Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting the Myofibroblastic Cancer-Associated Fibroblast Phenotype Through Inhibition of NOX4

Abstract Background Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry. Mechanisms regulating fibroblast-to-myofibroblast transdifferentiation were investigated in vitro using RNA interference/pharmacological inhibitors followed by polymerase chain reaction (PCR), immunoblotting, immunofluorescence, and functional assays. RNA sequencing/bioinformatics and immunohistochemistry were used to analyze NAD(P)H Oxidase-4 (NOX4) expression in different human tumors. NOX4’s role in CAF-mediated tumor progression was assessed in vitro, using CAFs from multiple tissues in Transwell and organotypic culture assays, and in vivo, using xenograft (n = 9–15 per group) and isograft (n = 6 per group) tumor models. All statistical tests were two-sided. Results Patients with moderate/high levels of myofibroblastic-CAF had a statistically significant decrease in cancer-specific survival rates in each cancer type analyzed (hazard ratios [HRs] = 1.69–7.25, 95% confidence intervals [CIs] = 1.11 to 31.30, log-rank P ≤ .01). Fibroblast-to-myofibroblast transdifferentiation was dependent on a delayed phase of intracellular reactive oxygen species, generated by NOX4, across different anatomical sites and differentiation stimuli. A statistically significant upregulation of NOX4 expression was found in multiple human cancers (P < .001), strongly correlating with myofibroblastic-CAFs (r = 0.65–0.91, adjusted P < .001). Genetic/pharmacological inhibition of NOX4 was found to revert the myofibroblastic-CAF phenotype ex vivo (54.3% decrease in α-smooth muscle actin [α-SMA], 95% CI = 10.6% to 80.9%, P = .009), prevent myofibroblastic-CAF accumulation in vivo (53.2%–79.0% decrease in α-SMA across different models, P ≤ .02) and slow tumor growth (30.6%–64.0% decrease across different models, P ≤ .04). Conclusions These data suggest that pharmacological inhibition of NOX4 may have broad applicability for stromal targeting across cancer types.
Neural Indices of Vowel Discrimination in Monolingual and Bilingual Infants and Children.

OBJECTIVES To examine maturation of neural discriminative responses to an English vowel contrast from infancy to 4 years of age and to determine how biological factors (age and sex) and an experiential factor (amount of Spanish versus English input) modulate neural discrimination of speech. DESIGN Event-related potential (ERP) mismatch responses (MMRs) were used as indices of discrimination of the American English vowels [ε] versus [I] in infants and children between 3 months and 47 months of age. A total of 168 longitudinal and cross-sectional data sets were collected from 98 children (Bilingual Spanish-English: 47 male and 31 female sessions; Monolingual English: 48 male and 42 female sessions). Language exposure and other language measures were collected. ERP responses were examined in an early time window (160 to 360 msec, early MMR [eMMR]) and late time window (400 to 600 msec, late MMR). RESULTS The eMMR became more negative with increasing age. Language experience and sex also influenced the amplitude of the eMMR. Specifically, bilingual children, especially bilingual females, showed more negative eMMR compared with monolingual children and with males. However, the subset of bilingual children with more exposure to English than Spanish compared with those with more exposure to Spanish than English (as reported by caretakers) showed similar amplitude of the eMMR to their monolingual peers. Age was the only factor that influenced the amplitude of the late MMR. More negative late MMR was observed in older children with no difference found between bilingual and monolingual groups. CONCLUSIONS Consistent with previous studies, our findings revealed that biological factors (age and sex) and language experience modulated the amplitude of the eMMR in young children. The early negative MMR is likely to be the mismatch negativity found in older children and adults. In contrast, the late MMR amplitude was influenced only by age and may be equivalent to the Nc in infants and to the late negativity observed in some auditory passive oddball designs.
Aleuria Aurantia Lectin (AAL)-Reactive Immunoglobulin G Rapidly Appears in Sera of Animals following Antigen Exposure

We have discovered an Aleuria Aurantia Lectin (AAL)-reactive immunoglobulin G (IgG) that naturally occurs in the circulation of rabbits and mice, following immune responses induced by various foreign antigens. AAL can specifically bind to fucose moieties on glycoproteins. However, most serum IgGs are poorly bound by AAL unless they are denatured or treated with glycosidase. In this study, using an immunogen-independent AAL-antibody microarray assay that we developed, we detected AAL-reactive IgG in the sera of all animals that had been immunized 1–2 weeks previously with various immunogens with and without adjuvants and developed immunogen-specific responses. All of these animals subsequently developed immunogen-specific immune responses. The kinetics of the production of AAL-reactive IgG in mice and rabbits were distinct from those of the immunogen-specific IgGs elicited in the same animals: they rose and fell within one to two weeks, and peaked between four to seven days after exposure, while immunogen-specific IgGs continued to rise during the same period. Mass spectrometric profiling of the Fc glycoforms of purified AAL-reactive IgGs indicates that these are mainly comprised of IgGs with core-fucosylated and either mono-or non-galactosylated Fc N-glycan structures. Our results suggest that AAL-reactive IgG could be a previously unrecognized IgG subset that is selectively produced at the onset of a humoral response.
Reduction of oral corticosteroids in patients with severe eosinophilic asthma treated with Benralizumab: could it represent a marker of treatment efficacy?

ABSTRACT Introduction: Subjects with severe Th2-high endotype usually respond to oral corticosteroids (OCS). However, they often require high dosages with incremental side effects and health-care costs. The advent of biological therapies provides an effective strategy to improve asthma control, as well as reduce OCS use. Various molecules have been developed, each targeting different pathways. We analyzed the two anti-IL-5 strategies, benralizumab and mepolizumab, based on pivotal trials (RCTs), mechanisms of action and their possible role on the steroid-sparing effect. Areas covered: This review analyzes the data from the benralizumab and mepolizumab RCTs, focusing on the advantages of each drug on clinical efficacy and the steroid-sparing effect. Expert opinion: Benralizumab may represent a promising therapeutic option in the treatment of eosinophilic asthma, due to its mechanism of action, which rapidly allows a reduction in the eosinophils’ number, and a greater steroid-sparing effect.
Measurements and Analysis of Angular Characteristics and Spatial Correlation for High-Speed Railway Channels

Spatial characteristics of the propagation channel have a vital impact on the application of multi-antenna techniques. This paper analyzes angular characteristics and the spatial correlation for high-speed railway (HSR) channels, based on a novel moving virtual antenna array (MVAA) measurement scheme. The principle of the MVAA scheme is deeply investigated and is further verified by a theoretical geometry-based stochastic model. Using the MVAA scheme, virtual single-input multiple-output (SIMO) channel impulse response data are derived from single-antenna measurements in typical HSR scenarios, involving viaduct, cutting, and station. Based on the SIMO channel data, angle of arrival is extracted according to the unitary estimation of signal parameters by the rotational invariance techniques algorithm, and is compared with the theoretical result. Moreover, power angular spectrum and root mean square (rms) angular spread (AS) are provided, and the rms AS results are statistically modeled and comprehensively compared. In addition, spatial correlation is calculated and analyzed, and a rms AS-dependent spatial correlation model is newly proposed to describe the relationship between the angular dispersion and the spatial correlation. The presented results could be used in multi-antenna channel modeling and will facilitate the assessment of multi-antenna technologies for future HSR mobile communication systems.
Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder

Abstract There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation‐based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high‐functioning, school‐age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto‐temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto‐temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD.
Convolutional Recurrent Neural Network Based Deep Clustering for 2-speaker Separation

Speech separation is to separate the mixed signals into respective original signals. In speaker independent separation, where the speaker is not fixed, it is difficult to model because the time-frequency characteristics vary widely. Due to the development of deep learning, there has been massive progress in speaker independent separation based on single channel signal. DC algorithm, one of the deep learning based algorithms, introduced recurrent neural network to handle time context information. In this paper, convolutional neural network(CNN) is added to deep clustering algorithm train high-dimensional embedding vector more precisely. We compared the performance of the proposed algorithm with baseline deep clustering algorithm using Wall Street Journal dataset(WSJ0). Signal-distortion-ratio(SDR) and signal-interference-ratio(SIR) for both of segment-level and utterance-level is used as performance measure.
Reliability‐Based Transit Assignment for Congested Stochastic Transit Networks

Abstract: This article proposes a nonlinear complementarity problem (NCP) formulation for the risk‐aversive stochastic transit assignment problem in which in‐vehicle travel time, waiting time, capacity, and the effect of congestion are considered as stochastic variables simultaneously and both their means and variances are incorporated into the formulation. A new congestion model is developed and captured in the proposed NCP formulation to account for different effects of on‐board passengers and passengers waiting at stops. A reliability‐based user equilibrium condition is also defined based on the proposed generalized concept of travel time budget referred to as effective travel cost, and is captured in the formulation. A column generation based algorithm is proposed to solve the NCP formulation. A survey was conducted to validate that the degree of risk aversion of transit passengers affects their route choices. Numerical studies were performed to demonstrate the problem and the effectiveness of the proposed algorithm. The results obtained show that underestimating the congestion effect and ignoring the risk aversion behavior can overestimate the patronage of transit service, which have profound implications on the profit of the operators involved and the development of transit network design models.
Measurement of thumb pronation and palmar abduction angles with a small motion sensor: a comparison with Kapandji scores

The Kapandji score is used widely to record thumb opposition and is the only alternative to angular measurements. We aimed to verify the extent to which the Kapandji score reflects the angle of pronation. We recruited volunteers with unaffected upper limbs (33 hands) and patients with carpal tunnel syndrome (20 hands). We attached a small gyroscope to the thumb metacarpal and measured the pronation and palmar abduction angles at each position of the Kapandji score in both groups. The Kapandji score showed a strong ceiling effect, and the increase in angle size at each Kapandji score levelled off around a score of 6 in both groups. A Kapandji score greater than 6 does not necessarily reflect thumb opposition. Level of Evidence: III
Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1

The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.
High Expression of Retinoic Acid Induced 14 (RAI14) in Gastric Cancer and Its Prognostic Value

Background To explore the expression level of retinoic acid induced 14 (RAI14) in gastric cancer (GC) patients and its potentially clinical prognostic value. Material/Methods Initially, The Cancer Genome Atlas (TCGA) and Oncomine databases were mined to examine the differential expression levels and clinical prognostic significance of RAI14 mRNA in GC patients. Subsequently, 68 cases of GC and paired adjacent normal tissues were collected retrospectively, and the expression level of RAI14 protein was detected by immunohistochemical staining. In addition, Kaplan-Meier univariate and Cox multivariate survival analyses were used to verify the correlation between RAI14 expression and clinicopathological parameters in GC patients and its clinical prognostic significance. Results TCGA and GEO (from Oncomine database) data mining results found that RAI14 mRNA level was remarkably higher in GC than normal gastric tissues (All P<0.05). Besides, immunohistochemical results detected that RAI14 protein level in GC was dramatically higher (P=0.004) compared to that in the matched normal tissues. Moreover, TCGA database and Kaplan-Meier Plotter mining results showed that compared to those with RAI14 low mRNA expression levels, GC patients with RAI14 high mRNA expression levels had remarkably lower time of both overall survival and disease-free survival (All P<0.05). Additionally, based on the immunohistochemical results, Kaplan-Meier univariate and Cox multivariate survival analyses indicated that high expression of RAI14 was the only independent predictor of unfavorable prognosis in patients with gastric cancer (P=0.000). Conclusions RAI14 was highly expressed in GC, and the high expression of RAI14 could be an independent predictor of poor prognosis in GC patients.
Efficient Phase Diagram Sampling by Active Learning

We address the problem of efficient phase diagram sampling by adopting active learning techniques from machine learning, and achieve an 80% reduction in the sample size (number of sampled statepoints) needed to establish the phase boundary up to a given precision in example application. Traditionally, data is collected on a uniform grid of predetermined statepoints. This approach, also known as grid search in the machine learning community, suffers from low efficiency by sampling statepoints that provide no information about the phase boundaries. We propose an active learning approach to overcome this deficiency by adaptively choosing the next most informative statepoint(s) every round. This is done by interpolating the sampled statepoints' phases by Gaussian Process regression. An acquisition function quantifies the informativeness of possible next statepoints, maximizing the information content in each subsequently sampled statepoint. We also generalize our approach with state-of-the-art batch sampling techniques to better utilize parallel computing resources. We demonstrate the usefulness of our approach in a few example simulations relevant to soft matter physics, although our algorithms are general. Our active learning enhanced phase diagram sampling method greatly accelerates research and opens up opportunities for extra-large scale exploration of a wide range of phase diagrams by simulations or experiments.
RESOURCES FROM A MULTIMEDIA KNOWLEDGE BASE

In this paper we present an e-librarian servicewhich is able to retrieve multimedia resources from a knowledge base in a more efficient way than by browsing through an index or by using a simple keyword search. We explored the approach to allow the user to formulate a complete question in natural language. Our background theory is composed of three steps. Firstly, there is the linguistic pre-processing of the user question. Secondly, there is the semantic interpretation of the user question into a logical and unambiguous form, i.e. ALC terminology. Thefocus functionresolves ambiguities in the question; it returns the best interpretation for a given word in the context of the complete user question. Thirdly, there is the generation of a semantic query, and the retrieval of pertinent documents. We developed two prototypes: one about computer history (CHESt), and one about fractions in mathematics (MatES). We report on experiments with these prototypes that confirm the feasibility, the quality and the benefits of such an e-librarian service. From 229 different user questions, the system returned for 97% of the questions the right answer, and for nearly half of the questions only one answer, the best one.
Age differences in treatment response to a collaborative care intervention for anxiety disorders

Background Some data suggest that older adults with anxiety disorders do not respond as well to treatment as do younger adults. Aims We examined age differences in outcomes from the Coordinated Anxiety Learning and Management (CALM) study, an effectiveness trial comparing usual care to a computer-assisted collaborative care intervention for primary care patients with panic disorder, generalised anxiety disorder, post-traumatic stress disorder (PTSD), and/or social anxiety disorder. This is the first study to examine the efficacy of a collaborative care intervention in a sample that included both younger and older adults with anxiety disorders. We hypothesised that older adults would show a poorer response to the intervention than younger adults. Method We examined findings for the overall sample, as well as within each diagnostic category (clinicaltrials.gov identifier: NCT00347269). Results The CALM intervention was more effective than usual care among younger adults overall and for those with generalised anxiety disorder, panic disorder and social anxiety disorder. Among older adults, the intervention was effective overall and for those with social anxiety disorder and PTSD but not for those with panic disorder or generalised anxiety disorder. The effects of the intervention also appeared to erode by the 18-month follow-up, and there were no significant effects on remission among the older adults. Conclusions These results are consistent with the findings of other investigators suggesting that medications and psychotherapy for anxiety disorders may not be as effective for older individuals as they are for younger people.
Disruption of giant molecular clouds and formation of bound star clusters under the influence of momentum stellar feedback

Energetic feedback from star clusters plays a pivotal role in shaping the dynamical evolution of giant molecular clouds (GMCs). To study the effects of stellar feedback on the star formation efficiency of the clouds and the dynamical response of embedded star clusters, we perform a suite of isolated GMC simulations with star formation and momentum feedback subgrid models using the moving-mesh hydrodynamics code Arepo. The properties of our simulated GMCs span a wide range of initial mass, radius, and velocity configurations. We find that the ratio of the final stellar mass to the total cloud mass, ϵint, scales strongly with the initial cloud surface density and momentum feedback strength. This correlation is explained by an analytic model that considers force balancing between gravity and momentum feedback. For all simulated GMCs, the stellar density profiles are systematically steeper than that of the gas at the epochs of the peaks of star formation, suggesting a centrally concentrated stellar distribution. We also find that star clusters are always in a sub-virial state with a virial parameter ∼0.6 prior to gas expulsion. Both the sub-virial dynamical state and steeper stellar density profiles prevent clusters from dispersal during the gas removal phase of their evolution. The final cluster bound fraction is a continuously increasing function of ϵint. GMCs with star formation efficiency smaller than 0.5 are still able to form clusters with large bound fractions.