bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A pilot two-center study
Authors: Eisert Albrecht , Lanckohr Christian , Frey Janina , Frey Otto , Wicha Sebastian G. , Horn Dagmar , Ellger Bjoern , Schuerholz Tobias , Marx Gernot , Simon Tim Philipp
Published: August 2020

Background : Sepsis is a severe disease with complex pathophysiology and high mortality. Meropenem is frequently used in sepsis to treat the underlying infection. Studies have shown that standard doses of meropenem are frequently inadequate due to high pharmacokinetic and pharmacodynamic variability. Therapeutic drug monitoring (TDM) of meropenem is not widely available, and increased empiric dosing recommendations are needed. Methods : We compared two empiric dosing schemes of meropenem using extended infusion (120 minutes) in 32 patients with sepsis in the ICUs at two different hospitals. One regimen was 3x 2 g meropenem/ 24 h for two days, followed by 3x 1 g meropenem/ 24 h; the other regimen was 4x 1 g meropenem/ 24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the dosing interval was above various target minimal inhibitory concentrations (MICs) for each regimen (%fT >MIC ). Results : Both regimens led to a sufficiently high %fT >MIC for pathogens with target MICs below 4 mg/L. When higher MICs were targeted, the %fT >MIC of 4x 1 g meropenem decreased faster than that of 3x 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide drug concentrations deemed appropriate for clinical improvement. Conclusions : The results of this pilot study can guide clinicians in their choice of an empirical dosing scheme when prescribing meropenem in the absence of TDM. If pathogens with low MICs (<4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant clones require higher doses. The control of β-lactam therapy by therapeutic drug monitoring is desirable.
Degradation and sorption of the herbicides 2,4-D and quizalofop-P-ethyl and their metabolites in soils from railway tracks
Authors: Buerge Ignaz J , Pavlova Pavlina , Hanke Irene , Bächli Astrid , Poiger Thomas
Published: August 2020

Background: Broad spectrum of activity and low risk of groundwater contamination are important arguments for the application of the herbicide glyphosate on railway tracks. Nevertheless, certain weeds are insufficiently controlled or develop resistance, and there is also an ongoing controversial discussion about possible carcinogenicity of glyphosate. Alternatives are thus strongly desired. 2,4-D and quizalofop-P-ethyl (QE) are two selective herbicides with a complementary spectrum of activity. When used in agriculture, the compounds and their metabolites pose low risk to groundwater. Uses on railway tracks are, however, more critical since degradation likely is slower and mobility higher than in agricultural soils. In this study, we investigated degradation and sorption of the two active substances as well as five metabolites in three soils collected from railway tracks and in a crushed sand, used for construction works.Results: In these railway materials, the compounds were indeed degraded slower than in agricultural soils (mean half-lives differed by a factor of 2-26) and mobility was higher (mean sorption coefficients differed by a factor of 3-19). Half-lives and sorption coefficients were also estimated by extrapolation of data from agricultural soils, considering the organic carbon content of railway soils and agricultural soils. Estimated values were more conservative than measured values, i.e., for herbicides, for which no measured parameters are available for railway soils, estimated values may be a viable alternative for a first tier groundwater assessment.Conclusions: Based on our experimental data, possible leaching to groundwater is predicted to be highest for 2,4-D and quizalofop-acid, the primary metabolite of QE, moderate for 2,4-dichlorophenol, the primary metabolite of 2,4-D, but low for QE. Secondary and tertiary metabolites were formed in only low quantities. For an advanced groundwater risk assessment, leaching studies, e.g., with lysimeters, would be a reasonable next step.
A New grading system based on T2-weighted axial MRI for Cervical Canal stenosis
Authors: Wang Shaoyi , Zhao Yunpeng , Wei Jianlu , Pan Xin , Nie Lin , Shi Jie , Cheng Lei
Published: August 2020

Background: Cervical Canal Stenosis (CCS) is a common cervical disease that occurs during and after middle age. There are a variety of grading systems and Measurement methods based on X-ray, Computed Tomography(CT) for cervical canal stenosis. Although many authors measured and classified cervical canal stenosis on the basis of T2-weighted sagittal MRI after the appearance of magnetic resonance, the research on Cervical Canal Stenosis remains to be improved. To explore a more detailed grading system on MRI for cervical canal stenosis and could be used to the clinical diagnosis and treatment.Methods: We retrospectively studied 200 patients with cervical spinal stenosis. Cervical canal stenosis was classified according to the T2-weighted axial MRI with the most serious compression into the following grades: grade 0,normal; grade 1, mild canal stenosis with obliteration of anterior or posterior of cerebrospinal fluid (CSF) space ; grade 2, moderate canal stenosis with obliteration of both sides of the CSF space but no significant changes in spinal morphology; Grade 3, severe canal stenosis with spinal cord deformity, 3A the oppression ratio of cervical spinal cord is under 50%, 3B the angle of the protrusion less than 90°; Grade 4, serious canal stenosis with spinal cord deformity and the oppression ratio of cervical spinal cord is exceeding 50%, 4A the non-ossification protrusion, 4B the ossific protrusion. We collected the relevant clinical and imaging data of the patients and analyzed the relationship between them and our new grading system. Patients were followed up one year later.Results: Our new grading system was easy to learn and communication. The the ICC reliabilities between six readers was between 0.817-0.865. And the Effective sagittal spinal canal was significantly different along with our grades at each disc level. In terms of clinical data, our grading system is correlated with the patient's preoperative mJOA score and had impact on the choice of surgical strategy. Conclusions: We suggest our new grading system can provided as a reliable assessment that can guide clinical treatment for Cervical Canal Stenosis.
An Annotation-free Whole-slide Training Approach to Pathological Classification of Lung Cancer Types by Deep Neural Network
Authors: Chen Chi-Long , Chen Chi-Chung , Yu Wei-Hsiang , Chen Szu-Hua , Chang Yu-Chan , Hsu Tai-I , Hsiao Michael , Yeh Chao-Yuan , Chen Cheng-Yu
Published: August 2020

Deep learning for digital pathology is hindered by the extremely high spatial resolution of whole slide images (WSIs). Most studies adopt patch-based methods which, however, require well annotated data for training. These are typically done by laboriously free-hand contouring on the WSI by experts. To both alleviate annotation burdens of experts and enjoy benefits from scaling up amounts of data, we develop a whole-slide training method for entire WSIs to classify types of lung cancers using slide-level diagnoses. Our method leverages unified memory to offload the excessive amount of memory consumption to host memory to train a classifier by entire hundreds-of-million-pixels slides. Experiments were conducted on the lung cancer dataset which contains 9,662 digital slides with various main types. The results showed that the proposed method can achieve an AUC of 0.950 and 0.924 for adenocarcinoma and squamous cell carcinoma on a separate testing set respectively. Furthermore, critical regions highlighted by the class activation map (CAM) technique of our model reveals a high correspondence to cancerous areas annotated by pathologists.
Flightless I Homolog Reverses Neo-Endocrine Therapy Resistance through YBX1/PD-L1 Axis Mediated-Immune Evasion in Prostate Cancer
Authors: Ruan Hailong , Bao Lin , Tao Zhen , Chen Ke
Published: August 2020

Background: Tumor cells can evade immune surveillance and immune killing effects during neo-endocrine therapy resistance, but the mechanisms that induce this phenomenon are still unclear. Flightless I homolog (FLII) functions as a coregulator of transcription factors in malignancies. Here, we aim to identify the functions and mechanisms of FLII-mediated neo-endocrine therapy resistance and immune evasion in prostate cancer (PCa).Methods: Bioinformatics analysis and PCa tissue microarray were used to assess the correlation between FLII and the immune checkpoint PD-L1. Immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) were used to investigate the regulation of PD-L1 expression by FLII. Enzyme-linked immunosorbent assay (ELISA) was used to study the effect of FLII on cytokine secretion. The number of effector T cells and immunosuppressive lymphocytes was detected by flow cytometry (FCM).Results: FLII was negatively correlated with the expression of PD-L1 in PCa. Mechanistic studies demonstrated that FLII physically interacted with YBX1 to inhibit the nuclear localization of YBX1 and thereby suppressed the transcriptional expression of PD-L1 in enzalutamide-resistant tumors. Restoration of FLII expression reversed neo-endocrine therapy resistance by activating the T cell response in the tumor microenvironment mediated by partial inhibition of the YBX1/PD-L1 pathway. The reversal of neo-endocrine therapy resistance and immune evasion was mediated by the proliferation of effector CD8+ T cells and inhibition of the infiltration of regulatory T cells and myeloid-derived suppressor cells in the tumor microenvironment.Conclusions: FLII inhibits tumor progression in part through repressing YBX1/PD-L1-mediated immune evasion. Combination therapy with FLII and neo-endocrine therapy may improve the benefits in prostate cancer patients and avoid immune evasion.
Healthy Mitochondria: The Brake of Cell Proliferation of Malignant Melanoma
Authors: Yu Zhenyao , Zhao Zizhen , Fu Chen , Zhou Wei , Wang Junchen , Fu Ailing
Published: August 2020

Background: Melanoma has become the leading cause of death from skin disease, and male patients show higher mortality rate than female. Mitochondrial transplantation therapy is an active area of current research but the anti-melanoma activity and specific mechanism involved in the therapy remain to be fully characterized.Methods: In the study, we intravenously administrated mitochondria extracted from male and female mouse livers respectively to the mice bearing malignantly subcutaneous and metastatic melanoma, and identified the signal mechanism responsible for the mitochondrial treatment through transcriptomic analysis. Meanwhile, the efficiency of female mitochondria and male mitochondria was compared in the cultured melanoma cells and transplanted melanoma in mice. Results: The results suggested that the mitochondria significantly inhibited the tumor growth, and the transcriptomic analysis suggested that general chromosome silencing and local opening of UPRmt effect region were strongly associated with the mitochondria against melanoma., which represented cell cycle arrest, autophagy, and cell apoptosis in the mitochondrial therapy on the metastasis melanoma. Moreover, the anti-tumor activity of mitochondria from female animals was more efficient in comparison to the males, and the female mitochondria could probably induce more persuasive mitochondria-nuclear communication than the mitochondria from male mice.Conclusions: The study not only reveals the anti-tumor mechanism of the mitochondria but also provides a novel insight into the effect of mitochondria in different genders.
Intravenous Iron Therapy Replenishes Iron Stores without Enhancing Tumour Responses in Anaemic Patients with Colorectal Cancer: Comparison with Oral Iron Supplementation.
Authors: Al-Hassi Hafid O , Ng Oliver , Evstatiev Rayko , Mangalika Manel , Worton Natalie , Jambrich Manuela , Khare Vineeta , Phipps Oliver , Keeler Barrie , Gasche Christoph , Acheson Austin G , Brookes Matthew J.
Published: August 2020

Background: Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examines whether the route of iron therapy alters iron transport and tumour growth. Methods: Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n=15), or intravenous ferric carboxymaltose (n=15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis, Wnt signalling pathway and microsatellite instability using immunohistochemistry and RT-PCR. Results: Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. The protein and mRNA expression of iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours (p<0.001) and successfully replenished body iron stores without increasing tumour growth, DNA damage markers, proliferation or apoptosis compared with oral iron treatment. Conclusion: Iron distribution to non-epithelial cells in intravenous iron treatment suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron supplementation could be a safer option in the treatment of colorectal cancer patients with iron deficiency anaemia due to the differential compartmentalisation of iron within the intestinal mucosa and its efficiency in replenishing body iron levels without increasing the risk of tumour growth.Trial registration: The study was registered with the Medicines and Healthcare Regulatory Agency, clinical trials.gov (NCT01927328) and EudraCT (2013-000209-22).
GSK3β Inhibition Synergizes with PARP Inhibitors through the Induction of Homologous Recombination Deficiency in Colorectal Cancer
Authors: Zhang Ning , Tian Yu-Nan , Zhou Li-Na , Li Meng-Zhu , Song Shan-Shan , Huan Xia-Juan , Bao Xu-Bing , Zhang Ao , Miao Ze-Hong , He Jin-Xue
Published: August 2020

Background: Monotherapy with poly ADP-ribose polymerase (PARP) inhibitors results in limited objective response rate (≤ 60% in most cases) in patients with homologous recombination repair (HRR)-deficient cancer, which suggests a high rate of resistance in this subset of patients to PARP inhibitors (PARPi). To overcome resistance to PARPi and to broaden their clinical use, we performed high-throughput screening of 99 anticancer drugs in combination with PARPi to identify potential therapeutic combinations. Methods: The effects of PARPi combined with glycogen synthase kinase 3 (GSK3) inhibitors were investigated in vitro with respect to cell viability, cell cycle and apoptosis. The synergy was assessed by calculation of the combination index (CI). GSK3α null and GSK3β null cells were generated using CRISPR/Cas9 technique. The underlying mechanism was examined by western blotting, flow cytometry, qRT-PCR and fluorescence microscopy. This combination was also evaluated in the mouse xenograft model; tumor growth and tumor lysates were analyzed, and the immunohistochemistry assay was performed. All data are presented as mean ± SD. Comparison between two groups was performed with the Student’s t-test.Result: The data showed that ~25% of oncological drugs and kinase inhibitors that were evaluated displayed synergy with PARPi in HCT-15 cells. Among the tested agents, GSK3 inhibitors (GSK3i) exhibited the strongest synergistic effect with PARPi. Moreover, the synergistic antitumor effect of GSK3 and PARP inhibition was confirmed in a panel of colorectal cancer (CRC) cell lines with diverse genetic backgrounds. Additionally, inhibition or genetic depletion of GSK3β was found to impair HRR of DNA and reduce the mRNA and protein level of BRCA1. Finally, we demonstrated that inhibition or depletion of GSK3β could enhance the in vivo sensitivity to simmiparib without toxicity.Conclusion: Our results provide a mechanistic understanding of combination of PARP and GSK3 inhibition, and support the clinical development of this combination therapy for CRC patients.
Compositional Analysis Of The Bacterial Community In Colostrum Samples From Women With Gestational Diabetes Mellitus And Obesity
Authors: Gámez-Valdez July Stephany , García-Mazcorro José Francisco , Rincón Alan Heriberto Montoya , Reyes Dalia Liliana Rodríguez , Blanco Gelacio Jiménez , Rodriguez Melissa Tatiana Alanís , Vaca Rebeca Pérez-Cabeza de , García Mario René Alcorta , Brunck Marion Emilie Genevieve , Díaz Víctor Javier Lara , Licona-Cassani Cuauhtemoc
Published: August 2020

Background. Obesity and Gestational Diabetes Mellitus (GDM) are major concerns during pregnancy as they compromise both mother and newborn health. These pathophysiology leads to variations in gut and breastmilk microbiota, threatening the settlement of neonate’s gut microbiota and the stimulation of immune cells. While several studies have described compositional changes of breast milk, placenta and maternal and newborn intestinal microbiota, it is unknown how breastmilk microbiota is affected under maternal GDM. The molecular mechanisms in which microbial-unbalanced breastmilk affect development of infants is not well understood for the case of obesity and GDM. As a first step, we used 16S- amplicon sequencing to describe the taxonomical bias of breastmilk of 43 women with GDM and women with obesity. We sampled colostrum within the first 24 h taken after birth in order to identify and quantify the first microbial community potentially colonizing infants gut.Results. A total of 1,675 amplicon sequence variants (ASVs) were identified, being Proteobacteria and Firmicutes the dominant phyla. We found Pseudomonas, Gemellales and Enterobacter overrepresented in samples of women with obesity and GDM. We used observed ASV´s, Shannon index and Faith´s phylogenetic diversity scores as alpha diversity indicators and UniFrac and robust Aitchison distances beta diversity indicators. Both metrics show a distinct microbial composition for GDM (female sub-group) and Obesity (male subgroup) compared to controls. Finally, differentially abundance analysis showed that Rhodococcaceae was distinct for GDM and 7 families (Bdellovibrionaceae, Burkholderiaceae, Halomonadaceae, Pseudomonadaceae, Shewanallaceae, TM7-1 and Vibrionaceae) with an absolute effect size greater than 1, of which 5 had a q-value ≤ 0.05 were distinct for obesity groups.Conclusions. To our knowledge, this study represents the first approach to the breastmilk bacteria composition of mothers with GDM. Our work provides the foundation for the design of functional metagnomic studies aiming to understand molecular mechanisms of which breastmilk from individuals with GDM and obesity affect the physiology of the infants.
Distinct profiles of stimulus specific cortical activity for ignoring distraction during working memory encoding and maintenance, and associations with performance
Authors: Ashton Charlotte , Gouws André , Glennon Marcus , ZANTO THEODORE , Tipper Steve , McNab Fiona
Published: August 2020

Our ability to hold information in mind for a short time (working memory) is separately predicted by our ability to ignore two types of distraction: distraction that occurs while we put information into working memory (encoding) and distraction that occurs while we maintain already encoded information within working memory. This suggests that ignoring these different types of distraction involves distinct mechanisms which separately limit performance. Here we used fMRI to measure category-sensitive cortical activity and probe these mechanisms. The results reveal speciﬁc neural mechanisms by which relevant information is remembered and irrelevant information is ignored, which contribute to intra-individual differences in WM performance.
Synthesis of monocarboxylic acids via direct CO2 conversion over Ni–Zn alloy catalysts
Authors: Sibi Malayil , Verma Deepak , Setiyadi Handi , Butolia Paresh , KHAN MUHAMMAD KASHIF , Kwak Sang Kyu , Chung Kyung Yoon , Park Jeaho , Han Daseul , Nam Kyung-Wan , Kim Jaehoon
Published: August 2020

The direct conversion of CO2 to methane, gasoline-to-diesel range fuels, methanol, and light olefins using renewable electricity sources is considered a promising approach for mitigating global warming. Nevertheless, the direct conversion of CO2 to high value-added chemicals, such as acetic and propanoic acids (AA and PA, respectively), has not been explored to date. Herein, we report a Ni–Zn alloy/Zn-rich NixZnyO catalyst that directly converted CO2 to AA and PA with an overall selectivity of 77.1% at a CO2 conversion of 13.4% at 325 °C. The surface restructuring of the ZnO and NiO phases during calcination and subsequent reduction led to the formation of a Ni–Zn alloy on the Zn-rich NixZnyO phase. Surface-adsorbed (*CHx)n species were formed via the reverse water-gas shift reaction and subsequent CO hydrogenation. Afterward, monocarboxylic acids were produced via the direct insertion of CO2 into the (*CHx)n species and subsequent hydrogenation. The synthesis of monocarboxylic acid was highly stable up to 216 h on-stream over the Ni–Zn alloy catalyst, and the catalyst maintained its phase structure and morphology during long-term CO2 hydrogenation. The high selectivity toward monocarboxylic acids and high stability of the Ni–Zn alloy demonstrated its excellent potential for the conversion of CO2 into value-added chemicals.
Simultaneous Determination of Fexofenadine Hydrochloride and Montelukast Sodium Using New Pencil Graphite Electrode in Their Pure, Synthetic Mixtures, and Combined Dosage Form
Authors: Nashed Dania , Noureldin Imad , Sakur Amir Alhaj
Published: August 2020

This paper introduces a new electrochemical approach for the concomitant determination of fexofenadine hydrochloride and montelukast sodium by constructing three new graphite electrodes coated with a polymeric membrane. The first electrode was constructed using ammonium molybdate reagent as an ion pair with fexofenadine cation for the determination of fexofenadine drug, the second electrode was constructed using cobalt nitrate as an ion pair with montelukast anion for the determination of montelukast drug, the third electrode was prepared by incorporating the two previously mention ion pairs in the same graphite sensor, which make this sensor sensitive to each fexofenadine and montelukast drug. The coating material was a polymeric film comprises of Poly Vinyl Chloride (PVC), Di-butyl phthalate as a plasticizer (DBP), ion pairs of drugs with previously mentioned reagents. The electrodes showed a Nernstian response with a mean calibration graph slopes of [58.97, 28.43, (59.048 , 28,643 )] mv.decade-1 for the three pencil electrodes respectively. The electrodes work effectively over pH range (2-4.5) for fexofenadine hydrochloride and (5-9.5) for montelukast sodium. The influence of the proposed interfering species was negligible. The effectiveness of the electrodes continued in a period of time (45-69) days. The suggested sensors demonstrated useful analytical features for the determination of both drugs in bulk powder, in laboratory prepared mixtures and their combined dosage form. We have validated the method in accordance with ICH protocol.
Enhanced biochemical process for purifying xylo-oligosaccharides from pre-hydrolysis liquor
Authors: Yang Guihua , Xu Feng , Ji Xingxiang , Dong Jiran , Ni Yonghao , Fatehi Pedram , Zhang Kai , Chen Jiachuan
Published: August 2020

Background

Xylo-oligosaccharides (XOS) are promising biomass-derived chemicals that can be widely used in preparing medicines, food additives, and industrial chemicals. The pre-hydrolysis liquor (PHL) produced in the kraft-based dissolving pulp production process is rich in hemicelluloses and especially in XOS/xylan.
Results

In this study, a sustainable sequential process that included calcium hydroxide (CH), simultaneous laccase and xylanase (LX) and activated carbon (AC) treatments was proposed for more efficient recovery of XOS/xylan from PHL. Overall, the concentration of lignin, furfural and xylosugars decreased by 81.7 wt.%, 100 wt.% and 5.1 wt.%, respectively, but XOS concentration was increased by 36.6 wt.%. More importantly, the 2D-HSQC NMR and FT-IR were used in understanding the structure of sugar and lignin components in each step of the process and in the final products. The CH treatment mainly altered the chemical structure of XOS due to the release of acetyl groups, and downstream treatment steps have insignificant effect on XOS structures. Also, lignin carbohydrate complexes (LCC, i.e. PhGlc3) minimally existed in the purified XOS. The GPC and DSC results revealed that the molecular weight of the extracted lignin was 1768 ~ 2532 g/mol and it had a wide glass transition temperature (Tg) range (63 ~ 115 °C).
Conclusions

The results confirmed that a combination of sequentially treating PHL with calcium hydroxide (CH), simultaneous laccase and xylanase (LX) and activated carbon (AC) was effective in removing lignin and concentrating XOS in the PHL.
Investigating Patients’ Preferences to Inform Drug Development Decisions: Novel Insights From a Discrete Choice Experiment in Migraine
Authors: Torbica Aleksandra , Rognoni Carla , Tarricone Rosanna
Published: August 2020

Background: Chronic conditions have important long-term consequences for patients’ personal and social lives and require patient commitment to their management. In this context, the assessment of patients’ preferences for treatment characteristics would increase the current evidence on the impact of diseases to support decision-making processes in the field of public policies and research and development in pharmaceutical industries.The present study used cases of chronic migraine to assess patients’ preferences, including the analysis of gender differences, for the characteristics of an ideal migraine treatment. Methods: A discrete choice experiment was performed with 466 adults with migraine in Italy who experienced at least 4 attacks per month. We investigated the preferences of patients with respect to ﬁve treatment attributes that were identified from a systematic literature review and two focus group elicitations. The heterogeneity of preferences was investigated in a mixed logit model with normally distributed random coefﬁcients.Results: Overall, the respondents considered the presence of adverse events, duration of the treatment effect, reduction of symptom intensity, speed of the effect and the cost born by the patient as the most relevant treatment features. As expected, the patients preferred treatments with lower levels of adverse events and costs and treatments with greater speed, duration of treatment effect and effectiveness in reducing symptom intensity. There was significant preference heterogeneity only for the presence of adverse events. Compared to men, women had significantly higher preferences for quicker treatment effect and limited adverse events and reported higher preferences for costly treatments.Conclusions: The results of our survey help address research and development strategies in the pharmaceutical industry and public policy regarding treatments that are clinically effective and responsive to the needs expressed by patients.
Resistin-like Molecule β Acts as a Mitogenic Factor in Hypoxic Pulmonary Hypertension via Ca2+ dependent PI3K/Akt/mTOR and PKC/MAPKs Signaling Pathway
Authors: Tian Heshen , Liu Lei , Yin Wu , Wang Ruiwen , Jiang Yongliang , Hu Ruicheng , Zhu Liming , Li Liwei , Fang Yanyan , Yang Chunlan , Ji Lianzhi , Liu Guoyu , Dai Aiguo
Published: August 2020

BACKGROUND: Pulmonary arterial smooth muscle cells(PASMCs) proliferation plays a crucial role in Hypoxia-induced pulmonary hypertension(HPH). Previous studies have found that Resistin-like molecule β(RELM-β) up-regulated de novo in response to hypoxia in cultured primary human PASMCs(HASMCs). RELM-β has been proved to promote PASMCs proliferation and involved in pulmonary vascular remodeling of patients with PAH. However, the expression pattern, the effects, and the mechanisms of RELM-β in HPH keep unknown. METHODS: We assessed the expression pattern, mitogenetic effect, and underlying mechanism of RELM-β in the rat HPH model and HASMCs. RESULTS: Overexpression of RELM-β alone caused the hemodynamic change in the rat model of HPH, similar to that caused by chronic hypoxia, with increased mean pulmonary arterial pressure(mPAP), right ventricle hypertrophy(RVSP), and thickening of small pulmonary arterioles. Knocking down of RELM-β partially blocked the increased mPAP, RVSP, and vascular remodeling induced by hypoxia. Phosphorylated PI3K/Akt/mTOR and PKC/MAPKs proteins were significantly up- or down-regulated by RELM-β gene overexpression or silencing. Recombinant RELM-β protein increase primary cultured human PASMCs intracellular Ca 2+ concentration and promote HASMCs proliferation. The mitogenic effect of RELM-β on HASMCs and phosphorylated PI3K/Akt/mTOR and PKC/MAPKs was suppressed by Ca 2+ inhibitor. CONCLUSIONS: Our findings suggested that RELM-β acts as a cytokine-like growth factor in the development of HPH and that this process is likely mediated by the Ca 2+ dependent PI3K/Akt/mTOR and PKC/MAPKs pathway. Keywords : hypoxic pulmonary arterial hypertension; resistin-like molecule β; Ca 2+ ; pulmonary vascular remodeling; signaling pathway
COVID-19 Pandemic and its Implication on Hand Hygiene Status by Alcohol-based Hand Sanitizers Among Healthcare Workers in Jimma University Medical Center, Ethiopia
Authors: Assefa Desta , Melaku Tsegaye , Bayisa Bodena , Alemu Sintayehu
Published: August 2020

Background: Pandemic corona virus disease (COVID-19) is a global health crisis of our time. The consistent practice of hand hygiene, especially by proper use of alcohol-based hand sanitizers in health facilities and community is a cardinal step in combating it. This study was designed to assess self-reported level of knowledge, attitude and compliance to WHO recommended hand hygiene status by alcohol-based hand sanitizers among healthcare workers during a COVID-19 pandemic in Jimma University Medical Center, Ethiopia.Methods: Questionnaire-based descriptive cross-sectional study was conducted between April and June 2020. Data were analyzed using SPSS version 21 with significance level at p<0.05.Results: From a total of 96 volunteer study participants (27nurses; 21pharmacists, 15academicians, 13medical laboratory technicians, 7physician, 7dental doctors, 6midwives) 61 were males. Their mean age was 28.69+4.048years. Alcohol-based hand sanitizers were used by 95.8% respondents to prevent spreading of COVID-19. The majority (93.8%) of the respondents had good knowledge; 74% had a good attitude and 76% had good hand hygiene practices by alcohol-based hand sanitizers. They got information about this technique mainly from mass media 71(74%) and training (40.6%). 84.5% respondents were facing challenges during alcohol-based hand sanitizer use due to it is unavailable 66(68.8%), expensive 50(52.1%), forgetting 11(11.5%), experiencing and/or fearing health-associated risks (skin irritation(28.1%), skin dryness(62.5%), ocular irritation(11.5%), etc).Conclusion and recommendationThe majority of respondents had good knowledge; but the attitude and adherence to standard guidelines need improvement. The hospital should catalyze behavioral change, provide emollient containing hand sanitizers and educational courses to achieve and sustain improvements.
The role of long noncoding RNA AL161431.1 in the development and progression of pancreatic cancer
Authors: Ma Gang , Li Guichen , Fan Wufeng , Xu Yuanhong , Song Shaowei , Guo Kejian , Liu Zhe
Published: August 2020

Background: Pancreatic cancer is known for its notorious fast progression and poor prognosis. Various long noncoding RNAs (lncRNAs) have been shown to be involved in the pathogenesis processes of pancreatic cancer.Methods: We first identified lncRNA AL161431.1 through bioinformatic analysis. Then, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by in vitro and in vivo experiments, including qRT-PCR, Western blot, immunofluorescence and immunohistochemistry assays, and flow cytometry, in BxPC-3 and SW1990 cells, as well as clinical samples. Results: We found that lncRNA AL161431.1 was highly expressed in patients with pancreatic cancer. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of the epithelial mesenchymal transition pathway.Conclusions: LncRNA AL161431.1 is involved in the progression of pancreatic cancer through its promotion of the epithelial mesenchymal transition pathway.
SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic
Authors: Schneider Jochen , Mijocevic Hrvoje , Ulm Kurt , Ulm Bernhardt , Weidlich Simon , Wuerstle Silvia , Rothe Kathrin , Treiber Matthias , Iakoubov Roman , Mayr Ulrich , Lahmer Tobias , Rasch Sebastian , Herner Alexander , Burian Egon , Lohöfer Fabian , Braren Rickmer , Makowski Marcus , Schmid Roland , Protzer Ulrike , Spinner Christoph , Geisler Fabian
Published: August 2020

Background: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. Methods: IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR+; CT±) and 46 patients with suspected (group B: repetitive PCR-; CT+) COVID-19, admitted to a German university hospital during the pandemic’s first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19. Results: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p<0.01). Compared to hospitalized patients with a non-complicated course, seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 9%, 26%, 65%, 77% and 92% in group A, compared with 0%, 10%, 20%, 40% and 50% in group B (p<0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology >14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR >17d after symptom onset. Conclusions: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2 nd week following symptom onset.
Computing Simulation and Spatial difference Analysis of Resources and Environment Ecological footprint out of Control
Authors: Chen Roulin , Zhang Duanmin , Li Bo
Published: August 2020

As a quantitative evaluation method, the ecological footprint theory analysis method (EFA) is a frontier subject in the field of sustainable development. The production activities of human beings will inevitably produce certain consumption, including the occupation of natural resources, consumption of W and the production of waste, which will have a certain impact on the ecological environment, just as one foot on the ground will leave footprints. On the other hand, the ecological environment itself will also provide a certain bearing capacity, supply human material consumption. The ecological footprint theory is to quantitatively convert the material consumption produced by human activities into the biological productive land area, and compare it with the supply area in the study area. Since Rees put forward the theory of ecological footprint, the development of ecological footprint model has gone from one-dimensional model to two-dimensional model, and from two-dimensional model to three-dimensional model. This paper reviews the evolution of ecological footprint model from four aspects: scientific problem, model connotation, interpretation ability and application direction, in order to cause new thinking on ecological footprint model.
Epidemiology, Risk Factors and Outcomes of Bloodstream Infection Caused by ESKAPEEc Pathogens Among Hospitalized Children
Authors: Peng Xiaoshan , Zhou Wei , Zhu Yu , Wan Chaomin
Published: August 2020

Background: Bloodstream infection (BSI) resulting from the ESKAPEEc pathogens is relevant to high mortality and economic cost. Data concerning the impact of BSI due to ESKAPEEc in pediatric population was virtually scant. Our purpose was to summarize the epidemiology, risk factors and outcomes of ESKAPEEc BSI among hospitalized children.Methods: Inpatients diagnosed with BSI with definite etiology between January 2016 and December 2018 were enrolled retrospectively at the West China Second University Hospital. Data were systematically reviewed on patient’ clinical characteristics and laboratory findings to ascertain independent predictors, clinical features and outcomes.Results: Of the 228 patients with BSI, 174 (76.0%) were caused by ESKAPEEc (124 MDR-ESKAPEEc). Multivariate analysis demonstrated that premature and/ or low birth weight (odds ratio [OR] = 2.981, P=0.036), previous surgery and/or trauma (OR=5.71, P=0.029) and source of urinary tract infection (OR=10.6, P=0.004) were independently associated with ESKAPEEc BSI. The independent risk factor for MRD-ESKAPEEc BSI was nosocomial infection (OR=3.314, P=0.037). The overall mortality rate in patients with ESKAPEEc BSI was 14.0% (25/174), and no significant difference was ascertained in mortality between MRD-ESKAPEEc and non-MRD ESKAPEEc BSI groups (13.7% vs. 11.4%, P=0.692).In addition, previous surgery and/or trauma, thrombocytopenia, mechanical ventilation were significant risk factors for mortality caused by ESKAPEEc BSI. Conclusions: More than two-thirds of BSI among hospitalized children were caused by ESKAPEEc. Previous surgery and/or trauma, thrombocytopenia and mechanical ventilation increased the risk rate for mortality in ESKAPEEc BSI. The risk factors ascertained could assist physicians to early suspect ESKAPEEc and MDR ESKAPEEc.
Parasitism of Aedes Albopictus by Ascogregarina Taiwanensis Lowers Its Competitive Ability Against Aedes Triseriatus.
Authors: Stump Emma , Childs Lauren M , Walker Melody
Published: August 2020

Background: Mosquitoes are carriers for many diseases that significantly impact the human population such as dengue, malaria and La Crosse virus. When multiple mosquito species are present, the competition between species may alter disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus, both inhabit areas where La Crosse Encephalitis Virus is found. Infection of Aedes albopictus by the parasite Ascogregarina taiwanensis can decrease the mosquito’s fitness and impact its initial competitive advantage over Aedes triseriatus. The decrease in fitness occurs through the impact of Ascogregarina taiwanensis on female fecundity, larval development rate, and larval mortality. Methods: In this paper, we examine the effects of parasitism of Ascogregarina taiwanensis on Aedes albopictus and Aedes triseriatus population dynamics and competition. We build a compartmental model using parameters based on published literature, simulate the dynamics of the system, and analyze the effect of parasitism on competition between the mosquito species. Results: We show that increased levels of parasitism in Aedes albopictus will decrease the initial competitive advantage of the species over Aedes triseriatus and increase the survivorship of Aedes triseriatus. An understanding of how population dynamics are affected by this parasite can inform future mosquito control and mosquito-borne disease mitigation efforts. Conclusions: Mosquito population dynamics are affected by many factors, including abiotic factors (e.g. temperature and humidity) and competition between mosquito species. This is especially true when multiple mosquito species are vying to live in the same area. An understanding of mosquito population dynamics is vital to preventing spread of these diseases.
High Expression Level of Serpin Peptidase Inhibitor Clade E Member 2 is Associated with Poor Prognosis in Lung Adenocarcinoma
Authors: Dokuni Ryota , Nagano Tatsuya , Jimbo Naoe , Sato Hiroki , Kiriu Tatsunori , Yasuda Yuichiro , Yamamoto Masatsugu , Tachihara Motoko , Kobayashi Kazuyuki , Maniwa Yoshimasa , Nishimura Yoshihiro
Published: August 2020

Background: Recent studies have revealed that serpin peptidase inhibitor clade E member 2 (SERPINE2) is associated with tumorigenesis. However, SERPINE2 expression and its role in non-small cell lung cancer are still unknown.Methods: The expression levels of SERPINE2 in 74 consecutively resected lung adenocarcinomas were analyzed by using immunostaining. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by quantitative PCR. Proliferation assays and cell apoptosis assays were performed to clarify the cell-autonomous function of SERPINE2 in A549 and PC9 lung cancer cells.Results: The overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P=0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P=0.03237). The interference of SERPINE2 decreased proliferation and increased apoptosis in A549 and PC9 cellsConclusion: These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma.
Fiscal Regime and Tax Policy in Resource-Rich Countries In The Process Of Globalization: Literature Review
Authors: Eddassi Hassane
Published: August 2020

The sudden collapse of oil prices combined with the COVID 19 pandemic is considered to be the worst economic crisis in the history of Resource-Rich Countries. These two events put immense pressure on the economic performance of these countries even with the huge reserves and volume of exports they enjoyed during the past. This raises the question of what are the particularities of these countries that made them very vulnerable to such shocks. This paper is a gathering of multiple studies and reports dealing with the specific topic of Resource-Rich Countries. More precisely, I try to analyze, based on a literature review, the nature of the Fiscal Regime applied in these nations and what makes it different than other countries. In addition, I investigate the Tax Regime applied in Resource-Rich Countries, with an emphasis on observed strengths or weaknesses. I conclude that the Fiscal Regime in Resource-Rich Countries is generally different in many aspects: these countries are subject to severe price volatility, shocks easily affect the economy, and the nature of the Extractive Industry (EI) is very different and needs adequate policy. I also highlight that the Tax System in Resource-Rich Countries is different as well: low investment in human resources and IT and low reliance on tax revenues. This study provides many recommendations to policymakers and authorities in Resource-Rich Countries. The most important is the necessity to implement a Counter-Cyclical Fiscal Policy. Such a measure can enhance savings during periods of high prices while allowing the government to spend more during periods of crisis. In addition, the paper recommends investing more in the tax administration and enhancing the volume of tax revenues as this can allow more diversification. Many other recommendations are presented to help absorb the shocks caused by a severe drop in commodity prices. This paper is a good reference for experts or researchers in the fields of Fiscal Regimes, Tax Policy, and Resource Riche Countries. It is also useful for any research in the domain of the Extractive Industries as it analyzes many of the aspects related to that industry.

Keywords: resource-rich countries, fiscal policy, tax policy, countercyclical fiscal policy, mining.
Plasma Non-cholesterol Sterols as Markers of Cholesterol Synthesis and Intestinal Absorption: A Critical Review
Authors: Quintão Eder Carlos Rocha
Published: August 2020

Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis
have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias
and in population-based investigations to evaluate the risk for cardiovascular disease, respectively. The
method aims at replacing initial research procedures such as the use of stable isotopes associated with fecal steroid
balance, which are limited by the high cost and tedious procedures. However, we show in this review that
numerous results obtained with serum sterol measurements are contradictory. In this regard, the following points
are discussed: 1) how phytosterols relate to atherosclerosis considering that defects in biliary output or in the
transport of phytosterols from the intestinal mucosa back into the intestinal lumen provide increased content of
phytosterols and other sterols in plasma and tissues, thus not allowing to conclude that their presence in arteries
and atheromas represents the etiology of atherosclerosis; 2) serum non-cholesterol sterols as markers of cholesterol
synthesis and absorption, such as cholestanol, present discrepant results, rendering them often inadequate to
identify cases of coronary artery disease as well as alterations in the whole body cholesterol metabolism; 3) such
methods of measurement of cholesterol metabolism are confounded by factors like diabetes mellitus, body weight
and other pathologies including considerable hereditary hyperlipidemias biological variabilities that influence the
efficiency of synthesis and intestinal absorption of cholesterol.
The Quinazoline-Chalcone and Quinazolinone-Chalcone Hybrids: A Promising Combination for Biological Activity
Authors: Mass Eduardo Bustos , Duarte Gilmar Vieira , Russowsky Dennis
Published: August 2020

Quinazoline and/or chalcones derivatives are important targets in several areas of chemical
sciences, mainly, in the medicinal chemistry and pharmaceutical research. The purpose of this review
was to systematize the information available in the literature, including patents, regarding the benefits,
exerted by the combination of these two pharmacophores into single molecules. These hybrid compounds
can exhibit different biological activities, causing a synergistic or a new effect, compared to the
individuals. The variability of biological activities includes anticancer, anti-Alzheimer, antiviral and
antimicrobial activities, among others. Additionally, synthetic methodologies to prepare the different
molecular architectures were discussed based on their similarities. The increasing number of publications
indicates the importance of molecular hybridization in the field of drug discovery.