Miracle-dz/UniFAR-FTUs huggingface dataset:
All-trans retinoic acid in anticancer therapy: how nanotechnology can enhance its efficacy and resolve its drawbacks

ABSTRACT Introduction: All-trans retinoic acid (ATRA, tretinoin) is the main drug used in the treatment of acute promyelocytic leukemia (APL). Despite its impressive activity against APL, the same could not be clinically observed in other types of cancer. Nanotechnology can be a tool to enhance ATRA anticancer efficacy and resolve its drawbacks in APL as well as in other malignancies. Areas covered: This review covers ATRA use in APL and non-APL cancers, the problems that were found in ATRA therapy and how nanoencapsulation can aid to circumvent them. Pre-clinical results obtained with nanoencapsulated ATRA are shown as well as the two ATRA products based on nanotechnology that were clinically tested: ATRA-IV® and Apealea®. Expert opinion: ATRA presents interesting properties to be used in anticancer therapy with a notorious differentiation and antimetastatic activity. Bioavailability and resistance limitations impair the use of ATRA in non-APL cancers. Nanotechnology can circumvent these issues and provide tools to enhance its anticancer activities, such as co-loading of multiple drug and active targeting to tumor site.
Performance assessment of SD Bioline TB MPT64 assay for the diagnosis of Mycobacterium tuberculosis complex in Lagos, Nigeria

ABSTRACT This study assessed the performance of SD Bioline MPT64 immunochromatographic test for the identification of Mycobacterium tuberculosis complex (MTBC) in Nigeria. A total of 157 mycobacterial isolates, comprising 120 (76.4%) MTBC (M. tuberculosis, 112; M. africanum, 5; M. bovis, 3) and 37 (23.6%) non-tuberculous mycobacteria (NTM) isolates from patients attending six DOTS centers in Lagos between June 2012 and July 2014 were analyzed. All the isolates were grown on Bactec MGIT960 liquid media and identified in parallel by the conventional method and MPT64 immunochromatographic test. Discrepant results were resolved using the line probe assay. The comorbid disease rates for HIV and type 2 diabetes were 20.9% and 8.2%, respectively. Compared to the conventional method, SD Bioline MPT64 identified 117 MTBC isolates correctly, producing a sensitivity of 97.5% (95% CI, 92.9–99.2) at a shorter growing median time of 11 days compared to 26 days by the conventional method. The three undetected MTBC were confirmed by the line probe assay to be M. tuberculosis strains. The test also identified all the NTM correctly producing a specificity of 100% (95% CI, 90.7–100). This study supports the integration of SD Bioline TB MPT64 antigen test into diagnostic workflow for rapid MTBC case identification in Nigeria.
Age and gender differences in the prevalence of chronic diseases and atherosclerotic cardiovascular disease risk scores in adults in Riyadh city, Saudi Arabia

Objectives: To evaluate age and gender differences in the prevalence of chronic diseases and to calculate atherosclerotic cardiovascular disease (ASCVD) risk scores in adults aged 30-75 years in Riyadh city, Saudi Arabia. Methods: This cross-sectional, interview-based study was conducted with 2997 men and women, visiting primary health care centers in Riyadh, during the years 2015 to 2016. Serum glycosylated hemoglobin and lipid levels were measured by ion-exchange high-performance liquid chromatography and fully automated analyzer using enzymatic methods, respectively. The 10-year and lifetime ASCVD risk scores were calculated using an online calculator. Results: The mean age of men was 43.1 (±11.7) and women was 43.8 (± 10.9) years. Prevalence rates of diabetes mellitus, hypertension, hypercholesterolemia, and obesity in men versus women were 20.3% versus 24.8% (p=0.006), 15% versus 19.5% (p=0.003), 50.7% versus 53.4% (p=0.16), and 41.2% versus 56.7% (p<0.001), respectively. Majority of men and women with chronic diseases belonged to the age groups 30-39 and 50-59 years, respectively. High 10-year ASCVD risk was found in 32% men and 7.6% women, whereas lifetime risk was present in 67% and 51%, respectively. Conclusion: Women in the age group 50-59 years, with multiple risk factors are at a greater risk of developing cardiovascular diseases than men of same age. Young adults were at more risk for lifetime ASCVD, whereas the 10-year ASCVD risk increased with increasing age.
Multilevel Pathways of Colorectal Cancer Screening Among Low-Income Vietnamese Americans: A Structural Equation Modeling Analysis

Background: Colorectal cancer (CRC) disproportionately affects Vietnamese Americans, especially those with low income and were born outside of the United States. CRC screening tests are crucial for prevention and early detection. Despite the availability of noninvasive, simple-to-conduct tests, CRC screening rates in Asian Americans, particularly Vietnamese Americans, remain suboptimal. The purpose of this study was to evaluate the interplay of multilevel factors – individual, interpersonal, and community – on CRC screening behaviors among low-income Vietnamese Americans with limited English proficiency. Methods: This study is based on the Sociocultural Health Behavior Model, a research-based model that incorporates 6 factors associated with decision-making and health-seeking behaviors that result in health care utilization. Using a community-based participatory research approach, we recruited 801 Vietnamese Americans from community-based organizations. We administered a survey to collect information on sociodemographic characteristics, health-related factors, and CRC screening-related factors. We used structural equation modeling (SEM) to identify direct and indirect predictors of lifetime CRC screening. Results: Bivariate analysis revealed that a greater number of respondents who never screened for CRC reported limited English proficiency, fewer years of US residency, and lower self-efficacy related to CRC screening. The SEM model identified self-efficacy (coefficient = 0.092, P < .01) as the only direct predictor of lifetime CRC screening. Educational attainment (coefficient = 0.13, P < .01) and health beliefs (coefficient = 0.040, P < .001) had a modest significant positive relationship with self-efficacy. Health beliefs (coefficient = 0.13, P < .001) and educational attainment (coefficient = 0.16, P < .01) had significant positive relationships with CRC knowledge. Conclusions: To increase CRC screening uptake in medically underserved Vietnamese American populations, public health interventions should aim to increase community members’ confidence in their abilities to screen for CRC and to navigate associated processes, including screening preparation, discussions with doctors, and emotional complications.
Lateralized Periodic Discharges During Remifentanil Infusion

Lateralized periodic discharges (LPDs) are a common electroencephalographic (EEG) pattern in the neurointensive care unit setting. LPDs are typically observed in association with acute structural lesions of the brain with different etiologies. There are no reports describing a link between the occurrence of LPDs and the administration of remifentanil. Remifentanil is a rapid-acting pure μ-opioid receptor agonist, which is indicated to provide analgesia and sedation in mechanically ventilated patients in intensive care units. We present a case of an 84-year-old man with neuroglycopenia who developed LPDs while sedated with remifentanil. We report, for the first time, a potential relationship between remifentanil and the induction of LPDs.
Prevalence of the anatomical variations of concha bullosa and its relation with sinusitis among Saudi population: a computed tomography scan study

Concha bullosa (CB) is a pneumatic cavitation inside a concha in the nasal cavity. It is one of the most widely recognized nasal variations and is mostly found in the middle concha. CB is divided according to its site into three types; lamellar, bulbous and extensive. The goal of our study was to estimate the prevalence of CB among Saudi adult population and its association with sinusitis by using multidetector computed tomography (MDCT). This was a retrospective study carried out over a three-year period on 879 adult Saudi patients aged 18 years or older, referred for MDCT assessment of paranasal sinuses. Males were 540 and females were 339. Patients with facial congenital anomalies or nasal trauma were excluded from our study. CB was prevalent in both males and females among Saudi population (55.4%, 55.7%) respectively. Bilateral CB (55.5%) was more frequent than unilateral (44.5%). Extensive CB (44.0%) was the most frequent type. Sinusitis was associated more in patients with CB (48.0%) versus those who have no CB (5.9%). In conclusion, CB was prevalent among Saudi population and the most frequently recorded is the extensive type. Furthermore, the most common type associated with sinusitis was extensive CB (49.6%).
N-syndecan: structure and function of a transmembrane heparan sulfate proteoglycan.

: N-syndecan is a member of the syndecan family of transmembrane heparan sulfate proteoglycans that was cloned initially from neonatal rat Schwann cells and is the principal syndecan expressed during early postnatal development in the central and peripheral nervous systems. Purified N-syndecan binds in vitro with high affinity to several extracellular regulatory ligands, including basic fibroblast growth factor, the secreted adhesive protein heparin binding growth-associated molecule, and a novel collagen-like protein secreted by Schwann cells. These extracellular ligands utilize the heparan sulfate chains of N-syndecan for binding. Based on the striking amino acid sequence homology of the cytoplasmic domain of N-syndecan to syndecan-1, it is proposed that N-syndecan associates with the actin-based cytoskeleton. N-syndecan core proteins self associate by means of an unusual dimerization motif comprised of the transmembrane domain and a short flanking sequence in the ectodomain. Similar to other single transmembrane domain receptor proteins, it is suggested that ligand-regulated dimerization of N-syndecan represents a mechanism for regulating downstream signaling activities. In rat brain tissue a significant fraction of the N-syndecan molecules are present in a soluble form, presumably as a result of proteolytic membrane shedding. A model is presented for morphoregulatory activity of N-syndecan in which extracellular ligand-induced clustering of N-syndecan molecules on the cell surface promotes cytoskeletal association and reorganization. Membrane shedding separates the functional domains of the proteoglycan and terminates this activity.
Efficacy of modified coronally advanced flap in the treatment of multiple adjacent gingival recessions: a systematic review and meta-analysis

Abstract Objective This systematic review (SR) aims to evaluate the efficacy of modified coronally advanced flap (mCAF) on clinical and patient-reported outcomes in the treatment of multiple adjacent gingival recessions (MAGRs). Materials and methods Randomized controlled trials (RCTs), case-series and prospective clinical studies on treatment of Miller class I/II or RT1 MAGRs with ≥ 6 months follow-up were identified from the electronic databases and hand-searched journals. Complete root coverage (CRC) was the primary outcome variable. To evaluate treatment effects, meta-analysis was conducted, wherever appropriate. Results A total of 1395 recessions in 408 patients were evaluated in SR and meta-analysis was performed for four RCTs. Overall CRC achieved with mCAF was 70% and mean root coverage (MRC) ranged from 51.58 to 97.27%. Meta-analysis showed that combination of mCAF with connective tissue graft (CTG) or collagen matrix (CM) demonstrated significantly higher CRC% and recession reduction than mCAF alone. Limited evidence is available to support the use of platelet rich fibrin or enamel matrix derivative or acellular dermal matrix graft along with mCAF to further enhance its efficacy. Conclusions mCAF is an effective procedure for treating MAGRs and in terms of achieving CRC and MRC. Additional use of CTG or CM further enhances treatment outcomes.
Robustness of single-isocenter multiple-metastasis stereotactic radiosurgery end-to-end testing across institutions

The accuracy of stereotactic radiosurgery (SRS) to multiple metastases with a single-isocenter using high definition dynamic radiosurgery (HDRS) was evaluated across institutions. An SRS plan was delivered at six HDRS-capable institutions to an anthropomorphic phantom consisting of point, film, and 3D-gel dosimeters. Direct dose comparison and gamma analysis were used to evaluate the accuracy. Point measurements averaged across institutions were within 1.2±0.5%. The average gamma passing rate in the film was 96.6±2.2% (3%/2 mm). For targets within 4 cm of the isocenter, the 3D dosimetric gel gamma passing rate averaged across institutions was >90% (3%/2 mm). The targeting accuracy of high definition dynamic radiosurgery assessed by geometrical offset of the center of dose distributions across multiple institutions in this study was within 1 mm for targets within 4 cm of isocenter. Across variations in clinical practice, comparable dosimetry and localization is possible with this treatment planning and delivery technique.
Determinants of mortality of patients with COVID-19 in Wuhan, China: a case-control study.

BACKGROUND Coronavirus disease 2019 (COVID-19) has resulted in an overwhelmed challenge to the healthcare system worldwide. METHODS A case-control study of COVID-19 patients in Wuhan Third Hospital was conducted. 96 deceased COVID-19 patients and 230 discharged patients were included as the case group and control group, respectively. Demographic, epidemiological, clinical and laboratory variables on admission were collected from electronic medical records. Univariate and multivariate logistic regression were adopted to investigate the independent predictors of mortality. A nomogram was formed for predicting the mortality risk. RESULTS The multivariate stepwise logistic model demonstrated that age of 60+ years (OR =4.426, 95% CI: 1.955-10.019), comorbidity of cerebrovascular disease (OR =7.084, 95% CI: 1.545-32.471), white blood cell (WBC) count >9.5×109 /L (OR =7.308, 95% CI: 1.650-32.358), platelet count <125×109/L (OR =5.128, 95% CI: 2.157-12.191), aspartate aminotransferase (AST) >40 U/L (OR =2.554, 95% CI: 1.253-5.206), cystatin C >1.1 mg/L (OR =4.132, 95% CI: 2.118-8.059), C reactive protein (CRP) ≥100 mg/L (OR =2.830, 95% CI: 1.311-6.109), creatine kinase isoenzymes (CK-MB) >24 U/L (OR =6.015, 95% CI: 2.119-17.07) and D-dimer >5 μg/L (OR =4.917, 95% CI: 1.619-14.933) were independent predictors of mortality of COVID-19 patients. The nomogram demonstrated a well discriminatory accuracy for mortality prediction with a C-index of 0.903. CONCLUSIONS The determinants identified may help to determine patients at high risk of death at an early stage and guide the optimal treatment.
Hindsight bias in metamemory: outcome knowledge influences the recollection of judgments of learning

ABSTRACT Hindsight bias describes people’s tendency to overestimate how accurately they have predicted an event’s outcome after obtaining knowledge about it. Outcome knowledge has been shown to influence various forms of judgments, but it is unclear whether outcome knowledge also produces a hindsight bias on Judgments of Learning (JOLs). Three experiments tested whether people overestimated the accuracy of their memory predictions after obtaining knowledge about their actual memory performance. In all experiments, participants studied 60 cue-target word pairs, made a JOL for each word pair, and tried to recall the targets in a cued-recall test. In Experiments 1a and 1b, people recollected their original JOLs after attempting to recall each target, that is, after they obtained outcome knowledge for all items. In Experiments 2 and 3, people recollected their original JOLs in a separate phase after attempting to recall half the targets so that they had outcome knowledge for some but not all items. In all experiments, recollected JOLs were closer to actual memory performance than original JOLs for items with outcome knowledge only. Thus, outcome knowledge produced a hindsight bias on JOLs. Our results demonstrate that people overestimate the accuracy of their memory predictions in hindsight.
Clinical characteristics and outcomes of infective endocarditis: impact of haemodialysis status, especially vascular access infection on short-term mortality

Abstract Background Patients on haemodialysis (HD) are at high risk of infective endocarditis (IE). Research comparing the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE is limited. Specifically, no data focussed on vascular access infections (VAIs) have been reported. Methods The medical records of patients with IE were retrospectively reviewed from January 2010 to February 2020 in a referral hospital in Korea. Those with definite or possible IE by modified Duke criteria were included in the study. The clinical characteristics, microbiological features, echocardiographic findings and outcomes of the patients were analysed. Results Of the 80 patients with IE, 34 had undergone HD and 46 had not. HD patients with IE had a higher in-hospital mortality rate (50% vs. 17.4%, p = .004) than non-HD patients. In multivariable stepwise Cox proportional hazards regression analysis, HD (hazard ratio = 2.633; 95% confidential interval: 1.053–6.582; p = .038) was predictors of 60-day mortality in IE patients. In HD patients, the presence of VAI was associated with a high in-hospital mortality rate (70.59% vs. 29.41%, p = .039) and all of the patients with VAIs (100%) had methicillin-resistant S. aureus (MRSA) as a causative pathogen. Conclusions HD patients with IE showed high in-hospital mortality. HD, high C-reactive protein levels and lower left ventricular ejection fraction were predictors of 60-day mortality in IE patients. In particular, HD patients with VAIs had higher mortality rates and MRSA should be considered as the causative microorganism.
“This Life is Normal for Me”: A Study of Everyday Life Experiences and Coping Strategies of Live-in Carers in Taiwan

ABSTRACT Recruiting migrant live-in carers has become the main strategy to address the rapid increase in the number of older persons with intensive care needs in many parts of the developed world. This is also the case in northern Taiwan, where this study took place. Thirteen live-in carers from Indonesia and the Philippines were interviewed in the fall of 2019. In this article, we discuss their two main coping strategies: a) “accepting destiny”, which refers to carers accepting their life and viewing their role as a live-in carer as a job that allowed them to meet their parents’ expectations of financial support; and b) “connecting to significant others”, which is the most important way carers found motivation to keep going. However, despite their coping strategies, working as a live-in carer was experienced as a challenging and precarious lifestyle. In the conclusion, we discuss how professional social workers in collaboration with decision-makers and non-governmental organizations in Taiwan could contribute to fostering a system that would support live-in carers in ways that allow them, and the older persons they care for, to thrive.
Importance of WNT-dependent signaling for derivation and maintenance of primed pluripotent bovine embryonic stem cells†

Abstract The WNT signaling system plays an important but paradoxical role in the regulation of pluripotency. In the cow, IWR-1, which inhibits canonical WNT activation and has WNT-independent actions, promotes the derivation of primed pluripotent embryonic stem cells from the blastocyst. Here, we describe a series of experiments to determine whether derivation of embryonic stem cells could be generated by replacing IWR-1 with other inhibitors of WNT signaling. Results confirm the importance of inhibition of canonical WNT signaling for the establishment of pluripotent embryonic stem cells in cattle and indicate that the actions of IWR-1 can be mimicked by the WNT secretion inhibitor IWP2 but not by the tankyrase inhibitor XAV939 or WNT inhibitory protein dickkopf 1. The role of Janus kinase-mediated signaling pathways for the maintenance of pluripotency of embryonic stem cells was also evaluated. Maintenance of pluripotency of embryonic stem cells lines was blocked by a broad inhibitor of Janus kinase, even though the cells did not express phosphorylated signal transducer and activator of transcription 3 (pSTAT3). Further studies with blastocysts indicated that IWR-1 blocks the activation of pSTAT3. A likely explanation is that IWR-1 blocks differentiation of embryonic stem cells into a pSTAT3+ lineage. In conclusion, results presented here indicate the importance of inhibition of WNT signaling for the derivation of pluripotent bovine embryonic stem cells, the role of Janus kinase signaling for maintenance of pluripotency, and the participation of IWR-1 in the inhibition of activation of STAT3. Summary sentence Derivation of pluripotent embryonic stem cells from bovine blastocysts depends upon blocking WNT signaling; maintenance of pluripotency depends upon JAK signaling in a STAT3-independent manner. Graphical Abstract
Tumor secreted extracellular vesicles regulate T-cell costimulation and can be manipulated to induce tumor specific T-cell responses

Tumor intrinsic factors negatively regulate tumor immune cell infiltration and function. Deciphering the underlying mechanisms is critical to improving immunotherapy in cancers. Our analyses of human colorectal cancer (CRC) immune profiles and tumor-immune cell interactions revealed that tumor cell secreted extracellular vesicles (TEVs) induced immunosuppression in CRC. Specifically, TEVs containing microRNA miR-424 suppressed the CD28-CD80/86 costimulatory pathway in tumor infiltrating T cells and dendritic cells. Modified TEVs with miR-424 knocked down enhanced T-cell mediated antitumor immune response in CRC tumor models and increased the response to immune checkpoint blockade therapies (ICBT). Intravenous injections of modified TEVs induced tumor antigen specific immune responses. Moreover, injections of modified TEVs boosted the ICBT efficacy in CRC models that mimic treatment refractory late-stage disease. Collectively, we demonstrate a critical role for TEVs in antitumor immune regulation and immunotherapy response, which could be developed as a novel treatment for ICBT resistant human CRC.
Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer.

BACKGROUND MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.