Miracle-dz/UniFAR-FTUs huggingface dataset:
USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta

ABSTRACT USP22, a component of the SAGA complex, is overexpressed in highly aggressive cancers, but the normal functions of this deubiquitinase are not well defined. We determined that loss of USP22 in mice results in embryonic lethality due to defects in extra-embryonic placental tissues and failure to establish proper vascular interactions with the maternal circulatory system. These phenotypes arise from abnormal gene expression patterns that reflect defective kinase signaling, including TGFβ and several receptor tyrosine kinase pathways. USP22 deletion in endothelial cells and pericytes that are induced from embryonic stem cells also hinders these signaling cascades, with detrimental effects on cell survival and differentiation as well as on the ability to form vessels. Our findings provide new insights into the functions of USP22 during development that may offer clues to its role in disease states. Highlighted Article: Global loss of the USP22 deubiquitinase, an integral subunit of the SAGA chromatin remodeler, reveals an unexpected role in the regulation of signaling cascades in endothelial and perivascular cells of the developing mouse placenta.
Genomic Characterization of Orf Virus Strain D1701-V (Parapoxvirus) and Development of Novel Sites for Multiple Transgene Expression

The Orf virus (ORFV; Parapoxvirus) strain D1701 with an attenuated phenotype and excellent immunogenic capacity is successfully used for the generation of recombinant vaccines against different viral infections. Adaption for growth in Vero cells was accompanied by additional major genomic changes resulting in ORFV strain variant D1701-V. In this study, restriction enzyme mapping, blot hybridization and DNA sequencing of the deleted region s (A, AT and D) in comparison to the predecessor strain D1701-B revealed the loss of 7 open reading frames (ORF008, ORF101, ORF102, ORF114, ORF115, ORF116, ORF117). The suitability of deletion site D for expression of foreign genes is demonstrated using novel synthetic early promoter eP1 and eP2. Comparison of promoter strength showed that the original vegf-e promoter Pv as well as promoter eP2 display an up to 11-fold stronger expression than promoter eP1, irrespective of the insertion site. Successful integration and expression of the fluorescent marker genes is demonstrated by gene- and insertion-site specific PCR assays, fluorescence microscopy and flow cytometry. For the first time ORFV recombinants are generated simultaneously expressing transgenes in two different insertion loci. That allows production of polyvalent vaccines containing several antigens against one or different pathogens in a single vectored ORFV vaccine.
A Context Aware Smart Classroom Architecture for Smart Campuses

The Smart campus is a concept of an education institute using technologies, such as information systems, internet of things (IoT), and context-aware computing, to support learning, teaching, and administrative activities. Classrooms are important building blocks of a school campus. Therefore, a feasible architecture for building and running smart classrooms is essential for a smart campus. However, most studies related to the smart classroom are focused on studying or addressing particular technical or educational issues, such as networking, AI applications, lecture quality, and user responses to technology. In this study, an architecture for building and running context-aware smart classrooms is proposed. The proposed architecture consists of three parts including a prototype of a context-aware smart classroom, a model for technology integration, and supporting measures for the operation of smart classrooms in this architecture. The classroom prototype was designed based on our study results and a smart classroom project in Ming Chuan University (MCU). The integration model was a layered model uses Raspberry Pi in the bottom layer of the model to integrate underlying technologies and provide application interfaces to the higher layer applications for the ease of building context-aware smart classroom applications. As a result, application interfaces were implemented using Raspberry Pi based on the proposed technology integration model, and a context-aware energy-saving smart classroom application was implemented based on the proposed classroom prototype and the implemented web application interface. The result shows that, in terms of technology, the proposed architecture is feasible for building context-aware smart classrooms in smart campuses.
Label‐free optical projection tomography for quantitative three‐dimensional anatomy of mouse embryo

Recent progress in three‐dimensional optical imaging techniques allows visualization of many comprehensive biological specimens. Optical clearing methods provide volumetric and quantitative information by overcoming the limited depth of light due to scattering. However, current imaging technologies mostly rely on the synthetic or genetic fluorescent labels, thus limits its application to whole‐body visualization of generic mouse models. Here, we report a label‐free optical projection tomography (LF‐OPT) technique for quantitative whole mouse embryo imaging. LF‐OPT is based on the attenuation contrast of light rather than fluorescence, and it utilizes projection imaging technique similar to computed tomography for visualizing the volumetric structure. We demonstrate this with a collection of mouse embryo morphologies in different stages using LF‐OPT. Additionally, we extract quantitative organ information applicable toward high‐throughput phenotype screening. Our results indicate that LF‐OPT can provide multi‐scale morphological information in various tissues including bone, which can be difficult in conventional optical imaging technique.
Ab Initio Computation of Rotationally-Averaged Pump-Probe X-ray and Electron Diffraction Signals.

We develop a new algorithm for the computation of the rotationally averaged elastic molecular diffraction signal for the cases of perpendicular or parallel pump-probe geometries. The algorithm first collocates the charge density from an arbitrary ab initio wave function onto a Becke quadrature grid [A. Becke, J. Chem. Phys. 1988 , 88 , 2457 ], providing a high-fidelity multiresolution representation of the charge density. A double sum is then performed over the Becke grid points, and the interaction between points computed using the scattering kernels of Williamson and Zewail [J. C. Williamson and A. H. Zewail, J. Phys. Chem. 1994 , 98 , 2766 ]. These kernels analytically average over the molecular orientations with the cos2 γ selection factor appropriate for one-photon dipole absorption in a perpendicular pump-probe geometry. We show that the method is converged with small grids containing <500 points/atom. We implement the algorithm on a GPU for increased efficiency and emonstrate the algorithm for molecules with up to a few dozen atoms. We explore the accuracy of the independent atom model (IAM) by comparison with our new and more accurate method. We also investigate the possibility of detecting signatures of electronic transitions in polyatomic pump-probe diffraction experiments.
QTc modification after risperidone administration – insight into the mechanism of action with use of the modeling and simulation at the population level approach

Abstract Context: Ensuring the safety of therapy is both expensive and time-consuming process, which may be supported by modeling and simulation. Objective: The objective of this study was to gain insight into the effect of risperidone administration on QT interval by in silico evaluation of the effect in the individuals with different metabolic status of CYP2D6. Materials and methods: Evaluation was performed through the combination of empirical and mechanistic modeling with the use of the Cardiac Safety Simulator platform allowing for simulation of electrophysiological consequences of drug administration at the population level. The performance of the proposed approach was evaluated by in silico mimicking of the clinical trial conducted by Novalbos. Results: The simulation results depict differences in ΔQT correlated with change in metabolic activity, but not as significant as observed clinically. For poor metabolizers (PMs), ΔQTc was 8.0 and 5.1 ms, for Fridericia’s and Bezett’s correction, respectively, in comparison to 13.9 in Novalbos’s study. For intermediate metabolizers (IMs), there was 9.3 and 7.3 ms versus 4 ms observed clinically, for ultrarapid metabolizers (UMs) −4.0 and 1 ms versus 0.60 ms, for EMs −5.9 and 7.7 ms versus 6.1 ms. Discussion and conclusion: Simulated results underestimate changes observed in the PMs and overestimate the results for the IMs and UMs groups. EM individuals were properly predicted. The results of various QTc studies vary considerably and it is not clear which factors have a decisive influence. Nevertheless, presented differences are still more consistent with clinical results than results obtained clinically by other researchers.
Flap selection for reconstruction of wide palatal defect after cancer surgery

Background The resection of head and neck cancer can result in postoperative defect. Many patients have difficulty swallowing and masticating, and some have difficulty speaking. Various types of flaps are used for palatal reconstruction, but flap selection remains controversial. Therefore, our study will suggest which flap to choose during palatal reconstruction. Methods Thirteen patients who underwent palatal reconstruction from 30 January, 1989 to 4 October, 2016 at our institution. Size was classified as small when the width was < 4 cm², medium when it was 4–6 cm², and large when it was ≥ 6 cm². Based on speech evaluation, the subjects were divided into a normal group and an easily understood group. After surgery, we assessed whether flap selection was appropriate through the evaluation of flap success, complications, and speech evaluation. Results Defect size ranged from 1.5× 2.0 cm to 5.0× 6.0 cm. In four cases, the defect was in the anterior third of the palate, in eight cases it was in the middle, and there was one case of whole palatal defect. There were three small defects, two medium-sized defects, and eight large defects. Latissimus dorsi free flaps were used in six of the eight large defects in the study. Conclusion The key to successful reconstructive surgery is appropriate selection of the flap with reference to the characteristics of the defect. Depending on the size and location of the defect, the profiles of different flaps should be matched with the recipient from the outset.
Statistical Methodology in Studies of Prenatal Exposure to Mixtures of Endocrine-Disrupting Chemicals: A Review of Existing Approaches and New Alternatives

Background: Prenatal exposures to endocrine-disrupting chemicals (EDCs) during critical developmental windows have been implicated in the etiologies of a wide array of adverse perinatal and pediatric outcomes. Epidemiological studies have concentrated on the health effects of individual chemicals, despite the understanding that EDCs act together via common mechanisms, that pregnant women are exposed to multiple EDCs simultaneously, and that substantial toxicological evidence of adverse developmental effects has been documented. There is a move toward multipollutant models in environmental epidemiology; however, there is no current consensus on appropriate statistical methods. Objectives: We aimed to review the statistical methods used in these studies, to identify additional applicable methods, and to determine the strengths and weaknesses of each method for addressing the salient statistical and epidemiological challenges. Methods: We searched Embase, MEDLINE, and Web of Science for epidemiological studies of endocrine-sensitive outcomes in the children of mothers exposed to EDC mixtures during pregnancy and identified alternative statistical methods from the wider literature. Discussion: We identified 74 studies and analyzed the methods used to estimate mixture health effects, identify important mixture components, account for nonmonotonicity in exposure–response relationships, assess interactions, and identify windows of exposure susceptibility. We identified both frequentist and Bayesian methods that are robust to multicollinearity, performing shrinkage, variable selection, dimension reduction, statistical learning, or smoothing, including methods that were not used by the studies included in our review. Conclusions: Compelling motivation exists for analyzing EDCs as mixtures, yet many studies make simplifying assumptions about EDC additivity, relative potency, and linearity, or overlook the potential for bias due to asymmetries in chemical persistence. We discuss the potential impacts of these choices and suggest alternative methods to improve analyses of prenatal exposure to EDC mixtures. https://doi.org/10.1289/EHP2207
Diagnosis of Murine Typhus by Serology in Peninsular Malaysia: A Case Report Where Rickettsial Illnesses, Leptospirosis and Dengue Co-Circulate

Murine typhus is a rarely diagnosed cause of acute febrile illness in Malaysia, and its true disease burden is unknown. We report a case of an acute murine typhus infection in a patient living in a small city in Peninsular Malaysia, presenting with fever, rash, and headache. Unresponsive to the initial empirical treatment for leptospirosis, he showed a rapid response to doxycycline when murine typhus was diagnosed later. This case highlights the importance of considering murine typhus as a diagnostic in cases of acute febrile illness in urban and sub-urban areas, such as that of in Peninsular Malaysia.
Soluble FcɛRI: A biomarker for IgE‐mediated diseases

To the Editor, Soluble IgE receptors interact with IgE in the extracellular matrix and are important in the regulation of immune diseases. Soluble FcεRII (sCD23) and galectin‐3 (εBP) are currently used as biomarkers, though correlation data on serum titers and severity of allergies are controversial. FcεRI, the high‐affinity IgE Fc receptor, is expressed on several innate cell types, and a truncated version of the IgE‐binding alpha subunit is found as a soluble isoform (sFcεRI) in human serum. In circulation, sFcεRI is mostly detected as a complex with IgE. This observation raises the question of how sFcεRI affects detection of serum IgE titers. In order to assign clinical implications of sFcεRI, we assessed serum titers in its total and IgE‐bound forms in different IgE‐ mediated diseases in 312 individuals. We compared pediatric populations with primary food allergies (n = 59), insect venom allergies (n = 9), allergic asthma (n = 24), atopic dermatitis (n = 25), food‐sensitized nonallergic children (n = 31), and nonallergic controls (n = 17). Additionally, other sensitized groups and controls (n = 147) were included in the study (Table S1-S4).
Detection of Small Pulmonary Nodules with Ultrashort Echo Time Sequences in Oncology Patients by Using a PET/MR System.

PURPOSE To investigate the utility of a free-breathing ultrashort echo time (UTE) sequence for the evaluation of small pulmonary nodules in oncology patients by using a hybrid positron emission tomography (PET)/magnetic resonance (MR) imaging system and to compare the nodule detection rate between UTE and a conventional three-dimensional gradient-recalled-echo (GRE) technique. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board-approved prospective study, 82 pulmonary nodules were identified in eight patients with extrathoracic malignancies. Patients underwent free-breathing UTE and dual-echo three-dimensional GRE imaging of the lungs in a hybrid PET/MR imaging unit immediately after clinical PET/computed tomography (CT). CT was considered the reference standard for nodule detection. Two reviewers identified nodules and obtained measurements on MR images. The McNemar test was used to evaluate differences in nodule detection rate between MR techniques, and interrater agreement was assessed by using Bland-Altman plots. RESULTS Mean nodule diameter ± standard deviation was 6.2 mm ± 2.7 (range, 3-17 mm). The detection rate was higher for UTE imaging than for dual-echo GRE imaging for nodules of at least 4 mm (82% vs 34%, respectively; P < .001), with the largest difference in detection noted in the 4-8-mm nodule group (79% vs 21%, P < .001). UTE imaging displayed a higher detection rate than dual-echo GRE imaging for nodules without fluorodeoxyglucose avidity (68% vs 22%, respectively; P < .001). Interrater reliability of nodule detection with MR imaging was high (κ = 0.90 for UTE imaging and κ = 0.92 for dual-echo GRE imaging). CONCLUSION A free-breathing UTE sequence has high sensitivity for the detection of small pulmonary nodules (4-8 mm) and outperformed a three-dimensional dual-echo GRE technique for the detection of small, non-fluorodeoxyglucose-avid nodules.
The complete mitochondrial genome sequence of Symphysodon discus Heckel (1840)

Abstract The complete mitochondrial genome of Symphysodon discus Heckel was 16 544 bp in length, consisting of 22 tRNA genes, 13 protein-coding genes, 2 ribosomal rRNA genes, and a control region or displacement loop (D-loop). With the exception of 8 tRNAs and ND6 genes, the others were encoded on H-strand. The base composition on H-strand was 30.04% C, 28.39% A, 26.49% T and 15.07% G, exhibiting an A + T rich pattern. The codon usage was consistent with the other vertebrate mitochondrial pattern, i.e. start codon is ATG or GTG and stop codons are TAA, TAG or T– –. Stop codon TAG was only found in the ND6. There were 8 regions of gene overlapped with the length of 26 bp in total and 12 intergenic spacer regions (99 bp in total).
Contributions of Soil Meso- and Microfauna to Nutrient Release During Broadleaved Tree Litter Decomposition in the Changbai Mountains

Abstract Soil meso- and microfauna (<2 mm in size) play an important role in the decomposition and nutrient release of litter. However, most research has focused on the influences of soil fauna on decomposition rates, while the impact of soil fauna on nutrient release has not been fully understood. We evaluated the influence of soil meso- and microfauna communities on nutrient release from decomposing Tilia amurensis Rupr. (Malvales:Tiliaceae) and Acer mono Maxim. (Sapindales:Aceraceae) leaves from the coniferous and broadleaved mixed forests of the Changbai Mountains. Litter decomposition and nutrient release were assessed using litterbags placed at the surface of the litter and using designs both with and without 2-mm mesh to either permit or exclude soil meso- and microfauna. The soil meso- and microfauna increased the decomposition of T. amurensis (not significantly) and A. mono (significantly, by 15%) litters. Presence of the soil meso- and microfauna accelerated the release rate of Mn in the A. mono litter by 59%, whereas it significantly decreased the release rates of Ca (in the T. amurensis litter) and P (in the A. mono litter) by 28 and 48%, respectively.These results suggest that a stronger understanding of the influence of soil fauna on nutrient cycling is necessary to understand the mechanisms of matter circulation.
Ten microsatellite markers in endangered species Sauvagesia rhodoleuca (Ochnaceae).

UNLABELLED PREMISE OF THE STUDY We developed microsatellite markers to investigate the level of genetic diversity within and among populations of the endemic shrub Sauvagesia rhodoleuca in China. • METHODS AND RESULTS Ten polymorphic microsatellite loci were identified in five populations. The number of alleles per locus varied from 2 to 16. Observed and expected heterozygosities ranged from 0.000 to 1.000 and from 0.000 to 0.726, respectively. • CONCLUSIONS The results provide basic information on genetic diversity for future studies of population genetics in S. rhodoleuca.
Phase 1 study of lenalidomide plus dose‐adjusted EPOCH‐R in patients with aggressive B‐cell lymphomas with deregulated MYC and BCL2

Dual translocation of MYC and BCL2 or the dual overexpression of these proteins in patients with aggressive B‐cell lymphomas (termed double‐hit lymphoma [DHL] and double‐expressor lymphoma [DEL], respectively) have poor outcomes after chemoimmunotherapy with the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP). Retrospective reports have suggested improved outcomes with dose‐intensified regimens. In the current study, the authors conducted a phase 1 study to evaluate the feasibility, toxicity, and preliminary efficacy of adding lenalidomide to dose‐adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with rituximab (DA‐EPOCH‐R) in patients with DHL and DEL.
The ubiquitin-like modifier FAT10 stimulates the activity of deubiquitylating enzyme OTUB1

The deubiquitylation of target proteins is mediated by deubiquitylating enzymes (DUB) such as OTUB1, which plays an important role in immune response, cell cycle progression, and DNA repair. Within these processes, OTUB1 reduces the ubiquitylation of target proteins in two distinct ways, either by using its catalytic DUB activity or in a noncatalytic manner by inhibiting the E2-conjugating enzyme. Here, we show that the ubiquitin-like modifier FAT10 regulates OTUB1 stability and functionality in different ways. Covalent FAT10ylation of OTUB1 resulted in its proteasomal degradation, whereas a noncovalent interaction stabilized OTUB1. We provide evidence that OTUB1 interacts directly with FAT10 and the E2-conjugating enzyme USE1. This interaction strongly stimulated OTUB1 DUB activity toward Lys-48–linked diubiquitin. Furthermore, the noncovalent interaction between FAT10 and OTUB1 not only enhanced its isopeptidase activity toward Lys-48–linked ubiquitin moieties but also strengthened its noncatalytic activity in reducing Lys-63 polyubiquitylation of its target protein TRAF3 (TNF receptor–associated factor 3). Additionally, the cellular clearance of overall polyubiquitylation by OTUB1 was strongly stimulated through the presence of FAT10. The addition of FAT10 also led to an increased interaction between OTUB1 and its cognate E2 UbcH5B, implying a function of FAT10 in the inhibition of polyubiquitylation. Overall, these data indicate that FAT10 not only plays a role in covalent modification, leading its substrates to proteasomal degradation, but also regulates the stability and functionality of target proteins by interacting in a noncovalent manner. FAT10 is thereby able to exert a major influence on ubiquitylation processes.
Cognitive mapping style relates to posterior–anterior hippocampal volume ratio

As London taxi drivers acquire “the knowledge” and develop a detailed cognitive map of London, their posterior hippocampi (pHPC) gradually increase in volume, reflecting an increasing pHPC/aHPC volume ratio. In the mnemonic domain, greater pHPC/aHPC volume ratios in young adults have been found to relate to better recollection ability, indicating that the balance between pHPC and aHPC volumes might be reflective of cross‐domain individual differences. Here, we examined participants' self‐reported use of cognitive map‐based navigational strategies in relation to their pHPC/aHPC hippocampal volume ratio. We find that greater reported cognitive map use was related to significantly greater posterior, relative to anterior, hippocampal volume in two separate samples of young adults. Further, greater reported cognitive map usage correlated with better performance on a self‐initiated navigation task. Together, these data help to advance our understanding of differences between aHPC and pHPC and the greater role of pHPC in spatial mapping.