bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technologic Considerations of Creation Dosage Form of Original Substance 3,7-diazabicyclo[3.3.1]nonane
Authors: Brkich G. E. , Pyatigorskaya N. V. , Zyryanov O. A. , Demina N. B. , Bakhrushina E. O. , Krasnyuk I. I. 
Published: November 2020

Introduction. An innovative pharmaceutical substance based on the 3,7-diazabicyclo[3.3.1]nonane derivative provides long-term activation of AMPA receptors and the production of neurotrophic factors, which makes it possible to use it for the treatment of cognitive impairments and rehabilitation of patients who have undergone acute brain hypoxia. Given that this substance is able to be absorbed through the walls of the gastrointestinal tract and pass through the blood-brain barrier, there are no restrictions on the development of an oral dosage form. In addition, the oral dosage form has significant advantages when used in geriatric and pediatric practice.Aim. The aim of the work was to carry out a comparative study of the possibility of using gelatin and hypromellose capsules for the development of the composition and technology for obtaining a dosage form containing a pharmaceutical substance based on a 3,7-diazabicyclo[3.3.1]nonane derivative.Materials and methods. The study of the «Dissolution» test of gelatinous and hypromellose capsules was carried out on an ERWEKA DT 720 «Paddle stirrer» apparatus at a stirrer rotation speed of 50 rpm in three media: pH 1.2, pH 4.5 and pH 6.8. The content of the substance in each sample was determined by high performance liquid chromatography with UV detection.Results and discussion. The results of the development and testing of capsules containing an original pharmaceutical substance of nootropic action based on a derivative of 3,7-diazabicyclo[3.3.1]nonane, which has low pharmaceutical and technological characteristics and is practically insoluble in water, are presented. The D/S value was ≥250.00 ml in each physiological pH range. The results of determining the dissolution of the developed dosage form in three media at pH values of 1.2, 4.5 and 6.8 showed a positive effect of the technology used on the solubility of the substance.Conclusion. A significant increase in the solubility of the practically insoluble substance of the 3,7-diazabicyclo[3.3.1]nonane derivative in the developed dosage form was shown, which is the result of the use of a well-founded complex of excipients and the technology of moisture-activated granulation. According to the results obtained, (77.60 ± 2.50) % of the substance passes into the dissolution medium with a pH of 4.5 in 45 minutes. The research results are used to develop a technological scheme for obtaining a finished dosage form, its indicators and quality standards.
Sexual Behavioral Patterns of Kenyan University Student-Athletes: Implications for Sports Managers
Authors: G. Rintaugu Elijah , K. Thangu Edna , Oyeyemi Adewale , A. Monyeki Makama 
Published: November 2020

Background. The debate on whether participation in sports enhances or curtails risky sexual behavior among athletes continues. The purpose of the study was to establish the sexual behavior patterns and associated high risks among University student-athletes.
Methods. A cross-sectional survey research design was used to collect self-report data on sexual behaviors from university student-athletes (n = 151) who participated in a University sports tournament. Descriptive statistics of frequencies and proportions and inferential statistics of chi-square test of independent measures were used to analyze the data. Majority (65%) of the student-athletes were taking part in Ball games and Racket games (13.9%).
Results. About a third (33%) of the student-athletes had their first sexual debut while aged between 18 and 20 years, 60% had regular sexual partners, over 30% had more than one sexual partner and 67% would have sexual intercourse with strangers; only 58% of these would seek the sexual history of the strangers. More than half (55%) of the student-athletes frequently used condoms to prevent pregnancies and sexually transmitted diseases, but only 39% of them always used condoms with their sexual partners in the last six months. The participants’ sexual behaviors differed significantly (p < .05) by their gender. Males tended to start having sexual intercourse earlier (p < .002), had more than one sexual partner (p < 0.001) and would always use condoms (p < .001) than females, but more females than males would have sexual intercourse with a stranger (p < .001).
Conclusions. Kenyan University student-athletes are sexually active and are faced with high risk sexual behaviors like multiple sexual partners and sexual intercourse with strangers. The difference in patterns of sexual behavior between male and female student-athletes calls for gender specific interventions by programmers, policy makers and health workers.
Keywords: sexual behaviors, student-athletes, sexually transmitted diseases (STD’s).
If really “without school and inheritors”?
Authors: Ilnytskyi Mykola 
Published: November 2020

The paper analyzes the return of Bohdan Ihor Antonych’s name to the literature after several decades of suppression and prohibition by the Soviet totalitarian regime. The author also focuses on the interpretation of the poet’s work in Ukrainian and foreign literary studies.
The researcher points out the following historical and cultural factors: partial liberalization of the communist regime in the Soviet Union; high appreciation of Antonych’s work by leading poets and literary critics in Ukraine and the Ukrainian diaspora; translations of works into foreign languages, in particular, Slavic ones; the influence of the poet’s work on the generations of the 1960s—1980s.
Special attention is paid to the cooperation of American scholars and translators Watson Kirkconnell and Constantine H. Andrysyshen in translating the Ukrainian poet’s texts into English.
The researcher traces the changes in views on Antonych’s poetry: the claims that he was a talented poet who did not have time to fully realize his talent due to his early death were eventually substituted by recognition of his poetry’s kinship with the works of Western European modernist poets such as R. M. Rilke, T. S. Eliot, F. G. Lorca, Cz. Miłosz.
The paper also highlights the discussion on the stylistic dominant of Antonych’s poetry and focuses on the elements of different literary movements, namely futurism, imagism, and surrealism. It is emphasized that the poet was not only interested in the issues of style but also shaped the different styles of the time with his special features. He characterized impressionism as the relation of color to light, pointed out the idea of movement in futurism, focused on the geometric outlines of real objects in cubism, appreciated pure harmony of geometric patterns in suprematism. Moreover, Antonych’s poetry was related to creating myths, based on the tradition of the national folklore worldview.
Risk Factors and Outcomes of Treatment Delays in Lyme Disease: A Population-Based Retrospective Cohort Study
Authors: Hirsch Annemarie G. , Poulsen Melissa N. , Nordberg Cara , Moon Katherine A. , Rebman Alison W. , Aucott John N. , Heaney Christopher D. , Schwartz Brian S. 
Published: November 2020

Background: Longer time between symptom onset and treatment of Lyme disease has been associated with poor outcomes. Reducing time-to-treatment requires knowledge of risks for treatment delays. We conducted a population-based study to evaluate factors associated with delayed treatment of Lyme disease and the relation between delayed treatment and post-treatment Lyme disease syndrome (PTLDS).Methods: We mailed questionnaires to 5,314 individuals with a Lyme disease diagnosis or blood test followed by an antibiotic order in the medical record of a Pennsylvania health system from 2015 to 2017. Analyses were confined to 778 respondents who reported that they were treated for Lyme disease within the past 5 years and reported a rash and/or a positive blood test for Lyme disease. Time-to-treatment was calculated as the sum of two windows before and after seeking care for Lyme disease symptoms: time to first medical contact and time under care. We used logistic regression to evaluate factors associated with delayed time-to-treatment in each time window (&gt;14 days vs. ≤14 days) and the association between total time-to-treatment (&gt;30 days vs. ≤30 days) and PTLDS. We used inverse probability weighting to calculate estimates for the study's source population (5,314 individuals sent questionnaires).Results: In the source population, 25% had time to first contact &gt;14 days, 21% had time under care &gt;14 days, and 31% had a total time-to-treatment &gt;30 days. Being uninsured and attributing initial symptoms to something other than Lyme disease were positively associated with delayed time to first medical contact, while seeking care at an urgent care or emergency setting (vs. primary care) was negatively associated. Diagnoses between November and April, and the absence of rash were positively associated with delays. Individuals whose treatment was delayed, defined as time-to treatment &gt;30 days had 2.26 (95% confidence interval: 1.25, 4.05) times the odds of PTLDS as those who were treated within 30 days of symptom onset.Conclusions: In a population-based study in Pennsylvania, one-third of Lyme disease patients reported delayed treatment, which was associated with PTLDS. To improve Lyme disease outcomes, prevention efforts should aim to reduce the time before and after seeking care.
Divergent Effects of the N-Methyl-D-Aspartate Receptor Antagonist Kynurenic Acid and the Synthetic Analog SZR-72 on Microcirculatory and Mitochondrial Dysfunction in Experimental Sepsis
Authors: Juhász László , Rutai Attila , Fejes Roland , Tallósy Szabolcs P. , Poles Marietta Z. , Szabó Andrea , Szatmári István , Fülöp Ferenc , Vécsei László , Boros Mihály , Kaszaki József 
Published: November 2020

Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynamic deterioration. Kynurenic acid (KYNA) is a metabolite of the kynurenine pathway of tryptophan catabolism with pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenously administered KYNA or the synthetic analog SZR-72 affects the microcirculation and mitochondrial function in a clinically relevant rodent model of intraabdominal sepsis.Methods: Male Sprague–Dawley rats (n = 8/group) were subjected to fecal peritonitis (0.6 g kg−1 feces ip) or a sham operation. Septic animals were treated with sterile saline or received ip KYNA or SZR-72 (160 μmol kg−1 each) 16 and 22 h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions (PaO2/FiO2 ratio, mean arterial pressure, urea, AST/ALT ratio and lactate levels, respectively) based on the Rat Organ Failure Assessment (ROFA) score. The ratio of perfused vessels (PPV) of the ileal serosa was quantified with the intravital imaging technique. Complex I- and II-linked (CI; CII) oxidative phosphorylation capacities (OXPHOS) and mitochondrial membrane potential (ΔΨmt) were evaluated by High-Resolution FluoRespirometry (O2k, Oroboros, Austria) in liver biopsies. Plasma endothelin-1 (ET-1), IL-6, intestinal nitrotyrosine (NT) and xanthine oxidoreductase (XOR) activities were measured as inflammatory markers.Results: Sepsis was characterized by an increased ROFA score (5.3 ± 1.3 vs. 1.3 ± 0.7), increased ET-1, IL-6, NT and XOR levels, and decreased serosal PPV (65 ± 12% vs. 87 ± 7%), ΔΨmt and CI–CII-linked OXPHOS (73 ± 16 vs. 158 ± 14, and 189 ± 67 vs. 328 ± 81, respectively) as compared to controls. Both KYNA and SZR-72 reduced systemic inflammatory activation; KYNA treatment decreased serosal perfusion heterogeneity, restored PPV (85 ± 11%) and complex II-linked OXPHOS (307 ± 38), whereas SZR-72 improved both CI- and CII-linked OXPHOS (CI: 117 ± 18; CII: 445 ± 107) without effects on PPV 24 h after sepsis induction.Conclusion: Treatment with SZR-72 directly modulates mitochondrial respiration, leading to improved conversion of ADP to ATP, while administration of KYNA restores microcirculatory dysfunction. The results suggest that microcirculatory and mitochondrial resuscitation with KYNA or the synthetic analog SZR-72 might be an appropriate supportive tool in sepsis therapy.
Effects of Exosomes on Neurological Function Recovery for Ischemic Stroke in Pre-clinical Studies: A Meta-analysis
Authors: Huang Mudan , Hong Zhongqiu , Xiao Chongjun , Li Lili , Chen Lilin , Cheng Shimei , Lei Tingting , Zheng Haiqing 
Published: November 2020

Background: Exosomes, especially stem cell-derived exosomes, have been widely studied in pre-clinical research of ischemic stroke. However, their pooled effects remain inconclusive.Methods: Relevant literature concerning the effects of exosomes on neurological performance in a rodent model of ischemic stroke was identified via searching electronic databases, including PubMed, Embase, and Web of Science. The primary outcomes included neurological function scores (NFS) and infarct volume (IV), and the secondary outcomes were several pro-inflammatory factors and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells. Subgroup analyses regarding several factors potentially influencing the effects of exosomes on NFS and IV were also conducted.Results: We identified 21 experiments from 18 studies in the meta-analysis. Pooled analyses showed the positive and significant effects of exosomes on NFS (standardized mean difference −2.79; 95% confidence interval −3.81 to −1.76) and IV (standardized mean difference −3.16; 95% confidence interval −4.18 to −2.15). Our data revealed that the effects of exosomes on neurological outcomes in rodent stroke models might be related to routes of administration and exosomes sources. In addition, there was significant attenuation in pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and interleukin-1β, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells when undergoing exosomes treatment.Conclusion: Cell-derived exosomes treatment demonstrated statistically significant improvements in structural and neurological function recovery in animal models of ischemic stroke. Our results also provide relatively robust evidence supporting cell-derived exosomes as a promising therapy to promote neurological recovery in stroke individuals.
Peripheral Nervous System Involvement in Late-Onset Cobalamin C Disease?
Authors: Chu Xujun , Meng Lingchao , Zhang Wei , Luo Jinjun , Wang Zhaoxia , Yuan Yun 
Published: November 2020

Background: Cobalamin C (cblC) has a fundamental role in both central and peripheral nervous system function at any age. Neurologic manifestations may be the earliest and often the only manifestation of hereditary or acquired cblC defect. Peripheral neuropathy remains a classical but underdiagnosed complication of cblC defect, especially in late-onset cblC disease caused by mutations in the methylmalonic aciduria type C and homocysteinemia (MMACHC) gene. So the clinical, electrophysiological, and pathological characteristics of late-onset cblC disease are not well-known.Methods: A retrospective study of patients with late-onset cblC disease was conducted at our hospital on a 3-year period. The neuropathy was confirmed by the nerve conduction study. Sural biopsies were performed in 2 patients.Results: Eight patients were identified, with a mean onset age of 16.25 ± 6.07 years. All patients had methylmalonic aciduria, homocysteinemia, compound heterozygous MMACHC gene mutations were detected in all patients, and 7/8 patients with c.482G&gt;A mutation. One patient concomitant with homozygote c.665C&gt;T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. All patients showed limb weakness and cognitive impairment. Five patients had possible sensorimotor axonal polyneuropathy predominantly in the distal lower limbs. Sural biopsies showed loss of myelinated and unmyelinated fibers. Electro microscopy revealed crystalline-like inclusions bodies in Schwann cells and axonal degeneration.Conclusion: Late-onset cblC disease had possible heterogeneous group of distal axonal neuropathy. c.482G&gt;A mutation is a hot spot mutation in late-onset cblC disease.
Association of Odor Identification Ability With Amyloid-β and Tau Burden: A Systematic Review and Meta-Analysis
Authors: Tu Lihui , Lv Xiaozhen , Fan Zili , Zhang Ming , Wang Huali , Yu Xin 
Published: November 2020

Background: The associations between olfactory identification (OI) ability and the Alzheimer's disease biomarkers were not clear.Objective: This meta-analysis aimed to examine the associations between OI and Aβ and tau burden.Methods: Electronic databases (PubMed, Embase, PsycINFO, and Google Scholar) were searched until June 2019 to identify studies that reported correlation coefficients or regression coefficients between OI and Aβ or tau levels measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Pooled Pearson correlation coefficients were computed for the PET imaging and CSF biomarkers, with subgroup analysis for subjects classified into different groups.Results: Nine studies met the inclusion criteria. Of these, five studies (N = 494) involved Aβ PET, one involved tau PET (N = 26), and four involved CSF Aβ or tau (N = 345). OI was negatively associated with Aβ PET in the mixed (r = −0.25, P = 0.008) and cognitively normal groups (r = −0.15, P = 0.004) but not in the mild cognitive impairment group. A similar association with CSF total tau in the mixed group was also observed. No association was found between OI and CSF phosphorylated tau or Aβ42 in the subgroup analysis of the CSF biomarkers. Due to a lack of data, no pooled r value could be computed for the association between the OI and tau PET.Conclusion: The associations between OI ability and Aβ and CSF tau burden in older adults are negligible. While current evidence does not support the association, further studies using PET tau imaging are warranted.
Protein Kinase C Isozymes Associated With Relapse Free Survival in Non-Small Cell Lung Cancer Patients
Authors: Halvorsen Ann Rita , Haugen Mads Haugland , Öjlert Åsa Kristina , Lund-Iversen Marius , Jørgensen Lars , Solberg Steinar , Mælandsmo Gunhild M. , Brustugun Odd Terje , Helland Åslaug 
Published: November 2020

IntroductionProtein expression is deregulated in cancer, and the proteomic changes observed in lung cancer may be a consequence of mutations in essential genes. The purpose of this study was to identify protein expression associated with prognosis in lung cancers stratified by smoking status, molecular subtypes, and EGFR-, TP53-, and KRAS-mutations.MethodsWe performed profiling of 295 cancer-relevant phosphorylated and non-phosphorylated proteins, using reverse phase protein arrays. Biopsies from 80 patients with operable lung adenocarcinomas were analyzed for protein expression and association with relapse free survival (RFS) were studied.ResultsSpearman’s rank correlation analysis identified 46 proteins with significant association to RFS (p&lt;0.05). High expression of protein kinase C (PKC)-α and the phosporylated state of PKC-α, PKC-β, and PKC-δ, showed the strongest positive correlation to RFS, especially in the wild type samples. This was confirmed in gene expression data from 172 samples. Based on protein expression, unsupervised hierarchical clustering separated the samples into four subclusters enriched with the molecular subtypes terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI) (p=0.0001). Subcluster 2 contained a smaller cluster (2a) enriched with samples of the subtype PP, low expression of the PKC isozymes, and associated with poor RFS (p=0.003) compared to the other samples. Low expression of the PKC isozymes in the subtype PP and a reduced relapse free survival was confirmed with The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) samples.ConclusionThis study identified different proteins associated with RFS depending on molecular subtype, smoking- and mutational-status, with PKC-α, PKC-β, and PKC-δ showing the strongest correlation.
Total Flavonoids of Rhizoma Drynariae Enhances Angiogenic-Osteogenic Coupling During Distraction Osteogenesis by Promoting Type H Vessel Formation Through PDGF-BB/PDGFR-β Instead of HIF-1α/ VEGF Axis
Authors: Shen Zhen , Chen Zehua , Li Zige , Zhang Yan , Jiang Tao , Lin Haixiong , Huang Minling , Chen Huamei , Feng Junjie , Jiang Ziwei 
Published: November 2020

Background: Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney-tonifying traditional Chinese medicine Rhizoma Rrynariae, has been proved to be effective in treating osteoporosis, bone fractures and defects. However, pharmacological effects of TFRD on type H vessels, angiogenic-osteogenic coupling in distraction osteogenesis (DO) and the mechanism remain unclear. This study aims at investigating whether type H vessels exist in the DO model, effects of TFRD on angiogenic-osteogenic coupling and further elucidating the underlying mechanism.Methods: Rats models of DO and bone fracture (FR) were established, and then were separately divided into TFRD and control subgroups. Imageological and histological analyses were performed to assess bone and vessel formation. Immunofluorescent staining of CD31 and endomucin (Emcn) was conducted to determine type H vessel formation. Matrigel tube formation, ALP and Alizarin Red S staining assays were performed to test the effects of TFRD on angiogenesis or osteogenesis of endothelial precursor cells (EPCs) or bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, expression levels of HIF-1α, VEGF, PDGF-BB, RUNX2 and OSX were determined by ELISA, qPCR or western blot, respectively.Results: The in vivo results indicated more formed type H vessels in DO groups than in FR groups and TFRD obviously increased the abundance of type H vessels. Moreover, groups with higher abundance of type H vessels showed better angiogenesis and osteogenesis outcomes. Further in vitro experiments showed that TFRD significantly promoted while blocking PDGF-BB remarkably suppressed the angiogenic activity of EPCs under stress conditions. The levels of p-AKT and p-ERK1/2, downstream mediators of the PDGF-BB pathway, were up-regulated by TFRD but blocked by function blocking anti-PDGF-BB antibody. In contrast, the activated AKT and ERK1/2 and corresponding tube formation were not affected by the HIF-1α inhibitor. Besides, blocking PDGF-BB inhibited the osteogenic differentiation of the stretched BMSCs, but TFRD enhanced the osteogenic activity of BMSCs and ameliorated the inhibition, with more calcium nodes, higher ALP activity and mRNA and protein levels of RUNX2 and OSX.Conclusion: Type H vessels exist in the DO model and TFRD enhances angiogenic-osteogenic coupling during DO by promoting type H vessel formation via PDGF-BB/PDGFR-β instead of HIF-1α/VEGF axis.