Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized Controlled Clinical Trial of Bivalent Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine in Nigerian Children

Abstract Background We conducted a trial in Nigeria to assess the immunogenicity of the new bivalent oral poliovirus vaccine + inactivated poliovirus vaccine (bOPV+IPV) immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016–March 2017, well past the trivalent OPV-bOPV switch in April 2016. Methods This was an open-label, 2-arm, noninferiority, multicenter, randomized, controlled trial. We enrolled 572 infants aged ≤14 days and randomized them into 2 arms. Arm A received bOPV at birth, 6, and 10 weeks, bOPV+IPV at week 14, and IPV at week 18. Arm B received IPV each at 6, 10, and 14 weeks and bOPV at 18 weeks of age. Results Seroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95% confidence interval [CI], 96.7–99.8) and 98.1% (95% CI, 88.2–94.8) in Arm A and 89.6% (95% CI, 85.4–93.0) and 98.5% (95% CI, 96.3–99.6) in Arm B. Type 2 seroconversion with 1 dose IPV in Arm A was 72.0% (95% CI, 66.2–77.3), which increased significantly with addition of second dose to 95.9% (95% CI, 92.8–97.9). Conclusions This first trial on the new Expanded Program on Immunization (EPI) schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3 and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV, respectively.
Association Between Sudden Sensorineural Hearing Loss and History of Statin Use: A Nested Case-Control Study

Objective The effect of statin on sudden sensorineural hearing loss (SSNHL) remains unclear. Thus, this study aimed to investigate the association between prior statin use and SSNHL. Study Design A nested case-control study. Setting Participants aged ≥40 years were enrolled from the 2002-2015 Korean National Health Insurance Service–Health Screening Cohort. Methods A total of 5876 patients with SSNHL were matched with 23,504 control participants for age, sex, income, and region of residence. History of statin use for 2 years before SSNHL onset was investigated between the groups. The odds ratios (ORs) of the length of statin use for SSNHL stratified by age, sex, income, and region of residence were analyzed with conditional logistic regression. Dyslipidemia, total cholesterol, blood pressure, blood glucose, hemoglobin, obesity, smoking, alcohol consumption, and Charlson Comorbidity Index score were adjusted. The adjusted variables were subjected to subgroup analyses. Results The SSNHL group had a longer duration of statin use than the control group (mean [SD], 81.9 [197.7] days vs 72.7 [188.0] days; P = .001). However, statin use was not associated with SSNHL after adjusting for the confounders (adjusted OR, 1.04; 95% CI, 0.98-1.11; P = .245). There was a positive correlation between statin use and SSNHL in the crude model (crude OR, 1.10; 95% CI, 1.04-1.16; P = .001). However, there was no association between statin use and SSNHL in all subgroup analyses. Conclusion Previous statin use was not associated with SSNHL.
Risk of Developing Pancreatic Cancer in Patients with Chronic Pancreatitis

Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic ductal adenocarcinoma (PDAC). We present data on PDAC in one of the most extensive European single-centre cohort studies of patients with CP. Methods: Retrospective analysis of prospectively collected data of patients with CP was performed. Aetiology of CP was determined according to the M-ANNHEIM classification system and only patients with definite CP > 18 years at data analysis were included. The final dataset included 581 patients with definite CP diagnosed between 2003 and 2018. Results: At CP diagnosis, there were 371 (63.9%) males and 210 (36.1%) females (median age 57 years, range 2–86). During 3423 person-years of observation, six pancreatic cancers were diagnosed (0.2% year). The mean time between diagnosis of CP and the occurrence of PDAC was 5.0 years (range 2.7–8.6). None of the cancer patients had a family history of PDAC. Diabetes mellitus (DM) was present in five of six (83.3%) patients with PDAC: in three patients before and in two after CP diagnosis. Clinical/laboratory signs of pancreatic exocrine insufficiency (PEI) were present in five of six (83.3%) patients with PDAC: in two at diagnosis of CP and in three after diagnosis. The mean survival time was 4 months after the diagnosis of PDAC (range 0.5–13). PDAC occurred significantly more often (p < 0.001) in two groups of patients without previous acute pancreatitis (AP): 2 of 20 patients (10%) with low body mass index (BMI) and PEI and in 3 of 10 (30%) patients with high BMI and DM at diagnosis of CP. Conclusions: Patients with CP have a high risk of developing PDAC, although risk is low in absolute terms. Our data suggest the possibility of defining subgroups of patients with a particularly elevated risk of PDAC. Such a possibility would open a path to personalised decision making on initiation of PDAC surveillance of patients with no previous episode of AP, (i) with low BMI and PEI, or (ii) elevated BMI and DM.
Molecular Assembly and Structural Plasticity of Sensory Ribbon Synapses—A Presynaptic Perspective

In the mammalian cochlea, specialized ribbon-type synapses between sensory inner hair cells (IHCs) and postsynaptic spiral ganglion neurons ensure the temporal precision and indefatigability of synaptic sound encoding. These high-through-put synapses are presynaptically characterized by an electron-dense projection—the synaptic ribbon—which provides structural scaffolding and tethers a large pool of synaptic vesicles. While advances have been made in recent years in deciphering the molecular anatomy and function of these specialized active zones, the developmental assembly of this presynaptic interaction hub remains largely elusive. In this review, we discuss the dynamic nature of IHC (pre-) synaptogenesis and highlight molecular key players as well as the transport pathways underlying this process. Since developmental assembly appears to be a highly dynamic process, we further ask if this structural plasticity might be maintained into adulthood, how this may influence the functional properties of a given IHC synapse and how such plasticity could be regulated on the molecular level. To do so, we take a closer look at other ribbon-bearing systems, such as retinal photoreceptors and pinealocytes and aim to infer conserved mechanisms that may mediate these phenomena.
Pneumocystis jirovecii pneumonia PCR test on upper respiratory tract swab

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection with high morbidity and mortality among people living with HIV. Upper respiratory tract (URT) swabs are routinely taken for testing viral and bacterial pathogens when patients present with respiratory symptoms in our hospital. We conducted a pilot service improvement project to explore the utility of URT swabs for PCP diagnosis using in‐house real‐time polymerase chain reaction (PCR).
Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

The recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to those obtained from the actual experiments. Here, humoral and cellular immune responses to two major Yersinia pestis protective antigens, F1 and LcrV, were studied in human donors immunized with the live plague vaccine (LPV) based on the attenuated Y. pestis strain EV line NIIEG. The F1 antigen provided modest specific cellular (mixed T helper 1 (Th1)/Th2 type) and humoral immune responses in vaccinees irrespective of the amount of annual vaccinations and duration of the post-vaccination period. The probing of the F1 overlapping peptide library with the F1-positive sera revealed the presence of seven linear B cell epitopes, which were all also predicted by in silico assay. The immunoinformatics study evaluated their antigenicity, toxicity, and allergenic properties. The epitope TSQDGNNH was mostly recognized by the sera from recently vaccinated donors rather than antibodies from those immunized decades ago, suggesting the usefulness of this peptide for differentiation between recent and long-term vaccinations. The in silico analysis predicted nine linear LcrV-specific B-cell epitopes; however, weak antibody and cellular immune responses prevented their experimental evaluation, indicating that LcrV is a poor marker of successful vaccination. No specific Th17 immune response to either F1 or LcrV was detected, and there were no detectable serum levels of F1-specific immunoglobulin A (IgA) in vaccinees. Overall, the general approach validated in the LPV model could be valuable for the rational design of vaccines against other neglected and novel emerging infections with high pandemic potency.
Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease

Respiratory diseases place an immense burden on global health and there is a compelling need for the discovery of new compounds for therapeutic development. Here, we identify research priorities by critically reviewing pre-clinical and clinical studies using extracts and compounds derived from molluscs, as well as traditional molluscan medicines, used in the treatment of respiratory diseases. We reviewed 97 biomedical articles demonstrating the anti-inflammatory, antimicrobial, anticancer, and immunomodulatory properties of >320 molluscan extracts/compounds with direct relevance to respiratory disease, in addition to others with promising bioactivities yet to be tested in the respiratory context. Of pertinent interest are compounds demonstrating biofilm inhibition/disruption and antiviral activity, as well as synergism with approved antimicrobial and chemotherapeutic agents. At least 100 traditional medicines, incorporating over 300 different mollusc species, have been used to treat respiratory-related illness in cultures worldwide for thousands of years. These medicines provide useful clues for the discovery of bioactive components that likely underpin their continued use. There is particular incentive for investigations into anti-inflammatory compounds, given the extensive application of molluscan traditional medicines for symptoms of inflammation, and shells, which are the principal molluscan product used in these preparations. Overall, there is a need to target research toward specific respiratory disease-related hypotheses, purify bioactive compounds and elucidate their chemical structures, and develop an evidence base for the integration of quality-controlled traditional medicines.
Off-Target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent

Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. ABSTRACT Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. RDV has broad-spectrum activity against members of the coronavirus family, such as SARS-CoV-2, SARS-CoV, and MERS-CoV, as well as filoviruses and paramyxoviruses. To assess the potential for off-target toxicity, RDV was evaluated in a set of cellular and biochemical assays. Cytotoxicity was evaluated in a set of relevant human cell lines and primary cells. In addition, RDV was evaluated for mitochondrial toxicity under aerobic and anaerobic metabolic conditions, and for the effects on mitochondrial DNA content, mitochondrial protein synthesis, cellular respiration, and induction of reactive oxygen species. Last, the active 5′-triphosphate metabolite of RDV, GS-443902, was evaluated for potential interaction with human DNA and RNA polymerases. Among all of the human cells tested under 5 to 14 days of continuous exposure, the 50% cytotoxic concentration (CC50) values of RDV ranged from 1.7 to >20 μM, resulting in selectivity indices (SI, CC50/EC50) from >170 to 20,000, with respect to RDV anti-SARS-CoV-2 activity (50% effective concentration [EC50] of 9.9 nM in human airway epithelial cells). Overall, the cellular and biochemical assays demonstrated a low potential for RDV to elicit off-target toxicity, including mitochondria-specific toxicity, consistent with the reported clinical safety profile.
Effect of evaporation-induced osmotic changes in culture media in a dry-type incubator on clinical outcomes in in vitro fertilization-embryo transfer cycles

Objective This study investigated whether adding outer-well medium to inhibit osmotic changes in culture media in a dry-type incubator improved the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) cycles. Methods In culture dishes, the osmotic changes in media (20 µL)-covered oil with or without outer-well medium (humid or dry culture conditions, respectively) were compared after 3 days of incubation in a dry-type incubator. One-step (Origio) and G1/G2 (Vitrolife) media were used. Results The osmotic changes in the dry culture condition (308 mOsm) were higher than in the humid culture conditions (285–290 mOsm) after 3 days of incubation. In day 3 IVF-ET cycles, although the pregnancy rate did not significantly differ between the dry (46.2%) and humid culture (51.0%) groups, the rates of abortion and ongoing pregnancy were significantly better in the humid culture group (1.5% and 49.5%, respectively) than in the dry culture group (8.3% and 37.8%, respectively, p<0.05). In day 5 IVF-ET cycles, the abortion rate was significantly lower in the humid culture group (2.2%) than in the dry culture group (25.0%, p<0.01), but no statistically significant difference was observed in the rates of clinical and ongoing pregnancy between the dry (50.0% and 25.0%, respectively) and humid culture groups (59.5% and 57.3%, respectively) because of the small number of cycles. Conclusion Hyperosmotic changes in media occurred in a dry-type incubator by evaporation, although the medium was covered with oil. These osmotic changes were efficiently inhibited by supplementation of outer-well medium, which resulted in improved pregnancy outcomes.
Epstein–Barr Virus: How Its Lytic Phase Contributes to Oncogenesis

Epstein–Barr Virus (EBV) contributes to the development of lymphoid and epithelial malignancies. While EBV’s latent phase is more commonly associated with EBV-associated malignancies, there is increasing evidence that EBV’s lytic phase plays a role in EBV-mediated oncogenesis. The lytic phase contributes to oncogenesis primarily in two ways: (1) the production of infectious particles to infect more cells, and (2) the regulation of cellular oncogenic pathways, both cell autonomously and non-cell autonomously. The production of infectious particles requires the completion of the lytic phase. However, the regulation of cellular oncogenic pathways can be mediated by an incomplete (abortive) lytic phase, in which early lytic gene products contribute substantially, whereas late lytic products are largely dispensable. In this review, we discuss the evidence of EBV’s lytic phase contributing to oncogenesis and the role it plays in tumor formation and progression, as well as summarize known mechanisms by which EBV lytic products regulate oncogenic pathways. Understanding the contribution of EBV’s lytic phase to oncogenesis will help design ways to target it to treat EBV-associated malignancies.
Mindfulness in Motion and Dietary Approaches to Stop Hypertension (DASH) in Hypertensive African Americans

Hypertension increases the risk of developing Alzheimer's disease or related dementias. This pilot study's purpose was to examine the feasibility and acceptability of a novel intervention, Mindfulness in Motion (MIM) and Dietary Approaches to Stop Hypertension DASH (MIM DASH), to improve diet, mindfulness, stress, and systolic blood pressure (BP) in older African Americans with mild cognitive impairment (MCI) and hypertension.
Clinical outcomes of patients hospitalized for COVID-19 versus SARS: a meta-analysis

Estimating the case-fatality rate and clinical outcomes for patients with coronavirus disease 2019 (COVID-19) is crucial because health care systems must adequately prepare for outbreaks and design appropriate policies. A systematic search of PubMed, Embase, and Medline+Journal (via OVID) were conducted for relevant journal publications from database inception to May 4, 2020. Articles that reported the fatality rates and clinical outcomes of patients hospitalized for COVID-19 or severe acute respiratory syndrome (SARS) infection were included. Nine clinical reports (four SARS reports and five COVID-19 reports) with a total of 851 patients (367 and 484 patients with SARS and COVID-19, respectively) were analyzed. A greater proportion of hospitalized patients with COVID-19 had bilateral pneumonia (90.0% [76.3%–96.2%] vs. 35.9% [21.4%–53.6%], p < 0.001) and required ventilators (23.8% [18.8%–29.6%] vs. 15.3% [11.9%–19.4%], p = 0.010) compared with hospitalized patients with SARS. The case-fatality rate was 9.5% (6.5%–13.7%) and 6.1% (3.5%–10.3%) among patients with COVID-19 and SARS, respectively (p = 0.186). The case-fatality rate among hospitalized patients with COVID-19 was comparable to that during the 2003 SARS outbreak. A higher incidence of bilateral pneumonia and increased ventilator usage were noted among patients with COVID-19 compared with patients with SARS.
Expression levels of maternal plasma microRNAs in preeclamptic pregnancies

Abstract The present study aimed to identify the differential expression profiles of microRNAs in the plasma between patients with preeclampsia (PE) and healthy pregnancies using quantitative real-time PCR. The expression profiles of 32 miRNAs in maternal plasma from 31 patients with PE and 32 healthy pregnancies were evaluated. The expression levels of eight miRNAs including miR-210, miR-375, miR-197-3p, miR-132-3p, miR-29a-3p, miR-328, miR-24-3p, and miR-218-5p were significantly upregulated and the expression levels of three miRNAs, including miR-302b-3p, miR-191-5p, and miR-17-5p, were significantly downregulated in patients with preeclampsia when compared to healthy pregnant women. In conclusion, we identified 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings. IMPACT STATEMENT What is already known on this subject? The alterations in the release pattern of placenta-specific miRNAs detected in maternal serum have been found to be associated with pregnancy-related complications such as preeclampsia (PE). What do the results of this study add? In the present study, the release pattern of seven miRNAs had consistency and two of them had inconsistency with previous researches. Moreover, two novel miRNAs were also defined to demonstrate the interrelationship between PE and miRNAs. What are the implications of these findings for clinical practice and/or future research? The identification of 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings.
Assessing the Intestinal Permeability and Anti-Inflammatory Potential of Sesquiterpene Lactones from Chicory

Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed the capacity of SLs to permeate the intestinal barrier to become physiologically available, using in silico predictions and in vitro studies with the well-established cell model of the human intestinal mucosa (differentiated Caco-2 cells). The potential of SLs to modulate inflammatory responses through modulation of the nuclear factor of activated T-cells (NFAT) pathway was also evaluated, using a yeast reporter system. Lactucopicrin was revealed as the most permeable chicory SL in the intestinal barrier model, but it had low anti-inflammatory potential. The SL with the highest anti-inflammatory potential was 11β,13-dihydrolactucin, which inhibited up to 54% of Calcineurin-responsive zinc finger (Crz1) activation, concomitantly with the impairment of the nuclear accumulation of Crz1, the yeast orthologue of human NFAT.
Isokinetic Testing: Sensitivity of the Force-Velocity Relationship Assessed through the Two-Point Method to Discriminate between Muscle Groups and Participants’ Physical Activity Levels

Background: Isokinetic testing has been routinely used to assess the capacities of individual muscle groups. In this study we aimed to evaluate the sensitivity of the force-point (F-v) relationship assessed through the two-point method to discriminate between antagonist muscle groups and males with different physical activity levels. Methods: The concentric force output of the knee, hip, elbow, and shoulder flexors and extensors of 27 active and 13 non-active men was recorded at 60 and 180°/s to determine the F-v relationship parameters (maximum force [F0], maximum velocity [v0], and maximum power [Pmax]). Results: F0 and Pmax were higher for knee extensors (effect size [ES] = 1.97 and 0.57, respectively), hip extensors (ES = 2.52 and 0.77, respectively), and shoulder flexors (ES = 1.67 and 0.83, respectively) compared to their antagonist muscles, while v0 was higher for knee flexors compared to knee extensors (ES = 0.59). Active males revealed higher F0 for knee extensors (ES = 0.72) and knee flexors (ES = 0.83) and higher Pmax for knee flexors (ES = 0.70), elbow extensors (ES = 0.83) and shoulder extensors (ES = 0.36). Conclusions: The sensitivity of the two-point method for testing the maximal mechanical capacities was high for the knee, moderate for the hip and shoulder, and low for the elbow joint.