bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Non-Rigid Registration for Scanning Transmission Electron Microscopy Image Series
Authors: Zhang Chenyu , Feng Jie , Yankovich Andrew B , Kvit Alexander , Berkels Benjamin , Voyles Paul
Published: May 2020

Achieving sub-picometer precision measurements of atomic column positions in high-resolution scanning transmission electron microscope images using non-rigid registration (NRR) and averaging of image series requires careful optimization of experimental conditions and the parameters of the registration algorithm. On experimental data from SrTiO3 [100], sub-pm precision requires alignment of the sample to the zone axis to within 1 mrad tilt and sample drift of less than 1 nm/min. At fixed total electron dose for the series, precision in the fast scan direction improves with shorter pixel dwell time to the limit of our microscope hardware, but the best precision along the slow scan direction occurs at 6 µs/px dwell time. Within the NRR algorithm, the “smoothness factor” that penalizes large estimated shifts is the most important parameter for sub-pm precision, but in general the precision of NRR images is robust over a wide range of parameters.
Network pharmacology-based identification of potential targets of Triterpenoids from Liquidambaris Fructus on the treatment of Rheumatoid Arthritis
Authors: Li Wenxuan , Qian Ping , Gu Li , Zhang Dongfang
Published: May 2020

Background

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and its exact etiology and pathogenesis are still unclear by now, therefore it is urgent to develop new therapeutic targets for RA treatment. Liquidambaris Fructus (LF) is used for joint pain, numbness and edema, and triterpenoids, the main effective compounds of LF, have a clear anti-inflammatory effect. The aim of this study was to clarify the mechanism of triterpenoids from LF on the treatment of RA.
Methods

A comprehensive network pharmacology strategy that consists of three sequential modules (pharmacophore matching, enrichment analysis and molecular docking) was carried out.
Results

We collected 21 triterpenoids from LF and predicted 61 targets strongly correlated with 15 biological processes and 8 related pathways. SYK and MAPK14 were key targets related to triterpenoids from LF and RA. LCK and GSK3B were potential targets and two effective triterpenoids from LF played a crucial role in the process of RA by targeting LCK and GSK3B.
Conclusions

The comprehensive strategy can serve as a universal method to illuminate the mechanism of triterpenoids from LF acting on treatment of RA by identifying the targets and pathways, and provided new ideas for RA treatment and evidence for clinical research and application of LF.
Salmonella Phage cocktail, its effects and benefits on the gut of chickens in a commercial farm.
Authors: Clavijo Viviana , Morales Laura Tatiana , Flores Martha Josefina Vives , Reyes Alejandro
Published: May 2020

BackgroundThe microbiota of broiler chicken gut affects positively or negatively the health, metabolism and immunity of chickens thus it has a significant impact on the animal productivity. Phages, host-specific parasites of bacterial cells, are a promising antimicrobial alternative that selectively target pathogens without disturbing the microbiota. The aim of the study is further characterizing the behaviour of phages and its effect on the commensal microbial community.MethodsWe used 16S rRNA gene amplicon sequencing to evaluate the effect of SalmoFree® (a phage cocktail against Salmonella) on the microbiota of the cecum of broilers reared in a commercial farming system. Two field trials were carried out including 2 control and 2 experimental houses. Phages were incorporated in the broilers’ drinking water using three doses at the grower stage. The core microbiome, differentially abundant taxa between treatments as well as taxa associated with age were identified using Qiime2 and the R-Project for statistics.ResultsAnalyses of similarities among communities over time allowed us to identify two stages of microbiota development at the last stage of the production cycle. The core microbiome identified some key species in the adaptation of the microbiota at the last stage of the cycle. Among these there are important degraders of complex polysaccharides and producers of short chain fatty acids such as Eisenbergiella and Lachnoclostridium. Additionally, the phage cocktail did not affect the normal development of the microbiota structure while its application contributes to reduce the presence of pathogenic Enterobacteria including Salmonella. The addition of the phage cocktail led to a significant reduction in the abundance of Campylobacter and Helicobacter and increase in Butyricimonas and Rikenellaceae abundance which are common inhabitants of the chicken gut with known negative and positive effects in the health, respectively.ConclusionsOur results suggest that phages can contribute to improve the chicken health and reduce pathogens burden at the end of the production cycle of broilers. Furthermore, it presents for the first time a detailed look of the microbiota composition and changes in broilers in a commercial scenario, information that will valuable towards the implementation of phage therapy technologies in the field.
Autonomous replication sequences from the Amaranthus palmeri eccDNA replicon enable replication in yeast
Authors: Molin William T. , Yaguchi Allison , Blenner Mark , Saski Christopher
Published: May 2020

Objective
The objective of the research presented here was to determine whether autonomous replication sequences (ARS) discovered in the eccDNA replicon of glyphosate resistant Amaranthus palmeri enable self-replication in a yeast system.
Results
Sequence analysis of the eccDNA replicon revealed a region of sharp changes in A + T/G + C content with characteristic bending indicative of an autonomous replication sequence. Further sequence analysis revealed an extended autonomous replication sequence (EACS) in close proximity to multiple DNA unwinding element (DUE) sequences. This region of the eccDNA replicon enabled autonomous replication of an ARS-less yeast plasmid.
Application of refrigerated and frozen sorghum malt slurries in preservation of starter cultures of traditional fermented cereal-based beverages - a case of Obushera from Uganda
Authors: Mukisa Ivan Muzira , Serwanga Arnold , Byakika Stellah
Published: May 2020

Objective
Industrial production of traditional fermented beverages in developing countries is limited by lack of commercial starter cultures. Saccharomyces (S.) cerevisiae MNC 21Y and Lactobacillus (L.) plantarum MNC 21 were identified as starter cultures for a Ugandan cereal beverage, Obushera. However, they are commercially unavailable due to lack of affordable appropriate propagating and preservation methods. In this study the starters were propagated in sorghum malt slurries (30 °C for 24 h) and stored at 5 °C and − 18 °C for 90 days. Viability and fermentation ability of the cultures was monitored.
Results
Viability was higher for starters stored at 5 °C (S. cerevisiae: 6 log cfu/g and L. plantarum: 7–9 log cfu/g during 90 days) than those at -18 °C (S. cerevisiae: 2 cfu/g and L. plantarum: 4 log cfu/g after 30 days). Refrigerated starters acidified Obushera (pH ≤ 4.5) faster (10–20 h) than frozen ones (18–24 h). Refrigerating the starters in sorghum malt slurries preserves them for at least three months. This provides an affordable option for starter commercialization and industrial production of traditional fermented foods.
Predictors of long-term post-thrombotic syndrome following high proximal deep vein thrombosis: a cross-sectional study
Authors: Engeseth Marit , Enden Tone , Sandset Per Morten , Wik Hilde Skuterud
Published: May 2020

Background Post-thrombotic syndrome (PTS) is a frequent chronic complication of proximal deep vein thrombosis (DVT) of the lower limb, but predictors of PTS are not well established. We aimed to examine predictors of PTS in patients with long-term PTS following proximal DVT. Methods During 2006-09, 209 patients with a first time acute upper femoral or iliofemoral DVT were randomized to receive either additional catheter-directed thrombolysis or conventional therapy alone. In 2017, the 170 still-living participants were invited to participate in a cross-sectional follow-up study. In the absence of a gold standard diagnostic test, PTS was defined in line with clinical practice by four mandatory, predefined clinical criteria: 1. An objectively verified DVT; 2. Chronic complaints (>1 month) in the DVT leg; 3. Complaints appeared after the DVT; and 4. An alternative diagnosis was unlikely. Possible predictors of PTS were identified with multivariate logistic regression. Results 88 patients (52%) were included 8-10 years following the index DVT, and 44 patients (50%) were diagnosed with PTS by the predefined clinical criteria. Younger age and higher baseline Villalta score were found to be independent predictors of PTS, i.e., OR 0.96 (95% CI, 0.93-0.99), and 1.23 (95% CI, 1.02-1.49), respectively. Lack of iliofemoral patency at six months follow-up was significant in the bivariate analysis, but did not prove to be significant after the multivariate adjustments.Conclusions In long-term follow up after high proximal DVT, younger age and higher Villalta score at DVT diagnosis were independent predictors of PTS.
Experimental study on proportioning and properties of cemented filling material with a large mass ratio of construction demolition waste
Authors: Bi Yewu , Chen Weixin , Huang Yucheng
Published: May 2020

Supply of cheap and abundant raw materials is a key factor in reducing the cost of cemented filling materials. To solve this problems of the high cost of cemented filling materials and insufficient sources of raw materials, an experimental study on cemented filling material with a large mass ratio of construction demolition waste was performed. A large amount of recycled aggregate of construction demolition waste was added to cemented material to prepare a high concentration slurry, from which the influences of aggregate/cement mass ratio, admixture/cement mass ratio, water/solid mass ratio, recycled aggregate gradation and mud content of recycled aggregate on slump, setting time and compressive strength of cemented filling material with a large mass ratio of construction demolition waste were analysed via the orthogonal test method and regression equation analysis. Finally, an industrial formula for cemented filling material with a large mass ratio of construction demolition waste was determined, and the mechanical and microscopic properties were analysed. The results indicate that the industrial formula with an aggregate/cement mass ratio of 3.0, an admixture/cement mass ratio of 1.5%, a water/solid mass ratio of 0.35, a recycled aggregate gradation of 40:30:15:15, a mud content of recycled aggregate of 0ཞ4% and a mass ratio of construction demolition waste to solid material of 75% exhibits the properties of rapid strength growth and high residual strength, and can be applied in underground coal mines conditions.
KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimickers
Authors: Jiang Lucen , Liu Jianghuan , Wei Qingzhu , Wang Yiyang
Published: May 2020

Background Karyopherin α 2 (KPNA2), a member of the Karyopherin α family, has been observed in several cancers but lack substantial investigation in malignant bone tumors. The purpose of the current study was to evaluate KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and their malignant bone tumor mimickers, such as chondrosarcomas and Ewing sarcomas.Method We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin embedded surgical specimens from 217 patients with malignant and benign tumors of bone, including 81 osteosarcomas, 42 chondrosarcomas, 9 Ewing sarcomas, 28 osteoid osteoma, 20 osteochondroma and 37 Chondroblastoma. Immunoreactivity was scored semi quantitatively based on stain extent and intensity.Results Seventy one of 81 (87.7%) osteosarcomas, zero of 42 (0%) chondrosarcomas and one of 9 (11.1%) Ewing sarcomas showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all of benign bone tumors. Much more positive expression of KPNA2 was found in osteosarcomas as compared with chondrosarcomas and Ewing sarcomas. The sensitivity and specificity of KPNA2 immuno-expression for osteosarcoma was 87.7% and 100%, respectively. In several subtypes of osteosarcomas, immunohistochemical expression of KNA2 was more frequent in osteoblastic (94.5%), with 39 (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in eleven of 13 (84.6%) chondroblastic, three of 6 (50%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma. Stronger-intensity staining was observed in osteoblastic osteosarcoma.Conclusion KPNA2 is most frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and Ewing sarcomas. This feature may have diagnostic value since it is very useful for distinguishing between osteosarcomas and other bone sarcomas mimickers. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.
Defective phagocytic function of induced microglia-like cells is correlated with rapid progression of sporadic ALS
Authors: Noh Min-Young , Kwon Min-Soo , Oh Ki-WooK , Nahm Minyeop , Park Jinseok , Kim Young-Eun , Ki Chang-Seok , Jin Hee Kyung , Bae Jae-sung , Kim Seung Hyun
Published: May 2020

Background: Microglia play a key role in determining the progression of amyotrophic lateral sclerosis (ALS), yet their precise role in ALS has not been identified in humans. The objective of this study was to identify the functional characteristics of microglia and related factors in patients with sporadic ALS that is rapidly progressing.Methods: After confirming that microglia-like cells (iMGs) induced by human monocytes could recapitulate the main signatures of brain microglia, serial comparative studies were conducted to delineate functional differences in iMGs from patients with slowly progressive ALS [ALS(S), n = 14] versus rapidly progressive ALS [ALS(R), n = 15].Results: Despite an absence of significant differences in the expression of microglial homeostatic genes, ALS(R)-iMGs preferentially showed defective phagocytosis and an exaggerated pro-inflammatory response to LPS stimuli compared to ALS(S)-iMGs. Transcriptome analysis revealed that the perturbed phagocytosis seen in ALS(R)-iMGs was closely associated with decreased NCKAP1 (NCK-associated protein 1)-mediated abnormal actin polymerization. NCKAP1 overexpression was sufficient to rescue impaired phagocytosis in ALS(R)-iMGs. To leverage our findings and identify biological markers of rapidly progressing ALS, we measured plasma miRNA-214-3p (negative regulator targeting NCKAP1) levels. Post-hoc analysis indicated that decreased NCKAP1 expression in iMGs and a concomitant increase in plasma miRNA-214-3p levels was correlated with rapid progression of ALS.Interpretation: Our data suggest that microglial NCKAP1 may be an alternative therapeutic target in rapidly progressive sporadic ALS. In addition, miRNA-214-3p levels could be a serological biomarker for predicting the speed of disease progression.
Data-driven remanufacturing assembly intelligent control system for improving resource and production efficiency
Authors: Liu Conghu , Cai Wei , Zhu Guang , Gao Mengdi
Published: May 2020

Remanufacturing has been considered to be one of the most effective ways to deal with sustainable manufacturing. This paper proposes a data-driven intelligent control system for improving the production and resource efficiency of the remanufacturing assembly systems. First, an optimization model of the reassembly scheme is established for minimizing the quality loss and comprehensive cost. Remanufactured parts are measured, grouped, coded, and dimensional chain calculated based on the data acquisition and processing technology. Then, an intelligent control method for remanufacturing assembly process is proposed, which is a real-time monitoring and dynamic compensation response to abnormal quality to achieve intelligent control of reassembly process. The intelligent control information system that include information perception and fusion technology, real-time monitoring and dynamic compensation architecture are studied and implemented through data-driven technologies. Finally, a case study illustrates its practicability offering a technical support for sustainability of remanufacturing.
Applying the health belief model to identify predictors of self-perceived risk of HIV infection among undergraduates in mainland China
Authors: Ruan Fang , Fu Guochen , Zhou Mingyu , Li Xin , Chen Yuhua , Li Yilin , Lu Can , Ke Shuhui , Pan Mengge , Li Yajie , Zhang Yu , Shi Bin , Gong Qinxin , Fu Zihan , Shi Ting , Liu Yusi , Liu Fuqiang , Zhan Jihong , wang Junfang
Published: May 2020

Objective This cross-sectional study aimed to identify predictors of self- perceived risk of HIV infection among undergraduates in mainland China, based on the health belief model.Methods A self-administered questionnaire survey method was used to collect information from 10665 eligible undergraduates across the whole country (except for Tibet). Multivariate Logistic regression analysis was chosen to explore the predictors of self-perceived risk of HIV infection.Results Approximately half (48.2%) of the undergraduates perceived themselves to be at risk of contracting HIV, yet only 8.9% reported to engage in risky sexual behaviors. After controlling for potential confounders, males [adjusted odd ratio (AOR)=0.72, 95% confidence interval (CI)=0.66-0.77], those residing in urban areas (AOR=0.86, 95% CI= 0.79-0.93), having higher levels of condom use self-efficacy (AOR=0.64, 95% CI=0.58-0.69) and knowing the national AIDS policy (AOR=0.68, 95% CI=0.62-0.74) were less likely to perceive themselves to be at risk of acquiring HIV. Conversely, freshmen (AOR=1.27, 95% CI=1.16-1.38), non-heterosexuals (AOR=1.57, 95% CI=1.39-1.77), and those who had expressed less stigma towards people living with HIV (PLHIV) (AOR=1.25, 95% CI=1.15-1.35) and had the intention of utilizing voluntary counseling and testing (VCT) services (AOR=1.29, 95% CI=1.16-1.43) perceived themselves to be at increased risk for HIV infection.Conclusions Undergraduates tended to overestimate their own risk of acquiring HIV infection. In order to help undergraduates accurately assess their risk of being infected with HIV and effectively avoid risk, a comprehensive intervention measure should be taken to target females, non-heterosexuals, freshmen and those residing in rural areas, raise their awareness of the national AIDS policy, relieve their stigma against PLHIV, improve their condom use self-efficacy and provide VCT services in college campus.
Reduced child maltreatment prevention service case openings during COVID-19
Authors: Whaling Kelly , Sarkissian Alissa Der , Larez Natalie A. , Sharkey Jill D. , Allen Michael A. , Nylund-Gibson Karen
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19), is a novel virus that has swept the world causing illness and death. Youth are at a heightened risk of experiencing increased rates of abuse given necessary measures required to slow the spread of the virus (e.g., indefinite school closures). We analyzed data from New York City’s Administration for Children’s Services (ACS) to investigate the frequency of child maltreatment prevention service case openings during this time of unprecedented stress. Two descriptive investigations were conducted. An examination of trend lines demonstrated that for 2013-2019, New York City’s new prevention case openings have consistently peaked in the month of March, for all seven years. New prevention case service openings in March 2020 do not peak, as they do in the preceding seven years. An independent samples t-test indicated that the frequency of case openings of March 2020 is significantly different than the frequency of case openings in March 2013-2019. Further, a Poisson regression model estimated that the odds of opening a new child maltreatment prevention case post-COVID-19 are 179% lower than opening a new child maltreatment case pre-COVID-19 (OR = -0.79, p < .001). These findings highlight the necessity of future research and innovation regarding child maltreatment prevention and intervention services during a global pandemic. This study has important implications for identification, prevention, and documentation for current support, and recommendations for local governments, community members, and practitioners are provided.
COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
Authors: Malone Robert W. , Tisdall Philip , Fremont-Smith Philip , Liu Yongfeng , Huang Xi-Ping , White Kris M. , Miorin Lisa , Olmo Elena Moreno Del , Alon Assaf , Delaforge Elise , Hennecker Christopher D. , Wang Guanyu , Pottel Joshua , Bona Robert , Smith Nora , Hall Julie M. , Shapiro Gideon , Clark Howard , Mittermaier Anthony , Kruse Andrew C. , García-Sastre Adolfo , Roth Bryan L. , Glasspool-Malone Jill , Francone Victor , Hertzog Norbert , Fremont-Smith Maurice , Ricke Darrell O.
Published: May 2020

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.
Fuzzy AHP-TOPSIS multi-criteria decision analysis applied to the Indus Reservoir system in Pakistan
Authors: Janjua Shahmir , Hassan Ishtiaq
Published: May 2020

The ranking of the reservoirs in Pakistan is an important decision and it has a vital impact on the sustainability of the region and the economic operation of the reservoir. The reservoirs ranking is a vital problem which involves multi-criteria decision-making. The framework proposed in this paper involves the fuzzy AHP-TOPSIS method for the ranking of reservoirs in Pakistan. Potential feasible locations are identified from the Water and Power Development Authority, Pakistan. Weight calculation for the criteria is done by the fuzzy AHP method, which is a multi-criteria decision-making method. In order to model the fuzziness, equivocacy, incomplete knowledge and ambiguity, the fuzzy AHP is used. Furthermore, in order to rank the selected reservoirs based on their performance, the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) is applied, which is a multicriteria decision making method. We demonstrate the application of the above-mentioned methods to the case study of the Indus Reservoir system in Pakistan. A decision support tool is provided for the decision makers in this paper to manage, evaluate and rank the planned reservoirs in the Indus River.
Injectable Drug-Loaded Nanocarriers for Lung Cancer Treatments
Authors: Yu Huang-Ping , Aljuffali Ibrahim A. , Fang Jia-You
Published: May 2020

Different types of injectable nanoparticles, including metallic nanoparticles, polymeric nanocarriers,
dendrimers, liposomes, niosomes, and lipid nanoparticles, have been employed to load drugs for lung delivery.
Nanoparticles used for lung delivery offer some benefits over conventional formulations, including increased
solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tumor
targeting, and minimal side effects. In recent years, the concept of using injectable nanocarriers as vehicles for
drug delivery has attracted increasing attention. This review highlights recent developments using nanomedical
approaches for drug targeting to the lungs. We systematically introduce the concepts and amelioration mechanisms
of the nanomedical techniques for lung cancer therapy. Passive targeting by modulating the nanoparticulate
structure and the physicochemical properties is an option for efficient drug delivery to the lungs. In addition,
active targeting such as antibody or peptide conjugation to nanoparticles is another efficient way to deliver the
drugs to the targeted site. This review describes various nanocarriers loaded with anticancer drugs for passive or
active targeting of lung malignancy. In this review, we principally focus on the nanomedical application in animal
studies. The article excludes investigations limited to cell-based experiments. The review ends by anticipating
future developments and trends.
Liposomes for Pulmonary Drug Delivery: The Role of Formulation and Inhalation Device Design
Authors: Elhissi Abdelbary
Published: May 2020

Liposomes are established drug carriers for inhalation owing to their safety and ability to provide controlled
drug release in the lung. These carriers can entrap a wide range of therapeutic molecules for delivery in
large volumes to the peripheral airways using medical nebulizers. Pressurized metered inhalers (pMDIs), soft mist
inhalers (SMIs) and dry powder inhalers (DPIs) can deliver relatively small quantities of medication to the lung
when compared to medical nebulizers which can deliver large volumes using simple liposome preparation techniques.
Unfortunately, the shearing provided during nebulization to convert the aqueous liposome dispersions into
“respirable” aerosol droplets may exert physical stress on liposome bilayers, causing losses of the originally entrapped
drug. The development of successful liposome carriers for inhalation depends on two main factors which
are formulation composition and nebulizer design, with the aim of reducing the detrimental effect of shearing on
liposome stability and maximizing the deposition of vesicles in the ‘deep lung’. A number of nebulizable
liposome formulations have reached clinical trials. For example, Arikace® (liposomal amikacin) and Pulmaquin®
(liposomal ciprofloxacin) are antibacterial formulations currently in advanced stages of development. In this
review, the role of liposome formulation and inhalation device design on the suitability of liposomes for eliciting
controlled drug release in the lung was evaluated. Moreover, the factors contributing to the success of Arikace® in
clinical trials were appraised.
Human Health Effects of Lactose Consumption as a Food and Drug Ingredient
Authors: Seoane Rafael G. , Garcia-Recio Verónica , Garrosa Manuel , Rojo María Á. , Jiménez Pilar , Girbés Tomás , Cordoba-Diaz Manuel , Cordoba-Diaz Damián
Published: May 2020

:

Lactose is a reducing sugar consisting of galactose and glucose, linked by a β (1→4) glycosidic bond,
considered as an antioxidant due to its α-hydroxycarbonyl group. Lactose is widely ingested through the milk and
other unfermented dairy products and is considered to be one of the primary foods. On the other hand, lactose is
also considered as one of the most widely used excipients for the development of pharmaceutical formulations. In
this sense, lactose has been related to numerous drug-excipient or drug-food pharmacokinetic interactions.

:

Intolerance, maldigestion and malabsorption of carbohydrates are common disorders in clinical practice, with
lactose-intolerance being the most frequently diagnosed, afflicting 10% of the world’s population. Four clinical
subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital
lactase deficiency, adult-type hypolactasia and secondary lactase intolerance. An overview of the main uses of
lactose in human nutrition and in the pharmaceutical industry and the problems derived from this circumstance
are described in this review.
Effect of Proton-Pump Inhibitors on Glucose and Insulin Metabolism on Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Sánchez-García Adriana , Simental-Mendía Mario , Simental-Mendía Luis E.
Published: May 2020

Background:

Some studies have revealed an improvement in glucose metabolism after proton-pump
inhibitors (PPI) therapy; however, this evidence is inconclusive and limited.

Objective:

The study aimed to examine the effect of PPI on glucose and insulin metabolism in patients with type
2 diabetes through a systematic review and meta-analysis.

Methods:

Only randomized controlled trials evaluating the impact of PPI on glucose or insulin concentrations in
type 2 diabetes were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A
meta-analysis was conducted using a random-effects model and generic inverse variance method. Sensitivity
analysis was performed using the leave-one-out method.

Results:

Meta-analysis revealed no significant effect of PPI intervention on fasting glucose (mean difference
[MD] -11.42 [95% CI, -29.68 to 6.83], I2 = 80%, p = 0.22), fasting insulin (MD 1.51 [95% CI, -0.36 to 3.37], I2 =
32%, p = 0.11), HOMA-IR (MD -0.16 [-0.98 to 0.65], I2 = 0%, p = 0.70), HOMA-β (MD 19.97 [-21.59 to 61.52],
I2 = 71%, p = 0.35), and HbA1c concentrations (MD -0.34 [-0.99 to 0.31], I2 = 89%, p = 0.30).

Conclusion:

The treatment with PPI, in the short term, had no significant effects on glucose and insulin metabolism
in patients with type 2 diabetes.
Oral Health-Related Quality of Life during Pregnancy: A Systematic Review
Authors: Fakheran Omid , Saied-Moallemi Zahra , Khademi Abbasali , Sahebkar Amirhossein
Published: May 2020

Objective:

High prevalence of Dental and periodontal problems during the gestation period may have a
negative effect on oral health-related quality of life (OHRQoL) in pregnant women. This systematic review aimed
to perform a quality assessment and provide a critical overview of the current research available on OHRQoL in
pregnant women.

Methods:

For this systemic review, all original and peer-reviewed human studies, which investigated OHRQoL
of women during pregnancy or post- partum period, were searched. Studies were screened in title and abstract for
the relevance by two independent investigators. Methodological quality was assessed using modified items recommended
by the Newcastle–Ottawa Scale for observational studies.

Results:

All of the eight included studies had a cross-sectional design. Meta-analysis was not possible due to the
heterogeneity of key aspects among the included studies. Thus, the data from the studies were evaluated qualitatively.
The overall risk of bias of the included studies was low.

Conclusion:

The main conclusion of this review is that the presence of signs and symptoms of dental and gingival
disease negatively affects the self-perception of OHRQoL in pregnant women. The most affected domains of
OHRQoL in pregnant women were related to mental and psychological discomfort, followed by physical and
functional problems.
AMPK and its Activator Berberine in the Treatment of Neurodegenerative Diseases
Authors: Qin Siru , Tang Huiling , Li Wei , Gong Yinan , Li Shanshan , Huang Jin , Fang Yuxin , Yuan Wenjuan , Liu Yangyang , Wang Shenjun , Guo Yongming , Guo Yi , Xu Zhifang
Published: May 2020

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.
A Review on the Progress and Prospects of Dengue Drug Discovery Targeting NS5 RNA- Dependent RNA Polymerase
Authors: Maddipati Venkatanarayana C. , Mittal Lovika , Mantipally Manohar , Asthana Shailendra , Bhattacharyya Sankar , Gundla Rambabu
Published: May 2020

Dengue virus (DENV) infection threatens the health and wellbeing of almost 100 million people in the
world. Vectored by mosquitoes, DENV may cause a severe disease in human hosts called Dengue hemorrhagic
fever (DHF)/Dengue shock syndrome (DSS), which is not preventable by any known drug. In the absence of a
universally-accepted vaccine, a drug capable of inhibiting DENV multiplication is an urgent and unmet clinical
need. Here we summarize inhibitory strategies by targeting either host biochemical pathways or virus-encoded
proteins. A variety of approaches have been generated to design Directly-acting anti-virals or DAAs targeting
different DENV proteins, with diverse success. Among them, DAAs targeting genome replicating viral enzymes
have proven effective against many viruses including, Human Immuno-deficiency Virus and Hepatitis C Virus.
DAAs may be derived either from existing compound libraries of novel molecules and plant secondary metabolites
or devised through Computer-aided Drug design (CADD) methods. Here, we focus on compounds with
reported DAA-activity against the DENV RNA-dependent RNA polymerase (RdRp), which replicate the viral
RNA genome. The structure-activity relationship (SAR) and toxicity of the natural compounds, including secondary
plant metabolites, have been discussed in detail. We have also tabulated novel compounds with known
anti-RdRp activity. We concluded with a list of DAAs for which a co-crystal structure with RdRp is reported.
Promising hit compounds are often discarded due to poor selectivity or unsuitable pharmacokinetics. We hope
this review will provide a useful reference for further studies on the development of an anti-DENV drug.
Modulation of the Drug Resistance by Platonia insignis Mart. Extract, Ethyl Acetate Fraction and Morelloflavone/Volkensiflavone (Biflavonoids) in Staphylococcus aureus Strains Overexpressing Efflux Pump Genes
Authors: e Silva Andressa K.F. , dos Reis Antonielly C. , Pinheiro Emanuelly E.A. , de Sousa Jonas N. , de Alcântara Oliveira Felipe A. , Moura Arkellau K.S. , de Sousa L. Neto José , das Graças L. Citó Antonia M. , Siqueira-Júnior José P. , Kaatz Glenn W. , Barreto Humberto M.
Published: May 2020

Background:

Microbial resistance to antibiotics is a global public health problem, which requires urgent
attention. Platonia insignis is a native species from the eastern Brazilian Amazon, used in the treatment of burns and
wounds.

Objectives:

To evaluate the antimicrobial activity of the hydroalcoholic extract of P. insignis (PIHA), the ethyl acetate
fraction (PIAE), and its subfraction containing a mixture of biflavonoids (BF). Moreover, the effect of these
natural products on the antibiotic activity against S. aureus strains overexpressing efflux pump genes was also evaluated.

Methods:

Minimal inhibitory concentrations were determined against different species of microorganisms. To evaluate
the modulatory effect on the Norfloxacin-resistance, the MIC of this antibiotic was determined in the absence and
presence of the natural products at subinhibitory concentrations. Inhibition of the EtBr efflux assays were conducted
in the absence or presence of natural products.

Results:

PIHA showed a microbicidal effect against S. aureus and C. albicans, while PIAE was bacteriostatic for S.
aureus. PIAE and BF at subinhibitory concentrations were able to reduce the MIC of Norfloxacin acting as modulating
agents. BF was able to inhibit the efflux of EtBr efflux in S. aureus strains overexpressing specific efflux pump
genes.

Conclusion:

P. inignisis, a source of efflux pump inhibitors, including volkensiflavone and morelloflavone, which
were able to potentiate the Norfloxacin activity by NorA inhibition, being also able to inhibit QacA/B, TetK and
MsrA. Volkensiflavone and morelloflavone could be used as an adjuvant in the antibiotic therapy of multidrug resistant
S. aureus strains overexpressing efflux pumps.
Nano Phytomedicine Based Delivery System for CNS Disease
Authors: Jahangir Mohammed Asadullah , Anand Chettupalli , Muheem Abdul , Gilani Sadaf Jamal , Taleuzzaman Mohamad , Zafar Ameeduzzafar , Jafar Mohammed , Verma Surajpal , Barkat Md. Abul
Published: May 2020

Herbal medicines are being used since ancient times and are an important part of the alternative and traditional
medicinal system. In recent decades, scientists are embracing herbal medicines based on the fact that a number
of drugs that are currently in use are derived directly or indirectly from plant sources. Moreover, herbal drugs have
lesser side effects, albeit are potentially strong therapeutic agents. The herbal medicine market is estimated to be
around US $62 billion globally. Herbal medicine has gained widespread acceptance due to its low toxicity, low cost,
ease of accessibility and efficacy in treating difficult diseases. Safety and efficacy are another important factors in the
commercialization process of herbal medicines. Nanotechnology has been shown to be potentially effective in improving
the bioactivity and bioavailability of herbal medicines. Development of nano-phytomedicines (or by reducing
the size of phytomedicine), attaching polymers with phytomedicines and modifying the surface properties of
herbal drugs, have increased the solubility, permeability and eventually the bioavailability of herbal formulations.
Novel formulations such as niosomes, liposomes, nanospheres, phytosomes etc., can be exploited in this area. This
article reviews herbal medicines, which have prominent activity in the Central Nervous System (CNS) disorders and
reported nano-phytomedicines based delivery systems.
Anti-vascular Endothelial Growth Factor Antibody Limits the Vascular Leakage and Decreases Subretinal Fibrosis in a Cynomolgus Monkey Choroidal Neovascularization Model
Authors: Inagaki Satoshi , Shimazawa Masamitsu , Hamaguchi Koji , Otsu Wataru , Araki Tomoaki , Sasaki Yuji , Numata Yosuke , Tsusaki Hideshi , Hara Hideaki
Published: May 2020

Objective:

This study was conducted to evaluate the effects of anti-vascular endothelial
growth factor (VEGF) antibody (bevacizumab) on vascular leakage and fibrosis in a monkey
choroidal neovascularization (CNV) model. The relationship between fibrotic tissue and subretinal
hyper-reflective material (SHRM), in optical coherence tomography (OCT) images, was also investigated.

Methods:

Experimental CNV was induced in male cynomolgus monkeys by laser photocoagulation.
Intravitreal injection of bevacizumab at 0.5 mg/eye/dosing was initiated 2 weeks before or after laser
irradiation and thereafter, conducted intermittently at 2- or 3-week intervals. Fluorescein fundus angiography
(FA) and OCT imaging were conducted weekly from 2 to 7 weeks after laser irradiation.
CNV leakage was evaluated by an established grading method using FA images. To assess the fibrosis
and scarring, Masson’s trichrome specimens of each CNV lesion were prepared, and morphometric
analysis was conducted using an image analysis software.

Results:

The effects of bevacizumab on vascular leakage were shown using an established evaluation
method. Morphometric analysis of Masson’s trichrome-stained (MT) specimens revealed that
collagen fiber synthesis was suppressed by bevacizumab pre-treatment (-29.2%) or post-treatment
(-19.2%). SHRM was detected in OCT images in a monkey CNV model, and a significant correlation
between the SHRM area in the OCT images and the collagen fiber area in the MT specimens
was noted.

Conclusion:

In the established cynomolgus monkey CNV model, bevacizumab prevented blood
leakage but could not completely suppress fibrosis. SHRM in the OCT images reflected retinal
fibrous tissue in a laser-induced CNV monkey model. This model might be useful for elucidating the
pathology and development therapy for neovascularization or fibrosis.
Investigating the Link between Psoriasis and Cardiovascular Disease: Current Evidence, Therapeutic Implications and Perspectives
Authors: Kapniari Eirini , Papadimitriou Prokopios , Dalamaga Marianna , Makavos George , Piaserico Stefano , Egeberg Alexander , Ikonomidis Ignatios , Papadavid Evangelia
Published: May 2020

Psoriasis; a chronic inflammatory disease is characterized by symmetric hyperkeratotic
plaques affecting any part of the body. Psoriasis is nowadays considered as a systemic inflammation
linked with several comorbidities as metabolic syndrome, depression, anxiety and increased prevalence
of cardiovascular (CV) disease. The hypothesis that psoriasis is an independent CV risk factor leading to
atherosclerosis via inflammation is now widely accepted. Deciphering the underlying mechanisms interconnecting
psoriasis and CV disease may have significant implications in treatment decisions. Accumulating
evidence suggests that systematic therapies and recently introduced biologic agents, that control
psoriasis by suppressing the chronic and systemic inflammation, may alter the progression of CV disease.
We herein attempt a review of current evidence analysing the relationship between psoriasis and
CV comorbidities, comment on the mechanisms underlying this association and investigate the consequences
for the management of psoriasis.
Frequency of Iron Uptake Proteins Related Genes Among Klebsiella pneumoniae Isolates
Authors: Elhaki Tahereh , Gheysarzadeh Ali , Sadeghifard Nourkhoda , Pakzad Iraj , Behrouzi Ava , Taherikalani Morovat , Jalilian Farid A. , Tabasi Mohsen , Azizian Reza
Published: May 2020

Aims:

The present study aimed to evaluate Iron uptake protein-related genes in clinical and environmental Klebsiella pneumoniae isolates.

Background:

Klebsiella pneumoniae as an opportunistic pathogen cause infections in immunocompromised patients. Iron uptake systems play an important role in the pathogenesis of Klebsiella pneumonia.

Objectives:

This study was designed to investigate the prevalence of iron uptake coding genes among isolates of Klebsiella pneumonia.

Materials and Methods:

A total of 300 isolates of Klebsiella pneumonia including 150 clinical isolates and 150 environmental isolates were selected. Finally, the frequency of iroN, iucD, kfuA,hmuR, and ybt [yHPI] genes were detected by PCR method.

Results:

The frequency of kfuA, iucD, iroN, yHPI in clinical isolates were 33.3%, 16.7%, 24.7%, 15.3%, respectively and these genes among environmental isolates were 20.7%, 6%, 49.3% and 0.7%, respectively. Among the clinical isolates, the most frequency genes were kfuA gene [50 isolates] and after that iroN [37 isolates], iucD [25 isolates] and yHPI [23 isolates], the genes with the most frequency among environmental isolates were iroN gene [74 isolates] and following that kfuA [31 isolates], iucD [9 isolates] and yHPI [1 isolate]. No hmuR positive samples among all clinical or environmental isolates were found.

Conclusion:

The result of this study showed that because of the high frequency of ferric iron system coding gene kfu among clinical isolates, this system might play an important role in the survival of bacteria against its host.
Importance of comprehensive reading: its value in basic
Authors: Alava Romina Adelina Quevedo , Laz Esthela María San Andrés , Palmac Josefa Katiuska Toala , Parrales Enrrique Byron Ayón
Published: May 2020

A study of the comprehensive reading, its importance and the basic value of an educational institution in the province of Manabí was conducted, it was investigated what is the impact on students, in which it benefits them to understand what is found in the pages of a text, how to broaden its criticality, the concentration of reading, writing and oral skills, to have a better communication and how reading influenced values, it was elaborated in a research way with the help of ICT, not practical, with the inductive method - deductive, finally, the linguistic norms, pauses, emphasis, vowel sounds that are used when reading are analyzed, such as strategies that can be used for images, graphics, mental or conceptual maps, together with teacher support inside or outside the classroom, coordinate the ways of studying the topics because each student thinks and analyzes differently.
Diagnostic evaluation for strengthening the teaching-learning process
Authors: Hidrovo Gabriela Maricela Sánchez , Macías Martha Elizabeth Mendoza , Baque Katy Yadira Pinargote , Valdez Cristina Alexandra Escobar
Published: May 2020

In this research, which aims to identify the application of diagnostic evaluation to strengthen the teaching-learning process in students. He focused on the diagnostic evaluation and what is the correct way to perform it, to strengthen the teaching-learning process by improving the techniques and methods that are used to achieve positive results in this process, concluding that teacher training is very important for the application of the instruments that facilitate the taking of the diagnostic test, however, have not been trained. The study has been an exploratory type with a quantitative approach, using scientific, analytical, and synthetic methods. To base the research, the bibliographic method was used and as a study technique the survey was used, in which questions were formulated according to the study variables. The results guide the improvement of students' cognitive meta strategies and guide both teaching and their school learning.
Riesgos maternos, reproductivos y perinatales de las enfermedades tropicales: Dengue
Authors: Romero Guzmán Ivonne , Amador Ahumada Concepción , Padilla Choperena Candelaria , Benitez Cheij Lucelly
Published: May 2020

Among tropical diseases, the potential effect or risk of some particular diseases such as Malaria, Zika and Chikungunya on the health of pregnant women and their gestational product has been analyzed and recognized; However, the same is not true among Dengue professionals, but this type of information seems to be unknown. The objective of this review is to present the scientific generated from various perspectives, about the maternal and perinatal implications associated with Dengue; which is one of the viral diseases with the greatest infectious potential, capable of generating epidemics of great magnitude. The information was obtained in medical databases such as PUBMED, LILACS, MEDES. ELSEVIER, of which the results of research conducted in the different continents affected by this disease were compiled.