Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms. This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.
Recombinant Live Attenuated Influenza Vaccine Viruses Carrying Conserved T Cell Epitopes of Human Adenoviruses Induce Functional Cytotoxic T Cell Responses and Protect Mice against both Infections

Human adenoviruses (AdVs) are one of the most common causes of acute respiratory viral infections worldwide. Multiple AdV serotypes with low cross-reactivity circulate in the human population, making the development of an effective vaccine very challenging. In the current study, we designed a cross-reactive AdV vaccine based on the T-cell epitopes conserved among various AdV serotypes, which were inserted into the genome of a licensed cold-adapted live attenuated influenza vaccine (LAIV) backbone. We rescued two recombinant LAIV-AdV vaccines by inserting the selected AdV T-cell epitopes into the open reading frame of full-length NA and truncated the NS1 proteins of the H7N9 LAIV virus. We then tested the bivalent vaccines for their efficacy against influenza and human AdV5 in a mouse model. The vaccine viruses were attenuated in C57BL/6J mice and induced a strong influenza-specific antibody and cell-mediated immunity, fully protecting the mice against virulent influenza virus infection. The CD8 T-cell responses induced by both LAIV-AdV candidates were functional and efficiently killed the target cells loaded either with influenza NP366 or AdV DBP418 peptides. In addition, high levels of recall memory T cells targeted to an immunodominant H2b-restricted CD8 T-cell epitope were detected in the immunized mice after the AdV5 challenge, and the magnitude of these responses correlated with the level of protection against pulmonary pathology caused by the AdV5 infection. Our findings suggest that the developed recombinant vaccines can be used for combined protection against influenza and human adenoviruses and warrant further evaluation on humanized animal models and subsequent human trials.
Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study

Abstract Objective To assess the prevalence of diabetes and its risk factors. Design Population based, cross sectional study. Setting 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017. Participants 75 880 participants aged 18 and older—a nationally representative sample of the mainland Chinese population. Main outcome measures Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA1c). Results The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%). Conclusion The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.
Inhibition of RNA Helicase Activity Prevents Coxsackievirus B3-Induced Myocarditis in Human iPS Cardiomyocytes

Aims: Coxsackievirus B3 (CVB3) is known to be an important cause of myocarditis and dilated cardiomyopathy. Enterovirus-2C (E2C) is a viral RNA helicase. It inhibits host protein synthesis. Based on these facts, we hypothesize that the inhibition of 2C may suppress virus replication and prevent enterovirus-mediated cardiomyopathy. Methods and Results: We generated a chemically modified enterovirus-2C inhibitor (E2CI). From the in vitro assay, E2CI was showed strong antiviral effects. For in vivo testing, mice were treated with E2CI intraperitoneally injected daily for three consecutive days at a dose of 8 mg/kg per day, after CVB3 post-infection (p.i) (CVB3 + E2CI, n = 33). For the infected controls (CVB3 only, n = 35), mice were injected with PBS (phosphate buffered saline) in a DBA/2 strain to establish chronic myocarditis. The four-week survival rate of E2CI-treated mice was significantly higher than that of controls (92% vs. 71%; p < 0.05). Virus titers and myocardial damage were significantly reduced in the E2CI treated group. In addition, echocardiography indicated that E2CI administration dramatically maintained mouse heart function compared to control at day 28 p.i chronic stage (LVIDD, 3.1 ± 0.08 vs. 3.9 ± 0.09, p < 0.01; LVDS, 2.0 ± 0.07 vs. 2.5 ± 0.07, p < 0.001; FS, 34.8 ± 1.6% vs. 28.5 ± 1.5%; EF, 67. 9 ± 2.9% vs. 54.7 ± 4.7%, p < 0.05; CVB3 + E2CI, n = 6 vs. CVB3, n = 4). Moreover, E2CI is effectively worked in human iPS (induced pluripotent stem cell) derived cardiomyocytes. Conclusion: Enterovirus-2C inhibitor (E2CI) was significantly reduced viral replication, chronic myocardium damage, and CVB3-induced mortality in DBA/2 mice. These results suggested that E2CI is a novel therapeutic agent for the treatment of enterovirus-mediated diseases.
Chemical signatures of soft tissues distinguish between vertebrates and invertebrates from the Carboniferous Mazon Creek Lagerstätte of Illinois

The chemical composition of fossil soft tissues is a potentially powerful and yet underutilized tool for elucidating the affinity of problematic fossil organisms. In some cases, it has proven difficult to assign a problematic fossil even to the invertebrates or vertebrates (more generally chordates) based on often incompletely preserved morphology alone, and chemical composition may help to resolve such questions. Here, we use in situ Raman microspectroscopy to investigate the chemistry of a diverse array of invertebrate and vertebrate fossils from the Pennsylvanian Mazon Creek Lagerstätte of Illinois, and we generate a ChemoSpace through principal component analysis (PCA) of the in situ Raman spectra. Invertebrate soft tissues characterized by chitin (polysaccharide) fossilization products and vertebrate soft tissues characterized by protein fossilization products plot in completely separate, non‐overlapping regions of the ChemoSpace, demonstrating the utility of certain soft tissue molecular signatures as biomarkers for the original soft tissue composition of fossil organisms. The controversial problematicum Tullimonstrum, known as the Tully Monster, groups with the vertebrates, providing strong evidence of a vertebrate rather than invertebrate affinity.
Comparison of self-report versus accelerometer – measured physical activity and sedentary behaviors and their association with body composition in Latin American countries

Background Most population-based studies from Latin America have used questionnaires to measure physical activity (PA) and sedentary behaviors (SB). Low reliability and validity of the questionnaires has limited the capacity to examine associations between PA and health. The purpose of this study was to compare self-reported and accelerometer–measured PA and SB and their associations with body composition in Latin American countries. Methods Data were obtained from the Latin American Study of Nutrition and Health (aged 15–65 years), collected from September 2014 to February 2015. PA and SB were assessed using the International Physical Activity Questionnaire (long version) and the Actigraph GT3X+ accelerometer. Outcomes of interest included: body mass index (BMI), waist (WC) and neck circumference (NC). We used the Pearson and intraclass correlation coefficient, Bland-Altman plots, and multilevel linear regression models. Results Mean moderate-to-vigorous physical activity (MVPA) by accelerometer and IPAQ were 34.4 min/day (95% CI: 33.4 to 35.4) and 45.6 min/day (95% CI: 43.2 to 48.1), respectively. For SB (accelerometer and IPAQ) the means were 573.1 (95% CI: 568.2 to 577.9) and 231.9 min/day (95% CI: 225.5 to 238.3). MVPA, measured by the accelerometer was negatively associated with BMI (β = -1.95; 95% CI: -2.83 to -1.08), WC (β = -5.04; 95% CI: -7.18 to -2.89) and NC (β = -1.21; 95% CI: -1.79 to -0.63). The MVPA estimated through IPAQ was not significantly associated with any of the three outcome variables. SB, measured by the accelerometer, was positively associated with BMI (β = 0.26; 95% CI: 0.08 to 0.44) and WC (β = 0.48; 95% CI: 0.13 to 0.91). SB estimated through IPAQ was positively associated with NC only. Conclusions Low correlation coefficients were observed for accelerometer-derived and IPAQ-reported estimates of PA and SB. Caution is advised when making comparisons between accelerometer-measured and self-reported PA and SB. Further, studies examining associations between movement and health should discuss the impact of PA and SB measurement methodology on the results obtained.
Genetic parameters for linear type traits in Czech Holstein cattle.

The objectives of this study were to estimate genetic parameters for 18 currently recorded linear conformation traits in Czech Holstein cattle. The data set consisted of 78 886 first-lactating Holstein cows. Traits, all scored on a 9-point scale, were fore udder attachment, rear udder height, udder depth, rear udder width, central ligament, teat length, front teat placement, rear teat position, stature, angularity, chest width, body depth, rump angle, rump width, rear legs rear view, rear leg set (side view), foot angle, and bone quality. Uni- and bivariate animal models were used. The models included fixed effects of herd-date of clas - sification-classifier, classifier, and season of calving, quadratic regressions on age at calving and on days in milk and the random effect of animal. Heritability estimates obtained in univariate and in bivariate analyses were of similar magnitude. Heritabilities ranged from 0.17 to 0.32 for udder traits, 0.10 to 0.16 for foot and leg traits, and 0.18 to 0.45 for traits related to body size. Genetic correlations among the currently recorded linear traits ranged from -0.67 between foot angle and rear leg set (side view) to 0.75 between fore udder attachment and udder depth. Substantial genetic correlations were found for the following pairs of traits: rear udder height and rear udder width (0.70), chest width and body depth (0.69), front teat placement and rear teat position (0.68), angularity and bone quality (0.67). Corresponding phenotypic correlations for most pairs of traits were similar in direction but smaller in magnitude than the genetic correlations .
Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns.
Predicting bone and soft tissue alterations of immediate implant sites in the esthetic zone using clinical parameters.

BACKGROUND Immediate implantation is generally a predictable treatment, but sometimes there are significant tissue alterations at the surgical site which compromise clinical outcomes. PURPOSE This study aimed to investigate the association between tissue alterations and different clinical parameters in esthetic areas following immediate implant placement and provisionalization. MATERIALS AND METHODS Clinical parameters were measured at 36 non-grafted immediate implant sites enrolled in a randomized controlled trial. Alterations of bone and soft tissue were measured at 12 months after the treatment. Stepwise linear regression analysis was performed to analyze the association between different clinical parameters and outcomes of interest. RESULTS Gingival thickness 3 mm apical to the gingival margin (GT3) was positively associated with recession of mid-buccal gingival margin, while vertical distance between the buccal gingival margin and the crest (GM-bone) was negatively associated (P = .03, .01). Flap elevation and older age were positively associated with recession of the interproximal gingival margin (P = .04, .01). Horizontal defect dimension was positively associated with buccal ridge dimensional reduction while gingival thickness at free gingival margin (GT1) was negatively associated (P = .01, .04). Regarding interproximal bone level change, none of the clinical parameters was significantly associated. CONCLUSIONS Gingival phenotype was the only parameter significantly associated with both buccal gingival recession and buccal ridge dimensional reduction. It is important to assess clinical parameters before and during immediate implant procedure.
Assessments of Water-Soluble Inorganic Ions and Heavy Metals in Atmospheric Dustfall and Topsoil in Lanzhou, China

The chemical features of atmospheric dustfall and topsoil in the same region could reflect the processes of the migration, transport, and diffusion of pollutants in the atmospheric-soil system. Samples of atmospheric dustfall and topsoil were collected in Lanzhou City. The contents and correlation of water-soluble inorganic ions (WSIIs) and heavy metals in dustfall and topsoil were analyzed, the sources of heavy metals and WSIIs in dustfall were distinguished, and the potential ecological risks of heavy metals in dustfall and topsoil were evaluated. The highest contents of WSIIs are SO42− (18,594 mg·kg−1) and Ca2+ (10,070 mg·kg−1) in dustfall, and for SO42− (8271 mg·kg−1) and Na+ (1994 mg·kg−1) in topsoil. The concentrations of heavy metals (Pb, Cu, Zn, Cr, Cd, and Ni) in dustfall are considerably higher than those in topsoil. Combustion of biomass and coal, transportation and industrial activities are the major anthropogenic sources of WSIIs and heavy metals in Lanzhou. Pollution of heavy metals except Cr and Ni in dustfall, and Cu, Cr, and Ni in topsoil was up to different degrees, where the pollution of Cd was serious. The risk of Cd in dustfall is high while moderate in topsoil. This research could offer a reference for the atmospheric particle pollution prevention and control in Lanzhou.
Obstructive Sleep Apnea: A View from the Back Door

Obstructive sleep apnea (OSA) is a common disease that may affect up to 50% of the adult population and whose incidence continues to rise, as well as its health and socio-economic burden. OSA is a well-known risk factor for motor vehicles accidents and decline in work performance and it is frequently accompanied by cardiovascular diseases. The aim of this Special Issue is to focus on the characteristics of OSA in special populations which are less frequently investigated. In this regard, seven groups of experts in the field of sleep medicine gave their contribution in the realization of noteworthy manuscripts which will support all physicians in improving their understanding of OSA with the latest knowledge about its epidemiology, pathophysiology and comorbidities in special populations, which will serve as a basis for future research.
Effect of selenium supplementation on the presence of mastitis in dairy cows.

Resumen La mastitis es la enfermedad infectocontagiosa de mayor relevancia en la producción lechera. Los objetivos de este trabajo fueron: determinar el efecto de la suplementación con selenio mediante variaciones de la actividad enzimática de la glutatión peroxidasa; detectar una posible interacción entre la suplementación y la antibióticoterapia de rutina aplicada durante la lactancia y hallar una relación entre concentraciones de oligoelementos y presencia de mastitis clínica en vacas lecheras. Se trabajó con 50 animales adultos entre tercera y cuarta lactancia, divididos en cinco grupos de acuerdo a su sanidad y tratamiento: Grupo 1: 10 animales sanos (sin mastitis), Grupo 2: 10 animales con mastitis y suplementados con selenio, Grupo 3: 10 animales con mastitis y tratados con antibióticos, Grupo 4: 10 animales con mastitis, suplementados con selenio y tratados con antibióticos, y Grupo 5: 10 animales con mastitis. Se efectuaron dos muestreos, uno en sangre para medir la actividad de la glutatión peroxidasa, contenido de cobre, hierro y zinc y otro en leche para realizar la medición de indicadores de salud de la ubre: recuento de células somáticas y unidades formadoras de colonias. La presencia de mastitis clínica en vacas lecheras se vinculó con bajos niveles de actividad de glutatión peroxidasa y los indicadores de salud de la ubre mostraron una tendencia a incrementar a medida que el nivel de actividad de la enzima disminuía. El efecto de la suplementación con selenio se evidenció mediante un incremento en la actividad de la glutatión peroxidasa. Sin embargo, no mejoró el estado de salud de los animales ni el recuento de células somáticas o el número de unidades formadoras de colonias/ml de leche. Esto indicaría que la suplementación con selenio podría utilizarse sólo como una herramienta auxiliar en la maximización de la respuesta inmune del animal, pero no para sustituir la implementación de las medidas tradicionales de control de mastitis. El tratamiento con antibiótico no modificó en ningún caso el efecto de la suplementación con selenio. Palabras clave: selenio, mastitis, glutatión peroxidasa, vaca lechera.
Clostridioides difficile in national food surveillance, Slovenia, 2015 to 2017

Background Clostridioides difficile is an important human and animal intestinal pathogen. Because of increasing indications of an association between C. difficile and food, in 2015, the Administration of the Republic of Slovenia for Food Safety, Veterinary Sector and Plant Protection (UVHVVR) included C. difficile in its national food surveillance. Aim We aim to report the results and experience with a nationwide and long-term testing of food for C. difficile as a part of a regular national food surveillance programme. Methods Retail minced meat and meat preparations (beef, pork and poultry) were sampled within a three-year period, 2015 to 2017. Selected raw retail vegetables, leaf salads and root vegetables, and ready-to-eat salads were only sampled during 2016 and 2017. Seafood was only sampled in 2017. Results Altogether, 434 samples were tested, with 12 of 336 (3.6%) meat samples and 6 of 98 (6.1%) raw vegetables contaminated with C. difficile. Twelve of 18 recovered food isolates were toxigenic (toxinotypes 0, III, V, XII). The isolates belonged to 13 different PCR ribotypes, 001 being most common (5 isolates). Several food types with an increased potential of being contaminated with C. difficile were detected by surveillance. Conclusion The three-year C. difficile testing within the national food surveillance revealed a low proportion of C. difficile-contaminated food and high genotype variability. Because the risk of C. difficile infection associated with C. difficile-contaminated food is unknown, no measures were recommended in the case of positive results.
OPTIMISATION DES PARAMETRES DE DOSAGE DE LA LDH TOTALE (LACTATE –DESHYDROGENASE) PAR SPECTROPHOTOMETRIE DANS LA VIANDE OVINE

Les differents parametres de dosage spectrophotometriques de l’activite de l’enzyme lactate-deshydrogenase (LDH) dans la viande ovine ont ete optimises, et ce dans le but d’etudier par la suite l’influence de l’application de facteurs technologiques tels que la chaleur ou le froid sur son activite et permettre d’en deduire si cette viande a subi ou pas un de ces traitements. Le muscle retenu pour notre etude est le diaphragme, car ce muscle peut etre preleve sans deprecier la carcasse. L'influence de la concentration de substrat (Km), du pH, du tampon, de la temperature de pre-incubation, de la duree d’incubation sur les activites enzymatiques dans le muscle ont ete etudies. Nous avons egalement etudie la repetabilite ainsi que la reproductibilite de la methode de dosage.