bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis of a hom-disrupted, cephamycin C overproducing Streptomyces clavuligerus
Authors: Ünsaldı Eser , Kurt-Kızıldoğan Aslıhan , Özcan Servet , Becher Dörte , Voigt Birgit , Aktaş Caner , Özcengiz Gülay 
Published: July 2020

Background:
Streptomyces clavuligerus is prolific producer of cephamycin C, a medically
important antibiotic. In our former study, cephamycin C titer was 2-fold improved by disrupting
homoserine dehydrogenase (hom) gene of aspartate pahway in Streptomyces clavuligerus NRRL
3585.

Objective:
In this article, we aimed to provide a comprehensive understanding at the proteome level
on potential complex metabolic changes as a consequence of hom disruption in Streptomyces
clavuligerus AK39.

Methods:
A comparative proteomics study was carried out between the wild type and its hom disrupted
AK39 strain by 2 Dimensional Electrophoresis-Matrix Assisted Laser Desorption and Ionization
Time-Of-Flight Mass Spectrometry (2DE MALDI-TOF/MS) and Nanoscale Liquid Chromatography-
Tandem Mass Spectrometry (nanoLC-MS/MS) analyses. Clusters of Orthologous
Groups (COG) database was used to determine the functional categories of the proteins. The theoretical
pI and Mw values of the proteins were calculated using Expasy pI/Mw tool.

Results:
“Hypothetical/Unknown” and “Secondary Metabolism” were the most prominent categories
of the differentially expressed proteins. Upto 8.7-fold increased level of the positive regulator
CcaR was a key finding since CcaR was shown to bind to cefF promoter thereby direcly controlling
its expression. Consistently, CeaS2, the first enzyme of CA biosynthetic pathway, was 3.3-
fold elevated. There were also many underrepresented proteins associated with the biosynthesis of
several Non-Ribosomal Peptide Synthases (NRPSs), clavams, hybrid NRPS/Polyketide synthases
(PKSs) and tunicamycin. The most conspicuously underrepresented protein of amino acid
metabolism was 4-Hydroxyphenylpyruvate dioxygenase (HppD) acting in tyrosine catabolism. The
levels of a Two Component System (TCS) response regulator containing a CheY-like receiver domain
and an HTH DNA-binding domain as well as DNA-binding protein HU were elevated while
a TetR-family transcriptional regulator was underexpressed.

Conclusion:
The results obtained herein will aid in finding out new targets for further improvement
of cephamycin C production in Streptomyces clavuligerus.
Advances in Research on the Preparation and Biological Activity of Maslinic Acid
Authors: Deng Jianqiang , Wang Huiyun , Mu Xiaodong , He Xiuting , Zhao Fenglan , Meng Qingguo 
Published: July 2020

:
Maslinic acid, a pentacyclic triterpene acid, is mainly isolated from olives. Maslinic acid
and its derivatives exhibit a broad range of biological properties, such as anti-inflammatory, anticancer,
anti-diabetic, antimicrobial, neuroprotective and hepatoprotective activities. In this minireview,
the progress of research on maslinic acid with regard to its bioactivities, extraction, semisynthetic
preparation and patents is reported. The relationships between the structure and the activity
of maslinic acid and its derivatives are also discussed.
Matrix Metalloproteinases (MMPs) in Targeted Drug Delivery: Synthesis of a Potent and Highly Selective Inhibitor against Matrix Metalloproteinase-7
Authors: Wang Ling-Li , Zhang Bing , Zheng Ming-Hua , Xie Yu-Zhong , Wang Chang-Jiang , Jin Jing-Yi 
Published: July 2020

Background:
Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that
play a key role in both physiological and pathological tissue degradation. MMPs have reportedly shown
great potentials in the degradation of the Extracellular Matrix (ECM), have shown great potentials in
targeting bioactive and imaging agents in cancer treatment. MMPs could provoke Epithelial to Mesenchymal
Transition (EMT) of cancer cells and manipulate their signaling, adhesion, migration and invasion
to promote cancer cell aggressiveness. Therefore, targeting and particularly inhibiting MMPs
within the tumor microenvironment is an effective strategy for cancer treatment. Based on this idea, different
MMP inhibitors (MMPIs) have been developed to manipulate the tumor microenvironment towards
conditions appropriate for the actions of antitumor agents. Studies are ongoing to improve the selectivity
and specificity of MMPIs. Structural optimization has facilitated the discovery of selective inhibitors
of the MMPs. However, so far no selective inhibitor for MMP-7 has been proposed.

Aims:
This study aims to comprehensively review the potentials and advances in applications of MMPs
particularly MMP-7 in targeted cancer treatment approaches with the main focus on targeted drug delivery.
Different targeting strategies for manipulating and inhibiting MMPs for the treatment of cancer are
discussed. MMPs are upregulated at all stages of expression in cancers. Different MMP subtypes have
shown significant targeting applicability at the genetic, protein, and activity levels in both physiological
and pathophysiological conditions in a variety of cancers. The expression of MMPs significantly increases
at advanced cancer stages, which can be used for controlled release in cancers in advance stages.

Methods:
Moreover, this study presents the synthesis and characteristics of a new and highly selective
inhibitor against MMP-7 and discusses its applications in targeted drug delivery systems for therapeutics
and diagnostics modalities.

Results:
Our findings showed that the structure of the inhibitor P3’ side chains play the crucial role in
developing an optimized MMP-7 inhibitor with high selectivity and significant degradation activities
against ECM.

Conclusion:
Optimized NDC can serve as a highly potent and selective inhibitor against MMP-7 following
screening and optimization of the P3’ side chains, with a Ki of 38.6 nM and an inhibitory selectivity
of 575 of MMP-7 over MMP-1.
Cedrus deodara (Bark) Essential Oil Induces Apoptosis in Human Colon Cancer Cells by Inhibiting Nuclear Factor kappa B
Authors: Bhagat Madhulika , Kumar Ajay , Suravajhala Renuka 
Published: July 2020

Aims:
The aim of this study is to explore essential oil from the bark of Cedrus deodara
(CDEO) as an potential anticancer agent.

Background:
The frontline drugs against cancer in clinical settings are posing challenges of resistance
and other detrimental side-effects. This has led to the exploration of new anticancer chemical entities
from natural sources, particularly plant-based products such as essential oils that serve as vast repositories
of pharmacologically active substances for combating cancer.

Objective:
The objective is to isolate and characterize the essential oil from the bark of Cedrus deodara
(CDEO) and evaluate its potential as an anticancer agent and delineate the possible underlying mechanism
of action.

Methods:
Cedrus deodara essential oil from bark (CDEO) was obtained by hydro-distillation and analyzed
by GC/MS for vital constituents. Further, in vitro cytotoxic potential was measured by MTT assay
against a panel of cancer cell lines. The apoptosis-inducing potential of CDEO was analyzed by mitochondrial
membrane potential loss (ΔΨm) and nuclear fragmentation assay. Besides, wound healing assay
and colonogenic assay were employed to check the anti-metastatic potential of CDEO. Molecular
docking approaches were employed for target identification, while immuno-blotting was carried out for
target validation.

Results and Discussion:
The major components identified were 2-(tert-Buyl)-6-methyl-3-(2- (trifluoromethyl)
benzyl)imidazo [1,2-a]pyridine (26.32 %);9- Octadecenoic acid (8.015 %); Copaene (5.181
%);2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H- benzo[g]indazole(4.36 %) and 9(E),11(E)-
Conjugated linoleic acid (4.299 %). Further, potent in vitro cytotoxic activity with IC50 values of 11.88
μg/ ml and 14.63 μg/ ml in colon cancer cell lines of HCT-116 and SW-620, respectively. Further, a
significant and dose-dependent decrease in colony formation, cell migration, induction of ROS formation
and loss in ΔΨm was observed. Additionally, major compounds identified were chosen for ligandprotein
binding interaction studies to predict the molecular targets in colon cancer. It was observed that
compounds such as 9-Octadecenoic acid;4H-1- Benzopyran-4-one, 3-(3,4-dimethoxyphenyl)-6,7-
dimethoxy; 2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H-benzo [g]indazole and 2-Bornanol,5-(2,4-
dinitro phenyl) hydrazono have a prominent binding affinity with NF-κB. This was also further validated
by immuno-blotting results wherein CDEO treatment in colon cancer cells led to the abrogation of
NFκB, and the Bcl-2-associated X protein (Bax): B-cell lymphoma (Bcl)-2 ratio was up-regulated leading
to enhanced cleaved caspase 3 formation and subsequent apoptosis.

Conclusion:
These results unveil CDEO inhibits cell proliferation and induces apoptosis in colon cancer
cells, which can be attributed to the abrogation of the NFκB signaling pathway.
Lead Generation for Human Mitotic Kinesin Eg5 Using Structure-based Virtual Screening and Validation by In-vitro and Cell-based Assays
Authors: Makala Himesh , Alexandar Soundarya Priya , Nagarajan Devipriya , Mahapatra Santanu Kar , Ulaganathan Venkatasubramanian 
Published: July 2020

Background:
Human mitotic kinesins play a crucial role in mitotic cell division. Targeting the spindle
separation phase of mitosis has gained much attention pharmaceutically in cancer chemotherapy. Spindle segregation is
carried out mainly by Eg5 kinesin, and currently, it has many inhibitors in different phases of clinical trials. All the
current drug candidates bind un-competitively with ATP/ADP at allosteric site 1 (formed by loop L5, helix α2 and helix
α3). Recent experiments show that inhibitors that bind to the site 2 (formed by helix α4 and helix α6) are either
competitive or uncompetitive to ATP/ADP.

Objectives:
To identify suitable lead compounds that target the mitotic kinesin Eg5, using in silico screening and their
validation using in vitro and cell-based assays.

Methodology:
We have screened for potential inhibitors for human Eg5 (kinesin-5) through structure-based virtual
screening and validated the top-scoring compounds using steady-state ATPase assay, differential scanning fluorimetry
and microscale thermophoresis. The anticancer activity of the compounds was evaluated in the epithelial (A549) and
chronic myelogenous leukaemia (K562) cancer cell lines. A known strong binding inhibitor S-trityl-L-cystine is used as a
reference compound.

Results & Conclusion:
Of the many compounds tested, MM01 and MM03 showed good cell-based activity against the
cancer cell lines A549 and K562 and can be further studied in animal models.
Preparation and Characterization of Calcium Carbonate Reinforced Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) Biocomposites
Authors: Kirboga Semra , Öner Mualla , Deveci Süleyman 
Published: July 2020

Background:The objective of this work was to develop biopolymer/calcium carbonate biocomposites with enhanced properties, relative to the neat polymer, by using low-cost filler calcium carbonate (CaCO3). To this end, we selected as matrices Poly (3-hydroxybutyrate-co-3- hydroxyvalerate, PHBV), which has attracted the most considerable interest among the biopolymers in industry.Methods:Novel biodegradable PHBV/CaCO3composites with 0.1-1 wt% of CaCO3content were manufactured by melt extrusion. The effect of the CaCO3on the thermal, barrier and dynamic mechanical properties of the PHBV was comprehensively investigated by SEM, XRD, FTIR, TGA, DSC, and DMA. The water and oxygen barrier properties of the biocomposites were also measured.Results:DSC and XRD analysis showed that CaCO3served as a nucleating agent, promoting crystallinity and crystal size. The addition of CaCO3particles has a small effect on lamellae thickness and distribution. DMA measurements showed considerable improvements in storage modulus and viscose damping by incorporating CaCO3particles. The storage modulus of the PHBV at 20°C in the DMA was increased up to 76% and loss modulus was increased up to 175% when composite was prepared with 0.1wt% coated CaCO3particle. Water vapor and oxygen permeability were measured to study the effect of particles on the barrier properties of composite samples. Biocomposites exhibited smaller oxygen transmission rate (OTR) and water vapor transmission rate (WVTR) due to the increase in crystallinity and tortuosity of the composite samples.Conclusion:The results of this study have demonstrated that properties of biocomposites prepared by using low-cost commercially available filler are greatly improved to obtain the high-performance composites.
Propitious Profile of Peppery Piperine
Authors: Bakshi Harman , Nagpal Manju , Singh Manjinder , Dhingra Gitika A. , Aggarwal Geeta 
Published: July 2020

Background:
Piperine is a key bioactive alkaloid found in plants of piperaceae family.
The compound possesses various medicinal and pharmacological activities (cholesterol-lowering,
anti-cancer, Alzheimer’s disease etc.). Owing to its various target receptors (TRPV1, P-gp,
CYP3A4 etc.) and several mechanisms, piperine has been studied as bio-enhancer for other drugs
and its role has been evidenced in the literature. When administered with other drugs, it increases
the absorption of other drugs, thereby reducing the dose and dose-related toxic potential. There are
various mechanisms of piperine as a bio-enhancer and the common ones are i) prevention of efflux
of drug molecules out of the cells; ii) decreased metabolism of drugs, thereby prolonging the halflife
of drugs resulting in reduced urinary excretion. The detailed mechanism indicating the bio-enhancing
role of piperine along with various target receptors has not been comprehensively summarised
to date.

Methods:
Literature related to the molecular, enzymatic and receptor targets of piperine were studied and database was
collected using various search engines such as j-gate, google scholar, scihub, pubmed, sciencedirect etc. The literature
related to therapeutic activities of piperine and its bio-enhancer role for other drugs has been thoroughly studied and
compiled in brief.

Results:
A detailed summary of piperine targets along with related mechanisms has been stated. A brief therapeutic
profile of piperine alone has been produced with supporting literature. Piperine role as a potential bio-enhancer for other
drugs has been summarized.

Conclusion:
Piperine is a fascinating molecule of natural origin with several modes of its action,
not only possesses its own therapeutic activity but also enhances the therapeutic efficacy of other
synthetic and natural drug molecules. Combination dosage forms of various API incorporating
piperine as a bio-enhancer can be a potential area of thrust for upcoming drug design and development.
Multipliers Based on Approximate Compressors
Authors: Maitra Subhashis 
Published: July 2020

Background:
Approximate computing is an emerging trend in recent year that trades off the requirement of exact computation
for the improvement of speed and power performance.

Objective:
Researchers are trying to improve the speed and power performance proposing different algorithm.

Method:
This paper proposes approximate compressors used for the design of approximate multipliers.

Results:
By using the proposed method, approximate multipliers of different length have been synthesized and a comparative study with
previously presented multipliers have been dealt here which shows that the proposed circuits have better speed and power.

Conclusion:
Finally the proposed circuits have been used for image processing applications.
Acceptability and Effectiveness of NHS-Recommended e-Therapies for Depression, Anxiety, and Stress: Meta-Analysis
Authors: Simmonds-Buckley Melanie , Bennion Matthew Russell , Kellett Stephen , Millings Abigail , Hardy Gillian E , Moore Roger K 
Published: July 2020

Background
There is a disconnect between the ability to swiftly develop e-therapies for the treatment of depression, anxiety, and stress, and the scrupulous evaluation of their clinical utility. This creates a risk that the e-therapies routinely provided within publicly funded psychological health care have evaded appropriate rigorous evaluation in their development.

Objective
This study aims to conduct a meta-analytic review of the gold standard evidence of the acceptability and clinical effectiveness of e-therapies recommended for use in the National Health Service (NHS) in the United Kingdom.

Methods
Systematic searches identified appropriate randomized controlled trials (RCTs). Depression, anxiety, and stress outcomes at the end of treatment and follow-up were synthesized using a random-effects meta-analysis. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of each meta-analytic comparison. Moderators of treatment effect were examined using subgroup and meta-regression analysis. Dropout rates for e-therapies (as a proxy for acceptability) were compared against controls.

Results
A total of 24 studies evaluating 7 of 48 NHS-recommended e-therapies were qualitatively and quantitatively synthesized. Depression, anxiety, and stress outcomes for e-therapies were superior to controls (depression: standardized mean difference [SMD] 0.38, 95% CI 0.24 to 0.52, N=7075; anxiety and stress: SMD 0.43, 95% CI 0.24 to 0.63, n=4863), and these small effects were maintained at follow-up. Average dropout rates for e-therapies (31%, SD 17.35) were significantly higher than those of controls (17%, SD 13.31). Limited moderators of the treatment effect were found.

Conclusions
Many NHS-recommended e-therapies have not been through an RCT-style evaluation. The e-therapies that have been appropriately evaluated generate small but significant, durable, beneficial treatment effects.

Trial Registration
International Prospective Register of Systematic Reviews (PROSPERO) registration CRD42019130184; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130184
Causality Analysis of Google Trends and Dengue Incidence in Bandung, Indonesia With Linkage of Digital Data Modeling: Longitudinal Observational Study
Authors: Syamsuddin Muhammad , Fakhruddin Muhammad , Sahetapy-Engel Jane Theresa Marlen , Soewono Edy 
Published: July 2020

Background
The popularity of dengue can be inferred from Google Trends that summarizes Google searches of related topics. Both the disease and its Google Trends have a similar source of causation in the dengue virus, leading us to hypothesize that dengue incidence and Google Trends results have a long-run equilibrium.

Objective
This research aimed to investigate the properties of this long-run equilibrium in the hope of using the information derived from Google Trends for the early detection of upcoming dengue outbreaks.

Methods
This research used the cointegration method to assess a long-run equilibrium between dengue incidence and Google Trends results. The long-run equilibrium was characterized by their linear combination that generated a stationary process. The Dickey-Fuller test was adopted to check the stationarity of the processes. An error correction model (ECM) was then adopted to measure deviations from the long-run equilibrium to examine the short-term and long-term effects. The resulting models were used to determine the Granger causality between the two processes. Additional information about the two processes was obtained by examining the impulse response function and variance decomposition.

Results
The Dickey-Fuller test supported an implicit null hypothesis that the dengue incidence and Google Trends results are nonstationary processes (P=.01). A further test showed that the processes were cointegrated (P=.01), indicating that their particular linear combination is a stationary process. These results permitted us to construct ECMs. The model showed the direction of causality of the two processes, indicating that Google Trends results will Granger-cause dengue incidence (not in the reverse order).

Conclusions
Various hypothesis testing results in this research concluded that Google Trends results can be used as an initial indicator of upcoming dengue outbreaks.
QardioArm Blood Pressure Monitoring in a Population With Type 2 Diabetes: Validation Study
Authors: Mazoteras-Pardo Victoria , Becerro-De-Bengoa-Vallejo Ricardo , Losa-Iglesias Marta Elena , Martínez-Jiménez Eva María , Calvo-Lobo César , Romero-Morales Carlos , López-López Daniel , Palomo-López Patricia 
Published: July 2020

Background
Home blood pressure monitoring has many benefits, even more so, in populations prone to high blood pressure, such as persons with diabetes.

Objective
The purpose of this research was to validate the QardioArm mobile device in a sample of individuals with noninsulin-dependent type 2 diabetes in accordance with the guidelines of the second International Protocol of the European Society of Hypertension.

Methods
The sample consisted of 33 patients with type 2 diabetes. To evaluate the validity of QardioArm by comparing its data with that obtained with a digital sphygmomanometer (Omron M3 Intellisense), two nurses collected diastolic blood pressure, systolic blood pressure, and heart rate with both devices.

Results
The analysis indicated that the test device QardioArm met all the validation requirements using a sample population with type 2 diabetes.

Conclusions
This paper reports the first validation of QardioArm in a population of individuals with noninsulin-dependent type 2 diabetes. QardioArm for home monitoring of blood pressure and heart rate met the requirements of the second International Protocol of the European Society of Hypertension.
The Anatomy of the SARS-CoV-2 Biomedical Literature: Introducing the CovidX Network Algorithm for Drug Repurposing Recommendation
Authors: Gates Lyndsey Elaine , Hamed Ahmed Abdeen 
Published: July 2020

Background
Driven by the COVID-19 pandemic and the dire need to discover an antiviral drug, we explored the landscape of the SARS-CoV-2 biomedical publications to identify potential treatments.

Objective
The aims of this study are to identify off-label drugs that may have benefits for the coronavirus disease pandemic, present a novel ranking algorithm called CovidX to recommend existing drugs for potential repurposing, and validate the literature-based outcome with drug knowledge available in clinical trials.

Methods
To achieve such objectives, we applied natural language processing techniques to identify drugs and linked entities (eg, disease, gene, protein, chemical compounds). When such entities are linked, they form a map that can be further explored using network science tools. The CovidX algorithm was based upon a notion that we called “diversity.” A diversity score for a given drug was calculated by measuring how “diverse” a drug is calculated using various biological entities (regardless of the cardinality of actual instances in each category). The algorithm validates the ranking and awards those drugs that are currently being investigated in open clinical trials. The rationale behind the open clinical trial is to provide a validating mechanism of the PubMed results. This ensures providing up to date evidence of the fast development of this disease.

Results
From the analyzed biomedical literature, the algorithm identified 30 possible drug candidates for repurposing, ranked them accordingly, and validated the ranking outcomes against evidence from clinical trials. The top 10 candidates according to our algorithm are hydroxychloroquine, azithromycin, chloroquine, ritonavir, losartan, remdesivir, favipiravir, methylprednisolone, rapamycin, and tilorone dihydrochloride.

Conclusions
The ranking shows both consistency and promise in identifying drugs that can be repurposed. We believe, however, the full treatment to be a multifaceted, adjuvant approach where multiple drugs may need to be taken at the same time.