneficial, and the yellow zone is not a 'one size fits all' narrative.

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The impact of exercise on asthma

Purpose of review Asthma is one of the most common chronic diseases in children and adults in developed countries around the world. Despite international treatment guidelines, poor asthma control remains a frequent problem leading to missed school and work, and emergency room visits and hospitalizations. Many patients with asthma report exercise as a trigger for their asthma, which likely leads to exercise avoidance as a means to control symptoms. Evolving research has suggested that routine exercise may actually help improve some aspects of asthma control. This review discusses the recent research addressing how routine exercise affects important asthma-related outcomes including symptoms, lung function and quality of life. Recent findings Several systematic reviews and meta-analyses have been conducted in recent years, which strongly support the safety of routine exercise in children and adults with asthma. Exercise appears to favor improvements in aerobic fitness, asthma symptoms and quality of life, but results so far are less consistent in demonstrating improvements to lung function and airway hyperresponsiveness. Summary In addition to routine management guidelines, clinicians should recommend for their patients with asthma routine exercise for its general health benefits and likely improvement in asthma symptoms and quality of life.

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Symptom-based patient-reported outcomes in adults with eosinophilic esophagitis: value for treatment monitoring and randomized controlled trial design

Purpose of review In adults with eosinophilic esophagitis (EoE), a chronic, inflammatory immune-mediated condition of the esophagus, both inflammation and fibrosis are likely associated with symptom generation. Therefore, assessing symptom-based patient-reported outcomes (PROs), defined by US Food and Drug Administration as 'any report of the status of a patient's health condition that comes directly from the patients, without interpretation of the patient's response by a clinician or anyone else', is important in the context of trials and observational studies of emerging therapies. Recent findings For purposes of treatment monitoring, lack of symptoms does not predict the absence of biologic inflammation; hence, endoscopy with esophageal biopsies should be performed to check for residual inflammation. Lack of inflammation does not predict lack of symptoms, and the presence of subepithelial fibrosis cannot be excluded. No published instrument currently measures the frequency of dysphagia described all possible ways, strategies of living with this symptom and various pain types. In randomized controlled trials, in which symptom response was detected using validated PRO measures, only modest decreases in symptom scores were observed. Summary Accessing full EoE symptom spectrum and optimizing PRO measures remains a challenge that should be tackled to reliably assess response to existing and emerging therapies.

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Vitamin D and childhood asthma: causation and contribution to disease activity

Purpose of review To review the literature of the past 18 months (April 2017 through September, 2018) relating to vitamin D and childhood asthma. Recent findings A combined analysis of two clinical trials of maternal vitamin D supplementation trials showed a significant protective effect of vitamin D supplementation trials in the primary prevention of asthma and recurrent wheeze up to age 3 years. Secondary analyses from these trials have also suggested that initial maternal vitamin D status could affect the response to supplementation during pregnancy, with the biggest protective effect in children born to mothers with initial 25hydroxyvitamin D (25OHD) levels of at least 30 ng/ml. A postnatal, 6-month vitamin D supplementation trial in black, premature babies showed a 34% decreased risk of recurrent wheezing at 1 year among the infants who received supplementation. An individual patient data meta-analysis of published clinical trials concluded that vitamin D supplementation decreased the risk of asthma exacerbations in those with 25OHD levels less than 10 ng/ml. Results of observational analyses on primary prevention of asthma and in prevention of exacerbations remain mixed, with the bulk of the evidence suggesting that there is a protective effect of higher vitamin D levels. Summary Evidence continues to accumulate that vitamin D supplementation helps to prevent the development of asthma and recurrent wheeze in early life, and may also help in the management of asthma. The level(s) of circulating vitamin D that maximizes these effects remains to be identified.

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How guideline can shape clinical practice globally: the diagnosis and rationale for action against cow's milk allergy experience

Purpose of review Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice. Recent findings DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable. Summary DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context.

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[ASAP] All-Scale Hierarchically Structured p-Type PbSe Alloys with High Thermoelectric Performance Enabled by Improved Band Degeneracy

Journal of the American Chemical Society

DOI: 10.1021/jacs.9b00967

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Huge US institution cancels subscription with Elsevier

Huge US institution cancels subscription with Elsevier

Huge US institution cancels subscription with Elsevier , Published online: 28 February 2019; doi:10.1038/d41586-019-00758-x

University of California and Dutch publisher fail to strike deal that would allow researchers to publish under open-access terms.

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Bosniak IIF and III Renal Cysts: Can Apparent Diffusion Coefficient–Derived Texture Features Discriminate Between Malignant and Benign IIF and III Cysts?

Objective The aim of this study was to determine which apparent diffusion coefficient–derived texture features are associated with malignancy in Bosniak IIF and III renal cystic lesions. Methods Twenty benign and 7 malignant Bosniak IIF (22) or III (5) renal cysts, as evaluated with magnetic resonance imaging, were assessed for progression to pathology-confirmed malignancy. Whole-cyst volumes of interest were manually segmented from apparent diffusion coefficient maps. Texture features were extracted from each volume of interest, including first-order histogram-based features and higher-order features, and data were analyzed with the Mann-Whitney U test to predict malignant progression. Results Eleven of 17 first-order features were significantly greater in benign compared with malignant cysts. Eight higher-order gray-level co-occurrence matrix (GLCM) texture features were significantly different between groups, 5 of which were greater in the benign population. Conclusions Apparent diffusion coefficient–derived texture measures may help differentiate between benign and malignant Bosniak IIF and III cysts. Received for publication November 18, 2018; accepted January 7, 2019. Correspondence to: Nicolas Gillingham, BA, 660 First Avenue, Third Floor, New York, NY 10016 (e-mail: Nicolas.Gillingham@nyulangone.org). OCRID ID: 0000-0003-3346-2044. This study was not grant funded. The authors declare no conflict of interest. Institutional review board approval was obtained for this study, and all procedures performed were in accordance with the Helsinki Declaration of 1964 and later versions. The requirement for individual informed consent for this study was waived. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Imaging of Usual and Unusual Complication of Rotator Cuff Repair

Several complications may be encountered after rotator cuff (RC) repair. A thorough knowledge of surgical interventions, normal postoperative findings, and postoperative complications is crucial to provide a timely diagnosis, improving the clinical outcome of patients. Postoperative complications may involve RC, implanted device, osteochondral tissue, surgical-site infection, peripheral nerves, soft tissues, and vascular structures. In this review, we discuss the usual and unusual complications detectable after RC repair. Received for publication July 24, 2018; accepted December 17, 2018. Correspondence to: Francesco Di Pietto, MD, PhD, Calata Trinità Maggiore 4, 80134, Napoli, Italy (e-mail: fdipietto@gmail.com). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no conflict of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Circulatory Stasis or Thrombus in Left Atrial Appendage, An Easy Diagnostic Solution

Objective The purpose of this study was to assess the diagnostic performance of prone position cardiac multidetector computed tomography (MDCT) in the detection of left atrial appendage (LAA) thrombi and to make differentiate between thrombus and circulatory stasis using transesophageal echocardiography (TEE) as the criterion-standard imaging modality. Methods From December 2014 to April 2016, 53 consecutive patients were admitted to the hospital because of circulatory stasis or/and thrombus. All patients underwent prone-position MDCT and TEE. Prone-position MDCT and TEE sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results For the MDCT scan in the prone position, the sensitivity, specificity, positive predictive value, and negative predictive value results were 100%, 100%, 100%, and 100%, respectively. Conclusions Multidetector computed tomography scanning in the prone position differentiates circulatory stasis and LAA thrombus, is clinically useful for detecting and ruling out LAA thrombus, and may be an alternative to TEE as a diagnostic tool. Received for publication October 7, 2018; accepted November 27, 2018. Correspondence to: Mecit Kantarci, MD, PhD, Selçuklu Mah. Kanarya Sok No. 17 Aziziye, Erzurum, Turkey (e-mail: akkanrad@hotmail.com). The authors declare no conflict of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Pacifier-Activated Lullaby Helps Preemies Learn to Suck for Milk

Babies love lullabies, and it is hoped that they love them so much that they'll work for them. The PAL is a pacifier that can detect whether a baby is sucking on it, and in turn the baby gets to hear a lullaby. The lullabies are pre-recorded and can be sung by the parents, to encourage the kids to connect with family that might not always be around while they're in the neonatal unit. The clinicians are still testing the technology, but so far they have shown that about 70% of preemies impr...

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A readily available, inexpensive, and scientifically sound wound lavage system

In the horse world, the common garden hose is virtually indispensable. A good, firm jet of cool water run vigorously over a fresh cut, a swollen limb, or a large deep wound at the very least makes a person feel as if something important is being done for the horse. There are many undeniable advantages to using a garden hose for wound lavage. 1) A firm stream of water can certainly help remove surface debris that can contaminate a wound. Removal of debris in this way is effective, less t...

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The Fear of Fat

The link between cellular senescence and the pro-inflammatory signaling networks that contribute to aging and age-related diseases is well established (1). But what drives the link between senescence and neuropsychiatric disorders, such as obesity-induced anxiety – a common condition with serious implications that range from social isolation to suicidal ideation? To find out more, a multinational team of researchers induced obesity in mouse models using a high-fat diet feeding regimen (2)....

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Portable, Battery Powered Viral Detector Takes Only a Drop of Blood

The technology relies on strips of a paper-like material that can become saturated and can slowly move a liquid from its one end to another. The electronics are used to mix a small blood sample with a buffer solution and to then heat it as it moves across the paper. The heat helps to amplify the RNA and for the material to absorb the sample properly. Temperature sensors monitor the process so the liquid moves at the desired rate across the special strips. A band shows up on the end of the...

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Quick and gentle, on the spot blood test at the pediatric clinic

From now on pediatricians in Budakalász are using a unique hematology analyzer from Hungary. The device provides immediate and accurate results in one minute using only a few drops of blood. As a result, in most cases, it now won't be necessary to take children to a nearby hospital for blood sample collection from their vein. The purchase of the device was initiated by the local pediatricians, by Dr. Tordas Dániel, Dr. Dalloul Hicham and Dr. Németh Márta, and was sponsored by Mayor Rogán L...

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Can High-Intensity Interval Training Benefit Schoolchildren

Obesity is a worldwide health problem, and it has become more prevalent in children and adults alike over the past few decades. The increase in rates of childhood obesity is associated with an increase in the number of chronic illnesses. These illnesses include cardiovascular disease, type two diabetes, and cancer. Additionally, increased weight in childhood is related to a low cardiorespiratory capacity in adults. This is important to know because higher cardiorespiratory capacity plays a...

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Norma was selected to participate in EU Gateway in Korea

Norma is among those honoured European companies which have been selected to participate in EU Gateway to Korea Healthcare and Medical Technologies Programme in Seoul between 12th and 16th March. EU Gateway Business Avenues is an initiative funded by the European Union helping European companies to establish long-lasting business collaborations in Asia. EU Gateway Programme's aim is to deepen economic interaction and cooperation between Europe and Asia. After more than 25 years of market p...

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Norma launches the only retrofittable Autoloader available on the market

Norma's hematology product portfolio is continuously expanding. Norma's newest hematology accessory, the Norma Autoloader is an automatic sample vial loading device that allows better workflow and improved time efficiency for your laboratory. Besides its space-saving dimensions similar to any Icon's compact size, what makes the Autoloader a unique instrument is that it is the only retrofittable autosampler on the IVD market; it can be simply connected via USB to existing Icon-5 hematology ...

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Western Blotting- The Complete Solution

At Cleaver Scientific we offer the complete solution for Western Blotting. With a range of Vertical Gel Systems, Power Supplies, Blot Transfer Systems, Reagents and Chemicals and Gel Documentation and Analysis, we provide the complete solution for the Life Scientist. Step 1: Vertical Gel Systems The omniPAGE range comprises three sizes of gel chamber, Mini 10x10cm, Mini Wide 20x10xm and WAVE MAXI 20x20cm. These systems are ideal for running precast or handcast polycrylamide gels f...

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Point-of-care Hematology Company Norma Instruments Receives Prestigious Millennium Innovation Prize

Norma Instruments, an innovative technology company developing novel proprietary trend setting products in the field of hematology, announced today that it has won the prestigious Millennium Innovation Prize. The Prize was established by the Hungarian Intellectual Property Office (HIPO) and is awarded annually to companies who are considered technology leaders and developing innovations of significant societal impact. The prize is handed over on April 26, 2016, the World Intellectual Prope...

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Huge US institution cancels subscription with Elsevier

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[ASAP] Nanoparticle-Assisted NMR Spectroscopy: Enhanced Detection of Analytes by Water-Mediated Saturation Transfer

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b13225

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[ASAP] A Strategy for Increasing the Efficiency of the Oxygen Reduction Reaction in Mn-Doped Cobalt Ferrites

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b13296

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[ASAP] High Li+ and Mg2+ Conductivity in a Cu-Azolate Metal–Organic Framework

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b13418

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Weekend lie-ins don’t compensate for week-long exhaustion

Weekend lie-ins don't compensate for week-long exhaustion

Weekend lie-ins don't compensate for week-long exhaustion, Published online: 28 February 2019; doi:10.1038/d41586-019-00723-8

Catching up on sleep over the weekend doesn't undo the negative metabolic effects of sleep deprivation.

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Night-vision ‘super-mice’ created using light-converting nanoparticles

Night-vision 'super-mice' created using light-converting nanoparticles

Night-vision 'super-mice' created using light-converting nanoparticles, Published online: 28 February 2019; doi:10.1038/d41586-019-00735-4

The particles bind to photoreceptors in the eyes and convert infrared wavelengths to visible light.

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Walter Munk (1917-2019)

Walter Munk (1917-2019)

Walter Munk (1917-2019), Published online: 28 February 2019; doi:10.1038/d41586-019-00750-5

A founder of modern oceanography.

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RNA snippets snare protein linked to degeneration of neurons

RNA snippets snare protein linked to degeneration of neurons

RNA snippets snare protein linked to degeneration of neurons, Published online: 28 February 2019; doi:10.1038/d41586-019-00700-1

Technique ties up an innocuous protein before it gathers into dangerous clumps.

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Paul Nurse on Brexit: ‘UK is sleepwalking into a disaster’

Paul Nurse on Brexit: 'UK is sleepwalking into a disaster'

Paul Nurse on Brexit: 'UK is sleepwalking into a disaster', Published online: 28 February 2019; doi:10.1038/d41586-019-00694-w

As departure day approaches, chief of top UK lab says he fears science will drop off the government's agenda.

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Publisher Correction: Damage-tolerant architected materials inspired by crystal microstructure

Publisher Correction: Damage-tolerant architected materials inspired by crystal microstructure

Publisher Correction: Damage-tolerant architected materials inspired by crystal microstructure, Published online: 28 February 2019; doi:10.1038/s41586-019-0968-y

Publisher Correction: Damage-tolerant architected materials inspired by crystal microstructure

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NIH revoked funding from 14 scientists over sexual harassment last year

NIH revoked funding from 14 scientists over sexual harassment last year

NIH revoked funding from 14 scientists over sexual harassment last year, Published online: 28 February 2019; doi:10.1038/d41586-019-00753-2

The agency has faced sharp criticism over its handling of harassment allegations.

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Managing nitrogen to restore water quality in China

Managing nitrogen to restore water quality in China

Managing nitrogen to restore water quality in China, Published online: 28 February 2019; doi:10.1038/s41586-019-1001-1

Managing nitrogen to restore water quality in China

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Spanish science reforms aim to make life easier for parents

Spanish science reforms aim to make life easier for parents

Spanish science reforms aim to make life easier for parents, Published online: 28 February 2019; doi:10.1038/d41586-019-00649-1

Researchers welcome changes that should also make it easier to hire researchers and buy equipment.

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Sexual harassment rife in Australian science, suggests first workplace survey

Sexual harassment rife in Australian science, suggests first workplace survey

Sexual harassment rife in Australian science, suggests first workplace survey , Published online: 28 February 2019; doi:10.1038/d41586-019-00736-3

One in two female respondents to a national poll has been sexually harassed at work.

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Daily briefing: The Denisova Cave rewrote human history — where to next?

Daily briefing: The Denisova Cave rewrote human history — where to next?

Daily briefing: The Denisova Cave rewrote human history — where to next?, Published online: 25 February 2019; doi:10.1038/d41586-019-00755-0

Going beyond the cave that changed everything, brewing cannabinoids from yeast and the most-censored science topics in China.

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Spatially variable bioturbation and physical mixing drive the sedimentary biogeochemical seascape in the Louisiana continental shelf hypoxic zone

Abstract

Seasonal hypoxia on the Louisiana continental shelf (LCS) has grown to over 22,000 km² with limited information available on how low oxygen effects the benthos. Benthic macrofaunal colonization and sediment biogeochemical parameters were characterized at twelve stations in waters 10–50 m deep along four transects spanning 320 km across the LCS hypoxic zone in the early fall of 2010 when bottom waters typically return to oxic conditions. Chemical data and sediment profile imaging (SPI) support three primary mechanistic pathways of organic matter degradation on the LCS: (i) metal oxide cycling in depositional muds, (ii) infauna-driven bioturbation delivering oxygen below the sediment–water interface, and (iii) sulfate reduction in sediments where iron oxide availability is limited. The transect nearest the Mississippi River delta had the highest concentrations of porewater and solid phase Mn and Fe with SPI images of recently deposited reddish, mixed muddy sediments suggestive of metal cycling. The deepest stations had high oxidized iron concentrations and rust colored sediments with faunal colonization that suggests sediments are oxidized via bioturbation. Many nearshore and central LCS stations had more black sediments, more disturbed clay layers, lower amounts of oxidized iron, and higher sulfate reduction rates than the deepest stations. Sediment mixing coefficients, D_B, determined from chlorophyll-a concentration profiles varied between 33 and 183 cm⁻² year⁻¹. D_B values were highest at the deepest stations where sediments were colonized. D_B were not determined at two nearshore stations where chlorophyll-a concentrations were highly variable in surficial sediments, and on the eastern shelf where sedimentation is high. This study provides a regional view of benthic faunal colonization and sediment biogeochemistry on the LCS, describes regions with potentially different pathways of organic matter degradation, and demonstrates the importance of both bioturbation and physical mixing in processing the large amounts of organic matter in river-dominated continental shelf systems.

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Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care

Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU. Preliminary studies on neonates admitted to operating NICUs demonstrate performance comparable to the most advanced clinical-standard monitoring systems.

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Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel

Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca²⁺)–permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP₂), but lack of structural information has thus far precluded a mechanistic understanding of ligand and lipid sensing by TRPM8. Using cryo–electron microscopy, we determined the structures of TRPM8 in complex with the synthetic cooling compound icilin, PIP₂, and Ca²⁺, as well as in complex with the menthol analog WS-12 and PIP₂. Our structures reveal the binding sites for cooling agonists and PIP₂ in TRPM8. Notably, PIP₂ binds to TRPM8 in two different modes, which illustrate the mechanism of allosteric coupling between PIP₂ and agonists. This study provides a platform for understanding the molecular mechanism of TRPM8 activation by cooling agents.

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Erratum for the Research Article "Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy" by R. Cristescu, R. Mogg, M. Ayers, A. Albright, E. Murphy, J. Yearley, X. Sher, X. Q. Liu, H. Lu, M. Nebozhyn, C. Zhang, J. K. Lunceford, A. Joe, J. Cheng, A. L. Webber, N. Ibrahim, E. R. Plimack, P. A. Ott, T. Y. Seiwert, A. Ribas, T. K. McClanahan, J. E. Tomassini, A. Loboda, D. Kaufman

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Coupled ripple oscillations between the medial temporal lobe and neocortex retrieve human memory

Episodic memory retrieval relies on the recovery of neural representations of waking experience. This process is thought to involve a communication dynamic between the medial temporal lobe memory system and the neocortex. How this occurs is largely unknown, however, especially as it pertains to awake human memory retrieval. Using intracranial electroencephalographic recordings, we found that ripple oscillations were dynamically coupled between the human medial temporal lobe (MTL) and temporal association cortex. Coupled ripples were more pronounced during successful verbal memory retrieval and recover the cortical neural representations of remembered items. Together, these data provide direct evidence that coupled ripples between the MTL and association cortex may underlie successful memory retrieval in the human brain.

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Pantropical climate interactions

The El Niño–Southern Oscillation (ENSO), which originates in the Pacific, is the strongest and most well-known mode of tropical climate variability. Its reach is global, and it can force climate variations of the tropical Atlantic and Indian Oceans by perturbing the global atmospheric circulation. Less appreciated is how the tropical Atlantic and Indian Oceans affect the Pacific. Especially noteworthy is the multidecadal Atlantic warming that began in the late 1990s, because recent research suggests that it has influenced Indo-Pacific climate, the character of the ENSO cycle, and the hiatus in global surface warming. Discovery of these pantropical interactions provides a pathway forward for improving predictions of climate variability in the current climate and for refining projections of future climate under different anthropogenic forcing scenarios.

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Revised paleoaltimetry data show low Tibetan Plateau elevation during the Eocene

Paleotopographic reconstructions of the Tibetan Plateau based on stable isotope paleoaltimetry methods conclude that most of the Plateau's current elevation was already reached by the Eocene, ~40 million years ago. However, changes in atmospheric and hydrological dynamics affect oxygen stable isotopes in precipitation and may thus bias such reconstructions. We used an isotope-equipped general circulation model to assess the influence of changing Eocene paleogeography and climate on paleoelevation estimates. Our simulations indicate that stable isotope paleoaltimetry methods are not applicable in Eocene Asia because of a combination of increased convective precipitation, mixture of air masses, and widespread aridity. Rather, a model-data comparison suggests that the Tibetan Plateau only reached low to moderate (less than 3000 meters) elevations during the Eocene, reconciling oxygen isotope data with other proxies.

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New Products

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Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.

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A lipase-independent pathway of lipid release and immune modulation by adipocytes

To meet systemic metabolic needs, adipocytes release fatty acids and glycerol through the action of neutral lipases. Here, we describe a secondary pathway of lipid release from adipocytes that is independent of canonical lipolysis. We found that adipocytes release exosome-sized, lipid-filled vesicles (AdExos) that become a source of lipid for local macrophages. Adipose tissue from lean mice released ~1% of its lipid content per day via exosomes ex vivo, a rate that more than doubles in obese animals. AdExos and associated factors were sufficient to induce in vitro differentiation of bone marrow precursors into adipose tissue macrophage–like cells. Thus, AdExos are both an alternative pathway of local lipid release and a mechanism by which parenchymal cells can modulate tissue macrophage differentiation and function.

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Motor cortical control of vocal interaction in neotropical singing mice

Like many adaptive behaviors, acoustic communication often requires rapid modification of motor output in response to sensory cues. However, little is known about the sensorimotor transformations that underlie such complex natural behaviors. In this study, we examine vocal exchanges in Alston's singing mouse (Scotinomys teguina). We find that males modify singing behavior during social interactions on a subsecond time course that resembles both traditional sensorimotor tasks and conversational speech. We identify an orofacial motor cortical region and, via a series of perturbation experiments, demonstrate a hierarchical control of vocal production, with the motor cortex influencing the pacing of singing behavior on a moment-by-moment basis, enabling precise vocal interactions. These results suggest a systems-level framework for understanding the sensorimotor transformations that underlie natural social interactions.

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Impacts of historical warming on marine fisheries production

Climate change is altering habitats for marine fishes and invertebrates, but the net effect of these changes on potential food production is unknown. We used temperature-dependent population models to measure the influence of warming on the productivity of 235 populations of 124 species in 38 ecoregions. Some populations responded significantly positively (n = 9 populations) and others responded significantly negatively (n = 19 populations) to warming, with the direction and magnitude of the response explained by ecoregion, taxonomy, life history, and exploitation history. Hindcasts indicate that the maximum sustainable yield of the evaluated populations decreased by 4.1% from 1930 to 2010, with five ecoregions experiencing losses of 15 to 35%. Outcomes of fisheries management—including long-term food provisioning—will be improved by accounting for changing productivity in a warmer ocean.

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Compact radio emission indicates a structured jet was produced by a binary neutron star merger

The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios. We present very-long-baseline interferometry observations, performed 207.4 days after the merger by using a global network of 32 radio telescopes. The apparent source size is constrained to be smaller than 2.5 milli–arc seconds at the 90% confidence level. This excludes the isotropic outflow scenario, which would have produced a larger apparent size, indicating that GW170817 produced a structured relativistic jet. Our rate calculations show that at least 10% of neutron star mergers produce such a jet.

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Precipitation strengthening of aluminum alloys by room-temperature cyclic plasticity

High-strength aluminum alloys are important for lightweighting vehicles and are extensively used in aircraft and, increasingly, in automobiles. The highest-strength aluminum alloys require a series of high-temperature "bakes" (120° to 200°C) to form a high number density of nanoparticles by solid-state precipitation. We found that a controlled, room-temperature cyclic deformation is sufficient to continuously inject vacancies into the material and to mediate the dynamic precipitation of a very fine (1- to 2-nanometer) distribution of solute clusters. This results in better material strength and elongation properties relative to traditional thermal treatments, despite a much shorter processing time. The microstructures formed are much more uniform than those characteristic of traditional thermal treatments and do not exhibit precipitate-free zones. These alloys are therefore likely to be more resistant to damage.

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Vernier spectrometer using counterpropagating soliton microcombs

Determination of laser frequency with high resolution under continuous and abrupt tuning conditions is important for sensing, spectroscopy, and communications. We show that a single microresonator provides rapid and broadband measurement of optical frequencies with a relative frequency precision comparable to that of conventional dual-frequency comb systems. Dual-locked counterpropagating solitons having slightly different repetition rates were used to implement a vernier spectrometer, which enabled characterization of laser tuning rates as high as 10 terahertz per second, broadly step-tuned lasers, multiline laser spectra, and molecular absorption lines. Besides providing a considerable technical simplification through the dual-locked solitons and enhanced capability for measurement of arbitrarily tuned sources, our results reveal possibilities for chip-scale spectrometers that exceed the performance of tabletop grating and interferometer-based devices.

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Interface and heterostructure design in polyelemental nanoparticles

Nanomaterials that form as heterostructures have applications in catalysis, plasmonics, and electronics. Multielement nanoparticles can now be synthesized through a variety of routes, but how thermodynamic phases form in such structures and how specific interfaces between them can be designed and synthesized are still poorly understood. We explored how palladium-tin alloys form mixed-composition phases with metals with known but complex miscibilities. Nanoparticles with up to seven elements were synthesized, and many form triphase heterostructures consisting of either three-interface or two-interface architectures. Density functional theory calculations and experimental work were used to determine the balance between the surface and interfacial energies of the observed phases. From these observations, design rules have been established for making polyelemental systems with specific heterostructures, including tetraphase nanoparticles with as many as six junctions.

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Impact craters on Pluto and Charon indicate a deficit of small Kuiper belt objects

The flyby of Pluto and Charon by the New Horizons spacecraft provided high-resolution images of cratered surfaces embedded in the Kuiper belt, an extensive region of bodies orbiting beyond Neptune. Impact craters on Pluto and Charon were formed by collisions with other Kuiper belt objects (KBOs) with diameters from ~40 kilometers to ~300 meters, smaller than most KBOs observed directly by telescopes. We find a relative paucity of small craters 13 kilometers in diameter, which cannot be explained solely by geological resurfacing. This implies a deficit of small KBOs (1 to 2 kilometers in diameter). Some surfaces on Pluto and Charon are likely 4 billion years old, thus their crater records provide information on the size-frequency distribution of KBOs in the early Solar System.

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Glutamate signaling at cytoneme synapses

We investigated the roles of components of neuronal synapses for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp (Decapentaplegic, a homolog of the vertebrate bone morphogenetic protein) from the wing imaginal disc. Dpp signaling in the ASP was compromised if disc cells lacked Synaptobrevin and Synaptotagmin-1 (which function in vesicle transport at neuronal synapses), the glutamate transporter, and a voltage-gated calcium channel, or if ASP cells lacked Synaptotagmin-4 or the glutamate receptor GluRII. Transient elevations of intracellular calcium in ASP cytonemes correlate with signaling activity. Calcium transients in ASP cells depend on GluRII, are activated by l-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and by the GluR inhibitor NASPM (1-naphthylacetyl spermine trihydrochloride). Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.

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Unblocking the brain

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Free news, but who's reading?

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Publisher Correction: Damage-tolerant architected materials inspired by crystal microstructure

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Weekend lie-ins don’t compensate for week-long exhaustion

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2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical pa...

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Draft Genome of Burkholderia cenocepacia TAtl-371, a Strain from the Burkholderia cepacia Complex Retains Antagonism in Different Carbon and Nitrogen Sources

Abstract

Burkholderia cenocepacia TAtl-371 was isolated from the rhizosphere of a tomato plant growing in Atlatlahucan, Morelos, Mexico. This strain exhibited a broad antimicrobial spectrum against bacteria, yeast, and fungi. Here, we report and describe the improved, high-quality permanent draft genome of B. cenocepacia TAtl-371, which was sequenced using a combination of PacBio RS and PacBio RS II sequencing methods. The 7,496,106 bp genome of the TAtl-371 strain is arranged in three scaffolds, contains 6722 protein-coding genes, and 99 RNA only-encoding genes. Genome analysis revealed genes related to biosynthesis of antimicrobials such as non-ribosomal peptides, siderophores, chitinases, and bacteriocins. Moreover, analysis of bacterial growth on different carbon and nitrogen sources shows that the strain retains its antimicrobial ability.

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Soil carbon dioxide and methane fluxes from forests and other land use types in an African tropical montane region

Abstract

In the last 40 years, large areas of the Mau forest, the largest contiguous tropical montane forest in East Africa, have been cleared for agriculture. To date, there are no empirical data on how this land use change affects carbon dioxide (CO₂) fluxes from soil respiration and soil methane (CH₄) fluxes. This study reports measured annual soil CO₂ and CH₄ fluxes from the native Mau forest and previously forested lands converted to smallholder grazing land, smallholder and commercial tea plantations and eucalyptus plantations. Fluxes were measured weekly from August 2015 to August 2016 using the static chamber method. Grazing lands had the highest (p = 0.028) cumulative respiratory CO₂ fluxes (25.6 ± 2.9 Mg CO₂–C ha⁻¹ year⁻¹), whereas lowest fluxes were observed in commercial tea plantations (5.6 ± 0.5 Mg CO₂–C ha⁻¹ year⁻¹). Soil respiratory CO₂ fluxes were positively correlated with soil pH, but negatively correlated with soil C:N ratio. Annual soil fluxes were explained by soil pH, bulk density and the interaction between soil pH and C:N ratio. Most soils were sinks for atmospheric CH₄ across all land use types. Methane uptake was highest for native forest sites (− 3.08 ± 0.35 to − 5.84 ± 0.61 kg CH₄–C ha⁻¹ year⁻¹) and for eucalyptus plantations (− 3.43 ± 0.19 kg CH₄–C ha⁻¹ year⁻¹). Uptake decreased significantly with increasing land use intensity (smallholder tea plantations: − 1.42 ± 0.09 kg CH₄–C ha⁻¹ year⁻¹, commercial tea plantations: − 1.44 ± 0.29 kg CH₄–C ha⁻¹ year⁻¹). Soils of smallholder grazing lands had the lowest CH₄ uptake rates (− 0.36 ± 0.25 kg CH₄–C ha⁻¹ year⁻¹). Annual CH₄ uptake was negatively correlated with mean annual soil water-filled pore space (p < 0.01) and bulk density (p = 0.003) and decreased with increasing soil inorganic NH₄⁺ concentrations (p = 0.03). Annual soil CH₄ can be explained by mainly soil water content and bulk density and these factors are related to gas diffusion. Our study shows that converting tropical montane forests to managed land use types affects soil CO₂ and CH₄ fluxes. Specifically, the CH₄ sink strength in managed land use types of these montane tropical soils was reduced to less than half of the sink strength in the native forest. Soil respiratory CO₂ fluxes were also altered by land use with grazing lands emitting 3–4 times more CO₂ than the other land use types.

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Spanish science reforms aim to make life easier for parents

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Social marketing including financial incentive programs at worksite cafeterias for preventing obesity: a systematic review

As with food-taxation strategies, such interventions as discounted healthy menus, point-of-purchase advertisements, and sugar-free beverages for employees at worksites could help prevent obesity. This study as...

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Sonocatalytic degradation of butylparaben in aqueous phase over Pd/C nanoparticles

Abstract

In the present work, the sonocatalytic degradation of butylparaben was investigated using Pd immobilized on carbon black as the sonocatalyst. The presence of 25 mg/L 10Pd/C significantly increased the removal rate of butylparaben and the observed kinetic constant increased from 0.0126 to 0.071 min⁻¹, while the synergy index between sonolysis and adsorption was 70.7%. The BP degradation followed pseudo-first-order kinetics with the apparent kinetic constant decreased from 0.071 to 0.030 min⁻¹ when the initial concentration of butylparaben increased from 0.5 to 2 mg/L. The process was being favored slightly under alkaline conditions. The presence of organic matter (20 mg/L humic acid) reduced the apparent kinetic constant more than two times. The addition of chlorides up to 250 mg/L did not significantly reduce the rate of reaction, while the presence of 250 mg/L bicarbonates reduced the observed kinetic constant from 0.071 to 0.0472 min⁻¹. The prepared catalyst retains the efficiency after five subsequent experiments since the apparent kinetic constant was only slightly decreased from 0.071 to 0.059 min⁻¹.

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[ASAP] Naphthocage: A Flexible yet Extremely Strong Binder for Singly Charged Organic Cations

Journal of the American Chemical Society

DOI: 10.1021/jacs.9b00445

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