Miracle-dz/UniFAR-FTUs huggingface dataset:
LncRNA RP11-499E18.1 Inhibits Proliferation, Migration, and Epithelial–Mesenchymal Transition Process of Ovarian Cancer Cells by Dissociating PAK2–SOX2 Interaction

Background: Ovarian cancer (OC)is a deadly gynecological malignancy worldwide. It is urgent to identify diagnostic biomarkers of OC to disclose the underlying mechanism. Methods and Materials: Bioinformatics analysis was used to identify target genes. Gene expression was detected and altered by qRT-PCR and cell transfection, respectively. The interaction between RP11-499E18.1 and PAK2, as well as that between PAK2 and SOX2, was determined using RNA pulldown, RNA immunoprecipitation (RIP), and co-immunoprecipitation (co-IP) assay, respectively. Localizations of RP11-499E18.1, PAK2, and SOX2 were respectively determined employing immunohistochemical (IHC), IF, and FISH. The regulatory effects of RP11-499E18.1, PAK2, and SOX2 on OC cell proliferation, migration, colony formation, epithelial–mesenchymal transition (EMT)-related factor expression, and SOX2 nuclear translocation were determined. Finally, the effects of RP11-499E18.1 and PAK2 expression on the tumor growth in nude mice were determined. Results: RP11-499E18.1, PAK2, and SOX2 were selected in our study. RP11-499E18.1 was downregulated, while PAK2 and SOX2 was upregulated in OC tissues and cells. RP11-499E18.1 coexists in the nucleus and cytoplasm of OC cells. There is an interaction between RP11-499E18.1 and PAK2, as well as PAK2 and SOX2 in OC cells. Alteration of RP11-499E18.1 and PAK2 expression both had no influence on PAK2 and SOX2 levels, but PAK2 upregulation notably augmented p-SOX2 level. RP11-499E18.1 overexpression suppressed OC cell proliferation, migration, and colony formation, as well as SOX2 nuclear translocation. Besides, it inhibited tumor growth in nude mice. However, these effects were notably reversed by PAK2 upregulation and eventually offset by SOX2 knockdown. Additionally, RP11-499E18.1 overexpression reduced PAK2–SOX2 interaction and SOX phosphorylation, and increased the binding of RP11-499E18.1 by PAK2. Conclusion: These lines of evidence demonstrated that RP11-499E18.1 might play its tumor suppressor roles in OC via regulation of the RP11-499E18.1–PAK2–SOX2 axis. This research indicated that RP11-499E18.1 might be used as a diagnostic biomarker for OC in the future.
Prognostic and Predicted Significance of FENDRR in Colon and Rectum Adenocarcinoma

Background The role of fetal-lethal non-coding developmental regulatory RNA (FENDRR) has been explored in various cancers; however, its relationship with colon adenocarcinoma/rectum adenocarcinoma (COAD/READ) remains unclear. The objectives of this study were to identify and assess any associations between FENDRR and COAD/READ using The Cancer Genome Atlas (TCGA) database and the Genetic Data Commons (GDC) Data Portal. Methods The records of patients with COAD/READ were collected from the GDC Data Portal. After comparing the expression level of FENDRR in COAD/READ and healthy tissues, we evaluated the association of FENDRR with clinicopathological characters and the survival rate, the impact of FENDRR on prognosis, the biological function of FENDRR, and the relative abundance of tumor-infiltrating immune cells in patients with COAD/READ. Moreover, we aimed to construct a protein-protein interaction (PPI) network for selecting genes and a ceRNA network for presenting mRNA-miRNA-lncRNA interactions. Results In patients with COAD/READ, FENDRR expression could differentiate tumor tissues from the adjacent healthy tissues since it was significantly lower in the former than in the latter. High FENDRR expression was correlated with poorer survival and higher tumor stage, current tumor stage, and metastasis stage, and also exhibited high scores for apoptosis, autophagy, and senescence. Immune cell infiltration analysis showed that the high expression group had significantly lower immune and stromal scores. Low FENDRR expression was correlated with poor overall survival (OS), and thus, it could serve as an independent risk factor. The prognostic models constructed in the study performed well for the prediction of OS and disease-specific survival (DFS) using FENDRR expression. Gene set enrichment analysis revealed that vascular smooth muscle contraction, melanogenesis, basal cell carcinoma, and Hedgehog signaling pathways were significantly enriched in patients with high FENDRR expression. Eight hub genes, namely, PKM, ALDOA, PFKP, ALDOC, PYGL, CTNNB1, PSMA5, and WNT5A, were selected from the PPI network, and a ceRNA network was constructed based on the differentially expressed mRNAs, miRNAs, and lncRNAs to illustrate their regulatory relationships. Conclusion FENDRR may serve as a potential biomarker for the diagnosis and prognosis of COAD/READ.
Chromosomal Differentiation of Deschampsia (Poaceae) Based on Four Satellite DNA Families

Diverse families of satellite DNA (satDNA) were detected in heterochromatin regions of Deschampsia. This kind of repetitive DNA consists of tandem repeat sequences forming big arrays in genomes, and can contribute to lineages differentiation. The differentiation between types of satDNA is related to their sequence identity, the size and number of monomers forming the array, and their chromosomal location. In this work, four families of satDNA (D2, D3, D12, D13), previously isolated by genomic analysis, were studied on chromosomal preparations of 12 species of Deschampsia (D. airiformis, D. antarctica, D. cespitosa, D. cordillerarum, D. elongata, D. kingii, D. laxa, D. mendocina, D. parvula, D. patula, D. venustula, and Deschampsia sp) and one of Deyeuxia (D. eminens). Despite the number of satDNA loci showing interspecific variation, the general distribution pattern of each satDNA family is maintained. The four satDNA families are AT-rich and associated with DAPI + heterochromatin regions. D2, D3, and D12 have mainly subterminal distribution, while D13 is distributed in intercalary regions. Such conservation of satDNA patterns suggests a not random distribution in genomes, where the variation between species is mainly associated with the array size and the loci number. The presence of satDNA in all species studied suggests a low genetic differentiation of sequences. On the other hand, the variation of the distribution pattern of satDNA has no clear association with phylogeny. This may be related to high differential amplification and contraction of sequences between lineages, as explained by the library model.
Development and Validation of a Gene Mutation-Associated Nomogram for Hepatocellular Carcinoma Patients From Four Countries

Background: Genomic alteration is the basis of occurrence and development of carcinoma. Specific gene mutation may be associated with the prognosis of hepatocellular carcinoma (HCC) patients without distant or lymphatic metastases. Hence, we developed a nomogram based on prognostic gene mutations that could predict the overall survival of HCC patients at early stage and provide reference for immunotherapy. Methods: HCC cohorts were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The total patient was randomly assigned to training and validation sets. Univariate and multivariate cox analysis were used to select significant variables for construction of nomogram. The support vector machine (SVM) and principal component analysis (PCA) were used to assess the distinguished effect of significant genes. Besides, the nomogram model was evaluated by concordance index, time-dependent receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA). Gene Set Enrichment Analysis (GSEA), CIBERSORT, Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS) were utilized to explore the potential mechanism of immune-related process and immunotherapy. Results: A total of 695 HCC patients were selected in the process including 495 training patients and 200 validation patients. Nomogram was constructed based on T stage, age, country, mutation status of DOCK2, EYS, MACF1 and TP53. The assessment showed the nomogram has good discrimination and high consistence between predicted and actual data. Furthermore, we found T cell exclusion was the potential mechanism of malignant progression in high-risk group. Meanwhile, low-risk group might be sensitive to immunotherapy and benefit from CTLA-4 blocker treatment. Conclusion: Our research established a nomogram based on mutant genes and clinical parameters, and revealed the underlying association between these risk factors and immune-related process.
Changes in B Cell Pool of Patients With Multibacillary Leprosy: Diminished Memory B Cell and Enhanced Mature B in Peripheral Blood

Despite being treatable, leprosy still represents a major public health problem, and many mechanisms that drive leprosy immunopathogenesis still need to be elucidated. B cells play important roles in immune defense, being classified in different subgroups that present distinct roles in the immune response. Here, the profile of B cell subpopulations in peripheral blood of patients with paucibacillary (TT/BT), multibacillary (LL/BL) and erythema nodosum leprosum was analyzed. B cell subpopulations (memory, transition, plasmablasts, and mature B cells) and levels of IgG were analyzed by flow cytometry and ELISA, respectively. It was observed that Mycobacterium leprae infection can alter the proportions of B cell subpopulations (increase of mature and decrease of memory B cells) in patients affected by leprosy. This modulation is associated with an increase in total IgG and the patient’s clinical condition. Circulating B cells may be acting in the modulation of the immune response in patients with various forms of leprosy, which may reflect the patient’s ability to respond to M. leprae.
An Overview of Ocean Climate Change Indicators: Sea Surface Temperature, Ocean Heat Content, Ocean pH, Dissolved Oxygen Concentration, Arctic Sea Ice Extent, Thickness and Volume, Sea Level and Strength of the AMOC (Atlantic Meridional Overturning Circulation)

Global ocean physical and chemical trends are reviewed and updated using seven key ocean climate change indicators: (i) Sea Surface Temperature, (ii) Ocean Heat Content, (iii) Ocean pH, (iv) Dissolved Oxygen concentration (v) Arctic Sea Ice extent, thickness, and volume (vi) Sea Level and (vii) the strength of the Atlantic Meridional Overturning Circulation (AMOC). The globally averaged ocean surface temperature shows a mean warming trend of 0.062 ± 0.013°C per decade over the last 120 years (1900–2019). During the last decade (2010–2019) the rate of ocean surface warming has accelerated to 0.280 ± 0.068°C per decade, 4.5 times higher than the long term mean. Ocean Heat Content in the upper 2,000 m shows a linear warming rate of 0.35 ± 0.08 Wm–2 in the period 1955–2019 (65 years). The warming rate during the last decade (2010–2019) is twice (0.70 ± 0.07 Wm–2) the warming rate of the long term record. Each of the last six decades have been warmer than the previous one. Global surface ocean pH has declined on average by approximately 0.1 pH units (from 8.2 to 8.1) since the industrial revolution (1770). By the end of this century (2100) ocean pH is projected to decline additionally by 0.1–0.4 pH units depending on the RCP (Representative Concentration Pathway) and SSP (Shared Socioeconomic Pathways) future scenario. The time of emergence of the pH climate change signal varies from 8 to 15 years for open ocean sites, and 16–41 years for coastal sites. Global dissolved oxygen levels have decreased by 4.8 petamoles or 2% in the last 5 decades, with profound impacts on local and basin scale habitats. Regional trends are varying due to multiple processes impacting dissolved oxygen: solubility change, respiration changes, ocean circulation changes and multidecadal variability. Arctic sea ice extent has been declining by −13.1% per decade in summer (September) and by −2.6% per decade in winter (March) during the last 4 decades (1979–2020). The combined trends of sea ice extent and sea ice thickness indicate that the volume of non-seasonal Arctic Sea Ice has decreased by 75% since 1979. Global mean sea level has increased in the period 1993–2019 (the altimetry era) at a mean rate of 3.15 ± 0.3 mm year–1 and is experiencing an acceleration of ∼ 0.084 (0.06–0.10) mm year–2. During the last century (1900–2015; 115y) global mean sea level (GMSL) has rised 19 cm, and near 40% of that GMSL rise has taken place since 1993 (22y). Independent proxies of the evolution of the Atlantic Meridional Overturning Circulation (AMOC) indicate that AMOC is at its weakest for several hundreds of years and has been slowing down during the last century. A final visual summary of key ocean climate change indicators during the recent decades is provided.
Psychological Inflexibility and Loneliness Mediate the Impact of Stress on Anxiety and Depression Symptoms in Healthcare Students and Early-Career Professionals During COVID-19

Background: The current mental health state of healthcare professionals and students during the COVID-19 pandemic in Ecuador remains understudied and how to improve their mental health is a challenge. Objective: This study aimed to explore the anxiety and depressive symptomatology among healthcare students and professionals in Ecuador and to examine the role of psychological inflexibility, loneliness, and psychological stress as predictors of anxiety and depression symptoms. Methods: A total of 191 undergraduate and graduate healthcare students in clinical practice (early-career healthcare professionals) in Ecuador were surveyed between January and March 2021 using standardized measures of psychological stress (PSS), psychological inflexibility (AAQ), loneliness (UCLA), alcohol consumption (AUDIT-C), and anxiety and depressive symptomatology (PHQ). Macro Process for SPSS (models 4 and 7) were used to test mediation effects. Results: Alcohol consumption varied between men and women and anxiety and depression symptomatology was generally low among the sample. Psychological inflexibility and loneliness mediated the impact of stress on anxiety and depressive mood in participants, regardless of gender and previous personal history of COVID-19. Discussion: Implications of psychological inflexibility and the prevention and coping with stress in healthcare professionals during COVID-19 are further discussed.
Human Three-Finger Protein Lypd6 Is a Negative Modulator of the Cholinergic System in the Brain

Lypd6 is a GPI-tethered protein from the Ly-6/uPAR family expressed in the brain. Lypd6 enhances the Wnt/β-catenin signaling, although its action on nicotinic acetylcholine receptors (nAChRs) have been also proposed. To investigate a cholinergic activity of Lypd6, we studied a recombinant water-soluble variant of the human protein (ws-Lypd6) containing isolated “three-finger” LU-domain. Experiments at different nAChR subtypes expressed in Xenopus oocytes revealed the negative allosteric modulatory activity of ws-Lypd6. Ws-Lypd6 inhibited ACh-evoked currents at α3β4- and α7-nAChRs with IC50 of ∼35 and 10 μM, respectively, and the maximal amplitude of inhibition of 30–50%. EC50 of ACh at α3β4-nAChRs (∼30 μM) was not changed in the presence of 35 μM ws-Lypd6, while the maximal amplitude of ACh-evoked current was reduced by ∼20%. Ws-Lypd6 did not elicit currents through nAChRs in the absence of ACh. Application of 1 μM ws-Lypd6 significantly inhibited (up to ∼28%) choline-evoked current at α7-nAChRs in rat hippocampal slices. Similar to snake neurotoxin α-bungarotoxin, ws-Lypd6 suppressed the long-term potentiation (LTP) in mouse hippocampal slices. Colocalization of endogenous GPI-tethered Lypd6 with α3β4- and α7-nAChRs was detected in primary cortical and hippocampal neurons. Ws-Lypd6 interaction with the extracellular domain of α7-nAChR was modeled using the ensemble protein-protein docking protocol. The interaction of all three Lypd6 loops (“fingers”) with the entrance to the orthosteric ligand-binding site and the loop C of the primary receptor subunit was predicted. The results obtained allow us to consider Lypd6 as the endogenous negative modulator involved in the regulation of the cholinergic system in the brain.
Combination Immunotherapy Use and Withdrawal in Pediatric Inflammatory Bowel Disease—A Review of the Evidence

Evidence-based guidelines have been developed outlining the concomitant use of anti-tumor necrosis factor alpha (anti-TNF) agents and immunomodulators including azathioprine (AZA) and methotrexate (MTX) in both adult and pediatric populations. However, there exists a paucity of data guiding evidence-based strategies for their withdrawal in pediatric patients in sustained remission. This narrative review focuses on the available pediatric evidence on this question in the context of what is known from the larger body of evidence available from adult studies. The objective is to provide clarity and practical guidance around who, what, when, and how to step down pediatric patients with inflammatory bowel disease (IBD) from combination immunotherapy. Outcomes following withdrawal of either of the two most commonly used anti-TNF therapies [infliximab (IFX) or adalimumab (ADA)], or immunomodulator therapies, from a combination regimen are examined. Essentially, a judicious approach must be taken to identify a significant minority of patients who would benefit from treatment rationalization. We conclude that step-down to anti-TNF (rather than immunomodulator) monotherapy after at least 6 months of sustained clinical remission is a viable option for a select group of pediatric patients. This group includes those with good indicators of mucosal healing, low or undetectable anti-TNF trough levels, lack of predictors for severe disease, and no prior escalation of anti-TNF therapy. Transmural healing and specific human leukocyte antigen (HLA) typing are some of the emerging targets and tools that may help facilitate improved outcomes in this process. We also propose a simplified evidence-based schema that may assist in this decision-making process. Further pediatric clinical studies are required to develop the evidence base for decision-making in this area.
Addressing Workforce Disparities by Improving the Academic Resilience and Professionalism of Health Science Students Through Structured and Targeted Supports

Background: The undergraduate program in Public Health of Saint Catherine University is the second most popular major of the institution, drawing students from diverse racial, economic, cultural, and educational backgrounds. This has presented significant opportunities and challenges with regard to providing students and faculty with the needed academic and professional development to ensure graduates embody the skills needed for Public Health workforce of today. The objective of this study was to identify potential structured institutional supports to graduate Public Health professionals from diverse communities to advance health equity. A secondary objective was to determine whether the needed supports for Public Health students might differ from peers in other health programs, specifically Nursing. Methods: Using a mixed methods approach and a convenience sample, data were gathered from Public Health students, nursing students, faculty, and staff from November 2019 through July 2020. The survey assessed stress, grit, and demographic factors. Focus group topics included: academic resilience and professionalism, supports and gaps in the current institutional structure with respect to mitigating student stressors, and opportunities for programmatic solutions. Results: In total, 53 Public Health and 32 in Nursing students completed the survey. Nursing students tended to be farther along in their undergraduate careers, less likely to have failed a class, and more likely to have recently been laid off from a job. Public Health students reported more support from parents, but less support from friends and classmates than their Nursing peers. Most Nursing and Public Health students reported unmanaged stress, and similar average grit scores (3.51 vs. 3.41, p = 0.43), respectively. In focus groups, students described a series of stressors including working full time while attending school, family expectations, difficulty with time management, and learning how to acclimate to college norms. University staff and faculty identified financial pressures as a primary student stressor in addition to complex lives including managing family crises. Conclusions: Study findings are being used to identify or adapt professional development supports in undergraduate Public Health programs. Through supporting a diverse undergraduate student population in Public Health, a future workforce from communities most impacted by health disparities will emerge.
Unraveling the Hidden Diversity of the Native White Claw Crayfish in the Iberian Peninsula

Several European freshwater crayfish species are currently included in one of the IUCN Red list categories. In the Iberian Peninsula, the native Austropotamobius pallipes species complex (the white clawed crayfish, WCC) has experienced a drastic decline since 1973. Implementing conservation management strategies for this species requires a better understanding of the patterns and structure of its genetic diversity. In this study, we assessed the levels and patterns of genetic variation in 71 populations along the whole distributional range of the WCC in the Iberian Peninsula. The two mitochondrial markers analyzed (Cytochrome Oxidase subunit I and 16S rRNA genes) indicated high levels of genetic diversity, which are significantly geographically structured in three main genetic groups, two corresponding to Northern and one to Central-Eastern and the westernmost Iberian Peninsula. The diversity found included new private haplotypes, and revealed the potential effect of paleogeographic barriers and last glaciations in the population structure observed. Current conservation and management programs for the WCC in the Iberian Peninsula should consider these three phylogeographic groups as essential management units in order to preserve the remaining genetic diversity in the species.
Assessment of the Perception of People Living With HIV Regarding the Quality of Outpatient Care at a Reference Facility in the Federal District, Brazil

The effectiveness of antiretroviral treatment has transformed HIV infection into a chronic transmissible condition, requiring health systems to adapt in order to care for people living with HIV. The Chronic Care Model (CCM) is the gold standard for this type of care in many countries. Among its tools, the Patient Assessment of Chronic Illness Care (PACIC) questionnaire gives the patient’s perspective of the care provided. The aim of the present study was to adapt and apply, for the first time, the questionnaire to people living with HIV to determine their perception of the quality of care provided at a reference hospital in the Federal District of Brazil. This is a case study conducted in 2019 at a teaching hospital, with a convenience sample of 30 individuals treated for at least 1 year at the facility. The median PACIC score (3.5 with a range of 1.0–5.0) seems to suggest that the users perceive the outpatient care provided by the hospital as being basic. The “delivery system design/decision support” component was deemed the best (5.0, with a range of 1.0–5.0) and “follow-up/coordination” the worst (1.0, with a range of 1.0–5.0). The results suggest the need to improve the organization of care and make adequate use of community resources, in line with the CCM. The questionnaire makes it possible to determine the strengths and weaknesses of the care provided to people living with HIV and can be used as a planning and monitoring tool to improve management of the condition, with the contribution of the patient, in particular, thereby strengthening self-care.