Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteogenic and Angiogenic Synergy of Human Adipose Stem Cells and Human Umbilical Vein Endothelial Cells Cocultured in a Modified Perfusion Bioreactor

ABSTRACT Synergistic promotion of angiogenesis and osteogenesis in bone tissue-engineered constructs remains a crucial clinical challenge, which might be overcome by simultaneous employment of superior techniques including coculture systems, differentiation-stimulated factors, combinatorial scaffolds and bioreactors. Current study investigated the effect of flow perfusion along with coculture of human adipose stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs) on osteogenic and angiogenic differentiation. Pre-treated hASCs with 1,25-dihydroxyvitamin D3 were seeded onto poly(lactic-co-glycolic acid)/β-tricalcium phosphate/polycaprolactone (PLGA/β-TCP/PCL) scaffold with/without HUVECs, and cultured for 14 days within a flask or modified perfusion bioreactor. Analysis of osteogenic and angiogenic gene expression, alkaline phosphatase (ALP) activity and ALP staining indicates a synergistic effect of perfusion flow and coculture system on osteogenic and angiogenic differentiation. The advantage of modified perfusion bioreactor is its five-branch flow distributor which directly connect to the porous PCL hollow fibers embedded in the 3D scaffold to improve flow and flow-induced shear stress uniformity. Dynamic coculture increased VEGF165 by 6-fold, VEGF189 by 2-fold, and Endothelin-1 by 4-fold, relative to dynamic monoculture. Static coculture enhanced osteogenic and angiogenic differentiation, compared with static monoculture. Although dynamic coculture is in preference to static coculture due to significant increase in ALP activity and promoted angiogenic marker expression. Our finding is the first to indicate that the modified perfusion bioreactor combined with the beneficial cell-cell crosstalk in pre-treated hASC/HUVEC cocultures provides a synergy between osteogenic and angiogenic differentiation of the accumulation of cells, suggesting that it represents a promising approach for regeneration of critical-sized bone defects.
A Histopathological Evaluation of Ovarian Hyperstimulation Syndrome on Reproductive and Vital Organs and the Role of the VEGF-PKA Pathway in a Mouse Model

Ovarian hyperstimulation syndrome (OHSS) is one of the most common and iatrogenic complications of in vitro fertilization therapy, which is an exaggerated response to excess hormones resulting in the development of a large number of maturing follicles. Although the complications of and reasons for the condition are well known, the overall histopathological effects on systemic organs and the extent of the damage have not been fully elucidated. Besides, the mechanism that underlies the situation is not very well known. The aim of the present work was to analyse the histopathological effects of OHSS on reproductive (uterus and ovary) and vital organs (liver and kidney) and the possible role of the VEGF-PKA pathway in triggering the condition. Balb/c mice were used to establish an OHSS model. The OHSS group were injected with overdose PMSG while the normal responder group were injected with an optimal dose. Histopathological evaluation was utilised in the liver, kidney, ovary, and uterus stained with hematoxylin and eosin, Masson’s trichrome, and periodic acid-Schiff stain. The expression profiles of VEGF (vascular endothelial growth factor), PKA (protein kinase A), and p-PKA (an activated form of PKA) were detected with immunohistochemistry and Western blotting. OHSS was demonstrated to have a negative histopathological effect on all of the organs analysed. These effects were associated with an overall increase in the expression levels of VEGF, PKA, and p-PKA. OHSS has a serious histopathological negative effect on the systemic and reproductive organs and is proven to affect overall health, and thus should be considered a dangerous complication during ART techniques. The activation of the VEGF-PKA pathway, which is indicated by the expression levels of VEGF, PKA, and p-PKA, is demonstrated to accompany this complication, which should be further elucidated to understand the mechanisms underlying the condition.
Effect of upper airway fat on tongue dilation during inspiration in awake people with obstructive sleep apnea.

STUDY OBJECTIVES To investigate the effect of upper airway fat composition on tongue inspiratory movement and obstructive sleep apnea (OSA). METHODS Participants without or with untreated OSA underwent a 3T magnetic resonance imaging (MRI) scan. Anatomical measurements were obtained from T2-weighted images. Mid-sagittal inspiratory tongue movements were imaged using tagged MRI during wakefulness. Tissue volumes and percentages of fat were quantified using an mDIXON scan. RESULTS 40 predominantly overweight participants with OSA were compared to 10 predominantly normal weight controls. After adjusting for age, BMI and gender, the percentage of fat in the tongue was not different between groups (ANCOVA, P=0.45), but apnoeic patients had a greater tongue volume (ANCOVA, P=0.025). After adjusting for age, BMI and gender, higher OSA severity was associated with larger whole tongue volume (r=0.51, P<0.001), and greater dilatory motion of the anterior horizontal tongue compartment (r=-0.33, P=0.023), but not with upper airway fat percentage. Higher tongue fat percentage was associated with higher BMI and older age (Spearman r=0.43, P=0.002, and r=0.44, P=0.001, respectively), but not with inspiratory tongue movements. Greater inspiratory tongue movement was associated with larger tongue volume (e.g. horizontal posterior compartment, r=-0.44, P=0.002) and smaller nasopharyngeal airway (e.g. oblique compartment, r=0.29, P=0.040). CONCLUSIONS Larger tongue volume and a smaller nasopharynx are associated with increased inspiratory tongue dilation during wakefulness in people with and without OSA. This compensatory response was not influenced by higher tongue fat content. Whether this is also true in more obese patient populations requires further investigation.
Rivaroxaban protects from the oxysterol-induced damage and inflammatory activation of the vascular endothelium

ABSTRACT Background Rivaroxaban is one of the direct factor Xa inhibitors. Its function in the inactivated coagulation cascade is unclear. The aim of the study was to assess the effect of rivaroxaban on the endothelial integrity and inflammatory properties of endothelial cells stimulated by 25-hydroxycholesterol (25-OHC). Methods HUVECs were stimulated with 25-OHC, rivaroxaban and 25-OHC+ rivaroxaban. HUVEC integrity and permeability were measured using the xCELLigence system and paracellular flux assay. The mRNA expression of tissue factor, ICAM-1, VEGF, IL-33, MCP-1, TNF-α was analyzed in the real-time PCR. Apoptosis and viability were measured by flow cytometry. The VEGF protein concentration was assessed by ELISA. The confocal microscope was used to evaluate the expression of VE-cadherin in endothelial cells. Results 25-OHC decreased endothelial cell integrity and increased the mRNA expression of IL-33, tissue factor, ICAM-1, MCP-1, VEGF, TNF-α as compared to unstimulated controls. Following the stimulation with rivaroxaban, HUVEC restored integrity disrupted by 25-OHC (p < .01). In HUVECs pre-stimulated with oxysterol, rivaroxaban decreased mRNA expression of IL-33, TNF-α, chemokines MCP-1, ICAM-1, VEGF and tissue factor (p < .01). Rivaroxaban 100 mg/ml+25-OHC increased the VE-cadherin expression in endothelium as compared to 25-OHC (p < .05). Conclusion Our finding suggests that rivaroxaban may restore the endothelial barrier and inhibit the inflammatory activation caused by oxysterol in vitro. Graphical abstract The effect of stimulation: 25-hydroksycholesterol (10µg/ml)+ rivaroxaban (100, 500ng/ml) on the barrier function and immune profile of human umbilical vascular endothelial cells (HUVECs)
Long non-coding RNA PTAR inhibits apoptosis but promotes proliferation, invasion and migration of cervical cancer cells by binding miR-101

ABSTRACT In this study, the expression of PTAR in cervical cancer tissues and cells was quantified by real-time PCR. Then, the roles of PTAR in HeLa cell proliferation and cell cycle were analyzed by a CCK-8 assay and flow cytometry, respectively.The effects of PTAR on cell migration and invasion were checked by Transwell and wound healing assays.The effect of PTAR on HeLa cell apoptosis was analyzed using annexin V/FITC staining. Finally, the interaction between PTAR and miR-101 in uterine cancer was verified through a dual-luciferase reporter assay and correlation analysis. The results showed that PTAR expression was aberrantly ascended in cervical cancer tissues and cell lines (Caski, SW756, SiHa, C33A and HeLa cells). Overexpressed PTAR could promote cell proliferation, migration and invasion in HeLa cells, which were suppressed by PTAR knockdown. Moreover, cell cycle progression stalled at the G1-G0 phase could be released with PTAR overexpression. The transfection of a PTAR vector inhibited apoptosis, while si-PTAR transfection increased apoptosis. Furthermore, PTAR could act as an endogenous sponge by directly binding to miR-101 and downregulating miR-101 expression. In conclusion, lncRNAPTAR plays a vital role and may be an effective target for the diagnosis and therapy of cervical cancer. Graphical abstract
Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: A retrospective observational study

Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea, but diagnosis can be challenging. The aim of this study was to investigate the clinical and biochemical features of FHA, compared to that of polycystic ovarian syndrome (PCOS) and assess the diagnostic performance of the different parameters for differentiating the two conditions.
Targeting Mycobacterium tuberculosis response to environmental cues for the development of effective antitubercular drugs

Sensing and response to environmental cues, such as pH and chloride (Cl−), is critical in enabling Mycobacterium tuberculosis (Mtb) colonization of its host. Utilizing a fluorescent reporter Mtb strain in a chemical screen, we have identified compounds that dysregulate Mtb response to high Cl− levels, with a subset of the hits also inhibiting Mtb growth in host macrophages. Structure–activity relationship studies on the hit compound “C6,” or 2-(4-((2-(ethylthio)pyrimidin-5-yl)methyl)piperazin-1-yl)benzo[d]oxazole, demonstrated a correlation between compound perturbation of Mtb Cl− response and inhibition of bacterial growth in macrophages. C6 accumulated in both bacterial and host cells, and inhibited Mtb growth in cholesterol media, but not in rich media. Subsequent examination of the Cl− response of Mtb revealed an intriguing link with bacterial growth in cholesterol, with increased transcription of several Cl−-responsive genes in the simultaneous presence of cholesterol and high external Cl− concentration, versus transcript levels observed during exposure to high external Cl− concentration alone. Strikingly, oral administration of C6 was able to inhibit Mtb growth in vivo in a C3HeB/FeJ murine infection model. Our work illustrates how Mtb response to environmental cues can intersect with its metabolism and be exploited in antitubercular drug discovery.
Be here now: Perceptions of uncertainty enhance savoring.

Savoring-an emotion-regulation strategy that involves deliberately upregulating positive affect-has many benefits, but what enhances savoring in the present moment? Drawing from life-history theory, affective and developmental science, and social-psychological frameworks, we examined the idea that perceptions of uncertainty--perceiving the world as random and unpredictable-enhance subsequent savoring. In a large experience-sampling study (Study 1, N = 6,680), we found that individuals who perceived more uncertainty showed increases in subsequent savoring in their daily lives. In a preregistered experiment (Study 2, N = 397), individuals who watched a film that induced uncertainty (vs. order or a control condition) subsequently reported higher savoring intentions. Finally, in a field experiment on a busy urban street (Study 3, N = 201), we found that passersby who received fliers that induced uncertainty (vs. order) subsequently engaged in more savoring behavior by stopping to smell a bouquet of roses. These findings from three studies with diverse samples and methodologies underscore an upside to the specter of uncertainty: it can cause people to savor the positives of the present. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Impact of clinical supervision on job satisfaction and emotional competence of nurses.

OBJECTIVE To evaluate the impact of implementing the SafeCare clinical supervision model on nurses' job satisfaction and emotional competence profile. METHODS This is a quasi-experimental study, with a sample of 28 nurses from a hospital in northern Portugal. A self-administered questionnaire was applied, used as pre and post-test, which included: sociodemographic and professional characterization; "Job Satisfaction Scale"; and "Veiga Emotional Competence Scale". We conducted descriptive statistical analysis and the Wilcoxon Test. RESULTS A significant decrease in the nurses' satisfaction with hierarchical superior was observed in the post-test. No significant differences were found in the nurses' job satisfaction and emotional competence after the implementation of the SafeCare Model. CONCLUSION The SafeCare Model needs improvement, suggesting increasing the amount of training time administered to nurses and strengthening the healthcare institution's link to the Model.
Acquired RAD51C Promoter Methylation Loss Causes PARP Inhibitor Resistance in High-Grade Serous Ovarian Carcinoma

Homozygous RAD51C methylation is a positive predictive biomarker for sensitivity to PARP inhibitors, whereas a single unmethylated gene copy is sufficient to confer resistance. In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene RAD51C are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. RAD51C promoter methylation (meRAD51C) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved. In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the RAD51C promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with RAD51C gene silencing and homologous recombination deficiency (HRD). PDX models lost meRAD51C following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of RAD51C was sufficient to drive PARPi resistance. Genomic copy number profiling of one of the PDX models using SNP arrays revealed that this resistance was acquired independently in two genetically distinct lineages. In a cohort of 12 patients with RAD51C-methylated HGSC, various patterns of meRAD51C were associated with genomic “scarring,” indicative of HRD history, but exhibited no clear correlations with clinical outcome. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain meRAD51C after six lines of therapy (four platinum-based), whereas another HGSC sample was found to have heterozygous meRAD51C and elevated RAD51C gene expression (relative to homozygous meRAD51C controls) after only neoadjuvant chemotherapy. As meRAD51C loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy. Significance: Homozygous RAD51C methylation is a positive predictive biomarker for sensitivity to PARP inhibitors, whereas a single unmethylated gene copy is sufficient to confer resistance.
Crocin exerts anti-proliferative and apoptotic effects on cutaneous squamous cell carcinoma via miR-320a/ATG2B

ABSTRACT Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent skin malignancy, and the effective therapy still remains a challenge. Crocin can be used for cSCC therapy. This study explored the effects of cSCC cells treatment with crocin in vitro and in vivo. The study used A431 and SCL-1 cells lines, cSCC human samples and BALB/C nude mice for investigations. Apoptosis was determined by MTT assays, while miR-320a and ATG2B expressions were validated through RT-qPCR. Interaction of miR-320a with ATG2B was examined via dual luciferase reporter assay. The autophagy and apoptosis proteins expressions were further confirmed through western blot and immunofluorescence staining assays. The results indicated a significantly upregulated miR-320a, but a down-regulated ATG2B expression in the cSCC clinical samples. Crocin significantly repressed cSCC cells growth, and induced apoptosis through autophagy. Furthermore, miR-320a expression was inhibited and ATG2B expression was increased. Dual luciferase reporter assay revealed that miR-320a regulated ATG2B expression directly. Additionally, the upregulation of ATG2B expression in cSCC cells inhibited cell proliferation and led to cell apoptosis. Crocin also reduced tumor growth and stimulated the apoptosis in vivo. In conclusion, miR-320a is upregulated and ATG2B is down-regulated in cSCC, Crocin suppresses the proliferation and induces apoptosis of cSCC cells. Further, Crocin increases autophagy while miR-320a hinders autophagy and the apoptotic effects of crocin on cSCC cells. MiR-320a binds ATG2B directly, and ATG2B expression is upregulated by crocin. Finally, Crocin triggers cSCC cells apoptosis in vivo. Crocin can target ATG2B/miR-320a and may be an effective alternative for cSCC treatment. GRAPHICAL ABSTRACT
Transperitoneal laparoscopic ureteropyeloplasty of retrocaval ureter: Single surgeon experience and review of literature

Retrocaval ureter (RCU) is a rare congenital abnormality, secondary to anomalous development of inferior vena cava (IVC) presenting as ipsilateral obstruction needing surgical intervention. The aim of this article is to present surgical techniques and outcome of transperitoneal laparoscopic ureteropyeloplasty in patients with RCU treated by a single surgeon at a tertiary care center and with review of literature.
Implicit learning of perceptual sequences is preserved in Parkinson's disease.

OBJECTIVE Various studies investigated implicit sequence learning in Parkinson's disease (PD) by means of the traditional motor Serial Reaction Time (SRT) task and found a general pattern of impaired sequence learning. However, as perceptual and motor sequences of the SRT-task were correlated in previous studies, implicit sequential knowledge acquisition that is tested independently from motor sequences remains to be determined in PD. In this study, we investigated implicit sequence learning independently from motor sequence learning in individuals with PD. To this end, we used a perceptual SRT-task that did not rely upon sequential motor knowledge. METHOD We measured response times (RTs) of 19 participants with PD (Hoehn & Yahr II or III; mean age 65) and 18 age-matched healthy controls (HC; mean age 61.5) in a perceptual SRT-task. General learning effects and sequence-specific learning effects were analyzed using repeated measures ANOVAs. RESULTS A significant decreasing linear trend (p < .001) in RTs was revealed in both the PD and HC groups as the SRT-task progressed, indicating general learning effects. Notably, a significant, strong main effect of sequence-specific learning occurred (p < .001), irrespective of group (p = .436). Sequence-specific learning did not differ significantly between the PD (M = 156.5 ms; SD = 50.7) and HC group (M = 173.0 ms; SD = 104.2). Bayesian analyses confirmed this as evidence of absence of an effect (B₁₀ = 3.543). CONCLUSIONS Our results suggest that, at least in Hoehn & Yahr stages II and III, implicit sequential knowledge acquisition may be preserved in individuals with PD, when tested independently from motor sequence learning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
SeqNet: An R Package for Generating Gene-Gene Networks and Simulating RNA-Seq Data

Gene expression data provide an abundant resource for inferring connections in gene regulatory networks. While methodologies developed for this task have shown success, a challenge remains in comparing the performance among methods. Gold-standard datasets are scarce and limited in use. And while tools for simulating expression data are available, they are not designed to resemble the data obtained from RNA-seq experiments. SeqNet is an R package that provides tools for generating a rich variety of gene network structures and simulating RNA-seq data from them. This produces in silico RNA-seq data for benchmarking and assessing gene network inference methods. The package is available on CRAN and on GitHub at https://github.com/tgrimes/SeqNet.
Policies and Interventions to Reduce Familial Mental Illness Stigma: A Scoping Review of Empirical Literature

Abstract Although research to date has shown that there can be no health or sustainable development without good mental health, mental illness continues to significantly impact societies. A major challenge confronting people with mental illnesses and their families is the stigma that they endure. In this study, empirical literature was reviewed to assess policies and interventions that seek to reduce familial mental illness stigma across four countries. We used Arksey and O’Malley methodological framework, and a qualitative content analysis was employed to augment the descriptive data extracted. Seven studies published between 2000 and 2020 were analyzed. We propose herein three themes that align with interventions to reduce familial mental illness stigma: transformative education, sharing and disclosure, and social networking and support. The findings indicate that persuasive and purposeful education directed at the public to correct misconceptions surrounding mental illness, with attention to language, may help in reducing familial mental illness stigma. Disclosure of mental illness is encouraged among persons with mental illnesses and their families as a strategy to enhance mutual understanding. Social sharing also affords persons with mental illnesses opportunities to engage with their peers at different levels within the public sphere. Apart from these recommendations, we have noted a paucity of broad governmental-level policies and interventions to comprehensively address the negative attitudes of families toward their relatives. Future work must address this gap to identify effective interventions to create healthier and supportive environments that address familial mental illness stigma.
Ovariectomy and high salt increase blood pressure and alter sodium transport proteins in peripheral blood mononuclear cells of adult Wistar rats

What is the central question of this study? In a model of salt‐sensitive hypertension in ovariectomized (oVx) adult Wistar rats, what is the expression of proteins related to sodium transport in peripheral blood mononuclear cells (PBMCs), and how does the response of proteins to high sodium intake compare with changes in blood pressure in intact female rats? What is the main finding and its importance? Sodium transport proteins in PBMCs react to high sodium and blood pressure markedly differently in oVx versus intact female rats. Protein expression shows sodium and pressure sensitivity. Renal immune cells increase in oVx under high salt.