Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-200b upregulation promotes migration of BEAS-2B cells following long-term exposure to cigarette smoke by targeting ETS1

Cigarette smoking is the leading cause of all histological types of lung cancer, and the role that microRNAs (miRNAs) serve in its pathogenesis is being increasingly recognized. The aim of the present study was to investigate the role of miR-200b on migration in cigarette smoke-induced malignant transformed cells. In the present study, miR-200b expression was found to be increased in cigarette smoke (CS)-exposed BEAS-2B cells, lung cancer cell lines and tumor tissue samples. Using wound healing and Transwell migration assays, the migratory ability was shown to be increased in miR-200b-overexpressing cells, whereas miR-200b knockdown resulted in reduced migration. Additionally, the expression of E-Cadherin was downregulated, whereas that of N-Cadherin was upregulated in miR-200b mimic-transfected cells, suggesting an increase in epithelial-mesenchymal transition. Downstream, using four target gene prediction tools, six target genes of miR-200b were predicted, amongst which, ETS proto-oncogene 1 transcription factor (ETS1) was shown to be significantly associated with tumor invasion depth and negatively associated with miR-200b expression. The interaction between miR-200b and ETS1 was confirmed using a dual-luciferase reporter assay. Using rescue experiments, the increased migratory ability of the miR-200b-overexpressing cells was reversed by ETS1 overexpression. In summary, this study showed that miR-200b overexpression serves a carcinogenic role and promotes the migration of BEAS-2B cells following long-term exposure to CS by targeting ETS1.
The effectiveness of bovine tuberculosis surveillance in Dutch badgers

Abstract Countries survey wildlife for bovine tuberculosis (bTB) to ensure case detection or to ascertain a high probability of freedom from bTB in wildlife. The Eurasian badger (Meles meles) is a potential bTB reservoir host. Between 2008 and 2019, 282 badgers were examined post‐mortem in the context of general wildlife disease and targeted bTB surveillance programmes in the Netherlands, and no bTB cases were detected. However, it was unclear how effective this surveillance effort was to demonstrate freedom from Mycobacterium bovis infection in the badger population of ±6000 or to detect cases if present. Therefore, surveillance effectiveness was assessed using scenario tree modelling. For lack of standards for wildlife, the models were run against three assumed levels of disease in the population called design prevalence P*: 0.1%, 0.5%, and 3%. A small risk of introduction (0.015/year) was applied, because the Netherlands are officially free from bTB in cattle, with rare import of bTB‐infected cattle and no bTB‐infected wildlife reported along the Belgian and German borders with the Netherlands. Surveillance more readily picks up bTB presence in badgers when case detection sensitivity tends towards 100% and demonstrates freedom best when the probability of freedom tends towards 100%. For P* 0.1%, 0.5% and 3%, respectively, maximum case detection sensitivity during 2008–2019 was 8%, 35% and 94% and the probability of freedom in 2019 was 46%, 67%, and 95%. At P* = 3%, performing targeted surveillance on 300 badgers in a year would make it extremely unlikely to miss a case (case detection sensitivity > 99.9%); and if no cases are detected, the adjusted probability of freedom would then reach nearly 98.5%. Stakeholders should be made aware that at P* = 3%, one case detected implies around 3% infected badgers. Additional surveillance system components to assess bTB in wildlife and its economics are to be explored further.
Identification and Reporting of Patient and Public Partner Authorship on Knowledge Syntheses: Rapid Review

Background Patient and public involvement (PPI) in health research is an area of growing interest. Several studies have examined the use and impact of PPI in knowledge syntheses (systematic, scoping, and related reviews); however, few studies have focused specifically on the patient or public coauthorship of such reviews. Objective This study seeks to identify published systematic and scoping reviews coauthored by patient or public partners and examine the characteristics of these coauthored reviews, such as which journals publish them, geographic location of research teams, and terms used to describe patient or public partner authors in affiliations, abstracts, or article text. Methods We searched CAB Direct, CINAHL, Cochrane Database of Systematic Reviews (Ovid), Embase (Ovid), MEDLINE (Ovid), and PsycInfo from 2011 to May 2019, with a supplementary search of several PPI-focused databases. We refined the Ovid MEDLINE search by examining frequently used words and phrases in relevant search results and searched Ovid MEDLINE using the modified search strategy in June 2020. Results We screened 13,998 results and found 37 studies that met our inclusion criteria. In line with other PPI research, we found that a wide range of terms were used for patient and public authors in author affiliations. In some cases, partners were easy to identify with titles such as patient, caregiver or consumer representative, patient partner, expert by experience, citizen researcher, or public contributor. In 11% (n=4) of studies, they were identified as members of a panel or advisory council. In 27% (n=10) of articles, it was either impossible or difficult to tell whether an author was a partner solely from the affiliation, and confirmation was found elsewhere in the article. We also investigated where in the reviews the partner coauthors’ roles were described, and when possible, what their specific roles were. Often, there was little or no information about which review tasks the partner coauthors contributed to. Furthermore, only 14% (5/37) of reviews mentioned patient or public involvement as authors in the abstract; involvement was often only indicated in the author affiliation field or in the review text (most often in the methods or contributions section). Conclusions Our findings add to the evidence that searching for coproduced research is difficult because of the diversity of terms used to describe patient and public partners, and the lack of consistent, detailed reporting about PPI. For better discoverability, we recommend ensuring that patient and public authorships are indicated in commonly searched database fields. When patient and public-authored research is easier to find, its impact will be easier to measure.
CORM-2 inhibits intracerebral hemorrhage-mediated inflammation

ABSTRACT Background and purpose: Low-dose of carbon monoxide delivered by CO-releasing molecule-2 (CORM-2) had been confirmed having anti-inflammatory efficacy in some inflammatory diseases. Herein, we assessed the usefulness of CORM-2 in correcting intracerebral hemorrhage (ICH)-mediated inflammation. Methods: Healthy male Sprague Dawley (SD) rats randomly entered into four groups: sham-ICH, ICH, ICH+CORM-2, and ICH+ inactive carbon monoxide releasing molecule 2 (iCORM-2). ICH was induced by 50 μl of autologous arterial blood injected in situ in the rat brain. Neuro-functions of the ICH rats were evaluated with Garcia 18 scores at the 6th, 24th , 48th hou, and the fifthh day post-ICH. And brain tissues surrounding the hematoma area were collected from all ICH rats and assayed with Western blot and immunofluoresence analysis. Results: Neuro-dysfunctions in ICH rats were very severe than those in ICH +CORM-2 rats. Compared to sham group, the levels of HO-1, IKKβ, NF-κB, and TNF-α in ICH group began to elevate at the 6th hour, and reached to peak at the 48th hour post-ICH, all p < 0.05. While in ICH +CORM-2 group, the expressions of IKKβ, NF-κB, and TNF-α were very weaker than that in ICH group at every time points mentioned above; however, this phenomenon was not reproduced in ICH + iCORM-2 group. HO-1 in ICH+CORM-2 group highlighted in perihematomal area with many activated microglia (Iba-1-positive cells) and co-expressed with TNF-α, all of which were diminished at the fifth day post-ICH. Conclusion: CORM-2 may attenuate ICH-mediated inflammation by inhibiting microglial activation, which may involve the IKK/NF-κB pathway. AbbreviationsICH: intracerebral hemorrhage; CO: carbon monoxide; CORM-2: carbon monoxide releasing molecule-2; iCORM-2: inactive carbon monoxide releasing molecule-2; HO-1: heme oxygenase 1; IKKβ: inhibitor of IκB kinases β; NF-κB: nuclear factor-κB; TNF-α: tumor necrosis factor-α; Iba-1: ionized calcium binding adaptor molecule-1; IκB: inhibitor of NF-κB; iNOS: inducible nitric oxide synthase; Keap1: Kelch-like ECH-associated protein 1; Nrf2: NF-E2-related factor 2; DMSO: dimethylsulfoxide
Responses of consumers with food allergy to the new allergen-labelling legislation in Saudi Arabia: a preliminary survey

Abstract Objective: Preventing a food allergy reaction depends primarily on eliminating allergens from the diet. In October 2019, the Saudi Food and Drug Authority (SFDA) introduced new legislation requiring food establishments providing and selling non-prepacked foods to state the presence of the top fourteen food allergens on their menus. The current study aimed to assess the allergen-labelling knowledge, practices, preferences and perceptions towards the new SFDA allergen-labelling legislation among consumers with food allergy in Saudi Arabia. Design: Observational cross-sectional study using an online questionnaire. Setting: Saudi Arabia; February – March 2020. Participants: Residents of Saudi Arabia with food allergy (n 427), aged 18–70 years. Results: Among participants, only 28·1 % knew that there were governmental regulations in Saudi Arabia regarding food-allergen labelling and approximately two-thirds (67 %) check labels on prepacked food products for allergens. The majority of the participants preferred food products carrying safety statements (84·1 %) and symbols (80·1 %). A total of 47·1 % were aware that regulations in Saudi Arabia require allergens to be declared in ingredient lists, while 51·3 % were aware that advisory allergen labelling is not required by law. Only 26·2 % were aware of the new SFDA legislation regarding provision of allergen information by food establishments. However, the majority (94·4 %) were supportive of the new legislation, and most of them were more likely to eat at restaurants that reported allergen information for food items on the menu. Conclusions: The new SFDA food allergen-labelling legislation needs to be more widely and effectively disseminated to increase the level of awareness among adults with food allergy in Saudi Arabia.
HIV-1 Gag Recruits Oligomeric Vpr via Two Binding Sites in p6, but Both Mature p6 and Vpr Are Rapidly Lost upon Target Cell Entry

The p12 protein of MLV and the p6 protein of HIV-1 are both supplementary Gag cleavage products that carry proline-rich motifs that facilitate virus budding. Importantly, p12 has also been found to be essential for early viral replication events. ABSTRACT The p12 region of murine leukemia virus (MLV) Gag and the p6 region of HIV-1 Gag contain late domains required for virus budding. Additionally, the accessory protein Vpr is recruited into HIV particles via p6. Mature p12 is essential for early viral replication events, but the role of mature p6 in early replication is unknown. Using a proviral vector in which the gag and pol reading frames are uncoupled, we have performed the first alanine-scanning mutagenesis screens across p6 to probe its importance for early HIV-1 replication and to further understand its interaction with Vpr. The infectivity of our mutants suggests that, unlike p12, p6 is not important for early viral replication. Consistent with this, we observed that p6 is rapidly lost upon target cell entry in time course immunoblot experiments. By analyzing Vpr incorporation into p6 mutant virions, we identified that the 15-FRFG-18 and 41-LXXLF-45 motifs previously identified as putative Vpr-binding sites are important for Vpr recruitment but that the 34-ELY-36 motif also suggested to be a Vpr-binding site is dispensable. Additionally, disrupting Vpr oligomerization together with removing either binding motif in p6 reduced Vpr incorporation ∼25- to 50-fold more than inhibiting Vpr oligomerization alone and ∼10- to 25-fold more than deleting each p6 motif alone, implying that multivalency/avidity is important for the interaction. Interestingly, using immunoblotting and immunofluorescence, we observed that most Vpr is lost concomitantly with p6 during infection but that a small fraction remains associated with the viral capsid for several hours. This has implications for the function of Vpr in early replication. IMPORTANCE The p12 protein of MLV and the p6 protein of HIV-1 are both supplementary Gag cleavage products that carry proline-rich motifs that facilitate virus budding. Importantly, p12 has also been found to be essential for early viral replication events. However, while Vpr, the only accessory protein packaged into HIV-1 virions, is recruited via the p6 region of Gag, the function of both mature p6 and Vpr in early replication is unclear. Here, we have systematically mutated the p6 region of Gag and have studied the effects on HIV infectivity and Vpr packaging. We have also investigated what happens to p6 and Vpr during early infection. We show that, unlike p12, mature p6 is not required for early replication and that most of the mature p6 and the Vpr that it recruits are lost rapidly upon target cell entry. This has implications for the role of Vpr in target cells.
Explaining the Help-Seeking Intentions of Adolescents Subject to Sexual Exploitation in Tanzania: An Application of the Theory of Planned Behavior

The sexual exploitation (SE) of children and adolescents is a universal concern. Numerous empirical studies have examined the prevalence and consequences of this phenomenon worldwide, but there is little information on the factors that determine the help-seeking intentions of adolescents subject to SE in Tanzania. We drew on the theory of planned behavior (TPB) to address this knowledge gap. The study had two main objectives. First, we examined four TPB variables (attitudes toward seeking help, perceived social support, perceived social stigma, and generalized self-efficacy) as determinants of the Tanzanian adolescents’ help-seeking intentions. Second, we explored the moderating effects of social stigma on the relationship between the examined TPB factors and the adolescents’ help-seeking intentions. A cross-sectional survey design was used to collect data from a stratified random sample of 1,116 secondary school adolescents aged 13-17 (M = 15.66; SD = 1.09). The participants were recruited from two regions in the east and northwest of Tanzania and data were analyzed using hierarchical multiple regression. The results indicate that the TPB variables of attitude toward seeking help, perceived social support, and generalized self-efficacy were positively associated with the help-seeking intentions of adolescents subject to SE, but not social stigma. Through moderation analyses, we found that social stigma significantly weakened the explanatory power of the attitude toward seeking help. The findings of this study in the context of Tanzania were discussed and implications for policy, practice, and future research were suggested.
Serum calprotectin (S100A8/A9): a promising biomarker in diagnosis and follow-up in different subgroups of juvenile idiopathic arthritis

Introduction In the management of juvenile idiopathic arthritis (JIA), there is a lack of diagnostic and prognostic biomarkers. This study assesses the use of serum calprotectin (sCal) as a marker to monitor disease activity, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. Methods Eighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 non-paediatric healthy controls. An ELISA method was used to quantify sCal with a commercial kit. Results Patients with an active disease compared with healthy controls and with patients with inactive disease showed an eightfold and a twofold increased level of sCal, respectively. sCal was found to be correlated with the C-reactive protein (CRP) and even more strongly with the erythrocyte sedimentation rate. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. With regard to CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis and systemic forms. However, sCal brought an added value compared with the CRP as a prognosis marker. Indeed, patients with active disease and reaching minimal disease activity (according to Juvenile Arthritis Disease Activity Score) at 6 months following the test had higher sCal levels, while patients with inactive disease had higher sCal levels if a flare was observed up to 3–9 months following the test. Conclusions This study confirms the potential uses of sCal as a biomarker in the diagnosis and follow-up of JIA.
Pressure ulcer risk assessment-registered nurses´ experiences of using PURPOSE T: A focus group study.

AIM To evaluate the clinical usability of PURPOSE T among registered nurses in Sweden. BACKGROUND Pressure ulcers are an adverse event and a problem worldwide. Risk assessment is a cornerstone, and a first step in pressure ulcer prevention is to identify possible risk patients and/or pressure ulcers. There are many pressure ulcer risk assessment instruments; however, they are not updated and/or evidence-based. PURPOSE T has been psychometrically evaluated in the UK and in Sweden with good inter-rater and test-retest reliability, and convergent validity was reported as moderate. DESIGN A descriptive study design with a qualitative approach. METHODS A total of six focus group interviews with 29 registered nurses were conducted. They were recruited from May 2018 to November 2018 from a university hospital and two nursing homes in Sweden. Data analysis was performed as described by Krueger. The study adheres to the COREQ guidelines. RESULTS Four categories were identified: "An efficient risk assessment instrument performed at the bedside," "Deeper understanding and awareness of risk factors," "Benefits compared to the Modified Norton Scale" and "Necessity of integration of PURPOSE T in the electronic health record and team collaboration. " CONCLUSION The registered nurses acknowledged an overall positive perception of PURPOSE T´s clinical usability. Future research is needed to evaluate the feasibility of PURPOSE T. RELEVANCE TO CLINICAL PRACTICE PURPOSE T has the potential to replace outdated pressure ulcers risk assessment instruments that are used today.
Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2

Key Points Question What was the incidence of multisystem inflammatory syndrome in children (MIS-C) among persons with SARS-CoV-2 infection in the US during April to June 2020? Findings In this cohort study of 248 persons with MIS-C, MIS-C incidence was 5.1 persons per 1 000 000 person-months and 316 persons per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. Incidence was higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons compared with White persons and in younger persons compared with older persons. Meaning These findings suggest that MIS-C was a rare complication of SARS-CoV-2 infection; further study is needed to understand why MIS-C incidence varied by race/ethnicity and age group.
Mechanisms of phase‐3 early afterdepolarizations and triggered activities in ventricular myocyte models

Early afterdepolarizations (EADs) are abnormal depolarizations during the repolarizing phase of the action potential, which are associated with cardiac arrhythmogenesis. EADs are classified into phase‐2 and phase‐3 EADs. Phase‐2 EADs occur during phase 2 of the action potential, with takeoff potentials typically above −40 mV. Phase‐3 EADs occur during phase 3 of the action potential, with takeoff potential between −70 and −50 mV. Since the amplitude of phase‐3 EADs can be as large as that of a regular action potential, they are also called triggered activities (TAs). This also makes phase‐3 EADs and TAs much more arrhythmogenic than phase‐2 EADs since they can propagate easily in tissue. Although phase‐2 EADs have been widely observed, phase‐3 EADs and TAs have been rarely demonstrated in isolated ventricular myocytes. Here we carry out computer simulations of three widely used ventricular action potential models to investigate the mechanisms of phase‐3 EADs and TAs. We show that when the T‐type Ca2+ current (ICa,T) is absent (e.g., in normal ventricular myocytes), besides the requirement of increasing inward currents and reducing outward currents as for phase‐2 EADs, the occurrence of phase‐3 EADs and TAs requires a substantially large increase of the L‐type Ca2+ current and the slow component of the delayed rectifier K+ current. The presence of ICa,T (e.g., in neonatal and failing ventricular myocytes) can greatly reduce the thresholds of these two currents for phase‐3 EADs and TAs. This implies that ICa,T may play an important role in arrhythmogenesis in cardiac diseases.
Inhibitors of ADAM10 reduce Hodgkin lymphoma cell growth in 3D microenvironments and enhance brentuximab-vedotin effect

Shedding of ADAM10 substrates, like TNFa or CD30, can affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. We have published two new ADAM10 inhibitors, LT4 and MN8 able to prevent such shedding in Hodgkin lymphoma (HL). Since tumor tissue architecture deeply influences the outcome of anti-cancer treatments, we set up a new threedimensional (3D) culture systems to verify whether ADAM10 inhibitors can contribute to, or enhance, the anti-lymphoma effects of the ADC brentuximab-vedotin (BtxVed). In order to recapitulate some aspects of lymphoma structure and architecture, we assembled two 3D culture models: mixed spheroids made of HL lymph node (LN) mesenchymal stromal cells (MSC) and Reed Sternberg/Hodgkin lymphoma cells (HL cells) or collagen scaffolds repopulated with LN-MSC and HL cells. In these 3D systems we found that: i) the ADAM10 inhibitors LT4 and MN8 reduce ATP content or glucose consumption, related to cell proliferation, increasing lactate dehydrogenase release as a cell damage hallmark; ii) these events are paralleled by mixed spheroids size reduction and inhibition of CD30 and TNFa shedding; iii) the effects observed can be reproduced in repopulated HL LN-derived matrix or collagen scaffolds; iv) ADAM10 inhibitors enhance the anti-lymphoma effect of the anti-CD30 ADC BtxVed both in conventional cultures and in repopulated scaffolds. Thus, we provide evidence for a direct and combined antilymphoma effect of ADAM10 inhibitors with BtxVed, leading to the improvement of ADC effects; this is documented in 3D models recapitulating features of the LN microenvironment, that can be proposed as a reliable tool for anti-lymphoma drug testing.