Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy profiling in single cells with open source CellProfiler-based image analysis

ABSTRACT Single cell-based analysis of macroautophagy/autophagy is largely achieved through the use of fluorescence microscopy to detect autophagy-related proteins that associate with autophagic membranes and therefore can be quantified as fluorescent puncta. In this context, an automated analysis of the number and size of recognized puncta is preferable to a manual count, because more reliable results can be generated in a short time. Here we present a method for open source CellProfiler software-based analysis for quantitative autophagy assessments using GFP-tagged WIPI1 (WD repeat domain, phosphoinositide interacting 1) images acquired with Airyscan or confocal laser-scanning microscopy. The CellProfiler protocol is provided as a ready-to-use software pipeline, and the creation of this pipeline is detailed in both text and video formats. In addition, we provide CellProfiler pipelines for endogenous SQSTM1/p62 (sequestosome 1) or intracellular lipid droplet (LD) analysis, suitable to assess forms of selective autophagy. All protocols and software pipelines can be quickly and easily adapted for the use of alternative autophagy markers or cell types, and can also be used for high-throughput purposes.Abbreviations: AF Alexa Fluor ATG autophagy related BafA1 bafilomycin A1 BSA bovine serum albumin DAPI 4,6-diamidino-2-phenylindole DMEM Dulbecco’s modified Eagle’s medium DMSO dimethyl sulfoxide EDTA ethylenediaminetetraacetic acid EBSS Earle’s balanced salt solution FBS fetal bovine serum GFP green fluorescent protein LD lipid droplet LSM laser scanning microscope MAP1LC3B microtubule associated protein 1 light chain 3 beta MTOR mechanistic target of rapamycin kinase PBS phosphate-buffered saline PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3 SQSTM1 sequestosome 1 TIFF tagged image file format U2OS U-2 OS cell line WIPI WD repeat domain, phosphoinositide interacting
An emerging class of new therapeutics targeting TGF, Activin, and BMP ligands in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is an often fatal condition, the primary pathology of which involves loss of pulmonary vascular perfusion due to progressive aberrant vessel remodeling. The reduced capacity of the pulmonary circulation places increasing strain on the right ventricle of the heart, leading to death by heart failure. Currently, licensed therapies are primarily vasodilators, which have increased the median post‐diagnosis life expectancy from 2.8 to 7 years. Although this represents a substantial improvement, the search continues for transformative therapeutics that reverse established disease. The genetics of human PAH heavily implicates reduced endothelial bone morphogenetic protein (BMP) signaling as a causal role for the disease pathobiology. Recent approaches have focused on directly enhancing BMP signaling or removing the inhibitory influence of pathways that repress BMP signaling. In this critical commentary, we review the evidence underpinning the development of two approaches: BMP‐based agonists and inhibition of activin/GDF signaling. We also address the key considerations and questions that remain regarding these approaches.
A Qualitative Study of Women’s Experiences with Cognitive-Behavioral and Mindfulness-Based Online Interventions for Low Sexual Desire

ABSTRACT Cognitive-behavioral (CBT) and mindfulness-based therapy (MBT) are among the most researched types of psychological interventions for low sexual desire in women. While both have been found effective in improving women’s sexual desire, little is known about how women personally experience these treatments. To closely examine both approaches from a participant’s perspective, semi-structured telephone-based interviews were conducted with 51 cis-women (M age = 39, SD = 11, range = 22 to 69) who participated in a randomized controlled study comparing internet-based CBT and MBT for low sexual desire with a waitlist. Interview data were analyzed using thematic and content analysis. Most women (n = 44, 86.3%) evaluated their respective treatment (i.e., CBT or MBT) as helpful in improving their sexual desire. CBT-techniques, such as cognitive restructuring, were mentioned as being helpful for challenging maladaptive thinking patterns, while formal mindfulness-exercises allowed women to disengage from negative sexuality-related thoughts. Elements of sex therapy, including self-stimulation exercises and sensate focus, were perceived as crucial for getting women in touch with their sexual desires and preferences. Strengths of the online format included anonymity, flexibility, and convenient access. Overall, women’s personal accounts supported feasibility, acceptability, and clinical usefulness of CBT- and MBT-based internet interventions targeting low sexual desire.
Cause analysis of unsafe acts of pilots in general aviation accidents in China with a focus on management and organizational factors

Objectives. General aviation (GA) safety has become a key issue worldwide and pilot errors have grown to be the primary cause of GA accidents. However, fewer empirical studies have examined the contribution of management and organizational factors for these unsafe acts. Flawed decisions at the organizational level have played key roles in the performance of pilots. This study provides an in-depth understanding of the management and organizational factors involved in GA accident reports. Methods. A total of 109 GA accidents in China between 1996 and 2021 were analysed. Among these reports, pilot-related accidents were analysed using the human factors analysis and classification system (HFACS) framework. Results. The significant effects of managerial and organizational factors and the failure pathways on GA accidents have been identified. Furthermore, unlike traditional HFACS-based analyses, the statistically significant relationships between failures at the organizational level and the sub-standard acts of the pilots in GA accidents were revealed. Conclusions. Such findings support that the GA accident prevention strategy that attempts to reduce the number of unsafe acts of pilots should be directed to the crucial causal categories at HFACS organizational levels: resource management, organizational process, failure to correct a known problem, inadequate supervision and supervisory violations.
Robust control scheme for a microgrid with PFC capacitor connected

Capacitors are widely used for power factor correction (PFC) in power systems. When a PFC capacitor is installed with a certain load in a microgrid, it may be in parallel with the filter capacitor of the inverter interfacing the utility grid and the local DG and thus change the effective filter capacitance. Another complication is the possibility of occurrence of resonance in the microgrid. This paper conducts an in-depth investigation of the effective shunt filter capacitance variation and resonance phenomena in a microgrid due to connection of a PFC capacitor. To compensate the capacitance parameter variation, an H/spl infin/ controller is designed for the VSI voltage control. By properly choosing the weighting functions the synthesized H/spl infin/ controller would exhibit high gains at the vicinity of the line frequency, similar to traditional high performance P+resonant controller, and thus would possess nearly zero steady state error. However with the robust H/spl infin/ controller, it will be possible to explicitly specify the degree of robustness in face of parameter variations. Furthermore, a thorough investigation is carried out to study the performance of inner current loop feedback variables under resonance conditions. It reveals that filter inductor current feedback is more effective in damping the resonance. This resonance can be further attenuated by employing the dual-inverter microgrid conditioner and controlling the series inverter as a virtual resistor affecting only harmonic components without affecting the fundamental power flow.
Unreliable Threats: Conflicts of Interest Disclosure and the Safeguarding of Biomedical Knowledge

ABSTRACT:Medical epistemology lately has seen a strengthening of the view that the construction of evidence should be sensitive to the social context in which it is produced. A poignant illustration of this is the undue influence of the pharmaceutical industry on research results and reporting. I challenge a particular application of this view by examining a common practice in the medical and scientific community: mandatory author disclosure of conflicts of interest (COIs) in published articles. In illustrating problems with COI disclosure policies in biomedical publishing, including unappreciated shortcomings of the scant empirical data supporting mandatory disclosure, I hope to demonstrate that the value given to journal COI disclosure policies as a way to protect the reliability of medical evidence might well be misplaced. Rather than extract away the "messy" details of the real world, the analysis is ultimately more responsive to how medical knowledge is produced and disseminated.
Integrating Technical and Emotional Competences in Hospitality Education

ABSTRACT Given that hospitality students are the main prospective labor source in the industry, employees, academicians, and practitioners agree that improving competences is central to the education, training, and development of hospitality employees. The current study used a competency-based framework to investigate the simultaneous application of training in technical and emotional competences on hospitality undergraduates in a service management class (N = 50). Data were gathered using a pre- and posttest design at a southwestern university in the United States. Competences increased after training, which supports the notion of including emotional competence in hospitality curricula. The findings of this study provide support for existing knowledge about emotional competences and the importance of including emotional competences in the hospitality curriculum.
The Cancer Research Database (CRDB): Integrated Platform to Gain Statistical Insight Into the Correlation Between Cancer and COVID-19

Background The advancement of cancer research has been facilitated through freely available cancer literature, databases, and tools. The age of genomics and big data has given rise to the need for cooperation and data sharing in order to make efficient use of this new information in the COVID-19 pandemic. Although there are many databases for cancer research, their access is not easy owing to different ways of processing and managing the data. There is an absence of a unified platform to manage all of them in a transparent and more comprehensible way. Objective In this study, an improved integrated cancer research database and platform is provided to facilitate a deeper statistical insight into the correlation between cancer and the COVID-19 pandemic, unifying the collection of almost all previous published cancer databases and defining a model web database for cancer research, and scoring databases on the basis of the variety types of cancer, sample size, completeness of omics results, and user interface. Methods Databases examined and integrated include the Data Portal database, Genomic database, Proteomic database, Expression database, Gene database, and Mutation database; and it is expected that this launch will sort, save, advance the understanding and encourage the use of these resources in the cancer research environment. Results To make it easy to search valuable information, 85 cancer databases are provided in the form of a table, and a database of databases named the Cancer Research Database (CRDB) has been built and presented herein. Furthermore, the CRDB has been herein equipped with unique navigation tools in order to be explored by three methods; that is, any single database can be browsed by typing the name in the given search bar, while all categories can be browsed by clicking on the name of the category or image expression icon, thus serving as a facility that could provide all the category databases on a single click. Conclusions The computational platform (PHP, HTML, CSS, and MySQL) used to build CRDB for the cancer scientific community can be freely investigated and browsed on the internet and is planned to be updated in a timely manner. In addition, based on the proposed platform, the status and diagnoses statistics of cancer during the COVID-19 pandemic have been thoroughly investigated herein using CRDB, thus providing an easy-to-manage, understandable framework that mines knowledge for future researchers.
Stabilization of Ferrihydrite and Lepidocrocite by Silicate during Fe(II)-Catalyzed Mineral Transformation: Impact on Particle Morphology and Silicate Distribution

Interactions between aqueous ferrous iron (Fe(II)) and secondary Fe oxyhydroxides catalyze mineral recrystallization and/or transformation processes in anoxic soils and sediments, where oxyanions, such as silicate, are abundant. However, the effect and the fate of silicate during Fe mineral recrystallization and transformation are not entirely understood and especially remain unclear for lepidocrocite. In this study, we reacted (Si-)ferrihydrite (Si/Fe = 0, 0.05, and 0.18) and (Si-)lepidocrocite (Si/Fe = 0 and 0.08) with isotopically labeled 57Fe(II) (Fe(II)/Fe(III) = 0.02 and 0.2) at pH 7 for up to 4 weeks. We followed Fe mineral transformations with X-ray diffraction and tracked Fe atom exchange by measuring aqueous and solid phase Fe isotope fractions. Our results show that the extent of ferrihydrite transformation in the presence of Fe(II) was strongly influenced by the solid phase Si/Fe ratio, while increasing the Fe(II)/Fe(III) ratio (from 0.02 to 0.2) had only a minor effect. The presence of silicate increased the thickness of newly formed lepidocrocite crystallites, and elemental distribution maps of Fe(II)-reacted Si-ferrihydrites revealed that much more Si was associated with the remaining ferrihydrite than with the newly formed lepidocrocite. Pure lepidocrocite underwent recrystallization in the low Fe(II) treatment and transformed to magnetite at the high Fe(II)/Fe(III) ratio. Adsorbed silicate inactivated the lepidocrocite surfaces, which strongly reduced Fe atom exchange and inhibited mineral transformation. Collectively, the results of this study demonstrate that Fe(II)-catalyzed Si-ferrihydrite transformation leads to the redistribution of silicate in the solid phase and the formation of thicker lepidocrocite platelets, while lepidocrocite transformation can be completely inhibited by adsorbed silicate. Therefore, silicate is an important factor to include when considering Fe mineral dynamics in soils under reducing conditions.
Adiponectin inhibits the activation of lung fibroblasts and pulmonary fibrosis by regulating the nuclear factor kappa B (NF-κB) pathway

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a common pulmonary interstitial disease with a high mortality rate. Adiponectin (APN) is reportedly an effective therapy for fibrosis-related diseases. This study aimed to investigate the potential effects of APN on IPF. Male BALB/c mice were injected with bleomycin (BLM) and treated with different doses of APN (0.1, 0.25, and 0.5 mg/kg). The body weights of the mice were recorded. Immunohistochemical, hematoxylin and eosin, and Masson staining were performed to evaluate pulmonary histopathological changes. Enzyme-linked immunosorbent assay (ELISA) and western blotting were performed to assess tissue inflammation. The human lung fibroblasts HELF were stimulated with TGF-β1 and treated with different doses of APN (2.5, 5, and 10 μg/ml). Cell proliferation, inflammation, and fibrosis were determined by MTT assay, EdU assay, colony formation assay, ELISA, and western blotting. APN significantly attenuated BLM-induced body weight loss, alveolar destruction, and collagen fiber accumulation in mice (p < 0.05). APN decreased the expression of α-SMA and collagen I and reduced the concentration of TNF-α, IL-6, IL-1β, and IL-18 in lung tissues (p < 0.05). In TGF-β1-treated HELF cells, cell proliferation and colony formation were inhibited by APN (p < 0.05). Additionally, the expression of α-SMA, collagen I, and pro-inflammatory cytokines were suppressed by APN (p < 0.05). APN inhibited the phosphorylation of IκB and nuclear translocation of p65. In conclusion, these findings suggest that APN is an effective agent for controlling IPF progression. The antifibrotic effects of APN might be mediated via inhibiting the NF-κB signaling pathway. Graphical Abstract
Adenovirus entry: Stability, uncoating, and nuclear import

Adenoviruses (AdVs) are widespread in vertebrates. They infect the respiratory and gastrointestinal tracts, the eyes, heart, liver, and kidney, and are lethal to immunosuppressed people. Mastadenoviruses infecting mammals comprise several hundred different types, and many specifically infect humans. Human adenoviruses are the most widely used vectors in clinical applications, including cancer treatment and COVID‐19 vaccination. AdV vectors are physically and genetically stable and generally safe in humans. The particles have an icosahedral coat and a nucleoprotein core with a DNA genome. We describe the concept of AdV cell entry and highlight recent advances in cytoplasmic transport, uncoating, and nuclear import of the viral DNA. We highlight a recently discovered “linchpin” function of the virion protein V ensuring cytoplasmic particle stability, which is relaxed at the nuclear pore complex by cues from the E3 ubiquitin ligase Mind bomb 1 (MIB1) and the proteasome triggering disruption. Capsid disruption by kinesin motor proteins and microtubules exposes the linchpin and renders protein V a target for MIB1 ubiquitination, which dissociates V from viral DNA and enhances DNA nuclear import. These advances uncover mechanisms controlling capsid stability and premature uncoating and provide insight into nuclear transport of nucleic acids.
Cortisol levels versus self-report stress measures during pregnancy as predictors of adverse infant outcomes: a systematic review

Abstract Systematically review existing evidence to (1) identify the association between self-report stress and cortisol levels measured during pregnancy; and, (2) assess their association with adverse infant outcomes to determine which is the better predictor. A systematic review was conducted in accordance with PRISMA guidelines. Search terms focused on pregnancy, psychological stress and cortisol. Nine electronic databases were searched, in addition to reference lists of relevant papers. Eligibility criteria consisted of studies that included measurement of self-reported psychological stress, cortisol and assessed their associations with any infant-related outcome. Further limits included studies published in English or Spanish with human female participants. A meta-regression was not feasible due to differences in study samples, measurement tools employed, types of cortisol assessed and outcomes reported. A narrative synthesis was provided. 28 studies were eligible for inclusion. Convergent validity between self-report measures and cortisol was reported by three studies (range r = 0.12–0.41). Higher levels of self-report stress were significantly associated with intrauterine growth restriction (fetal biparietal diameter, low fetal head circumference, abdominal circumference), low gestational age at birth, low anthropometric measures (birth length, head circumference, length of the neonate), poor infant neurodevelopment (cognitive development) and potentially pathogenic gut microbiota (Clostridiaceae Clostridium, Haemophilus) in six studies. Higher cortisol levels were significantly associated with intrauterine growth restriction (fetal biparietal diameter, low fetal head circumference, abdominal circumference), low gestational age at birth, low infant birth weight, poor infant neurodevelopment (attention scores on the Network Neurobehavioral Scale) and low levels of potentially protective gut microbiota (Lactobacillus, Slackia and Actinobaculum) in 13 studies. Of the studies that assessed which type of measure was a better predictor of infant outcomes (n = 6), there was agreement that cortisol levels were statistically better at predicting adverse outcomes than self-reported stress. Self-report stress measures appear to be modest predictors of adverse infant outcomes in comparison to cortisol. A number of methodological limitations need to be addressed in future studies to help understand the relationship between cortisol and self-reported stress and how they are related to adverse infant outcomes.
Prognostic value of NOTCH1 and OCT4 in gastric carcinoma

Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.