Miracle-dz/UniFAR-FTUs huggingface dataset:
Computer-aided discovery of pleiotropic effects: Anti-inflammatory action of dithioloquinolinethiones as a case study

ABSTRACT Most of pharmaceutical agents exhibit several or even many biological activities. It is clear that testing even one compound for thousands of biological activities is a practically not feasible task. Therefore, computer-aided prediction is the method-of-the-choice to select the most promising bioassays for particular compounds. Using PASS Online software, we determined the likely anti-inflammatory action of the 13 dithioloquinolinethione derivatives with antimicrobial activities. Chemical similarity search in the Cortellis Drug Discovery Intelligence database did not reveal close structural analogues with anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds was comparable with or higher than the reference drug Indomethacin. Thus, based on the in silico predictions, novel class of the anti-inflammatory agents was discovered.
Amyloid‐β protein and MicroRNA‐384 in NCAM‐Labeled exosomes from peripheral blood are potential diagnostic markers for Alzheimer's disease

We aimed to establish a method to determine whether amyloid‐β (Aβ) protein and miR‐384 in peripheral blood neural cell adhesion molecule (NCAM)/ATP‐binding cassette transporter A1 (ABCA1) dual‐labeled exosomes may serve as diagnostic markers for the diagnosis of Alzheimer's disease (AD).
Complex Material Properties of Gel-Amin: A Transparent and Ionically Conductive Hydrogel for Neural Tissue Engineering

The field of tissue engineering has benefited greatly from the broad development of natural and synthetic polymers. Extensive work in neural engineering has demonstrated the value of conductive materials to improve spontaneous neuron activity as well as lowering the necessary field parameters for exogenous electrical stimulation. Further, cell fate is directly coupled to the mechanical properties of the cell culture substrate. Increasing the conductivity of hydrogel materials often necessitates the addition of dopant materials that facilitate electron mobility. However, very little electron transfer is observed in native cell signaling and most of these materials are opaque, severely limiting microscopy applications commonly employed to assess cell culture morphology and function. To overcome these shortcomings, the inclusion of an ionic liquid, choline acrylate, into the backbone of a modified collagen polymer increases the bulk conductivity 5-fold at a 1:1 ratio while maintaining optical transmission of visible light. Here, we explore how the inclusion of choline acrylate influences bulk material properties including the mechanical, swelling, and optical properties of our hydrogels, referred to as Gel-Amin hydrogels, as a material for tissue culture. Despite an increase in swelling over traditional GelMA materials, the conductive hydrogels support whole dorsal root ganglia encapsulation and outgrowth. Our results indicate that our Gel-Amin system holds potential for neural engineering applications and lowering the required charge injection for the application of exogenous electrical stimulation. This is this first time an ionic liquid-hydrogel system has been used to culture and support primary neurons in vitro.
Needs for nurses to provide spiritual care and their associated influencing factors among elderly inpatients with stroke in China: A cross-sectional quantitative study

Abstract Objectives To investigate the spiritual care needs and associated influencing factors among elderly inpatients with stroke, and to examine the correlations among spiritual care needs, spiritual well-being, self-perceived burden, self-transcendence, and social support. Methods A cross-sectional quantitative design was implemented, and the STROBE Checklist was used as the foundation of the study. A convenience sample of 458 elderly inpatients with stroke was selected from three hospitals in China. The sociodemographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale, the Functional Assessment of Chronic Illness Therapy—Spiritual Well-being, the Self-Perceived Burden Scale, the Chinese Self-Transcendence Scale, and the Perceived Social Support Scale were used. Descriptive statistics, correlation, Student's t-test, ANOVA, non-parametric, and multiple linear regression analyses were used to analyze the data. Results The total score of spiritual care needs was 29.82 ± 7.65. Spiritual care needs were positively correlated with spiritual well-being (r = 0.709, p < 0.01), self-transcendence (r = 0.710, p < 0.01), and social support (r = 0.691, p < 0.01), whereas being negatively correlated with self-perceived burden (r = −0.587, p < 0.01). Religious beliefs, educational level, residence place, disease course, spiritual well-being, self-perceived burden, self-transcendence, and social support were found to be the main influencing factors. Significance of results The spiritual care needs were prevalent and moderate. It is suggested that nurses should enhance spiritual care knowledge and competence, take targeted spiritual care measures according to inpatients’ individual personality traits or characteristics and differences of patients, reduce their self-perceived burden and improve their spiritual well-being, self-transcendence and social support in multiple ways and levels, so as to meet their spiritual care needs to the greatest extent and enhance their spiritual comfort.
Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors: modeling the function of an inactivating receptor mutation

Abstract Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein–protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.
Friction and Wear in Automotive Journal Bearings Operating in Today’s Severe Conditions

A current trend in the transport sector seeks to increase the vehicle efficiency and to cut fuel consumption which leads to new technologies and advancements in modern and future combustion engines. Some of these technical progresses lead to highly stressed engine parts and new challenges arise, particularly for journal bearings. The increasing thermal and mechanical load caused by downsized and turbocharged engines, friction reduction by employing low-viscosity lubricants and other emission reduction measures—for utilizing stop-start systems—put additional stress on the crankshaft journal bearings. This contribution focuses on highly stressed journal bearings which operate in the boundary, mixed and hydrodynamic lubrication regime. Therefore, measurements on a journal bearing test-rig are performed which allow an extensive verification of the numerical investigation. For the numerical analysis of friction and wear, a mixed elasto-hydrodynamic simulation approach is developed, which considers the elastic deformation of the contacting components, the complex rheological behaviour of the lubricant and metal-metal contact if the lubricant is unable to separate the contacting surfaces. Both the rheological data and the surface roughness parameters are obtained from measurements. The current challenges are studied in four application-oriented examples and the influencing parameters on a reliable friction and wear prediction are explored.
Utilization of cardiac imaging in sarcoidosis

ABSTRACT Introduction Cardiac sarcoidosis (CS) is the cardiac, and occasionally the only manifestation, of a systemic disease of unknown etiology inherently challenging to definitively diagnose due to the lack of a reliable gold standard, the current being endomyocardial biopsy, the yield of which is low owing to the patchy nature of involvement. Societal guidelines employ specific criteria to make a probabilistic diagnosis, integrating clinical assessment with conventional and advanced cardiac imaging. Areas covered This review begins with an introduction to CS, followed by a discussion of diagnostic guidelines commonly used, then delves into an in-depth review of the imaging modalities currently available to assess for CS. Particular attention is made to discussing findings, strengths, limitations, and future directions for each modality. Expert opinion The burden of CS may be significantly larger than previously thought. With the low yield of endomyocardial biopsy, advanced cardiac imaging is increasingly employed to determine CS likelihood. Cardiac magnetic resonance is adept at detecting myocardial scar and able to differentiate between CS and other cardiomyopathies. F-18 Fluorodeoxyglucose positron emission tomography is superior at detecting active disease (myocardial inflammation) which may be amenable to immunosuppressive treatment, as well as detecting extracardiac involvement and identifying potential biopsy sites.
Introduction to the 60th Anniversary Virtual Special Edition: the prospect for Architectural Science

It is a pleasure to reflect on the progress of Architectural Science Review (ASR) over the last 60 years, in particular how the journal has adapted to the changes in the needs of the readership in recent years. The early years were shaped by Professor Henry Cowan who from its inception, visioned ASR as a vehicle for disseminating knowledge on science for research, teaching and the practice of architecture. Located in the southern hemisphere, there was an interest in working with warm climates and the development of regional issues. In the last 10 years, there has been an expansion of knowledge and a change in structure for ASR. Emeritus Professor Gary Moore passed on the Editor in Chief role to me in 2008. At the same time, there was a change in publishers from The University of Sydney Press to Earthscan and then to Taylor and Francis. Professor Moore had established the model for the journal, which was amixture of items: editorials, invited papers, unsolicited refereedpapers, technical notes, book reviews, PhD thesis abstracts and special editions (Moore 2007), and was positioned within Thomsen Reuters Humanities Index. In 2010 the journal comprised60 items andproduced10 citations. Taylor andFrancis has provided continued support inmanyareas includingpublication reports on the progress of the journal and has also enabled us to track the kind of themes that are of most interest. These reports show that the journal has changed focus considerably. By 2015 in order to maximize the space available for papers in ASR, the number of items has been halved and there has been an increase in the citations to 180. So what has changed? A new format was developed focusing on paper publications, thematic editions and special editions, with other items now published online through a newsletter. The development of Special Issues from international conferences has led to attracting key research and researchers to publish inASR. Notable are the Special Edition from theArchitectural Science Association (ANZAScA) and unsolicited proposals such as those from the Windsor Conference. The number of editions per year has grown from four to six: four general and two special editions per year; this will allow Special Editions from authors of the Passive Lower Energy Association Conference (PLEA). We welcome this year new Associate Editors from PLEA to assist with directing andmanaging this new direction. Associate Editors are the backbone of the ASR team, many of whom are drawn from the Editorial Board and manage and maintain the academic standard of the journal.ASRnow receives
Synergistic blocking of RAS downstream signaling and epigenetic pathway in KRAS mutant pancreatic cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy and lacks effective therapeutic targets. Trametinib is considered to be a promising potential indirectly targeted KRAS inhibitor in PDAC. However, the clinical outcomes were poor. JQ1 displayed a significant synergistic effect when combined with chemotherapy or potential targeted therapy in pancreatic cancer. The impact of Trametinib and JQ1 combination treatment in PDAC remains to be fully elucidated. Methods: The efficacy of trametinib and JQ1 on cell proliferation and cytotoxicity was assayed in 7 KRAS mutant pancreatic cancer cell lines. The cytotoxic effects of drugs either alone or in combination were evaluated using a luminescent cell viability assay. Immunoblot analysis was carried out to investigate changes in p62 and autophagy. Results: We found that either trametinib or JQ1 alone inhibited the proliferation of some pancreatic cancer cell lines with KRAS alterations, irrespective of the mutational loci of KRAS and the aberrant status of the other driver genes. The synergistic effects of combination treatment of trametinib and JQ1 were observed in both trametinib-resistant and trametinib-sensitive cells. In trametinib-sensitive PDAC cells, the combined treatment definitely inhibited p62 expression compared with trametinib alone, while LC3 expression at high levels changed little. In trametinib-resistant PDAC cells, the combination of MEK/BET inhibitor dramatically decreased p62 expression compared with single agent, while p62 expression increased after anti-autophagic therapy was added. Conclusions: Blocking RAS downstream signaling and epigenetic pathway synergistically increases the antiproliferative activity in KRAS mutant PDAC cells. Combination therapeutic synergism may induce different cell death modes in different pancreatic cancer subtypes.
Anti-Th17 and anti-Th2 responses effects of hydro-ethanolic extracts of Aframomum melegueta, Khaya senegalensis and Xylopia aethiopica in hyperreactive onchocerciasis individuals’ peripheral blood mononuclear cells

Hyperreactive onchocerciasis (HO) is characterized by a severe skin inflammation with elevated Th17-Th2 combined responses. We previously demonstrated the anthelminthic activity of Aframomum melegueta (AM), Xylopia aethiopica (XA) and Khaya senegalensis (KS) used by traditional healers to treat helminthiasis in the endemic area of Togo. However, their effect on severe onchocerciasis is poorly investigated. The present study aimed to investigate the anti-Th17 and anti-Th2 effects of hydro-ethanolic extracts of AM, XA and KS during HO. Onchocerca volvulus-infected individuals were recruited in the Central region of Togo in 2018. Isolated peripheral blood mononuclear cells (PBMCs) from both generalized onchocerciasis (GEO) and HO forms were activated with anti-CD3 and anti-CD28 monoclonal antibodies in the presence or absence of the hydro-ethanolic extracts of AM, XA and KS as well as their delipidated, deproteinized and deglycosylated fractions. After 72 hours, cytokines were assayed from cell culture supernatants. Then, flow cytometry was used to investigate the effects of the extracts on cell activation, proliferation, intracellular cytokines and T cells transcription factors. The production of both Th17 and Th2 cytokines IL-17A and IL-5 were significantly inhibited upon T-cell receptor (TCR) activation in the presence of the hydro-ethanolic extracts of AM, XA and KS in HO individuals’ PBMCs in vitro. AM and XA inhibited CD4+RORC2+IL-17A+ and CD4+GATA3+IL-4+ cell populations induction. This inhibition was not Th1 nor Treg-dependent since both IFN-γ and IL-10 were also inhibited by the extracts. AM and XA did not interfere with T cell activation and proliferation for their inhibitory pathways. Lipid and protein compounds from AM and XA were associated with the inhibition of IL-17A. This study showed that in addition to their anthelminthic effects, hydro-ethanolic extracts of Aframomum melegueta, Xylopia aethiopica and Khaya senegalensis could downregulate both Th17 and Th2 responses and prevent the severe skin disorder observed.
Differences in Occurrence, Risk Factors and Severity of Early-onset Atopic Dermatitis among Preterm and Term Children

This prospective birth cohort followed 150 preterm and 300 term newborns during the first year of life to assess possible differences in risk factors, age at onset, anatomical location, and severity of atopic dermatitis. Atopic dermatitis was diagnosed clinically, and severity was assessed using Eczema Area Severity Index (EASI). DNA was analysed for filaggrin gene mutations. Parents were asked about environmental exposures and emollient use. Atopic dermatitis during the first year of life was observed in 21.2% of children and was more common in term children compared with preterm children (26.7% vs 11.7%, p < 0.001), with lower age of onset (4 vs 6 months, p < 0.05) and more severe disease at onset (EASI: 4.8 vs 0.4, p < 0.0005). Environmental risk factors for atopic dermatitis were essentially similar for preterm and term born children, apart from winter and autumn births. Filaggrin gene mutations were less common in preterm than term children (4.1% vs 9.2%, p = 0.06).
Developing Non-Lethal Weapons: The Human Effects Characterization Process

Abstract : As these examples highlight, non-lethal weapons provide options to commanders on the escalation and de-escalation of force continuum, enhancing their capability sets in various environments. While the benefit of these options maybe seem self-evident, it may not be as obvious how the Department of Defense (DoD) defines a non-lethal weapon and procures systems which meet that definition. The need for non-lethal weapons was recognized with the 1996 establishment of the DoD Non-Lethal Weapons Program. This followed the asymmetric warfare experience in Somalia. Here, rock- and Molotov-cocktail-throwing crowds and open looting of military equipment were undeterred until U.S. forces adopted non-lethal weapons during the 1995 United Nations withdrawal from Somalia.
Myolink: A 128-Channel, $\text{18 nV}/\sqrt{\text{Hz}}$, Embedded Recording System, Optimized for High-Density Surface Electromyogram Acquisition

<italic>Objective:</italic> We present Myolink, a portable, modular, low-noise electrophysiology amplifier optimized for high-density surface electromyogram (HD sEMG) acquisition. <italic>Methods:</italic> Myolink consists of 4 modules. Each 10 × 8 cm module can concurrently acquire 32 unipolar electrode potentials at sampling rates of up to 8 kHz with 24-bit resolution. Modules may be stacked and operated synchronously, supporting the concurrent acquisition of up to 128 channels. A custom high-performance analog front-end provides an input-referred-noise <inline-formula><tex-math notation="LaTeX">$\mathbf {< 0.4}$</tex-math></inline-formula> <inline-formula><tex-math notation="LaTeX">$\mu \mathbf {V}_{\mathbf {RMS}}$</tex-math></inline-formula> for a bandwidth of 23–524 Hz (tuneable by design choices), which is lower than current commercial systems. Digitized signals are processed by a custom on-board FPGA-based controller and subsequently transmitted to a PC via a medical-grade isolated USB 2.0 interface. <italic>Results:</italic> The system has been tested by recording experimental HD sEMG signals, which have been subsequently decomposed into motor unit action potentials. Compared to commercially available systems, the proposed recording system led to higher-quality surface EMG acquisition, as well as higher decomposition accuracy across a wide range of forces, with the greater gain for forces <inline-formula><tex-math notation="LaTeX">$\leq$</tex-math></inline-formula> 20% of the maximum voluntary contraction. <italic>Significance:</italic> A portable, ultra-low-noise, HD sEMG amplifier design has been implemented and characterized. The system provides IRN performance beyond the capabilities of current state-of-the-art instrumentation and this improvement has a significant effect on HD sEMG decomposition.
Dawn and dusk peaks of outer segment phagocytosis, and visual cycle function require Rab28

RAB28 is a farnesylated, ciliary G‐protein. Patient variants in RAB28 are causative of autosomal recessive cone‐rod dystrophy (CRD), an inherited human blindness. In rodent and zebrafish models, the absence of Rab28 results in diminished dawn, photoreceptor, outer segment phagocytosis (OSP). Here, we demonstrate that Rab28 is also required for dusk peaks of OSP, but not for basal OSP levels. This study further elucidated the molecular mechanisms by which Rab28 controls OSP and inherited blindness. Proteomic profiling identified factors whose expression in the eye or whose expression at dawn and dusk peaks of OSP is dysregulated by loss of Rab28. Notably, transgenic overexpression of Rab28, solely in zebrafish cones, rescues the OSP defect in rab28 KO fish, suggesting rab28 gene replacement in cone photoreceptors is sufficient to regulate Rab28‐OSP. Rab28 loss also perturbs function of the visual cycle as retinoid levels of 11‐cRAL, 11cRP, and atRP are significantly reduced in larval and adult rab28 KO retinae (p < .05). These data give further understanding on the molecular mechanisms of RAB28‐associated CRD, highlighting roles of Rab28 in both peaks of OSP, in vitamin A metabolism and in retinoid recycling.