bluuebunny/crossref_metadata_2025 huggingface dataset:
Astragaloside IV enhances memory and modulates hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice
Authors: Huang Fei , Lan Yunyi , Zhou Jin , Yang Liu , Guan Hao , Shi Hailian , Wu Hui , Hu Zhibi , Wu Xiaojun
Published: June 2020

Background

Astragaloside IV (ASIV) is one of the saponins isolated from Astragalus membranaceus, a widely used traditional Chinese medicine and a health product sold all over the world. However, so far, the effect of ASIV on GABAergic synaptic transmission has not been elucidated yet. In the present study, the effect of ASIV on memory and hippocampal synaptic plasticity was investigated in mice and down-regulated early growth response protein 1 (EGR-1) knockout mice.
Methods

Behavior tests including radial-arm maze test and shuttle-box test, liquid chromatography-tandem mass spectrometry, western blotting analysis, quantitative PCR, electrophysiological recording, and electron microscopy were used in this study. The difference of data was detected by unpaired student t-test or two-factor analysis of variance (ANOVA) or Mann-Whitney U test.
Results

ASIV was shown to enhance the learning and memory of mice in behavior tests, such as radial-arm maze test and shuttle-box test, as well as the synaptic plasticity in electrophysiological experiments. Moreover, it significantly reduced the concentration of gamma-aminobutyric acid (GABA) and the expression of glutamate decarboxylase 2 (GAD65) in mouse hippocampus, which was accompanied with decreased ratio of inhibitory synapses, and EGR-1, brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). When EGR-1 was knocked out, the promotive effects of ASIV on memory and synaptic plasticity, as well as the inhibitory effects on GAD65, BDNF and TrkB, were abolished. In addition, ASIV was found to down-regulate the pre-existing EGR-1 baseline to better adapt to the learning stimuli.
Conclusions

Together, these results demonstrated a novel role of ASIV in enhancing memory and modulating hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice.
An Attempt of an Enhanced Recovery After Surgery (ERAS) Protocol in Oblique Lumbar Interbody Fusion(OLIF)
Authors: Li Renjie , Shao Xiaofeng , Jiang Weimin
Published: June 2020

Background Enhanced recovery after surgery (ERAS) attempts to decrease the surgical stress response to minimize postoperative complications and improve functional rehabilitation after major surgery, but it have not been widely utilized in spinal surgery. This study is to evaluate the implementation of an ERAS pathway for patients undergoing oblique lumbar interbody fusion (OLIF) surgery.Methods This was a retrospective cohort study of patient who underwent OLIF in 2018 prior to ERAS (“pre-ERAS” ,n=23) and in 2019 after ERAS was instituted (“ERAS”, n=24). Major outcomes were collected included demographics, length of hospital stay, financial cost, postoperative complications, off-bed time and perioperative factors. Visual Analogue Scale (VAS) was used to evaluate the pain. The ERAS pathway and compliance with pathway elements were also recorded.Results After ERAS implementation, we found no significant differences in the baseline characteristics between the two groups. In our study, the mean stay in the hospital was significantly lower (p= 0.033) in the ERAS group (15.3±3.9 days) compared to the standard pathway group (13.0±3.1 days). In comparison to the standard group, we also found a variation between the financial costs of surgery and hospitalization [(116312.1±30787.4)vs(100691.2±19695.1) yuan, P < 0.05]. The ERAS group manifested a lower blood loss compared with the pre-ERAS group with statistical significance [(68.3±57.1)vs(119.3±104.8) ml, P < 0.05]. There was no significant difference in operative time, complications, and 30-d readmission rates ( P > 0.05 ). Pain scores between the two groups showed a significant difference during the 3th hour and 6th hour (P < 0.05).Conclusion Institution of an ERAS protocol appears to accelerate functional recovery and reduce length of stay, financial costs and decreased pain.
AXL Promotes SARS-CoV-2 Infection of Pulmonary and Bronchial Epithelial Cells
Authors: Wang Shuai , Qiu Zongyang , Hou Yingnan , Deng Xiya , Zheng Tingting , Yan Renhong , Wu Peihan , Xie Shaofang , Zhou Qiang , Huang Jing , Li Xu
Published: June 2020

The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to a host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and virus entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression across different human tissues is extremely low, especially in pulmonary and bronchial cells. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system might exist. In this study, we have identified tyrosine-protein kinase receptor UFO (AXL), specifically interacts with SARS-CoV-2 S on the host cell membrane. When overexpressed in cells that do not highly express either AXL or ACE2, AXL promotes virus entry as efficiently as ACE2. Strikingly, deleting AXL, but not ACE2, significantly reduces infection of pulmonary cells by the SARS-CoV-2 virus pseudotype. Soluble human recombinant AXL, but not ACE2, blocks SARS-CoV-2 virus pseudotype infection in pulmonary cells. Taken together, our findings suggest AXL may play an important role in promoting SARS-CoV-2 infection of the human respiratory system and is a potential target in future clinical intervention strategies.
Effects of inorganic minerals replaced by complexed glycinates on growth, blood profiles, immune responses, intestinal morphology, and mineral excretion in piglets
Authors: Pei Xun , Wang Geng , Liu Lujie , Sun Wanjing , Xiao Zhiping , Tao Wenjing , Wang Minqi , Huai Mingyan , Li Lily , Pelletier Wolf
Published: June 2020

BACKGROUND: The effects of inorganic trace minerals (ITM) replaced by low-dose glycine-complexed trace minerals (GCM) on growth, serum parameters, immunity, intestinal morphology, and mineral excretion in piglets were investigated. One hundred and twenty-eight weaned piglets (14.18 ± 0.33kg body weight (BW)) were randomly assigned to 4 treatments with 4 replicates, 8 piglets per replicate. Treatments consist of: (T1) basal diet + 100% inorganic trace mineral (ITM) as the control group (20 ppm Cu, 150 ppm Fe, 150 ppm Zn, and 30 ppm Mn from sulfates); (T2) basal diet + 50% ITM (Cu, Fe, Zn, and Mn from sulfates, 50% of control) + 50% organic trace minerals (OTM, Cu, Fe, Zn, and Mn from glycine complexed trace minerals (GCM), 50% of control); (T3) basis diet + 50% OTM from GCM; (T4) basal diet + 70% OTM from GCM. The feeding period lasted 28 d and was divided into 2 stages (0 to 14 d and 15 to 28 d). After feeding trial , 6 pigs per treatment were randomly selected to slaughter for sampling. RESULTS: Average daily gain, feed intake, and G:F were not affected by dietary treatments during the overall period. During the second, and the overall feeding phases, the digestibility of Zn and Fe in T3 and T4 was higher than that of T1 ( P < 0.05). The concentration of serum ferritin in T2 was significantly higher than T3 and T4. Serum immunoglobulin A concentration in the ileal mucosa of T2 was higher than that of T1 ( P < 0.05), and the higher duodenum villus height was observed in T4 compared with the rest treatments ( P < 0.05). The lowest trace mineral excretion was overserved in T3 ( P < 0.01); in addition, the urinary concentrations of Zn and Fe in T2 were lower than that in T1 ( P < 0.05). CONCLUSION: These results indicate that GCM have higher bioavailability than ITM, and that supplementation of low-dose GCM to replace full dose ITM could reduce mineral excretion without affecting performance, blood profiles, immune responses, and intestinal morphology in piglets.
Empirical Investigation into the Determinants of Public Debts in Africa: New Insights Using a Panel Bayesian Model Averaging Approach
Authors: Bayale Nimonka
Published: June 2020

The determinants of public indebtedness in developing countries is still generating a lot of interest among academics and policy makers. This paper introduces model uncertainty into the empirical study on the determinants of public debt at continental level. This is done by adopting a Bayesian model averaging approach applied to data of 51 African countries spanning from 1990 to 2018. Our results suggest that, among the set of twenty-seven (27) regressors considered in the baseline model, those reflecting international financial and institutional conditions as well as internal economic prospects tend to receive high posterior inclusion probabilities. These findings are robust to changes in the model specification, the inclusion of economic crises and geographical heterogeneities of the continent.
Family–Based Index Testing for HIV: a qualitative study of barriers and challenges among clients in Cape Coast, Ghana
Authors: Ampofo Evelyn Asamoah , Commey Isaac Tetteh , Adu-Gyamfi Raphael , Enyan Nancy Innocentia Ebu , Agyare Elizabeth , Ayisi-Addo Stephen , Obiri-Yeboah Dorcas
Published: June 2020

Background

Family-based Index HIV Testing, (FBIT) approach is known to be associated with a relatively higher testing yield compared to Provider-Initiated Testing and Counseling. The implementation of this strategy in several countries has exposed some barriers to optimal FBIT outcomes. With the scale up of FBIT in Ghana, stakeholders’ engagement is key in identifying and addressing all barrier to implementation. This study explored index clients’ perspective of barriers and challenges of FBIT.
Methods

Using an exploratory descriptive qualitative design, 17 individual in-depth interviews were conducted among seventeen purposively selected clients who had been offered FBIT at the Cape Coast Teaching Hospital (CCTH) utilizing a semi-structured interview guide. Each interview lasted between 45–60 minutes and the transcripts were transcribed verbatim and analyzed using qualitative content analysis procedure. Themes and sub-themes from the transcripts were generated and supported with verbatim texts to provide a rich understanding of the barriers and challenges.
Results

Age of participants ranged between 24–71 years, majority of whom were females. Themes and sub- themes emerged on barriers and challenges and these related to good understanding of the benefits of FBIT by index clients, challenge with getting family members to accept testing opportunities, fear and uncertainty of reaction of family members to a positive status, and issues of confidentiality and privacy related to health facility service provision. Key findings were: 1. Index clients perceived FBIT as a good approach to reach family members for testing. 2. Stigmatization, lack of confidentiality and privacy at service centers and 3. Inadequate information on FBIT were identified as barriers that can affect the uptake of FBIT. Getting listed family members to agree to be tested was perceived as a challenge.
Conclusions

Despite the acceptance of FBIT as a good strategy to reach family members of index clients for testing, there are barriers of stigmatization, fear and uncertainty of reaction of family members to a positive status, lack of confidentiality and privacy, and inadequate information on FBIT. Efforts should be made to address these barriers and challenges. Index clients and their families need tailored support to improve acceptance of this strategy.
Molecular Docking suggests repurposing of Brincidofovir as a potential drug targeting SARS-CoV-2 "COVID-19" ACE2 receptor and main protease
Authors: Hussien Mostafa A. , Abdelaziz Ahmed E.M.
Published: June 2020

The current outbreak of the highly transmittable and life-threatening treme intense respiratory disorder coronavirus 2 (SARS-CoV-2) has advanced rapidly and posed a global health emergency. Many clinical trials are now being conducted to test possible therapies. To assist, the molecular docking was applied on some selected FDA-approved drugs, previously used in epidemics, and the top ten compounds were selected. These ten well-characterized drugs, previously used to treat Malaria and Ebola infections, were screened based on their interactions with the SARS-CoV-2 ACE2 Receptor and 3C-like Protease. Compared to the other nine medicines, Brincidofovir, an ether lipid ester analog of cidofovir with potent antiviral activity, showed the highest docking scores and binding interactions. Therefore, Brincidofovir worth further investigations and clinical trials as a possible therapeutic agent for the COVID-19 disease .
A single dose of an adenovirus-vectored vaccine provides complete protection of the upper and lower respiratory tracts against SARS-CoV-2 challenge
Authors: Wu Shipo , Zhong Gongxun , Zhang Jun , Shuai Lei , Zhang Zhe , Wen Zhiyuan , Wang Busen , Zhao Zhenghao , Song Xiaohong , Chen Yi , Liu Renqiang , Fu Ling , Zhang Jinlong , Guo Qiang , Wang Chong , Yang Yilong , Fang Ting , Lv Peng , Wang Jinliang , Xu Junjie , Li Jianmin , Yu Changming , Hou Lihua , Bu Zhigao , Chen Wei
Published: June 2020

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we found that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protected mice completely against SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protected ferrets from SARS-CoV-2 infection in the upper respiratory tract. This study suggested that a combination of intramuscular and mucosal vaccination maybe provide a desirable protective efficacy and different Ad5-nCoV delivery modes are worth further investigation in human clinical trials.
Targeting Connexin43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling
Authors: Yu Hailong , Cao Xiang , Li Wei , Liu Pinyi , Zhao Yuanyuan , Song Lilong , Chen Jian , Chen Beilei , Yu Wenkui , Xu Yun
Published: June 2020

Background: In the central nervous system(CNS),Connexin43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Like Cx43 overexpression,abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies.However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear.Methods: Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH modals in vitro and vivo.Cx43 mimetic peptide Gap19 was treated after ICH injury. Ethidium bromide (EtBr) uptake assays was used to measure the opening of Hcs. Western blot and immunofluorescence were used to measure the expression of protein. qRT-PCR and ELISA were used to determine the level of cytokines. Co-immunoprecipitation(Co-IP) and Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins.Results: In this study,Cx43 expression was upregulated, and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition,Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo, as determined by GFAP staining. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture.However,Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased YAP nuclear translocation, which upregulated SOCS1 and SOCS3 expression, and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury.Conclusions: This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs.Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 plays anti-inflammatory and neuroprotective roles after ICH injury.
Management of patients with suspected COVID-19 who underwent emergency surgery
Authors: Tan Yanzhe , Yan Chengwei , guo chunbao
Published: June 2020

Background: Since the outbreak of COVID-19, no official guidelines for urgent surgical management of patients with the COVID-19 concern have been recommended. The current study provides our experience about the management for the patients with suspected or confirmed COVID-19 who required urgent surgical intervention.Methods: From February 5, 2019, to May 26, 2020, there were 5 cases of patients with suspected or confirmed COVID-19 infection managed with urgent surgical intervention in two hospitals in Chongqing. Results: The five cases with COVID-19 concern were admitted with different diseases, including acute intussusception, strangulated inguinal indirect hernia, acute purulent appendicitis, femoral fracture and onset to delivery. Finally, four patients obtained negative results afterwards. One pregnant woman with confirmed COVID-19 infection underwent caesarean section. All medical staff involved in the patients management were well, and no in-hospital transmission occurredConclusion:Suspected COVID-19 patients must be managed as positive patients until proven or denied in order to minimize the spread and transmission of infection. The current protocol carried out in our practice might be plausible and technically feasible for hospitals when dealing with COVID-19 infection.
Brain Imaging Big Data Mining and Fusion Method Based on Cognitive Intelligence
Authors: Li Xiao-Yan , Zhang Feng , Zhang Yong-Heng
Published: June 2020

In order to improve the utilization rate of brain imaging big data and solve the fusion problem of multi-source and heterogeneous brain imaging big data, an improved brain imaging big data ant colony optimization algorithm (BigDataACO) is proposed to complete the multi-source brain imaging big data information in the feature layer and decision-making and the problem of multi-source data fusion was solved. The swarm intelligence algorithm is a process of simulating the complex problem of populations in nature through the mutual cooperation between individuals. The algorithm has potential parallelism and strong robustness, and the algorithm does not depend on specific problems. The definition, principle and implementation method of brain imaging big data fusion problem are studied. Then the insufficiency of big data fusion modeling algorithm is analyzed. Finally, the source and core steps of ant colony big data fusion algorithm are studied. The experimental results show that the improved BigDataACO algorithm is verified by the measured data. Compared with K-means, D-S evidence theory and Bayesian algorithm, the uncertainty of data fusion is greatly reduced by the improved algorithm proposed in this paper.
Lung Function Decline and Other Physiological Changes in Health Workers after Working in COVID-19 Isolation Wards: An Observational Study
Authors: Chen Kailei , Zhu Peipei , Wang Liyuan , Zuo Siting , Wu CuiPing , Hu Ying , Wang YiSi , Wu Feng , Tang Xin
Published: June 2020

Background:Global healthcare systems have been under huge pressure since Coronavirus Disease 2019 (COVID-19) was declared a pandemic. It is critical to prevent further spread of COVID-19 and to protect health workers from infection. This study aims to figure out short-term physiological impact on health workers induced by working in isolation wards for hours with personal protective equipment (PPE), so as to provide insights on reducing physiological impact and infection risk of health workers.Methods:Health workers who had worked in COVID-19 isolation wards for at least five weeks in Wuhan, China were recruited. Parameters including lung function, heart rate, oxygen saturation and weight were respectively measured before and after they worked in isolation wards. Comparison and regression analyses were conducted. Correlations between changing levels of measured parameters (lung function and heart rate) and baseline characteristics (body mass index, age, and working duration) were also analyzed. Results: After working in isolation wards for four to nine hours, the forced vital capacity (FVC) of health workers (74.32±17.59 versus 81.28±16.35, P<0.001) as well as weight (54.79 (48.50, 61.00) versus 55.50 (48.90, 61.00) P<0.01) showed significant decrease, while HR showed significant increase (110.31±14.65 versus 103.94±16.38, P=0.04). Correlation between BMI and the decline levels of FEV1/FVC (β=2.87, P=0.02) and correlation between BMI and the decline levels of FEF25-75 % predicted (β=1.80, P<0.05) were reported.Conclusions:After working in COVID-19 isolation wards with PPE for four to nine hours, the lung function of health workers declined. The decline levels were associated with BMI. HR increase and weight loss were reported. In order to reduce the potential infection risk of health workers, the balance between working duration and physiological changes should be considered when making shifting schedule.
Change of foulant concentration in an anaerobic membrane bioreactor
Authors: Hasegawa Susumu , Murakami Genki , Takagi Ryosuke , Matsuyama Hideto
Published: June 2020

Anaerobic membrane bioreactors (AnMBRs) have many advantages, such as producing methane gas for energy generation and little excess sludge. However, membrane fouling is a serious problem because the foulant, which causes the membrane to foul, may get rejected by the membrane and accumulate in the reactor, resulting in an acceleration of membrane fouling. However, there is no information related to a change in the foulant concentration in an AnMBR. Therefore, we examined the changes in the foulant concentration in the reactor, related to membrane fouling in an AnMBR. For the influent, reactor solution, and effluent, the concentration of each component of the foulant was analyzed by using a liquid chromatography-organic carbon detector (LC-OCD). It was found that fouling in the AnMBR was closely related to the components in the reactor, and the main foulant of the ultrafiltration (UF) membrane was biopolymers (BPs). BP accumulated in the reactor because of a high rejection by the UF membrane. However, once the BP accumulated in the reactor was biodegraded, the concentration of BP decreased with time even under a high organic loading rate of 1.9kg TOC/m3/day.
Adsorption onto MWCNTs Coupled with Cloud Point Extraction for Dye Removal from Aqueous Solutions: Optimization by Experimental Design
Authors: Safa Fariba , Osaghi Bahare
Published: June 2020

Aims:

The main aim of the study was to examine the feasibility and benefits of
adsorption onto multi-walled carbon nanotubes (MWCNTs) coupled with cloud point extraction
(CPE) for the removal of Rhodamine B (RB) from aqueous solutions.

Background:

MWCNTs offer the particular features of the ideal adsorbents for the organic dyes
such as hollow tubular structure and specific surface area. Nevertheless, they suffer from the
drawbacks of low dispersion in the aqueous solutions and separation inconvenience from the
media. Cloud point extraction, combined with the adsorption onto MWCNTs can be a promising
method to overcome the problems.

Objective:

In the study, adsorption onto MWCNTs coupled with CPE was applied for RB removal
from aqueous solutions. The process was optimized by the response surface modeling method.
Moreover, the applicability of the proposed method in the real sample analyses was investigated.

Methods:

MWCNTs were used as adsorbent and Triton X-100 (TX-100) as the nonionic surfactant
for CPE process. The experiments were carried out based on a Box-Behnken design (BBD) with
the input variables of MWCNTs dosage (0.6-1.2 mg), solution pH (3–9), clouding time (20-40
min) and TX-100 concentration (10-20 v/v%) using 5 mg L-1 RB solutions.

Result:

Regression analyses resulted in a statistically significant quadratic model (R2=0.9718,
F=24.96, p#60;0.0001) by which the optimum levels of the variables were predicted as: MWCNTs
dosage of 0.7 mg, pH=3, clouding time of 39.9 minutes and TX-100 concentration of 19.91%
(v/v). The predicted conditions were experimentally validated by achieving an RB removal of
94.24%.

Conclusion:

Based on the results, the combination of the environmentally friendly technique of
CPE with adsorption onto MWCNTs allows the efficient removal of RB from water samples and
the method can be effectively optimized by the response surface modeling.
Evidence Linking Protein Misfolding to Quality Control in Progressive Neurodegenerative Diseases
Authors: Kabir Md. Tanvir , Uddin Md. Sahab , Abdeen Ahmed , Ashraf Ghulam Md , Perveen Asma , Hafeez Abdul , Bin-Jumah May N. , Abdel-Daim Mohamed M.
Published: June 2020

Several proteolytic systems including ubiquitin (Ub)-proteasome system (UPS), chaperonemediated autophagy (CMA), and macroautophagy are used by the mammalian cells to remove misfolded proteins (MPs). UPS mediates degradation of most of the MPs, where Ub-conjugated substrates are deubiquitinated, unfolded, and passed through the proteasome’s narrow chamber, and eventually break into smaller peptides. It has been observed that the substrates that show a specific degradation signal, the KFERQ sequence motif, can be delivered to and go through CMA-mediated degradation in lysosomes. Macroautophagy can help in the degradation of substrates that are prone to aggregation and resistant to both the CMA and UPS. In the aforesaid case, cargoes are separated into autophagosomes before lysosomal hydrolase-mediated degradation. Even though the majority of the aggregated and MPs in the human proteome can be removed via cellular protein quality control (PQC), some mutant and native proteins tend to aggregate into β-sheet-rich oligomers that exhibit resistance to all identified proteolytic processes and can, therefore, grow into extracellular plaques or inclusion bodies. Indeed, the buildup of protease-resistant aggregated and MPs is a usual process underlying various protein misfolding disorders, including neurodegenerative diseases (NDs) for example Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. In this article, we have focused on the contribution of PQC in the degradation of pathogenic proteins in NDs.
Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors
Authors: Güngör Emine Merve , Altıntop Mehlika Dilek , Sever Belgin , Çiftçi Gülşen Akalın
Published: June 2020

Background:

Akt is overexpressed or activated in a variety of human cancers, including
gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction
of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted
to the discovery of potent antitumor drugs targeting Akt.

Objectives:

The objective of this work was to identify potent anticancer agents targeting Akt.

Methods:

New hydrazone derivatives were synthesized and investigated for their cytotoxic effects
on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast
cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were
evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric
assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME)
studies were also performed using Schrödinger’s Maestro molecular modeling package.

Results and Discussion:

Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells
(with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with
cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced
apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin-
2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared
with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed
good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the
compound also complies with Lipinski's rule of five and Jorgensen's rule of three.

Conclusion:

Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis
inducer targeting Akt.
Classifying Cognitive Normal and Early Mild Cognitive Impairment of Alzheimer’s Disease by Applying Restricted Boltzmann Machine to fMRI Data
Authors: Pei Shengbing , Guan Jihong
Published: June 2020

Background:

Neuroimaging is an important tool in early detection of Alzheimer’s disease
(AD), which is a serious neurodegenerative brain disease among the elderly subjects. Independent
component analysis (ICA) is arguably one of the most widely used algorithm for the analysis of
brain imaging data, which can be used to extract intrinsic networks of brain from functional
magnetic resonance imaging (fMRI).

Method:

Witnessed by recent studies, a more flexible model known as restricted Boltzmann
machine (RBM) can also be used to extract spatial maps and time courses of intrinsic networks from
resting state fMRI, moreover, RBM shows superior temporal features than ICA. Here, we seek to
employ RBM to improve the performance of classifying individuals. Experiments are performed on
healthy controls and subjects at the early stage of AD, i.e., cognitive normal (CN) and early mild
cognitive impairment participants (EMCI), and two types of data, i.e., structural magnetic resonance
imaging (sMRI) and fMRI data.

Results:

(1) By separately employing ICA for sMRI and fMRI, the features extracted from fMRI
improve classification accuracy by 7.5% for CN and EMCI; (2) instead of applying ICA to fMRI,
using RBM further improves classification accuracy by 7.75% for CN and EMCI; (3) the lesions at
the early stage of AD are more likely to occur in the regions around slices 4, 6, 10, 14, 19, 51 and 59
of the whole brain in the longitudinal direction.

Conclusion:

By using fMRI instead of sMRI and RBM instead of ICA, we can classify CN and
EMCI more efficiently.
Metabolic Adjustments by LncRNAs in Peripheral Neutrophils Partly Account for the Complete Compensation of Asymptomatic MMD Patients
Authors: Han Ziping , Li Lingzhi , Liu Ping , Huang Yuyou , Zhang Sijia , Li Guangwen , Li Fangfang , Zhao Haiping , Tao Zhen , Wang Rongliang , Ma Qingfeng , Luo Yumin
Published: June 2020

Backgrounds:

Due to the recent development of non-invasive examinations, more asymptomatic
patients with Moyamoya Disease (MMD) have been diagnosed than ever. However, its underlying
molecular mechanisms and clinical intervention guidelines are all still obscure.

Methods:

Microarray was used to explore those differentially expressed mRNAs and lncRNAs in peripheral
neutrophils of asymptomatic MMD patients. Then enrichment analyses based on Gene Ontology
(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for those differentially expressed
mRNAs and lncRNA associated mRNAs were performed for underlying molecular mechanisms.

Results:

Here, we identified a total of 2824 differentially expressed lncRNAs and 522 differentially
expressed mRNAs (fold change > 2 and P<0.05) in peripheral neutrophils of asymptomatic MMD patients,
compared with healthy controls. Then enrichment analyses based on GO and KEGG showed
that the neighboring protein-coding mRNAs of those up-regulated and down-regulated lncRNAs were
mainly involved in distinct metabolic processes respectively, which may act as a complementary response
to insufficient blood supplies in MMD. Further enrichment analyses of those differentially expressed
mRNAs preferentially listed essential physiological processes such as peptide cross-linking,
chromatin assembly among others. Moreover, altered mRNAs also revealed to be enriched in renin secretion,
platelet activation, inflammation and others.

Conclusion:

We demonstrated for the first time that metabolic adjustments by dysregulated lncRNAs
in peripheral neutrophils might partially account for the complete compensation of asymptomatic
MMD patients. In addition, more attention should be paid on renin secretion and platelet activation in
order to better understand the pathogenesis and guide clinical intervention for asymptomatic MMDs.
Optimizing Smartphone-Delivered Cognitive Behavioral Therapy for Body Dysmorphic Disorder Using Passive Smartphone Data: Initial Insights From an Open Pilot Trial (Preprint)
Authors: Weingarden Hilary , Matic Aleksandar , Calleja Roger Garriga , Greenberg Jennifer L , Harrison Oliver , Wilhelm Sabine
Published: June 2020

BACKGROUND

Smartphone-delivered cognitive behavioral therapy (CBT) is becoming more common, but research on the topic remains in its infancy. Little is known about how people typically engage with smartphone CBT or which engagement and mobility patterns may optimize treatment. Passive smartphone data offer a unique opportunity to gain insight into these knowledge gaps.

OBJECTIVE

This study aimed to examine passive smartphone data across a pilot course of smartphone CBT for body dysmorphic disorder (BDD), a psychiatric illness characterized by a preoccupation with a perceived defect in physical appearance, to inform hypothesis generation and the design of subsequent, larger trials.

METHODS

A total of 10 adults with primary diagnoses of BDD were recruited nationally and completed telehealth clinician assessments with a reliable evaluator. In a 12-week open pilot trial of smartphone CBT, we initially characterized natural patterns of engagement with the treatment and tested how engagement and mobility patterns across treatment corresponded with treatment response.

RESULTS

Most participants interacted briefly and frequently with smartphone-delivered treatment. More frequent app usage (r=–0.57), as opposed to greater usage duration (r=–0.084), correlated strongly with response. GPS-detected time at home, a potential digital marker of avoidance, decreased across treatment and correlated moderately with BDD severity (r=0.49).

CONCLUSIONS

The sample was small in this pilot study; thus, results should be used to inform the hypotheses and design of subsequent trials. The results provide initial evidence that frequent (even if brief) practice of CBT skills may optimize response to smartphone CBT and that mobility patterns may serve as useful passive markers of symptom severity. This is one of the first studies to examine the value that passively collected sensor data may contribute to understanding and optimizing users’ response to smartphone CBT. With further validation, the results can inform how to enhance smartphone CBT design.
VA Video Connect for Clinical Care in Older Adults in a Rural State During the COVID-19 Pandemic: Cross-Sectional Study (Preprint)
Authors: Padala Kalpana P , Wilson Kerrie B , Gauss C Heath , Stovall Jessica D , Padala Prasad R
Published: June 2020

BACKGROUND

The COVID-19 pandemic has accelerated the need for telehealth at home. Although the Department of Veterans Affairs is a leading provider of telehealth, disparities may exist in reaching older veterans living in rural areas. VA Video Connect (VVC) is a video conferencing app that enables veterans to connect with their health care provider via a secure and private session.

OBJECTIVE

The aim of this study was to examine the capability and willingness of older veterans to participate in a VVC visit during the COVID-19 pandemic.

METHODS

A cross-sectional study was conducted on older veterans (N=118) at the Central Arkansas Veterans Healthcare System. Participants were interviewed over the phone and responses to the following items were recorded: availability of internet, email, and an electronic device with a camera; veterans’ willingness to complete an appointment via a VVC visit; and availability of assistance from a caregiver for those who were unable to participate in a VVC visit alone.

RESULTS

Participants’ mean age was 72.6 (SD 8.3) years, 92% (n=108) were male, 69% (n=81) were Caucasian, 30% (n=35) were African Americans, and 36% (n=42) lived in a rural location. The majority reported having access to the internet (n=93, 77%) and email service (n=83, 70%), but only 56% (n=67) had a camera-equipped device. Overall, 53% (n=63) were willing and capable of participating in a VVC visit. The availability of internet access was significantly lower in rural compared to nonrural participants (P=.045) and in those with or less than a high school education compared to those who pursued higher education (P=.02). Willingness to participate in the VVC visit was significantly lower in rural compared to nonrural participants (P=.03). Of the participants who reported they were able and willing to partake in a VVC visit (n=54), 65% (n=35) opted for VVC and 35% (n=19) preferred a phone visit. In total, 77% (n=27) of the scheduled VVC visits were successful.

CONCLUSIONS

Despite advances in technology, and willingness on the part of health care systems, there are some lingering issues with capability and willingness to participate in video telehealth visits, particularly among older adults residing in rural areas.
SARS-CoV-2 Biology Insights, Part I. Genome-wide structure and druggability: literature review (Preprint)
Authors: Lafon-Hughes Laura
Published: June 2020

BACKGROUND

COVID-19 pandemic prompts the study of coronavirus biology and search of putative therapeutic strategies.

OBJECTIVE

To compare SARS-CoV-2 genome-wide structure and proteins with other coronaviruses, focusing on putative coronavirus-specific or SARS-CoV-2 specific therapeutic designs.

METHODS

The genome-wide structure of SARS-CoV-2 was compared to that of SARS and other coronaviruses in order to gain insights, doing a literature review through Google searches.

RESULTS

There are promising therapeutic alternatives. Host cell targets could be modulated to hamper viral replication, but targeting viral proteins directly would be a better therapeutic design, since fewer adverse side effects would be expected.

CONCLUSIONS

Therapeutic strategies (Figure 1) could include the modulation of host targets (PARPs, kinases) , competition with G-quadruplexes or nucleoside analogs to hamper RDRP. The nicest anti-CoV options include inhibitors of the conserved essential viral proteases and drugs that interfere ribosome slippage at the -1 PRF site.
Implementation of Genetic Algorithms and Momentum Backpropagation in Classification of Subtype Cells Acute Myeloid Leukimia
Authors: Mustikaningrum Dian , Wardoyo Retantyo
Published: June 2020

Acute Myeloid Leukimia (AML) is a type of cancer which attacks white blood cells from myeloid. AML subtypes M1, M2, and M3 are affected by the same type of cells called myeloblasts, so it needs more detailed analysis to classify.Momentum Backpropagation  is used to classified. In its application, optimal selection of architecture, learning rate, and momentum is still done by random trial. This is one of the disadvantage of Momentum Backpropagation. This study uses a genetic algorithm (GA) as an optimization method to get the best architecture, learning rate, and momentum of artificial neural network. Genetic algorithms are one of the optimization techniques that emulate the process of biological evolution.The dataset used in this study is numerical feature data resulting from the segmentation of white blood cell images taken from previous studies which has been done by Nurcahya Pradana Taufik Prakisya. Based on these data, an evaluation of the Momentum Backpropagation process was conducted the selection parameter in a random trial with the genetic algorithm. Furthermore, the comparison of accuracy values was carried out as an alternative to the ANN learning method that was able to provide more accurate values with the data used in this study.The results showed that training and testing with genetic algorithm optimization of ANN parameters resulted in an average memorization accuracy of 83.38% and validation accuracy of 94.3%. Whereas in other ways, training and testing with momentum backpropagation random trial resulted in an average memorization accuracy of 76.09% and validation accuracy of 88.22%.
Reviving the Urban Core: Ludhiana City, Punjab, India
Authors: Randhawa Aman , Kumar Dr. Ashwani
Published: June 2020

The urban cores are considered as the most crucial clusters of the contemporary urban cities as they are the foremost economic growth poles that cater to the needs of the city population. These clusters are facing urban development issues like congestion, longer travel distances and time, pollution, etc., hence, transforming into a non-livable environment. Smart development has been identified as a world-wide solution to the existing urban development issues which focuses on promoting a sustainable and livable environment with the integration of ICT; acts as an implementation tool. Ludhiana; regarded as the Manchester of India, is the most industrialized city of the northern India. The city has a strong economic base due to the presence of commercial hub and small and large manufacturing industries which have acted as a catalyst for rapid urbanization. The city has witnessed immense population growth over the last 5 decades which has led to issues such as pollution, environment degradation,, emergence of slums and failure of physical and social infrastructure; thus failing to be a livable city. The paper intends to identify the urban development issues in Ludhiana city core and provide appropriate strategies based on the Smart Development principles.
Determination of Optimal Bottomhole Operation Pressure of Lateral Horizontal Bar
Authors: Miroshnichenko S. S. , Sidelnikov K. A.
Published: June 2020

Для эффективной эксплуатации месторождений нефти необходима оптимизация технологических параметров. Нормативно не определены оптимальные параметры забойного давления скважин для эксплуатации боковых горизонтальных стволов. В статье оценивается, при каком оптимальном забойном давлении целесообразно эксплуатировать боковой горизонтальный ствол месторождения с максимально «безводным» дебитом. По результатам расчетов и на основе графиков зависимости дополнительной добычи нефти и жидкости от забойного давления, графиков динамики добычи и обводненности выделены 3 группы бурения (зарезки) боковых стволов (ЗБС): с высокой прогнозной стартовой обводненностью (>90 %), средней стартовой обводненностью (около 80 %) и низкой стартовой обводненностью (около 20–50 %) и определены оптимальные параметры забойного давления для каждой из групп.
Budgetary Impact of Covering “Me-Too” Drugs from Social Security: Buenos Aires State Case Report
Authors: Marin Gustavo H. , Marin Lupe , Agüero Daniel , Pagnotta Mariana , Marin Gina , Blanco Luis
Published: June 2020

The majority of new drugs that are register at Health Global Market are not considered real innovations and due to their chemical structure similarity of reference’s group drug, they are known as “me-too”. These “me too” drugs has no additional therapeutic benefits but greatly increasing treatment´s. PURPOSE: To demonstrate the economic impact in Social Security budget by covering “me too” medicines. METHODS: An epidemiological-descriptive-analytical study was performed in order to analyze the burden of anti-hypertensive prescription from patients under coverage by Buenos Aires State Social Security. Two types of medicines were compared: “pioneer” or “me-too”. Variables considered were: type of drug, class or therapeutical group of medicines, global costs, burden for social security and for patients. RESULTS: From 185865 patients that received medication; in 121748 of the cases the strategy was monotherapy while 64117 received at least two or more medicines. 189714 were reference drugs while 64393 of them were considered “me-too”. In average, “me-too” drugs were 41.23% more expensive than classical treatment. The percentage covered by IOMA varies according to the medicines (between 45 to 51%) and patients must complete the amount of money remaining from their pockets. Paradoxically, the percentage covered by IOMA some “me-too” were greater than the percentage paid for most classic medications of each group. CONCLUSIONS: By only choosing the drug of reference, with proven effectiveness, from each therapeutical group, the State Social Security could cover 100% of the cost of all anti-hypertensive treatment and all patients even saving almost 2 million dollars per year.

Keywords: Health, Policies, Medicines, Me too, Economical Burden, Coverage, anti-hypertensive
Development and Validation of UPLC-MS/MS Method for Rapid Simultaneous Determination of Levothyroxine and Liothyronine in Human Serum
Authors: Dutt Rohit , Malik Kailash Chander , Karwa Manoj , JAIN Gaurav Kumar
Published: June 2020

A simple ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated to simultaneously determine levothyroxine (LT4) and liothyronine (LT3) in human serum. Sample preparation was done through protein precipitation with acetonitrile. HyPURITY C18 column was selected to achieve rapid separation for LT4 and LT3 within 4 min. Electrospray ionization (ESI) under multiple reaction monitoring (MRM) was used to monitor the ion transitions for LT4 (m/z 777.54→731.52), LT3 (m/z 651.64→ 605.65) and internal standard LT4-D3 (m/z 780.53 →734.19), operating in the positive ion mode. The method was proved to be accurate (82.35% to 113.56%) and precise (0.73% to 8.28%) over concentration range of 50.37 ng/ml – 300.13 ng/ml for LT4 and 0.5 ng/ml – 50.37 ng/ml for LT3. The validated method could be applied for pharmacokinetic study or bioequivalence testing of combination products of LT4 and LT3.

Keywords: Levothyroxine; Liothyronine; Ultra Performance Liquid Chromatographic; Mass Spectrometry; Human Serum
The Economic Effects of Earnings Management Pre- and Post-SOX
Authors: Mason Terry W. , Morton Richard M.
Published: June 2020

Research suggests that following several high-profile accounting scandals and the passage of SOX legislation in 2002, firms substituted real earnings management strategies for accrual manipulation. However, the broader implications of this tradeoff from a public policy and financial oversight perspective are not well understood. Consistent with our expectations, we find that abnormal operating decisions are less informative about future ROA in the post-SOX period. We also find that the increase in real earnings management negatively impacts firm value, but investors appear slow to recognize and price the myopic behavior. We do not observe a corresponding increase in the quality of discretionary accruals after SOX, but market mispricing of abnormal accruals essentially disappears, consistent with greater investor scrutiny. Although the shift away from accrual manipulation to real earnings management should result in less distortion of underlying economic events, the net effect appears to be value destroying for the average firm.

Data Availability: Data are publicly available from sources identified in the paper.

JEL Classifications: G32; G38; M41; M48.