Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Fluid Flow Shear Stress and Substrate Stiffness on Yes-Associated Protein (YAP) Activity and Osteogenesis in Murine Osteosarcoma Cells

Simple Summary Primary bone cancers like osteosarcoma (OS) are driven by bone cells that develop mutations, and behave in an uncontrolled manner. All bone cells, including defective ones, are sensitive to their physical environment. We tested the response of osteosarcoma cells, at the gene level, to two different kinds of mechanical stimulus, which are relevant to the tumor microenvironment. The first was fluid flowing over their surface, and the second was stiffness or rigidity of the surface beneath. In our study we found that fluid flow in particular has the ability to change the behavior of OS cancer cells, and could potentially be used to reduce their harmful effects. Abstract Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in the osteoblast lineage. We silenced Sox2 (which regulates YAP) and tested the effect of fluid flow shear stress (FFSS) and substrate stiffness on YAP expression/activity—which was significantly reduced by loss of Sox2, but that effect was reversed by FFSS but not by substrate stiffness. Osteogenic gene expression was also reduced in the absence of Sox2 but again this was reversed by FFSS and remained largely unaffected by substrate stiffness. Thus we described the effect of two distinct stimuli on the mechanosensory and osteogenic profiles of OS cells. Taken together, these data suggest that modulation of fluid movement through, or stiffness levels within, OS tumors could represent a novel consideration in the development of new treatments to prevent their progression.
Adipokines and Arterial Stiffness in Obesity

Adipokines are active molecules with pleiotropic effects produced by adipose tissue and involved in obesity-related metabolic and cardiovascular diseases. Arterial stiffness, which is a consequence of arteriosclerosis, has been shown to be an independent predictor of cardiovascular morbidity and mortality. The pathogenesis of arterial stiffness is complex but incompletely understood. Adipokines dysregulation may induce, by various mechanisms, vascular inflammation, endothelial dysfunction, and vascular remodeling, leading to increased arterial stiffness. This article summarizes literature data regarding adipokine-related pathogenetic mechanisms involved in the development of arterial stiffness, particularly in obesity, as well as the results of clinical and epidemiological studies which investigated the relationship between adipokines and arterial stiffness.
On the Origin of Tetraploid Vernal Grasses (Anthoxanthum) in Europe

Polyploidy has played a crucial role in the evolution of many plant taxa, namely in higher latitudinal zones. Surprisingly, after several decades of an intensive research on polyploids, there are still common polyploid species whose evolutionary history is virtually unknown. Here, we addressed the origin of sweet vernal grass (Anthoxanthum odoratum) using flow cytometry, DNA sequencing, and in situ hybridization-based cytogenetic techniques. An allotetraploid and polytopic origin of the species has been verified. The chromosome study reveals an extensive variation between the European populations. In contrast, an autopolyploid origin of the rarer tetraploid vernal grass species, A. alpinum, has been corroborated. Diploid A. alpinum played an essential role in the polyploidization of both European tetraploids studied.
Association between Occupational Dysfunction and Social Isolation in Japanese Older Adults: A Cross-Sectional Study

We clarified the relationship between occupational dysfunction and social isolation among community-dwelling adults. We used a self-administered questionnaire with a cross-sectional study for 2879 independently living older adults in Kasama City, Japan. Participants responded to a self-reported questionnaire in November 2019. Occupational dysfunction and social isolation were assessed. The participants were classified into two groups: healthy occupational function group, and occupational dysfunction group. To examine the relationship between occupational dysfunction and social isolation, we performed a logistic regression analysis with social isolation as a dependent variable and occupational dysfunction as an independent variable. In the crude model, the occupational dysfunction group had a higher risk of social isolation than the healthy occupational function group (odds ratio (OR) = 2.04; 95% confidence interval (CI), 1.63–2.55; p < 0.001). In the adjusted model, the occupational dysfunction group had a higher risk of social isolation than the healthy occupational function group (OR = 1.51; 95% CI, 1.17–1.94; p = 0.001). The results showed that occupational dysfunction was significantly associated with social isolation. These results can be used in constructing a support method for social isolation from a new perspective.
Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development

Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell’s antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa regulates essential functional characteristics such as motility, capacitation, acrosome reaction, hyperactivation, and sperm-oocyte fusion. OS can have detrimental effects on sperm function through lipid peroxidation, protein damage, and DNA strand breakage, which can eventually affect the fertility of an individual. Substantial evidence in the literature indicates that spermatozoa experiencing OS during in vitro manipulation procedures in human- and animal-assisted reproduction are increasingly associated with iatrogenic ROS production and eventual impairment of sperm function. Although a direct association between sperm OS and human assisted reproductive techniques (ART) outcomes after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) is still a matter of debate, studies in animal models provide enough evidence on the adverse effects of sperm OS in vitro and defective fertilization and embryo development. This review summarized the literature on sperm OS in vitro, its effects on functional ability and embryo development, and the approaches that have been proposed to reduce iatrogenic sperm damage and altered embryonic development.
Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

Eltrombopag is a thrombopoietin receptor (MPL) agonist approved for the treatment of primary immune thrombocytopenia (ITP). Recent evidence shows that some patients may sustain platelet counts following eltrombopag discontinuation. The systemic immunomodulatory response that resolves ITP in some patients could result from an increase in platelet mass, caused either by the direct action of eltrombopag on megakaryocytes through MPL stimulation, or potential MPL-independent actions on other cell types. To uncover the possible mechanisms of action of eltrombopag, in silico analyses were performed, including a systems biology-based approach, a therapeutic performance mapping system, and structural analyses. Through manual curation of the available bibliography, 56 key proteins were identified and integrated into the ITP interactome analysis. Mathematical models (94.92% mean accuracy) were obtained to elucidate potential MPL-dependent pathways in non-megakaryocytic cell subtypes. In addition to the effects on megakaryocytes and platelet numbers, the results were consistent with MPL-mediated effects on other cells, which could involve interferon-gamma, transforming growth factor-beta, peroxisome proliferator-activated receptor-gamma, and forkhead box protein P3 pathways. Structural analyses indicated that effects on three apoptosis-related proteins (BCL2L1, BCL2, BAX) from the Bcl-2 family may be off-target effects of eltrombopag. In conclusion, this study proposes new hypotheses regarding the immunomodulatory functions of eltrombopag in patients with ITP.
In Vitro Compression Model for Orthodontic Tooth Movement Modulates Human Periodontal Ligament Fibroblast Proliferation, Apoptosis and Cell Cycle

Human Periodontal Ligament Fibroblasts (hPDLF), as part of the periodontal apparatus, modulate inflammation, regeneration and bone remodeling. Interferences are clinically manifested as attachment loss, tooth loosening and root resorption. During orthodontic tooth movement (OTM), remodeling and adaptation of the periodontium is required in order to enable tooth movement. hPDLF involvement in the early phase-OTM compression side was investigated for a 72-h period through a well-studied in vitro model. Changes in the morphology, cell proliferation and cell death were analyzed. Specific markers of the cell cycle were investigated by RT-qPCR and Western blot. The study showed that the morphology of hPDLF changes towards more unstructured, unsorted filaments under mechanical compression. The total cell numbers were significantly reduced with a higher cell death rate over the whole observation period. hPDLF started to recover to pretreatment conditions after 48 h. Furthermore, key molecules involved in the cell cycle were significantly reduced under compressive force at the gene expression and protein levels. These findings revealed important information for a better understanding of the preservation and remodeling processes within the periodontium through Periodontal Ligament Fibroblasts during orthodontic tooth movement. OTM initially decelerates the hPDLF cell cycle and proliferation. After adapting to environmental changes, human Periodontal Ligament Fibroblasts can regain homeostasis of the periodontium, affecting its reorganization.
Dengue Detection: Advances in Diagnostic Tools from Conventional Technology to Point of Care

The dengue virus (DENV) is a vector-borne flavivirus that infects around 390 million individuals each year with 2.5 billion being in danger. Having access to testing is paramount in preventing future infections and receiving adequate treatment. Currently, there are numerous conventional methods for DENV testing, such as NS1 based antigen testing, IgM/IgG antibody testing, and Polymerase Chain Reaction (PCR). In addition, novel methods are emerging that can cut both cost and time. Such methods can be effective in rural and low-income areas throughout the world. In this paper, we discuss the structural evolution of the virus followed by a comprehensive review of current dengue detection strategies and methods that are being developed or commercialized. We also discuss the state of art biosensing technologies, evaluated their performance and outline strategies to address challenges posed by the disease. Further, we outline future guidelines for the improved usage of diagnostic tools during recurrence or future outbreaks of DENV.
Possible Therapeutic Potential of Disulfiram for Multiple Myeloma

Multiple myeloma (MM) is a malignant disease of the plasma cells representing approximately 10% of all hemato-oncological diseases. Detection of the disease is most probable at around 65 years of age, and the average survival of patients is estimated to be 5–10 years, specifically due to frequent relapses and resistance to the therapy used. Thus, the search for new therapeutic approaches is becoming a big challenge. Disulfiram (DSF), a substance primarily known as a medication against alcoholism, has often been mentioned in recent years in relation to cancer treatment for its secondary anti-cancer effects. Recent studies performed on myeloma cell lines confirm high inhibition of the cell growth activity if a complex of disulfiram and copper is used. Its significant potential is now being seen in the cure of haematological malignities.
Agricultural Stakeholders’ Perceptions of Occupational Health and Safety in the Southeastern U.S. Coastal States

Agriculture remains a highly dangerous industry for occupational health and safety. This study sought to understand the perspective of agricultural professionals with respect to the current state of the industry, challenges, and opportunities relevant to occupational health and safety. Additional questions related to the COVID-19 pandemic emerged in the findings as well. Eleven industry professionals were interviewed, and the transcripts were qualitatively analyzed for emergent themes following a constant comparative method. Three themes emerged in our findings: a description of the current state of occupational health and safety in the agricultural industry, barriers to improving occupational health and safety, and enablers of occupational health and safety. Each theme contained subthemes. The description of the industry encompassed regulations, inherent danger, and attitudes and education. Barriers included education, health care access, logistics, discrimination and cultural competency, economic considerations, and the labor contracting system. Enablers included education, regulations, and health care and prevention. These findings are consistent with existing literature, revealing interconnected and overlapping challenges and opportunities. Further research is recommended with a broader sample of participants, especially farmworkers.
Coherence between Decomposed Components of Wrist and Finger PPG Signals by Imputing Missing Features and Resolving Ambiguous Features

Background: Feature extraction from photoplethysmography (PPG) signals is an essential step to analyze vascular and hemodynamic information. Different morphologies of PPG waveforms from different measurement sites appear. Various phenomena of missing or ambiguous features exist, which limit subsequent signal processing. Methods: The reasons that cause missing or ambiguous features of finger and wrist PPG pulses are analyzed based on the concept of component waves from pulse decomposition. Then, a systematic approach for missing-feature imputation and ambiguous-feature resolution is proposed. Results: From the experimental results, with the imputation and ambiguity resolution technique, features from 35,036 (98.7%) of 35,502 finger PPG cycles and 36307 (99.1%) of 36,652 wrist PPG cycles can be successfully identified. The extracted features became more stable and the standard deviations of their distributions were reduced. Furthermore, significant correlations up to 0.92 were shown between the finger and wrist PPG waveforms regarding the positions and widths of the third to fifth component waves. Conclusion: The proposed missing-feature imputation and ambiguous-feature resolution solve the problems encountered during PPG feature extraction and expand the feature availability for further processing. More intrinsic properties of finger and wrist PPG are revealed. The coherence between the finger and wrist PPG waveforms enhances the applicability of the wrist PPG.
Understanding Continuance Intention Determinants to Adopt Online Health Care Community: An Empirical Study of Food Safety

The purpose of this research is to determine whether users’ social interaction tie and trust have a mediating effect on the willingness to use the online healthcare community (OHC) platform on an ongoing basis to respond to food safety crises and monitor food safety practices. During the three-month survey, we conducted an online investigation of users who had experience sharing on the OHC platform and were concerned about food safety. Thereby, three hundred and fifty-two valid questionnaires were received and partial least squares was adopted in this study to test the proposed hypotheses. The empirical results show that perceived critical mass, image, and para-social interaction strengthen the social interaction tie between users and the food safety platform. In addition, this study found that social interaction tie and trust of OHC platform users increased users’ willingness to continue using the OHC platform. This research provides OHC platform managers with an in-depth understanding of online social interactions on food safety pages. Moreover, the results of this study can help food business owners, government regulators, hospitals, and physicians to improve the way they use the Web for opinion-led food safety crises and provide insight into the intent of promoting the ongoing use of OHC platforms.
Procaryotic Diversity and Hydrogenotrophic Methanogenesis in an Alkaline Spring (La Crouen, New Caledonia)

(1) Background: The geothermal spring of La Crouen (New Caledonia) discharges warm (42 °C) alkaline water (pH~9) enriched in dissolved nitrogen with traces of methane, but its microbial diversity has not yet been studied. (2) Methods: Cultivation-dependent and -independent methods (e.g., Illumina sequencing and quantitative PCR based on 16S rRNA gene) were used to describe the prokaryotic diversity of this spring. (3) Results: Prokaryotes were mainly represented by Proteobacteria (57% on average), followed by Cyanobacteria, Chlorofexi, and Candidatus Gracilibacteria (GN02/BD1-5) (each > 5%). Both potential aerobes and anaerobes, as well as mesophilic and thermophilic microorganisms, were identified. Some of them had previously been detected in continental hyperalkaline springs found in serpentinizing environments (The Cedars, Samail, Voltri, and Zambales ophiolites). Gammaproteobacteria, Ca. Gracilibacteria and Thermotogae were significantly more abundant in spring water than in sediments. Potential chemolithotrophs mainly included beta- and gammaproteobacterial genera of sulfate-reducers (Ca. Desulfobacillus), methylotrophs (Methyloversatilis), sulfur-oxidizers (Thiofaba, Thiovirga), or hydrogen-oxidizers (Hydrogenophaga). Methanogens (Methanobacteriales and Methanosarcinales) were the dominant Archaea, as found in serpentinization-driven and deep subsurface ecosystems. A novel alkaliphilic hydrogenotrophic methanogen (strain CAN) belonging to the genus Methanobacterium was isolated, suggesting that hydrogenotrophic methanogenesis occurs at La Crouen.
Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) to identify novel prognostic biomarkers. The gene expression data of 19 m6A methylation regulators in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. We selected three significantly differentially expressed m6A regulators in LUAD to construct the risk signature, and evaluated its prognostic prediction efficiency using the receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of the risk signature. The ROC curve indicated that the area under the curve (AUC) was 0.659, which means that the risk signature had a good prediction efficiency. The results of the Kaplan–Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD. In addition, we explored the differential signaling pathways and cellular processes related to m6A methylation regulators in LUAD.
Use and experiences of galactagogues while breastfeeding among Australian women

Background Galactagogues are substances thought to increase breast milk production, however evidence to support their efficacy and safety remain limited. We undertook a survey among Australian women to examine patterns of use of galactagogues and perceptions regarding their safety and effectiveness. Methods An online, cross-sectional survey was distributed between September and December 2019 via national breastfeeding and preterm birth support organisations, and networks of several research institutions in Australia. Women were eligible to participate if they lived in Australia and were currently/previously breastfeeding. The survey included questions about galactagogue use (including duration and timing), side effects and perceived effectiveness (on a scale of 1 [Not at all effective] to 5 [Extremely effective]). Results Among 1876 respondents, 1120 (60%) reported using one or more galactagogues. Women were 31.5 ± 4.8 years (mean ± standard deviation) at their most recent birth. Sixty-five percent of women were currently breastfeeding at the time of the survey. The most commonly reported galactagogues included lactation cookies (47%), brewer’s yeast (32%), fenugreek (22%) and domperidone (19%). The mean duration of use for each galactagogue ranged from 2 to 20 weeks. Approximately 1 in 6 women reported commencing galactagogues within the first week postpartum. Most women reported receiving recommendations to use herbal/dietary galactagogues from the internet (38%) or friends (25%), whereas pharmaceutical galactagogues were most commonly prescribed by General Practitioners (72%). The perceived effectiveness varied greatly across galactagogues. Perceived effectiveness was highest for domperidone (mean rating of 3.3 compared with 2.0 to 3.0 among other galactagogues). Over 23% of domperidone users reported experiencing multiple side effects, compared to an average of 3% of women taking herbal galactagogues. Conclusions This survey demonstrates that galactagogues use is common in Australia. Further research is needed to generate robust evidence about galactagogues’ efficacy and safety to support evidence-based strategies and improve breastfeeding outcomes.
Biosensors Designed for Clinical Applications

Emerging and validated biomarkers promise to revolutionize clinical practice, shifting the emphasis away from the management of chronic disease towards prevention, early diagnosis and early intervention. The challenge of detecting these low abundance protein and nucleic acid biomarkers within the clinical context demands the development of highly sensitive, even single molecule, assays that are also capable of selectively measuring a small number of defined analytes in complex samples such as whole blood, interstitial fluid, saliva or urine. Success relies on significant innovations in nanomaterials, bioreceptor engineering, transduction strategies and microfluidics. Primarily using examples from our work, this article discusses some recent advance in the selective and sensitive detection of disease biomarkers, highlights key innovations in sensor materials and identifies issues and challenges that need to be carefully considered especially for researchers entering the field.