Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical outcomes with ustekinumab as rescue treatment in therapy-refractory or therapy-intolerant ulcerative colitis

Background Recently, ustekinumab a monoclonal antibody targeting interleukin-12 and -23 and successfully used in Crohn's disease also has been shown to be effective in induction and maintaining remission in patients with moderate to severe ulcerative colitis in a large phase 3 trial. However, no observational data on the use of ustekinumab in ulcerative colitis in daily clinical practice is available. Aim The purpose of this study was to assess the clinical outcomes achieved with ustekinumab as rescue treatment in therapy-refractory or -intolerant ulcerative colitis in a real-life setting. Methods A retrospective data analysis was performed in 19 ulcerative colitis patients who were intolerant or refractory to all of the following drugs: steroids, purine-analogues, tumour necrosis factor antibodies and vedolizumab. To all patients ustekinumab was provided as a rescue treatment (intravenous induction with 6 mg/kg, followed by week subcutaneous injection once every eight weeks of 90 mg). The primary outcome was achievement of clinical remission at one year, defined as score of ≤ 3 points in the Lichtiger score (colitis activity index). Patients were evaluated regularly and a colonoscopy was performed before the start and at the end of the observation. Ethical approval was provided by Ethikkommission Ärztekammer Hamburg (PV 5539). Results In five patients, therapy was stopped due to refractory disease or side effects. In all remaining 14 patients the median colitis activity index dropped from 8.5 points (range 1–12) at start to 2.0 points at one year (range 0–5.5) and Mayo endoscopy scores fell from a median of two points (range 1–3, mean of 2.3) at start to a median of one point (range 1–3, mean of 1.4) at one year. Including the five drop-outs, clinical remission was achieved in 53% of the 19 patients at one year. Conclusions In accordance with the UNIFI (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) trial our real-life data support ustekinumab as an effective and safe treatment option in therapy refractory moderate to severe ulcerative colitis with a history of biological therapies.
ViWi Vision-Aided mmWave Beam Tracking: Dataset, Task, and Baseline Solutions

Vision-aided wireless communication is motivated by the recent advances in deep learning and computer vision as well as the increasing dependence on line-of-sight links in millimeter wave (mmWave) and terahertz systems. By leveraging vision, this new research direction enables an interesting set of new capabilities such as vision-aided mmWave beam and blockage prediction, proactive hand-off, and resource allocation among others. These capabilities have the potential of reliably supporting highly-mobile applications such as vehicular/drone communications and wireless virtual/augmented reality in mmWave and terahertz systems. Investigating these interesting applications, however, requires the development of special dataset and machine learning tasks. Based on the Vision-Wireless (ViWi) dataset generation framework [1], this paper develops an advanced and realistic scenario/dataset that features multiple base stations, mobile users, and rich dynamics. Enabled by this dataset, the paper defines the vision-wireless mmWave beam tracking task (ViWi-BT) and proposes a baseline solution that can provide an initial benchmark for the future ViWi-BT algorithms.
The Holographic Nature of Null Infinity

We argue that, in a theory of quantum gravity in a four dimensional asymptotically flat spacetime, all information about massless excitations can be obtained from an infinitesimal neighbourhood of the past boundary of future null infinity and does not require observations over all of future null infinity. Moreover, all information about the state that can be obtained through observations near a cut of future null infinity can also be obtained from observations near any earlier cut although the converse is not true. We provide independent arguments for these two assertions. Similar statements hold for past null infinity. These statements have immediate implications for the information paradox since they suggest that the fine-grained von Neumann entropy of the state defined on a segment (-infty,u) of future null infinity is independent of u. This is very different from the oft-discussed Page curve that this entropy is sometimes expected to obey. We contrast our results with recent discussions of the Page curve in the context of black hole evaporation, and also discuss the relation of our results to other proposals for holography in flat space.
Secretome Analysis Performed During in vitro Cardiac Differentiation: Discovering the Cardiac Microenvironment

Human pluripotent stem cells are an important tool for the study of developmental processes, such as cardiomyogenic differentiation. Despite the advances made in this field, the molecular and cellular signals involved in the commitment of embryonic stem cells to the cardiac phenotype are still under investigation. Therefore, this study focuses on identifying the extracellular signals involved in in vitro cardiac differentiation of human embryonic stem cells. Using a three-dimensional cardiomyogenic differentiation protocol, the conditioned medium and the extracellular matrix (ECM) of embryoid body cultures were collected and characterized at four specific time points. Mass spectrometry (MS) and antibody array analysis of the secretome identified a number of secreted proteins related to signaling pathways, such as Wnt and TGFβ, as well as many ECM proteins. When comparing the proteins identified at selected time points, our data pointed out protein interactions and biological process related to cardiac differentiation. Interestingly, the great changes in secretome profile occurred during the cardiac progenitor specification. The secretome results were also compared with our previous RNAseq data, indicating that the secreted proteins undergo some level of gene regulation. During cardiac commitment it was observed an increase in complexity of the ECM, and some proteins as IGFBP7, FN1, HSPG2, as well as other members of the basal lamina could be highlighted. Thus, these findings contribute valuable information about essential microenvironmental signals working on cardiomyogenic differentiation that may be used in future strategies for cardiac differentiation, cardiomyocyte maturation, and in advances for future acellular therapies.
Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection

“Functional cure” is being pursued as the ultimate endpoint of antiviral treatment in chronic hepatitis B (CHB), which is characterized by loss of HBsAg whether or not anti-HBs antibodies are present. “Functional cure” can be achieved in <10% of CHB patients with currently available therapeutic agents. The dysfunction of specific immune responses to hepatitis B virus (HBV) is considered the major cause of persistent HBV infection. Thus, modulating the host immune system to strengthen specific cellular immune reactions might help eliminate HBV. Strategies are needed to restore/enhance innate immunity and induce HBV-specific adaptive immune responses in a coordinated way. Immune and resident cells express pattern recognition receptors like TLRs and RIG I/MDA5, which play important roles in the induction of innate immunity through sensing of pathogen-associated molecular patterns (PAMPs) and bridging to adaptive immunity for pathogen-specific immune control. TLR/RIG I agonists activate innate immune responses and suppress HBV replication in vitro and in vivo, and are being investigated in clinical trials. On the other hand, HBV-specific immune responses could be induced by therapeutic vaccines, including protein (HBsAg/preS and HBcAg), DNA, and viral vector-based vaccines. More than 50 clinical trials have been performed to assess therapeutic vaccines in CHB treatment, some of which display potential effects. Most recently, using genetic editing technology to generate CAR-T or TCR-T, HBV-specific T cells have been produced to efficiently clear HBV. This review summarizes the progress in basic and clinical research investigating immunomodulatory strategies for curing chronic HBV infection, and critically discusses the rather disappointing results of current clinical trials and future strategies.
Non-coding RNAs Shaping Muscle

In 1957, Francis Crick speculated that RNA, beyond its protein-coding capacity, could have its own function. Decade after decade, this theory was dramatically boosted by the discovery of new classes of non-coding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and circular RNAs (circRNAs), which play a fundamental role in the fine spatio-temporal control of multiple layers of gene expression. Recently, many of these molecules have been identified in a plethora of different tissues, and they have emerged to be more cell-type specific than protein-coding genes. These findings shed light on how ncRNAs are involved in the precise tuning of gene regulatory mechanisms governing tissues homeostasis. In this review, we discuss the recent findings on the mechanisms used by lncRNAs and circRNAs to sustain skeletal and cardiac muscle formation, paying particular attention to the technological developments that, over the last few years, have aided their genome-wide identification and study. Together with lncRNAs and circRNAs, the emerging contribution of Piwi-interacting RNAs and transfer RNA-derived fragments to myogenesis will be also discussed, with a glimpse on the impact of their dysregulation in muscle disorders, such as myopathies, muscle atrophy, and rhabdomyosarcoma degeneration.
Living Without Temporal Cues: A Case Study

Isolation from external time cues allows endogenous circadian rhythmicity to be demonstrated. In this study, also filmed as a television documentary, we assessed rhythmic changes in a healthy man time isolated in a bunker for 9 days/nights. During this period the lighting conditions were varied between: (1) self-selected light/dark cycle, (2) constant dim light, and (3) light/dark cycle with early wake up. A range of variables was assessed and related to the sleep-wake cycle, psychomotor and physical performance and clock-time estimation. This case study using modern non-invasive monitoring techniques emphasizes how different physiological circadian rhythms persist in temporal isolation under constant dim light conditions with different waveforms, free-running with a period (τ) between 24 and 25 h. In addition, a significant correlation between time estimation and mid-sleep time, a proxy for circadian phase, was demonstrated.
Analysis of the Clinicopathologic Characteristics of Lung Adenocarcinoma With CTNNB1 Mutation

Introduction Lung adenocarcinoma with CTNNB1 mutation is relatively uncommon, and its clinicopathologic characteristics, disease course, and prognosis have not been well-studied. Methods A total of 564 lung adenocarcinoma patients were enrolled in this study. The relationship between CTTNB1 mutational status and clinicopathologic parameters, the rates of relapse-free survival (RFS) and overall survival (OS), and the mutational status of other genes commonly mutated in lung adenocarcinoma were analyzed. Results Of 564 lung adenocarcinoma patients, 30 (5.3%) harbored CTNNB1 mutations. Univariate analyses revealed that gender, smoking history, pleural invasion, and histological subtype were all significant predictors of RFS and OS. Pleural invasion and histological subtype remained significant predictors of RFS and OS in a multivariate analysis. There were no significant differences in RFS (p = 0.504) or OS (p = 0.054) between lung adenocarcinoma patients with CTNNB1 mutation and those without CTNNB1 mutation. However, patients with CTNNB1 mutation tended to have a worse OS. Conclusions Female patients and nonsmokers are likely to harbor CTNNB1 mutation and primary lung adenocarcinoma with mutated CTNNB1 has a poor prognosis.
TEAMwork: Testing Emotional Attunement and Mutuality During Parent-Adolescent fMRI

The parent-child relationship and family context influence the development of emotion regulation (ER) brain circuitry and related skills in children and adolescents. Although both parents’ and children’s ER neurocircuitry simultaneously affect how they interact with one another, neuroimaging studies of parent-child relationships typically include only one member of the dyad in brain imaging procedures. The current study examined brain activation related to parenting and ER in parent-adolescent dyads during concurrent fMRI scanning with a novel task – the Testing Emotional Attunement and Mutuality (TEAM) task. The TEAM task includes feedback trials indicating the other dyad member made an error, resulting in a monetary loss for both participants. Results indicate that positive parenting practices as reported by the adolescent were positively correlated with parents’ hemodynamic activation of the ventromedial prefrontal cortex, a region related to empathy, during these error trials. Additionally, during feedback conditions both parents and adolescents exhibited fMRI activation in ER-related regions, including the dorsolateral prefrontal cortex, anterior insula, fusiform gyrus, thalamus, caudate, precuneus, and superior parietal lobule. Adolescents had higher left amygdala activation than parents during the feedback condition. These findings demonstrate the utility of dyadic fMRI scanning for investigating relational processes, particularly in the parent-child relationship.
Predicting Microbiome Function Across Space Is Confounded by Strain-Level Differences and Functional Redundancy Across Taxa

Variation in the microbiome among individual organisms may play a critical role in the relative susceptibility of those organisms to infection, disease, and death. However, predicting microbiome function is difficult because of spatial and temporal variation in microbial diversity, and taxonomic diversity is not predictive of microbiome functional diversity. Addressing this issue may be particularly important when addressing pandemic diseases, such as the global amphibian die-off associated with Bd. Some of the most important factors in probiotic development for disease treatment are whether bacteria with desired function can be found on native amphibians in the local environment. To address this issue, we isolated, sequenced, and assayed the cutaneous bacterial communities of Plethodon cinereus along a gradient of land use change. Our results suggest that cutaneous community composition, but not overall diversity, change with changes in land use, but this does not correspond to significant change in Bd-inhibitory function. We found that Bd-inhibition is a functionally redundant trait, but that level of inhibition varies over phylogenetic, spatial, and temporal scales. This research provides further evidence for the importance of continued examination of amphibian microbial communities across environmental gradients, including biotic and abiotic interactions, when considering disease dynamics.
Sparse Convolutional Neural Networks for Genome-Wide Prediction

Genome-wide prediction (GWP) has become the state-of-the art method in artificial selection. Data sets often comprise number of genomic markers and individuals in ranges from a few thousands to millions. Hence, computational efficiency is important and various machine learning methods have successfully been used in GWP. Neural networks (NN) and deep learning (DL) are very flexible methods that usually show outstanding prediction properties on complex structured data, but their use in GWP is nevertheless rare and debated. This study describes a powerful NN method for genomic marker data that can easily be extended. It is shown that a one-dimensional convolutional neural network (CNN) can be used to incorporate the ordinal information between markers and, together with pooling and ℓ 1-norm regularization, provides a sparse and computationally efficient approach for GWP. The method, denoted CNNGWP, is implemented in the deep learning software Keras, and hyper-parameters of the NN are tuned with Bayesian optimization. Model averaged ensemble predictions further reduce prediction error. Evaluations show that CNNGWP improves prediction error by more than 25% on simulated data and around 3% on real pig data compared with results obtained with GBLUP and the LASSO. In conclusion, the CNNGWP provides a promising approach for GWP, but the magnitude of improvement depends on the genetic architecture and the heritability.
A Data Driven Approach to Investigate the Chemical Variability of Clinopyroxenes From the 2014–2015 Holuhraun–Bárdarbunga Eruption (Iceland)

The Holuhraun–Bárdarbunga (Iceland) eruption lasted approximately 6 months. Magma propagated laterally through a 40 km long dyke, while Bárdarbunga caldera was collapsing. This event was intensely monitored, providing an opportunity to investigate the relationships between eruption dynamics and erupted products. Whole rock and melt inclusion data do not show chemical variations of magma during the eruption. Nevertheless, zoning patterns in clinopyroxene suggest temporal variations of intensive parameters during crystallization. We investigated the chemical zoning of clinopyroxene using a data driven approach, on major and trace elements analyses from lava flow lobes emplaced during the eruption. We applied hierarchical clustering (HC) to identify compositional groups based on major and trace element chemistry. This analysis identifies five compositional groups, which can be associated with specific petrographic features. One cluster represents the chemistry of hourglass sectors, two constitute the oscillatory zoned mantle of the crystals, one cluster corresponds to a seldom present bright rim (in back scattered electron images) in the outer portions of the crystals, and a last one represents most of the outer rims. HC applied to trace elements also identifies five compositional clusters, which highlight progressively more evolved clinopyroxene compositions from the core to the rim of the crystals. Two of the clusters identified with trace elements corresponds to major element clusters. All together the data suggest that the chemical zoning in the inner portions of the clinopyroxene crystals was generated by crystallization in the magma reservoir and interaction between hot magma propagating through the dyke and unerupted magma cooling within the dyke. The fraction of zones produced by interaction with colder portion of the magma residing within the dyke dropped during the eruption, potentially signaling the thermal maturation of the dyke. Some of the analyses reveal that relatively close to the eruption time (i.e., the outer portions of the crystals) the dyke intercepted a lens of low temperature magma with a chemical composition that is distinguishable from the 2014 to 2015 Bárdarbunga eruption. Our approach can provide insights on the evolution of deep processes occurring during long-lasting eruptions by combining the analysis mineral chemistry of erupted products with multiparametric monitoring signals.
Remarks on Mastigodiaptomus (Calanoida: Diaptomidae) from Mexico using integrative taxonomy, with a key of identification and three new species

Background In Mexico, species of four families of free-living calanoid copepods have been recorded as inhabitants of several freshwater systems. These families are Centropagidae, Temoridae, Pseudodiaptomidae and Diaptomidae. The genera Leptodiaptomus and Mastigodiaptomus are the most speciose diaptomid genera in Mexico, and they inhabit natural and artificial lakes, ephemeral ponds, springs, and caverns. Leptodiaptomus is considered as an endemic Nearctic genus, whereas Mastigodiaptomus is a widely distributed Neotropical genus in the southern USA, Mexico, the Caribbean Islands and Central America. Based on new and recent evidence, Mastigodiaptomus diversity has been underestimated: six species of the genus were known before 2000. In this work three new Mastigodiaptomus species have been described from different regions of Mexico by using integrative taxonomy. We also gave amended diagnosis of M. nesus Bowman (1986) and M. patzcuarensis s. str. (Kiefer, 1938). Methods In this work, the taxonomic status of the species was clarified using modern, integrative method based on the COI gene as a DNA marker, plus micro-structural analysis (based on SEM and ligth microscopy). Results Three new species of Mastigodiaptomus were described based on genetic and morphological analyses: M. alexei sp. n. , M. ha sp. n. and M. cihuatlan sp. n. Also amended description of M. nesus, morphological variation of M. patzcuarensis s. str. , and a comparison of them with all known sequences within the genus are provided. These new findings show that in Mastigodiaptomus differences in several cuticular microstructures of several appendages (such as the antennules, the fifth legs, or the urosomites of these copepods) agree with the interspecific genetic divergence >3% observed in sequences of the COI gene, and the integration of this information is a powerful tool in species delineation.
Recombinant Factor VIII Fc Inhibits B Cell Activation via Engagement of the FcγRIIB Receptor

The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is a major complication of hemophilia A treatment. The sole clinical therapy to restore FVIII tolerance in patients with inhibitors remains immune tolerance induction (ITI) which is expensive, difficult to administer and not always successful. Although not fully understood, the mechanism of ITI is thought to rely on inhibition of FVIII-specific B cells (1). Its efficacy might therefore be improved through more aggressive B cell suppression. FcγRIIB is an inhibitory Fc receptor that down-regulates B cell signaling when cross-linked with the B cell receptor (BCR). We sought to investigate if recombinant FVIII Fc (rFVIIIFc), an Fc fusion molecule composed of FVIII and the Fc region of immunoglobulin G1 (IgG1) (2), is able to inhibit B cell activation more readily than FVIII. rFVIIIFc was able to bind FVIII-exposed and naïve B cells from hemophilia A mice as well as a FVIII-specific murine B cell hybridoma line (413 cells). An anti-FcγRIIB antibody and FVIII inhibited binding, suggesting that rFVIIIFc is able to interact with both FcγRIIB and the BCR. Furthermore, incubation of B cells from FVIII-exposed mice and 413 cells with rFVIIIFc resulted in increased phosphorylation of SH-2 containing inositol 5-phosphatase (SHIP) when compared to FVIII. B cells from FVIII-exposed hemophilia A mice also exhibited decreased extracellular signal-regulated kinase (ERK) phosphorylation when exposed to rFVIIIFc. These differences were absent in B cells from naïve, non-FVIII exposed hemophilic mice suggesting an antigen-dependent effect. Finally, rFVIIIFc was able to inhibit B cell calcium flux induced by anti-Ig F(ab)2. Our results therefore indicate that rFVIIIFc is able to crosslink FcγRIIB and the BCR of FVIII-specific B cells, causing inhibitory signaling in these cells.