Miracle-dz/UniFAR-FTUs huggingface dataset:
The COVID-19 Prevalence among Children: Hypotheses for Low Infection Rate and Few Severe Forms among This Age Group in Sub-Saharan Africa

Despite some cases of severe or critical manifestations of the coronavirus disease 2019 (COVID-19) described among children, the prevalence of this infection in the pediatric population is quite low worldwide, particularly in sub-Saharan Africa. Current data suggest indeed that, independent of the population considered overall, severe and critical cases of COVID-19 are rare among children. This observation prompted us to discuss the possible hypotheses which could explain the low prevalence of COVID-19 among children; amongst others, we discuss (1) immunomodulation by the Bacillus Calmette–Guerin vaccine or by some parasitic infections such as malaria, schistosomiasis, and helminthiasis and (2) cross immunization with other coronaviruses commonly found in the sub-Saharan African setting.
Long non-coding RNA SNHG17 promotes lung adenocarcinoma progression by targeting the microRNA-193a-5p/NETO2 axis

Long non-coding RNAs (lncRNAs) play vital roles in human cancers. It has been reported that lncRNA SNHG17 expression is dysregulated in different types of cancer and involved in cancer progression. However, the role of SNHG17 in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to investigate the role of SNHG17 in LUAD. Reverse transcription-quantitative (RT-q) PCR analysis was performed to detect SNHG17 expression in LUAD tissues and cells. The effects of SNHG17 on cancer cell migration, invasion, proliferation and epithelial-to-mesenchymal transition (EMT) were assessed via Transwell, MTT and western blot assays, respectively. The interactions between SNHG17 and microRNA (miRNA/miR)-193a-5p, miR-193a-5p and neuropilin and tolloid-like 2 (NETO2) were assessed via the dual-luciferase reporter assay. NETO2 expression and its potential role in LUAD were analyzed via RT-qPCR analysis and the UALCAN database. The results demonstrated that SNHG17 expression was significantly upregulated in LUAD tissues and cells, and high SNHG17 expression was associated with tumor-node-metastasis stage and poor prognosis of patients with LUAD. SNHG17 knockdown inhibited cell migration, invasion, proliferation and the EMT process. In addition, the results revealed that SNHG17 functions as a competing endogenous RNA of miR-193a-5p. The results of the dual-luciferase reporter assay confirmed that miR-193a-5p can directly target SNHG17. NETO2 was also predicted as a target protein of miR-193a-5p, which was confirmed via the dual-luciferase reporter assay. The roles of NETO2 knockdown in cancer cells were rescued following transfection with miR-193a-5p inhibitor or overexpression of SNHG17. Notably, high NETO2 expression was associated with poor prognosis of patients with LUAD. Bioinformatics analysis demonstrated that the promoter methylation level of NETO2 decreased in LUAD. Taken together, the results of the present study suggest that SNHG17 expression is upregulated in LUAD tissues and cells, and SNHG17 exerts tumor promoting effect by targeting the miR-193a-5p/NETO2 axis.
Comparison of Moderate Hypofractionated Volumetric-Modulated Arc Therapy Plans With and Without Flattening Filter for Localized Prostate Cancer

Background/Aim The aim of this study was to compare volumetric-modulated arc therapy (VMAT) radiation plans between conventional VMAT with flattening filter (cFF-VMAT) and flattening filter-free VMAT (FFF-VMAT) for localized prostate cancer. Materials and methods Ten patients with localized prostate cancer who underwent cFF-VMAT at Yokosuka General Hospital Uwamachi, Yokosuka, Japan, from July 2020 to October 2020 were enrolled. Dose-volume histogram (DVH) parameters of the target volume, normal organs, monitor units (MU), and beam-on time (BOT) were compared between cFF-VMAT and FFF-VMAT plans. Results No significant difference was observed for DVH parameters for the target volume. No significant difference was observed in all parameters for the bladder and rectum between the cFF-VMAT and FFF-VMAT groups. The mean values of MU were 686 ± 52 and 784 ± 80 in cFF-VMAT and FFF-VMAT, respectively (p < 0.001). The mean BOT was 97.0 ± 6.6 s and 72.9 ± 1.4 s for cFF-VMAT and FFF-VMAT, respectively (p < 0.001). Conclusion DVH parameters of the target volume and normal organs were not significantly different between the cFF-VMAT and FFF-VMAT plans. In FFF-VMAT, MU was significantly higher, and the BOT was significantly shorter than those in cFF-VMAT.
Trial watch: intratumoral immunotherapy

ABSTRACT While chemotherapy and radiotherapy remain the first-line approaches for the management of most unresectable tumors, immunotherapy has emerged in the past two decades as a game-changing treatment, notably with the clinical success of immune checkpoint inhibitors. Immunotherapies aim at (re)activating anticancer immune responses which occur in two main steps: (1) the activation and expansion of tumor-specific T cells following cross-presentation of tumor antigens by specialized myeloid cells (priming phase); and (2) the immunological clearance of malignant cells by these antitumor T lymphocytes (effector phase). Therapeutic vaccines, adjuvants, monoclonal antibodies, cytokines, immunogenic cell death-inducing agents including oncolytic viruses, anthracycline-based chemotherapy and radiotherapy, as well as adoptive cell transfer, all act at different levels of this cascade to (re)instate cancer immunosurveillance. Intratumoral delivery of these immunotherapeutics is being tested in clinical trials to promote superior antitumor immune activity in the context of limited systemic toxicity.
The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36β, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.
Increasing Black, Indigenous and People of Color participation in clinical trials through community engagement and recruitment goal establishment

Longstanding social and economic inequities elevate health risks and vulnerabilities for Black, Indigenous and People of Color (BIPOC) communities. Engagement of BIPOC communities in infectious disease research is a critical component in efforts to increase vaccine confidence, acceptability, and uptake of future approved products. Recent data highlight the relative absence of BIPOC communities in vaccine clinical trials. Intentional and effective community engagement methods are needed to improve BIPOC inclusion. We describe the methods utilized for the successful enrollment of BIPOC participants in the U.S. Government (USG)-funded COVID-19 Prevention Network (CoVPN)-sponsored vaccine efficacy trials and analyze the demographic and enrollment data across the efficacy trials to inform future efforts to ensure inclusive participation. Across the four USG-funded COVID-19 vaccine clinical trials for which data are available, 47% of participants enrolled at CoVPN sites in the US were BIPOC. White enrollment outpaced enrollment of BIPOC participants throughout the accrual period, requiring the implementation of strategies to increase diverse and inclusive enrollment. Trials opening later benefitted considerably from strengthened community engagement efforts, and greater and more diverse volunteer registry records. Despite robust fiscal resources and a longstanding collaborative and collective effort, enrollment of White persons outpaced that of BIPOC communities. With appropriate resources, commitment and community engagement expertise, the equitable enrollment of BIPOC individuals can be achieved. To ensure this goal, intentional efforts are needed, including an emphasis on diversity of enrollment in clinical trials, establishment of enrollment goals, ongoing robust community engagement, conducting population-specific trials, and research to inform best practices.
Efficacy of Probiotics as Prophylaxis for Urinary Tract Infections in Premenopausal Women: A Systematic Review and Meta-Analysis

Introduction: Although antibiotic therapy has been the mainstay of prophylaxis and treatment of urinary tract infections (UTIs), antibacterial resistance has led to increased incidence of infections and healthcare spending in both community-acquired and nosocomial UTIs. This has led to an active exploration of alternative remedies for both the prophylaxis and treatment of UTIs, especially in women with recurrent urinary tract infections. Probiotic supplementation is one novel intervention that has been studied as a prophylactic measure in patients with UTIs. The current systematic review and meta-analysis was conducted to evaluate the efficacy of probiotics for prophylaxis in UTIs in premenopausal women. Methods: Detailed search strategies for each electronic database were developed for PubMed, EMBASE, and Scopus to identify relevant literature published between 2001-2021. RevMan 5.3 statistical software was used to analyze data in studies. The random-effects model was used for pooling the data. The risk of bias and study quality were assessed using Cochrane Collaboration’s tool for assessing risk of bias in included studies. The scope of focus for this review was premenopausal adult women with a history of one or more UTI. The intervention consisted of a probiotic regimen for which the goal was to enhance the defensive microflora of the urogenital tract. Studies comparing a probiotic regimen to a placebo regimen were included. These studies’ primary outcome was the proportion of women with at least one symptomatic bacterial UTI in each group (i.e., UTI recurrence rate) in the 12-month period following probiotic intervention. This study extends the work of researchers who systematically investigated the scientific literature on probiotics in the prevention of urinary tract infections with a particular focus on premenopausal women. Results: After screening, three parallel-group randomized-controlled trials (RCTs) were included. We estimated the overall pooled data of these three studies with a total of 284 participants to have met the predefined inclusion criteria and were therefore included in this review. The results demonstrated that probiotics did not have a significant effect in the prophylaxis of UTIs. (Risk Ratio (RR): 0.59 confidence interval (CI): 0.26, 1.33), Heterogeneity: Chi² = 6.63, df = 2 (p = 0.04); I² =70%, Test for overall effect: Z = 1.27 (p = 0.20). Conclusions: Probiotics did not demonstrate a significant benefit in reducing UTI recurrence compared to placebo in premenopausal women. However, more conclusive data is needed to determine the effect that probiotics have on strengthening the urogenital microbial barrier against pathogenic bacteria and protecting against UTI recurrence.
Brain regions that support accurate speech production after damage to Broca’s area

Abstract Broca’s area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca’s area. Importantly, contemporary evidence suggests that, within Broca’s area, its posterior part (i.e. pars opercularis) plays a more prominent role in speech production than its anterior part (i.e. pars triangularis). In this study, we therefore investigated the brain activation patterns that underlie accurate speech production following stroke damage to the opercular part of Broca’s area. By combining functional MRI and 13 tasks that place varying demands on speech production, brain activation was compared in (i) seven patients of interest with damage to the opercular part of Broca’s area; (ii) 55 neurologically intact controls; and (iii) 28 patient controls with left-hemisphere damage that spared Broca’s area. When producing accurate overt speech responses, the patients with damage to the left pars opercularis activated a substantial portion of the normal bilaterally distributed system. Within this system, there was a lesion-site-dependent effect in a specific part of the right cerebellar Crus I where activation was significantly higher in the patients with damage to the left pars opercularis compared to both neurologically intact and patient controls. In addition, activation in the right pars opercularis was significantly higher in the patients with damage to the left pars opercularis relative to neurologically intact controls but not patient controls (after adjusting for differences in lesion size). By further examining how right Crus I and right pars opercularis responded across a range of conditions in the neurologically intact controls, we suggest that these regions play distinct roles in domain-general cognitive control. Finally, we show that enhanced activation in the right pars opercularis cannot be explained by release from an inhibitory relationship with the left pars opercularis (i.e. dis-inhibition) because right pars opercularis activation was positively related to left pars opercularis activation in neurologically intact controls. Our findings motivate and guide future studies to investigate (i) how exactly right Crus I and right pars opercularis support accurate speech production after damage to the opercular part of Broca’s area and (ii) whether non-invasive neurostimulation to one or both of these regions boosts speech production recovery after damage to the opercular part of Broca’s area.
Denosumab improves glucose parameters in patients with impaired glucose tolerance: a systematic review and meta-analysis

Abstract Objective Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI). Methods A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT). Results Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = −0.388, 95%CI: −0.705 to −0.070, p = .017) and with HOMA1-IR (SDM = −0.223, 95%CI: −0.388 to −0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = −0.037, 95%CI: −0.059 to −0.015, p < .005). Conclusions Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.
Identification of a Novel Serological Marker in Seronegative Rheumatoid Arthritis Using the Peptide Library Approach

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation mainly affecting the joints leading to cartilage and bone destruction. The definition of seropositive or seronegative RA is based on the presence or absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs). Other autoantibodies have been identified in the last decade such as antibodies directed against carbamylated antigens, peptidyl-arginine deiminase type 4 and v-Raf murine sarcoma viral oncogene homologue B. In order to identify relevant autoantigens, we screened a random peptide library (RPL) with pooled IgGs obtained from 50 patients with seronegative RA. Patients’ sera were then used in an ELISA test to identify the most frequently recognized peptide among those obtained by screening the RPL. Sera from age- and sex-matched healthy subjects were used as controls. We identified a specific peptide (RA-peptide) recognized by RA patients’ sera, but not by healthy subjects or by patients with other immune-mediated diseases. The majority of sera from seronegative and seropositive RA patients (73.8% and 63.6% respectively) contained IgG antibodies directed against the RA-peptide. Interestingly, this peptide shares homology with some self-antigens, such as Protein-tyrosine kinase 2 beta, B cell scaffold protein, Liprin-alfa1 and Cytotoxic T lymphocyte protein 4. Affinity purified anti-RA-peptide antibodies were able to cross react with these autoantigens. In conclusion, we identified a peptide that is recognized by seropositive and, most importantly, by seronegative RA patients’ sera, but not by healthy subjects, conferring to this epitope a high degree of specificity. This peptide shares also homology with other autoantigens which can be recognized by autoantibodies present in seronegative RA sera. These newly identified autoantibodies, although present also in a percentage of seropositive RA patients, may be considered as novel serum biomarkers for seronegative RA, which lacks the presence of RF and/or ACPAs.
Strong Twirling-Rotating Manual Acupuncture with 4 r/s Is Superior to 2 r/s in Relieving Pain by Activating C-Fibers in Rat Models of CFA-Induced Pain

Background Manual acupuncture (MA) with different stimulus frequencies may give rise to varying acupuncture effects. However, the intensity-effect relationship and the underlying mechanisms of MA remain unclear. Objective To compare the analgesic effects of different frequencies of twirling-rotating MA on rats with complete Freund's adjuvant- (CFA-) induced pain and explore the underlying mechanism via peripheral sensory nerves. Methods First, 36 healthy male Wistar rats were randomly divided into 6 groups: control group, 2 r/s MA group (twirling-rotating MA with the frequency of 2 revolutions per second), 4 r/s MA group (twirling-rotating MA with the frequency of 4 revolutions per second), CFA group, CFA + 2 r/s MA group, and CFA + 4 r/s MA group. Rats in three CFA groups received an intraplantar injection of CFA to establish a pain model, while the rats in other three groups received an intraplantar injection of saline. Rats in the 2 r/s MA group and 4 r/s MA group were treated with the corresponding frequencies of twirling-rotating MA on bilateral Zusanli (ST36) and Kunlun (BL60) for 7 days. The ipsilateral nociceptive thresholds (paw withdrawal latency; PWL) were tested to evaluate the analgesic effects. Second, 9 healthy male Wistar rats were randomly divided into 3 groups: control group, 2 r/s MA group, and 4 r/s MA group. The proportion of C-fiber neurons (calcitonin gene-related peptide- (CGRP-) positive neurons) and A-fiber neurons (neurofilament 200- (NF200-) positive neurons) in the dorsal root ganglia (DRG) activated by MA were quantitatively analyzed with the morphological immunofluorescence staining method. Third, 30 healthy male Wistar rats were randomly divided into 6 groups: control group, CFA group, CFA + 2 r/s MA group, CFA + 2 r/s MA + RTX group, CFA + 4 r/s MA group, and CFA + 4 r/s MA + RTX group. Resiniferatoxin (RTX) was injected into the acupoints before acupuncture. PWL was evaluated to investigate the analgesic effect. Results Both types of MA treatment increased the PWL of saline-injecting rats and pain model rats. Moreover, 4 r/s MA was superior to 2 r/s MA in increasing PWL. A higher quantity of excited C-fiber neurons was observed following 4 r/s MA than 2 r/s MA, while the reverse was observed in the activation of A-fiber neurons. Following the injection of RTX to inhibit the activation of C-fibers, the analgesic effect of 4 r/s MA reduced significantly but not of 2 r/s MA. Conclusion Strong MA (4 r/s MA) has superior analgesic effects to gentle MA (2 r/s MA) on CFA model rats, which is associated with C-fiber activation.
Health Outcomes among Adults Initiating Medical Cannabis for Chronic Pain: A 3-month Prospective Study Incorporating Ecological Momentary Assessment (EMA)

In response to the need of more rigorous data on medical cannabis and chronic pain, we conducted a 3-month prospective study incorporating ecological momentary assessment (EMA) to examine the effects of medical cannabis on pain, anxiety/depression, sleep, and quality of life. Data were collected from 46 adults (Mean age=55.7±11.9, 52.2% male) newly initiating medical cannabis treatment for chronic pain. Participants completed a baseline survey, EMA for approximately 1 week pre- and up to 3 weeks post-medical cannabis treatment, and a 3-month follow-up survey. The self-reported EMA data (2535 random and 705 daily assessments) indicated significant reductions in momentary pain intensity (b = -16.5, p < .001, 16.5 points reduction on 0-100 visual analog) and anxiety (b = -0.89, p < .05), and significant increase in daily sleep duration (b = 0.34, p < .01) and sleep quality (b = 0.32, p <.001) after participants initiated medical cannabis for a few weeks. At 3 months, self-reported survey data showed significantly lower levels of worst pain (t = -2.38, p < .05), pain interference (t = -3.82, p < .05), and depression (t = -3.43, p < .01), as well as increased sleep duration (t = 3.95, p < .001), sleep quality (t = -3.04, p < .01), and quality of life (t = 4.48, p < .001) compared to baseline. In our sample of primarily middle-aged and older adults with chronic pain, medical cannabis was associated with reduced pain intensity/inference, lower anxiety/depression, and improved sleep and quality of life.