bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for mortality in a multicenter cohort of mechanically ventilated COVID-19 patients in Belgium.
Authors: Lambermont Bernard , Ernst Marie , Demaret Pierre , Boccar Sandrine , Fraipont Vincent , Gurdebeke Christine , Brussel Cedric Van , Quinonez Manuel , Dubois Christophe J.J. , Lemineur Thierry , Njambou Thierry , Akando Benoit , Wertz Damien , Higny Julien , Thys Marie , Maes Nathalie , Canivet Jean-Luc , Kisoka Grace , Layios Nathalie , Ledoux Didier , Massion Paul , Morimont Philippe , Piret Sonia , Robinet Sebastien , Rousseau Anne-Françoise , Wiesen Patricia , Damas Pierre , Parzibut Gilles , Sottiaux Thierry , Lejeune François , François Pierre , Guntz Julien , Jadot Laurent , Foret Frédéric , Delanaye Pierre , Misset Benoit
Published: August 2020

Background: Considering the high mortality rate of severe Covid-19 patients, it is necessary to identify prognostic factors and therapies which could be valuable in this setting.Methods: The method consisted in a multicentric retrospective analysis in all consecutive Covid-19 patients admitted to intensive care unit (ICU) and mechanically ventilated for more than 24 hours from March 1 to April 25, 2020.Admission date, age, sex, body mass index, underlying conditions, treatments, physiological values, use of vasopressors, renal replacement therapy and extracorporeal membrane oxygenation, duration of mechanical ventilation, length of ICU stay, ICU and ventilator-free days at day 42 were collected. Primary outcome was survival. Simple and multiple time-dependent Cox regression models were used to assess the effects of factors on survival. Results: Out of 2003 patients hospitalized for SARS-CoV-2, 361 were admitted to the participating ICUs, 257 were ventilated for more than 24 hours and 247 were included in the study. The length of stay in ICU was 21 (12-32) days and the mortality rate was 45%. Using multiple regression, risk factors for mortality were age, high serum creatinine value, low mean arterial pressure, low lymphocytes count on day 0 and the absence of corticosteroid therapy during the first week of mechanical ventilation. The mortality rate of the patients who received corticosteroids was 34% and 48% for patients who did not (p = 0.01).Conclusion: In this multicenter cohort, the mortality of patients with SARS-CoV-2 pneumonia treated with mechanical ventilation was high. The risk factors for mortality included age, renal and circulatory dysfunction, lymphopenia and the absence of corticosteroid therapy during the first week of mechanical ventilation.
Continuous assessment of neuro-ventilatory drive during 12 hours of pressure support ventilation in critically ill patients
Authors: Mussi Rosa Di , Spadaro Savino , Volta Carlo Alberto , Bartolomeo Nicola , Trerotoli Paolo , Staffieri Francesco , Pisani Luigi , Iannuzziello Rachele , Dalfino Lidia , Murgolo Francesco , Grasso Salvatore
Published: August 2020

Introduction: Pressure support ventilation (PSV) should allow spontaneous breathing with a “normal” neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 hours the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of “Low” and/or “High” neuro-ventilatory drive during clinical application of PSV.Method: In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdiPEAK), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTPDI/b and PTPDI/min, respectively), breathing pattern and major asynchronies were continuously monitored for 12 hours (from 8 a.m. to 8 p.m.). We identified breaths with “Normal” (EAdiPEAK 5 - 15 mV), “Low” (EAdiPEAK < 5 mV) and “High” (EAdiPEAK >15 mV) neuro-ventilatory drive.Results: Within all the analyzed breaths (177.117), the neuro-ventilatory drive as expressed by the EAdiPEAK, was “low” (<5 mV) in 50.116 breath (28 %), Normal (5-15 mV) in 88.419 breaths (50 %) and High (>15 mV) in 38.582 breaths (22 %). The average times spent in “Low”, “Normal” and “High” class were 1.37 hours, 3.67 hours and 0,55 hours, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the “Low” neuro-ventilatory drive class for more than one hour, median 6.1 [3.9 - 8.5] hours and 6 in the “High” neuro-ventilatory drive class, median 3.4 [2.2 – 7.8] hours. The asynchrony index was significantly higher in the “Low” neuro-ventilatory class, mainly because of a higher number of missed efforts.Conclusions: We observed wide variations in EAdi amplitude and unevenly distributed “Low” and “High” neuro ventilatory drive periods during 12 hours of PSV in critically ill patients. Our data suggest that PSV might result in periods of over or under-assistance. Further studies are needed to assess the possible clinical implications of these physiological findings.
A stacking ensemble learning framework for genomic prediction
Authors: Liang Mang , Chang Tianpeng , An Bingxing , Duan Xinghai , Du Lili , Wang Xiaoqiao , Miao Jian , Xu Lingyang , Gao Xue , Zhang Lupei , Li Junya , Gao Huijiang
Published: August 2020

Background: Machine learning (ML) is perhaps the most useful for the interpretation of large genomic datasets. However, the performance of a single machine learning method in genomic selection (GS) was unsatisfactory in existing research. To improve the genomic predictions, we constructed a stacking ensemble learning framework (SELF) integrated three machine learning methods to predict genomic estimated breeding values (GEBVs). Results: We evaluated the prediction ability of SELF by three real datasets and compared the prediction accuracy of SELF, base learners, GBLUP and BayesB. For each trait, SELF performed better than base learners, which included support vector regression (SVR), kernel ridge regression (KRR) and elastic net (ENET). The prediction accuracy of SELF had an average 7.70% improvement compared with GBLUP in three datasets. Except for the milk fat percentage (MFP) traits of the German Holstein dairy cattle dataset, SELF more robust than BayesB in the remaining traits.Conclusions: In this study, we utilized a stacking ensemble learning framework (SELF) to genomic prediction and it performed much better than GBLUP and BayesB in three real datasets with different genetic architecture. Therefore, we believed SEFL had the potential to be promoted to estimate GEBVs in other animals and plants.
Ethnobotanical Characterization of Medicinal Plants Used in Kisantu and Mbanza-Ngungu Terroirs, Kongo-Central Province in DR Congo
Authors: kembelo Pathy Kibungu , Bakwaye Favien Nzuki , Katula Honoré Belesi , Vanhove Wouter , Damme Patrick Van
Published: August 2020

Background: The phytotherapeutic knowledge of the Kongo people in the terroirs of Kisantu and Mbanza-Ngungu in Kongo-Central Province (DR Congo) is rapidly eroding. To document the remaining knowledge, we conducted an ethnobotanical survey on the most important medicinal plant species and diseases treated with them, as well as plants with therapeutic potential. We also verified how medicinal knowledge differs between different social groups.Method: From June 2017 until February 2018 and from February until April 2019, we conducted a survey with 188 phytotherapists, selected using the snowball method and surveyed using semi-structured interviews. Voucher specimens were taken for identification. Ethnobotanical database was analyzed using medicinal Use Value (UVs), Informant Agreement Ratio (IARs), Informant Consensus Factor (ICF) and Species Therapeutic Potential (STP). Medicinal knowledge between different social groups was analyze using non parametric tests and the Poisson regression. Results: A total of 231 plants (i.e. 227 botanical species, representing 192 genera and 79 families) were reportedly used to treat 103 diseases. Most abundant taxa were reported for the Fabaceae family (11.9 %) and genus Solanum (1.8%). Most harvested species (45,0%) were from anthropized areas. Most frequent plant part, botanical form, preparation and administration method were leaves (39.4%), herbs (37.1%), decoction (41.7%) and oral ingestion (72%) respectively. Four of all inventoried species showed high UV S (> 0.05), whereas 8 had an IAR of 1. According to respondent consensus on plant use, 31 diseases were mentioned. Highest ICF (≥ 0,4) were observed for hemorrhoids (0.44), amoebiasis (0.43) and itchy rash (0.42). Fifty-four plant species were identified likely to have interesting therapeutic potential. Analysis of medicinal knowledge showed that the mean number of reported species and diseases vary considerably depending on gender, type and location of therapists (P < 0.05). Conclusion: Results prove that the Kongo phytopharmacopoeia makes use of interesting medicinal plant species that could be further studied for conservation and pharmacological applications.
Automatic load-distributing band CPR (AutoPulseTM) in prone position: A feasibility study in a mechanical model
Authors: Pietsch Urs , Knapp Jürgen , Wenzel Volker , Lischke Volker , Albrecht Roland
Published: August 2020

Background: Due to SARS-CoV-2 respiratory failure, prone positioning of patients with respiratory and hemodynamic instability has become a frequent intervention in intensive care units (ICUs), and even in patients undergoing transfer in an ambulance or helicopter. The question becomes how to perform safe and effective CPR in prone position, achieving both an optimal outcome for the patient and optimal protection of staff from infection.Materials and Methods: We conducted a feasibility study to assess the effects of CPR with an automatic load-distributing band (AutoPulseTM) in prone position. Results: In supine position, AutoPulseTM generated a constant pressure depth of 3 cm at a frequency of 84/min. In prone position, AutoPulseTM generated a constant pressure depth of 2.6 cm at a frequency of 84/min.Conclusion: We found that AutoPulseTM CPR was feasible in manikins in both prone and supine positions.
Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach
Authors: Mostafa  , Mohammed  , Hatem
Published: August 2020

Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 6M0K, 6Y2F and 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or more of the COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of the 4 drug targets. The top 7 hits are compounds; Flacourticin (3), Sagerinic acid (16), Hordatine A (23), Hordatine B (24), N-feruloyl tyramine dimer (25), Bisavenanthramides B-5 (29) and Vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than Remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.
Short Stem Hip Arthroplasty Provides a More Physiological Load Transfer: a Comparative Finite Element Analysis Study
Authors: Yan Shuang G , Chevalier Yan , Liu Fanxiao , Hua Xingyi , Schreiner Anna , Jansson Volkmar , Schmidutz Florian
Published: August 2020

Background: Short stem total hip arthroplasty (SHA) preserves femoral bone stock and is supposed to provide a more natural load transfer compared to standard stem total hip arthroplasty (THA). As comparative biomechanical reference data are rare we used a finite element analysis (FEA) approach to compare cortical load transfer after implantations of a cementless short and standard stem in native biomechanical femora.Methods: The subject specific finite element models of biomechanical femora, one native and two with implanted SHA (Metha, B.Braun Aesculap) and standard THA (CLS, Zimmer-Biomet), were generated from computed tomography datasets. The loading configuration was performed with an axial force of 1400 N. Von Mises stress was used to investigate the change of cortical stress distribution.Results: Compared to the native femur, a considerable reduction of cortical stress was recorded after implantation of SHA and standard THA. The SHA showed less reduction proximally with a significant higher metaphyseal cortical stress compared to standard THA. Moreover, the highest peak stresses were observed metaphyseal for the SHA stem while for the standard THA high stress pattern was observed more distally.Conclusions: Both, short and standard THA, cause unloading of the proximal femur. However, SHA features a clearly favorable pattern in terms of a lower reduction proximally and improved metaphyseal loading, while standard THA shows a higher proximal unloading and more distal load transfer. These load pattern implicate a reduced stress shielding proximally for SHA and might be able to translate in a better bone preservation.
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice
Authors: Zhang Wen , Wang Lei , Sun Xue-Hua , Liu Xian , Xiao Yang , Zhang Jie , Wang Ting , Chen Hui , Zhan Yi-Qun , Yu Miao , Ge Chang-Hui , Li Chang-Yan , Ren Guang-Ming , Yin Rong-Hua , Yang Xiao-Ming
Published: August 2020

Background
Toll-like receptor 5 (TLR5)-mediated pathways play critical roles in regulating hepatic immune response and show hepatoprotective effect in mouse models of liver injury. However, the role of TLR5 in experimental models of liver regeneration has not been investigated. This study aims to determine the role of TLR5 in the partial hepatectomy (PHx)-induced liver regeneration.
Methods
We performed 2/3 PHx in wild-type (WT) mice, TLR5 knockout mice, or TLR5 agonist CBLB502 treated mice as an established model of liver regeneration. Bacterial flagellin content was measured by ELISA, and hepatic TLR5 expression was determined by real-time PCR analyses and flow cytometry. To study the effects of TLR5 on hepatocyte proliferation, proliferating cell nuclear antigen (PCNA) and the incorporation of bromodeoxyuridine (BrdU) were analyzed by immunohistochemistry (IHC) staining. The role of TLR5 in the priming of liver regeneration was examined by real-time PCR analyses of immediate early gene mRNA levels, as well as western blot analysis of hepatic NF-κB and STAT3 activation. Cytokines and growth factors production after PHx were detected using real-time PCR analyses and cytometric bead array (CBA) assays. Oil Red O staining and hepatic lipids concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.
Results
The bacterial flagellin content in serum and liver was increased and the hepatic TLR5 expression was significantly up-regulated in WT mice upon PHx. TLR5-deficient mice exhibited reduced numbers of BrdU- and PCNA-positive cells, suppressed immediate early gene expression, and decreased cytokines and growth factors production. Moreover, PHx-induced NF-κB and STAT3 activation was inhibited in the liver of Tlr5−/− mice compared with WT mice. Consistently, administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation correlated with enhanced production of proinflammatory cytokines and recruitment of macrophages and neutrophils in liver. In addition, Tlr5−/− mice displayed significantly decreased hepatic lipids concentrations and Oil Red O positive areas compared with WT mice after PHx.
Conclusions
We reveal that TLR5 activation is involved in the initial events of liver regeneration after PHx. Our results demonstrate that TLR5 signaling positively regulates liver regeneration and suggest a potential application of TLR5 agonist in promoting liver regeneration.
Inhibition of SIRT6 Potentiates the Anti-Tumor Effect of Doxorubicin through Suppression of the DNA Damage Repair Pathway in Osteosarcoma
Authors: Zhang Zhongkai , Ha Sang Hoon , Moon Young Jae , Hussein Usama Khamis , Song Yiping , Kim Kyoung Min , Park See-Hyoung , Park Ho Sung , Park Byung-Hyun , Ahn Ae-Ri , Lee Sang-A , Ahn Su Jin , Kim Jung Ryul , Jang Kyu Yun
Published: August 2020

Background
SIRT6 has diverse roles in cells, and the role of SIRT6 in tumorigenesis is controversial. Considering the role of SIRT6 as an inducer of DNA damage repair, it might be involved in resistance to anti-cancer therapy.
Methods
We evaluated the prognostic significance of SIRT6 in 37 osteosarcomas and investigated the therapeutic efficacy of SIRT6 on the anticancer effects of doxorubicin, olaparib, and ATM inhibitor.
Results
Immunohistochemical expression of SIRT6 was significantly associated with shorter overall survival and relapse-free survival of osteosarcoma patients, especially in patients who received adjuvant chemotherapy. In U2OS and KHOS/NP osteosarcoma cells, knock-down of SIRT6 significantly potentiated apoptotic effects of doxorubicin and SIRT6 overexpression induced resistance to doxorubicin. Moreover, SIRT6 induced the DNA damage repair pathway and SIRT6-mediated resistance to doxorubicin was attenuated by blocking the DNA damage repair pathway with olaparib and ATM inhibitor.
Conclusions
This study suggests that suppression of SIRT6 in combination with doxorubicin might be an effective modality in the treatment of osteosarcoma patients, especially for osteosarcomas with shorter survival with high expression of SIRT6.
Two-stage laparoscopic resection of giant hepatoblastoma in infants combined with liver partial partition and artery ligation
Authors: Wu Yaohao , Zeng Lexiang , Qiu Ronglin , Zhang Jie , Su Jianhang , Liao Minyi , Deng Xiaogeng
Published: August 2020

Purpose
Laparoscopic resection of giant hepatoblastoma (HB) in children has long been a subject of controversy. Here a new procedure of two-stage laparoscopic resection of giant HB in infants was firstly reported and the feasibility was discussed.
Methods
The clinical data of 3 infants with HB were retrospectively reviewed, all of which received 3–5 cycles of neoadjuvant chemotherapy. Stage one laparoscopic selective hepatic artery ligation and liver partial partition were performed. Stage two laparoscopic hepatectomy was performed two weeks later.
Results
The results demonstrated that: 1) The tumors shrank considerably in size and had relatively clear boundaries after neoadjuvant chemotherapy; 2) After stage one surgery, the tumor volume further reduced, while the intratumoral necrosis expanded. 3) Two weeks later, stage two laparoscopic hepatectomy was performed successfully; 4) None of the cases had intraoperative complications such as tumor rupture, air embolism, hemorrhage, biliary fistula or liver failure, and there was no recurrence or metastasis during follow-up.
Conclusions
Two-stage laparoscopic hepatectomy associating selective hepatic artery ligation and liver partial partition for HB in infants has the benefits of small invasiveness, fast recovery, improved safety and high feasibility. However, more cases and longer follow-up are needed to assess its long-term efficacy.
An evolutionary system of mineralogy. Part III: Primary chondrule mineralogy (4566 to 4561 Ma)
Authors: Hazen Robert M. , Morrison Shaunna M. , Prabhu Anirudh
Published: August 2020

Information-rich attributes of minerals reveal their physical, chemical, and biological modes of origin in the context of planetary evolution, and thus they provide the basis for an evolutionary system of mineralogy. Part III of this system considers the formation of 43 different primary crystalline and amorphous phases in chondrules, which are diverse igneous droplets that formed in environments with high dust/gas ratios during an interval of planetesimal accretion and differentiation between 4566 and 4561 Ma. Chondrule mineralogy is complex, with several generations of initial droplet formation via various proposed heating mechanisms, followed in many instances by multiple episodes of reheating and partial melting. Primary chondrule mineralogy thus reflects a dynamic stage of mineral evolution, when the diversity and distribution of natural condensed solids expanded significantly.
The effectiveness of financial and economic regulation of land relations in the context of stimulating entrepreneurial activity in the regions of Ukraine
Authors: Vatamanyuk-Zelinska Uliana , V. Melnychenko Oleksandr
Published: August 2020

Solving the problem of enhancing the efficiency of the financial and economic regulation of land relations contributes to the development of entrepreneurship in Ukraine. The purpose of the paper is to determine new incentives for encouraging entrepreneurial activity by increasing the efficiency of the financial and economic regulation of land relations by local governments. The study is based on applying the method for predicting amounts of local budget revenues in Ukraine from the land tax and lease fees through the use of communally owned land plots to stimulate entrepreneurial initiatives of the unemployed. In the process of research, the projected amounts of local budget revenues from financial transactions with plots of industrial lands in each region of Ukraine have been determined, taking into account the possibilities of leasing the lands, for which lease fees are covered by a one-time benefit provided to the unemployed for organizing entrepreneurial activity. It is proposed to determine the efficiency of the financial and economic regulation of land relations in the regions of Ukraine, applying indicators such as the use of industrial lands together with objects of lease located on them and the involvement of the unemployed from among the economically active population in entrepreneurial activity. To improve the efficiency of financial and economic regulation of land relations, local governments are proposed to establish the optimal proportion of amounts of borrowed resources, taking into account the need for their saving and rational use.
Decision tree-based reduction of bias in monthly IMERG satellite precipitation dataset over India
Authors: Chaudhary Shushobhit , Dhanya C. T.
Published: August 2020

Decision trees are ideally suited for handling huge datasets and modelling non-linear relationships between different variables. Given the relationship between precipitation and bias may be very complex and non-linear, bias-correction of satellite precipitation is a challenge. We examine the applicability of Classification and Regression tree (CART) for bias-correction of the Integrated Multi-satellite Retrievals for Global Precipitation Mission (IMERG) precipitation dataset over India. The gauge-based 0.25° gridded precipitation dataset from India Meteorological Department is considered as the reference. The CART model is trained (2001–2011) and tested (2012–2016) over each 0.25° grids. The training dataset is subjected to 10-fold cross-validation and optimization of the minimum size of leaf node (one of the hyper-parameter). Efficiency of the CART model is evaluated using performance metrics like R2, RMSE and MAB over the whole of India and different climate and elevation zones in India. CART model is observed to be highly effective in capturing the bias during the training (average R2= 0.77) and testing (average R2 = 0.66) period. Significant improvement in average monthly MAB (−6.3 to 29.2%) and RMSE (8.7–37.3%) was obtained post bias-correction by CART. Better performance of CART model was observed when compared to two widely adopted bias-correction techniques.
Estimating the design flood under the influence of check dams by removing nonstationarity from the flood peak discharge series
Authors: Li Shi , Qin Yi , Liu Yixiu , Song Xiaoyu , Liu Qiang , Li Ziwen
Published: August 2020

The construction of check dams in northwestern China has resulted in nonstationary changes in flood peak discharge series; the stationary assumption of the conventional hydrological frequency analysis is no longer satisfied. According to the characteristics of the construction and operation of check dams, the nonstationarity of flood peak discharge series are largely induced by changes in the effective runoff generation area (i.e., the basin area minus the area controlled by check dams). Knowing the power function relationship between the flood peak discharge and the basin area, we can remove the influence of the effective runoff generation area and convert the original nonstationary series into a stationary series. This de-nonstationarity method can achieve stationarity in the first and second moments simultaneously. Therefore, we can calculate the design value of the reconstructed series using the conventional frequency analysis method. According to the effective runoff generation area under design conditions, we can then obtain the corresponding design flood of the original series. We applied this method to the Mahuyu River basin to obtain the design flood under nonstationarity. Due to the consideration of the deterministic influence of check dams during the de-nonstationarity process, the uncertainty analyzed by the bootstrap method is obviously small.
Development of a biogas distribution model for a wastewater treatment plant: a mixed integer linear programming approach
Authors: Laing Harry , O'Malley Chris , Browne Anthony , Rutherford Tony , Baines Tony , Willis Mark J.
Published: August 2020

In this paper, we propose a realistic model for gas distribution of an advanced municipal wastewater treatment works and through minimisation of the total cost of gas distribution we perform retrospective optimisation (RO) using historical plant data. This site is the first in the UK with a mixed operational strategy for biomethane produced on site: to burn in combined heat and power (CHP) engines to create electricity, burn in steam boilers for onsite steam use or inject the biomethane into the National Grid. In addition, natural gas can be imported to make up shortfalls in biomethane if required. Implemented using a novel mixed integer linear programming (MILP) approach, to ensure a fast and robust solution, our results indicate the plant operated optimally within accepted tolerance 98% of the time. However, improving plant robustness (such as reducing unexpected breakdown incidents) could yield a significant increase in gas revenue of 7.8%.
Effect of wetting agent on the dye filtration performance of ultrafiltration membrane
Authors: Keskin Başak , Ormancı-Acar Türkan , Türken Türker , Imer Derya Y. , Koyuncu Ismail
Published: August 2020

In this study, the wet phase inversion method was used for fabrication of the flat sheet ultrafiltration (UF) membranes. Three different polymer types and two different wetting agents were used for the fabrication. The effect of polymer types and wetting agents were investigated on the structural and dye performance of casted membranes. Two different synthetic dyes, 100 ppm Setazol Red and 100 ppm Setazol Blue, were used for the performance test. Viscosity, contact angle, and molecular weight cut off (MWCO) of casted membranes were measured and an electro kinetic analyzer, dynamic mechanical analyzer (DMA) and scanning electron microscope (SEM) were used to determine the structural properties. While the highest water and dye permeability were obtained with PES-PEG membrane, PSf-plain membrane gave the highest removal efficiency for Setazol Red and Setazol Blue dyes, which was found to be 78.33% and 82.52%, respectively, in the conditions of neutral pH and ambient temperature. Addition of PVP and PEG wetting agents improved the structural properties and permeability of membranes, but the dye removal was decreased as against plain ones. As the retention of PEG and PVP-based PSf and PES membrane was calculated at an average of 50%, they could be used for dye retention separately or could be a candidate as a pretreatment membrane prior to nanofiltration or reverse osmosis to make their lifetime longer.
Challenges in Oral Drug Delivery and Applications of Lipid Nanoparticles as Potent Oral Drug Carriers for Managing Cardiovascular Risk Factors
Authors: Okur Neslihan Ü. , Siafaka Panoraia I. , Gökçe Evren H.
Published: August 2020

Background:

The oral application of drugs is the most popular route through which the systemic effect can be
achieved. Nevertheless, oral administration is limited by difficulties related to physicochemical properties of the drug molecule, including low aqueous solubility, instability, low permeability, and rapid metabolism, all of which result in low and irregular oral bioavailability.

Objective:

The enhancement of oral bioavailability of drug molecules with such properties could lead to extreme complications in drug preparations. Oral lipid based nanoparticles seems to possess extensive advantages due to their ability to increase the solubility, simplifying intestinal absorption and decrease or eradicate the effect of food on the absorption of low
soluble, lipophilic drugs and therefore improving the oral bioavailability.

Method:

The present review provides a summary of the general theory of lipid based nanoparticles, their preparation methods as well as their oral applications. Moreover, the oral drug delivery challenges are discussed.

Results:

According to this review, the most frequent types of lipid-based nanoparticle, the solid lipid nanoparticles and
nanostructured lipid carriers are potent oral carriers due to their ability to penetrate the oral drug adsorption barriers. Moreover, such lipid nanoparticles can be beneficial drug carriers against cardiovascular risk disorders as diabetes, hypertension
etc.

Conclusion:

In this review, the most current and promising studies involving Solid Lipid Nanoparticles and Nanostructured
Lipid Carriers as oral drug carriers are reported aiming to assist researchers who focus their research on lipid based nanoparticles.
Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation
Authors: Harikrishnan A. , Khanna Sunali , Veena V.
Published: August 2020

Background:

Curcumin is a major active principle of Curcuma longa. There are more than 1700 citations in the Medline, reflecting various biological effects of curcumin. Most of these biological activities are associated with the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that include growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that target the cancer and inflammation.

Methodology:

In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules.

Results:

Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed.

Conclusion:

The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.
Recent Applications of Benzimidazole as a Privileged Scaffold in Drug Discovery
Authors: Guo Yongzhen , Hou Xuben , Fang Hao
Published: August 2020

Benzimidazole is an aromatic bicyclic heterocycle that is regarded as a valuable privileged
scaffold in medicinal chemistry. Many marketed drugs and natural products containing benzimidazole
scaffolds exert great influence in fighting various diseases, such as hypertension, peptic ulcers, parasitic
infections, and cancer. In this review, we introduce the pharmacological applications of some marketed
drugs and lead compounds with a focus on anticancer agents, reporting the corresponding data to
show the biological activities at their targets. The publications in this review encompass those from
2014 to 2019.
Development of Thymol Microsponges Loaded in situ Gel for the Treatment of Periodontitis
Authors: Patole Vinita C. , Chaudhari Shilpa P.
Published: August 2020

Objective:

Periodontitis is an oral disease categorized by disturbance of periodontal tissue and
the creation of periodontal pockets. Thymol (TH) loaded microsponge in situ gelling systems was formulated
for local action in the periodontal cavity for the management of periodontitis.

Methods:

Solvent evaporation technique was utilized for the preparation of microsponges. A Fractional
Factorial Design (FFD) was used to screen the high risk variables impacting the characteristics of the
(TH) microsponges and further optimized using Box-Behnken design. The optimized microsponges were
then characterized by DSC, SEM, antimicrobial activity, in-vitro release, and then incorporated in the in situ gelling system. A ligature model was used to induce periodontitis in Sprague Dawley rats.

Results:

The microsponges showed good characteristics, such as particle size, entrapment efficiency,
and mucoadhesiveness of 45 μm, 92.99 ± 0.2%, 96 ± 0.26%, respectively. SEM revealed the spherical
morphology of the microsponges with sustained release of TH for 10h and antimicrobial activity against
S. mutans and C. albicans. Treatment with Thymol Loaded in situ Gel (THLMG) showed a decrease in
gingival inflammation and tooth mobility as well as in serum biochemical parameters like serum Creactive
proteins, leucocyte count, alkaline phosphatase, and tartrate-resistant acid phosphatase, when
compared to disease group. The histopathological study of the periodontium confirmed a significant
reduction of inflammation and alveolar bone destruction (p<0.05) in rats.

Conclusion:

THLMG decreased the infiltration of inflammatory cells and prevented osteoclastogenesis
and osteoblast apoptosis, which further favored a decrease in inflammation and alveolar bone loss in
periodontitis. Thus, THLMG could be a better alternative to synthetic antimicrobials and antibiotics to
treat periodontitis.
CORM-3 Regulates Microglia Activity, Prevents Neuronal Injury, and Improves Memory Function During Radiation-induced Brain Injury
Authors: Lu Kui , Wu Wen-Jun , Zhang Cheng , Zhu Yu-Liang , Zhong Jian-Qiang , Li Jie
Published: August 2020

Objectives:

This study aims to explore in detail, the mechanism of the carbon monoxide
releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation
brain injury (RBI).

Methods:

The brain injury models of BV2 cells and Balb/C mice were established and randomly divided
into three groups: the normal control group (CON), the single radiation group (RAD), and
the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to
observe the effects on activation of the MG. The expressions of inflammatory factors, such as intercellular
adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected
by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI) model were
detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris
water maze was used to assess the spatial learning and memory of the mice.

Results:

Within 48 h after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation
of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might
alleviate MG-mediated neuronal apoptosis and promote neural regeneration in the subgranular
zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase the swimming distance
and platform-stay time of the mice in the target platform quadrant after radiation.

Conclusion:

CORM-3 could effectively improve the inflammatory response induced by activation
of the MG, reduce neuronal apoptosis, promote neural regeneration, and improve the learning and
memory performance of mice after radiation.
Advances in Regulating Tumorigenicity and Metastasis of Cancer Through TrkB Signaling
Authors: Zou Wujun , Hu Xiaoyan , Jiang Liang
Published: August 2020

The clinical pathology of various human malignancies is supported by tropomyosin receptor
kinase (Trk) B TrkB which is a specific binding receptor of the brain-derived neurotrophic
factor (BDNF). TrkB and TrkB fusion proteins have been observed to be over-expressed in many
cancer patients. Moreover, these proteins have been observed in multiple types of cells. A few signaling
pathways can be modulated by the abnormal activation of the BDNF/TrkB pathway. These
signaling pathways include PI3K/Akt pathway, transactivation of EGFR, phospholipase C-gamma
(PLCγ) pathway, Ras-Raf-MEK-ERK pathway, Jak/STAT pathway, and nuclear factor kappalight-
chain-enhancer of activated B cells (NF-kB) pathway. The BDNF/TrkB pathway, when overexpressed
in tumors, is correlated with reduced clinical prognosis and short survival time of patients.
Targeting the BDNF/TrkB pathway and the use of Trk inhibitors, such as entrectinib,
larotrectinib, etc. are promising methods for targeted therapy of tumors. The present review provides
an overview of the role of the TrkB pathway in the pathogenesis of cancer and its value as a
potential therapeutic target.
Prolonged Release of Anti-Retroviral Efavirenz From System Using ZIF-8 as Carrier
Authors: Tabosa Alinne Élida Gonçalves Alves , Ferreira Aline Silva , da Silva Natália Millena , da Silva Nascimento Débora Dolores Souza , de Moura Ferraz Leslie Raphael , Silva José Yago Rodrigues , Junior Severino Alves , da Silva Rosali Maria Ferreira , Rolim Larissa Araújo , Rolim-Neto Pedro Jose
Published: August 2020

Background:

Acquired Immunodeficiency Syndrome (AIDS) is a major public health
problem in the world. One of the highly effective drugs in anti-HIV therapy is efavirenz (EFZ),
which is classified as Class II according to the Classification System of Biopharmaceuticals, presenting
low solubility and high permeability, this being an obstacle related to the drug.

Objective:

This study aimed to obtain an innovative system based on EFZ and the Zeolitic Imidazolate
Framework (ZIF-8) to use in the development of prolonged-release pharmaceutical forms that
can circumvent this problem.

Methods:

The EFZ: ZIF-8 system was obtained by a selected ex-situ method due to its higher incorporation
efficiency. Different characterization techniques corroborated the obtainment of the system,
and drug release was analyzed by dissolution testing under sink conditions, the profiles being
adjusted to some kinetic models.

Results:

At pH 1.2, the structure of ZIF-8 breaks down rapidly, releasing a large amount of drug
within either 3h or short time. In the pH 4.5 and 6.8 medium, the EFZ release from the EFZ: ZIF-8
system obtained in ethanol was prolonged, releasing 95% of the drug in 24h at pH 4.5 and 75%
medium at pH 6.8.

Conclusion:

It is evident that a promising pH-sensitive system was obtained using ZIF-8 as a novel
carrier of EFZ intended for the alternative treatment of AIDS.
Clinical Outcomes of Post-exposure Prophylaxis following Occupational Exposure to Human Immunodeficiency Virus at Dental Departments of Hiroshima University Hospital
Authors: Shintani T. , Iwata T. , Okada M. , Nakaoka M. , Yamasaki N. , Fujii T. , Shiba H.
Published: August 2020

Background:

Dental professionals have so many opportunities to use injection needles and sharp instruments
during dental treatment that they face an increased risk of needlestick injuries. This retrospective study reports the utilization
and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially
exposed to HIV at dental departments of Hiroshima University Hospital.

Objective:

This study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with
anti-retroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital.

Methods:

Data on the clinical status of HIV-infected source patients and information on HIV-exposed dental professionals
from 2007 to 2018 were collected.

Results:

Five dentists with an average experience of 5.6 years (1-15 years) were exposed. The averaged CD4-positive cell
number and HIV-RNA load were 1176 (768-1898) / l and less than 20 copies/ml, respectively, in all the patients. Two of
the five HIV exposed dentists received PEP. Three months after the exposures, all of their results were negative in HIV antibody/antigen tests.

Conclusion:

These data might support the concept of “undetectable equals untransmittable”, although HIV exposure in this
study was not through sexual transmission.
Encapsulation by Electrospraying of Anticancer Compounds from Jackfruit Extract (Artocarpus heterophyllus Lam): Identification, Characterization and Antiproliferative Properties
Authors: Rivera-Aguilar José O. , Calderón-Santoyo Montserrat , González-Cruz Elda M. , Ramos-Hernández Jorge A. , Ragazzo-Sánchez Juan A.
Published: August 2020

Background:

Compounds with biological activities had been reported in the jackfruit. These compounds
are susceptible to structural changes such as isomerization and/or loss of bonds due to environmental
factors. Then, the encapsulation for protecting is a necessary process.

Objective:

In this study, encapsulation of High-Value Biological Compounds (HVBC) was performed using
High Degree of Polymerization Agave Fructans (HDPAF) and Whey Protein (WP) as encapsulating materials to
preserve the biological properties of the HVBC.

Methods:

The extract was characterized by HPLC-MS in order to show the presence of compounds with preventive
or therapeutic effects on chronic degenerative diseases such as cancer. The micrographs by Scanning Electron
Microscopy (SEM), Thermal Analysis (TGA and DSC), photostabilization and antiproliferation of
M12.C3.F6 cell line of capsules were evaluated.

Results:

The micrographs of the nanocapsules obtained by Scanning Electron Microscopy (SEM) showed
spherical capsules with sizes between 700 and 800nm. No cracks, dents or deformations were observed. The
Thermogravimetric Analysis (TGA) evidenced the decomposition of the unencapsulated extract ranging from 154
to 221°C. On the other hand, the fructan-whey protein mixture demonstrated that nanocapsules have a thermoprotective
effect because the decomposition temperature of the encapsulated extract increased 32.1°C. Differential
Scanning Calorimetry (DSC) exhibited similar values of the glass transition temperature (Tg) between the capsules
with and without extract; which indicates that the polymeric material does not interact with the extract
compounds. The photoprotection study revealed that nanocapsules materials protect the jackfruit extract compounds
from the UV radiation. Finally, the cell viability on the proliferation of M12.C3.F6 cell line was not
affected by powder nanocapsules without jackfruit extract, indicating that capsules are not toxic for these cells.
However, microcapsules with jackfruit extract (50μg/ml) were able to inhibit significantly the proliferation cells.

Conclusion:

The encapsulation process provides thermoprotection and photostability, and the antiproliferative
activity of HVBC from jackfruit extract was preserved.
Derivatives of Deoxypodophyllotoxin Induce Apoptosis through Bcl-2/Bax Proteins Expression
Authors: Li Ya-Nan , Ning Ni , Song Lei , Geng Yun , Fan Jun-Ting , Ma Chao-Ying , Jiang He-Zhong
Published: August 2020

Background:

Deoxypodophyllotoxin, isolated from the Traditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant anti-tumor activity with strong toxicity in vitro and in vivo.

Objective:

In this article, a series of deoxypodophyllotoxin derivatives were synthesized and their anti-tumor effectiveness was evaluated.

Methods:

The anti-tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT assay method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC.

Results:

The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29, and MG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit.

Conclusion:

The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.
Targeting CD47 Inhibits Tumor Development and Increases Phagocytosis in Oral Squamous Cell Carcinoma
Authors: Ye Xiao-Jing , Yang Jian-Guang , Tan Ya-Qin , Chen Xiao-Jie , Zhou Gang
Published: August 2020

Background:

Our previous work demonstrated upregulated CD47 in oral squamous cell carcinoma (OSCC).

Objective:

In the present study,we aimed to investigate the effects of CD47 on tumor cell development and phagocytosis in OSCC and elucidate the underlying mechanisms.

Methods:

The proliferation, apoptosis, migration, and invasion of oral cancer cells were analyzed after knocking down the expression of CD47. The effects of CD47 on tumor development were also evaluated using a murine model of OSCC. The involvement of CD47 in the phagocytosis of oral cancer cells was identified.

Results:

Cell proliferation was suppressed by knocking down the expression of CD47 in human OSCC cell line Cal-27 cells but there was no change in theapoptosis rate. Moreover, impaired expression of CD47 inhibited the migration and invasion of Cal-27 cells. Furthermore, we found that nude mice injected with CD47 knocked-down Cal-27 cells displayed decreased tumor volumes at week 9 compared to xenograft transplantations of blank Cal-27 cells. In addition, in vitrophagocytosis of Cal-27 cells by macrophages was significantly enhanced after the knockdown of CD47, which positively correlated with compromised STAT3/JAK2 signaling.

Conclusion:

In summary, the knockdown of CD47 down regulated the development of OSCC and increased the phagocytosis of Cal-27 cells, indicating that CD47 might be a promising therapeutic target.