Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Study of Inhaler Device Handling Technique and Risk Factors for Critical Inhaler Errors in Korean COPD Patients

Objective Critical inhaler handling errors are associated with an increased risk of adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). However, real-world data on inhaler device handling techniques and the risk factors for critical inhaler errors in the Asian population have been examined in only a few studies. We evaluated the rates and risk factors for critical inhaler errors in the COPD population in Korea. Methods COPD patients were prospectively enrolled from January 2018 to November 2019. An advanced practice nurse evaluated their inhaler technique. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (DPIs; Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair), a soft mist inhaler (SMI; Respimat), and pressurized metered dose inhalers (pMDIs). Results The percentage critical errors for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 60.0%, 41.0%, 27.8%, 12.5%, 44.4%, 45.5%, and 55.0%, respectively. In the multivariate analyses, female sex, short COPD duration, dissatisfaction with the inhaler (assessed by FSI-10), and moderate acute exacerbations (AEs) in the prior year were independent risk factors for any critical error in the DPI group. In the SMI group, a low education level and frequent AEs in the prior year were independent risk factors for any critical error, whereas a high COPD assessment test (CAT) score was the only risk factor in the pMDI group. Conclusion Critical inhaler errors are common among patients with COPD, regardless of their preferred inhaler device. The rates and risk factors for critical inhaler errors differed among patients using different devices. Optimal device selection considering the risk factors of inhaler misusage will improve disease control in COPD patients.
Cross-sectional associations between cognition and mobility in Parkinson’s disease

ABSTRACT. Cross-sectional studies show an association of decline in mental flexibility and inhibitory control with reduced gait speed and falls, as well as divided attention deficit and difficulty in initiating gait. Objective: To investigate the relationships between cognitive function and gait performance in patients with Parkinson’s disease (PD) who participated in a hospital neurorehabilitation program. Methods: A total of 107 patients (79 males, 28 females; mean age 61.00±8.2 years; mean schooling 11.7±4.1 years) with idiopathic PD (mean disease duration 5.5±4.1 years) were recruited for this study. Among them, 78.50% were in stages I and II of the Hoehn & Yahr Scale. Cognitive functions were evaluated through the Digit Span test, Trail Making Test, and Addenbrooke’s Cognitive Examination III. Motor function was assessed with the 10-Meter Walk Test, the short version of the Balance Evaluation Systems Test (Mini-BESTest), and the Timed Up and Go Test. Results: Balance skills were significantly correlated with global cognition and specific domains, including divided attention, verbal fluency, and visuospatial function. Functional mobility showed a significant association with all cognitive tests, except for the number of errors on TMT-A. Gait speed presented a significant correlation with global cognition scores, memory, and attention, including divided attention. Conclusions: These findings might help early identification of cognitive deficits or motor dysfunctions in PD patients who may benefit from rehabilitation strategies, as well as facilitate fall risk assessments and strategies to prevent falls. Future prospective studies are needed to investigate the effects of cognitive training on motor performance, since the difficulty in motor rehabilitation may be more related to cognitive loss than to motor damage.
A Concise Review: The Role of Stem Cells in Cancer Progression and Therapy

Abstract The properties of cancer stem cells (CSCs) have recently gained attention as an avenue of intervention for cancer therapy. In this review, we highlight some of the key roles of CSCs in altering the cellular microenvironment in favor of cancer progression. We also report on various studies in this field which focus on transformative properties of CSCs and their influence on surrounding cells or targets through the release of cellular cargo in the form of extracellular vesicles. The findings from these studies encourage the development of novel interventional therapies that can target and prevent cancer through efficient, more effective methods. These methods include targeting immunosuppressive proteins and biomarkers, promoting immunization against tumors, exosome-mediated CSC conversion, and a focus on the quiescent properties of CSCs and their role in cancer progression. The resulting therapeutic benefit and transformative potential of these novel approaches to stem cell-based cancer therapy provide a new direction in cancer treatment, which can focus on nanoscale, molecular properties of the cellular microenvironment and establish a more precision medicine-oriented paradigm of treatment.
Topical formulations containing Copaifera duckei Dwyer oleoresin improve cutaneous wound healing

Objective: Evaluation of the healing and toxicological effects of Copaifera duckei Dwyer oleoresin (CDO). Materials and Methods: Rodents with skin lesions were divided into nine groups, including daily treatments with 1, 3 and 10% CDO, collagenase, antibiotic ointment and control groups, for 14 days. Results: Treatment with 10% CDO reduced skin edema and hyperplasia, demonstrating anti-inflammatory effect of the oil. Reduction in the wound area was observed, indicating the healing effect of CDO. Histopathological analysis showed increases in angiogenesis and re-epithelialization in animals treated with the highest concentration. On the other hand, no alterations in ulcerations, inflammatory infiltrate, hemorrhage, congestion, degeneration, percentage of collagen fibers, number of cells stained with anti-macrophage migration inhibitory factor, or density of area stained with anti-collagen I and III were found. Toxicogenetic analysis revealed no differences in micronucleus frequencies or in the ratio of polychromatic erythrocytes to total erythrocytes between treated and negative control, demonstrating the absence of genotoxicity and cytotoxicity, respectively. There was no difference in levels of liver enzymes among groups, indicating the absence of hepatotoxicity. Conclusion: Formulations of CDO exerted beneficial effects on the stages of cutaneous wound healing and are promising options for the treatment of wounds.
Factors Associated with Chronic Obstructive Pulmonary Diseases in Nepal: Evidence from a Nationally Representative Population-Based Study

Background The Global Burden of Diseases Study 2017 predicted that chronic obstructive pulmonary disease (COPD) is the second leading cause of death, the fourth leading cause of premature death, and the third cause for DALYs lost in Nepal. However, data on the population-based prevalence of COPD in Nepal are very limited. This study aims to assess the prevalence of COPD and factors associated with the occurrence of COPD in Nepal. Methods From a nationally representative, population-based cross-sectional study on chronic non-communicable diseases, the prevalence of COPD and its associated factors was determined. Of 12,557 participants aged over 20 years, 8945 participants completed a questionnaire and spirometry. Eligible participants were also asked to answer a COPD diagnostic questionnaire for screening COPD cases, and if needed underwent pre-bronchodilator and post-bronchodilator spirometry. COPD was defined as a post-bronchodilator FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio of <0.70. Multivariate logistic regression was performed to identify factors associated with COPD. Sampling weights were used for all data analyses. Results The prevalence of COPD in Nepal was 11.7% (95% CI: 10.5% to 12.9 %), which increased with age, and higher in those with a low educational level, those who had smoked ≥50 pack-years, persons having a low body mass index (BMI), and residents of Karnali province. Multivariate analysis revealed that being aged 60 years and above, having a low BMI, low educational status, having smoked more than 50 pack-years, provincial distribution, and ethnicity were independent predictors of COPD. Conclusion COPD is a growing and serious public health issue in Nepal. Factor such as old age, cigarette smoking, low educational attainment, low BMI, ethnicity, and locality of residence (province-level variation) plays a vital role in the occurrence of COPD. Strategies aimed at targeting these risk factors through health promotion and education interventions are needed to decrease the burden of COPD.
Association of changes in waist circumference with cardiovascular disease and all-cause mortality among the elderly Chinese population: a retrospective cohort study

BACKGROUND To examine the association of baseline waist circumference (WC) and changes in WC with cardiovascular disease (CVD) and all-cause mortality among elderly people. METHODS A total of 30,041 eligible participants were included from a retrospective cohort in China. The same questionnaire, anthropometric and laboratory measurements were performed at baseline (2010) and the first follow-up (2013). The percent change in WC between baseline and the first follow-up was calculated to evaluate three years change of WC. We collected the occurrence of CVD and all-cause death from the first follow-up to December 31, 2018. Restricted cubic splines and Cox proportional-hazards regression models were used to evaluate the relationship between baseline WC/ changes in WC and mortality. RESULTS The dose-response relationships between baseline WC and CVD mortality were U- or J-shaped. In low WC group, compared with stable group, the fully adjusted hazard ratio (aHR) for CVD mortality was 1.60 (95% CI: 1.24−2.06) in WC gain group among men. In normal WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.86, 95% CI: 1.36−2.56; women: aHR = 1.83, 95% CI: 1.29−2.58). In moderate-high WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.76, 95% CI: 1.08−2.88; women: aHR = 1.46, 95% CI: 1.04−2.05) and risk decreased with WC loss (men: aHR = 0.54, 95% CI: 0.30−0.98; women: aHR = 0.59, 95% CI: 0.37−0.96). CONCLUSIONS For the elderly population, WC gain may increase CVD mortality risk regardless of baseline WC, whereas WC reduction could decrease the risk only in the moderate-high WC group.
Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Background Azoles are the most common antifungal drugs used in the treatment of vulvovaginal candidiasis (VVC). The frequency of azole-resistant Candida isolates has increased dramatically in the last two decades. Here, we assessed the antifungal activity of a combination of fluconazole (FLZ) and methanolic extract of ginger (Meth-Gin) against drug-resistant vulvovaginal candidiasis (VVC) in a murine model. Methods The in vitro activity of FLZ or a combination of FLZ and Meth-Gin was determined against Candida albicans by the agar well diffusion, macrodilution, time-kill and the biofilm eradication methods. The therapeutic efficacy of the formulations was assessed by analyzing the fungal load, pro-inflammatory cytokines, percent apoptotic cells and the histological changes in the vaginal tissues of the mice. Moreover, the renal toxicity the drug formulation was evaluated by analyzing the levels of the blood urea nitrogen (BUN) and creatinine. Results The results of in vitro study demonstrated that FLZ did not show any activity against C. albicans, whereas a combination of FLZ and Meth-Gin demonstrated greater activity as shown by the data of the zone of growth inhibition, MIC and time-kill assay. FLZ or Meth-Gin treatment could not completely cure VVC, whereas a combination of FLZ and Meth-Gin was greatly effective in the treatment of VVC. The vaginal tissue from mice of the infected control group had the highest fungal load of 155370 ± 20617 CFUs. Treatment with FLZ at a dose of 40 mg/kg reduced the fungal load to 120863 ± 10723 CFUs. Interestingly, the mice treated with a combination of FLZ (40 mg/kg) and Meth-Gin (200 mg/kg) had a fungal load of 256 ± 152 CFUs. Besides, FLZ and Meth-Gin combination effectively reduced the pro-inflammatory cytokines (IL-1β, TNF-α and IL-17) and the percentage of apoptotic cells in the vaginal tissues. Likewise, the histological analysis revealed the epithelial necrosis, shedding and ulceration in the vaginal tissue, whereas treatment with FLZ and Meth-Gin combination reversed the histopathological changes in the vaginal epithelium and lamina propria. Conclusion The findings of the current study suggest that the co-administration of Meth-Gin and FLZ may have a potential therapeutic effect in the treatment of azole-resistant candidiasis.
Assessment of contamination of Salmonella spp. in imported black pepper and sesame seed and salmonella inactivation by gamma irradiation

This study shows the frequency of seeds samples contaminated by Salmonella spp. collected randomly from local markets; on 30 black pepper sample no contaminated sample was found while Salmonella spp. was detected in 3 of 36 (8.3%) analyzed sesame samples; three different serotypes were identified: S. Montevideo, S. Stanleyville e S. Tilene. The efficacy of gamma irradiation to inactivate Salmonella Montevideo in black pepper and sesame irradiated between 1 and 5 kGy was evaluated. 3 kGy is sufficient to reduce of 3-4 log CFU/g; whereas 5 kGy have been need to reduce 5.5-6 log CFU/g for samples of black pepper and sesame. No statistically significant differences were found between black pepper and sesame.
Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art

Abstract Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic disorder, whose knowledge remains limited and the management of these patients changes continuously. This review provides a summary of the most recent advancements in the pathogenesis of this disease and the new drugs introduced into the market to overcome some of the unmet needs of traditional therapies. Nowadays, the most fruitful diagnostic examinations are 24-hour impedance-pH monitoring, which allows us to separate true NERD from esophageal functional disorders and high-resolution manometry, which helps to exclude the existence of motility disorders sharing the same symptoms of GERD. Proton pump inhibitors (PPIs) remain the first-choice therapy in the treatment of GERD, but a consistent proportion of these patients continue to experience symptoms despite their intake. These cases pertain mainly to the subpopulation with non-erosive reflux disease (NERD) and represent very challenging clinical situations, because it is mandatory to understand the reasons for PPI failure. The management of these difficult patients requires necessarily to test them and avoid the use of empiric treatments that are often unsuccessful, costly and potentially dangerous. Recently, several new drugs have been used to increase the defensive properties of this mucosa with promising results in randomized clinical trials.
SARS-CoV-2 Subgenomic RNA Kinetics in Longitudinal Clinical Samples

Abstract Background In light of numerous reports during the COVID-19 pandemic demonstrating an inexplicable persistence of viral RNA in clinically recovered patients, subgenomic RNAs (sgRNA) have recently been reported as potential molecular viability markers for SARS-CoV-2. However, few data are available on the longitudinal kinetics of sgRNA, compared with genomic RNA (gRNA), in clinical samples. Methods We analyzed 536 samples from 205 patients with COVID-19 from placebo-controlled, outpatient trials of Peginterferon Lambda-1a (Lambda; n=177) and favipiravir (n=359). Nasal swabs were collected at three time points in the Lambda (Day 1, 4 and 6) and favipiravir (Day 1, 5, and 10) trials. N-gene gRNA and sgRNA were quantified by RT-qPCR. To investigate the decay kinetics in vitro, we measured gRNA and sgRNA in A549ACE2+ cells infected with SARS-CoV-2, following treatment with remdesivir or DMSO control. Results At six days in the Lambda trial and ten days in Favipiravir trial, sgRNA remained detectable in 51.6% (32/62) and 49.5% (51/106) of the samples, respectively. Cycle threshold values for gRNA and sgRNA were highly linearly correlated (Pearsons r= 0.87) and the daily rate of increase did not differ significantly in Lambda (1.36 cycles/day vs 1.36 cycles/day; p = 0.97) or favipiravir (1.03 cycles/day vs 0.94 cycles/day; p=0.26) trials. From samples collected 15-21 days after symptom onset, sgRNA was detectable in 48.1% (40/83) of participants. In SARS-CoV-2 infected A549ACE2+ cells treated with remdesivir, the rate of Ct increase did not differ between gRNA and sgRNA. Conclusions In clinical samples and in vitro, sgRNA was highly correlated with gRNA and did not demonstrate different decay patterns to support its application as a molecular viability marker.
How the COVID-19 pandemic is shaping research in Africa: inequalities in scholarly output and collaborations and new opportunities for scientific leadership

Background: Scientometrics enables scholars to assess and visualize emerging research trends and hot-spots in the scientific literature from a quantitative standpoint. In the last decades, Africa has nearly doubled its absolute count of scholarly output, even though its share in global knowledge production has dramatically decreased. This limited contribution of African scholars to the global research output is in part impacted by the availability of adequate infrastructures and research collaborative networks. The still ongoing COVID-19 pandemic has profoundly impacted the way scholarly research is conducted, published and disseminated. However, the COVID-19 related research focus, the scientific productivity and the research collaborative network of African researchers during the ongoing COVID-19 pandemic remain to be elucidated yet. Methods: This study aimed to clarify the COVID-19 research patterns among African researchers and estimate the strength of collaborations and partnerships between African researchers and scholars from the rest of the world during the COVID-19 pandemic, collecting data from electronic scholarly databases such as Web of Sciences (WoS), PubMed/MEDLINE and African Journals OnLine (AJOL), the largest and prominent platform of African-published scholarly journals. Results: In the present bibliometric study, we found that COVID-19 related collaboration patterns varied among African regions, being shaped and driven by historical, social, cultural, linguistic, and even religious determinants. For instance, most of the scholarly partnerships occurred with formerly colonial countries (like European or North-American countries). In other cases, scholarly ties of North African countries were above all with the Kingdom of Saudi Arabia. In terms of amount of publications, South Africa and Egypt were among the most productive countries. Discussion: Bibliometrics and, in particular, scientometrics can help scholars identify research areas of particular interest, as well as emerging topics, such as the COVID-19 pandemic. With a specific focus on the still ongoing viral outbreak, they can assist decision- and policy-makers in allocating funding and economic-financial, logistic, organizational, and human resources, based on the specific gaps and needs of a given country or research area. Conclusions: In conclusion, the ongoing COVID-19 pandemic has exerting a subtle, complex impact on research and publishing patterns in African countries. On the one hand, it has distorted and even amplified existing inequalities and disparities in terms of amount of scholarly output, share of global knowledge, and patterns of collaborations. On the other hand, COVID-19 provided new opportunities for research collaborations.
A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL)

Objectives Chronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB. Methods In this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0–8 weeks) and at the end (5–6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible. Results Of the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA. Conclusion CPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.
The Potential Diagnostic Accuracy of Circulating MicroRNAs for Leukemia: A Meta-Analysis

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.