bluuebunny/crossref_metadata_2025_split huggingface dataset:
Worldwide Assessment of Low- and Middle-Income Countries' Regulatory Preparedness to Approve Medical Products During Public Health Emergencies
Authors: Khadem Broojerdi Alireza , Alfonso Claudia , Ostad Ali Dehaghi Razieh , Refaat Mohamed , Sillo Hiiti Baran 
Published: August 2021

Background: Regulatory preparedness for public health emergencies is critical. However, responses to past emergencies, such as the 2009 H1N1 influenza pandemic and medical product shortages, have revealed sizable gaps in countries' regulatory capacity and preparedness. A systematic analysis of the regulatory preparedness of countries around the world has not yet been performed. The purpose of this study was to analyze and document the current regulatory preparedness status, highlight the related gaps and challenges in order to propose strategic, harmonized, and sustainable regulatory solutions to improve future responses to public health emergencies.Methods: From 2016 to 2020, we used the World Health Organization (WHO)'s Global Benchmarking Tool (GBT), a standardized instrument for identifying national regulatory authorities' strengths and gaps, to analyze the regulatory preparedness of 84 Member States, 95% of which were low- or middle-income countries. We analyzed whether participating Member States had not implemented, displayed ongoing implementation, had partially implemented, or had fully implemented 10 of the GBT's 268 sub-indicators most relevant to regulatory preparedness for public health emergencies.Findings: Only 10 Member States (12%) that underwent benchmarking had fully implemented all 10 sub-indicators related to regulatory preparedness for public health emergencies; 34 (40%) had fully implemented ≥50% of the emergency sub-indicators, and 20 (24%) had not fully implemented any of the sub-indicators. With regard to individual sub-indicators, regulatory preparedness ranged from 19 Member States (23%) fully implementing reliance on clinical trial decisions of others to 45 (59%) fully implementing legal provisions to fast-track (or expedite) marketing authorization applications.Interpretation: Many WHO Member States have limited regulatory preparedness for a public health emergency. Strengthening regulatory systems and promoting Good Regulatory Practices and reliance in these countries, to enable efficient response to emergencies, should be a global health priority.
Ten Color Multiparameter Flow Cytometry in Bone Marrow and Apheresis Products for Assessment and Outcome Prediction in Multiple Myeloma Patients
Authors: Riebl Veronika , Dold Sandra Maria , Wider Dagmar , Follo Marie , Ihorst Gabriele , Waldschmidt Johannes M. , Jung Johannes , Rassner Michael , Greil Christine , Wäsch Ralph , Engelhardt Monika 
Published: August 2021

ObjectiveIn clinical trials (CTs), the assessment of minimal residual disease (MRD) has proven to have prognostic value for multiple myeloma (MM) patients. Multiparameter flow cytometry (MFC) and next-generation sequencing are currently used in CTs as effective tools for outcome prediction. We have previously described 6- and 8-color MFC panels with and without kappa/lambda, which were equally reliable in detecting aberrant plasma cells (aPC) in myeloma bone marrow (BM) specimens. This follow-up study a) established a highly sensitive single-tube 10-color MFC panel for MRD detection in myeloma samples carrying different disease burden (monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), MM), b) evaluated additional, rarely used markers included in this panel, and c) assessed MRD levels and the predictive value in apheresis vs. BM samples of MM patients undergoing autologous stem cell transplantation (ASCT).Methods + ResultsThe 10-color MFC was performed in BM and apheresis samples of 128 MM and pre-MM (MGUS/SMM) patients. The markers CD28, CD200, CD19, and CD117 underwent closer examination. The analysis revealed distinct differences in these antigens between MM, MGUS/SMM, and patients under treatment. In apheresis samples, the 10-color panel determined MRD negativity in 44% of patients. Absence of aPC in apheresis corresponded with disease burden, cytogenetics, and response to induction. It also determined MRD negativity in BM samples after ASCT and was associated with improved progression-free survival.ConclusionThese results highlight the significance of the evaluation of both BM and apheresis samples with a novel highly sensitive 10-color MFC panel.
Nicardipine Inhibits Breast Cancer Migration via Nrf2/HO-1 Axis and Matrix Metalloproteinase-9 Regulation
Authors: Chen Yen-Chang , Chen Jia-Hong , Tsai Cheng-Fang , Wu Chen-Teng , Wu Miao-Hsiang , Chang Pei-Chun , Yeh Wei-Lan 
Published: August 2021

Background: Metastasis represents an advanced stage of cancers, and matrix metalloproteinases are critical regulators. Calcium signal is crucial for appropriate cell behaviors. The efficacy and effects of calcium channel blockers in treating cancers are individually differ from each other. Here, we attempt to investigate the effects of nicardipine, a FDA-approved calcium channel blocker, in advanced breast cancers.Methods: We analyzed the influence of nicardipine on the colony-forming ability of triple negative breast cancer cell lines. Using cell culture inserts, cell migration was also examined. The expression of regulatory proteins was evaluated by real-time PCR, Western blot, and ELISA.Results: We have confirmed that nicardipine inhibits the breast cancer cells migration and colony formation. In addition, we also revealed that nicardipine increases the Nrf2 and HO-1 expression. The inhibition of HO-1 abrogates nicardipine-reduced matrix metalloproteinase-9 expression. Moreover, the end products of HO-1, namely, CO, Fe2+, and biliverdin (will converted to bilirubin), also decreases the expression of matrix metalloproteinase-9.Conclusion: These findings suggest that nicardipine-mediated matrix metalloproteinase-9 reduction is regulated by Nrf2/HO-1 axis and its catalytic end products. Therefore, nicardipine may be a potential candidate for repurposing against advanced breast cancers.
Assessing the Accuracy of Sales Forecasts Submitted by Pharmaceutical Companies Applying for Reimbursement in Austria
Authors: Kossmeier Michael , Themanns Madeleine , Hatapoglu Lena , Kogler Bernhard , Keuerleber Simon , Lichtenecker Jutta , Sauermann Robert , Bucsics Anna , Freissmuth Michael , Zebedin-Brandl Eva 
Published: August 2021

Objectives:Reimbursement decisions on new medicines require an assessment of their value. In Austria, when applying for reimbursement of new medicines, pharmaceutical companies are also obliged to submit forecasts of future sales. We systematically examined the accuracy of these pharmaceutical sales forecasts and hence the usefulness of these forecasts for reimbursement evaluations.Methods:We retrospectively analyzed reimbursement applications of 102 new drugs submitted between 2005 and 2014, which were accepted for reimbursement outside of hospitals, and for which actual reimbursed sales were available for at least 3 years. The main outcome variable was the accuracy ratio, defined as the ratio of forecasted sales submitted by pharmaceutical companies when applying for reimbursement to actual sales from reimbursement data.Results:The median accuracy ratio [95% confidence interval] was 1.33 [1.03; 1.74, range 0.15–37.5], corresponding to a median overestimation of actual sales by 33%. Forecasts of actual sales for 55.9% of all examined products either overestimated actual sales by more than 100% or underestimated them by more than 50%. The accuracy of sales forecasts did not show systematic change over the analyzed decade nor was it discernibly influenced by reimbursement status (restricted or unrestricted), the degree of therapeutic benefit, or the therapeutic area of the pharmaceutical product. Sales forecasts of drugs with a higher degree of innovation and those within a dynamic market tended to be slightly more accurate.Conclusions:The majority of sales forecasts provided by applicants for reimbursement evaluations in Austria were highly inaccurate and were on average too optimistic. This is in line with published results for other jurisdictions and highlights the need for caution when using such forecasts for reimbursement procedures.
Lock-Down Effect on the Mental Health Status of Healthcare Workers During COVID-19 Pandemic
Authors: Fageera Weam , Babtain Fawzi , Alzahrani Ahmad S. , Khrad Hussain M. 
Published: August 2021

Background: The psychological impact that outbreaks and pandemics could inflict on healthcare workers has been widely studied; yet, little is known about the impact of the lockdown measures.Objectives: To assess the magnitude of depression and anxiety among healthcare professionals before and after lifting of the lockdown restrictions in Saudi Arabia.Methods: Surveys targeting healthcare workers were circulated twice: during the lockdown, and 8 weeks after lifting of lockdown. Anxiety and depressive symptoms were assessed using Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales.Results: A total of 947 healthcare workers, with the mean age of (37 ± 8.9) responded to the surveys. Among these, 23–27% respondents reported clinically significant levels of anxiety and depression. Whereas, easing of the lockdown restrictions was shown to be associated with decreasing mean scores of PHQ-9 and GAD-7. The noted burden fell heavily on female workers, those with a current or a history of psychiatric disorders, suffering from chronic diseases, being in workplaces with high exposure to COVID-19 or in contact with COVID-19 patients, nurses, as well as those who were living with elderly and perceived their physical and mental health as “much worse” compared to the time before the pandemic.Conclusion: Our findings identified several predictors for anxiety and depression at different time-points of the pandemic. Thus, priority to psychological support measures might be needed for these groups.
Practical Limits on Nanosatellite Telescope Pointing: The Impact of Disturbances and Photon Noise
Authors: Douglas Ewan S. , Tracy Kevin , Manchester Zachary 
Published: August 2021

Accurate and stable spacecraft pointing is a requirement of many astronomical observations. Pointing particularly challenges nanosatellites because of an unfavorable surface area–to-mass ratio and a proportionally large volume required for even the smallest attitude control systems. This work explores the limitations on astrophysical attitude knowledge and control in a regime unrestricted by actuator precision or actuator-induced disturbances such as jitter. The external disturbances on an archetypal 6U CubeSat are modeled, and the limiting sensing knowledge is calculated from the available stellar flux and grasp of a telescope within the available volume. These inputs are integrated using a model-predictive control scheme. For a simple test case at 1 Hz, with an 85-mm telescope and a single 11th magnitude star, the achievable body pointing is predicted to be 0.39 arcseconds. For a more general limit, integrating available star light, the achievable attitude sensing is approximately 1 milliarcsecond, which leads to a predicted body pointing accuracy of 20 milliarcseconds after application of the control model. These results show significant room for attitude sensing and control systems to improve before astrophysical and environmental limits are reached.
RETRACTED: Open Nephroureterectomy Compared to Laparoscopic in Upper Urinary Tract Urothelial Carcinoma: A Meta-Analysis
Authors: Liu Guihong , Yao Zeqin , Chen Guoqiang , Li Yalang , Liang Bing 
Published: August 2021

Background: In this meta-analysis, we will focus on evaluating the effects of open nephroureterectomy compared with laparoscopic nephroureterectomy on postoperative results in upper urinary tract urothelial carcinoma subjects.Methods: A systematic literature search up to January 2021 was performed, and 36 studies included 23,013 subjects with upper urinary tract urothelial carcinoma at the start of the study; of them, 8,178 were laparoscopic nephroureterectomy, and 14,835 of them were open nephroureterectomy. They were reporting relationships between the efficacy and safety of open nephroureterectomy compared with laparoscopic nephroureterectomy in the treatment of upper urinary tract urothelial carcinoma. We calculated the odds ratio (OR) or the mean difference (MD) with 95% CIs to evaluate the efficacy and safety of open nephroureterectomy compared with laparoscopic nephroureterectomy in the treatment of upper urinary tract urothelial carcinoma using the dichotomous or continuous method with a random or fixed-effect model.Results: Laparoscopic nephroureterectomy in subjects with upper urinary tract urothelial carcinoma was significantly related to longer operation time (MD, 43.90; 95% CI, 20.91–66.90, p &lt; 0.001), shorter hospital stay (MD, −1.71; 95% CI, −2.42 to −1.00, p &lt; 0.001), lower blood loss (MD, −133.82; 95% CI, −220.92 to −46.73, p = 0.003), lower transfusion need (OR, 0.56; 95% CI, 0.47–0.67, p &lt; 0.001), and lower overall complication (OR, 0.79; 95% CI, 0.70–0.90, p &lt; 0.001) compared with open nephroureterectomy.However, no significant difference was found between laparoscopic nephroureterectomy and open nephroureterectomy in subjects with upper urinary tract urothelial carcinoma in 2–5 years recurrence-free survival (OR, 0.90; 95% CI, 0.69–1.18, p = 0.46), 2–5 years cancer-specific survival (OR, 0.94; 95% CI, 0.69–1.28, p = 0.68), and 2–5 years overall survival (OR, 1.31; 95% CI, 0.91–1.87, p = 0.15).Conclusion: Laparoscopic nephroureterectomy in subjects with upper urinary tract urothelial carcinoma may have a longer operation time, shorter hospital stay, and lower blood loss, transfusion need, and overall complication compared to open nephroureterectomy. Further studies are required to validate these findings.
Analysis of Selected Variants of DRD2 and ANKK1 Genes in Combat Athletes
Authors: Michałowska-Sawczyn Monika , Chmielowiec Krzysztof , Chmielowiec Jolanta , Trybek Grzegorz , Masiak Jolanta , Niewczas Marta , Cieszczyk Paweł , Bajorek Wojciech , Król Paweł , Grzywacz Anna 
Published: August 2021

The level of physical activity is conditioned by many different factors, including, among others, the personality traits of a person. Important is the fact that personality traits are a moderately heritable factor and on the basis of the analysis of several genes, various lifetime outcomes can be predicted. One of the most important pathways influencing personality traits is connected to the dopaminergic system; hence, we decided to analyze the DRD2 PROM. rs1799732, DRD2 rs1076560, DRD2 Tag1D rs1800498, DRD2 Ex8 rs6276, DRD2Tag1B rs1079597 and ANKK1 Tag1A rs180049. The research group included 258 male athletes (mean age = 26.02; SD = 8.30), whereas the control group was 284 healthy male volunteers matched for age (mean age = 22.89; SD = 4.78), both of Caucasian origin and without history of substance dependency or psychosis. Genomic DNA was extracted from venous blood using standard procedures. Genotyping was conducted with the real-time PCR method. Differences in the frequency of the DRD2Tag1B rs1079597 gene polymorphism were found between people practicing combat sports and the control group, and the DRD2 PROM. rs1799732, DRD2 rs1076560, DRD2 Tag1D rs1800498, DRD2 Ex8 rs6276, DRD2Tag1B rs1079597 and ANKK1 Tag1A rs1800497 genotypes and allele frequencies in the studied sample did not differ between the analyzed groups. Hence, we considered these polymorphic places as an interesting area for the further search for unambiguous associations between personality traits and attitude towards physical effort.
Saccharpiscinols A–C: Flavans with Potential Anti-Inflammatory Activities from One Actinobacteria Saccharomonospora piscinae
Authors: Su Yung-Shun , Chen Jih-Jung , Cheng Ming-Jen , Chai Chee-Yin , Kwan Aij-Lie , Huang Jheng-Cian , Kuo Yueh-Hsiung 
Published: August 2021

Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A–C (1–3, respectively), and three new natural products, namely (2S)-5,7,3′,4′-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4–6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production.
PENGARUH MANAJEMEN ASET TERHADAP OPTIMALISASI PEMANFATAAN ASET TETAP BADAN PENGELOLAAN KEUANGAN DAN ASET DAERAH KABUPATEN TANAH BUMBU
Authors: Muhammad Ridwan  
Published: August 2021

Abstract. This study aims to determine and analyze the Influence of inventory, legal audit and asset assessment in partially and simultaneously to the optimization of fixed assets in the Regional Financial and Asset Management Agency of Tanah Bumbu Regency. This research method uses a survey method with 63 respondents and then analyzes the data using the instrument test and multiple linear regression analysis. The results showed that the Inventory has a partial influence to the optimization of fixed assets, which is indicated by t count as 9,122. Legal audit partially influences to the optimization of fixed assets, which is indicated by t count as 8.452. The asset assessment has a partial Influence to the optimization of fixed assets, which is indicated by t count as 2.513. Inventory, Legal audit and Asset Assessments are simultaneously influence to the optimization of fixed assets in the Regional Financial and Asset Management Agency of Tanah Bumbu Regency, which is indicated by F count as 81.750.

Keywords: Inventory, Legal audit, Asset Assessment and Optimization of fixed assets.

Abstrak. Penelitian ini bertujuan untuk mengetahui dan menganalisis pengaruh inventarisasi, legal audit dan penilaian secara parsial dan secara simultan terhadap optimalisasi aset tetap di Badan Pengelolaan Keuangan dan Aset Daerah Kabupaten Tanah Bumbu. Metode penelitian ini menggunakan metode survey dengan jumlah responden sebanyak 63 orang kemudian dilakukan analisis data dengan menggunakan uji instrument dan analisis regresi liniear berganda. Hasil penelitian menunjukkan bahwa Inventarisasi berpengaruh secara parsial terhadap optimalisasi aset tetap yang ditunjukkan dengan nilai t hitung sebesar 9,122. Legal audit berpengaruh secara parsial terhadap optimalisasi aset tetap yang ditunjukkan dengan nilai t hitung sebesar 8,452. Penilaian berpengaruh secara parsial terhadap optimalisasi aset tetap yang ditunjukkan dengan nilai t hitung sebesar 2,513. Inventarisasi, Legal audit dan Penilaian berpengaruh secara simultan terhadap optimalisasi aset tetap Badan pengelolaan keuangan dan aset daerah yang ditunjukkan dengan nilai F hitung sebesar 81,750.

Kata kunci: Inventarisasi, Legal audit, Penilaian dan Optimalisasi Aset
Laboratory evaluation of the possibility of using the eggs of the chestnut moth Cameraria ohridella Deschka & Dimic, 1986 (Lepidoptera: Gracillariidae) to feed the trichogram
Authors: Bashchenko M. , Khudolii A. , Chaika V. 
Published: August 2021

Goal. Evaluation of the suitability and eggs of chestnut moth Cameraria ohridella for parasitism and development of trichogramma.
Methods. Laboratory cultures of Trichogramma pintoi Voeg were used for research. and Trichogramma evanescens Westw., which were bred on the eggs of Sitotroga cerealella Oliv. The experiment was performed according to the following scheme: female trichogramma after mating was placed in a test tube in 5 replicates for each species. The tube was closed with a stopper and the sex of individuals under binoculars was checked. In test tubes with trichogram laid strips of paper with one-day eggs of chestnut moth (25 copies.). In 5 replicates and kept in a thermostat (temperature — 24—25°C; relative humidity — 65—67%). The percentage of trichogram revival and the ratio of males to females, life expectancy and fertility of females were determined. Trichogramma individuals, which were fed with grain moth eggs, served as controls. The experiment lasted until the complete death of the trichogram. The obtained results were processed statistically according to standard methods.
Results. A small number of chestnut moth eggs pierced by trichogramma were detected, but embryonic development of the parasite’s eggs was not observed. Comparing the size of the eggs of the chestnut moth with the size of the eggs of the main squamous pests against which different species of trichogramma are effectively used, we can conclude that for the successful development of eggs T. pintoi and T. evanescens chestnut moth eggs are not suitable as feeders. Probably, in terms of size and biological quality, they do not correspond to the parameters of the ecological niche of the hosts of the family Trichogrammatidae.
Conclusions. In the laboratory, it was found that the eggs of the chestnut moth are not suitable for parasitizing the trichogramma of T. pintoi and T. evanescens. The main pests of crops, which are effectively parasitized by different species of trichogramma, have an egg size in the range of 0.4—1.0 mm, while the size of chestnut moth eggs does not exceed 0.27—0.32 mm. It is possible that the size and biological quality of chestnut moth eggs do not meet the parameters of the ecological niche of entomophagous feeders of the family Trichogrammatidae. Further researches with use of various types of a trichogramma, first of all — T. dendrolimi Mats appear actual.
The distribution of the Western Corn Rіootworm (Diabrotica virgifera virgifera Le Conte) in Ternopil region during 2016—2020
Authors: Prokopiak M. , Bezmenska L. , Paltsan N. , Holinei H. , Mayorova О. 
Published: August 2021

Goal. To analyze the distribution of the Western Corn Rootworm (Diabrotica virgifera virgifera Le Conte) in the Ternopil region during 2016—2020.
Methods. To generalize the results of phytosanitary monitoring of the spread of the regulated harmful organism on the territory of Ukraine and on the territory of Ternopil region according to the data provided by The Department of Phytosanitary Safety of Main Administration of State Service of Ukraine on Food Safety and Consumer Protection (SSUFSCP) in Ternopil region.
Results. In 2019 the area of D. virgifera virgifera distribution in Ukraine has increased 1.4 times compared to 2016, and the area of its distribution has expanded. Since D. virgifera virgifera was registered in the Ternopil region, the area of affected has increased by approximately 100 hectares per each year. The average annual temperature apparently contributed to the adaptation and the spread of D. virgifera virgifera throughout the region in 2016—2020, and the winter temperature were suitable for the wintering of the eggs.
Conclusions. The western corn rootworm belongs to the quarantine organisms. It needs the use all phytosanitary measures for the containment and restriction of its distribution in the territory of the Ternopil region. According to the average spread of this pest (40—50 km/ year), the further expansion of its population in other regions of Ukraine is predicted. The climatic conditions in the Ternopil region and the available fodder base will promote the development of D. virgifera virgifera.