Miracle-dz/UniFAR-FTUs huggingface dataset:
Maatschappelijke kosten van astma, COPD en respiratoire allergie.

Volgens schattingen van het Rijksinstituut voor Volksgezondheid en Milieu (RIVM) stijgt het aantal mensen in Nederland met astma en COPD de komende 25 jaar sterk, met respectievelijk 28% en 70%. Dit komt vooral door de bevolkingsgroei en de vergrijzing. Het aantal patienten met respiratoire allergie (zoals hooikoorts) blijft in deze periode ongeveer gelijk. Deze aandoening komt namelijk bij ouderen minder voor. De verwachting is dat de totale medische kosten voor alle drie de aandoeningen over 25 jaar (fors) zijn gestegen. Voor respiratoire allergie zal dat met 73% zijn; voor astma stijgen de kosten met 150%, voor COPD met 220%. Deze percentages zijn inclusief de jaarlijkse stijging van zorguitgaven door onder andere technologische veranderingen (zoals nieuwe medicijnen) en prijsstijgingen, volgens de trendanalyse van het Centraal Planbureau. Het RIVM heeft deze schattingen gemaakt op verzoek van het Longfonds. De cijfers zijn gebaseerd op nieuwe analyses van de kosten in 2007. Voor astma bedroegen de medische kosten in totaal 287 miljoen euro, gemiddeld 530 euro per patient. Dit bedrag bestaat voor bijna driekwart uit kosten voor medicijnen. Bij werknemers komt daar nog gemiddeld 1200 euro per persoon per jaar bovenop vanwege extra ziekteverzuim door astma. Van hen verzuimen werknemers die ouder zijn dan 55 jaar het meest. De medische kosten voor COPD in Nederland in 2007 waren 415 miljoen euro, gemiddeld 1400 euro per patient. Hierbij waren geneesmiddelen, ziekenhuisopnames en langdurige zorg (zoals thuiszorg en in verzorgingshuizen) de belangrijke kostenposten. Kosten van arbeidsongeschiktheid waren voor werkenden met COPD gemiddeld 1200 euro per persoon. Voor ziekteverzuim waren deze gemiddeld 1900 euro per werkende met COPD. Deze kosten overtreffen veruit de kosten van het zorggebruik voor COPD. De medische kosten voor respiratoire allergie waren 102 miljoen euro, gemiddeld 170 euro per patient. Medicatiekosten vormden hierin het grootste deel, 90%. Er waren te weinig data om de ziekteverzuimkosten betrouwbaar te schatten. De gepresenteerde cijfers over de verwachte stijging van het aantal mensen met deze drie aandoeningen en de kosten die hiermee gemoeid zijn, leveren belangrijke informatie op voor het beleid. Preventie en behandeling zijn daarbij onverminderd belangrijk, zoals stoppen met roken en doelmatiger gebruik van geneesmiddelen. Aangezien er steeds meer oudere patienten met astma en COPD komen, is specifieke ondersteuning ook voor hen van belang.
Structural mechanism for the recognition and ubiquitination of a single nucleosome residue by Rad6–Bre1

Significance Histone H2B monoubiquitination is important for gene expression. It is mediated by the yeast E3 ligase Bre1 (human RNF20/40) and the E2 conjugating enzyme Rad6. These enzymes associate with RNA polymerase II and their activity is counteracted by the H2B deubiquitinase of the Spt–Ada–Gcn5 acetyltransferase (SAGA) complex. In contrast to many other E3 ligases, the Rad6–Bre1 machinery exclusively modifies a single lysine on the nucleosome. Given the number of other nearby lysines, it was unknown how such specificity could be achieved. Our study shows how Rad6–Bre1 recognition of the nucleosome is mechanistically coupled to ubiquitin transfer, how a single target lysine is chosen, and how Rad6–Bre1 compete with SAGA for regulatory access to a specific region on the nucleosome. Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6–Bre1 machinery is unknown. Using chemical cross-linking and mass spectrometry, we identified the functional interfaces of Rad6, Bre1, and NCPs in a defined in vitro system. The Bre1 RING domain cross-links exclusively with distinct regions of histone H2B and H2A, indicating a spatial alignment of Bre1 with the NCP acidic patch. By docking onto the NCP surface in this distinct orientation, Bre1 positions the Rad6 active site directly over H2B Lys123. The Spt–Ada–Gcn5 acetyltransferase (SAGA) H2B deubiquitinase module competes with Bre1 for binding to the NCP acidic patch, indicating regulatory control. Our study reveals a mechanism that ensures site-specific NCP ubiquitination and fine-tuning of opposing enzymatic activities.
Vibrotactile Postural Control in Patients that have Sit-to-Stand Balance Deficit and Fall

Abstract : Vibrotactile displays have been found to be beneficial in improving balance test scores that correlate with a decrease in fall rate in laboratory studies. Investigations of these devices have been limited to upright stance and have not been done in clinical settings. Furthermore, transitional movements facilitated by vibrotactile displays, such as forward lean and rise found in sit-to-stand, have not been investigated. A prospective study investigated the relationship between force platform vibrotactile intervention and balance test scores, sit-to-stand and falls in subjects with abnormal NeuroCom Sit-to-Stand test results and 2 or more self-reported falls within the last 6 months. Subjects: Subjects included 30 community-dwelling adults, aged 60 to 79 years, 10 as off-site controls, 10 as on-site controls, and 10 as on-site device intervention subjects.
Flexible Aqueous Li‐Ion Battery with High Energy and Power Densities

A flexible and wearable aqueous symmetrical lithium‐ion battery is developed using a single LiVPO4F material as both cathode and anode in a “water‐in‐salt” gel polymer electrolyte. The symmetric lithium‐ion chemistry exhibits high energy and power density and long cycle life, due to the formation of a robust solid electrolyte interphase consisting of Li2CO3‐LiF, which enables fast Li‐ion transport. Energy densities of 141 Wh kg−1, power densities of 20 600 W kg−1, and output voltage of 2.4 V can be delivered during >4000 cycles, which is far superior to reported aqueous energy storage devices at the same power level. Moreover, the full cell shows unprecedented tolerance to mechanical stress such as bending and cutting, where it not only does not catastrophically fail, as most nonaqueous cells would, but also maintains cell performance and continues to operate in ambient environment, a unique feature apparently derived from the high stability of the “water‐in‐salt” gel polymer electrolyte.
A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity

Significance Parkinson’s disease is characterized by the presence in brain tissues of aberrant aggregates primarily formed by the protein α-synuclein. It has been difficult, however, to identify compounds capable of preventing the formation of such deposits because of the complexity of the aggregation process of α-synuclein. By exploiting recently developed highly quantitative in vitro assays, we identify a compound, squalamine, that blocks α-synuclein aggregation, and characterize its mode of action. Our results show that squalamine, by competing with α-synuclein for binding lipid membranes, specifically inhibits the initiation of the aggregation process of α-synuclein and abolishes the toxicity of α-synuclein oligomers in neuronal cells and in an animal model of Parkinson’s disease. The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson’s disease and related conditions.
A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes

Significance Plasmacytoid dendritic cells (pDCs) are specialized white blood cells responsible for a wide range of immune functions, most notably production of the antiviral factor, type I interferon. We have discovered a previously unknown population of pDCs in human blood, bone marrow, and tonsil that is morphologically, phenotypically, and genetically distinct from most pDCs. These cells, which can be identified based on their expression of CD2, CD5, and CD81 on their surface, fail to produce type I interferon, yet they strongly activate B and T lymphocytes. A functionally and phenotypically similar population of pDCs is present in mice. These pDCs likely play an important role in the immune response. Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5+CD81+ pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34+ progenitors. These CD2hiCD5+CD81+ cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5+CD81+ pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5−CD81− pDCs, human CD5+CD81+ pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.
Selective Surface Enhanced Raman Scattering for Quantitative Detection of Lung Cancer Biomarkers in Superparticle@MOF Structure

Surface enhanced Raman scattering (SERS) is a trace detection technique that extends even to single molecule detection. Its potential application to the noninvasive recognition of lung malignancies by detecting volatile organic compounds (VOCs) that serve as biomarkers would be a breakthrough in early cancer diagnostics. This application, however, is currently limited by two main factors: (1) most VOC biomarkers exhibit only weak Raman scattering; and (2) the high mobility of gaseous molecules results in a low adsorptivity on solid substrates. To enhance the adsorption of gaseous molecules, a ZIF‐8 layer is coated onto a self‐assembly of gold superparticles (GSPs) in order to slow the flow rate of gaseous biomarkers and depress the exponential decay of the electromagnetic field around the GSP surfaces. Gaseous aldehydes that are released as a result of tumor‐specific tissue composition and metabolism, thereby acting as indicators of lung cancer, are guided onto SERS‐active GSPs substrates through a ZIF‐8 channel. Through a Schiff base reaction with 4‐aminothiophenol pregrafted onto gold GSPs, gaseous aldehydes are captured with a 10 ppb limit of detection, demonstrating tremendous prospects for in vitro diagnoses of early stage lung cancer.
Nitrosomonas europaea cytochrome P460 is a direct link between nitrification and nitrous oxide emission

Significance Nitrous oxide (N2O) is a potent ozone-depleting greenhouse gas. This work identifies a means by which N2O is generated during nitrification, or biological ammonia oxidation. Fertilizer use in agriculture stimulates nitrification, thus increasing the volume of N2O emissions worldwide. The results presented herein will inform models and strategies toward optimized, sustainable agriculture. Moreover, these results highlight a rare example of biological N–N bond formation. Ammonia oxidizing bacteria (AOB) are major contributors to the emission of nitrous oxide (N2O). It has been proposed that N2O is produced by reduction of NO. Here, we report that the enzyme cytochrome (cyt) P460 from the AOB Nitrosomonas europaea converts hydroxylamine (NH2OH) quantitatively to N2O under anaerobic conditions. Previous literature reported that this enzyme oxidizes NH2OH to nitrite (NO2−) under aerobic conditions. Although we observe NO2− formation under aerobic conditions, its concentration is not stoichiometric with the NH2OH concentration. By contrast, under anaerobic conditions, the enzyme uses 4 oxidizing equivalents (eq) to convert 2 eq of NH2OH to N2O. Enzyme kinetics coupled to UV/visible absorption and electron paramagnetic resonance (EPR) spectroscopies support a mechanism in which an FeIII–NH2OH adduct of cyt P460 is oxidized to an {FeNO}6 unit. This species subsequently undergoes nucleophilic attack by a second equivalent of NH2OH, forming the N–N bond of N2O during a bimolecular, rate-determining step. We propose that NO2− results when nitric oxide (NO) dissociates from the {FeNO}6 intermediate and reacts with dioxygen. Thus, NO2− is not a direct product of cyt P460 activity. We hypothesize that the cyt P460 oxidation of NH2OH contributes to NO and N2O emissions from nitrifying microorganisms.
2D Organic Materials for Optoelectronic Applications

The remarkable merits of 2D materials with atomically thin structures and optoelectronic attributes have inspired great interest in integrating 2D materials into electronics and optoelectronics. Moreover, as an emerging field in the 2D‐materials family, assembly of organic nanostructures into 2D forms offers the advantages of molecular diversity, intrinsic flexibility, ease of processing, light weight, and so on, providing an exciting prospect for optoelectronic applications. Herein, the applications of organic 2D materials for optoelectronic devices are a main focus. Material examples include 2D, organic, crystalline, small molecules, polymers, self‐assembly monolayers, and covalent organic frameworks. The protocols for 2D‐organic‐crystal‐fabrication and ‐patterning techniques are briefly discussed, then applications in optoelectronic devices are introduced in detail. Overall, an introduction to what is known and suggestions for the potential of many exciting developments are presented.
Agrobacterium-delivered virulence protein VirE2 is trafficked inside host cells via a myosin XI-K–powered ER/actin network

Significance Agrobacterium causes diseases in a wide range of host plants. It has been developed as a genetic tool to transform a variety of plant species and nonplant organisms. It can achieve a transformation efficiency as high as 100%. However, it is not clear how Agrobacterium virulence factors are trafficked through host cytoplasm to achieve such a wide host range and a high efficiency. Here we report that Agrobacterium-delivered VirE2 is trafficked inside plant cells via the endoplasmic reticulum and F-actin network. This trafficking is powered by myosin XI-K. As the myosin-powered actin network is well conserved, our data suggest that Agrobacterium hijacks the conserved host network for virulence trafficking to transform a wide range of recipient cells with high efficiency. Agrobacterium tumefaciens causes crown gall tumors on various plants by delivering transferred DNA (T-DNA) and virulence proteins into host plant cells. Under laboratory conditions, the bacterium is widely used as a vector to genetically modify a wide range of organisms, including plants, yeasts, fungi, and algae. Various studies suggest that T-DNA is protected inside host cells by VirE2, one of the virulence proteins. However, it is not clear how Agrobacterium-delivered factors are trafficked through the cytoplasm. In this study, we monitored the movement of Agrobacterium-delivered VirE2 inside plant cells by using a split-GFP approach in real time. Agrobacterium-delivered VirE2 trafficked via the endoplasmic reticulum (ER) and F-actin network inside plant cells. During this process, VirE2 was aggregated as filamentous structures and was present on the cytosolic side of the ER. VirE2 movement was powered by myosin XI-K. Thus, exogenously produced and delivered VirE2 protein can use the endogenous host ER/actin network for movement inside host cells. The A. tumefaciens pathogen hijacks the conserved host infrastructure for virulence trafficking. Well-conserved infrastructure may be useful for Agrobacterium to target a wide range of recipient cells and achieve a high efficiency of transformation.
Promising Thermoelectric Bulk Materials with 2D Structures

Given that more than two thirds of all energy is lost, mostly as waste heat, in utilization processes worldwide, thermoelectric materials, which can directly convert waste heat to electricity, provide an alternative option for optimizing energy utilization processes. After the prediction that superlattices may show high thermoelectric performance, various methods based on quantum effects and superlattice theory have been adopted to analyze bulk materials, leading to the rapid development of thermoelectric materials. Bulk materials with two‐dimensional (2D) structures show outstanding properties, and their high performance originates from both their low thermal conductivity and high Seebeck coefficient due to their strong anisotropic features. Here, the advantages of superlattices for enhancing the thermoelectric performance, the transport mechanism in bulk materials with 2D structures, and optimization methods are discussed. The phenomenological transport mechanism in these materials indicates that thermal conductivities are reduced in 2D materials with intrinsically short mean free paths. Recent progress in the transport mechanisms of Bi2Te3‐, SnSe‐, and BiCuSeO‐based systems is summarized. Finally, possible research directions to enhance the thermoelectric performance of bulk materials with 2D structures are briefly considered.
Carbohydrates, glycemic index, glycemic load, and breast cancer risk: a systematic review and dose‐response meta‐analysis of prospective studies

Context: The investigation of dose‐response associations between carbohydrate intake, glycemic index, glycemic load, and risk of breast cancer stratified by menopausal status, hormone receptor status, and body mass index (BMI) remains inconclusive. Objective: A systematic review and dose‐response meta‐analyses was conducted to investigate these associations. Data Sources: As part of the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, PubMed was searched up to May 2015 for relevant studies on these associations. Study Selection: Prospective studies reporting associations between carbohydrate intake, glycemic index, or glycemic load and breast cancer risk were included. Data Extraction: Two investigators independently extracted data from included studies. Results: Random‐effects models were used to summarize relative risks (RRs) and 95%CIs. Heterogeneity between subgroups, including menopausal status, hormone receptor status, and BMI was explored using meta‐regression. Nineteen publications were included. The summary RRs (95%CIs) for breast cancer were 1.04 (1.00‐1.07) per 10 units/d for glycemic index, 1.01 (0.98‐1.04) per 50 units/d for glycemic load, and 1.00 (0.96‐1.05) per 50 g/d for carbohydrate intake. For glycemic index, the association appeared slightly stronger among postmenopausal women (summary RR per 10 units/d, 1.06; 95%CI, 1.02‐1.10) than among premenopausal women, though the difference was not statistically significant (Pheterogeneity = 0.15). Glycemic load and carbohydrate intake were positively associated with breast cancer among postmenopausal women with estrogen‐negative tumors (summary RR for glycemic load, 1.28; 95%CI, 1.08‐1.52; and summary RR for carbohydrates, 1.13; 95%CI, 1.02‐1.25). No differences in BMI were detected. Conclusions: Menopausal and hormone receptor status, but not BMI, might be potential influencing factors for the associations between carbohydrate intake, glycemic index, glycemic load, and breast cancer.
Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

Significance The spatial organization of chromatin within the nucleus regulates genomic functions including DNA repair, transcription, and replication. For example, replication origins cluster prior to initiating replication, likely to aggregate the many necessary factors, but the mechanism is poorly understood. We recently discovered yeast “Forkhead Box” (Fox) DNA binding proteins, Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2), as required for this origin clustering and regulation of initiation timing. This study reveals that Fkh1 and Fkh2 share a structural motif that allows dimerization to bring distal DNA binding sites into close proximity. Mutation that disrupts dimerization ablates origin clustering and deregulates origin activation, suggesting causality between origin clustering and initiation control. We propose that Fkh1 and Fkh2 and related Fox proteins in metazoans establish chromatin architecture. Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified Saccharomyces cerevisiae Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2) as required for the clustering of a subset of replication origins in G1 phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity. Here, we show that Fkh1 and Fkh2 share a unique structural feature of human FoxP proteins that enables FoxP2 and FoxP3 to form domain-swapped dimers capable of bridging two DNA molecules in vitro. Accordingly, Fkh1 self-associates in vitro and in vivo in a manner dependent on the conserved domain-swapping region, strongly suggestive of homodimer formation. Fkh1- and Fkh2-domain-swap-minus (dsm) mutations are functional as transcription factors yet are defective in replication origin timing control. Fkh1-dsm binds replication origins in vivo but fails to cluster them, supporting the conclusion that Fkh1 and Fkh2 dimers perform a structural role in the spatial organization of chromosomal elements with functional importance.
Electrical Textile Valves for Paper Microfluidics

This paper describes electrically‐activated fluidic valves that operate based on electrowetting through textiles. The valves are fabricated from electrically conductive, insulated, hydrophobic textiles, but the concept can be extended to other porous materials. When the valve is closed, the liquid cannot pass through the hydrophobic textile. Upon application of a potential (in the range of 100–1000 V) between the textile and the liquid, the valve opens and the liquid penetrates the textile. These valves actuate in less than 1 s, require low energy (≈27 µJ per actuation), and work with a variety of aqueous solutions, including those with low surface tension and those containing bioanalytes. They are bistable in function, and are, in a sense, the electrofluidic analog of thyristors. They can be integrated into paper microfluidic devices to make circuits that are capable of controlling liquid, including autonomous fluidic timers and fluidic logic.