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Abstract Background Atypical hemolytic uremic syndrome (aHUS) is a rare disease with poor outcomes when untreated, in which ravulizumab or eculizumab are the standard of care where available. It has been proposed to regularly monitor platelet counts as an early response to ravulizumab or eculizumab. This study aimed to investigate the association between the early response to ravulizumab treatment and renal outcomes through 26 weeks in complement inhibitor-naïve adults with aHUS. Methods Adult patients with aHUS enrolled in the ALXN1210-aHUS-311 phase III study of ravulizumab were divided into two groups according to the achievement of complete thrombotic microangiopathy (TMA) response, i.e., platelet count and lactate dehydrogenase (LDH) normalization and ≥ 25% improvement in serum creatinine (sCr) from baseline, by 26 weeks and baseline characteristics were compared. Changes in hematologic parameters, platelet count and LDH, were compared between the two groups. Finally, we examined whether early hematologic improvement was associated with renal recovery (dialysis discontinuation or ≥ 25% improvement in sCr from baseline) through 26 weeks. Results Of 56 ravulizumab-treated patients, 30 achieved complete TMA response for 26 weeks, and 26 did not. Patients with complete TMA response showed rapid improvements in platelet counts. In patients without complete TMA response, delayed normalization of platelet counts was observed. By day 15, 93.3% (28/30) of patients with complete TMA response at 26 weeks and 26.9% (7/26) of patients without complete TMA response achieved platelet normalization. At 26 weeks, 62.5% (35/56) achieved renal recovery; however, 37.5% (21/56) did not. In patients with renal recovery, 85.7% (30/35) of patients had platelet count normalization by day 15; in patients without renal recovery, 23.8% (5/21) of patients had platelet count normalization (P

Background: Although cancer patients' activities of daily living (ADL) are reported to decline before death, ADL trajectories have not been sufficiently clarified due to limitations in the assessment and analysis methods. Objectives: To clarify the multiple trajectories of ADL in patients with terminal cancer using a comprehensive assessment measure. Design: This was a retrospective observational study. Setting/Study Subjects: Cancer patients aged ?18 years discharged at death from a single-center palliative care unit. Measurements: Functional Independence Measure (FIM) total scores for eight weeks retrospectively. Results: In total, 306 patients were analyzed. Group-based trajectory modeling analysis estimated four groups as the best model for the FIM trajectory over eight weeks using the following trajectories: (1) a No Decline group, in which ADL did not decline until just before death; (2) a Rapid Decline group, in which ADL declined rapidly two weeks before death from a trajectory similar to the No Decline group; (3) a Moderate Disability and Slow Decline group, in which the patient slowly declined from requiring mild-to-severe assistance; and (4) a Severe Disability group, in which the patient continuously required severe assistance. Conclusions: Multiple ADL trajectories were identified in the last eight weeks of life of patients with terminal cancer. These findings suggest that palliative care needs to be tailored to the characteristics of each patient.

Prior research showed that interleaved practice (studying multiple skills at once) is more effective than blocked practice (studying only one skill at a time). This study aims to replicate the benefits of interleaved practice on the proceduralization of second language (L2) syntax and further examines the role of working memory (WM) in different practice schedules. Sixty English learners studied five types of relative-clause constructions under either blocked- or interleaved-practice conditions. The blocked-practice group engaged in systematic form-focused speaking practice with exemplars blocked by syntactic category, while the interleaved-practice group received mixed exemplars from the different categories. The proceduralization of grammatical knowledge was measured by analysing the accuracy and speed indices from a picture description test, which was administered immediately and one week after the training session. Learners' WM capacity was measured using a listening-span task. Results showed that interleaved practice led to more accurate performance on both immediate and delayed posttests than blocked practice. The advantage of interleaved practice was less pronounced for the speed dimension of performance. Furthermore, interleaved practice facilitated skill development regardless of learners' WM capacity, whereas in the blocked-practice condition, learners with higher WM capacity benefited more than those with lower WM capacity in speeding up of relative clause use, which presumably reflects the proceduralization--automatization stage.

Ticks are obligate hematophagous parasites that can transmit to vertebrate hosts several pathogens, including viruses, bacteria, protozoa and helminths. Among these agents, some Borrelia species some Borrelia species cause disease in humans and other vertebrate hosts; therefore, they have medical and veterinary health importance. To gather additional information on Borrelia species in Brazil, the current study aimed to detect the presence of these species in Ornithodoros cavernicolous ticks collected in September 2019 from cement pipes that are used by bats as shelter in a farm located in the midwestern region of Brazil. DNA samples obtained from 18 specimens of O. cavernicolous were subjected of two polymerase chain reactions, targeting a segment of the Borrelia fla B gene. Of the samples tested, only one (6 %, 1/18) showed amplification. The nucleotide sequence of the amplified DNA showed more than 97 % (293/300) identity with a sequence of a Borrelia sp. detected in blood collected from a bat from Macaregua Cave, Colombia, and more than 97 % (292/300) detected in lungs from vampire bats from northeastern Brazil. The deduced amino acid sequences were identical to each other. Phylogenetic analysis indicated that these sequences formed a group of Borrelia species (putatively associated with bats) that is closely related to sequences of Borrelia species of the Lyme borreliosis group. Further investigations should be carried out in order to determine whether the sequence of the Borrelia sp. we found belongs to a new taxon. It will also be of great importance to determine which vertebrate hosts, besides bats, O. cavernicolous ticks can parasitize in order to investigate whether the Borrelia sp. we found may be transmitted and cause disease to the other vertebrate hosts.

Steam reforming of bioethanol is a potential reaction for H2 production. The development of active Ni catalysts with sintering resistance, coking resistance and thermal stability is indispensable for practical application. In this study, the encapsulation structure of Ni nanoparticles inside Silicalite-1 was proposed as a catalyst (Ni@Silicalite-1). The catalyst was prepared by hydrothermal synthesis using Ni-phyllosilicate as a Ni precursor. An investigation of catalytic activity was conducted at 500–800 °C, along with an investigation of catalyst properties, including surface morphology, Ni properties, and coke formation on the spent catalysts, compared to a conventional Ni/Silicalite-1. Ni@Silicalite-1 exhibits a higher ethanol conversion, hydrogen production, and selectivity towards C1 products. Especially in a kinetic control condition (500–600 °C), Ni@Silicalite-1 exhibits 46.8% in ethanol conversion at 500 °C and two times higher in C2-to-C1 conversion at 600 °C than that of Ni/Silicalite-1. Moreover, a significant coke suppression of 2–5 times reduction form that of impregnation catalyst is obtained for Ni@Silicalite-1 in various reaction temperatures. It also shows a sintering resistance as maintaining the Ni size at 4.0–4.1 nm after ESR at high temperature (800 °C 4 h). Therefore, the encapsulation structure of ultrafine Ni nanoparticles inside Silicalite-1 is promising for bioethanol steam reforming.

Abstract Beyond their CO2 emittance when burned as fuels, hydrocarbons (HCs) serve as omnipresent raw materials and commodities. No matter if as liquid oil spills or the endless amounts of plastic roaming the oceans, HCs behave as persistent pollutants with water as main carrier to distribute. Even if their general chemical structure [‐(CH2)n‐] is quite simple, the endless range of n leads to contaminations of different appearances and properties. A water remediation method based on superparamagnetic iron oxide nanoparticles (SPIONs) modified with self‐assembled monolayers of alkyl phosphonic acid derivatives is presented. These molecules enable the SPIONs to non‐covalently bind HCs, independently from the molecular weight, size and morphology. The attractive interaction is mainly based on hydrophobic and Coulomb interaction, which allows recycling of the SPIONs. The superparamagnetic core allows a simple magnetic collection and separation from the water phase which makes it a promising addition to wastewater treatment. Agglomerates of collected plastic “waste” even exhibit superior adsorption properties for crude oil, another hydrocarbon waste which gives these collected wastes a second life. This upcycling approach combined with presented recycling methods enables a complete recycling loop.

Toll-like receptors (TLRs) induce innate immune responses through activation of intracellular signaling pathways, such as MAP kinase and NF-κB signaling pathways, and play an important role in host defense against bacterial or viral infections. Meanwhile, excessive activation of TLR signaling leads to a variety of inflammatory disorders, including autoimmune diseases. TLR signaling is therefore strictly controlled to balance optimal immune response and inflammation. However, its balancing mechanisms are not fully understood. In this study, we identified the E3 ubiquitin ligase LINCR/ NEURL3 as a critical regulator of TLR signaling. In LINCR-deficient cells, the sustained activation of JNK and p38 MAPKs induced by the agonists for TLR3, TLR4, and TLR5, was clearly attenuated. Consistent with these observations, TLR-induced production of a series of inflammatory cytokines was significantly attenuated, suggesting that LINCR positively regulates innate immune responses by promoting the activation of JNK and p38. Interestingly, our further mechanistic study identified MAPK phosphatase-1 (MKP1), a negative regulator of MAP kinases, as a ubiquitination target of LINCR. Thus, our results demonstrate that TLRs fine-tune the activation of MAP kinase pathways by balancing LINCR (the positive regulator) and MKP1 (the negative regulator), which may contribute to the induction of optimal immune responses.

Abstract Cross-modal correspondences refer to associations between feature dimensions of stimuli across sensory modalities. Research has indicated that correspondence between audiovisual stimuli influences whether these stimuli are integrated or segregated. On the other hand, the audiovisual integration process plastically changes to compensate for continuously observed spatiotemporal conflicts between sensory modalities. If and how cross-modal correspondence modulates the “recalibration” of integration is unclear. We investigated whether cross-modal correspondence between auditory pitch and visual elevation affected audiovisual temporal recalibration. Participants judged the simultaneity of a pair of audiovisual stimuli after an adaptation phase in which alternating auditory and visual stimuli equally spaced in time were presented. In the adaptation phase, auditory pitch and visual elevation were manipulated to fix the order within each pairing of audiovisual stimuli congruent with pitch-elevation correspondence (visual leading or auditory leading). We found a shift in the point of subjective simultaneity (PSS) between congruent audiovisual stimuli as a function of the adaptation conditions (Experiment 1, 2), but this shift in the PSS was not observed within incongruent pairs (Experiment 2). These results indicate that asynchronies between audiovisual signals congruent with cross-modal correspondence are selectively recalibrated.

Previous studies have reported that, in working memory, the processing of visuospatial information and phonological information have different neural bases. However, in these studies, memory items were presented via different modalities. Therefore, the modality in which the memory items were presented and the strategy for memorizing them were not rigorously distinguished. In the present study, we explored the neural basis of two working memory strategies. Nineteen right-handed young adults memorized seven sequential directions presented visually in a task in which the memory strategy was either visuospatial or phonological (visuospatial/phonological condition). Source amplitudes of theta-band (5–7 Hz) rhythm were estimated from magnetoencephalography during the maintenance period and further analyzed using cluster-based permutation tests. Behavioral results revealed that the accuracy rates showed no significant differences between conditions, while the reaction time in the phonological condition was significantly longer than that in the visuospatial condition. Theta activity in the phonological condition was significantly greater than that in the visuospatial condition, and the cluster in spatio-temporal matrix with p < 5% difference extended to right prefrontal regions in the early maintenance period and right occipito-parietal regions in the late maintenance period. The theta activity results did not indicate strategy-specific neural bases but did reveal the dynamics of executive function required for phonological processing. The functions seemed to move from attention control and inhibition control in the prefrontal region to inhibition of irrelevant information in the occipito-parietal region.

Abstract Understanding the underlying processes of biomineralization is crucial to a range of disciplines allowing us to quantify the effects of climate change on marine organisms, decipher the details of paleoclimate records and advance the development of biomimetic materials. Many biological minerals form via intermediate amorphous phases, which are hard to characterize due to their transient nature and a lack of long-range order. Here, using Monte Carlo simulations constrained by X-ray and neutron scattering data together with model building, we demonstrate a method for determining the structure of these intermediates with a study of amorphous calcium carbonate (ACC) which is a precursor in the bio-formation of crystalline calcium carbonates. We find that ACC consists of highly ordered anhydrous nano-domains of approx. 2 nm that can be described as nanocrystalline. These nano-domains are held together by an interstitial net-like matrix of water molecules which generate, on the mesoscale, a heterogeneous and gel-like structure of ACC. We probed the structural stability and dynamics of our model on the nanosecond timescale by molecular dynamics simulations. These simulations revealed a gel-like and glassy nature of ACC due to the water molecules and carbonate ions in the interstitial matrix featuring pronounced orientational and translational flexibility. This allows for viscous mobility with diffusion constants four to five orders of magnitude lower than those observed in solutions. Small and ultra-small angle neutron scattering indicates a hierarchically-ordered organization of ACC across length scales that allow us, based on our nano-domain model, to build a comprehensive picture of ACC formation by cluster assembly from solution. This contribution provides a new atomic-scale understanding of ACC and provides a framework for the general exploration of biomineralization and biomimetic processes.

Recently, automated guided vehicles (AGVs) have been deployed in factories to improve work efficiency and reduce labor shortages. However, current power supply systems, such as AGV shift systems and battery replacement systems, cannot fully utilize the advantages of these systems because of the time they are inactive. Therefore, to improve work efficiency, we have adopted an in-transit non-contact power supply system that can supply power while the work is in progress and while the machine is moving. There are several non-contact power supply methods; however, the most widely used electromagnetic induction method was used in this study. Compared to conventional non-contact power transfer, a stable power supply and reduction of magnetic leakage field are more important for non-contact power transfer while traveling because of its characteristic of transferring power over a long section of the track. Therefore, we investigated the characteristics of a cancellation coil with enhanced effectiveness based on an 8-shaped coil that reduces the leakage of magnetic fields using electromagnetic field analysis simulations. We then fabricated a feeding coil and verified its effectiveness using actual measurements. As a result, it was confirmed that the cancellation coil has superior magnetic field leakage reduction performance compared to the ordinary 8-shaped coil.

Abstract T-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-betfl/fl (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA.