Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust Estimation of Carbon Monoxide Measurements

This paper presents a robust analysis of carbon monoxide (CO) concentration measurements conducted at the Belisario air-quality monitoring station (Quito, Ecuador). For the analysis, the data collected from 1 January 2008 to 31 December 2019 were considered. Additionally, each of the twelve years analyzed was considered as a random variable, and robust location and scale estimators were used to estimate the central tendency and dispersion of the data. Furthermore, classic, nonparametric, bootstrap, and robust confidence intervals were used to group the variables into categories. Then, differences between categories were quantified using confidence intervals and it was shown that the trend of CO concentration at the Belisario station in the last twelve years is downward. The latter was proven with the precision provided by both nonparametric and robust statistical methods. The results of the research work robustly proved that the CO concentration at Belisario station in the last twelve years is not considered a health risk, according to the criteria established by the Quito Air Quality Index.
Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFβ-dependent Smad/YAP/TAZ signaling

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-β (TGFβ)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial–mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFβ through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFβ axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.
An analysis of the academic capacity of anaesthesia in the UK by publication trends and academic units

Over a decade ago, bibliometric analysis predicted the disappearance of UK publishing in anaesthesia by 2020. We repeated this analysis to assess if this had turned out to be the case, searching PubMed for papers associated with UK consultant anaesthetists for 2017–2019 across 15 journals. Although the rate of decline has flattened using the same search filter, including a wider range of publication types shows that outputs still remain at half 1990s levels (381 papers for all 3 years combined), authored by 769 anaesthetists, 274 of whom are associated with an academic centre. There are now 11 identifiable academic units, and a further 15 places where anaesthetists have affiliations with academic centres as individuals. The majority of papers (71%) are in secondary analysis (observational, database and association studies, surveys and meta‐analyses), rather than in primary research (clinical trials or laboratory studies). These data reflect the current academic capacity in terms of publications, academic units and staffing. We discuss how this information can be used to inform a new strategy for UK academic anaesthesia.
Psychosocial Moderators of the Impact of Diabetes Stigma: Results From the Second Diabetes MILES – Australia (MILES-2) Study

OBJECTIVE To examine the association of diabetes stigma with psychological, behavioral, and HbA1c outcomes and to investigate moderation effects of self-esteem, self-efficacy, and/or social support. RESEARCH DESIGN AND METHODS The national Second Diabetes MILES – Australia (MILES-2) survey included adults with type 1 diabetes (n = 959, 41% of whom were male, with mean ± SD age 44 ± 15 years), insulin-treated type 2 diabetes (n = 487, 60% male, age 61 ± 9 years), and non–insulin-treated type 2 diabetes (n = 642, 55% male, age 61 ± 10 years). (Un)adjusted linear regression analyses tested the association between diabetes stigma (Diabetes Stigma Assessment Scale [DSAS]) and psychological outcomes (depressive symptoms [eight-item version of the Patient Health Questionnaire (PHQ-8)], anxiety symptoms [Generalized Anxiety Disorder 7-item (GAD-7) questionnaire], and diabetes-specific distress [20-item Problem Areas In Diabetes (PAID) scale]), behavioral outcomes (healthy diet and physical activity [Summary of Diabetes Self-Care Activities (SDSCA)]), and self-reported HbA1c. Interaction effects tested whether associations varied by self-esteem (Rosenberg Self-Esteem Scale [RSES]), self-efficacy (Confidence in Diabetes Self-Care [CIDS] scale), or diabetes-specific social support (Diabetes Support Scale [DSS]). RESULTS Significant positive associations were observed between DSAS and PHQ-8, GAD-7, and PAID across diabetes type/treatment groups (all P < 0.001), whereby each SD increase in DSAS scores was associated with approximately one-half SD deterioration in emotional well-being. Associations between DSAS and SDSCA and HbA1c were nonmeaningful. Self-esteem moderated psychological outcomes among participants with type 1 and non–insulin-treated type 2 diabetes and diabetes distress among those with insulin-treated type 2 diabetes. Interaction effects were partially observed for social support but not for self-efficacy. CONCLUSIONS This study provides evidence of the association between diabetes stigma and depressive/anxiety symptoms and diabetes distress and for the moderating effects of self-esteem and social support among adults with type 1 and type 2 diabetes. Further research is needed to examine associations with objectively measured behavioral and clinical outcomes.
Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington’s Disease Patients and Healthy Control Subjects

Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington’s disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30–40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from n = 125 subjects, including n = 37 manifest HD patients, n = 36 premanifest patients, and n = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.
Ex vivo electroretinograms made easy: performing ERGs using 3D printed components

Rod and cone photoreceptors convert light into electrochemical signals that are transferred to second order cells, initiating image‐forming visual processing. Electroretinograms (ERGs) can detect the associated light‐induced extracellular transretinal events, allowing for physiological assessment of cellular activity from morphologically intact retinas. We outline a method for economically configuring a traditional patch‐clamp rig for performing high signal‐to‐noise ex vivo ERGs. We accomplish this by incorporating various 3D printed components and by modifying existing light pathways in a typical patch‐clamp rig. This methodology provides an additional set of tools to labs interested in studying the physiological function of neuronal populations in isolated retinal tissue.
Aberrant Methylation of LINE-1 Transposable Elements: A Search for Cancer Biomarkers

Cancer remains one of the main causes of human mortality despite significant progress in its diagnostics and therapy achieved in the past decade. Massive hypomethylation of retrotransposons, in particular LINE-1, is considered a hallmark of most malignant transformations as it results in the reactivation of retroelements and subsequent genomic instability. Accumulating data on LINE-1 aberrant methylation in different tumor types indicates its significant role in cancer initiation and progression. However, direct evidence that LINE-1 activation can be used as a cancer biomarker is still limited. The objective of this review was to critically evaluate the published results regarding the diagnostic/prognostic potential of the LINE-1 methylation status in cancer. Our analysis indicates that LINE-1 hypomethylation is a promising candidate biomarker of cancer development, which, however, needs validation in both clinical and laboratory studies to confirm its applicability to different cancer types and/or stages. As LINE-1 is present in multiple cell-free copies in blood, it has advantages over single-copy genes regarding perspectives of using its methylation status as an epigenetic cancer biomarker for cell-free DNA liquid biopsy.
Agents of change: Comparing HIV-related risk behavior of people attending ART clinics in Dar es Salaam with members of their social networks

The aim of the study is to compare sociodemographic characteristics, psychosocial factors, HIV knowledge and risk behaviors of people living with HIV (PLH) and their social network members (NMs) to inform HIV prevention programs that engage PLH as prevention educators in their communities. We compared baseline characteristics of PLH enrolled in an intervention to become HIV prevention Change Agents (CAs) (n = 458) and 602 NMs they recruited. CAs and NMs responded to questionnaires through a computer-driven interface with Audio Computer-Assisted Self Interview (ACASI) software. Although NMs scored higher on socio-economic status, self-esteem and general self-efficacy, they had lower HIV knowledge (AOR 1.5; 95% CI: 1.1–2.1), greater inconsistent condom use (AOR 3.2; 95% CI: 2.4–4.9), and recent experience as perpetrators of physical (AOR 2.5; 95% CI: 1.2–5.1) or sexual (AOR 4.1; 95% CI: 1.4–12.7) intimate partner violence; and as victims of physical (AOR 1.5; 95% CI: 1.0–2.3) or sexual (AOR 2.2; 95% CI: 1.3–3.8) forms of violence than CAs. Higher HIV knowledge and lower sexual risk behaviors among CAs suggest PLH’s potential as communicators of HIV prevention information to NMs. CAs’ training should also focus on improving self-esteem, general self-efficacy and social support to increase their potential effectiveness as HIV prevention educators and enhance their own overall health and well-being.
BDNF and nicotine dependence: associations and potential mechanisms

Abstract Smoking is the leading preventable cause of death worldwide and tobacco addiction has become a serious public health problem. Nicotine is the main addictive component of tobacco, and the majority of people that smoke regularly develop nicotine dependence. Nicotine addiction is deemed to be a chronic mental disorder. Although it is well known that nicotine binds to the nicotinic acetylcholine receptors (nAChRs) and activates the mesolimbic dopaminergic system (MDS) to generate the pleasant and rewarding effects, the molecular mechanisms of nicotine addiction are not fully understood. Brain-derived neurotrophic factor (BDNF) is the most prevalent growth factor in the brain, which regulates neuron survival, differentiation, and synaptic plasticity, mainly through binding to the high affinity receptor tyrosine kinase receptor B (TrkB). BDNF gene polymorphisms are associated with nicotine dependence and blood BDNF levels are altered in smokers. In this review, we discussed the effects of nicotine on BDNF expression in the brain and summarized the underlying signaling pathways, which further indicated BDNF as a key regulator in nicotine dependence. Further studies that aim to understand the neurobiological mechanism of BDNF in nicotine addcition would provide a valuable reference for quitting smoking and developing the treatment of other addictive substances.
Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment

During total joint replacement, high concentrations of mesenchymal stromal cells (MSCs) are released at the implantation site. They can be found in cell–tissue composites (CTC) that are regularly removed by surgical suction. A surgical vacuum suction handle was filled with bone substitute granules, acting as a filter allowing us to harvest CTC. The purpose of this study was to investigate the osteopromotive potential of CTC trapped in the bone substitute filter material during surgical suction. In the course of 10 elective total hip and knee replacement surgeries, β-tricalcium-phosphate (TCP) and cancellous allograft (Allo) were enriched with CTC by vacuum suction. Mononuclear cells (MNC) were isolated from the CTC and investigated towards cell proliferation and colony forming unit (CFU) formation. Furthermore, MSC surface markers, trilineage differentiation potential and the presence of defined cytokines were examined. Comparable amounts of MNC and CFUs were detected in both CTCs and characterized as MSC‰ of MNC with 9.8 ± 10.7‰ for the TCP and 12.8 ± 10.2‰ for the Allo (p = 0.550). CTCs in both filter materials contain cytokines for stimulation of cell proliferation and differentiation (EGF, PDGF-AA, angiogenin, osteopontin). CTC trapped in synthetic (TCP) and natural (Allo) bone substitute filters during surgical suction in the course of a joint replacement procedure include relevant numbers of MSCs and cytokines qualified for bone regeneration.
Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity

Purpose The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. Methods Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5–15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. Results After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. Conclusion In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention.
Clinical Significance of Timing of Intubation in Critically Ill Patients with COVID-19: A Multi-Center Retrospective Study

The effect of intubation timing on the prognosis of critically ill patients with coronavirus 2019 (COVID-19) is not yet well understood. We investigated whether early intubation is associated with the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS). This multicenter, retrospective, observational study was done on 47 adult COVID-19 patients with ARDS who were admitted to the intensive care unit (ICU) in Daegu, Korea between February 17 and April 23, 2020. Clinical characteristics and in-hospital mortality were compared between the early intubation and initially non-intubated groups, and between the early and late intubation groups, respectively. Of the 47 patients studied, 23 (48.9%) were intubated on the day of meeting ARDS criteria (early intubation), while 24 (51.1%) were not initially intubated. Eight patients were never intubated during the in-hospital course. Median follow-up duration was 46 days, and 21 patients (44.7%) died in the hospital. No significant difference in in-hospital mortality rate was noted between the early group and initially non-intubated groups (56.5% vs. 33.3%, p = 0.110). Furthermore, the risk of in-hospital death in the early intubation group was not significantly different compared to the initially non-intubated group on multivariate adjusted analysis (p = 0.385). Results were similar between early and late intubation in the subgroup analysis of 39 patients treated with mechanical ventilation. In conclusion, in this study of critically ill COVID-19 patients with ARDS, early intubation was not associated with improved survival. This result may help in the efficient allocation of limited medical resources, such as ventilators.
Allergic Inflammation Alters microRNA Expression Profile in Adipose Tissue in the Rat

Adipose tissue is a major source of circulating exosomal microRNAs (miRNAs) that are modulators of the immune response in various types of tissues and organs, including airways. Still, no evidence exists if allergic airway inflammation may affect fat tissue inflammation via alterations in the miRNA expression profile. Therefore, we investigated the miRNA expression profile in the adipose tissue upon induced allergic inflammation in the airways in the rat. Brown Norway rats were chronically sensitized to house dust mite extract for seven weeks. Body composition was performed using MiniSpec Plus. The eosinophil count and the total IgE level were determined to confirm the induction of allergic inflammation. MiRNA expression profiling was done using the next-generation sequencing with validation by qPCR. We found that allergic airway inflammation significantly increased fat in adipose tissue, glucose concentration, and the gene expression of adipose tissue-derived proinflammatory peptides (leptin, TNFα). In miRNA-seq analysis, we showed significant differences in the expression of 36 mature miRNAs, three precursors, and two miRNA families in adipose tissue of allergic rats. Two miRNAs—miRNA-151-5p and miRNA-423-3p—showed significantly increased expression in qPCR in adipose tissue and lungs of sensitized animals. Allergic airway inflammation affects fat tissue and alters miRNA expression profile in adipose tissue in the rat.
Cross-utilisation of template RNAs by alphavirus replicases

Most alphaviruses (family Togaviridae) including Sindbis virus (SINV) and other human pathogens, are transmitted by arthropods. The first open reading frame in their positive strand RNA genome encodes for the non-structural polyprotein, a precursor to four separate subunits of the replicase. The replicase interacts with cis-acting elements located near the intergenic region and at the ends of the viral RNA genome. A trans-replication assay was developed and used to analyse the template requirements for nine alphavirus replicases. Replicases of alphaviruses of the Semliki Forest virus complex were able to cross-utilize each other’s templates as well as those of outgroup alphaviruses. Templates of outgroup alphaviruses, including SINV and the mosquito-specific Eilat virus, were promiscuous; in contrast, their replicases displayed a limited capacity to use heterologous templates, especially in mosquito cells. The determinants important for efficient replication of template RNA were mapped to the 5' region of the genome. For SINV these include the extreme 5'- end of the genome and sequences corresponding to the first stem-loop structure in the 5' untranslated region. Mutations introduced in these elements drastically reduced infectivity of recombinant SINV genomes. The trans-replicase tools and approaches developed here can be instrumental in studying alphavirus recombination and evolution, but can also be applied to study other viruses such as picornaviruses, flaviviruses and coronaviruses.
Investigating HPV- and HPV Vaccine-Related Knowledge, Perceptions, and Information Sources among Health Care Providers in Three Big Cities in China

The limited access to vaccination and vaccine hesitancy are prevalent even among health care providers in less developed countries. This study assessed the relationships between (i) health care providers’ knowledge on human papillomavirus (HPV) and vaccination for HPV and (ii) their perceptions, demographic characteristics, and the use of information sources. In this large-scale online survey, participants (n = 1394) were recruited from hospitals of three big cities in China (Shanghai, Guangzhou, and Shenzhen). Descriptive analysis, the chi-square test, and logistic regression analysis were used to answer different research questions. Health care providers’ overall knowledge scores are consistent with their perceptions about HPV and HPV vaccine. Occupation, specialty, the type of hospitals, and the frequency of participants’ search for information using professional informational sources are the most significant characteristics that are closely associated with their knowledge of HPV and its vaccine. Targeted educational interventions are needed to improve health care providers’ engagement in the promotion of the HPV vaccine. Such interventions, besides increasing knowledge, should also emphasize the importance of appropriate information sources to acquire information.