bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/ Cas9 Off-targets: Computational Analysis of Causes, Prediction,
Detection, and Overcoming Strategies
Authors: Roy Roshan Kumar , Debashree Ipsita , Srivastava Sonal , Rishi Narayan , Srivastava Ashish 
Published: July 2021

:
CRISPR/Cas9 technology is a highly flexible RNA-guided endonuclease (RGEN)
based gene-editing tool that has transformed the field of genomics, gene therapy, and genome/
epigenome imaging. Its wide range of applications provides immense scope for understanding
as well as manipulating genetic/epigenetic elements. However, the RGEN is prone to
off-target mutagenesis that leads to deleterious effects. This review details the molecular and cellular
mechanisms underlying the off-target activity, various available detection tools and prediction
methodology ranging from sequencing to machine learning approaches, and the strategies to
overcome/minimise off-targets. A coherent and concise method increasing target precision would
prove indispensable to concrete manipulation and interpretation of genome editing results that
can revolutionise therapeutics, including clarity in genome regulatory mechanisms during development.
Retracted: miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in
Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway
Authors: Guo Lin , Bao Chen-hui 
Published: July 2021

The article entitled “miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway”, by Chen-Hui Bao and Lin Guo, has been retracted on the request of the Author in light of the changes to the University’s promotion policy, due to which the article needs further content.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

Kindly see Bentham Science Policy on Article retraction at the link https://benthamscience.com/journals/anti-canceragents-in-medicinal-chemistry/editorial-policies/

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Apoptotic Effect of Novel Benzimidazole Derivatives Bearing Pyridyl/Pyrimidinyl Piperazine Moiety
Authors: Çiftçi Gulsen A. , Temel Halide E. , Yurttaş Leyla 
Published: July 2021

Background:
Benzimidazole derivatives bearing pyridyl/pyrimidinyl piperazine moiety has attracted attention
in medicinal chemistry and modern drug discovery since it exhibited a variety of biological activities, including
anticancer activity.

Objective:
In this study, we designed and synthesized novel 1-[2-oxo-2-(4-substituted phenyl)ethyl]benzimidazol-2-
yl)methyl 4-(2-pyridyl/pyrimidin-2-yl)piperazine-1-carbodithioate derivatives (2a-m). We also investigated their anticancer
activities against A549 lung adenocarcinoma and C6 rat glioma cell lines. We further studied the selectivity of
the compounds against the NIH/3T3 mouse embryonic fibroblast cell line. Cholinesterase inhibition effects of these
compounds were also investigated to measure the relationship between anticancer activity and cholinesterases.

Method:
The cytotoxic activities of these acquired thirteen final compounds were screened using MTT assay on
A549, C6, and NIH/3T3 cell lines. Cell proliferation ELISA, BRDU (colorimetric) assay was used to measure the
proliferation in replicative cells in which DNA synthesis occurs. Flow cytometric analysis was used to measure apoptotic
cell percentages, caspase 3 activity, and mitochondrial membrane depolarised cell percentages.

Results:
Compounds 2e, 2f, and 2k were shown to be the most active antitumor agents with selective cytotoxicities
(the results for A549 were 76.58±6.43, 55.13±5.75, and 32.94±3.02 μM, respectively; and for C6 they were
86.48±3.60, 97.12±30.21, and 59.29±3.95 μM, respectively), high DNA synthesis inhibition rates and high apoptotic
cell percentages on both cell lines.

Conclusion:
The results showed that compounds 2e, 2f, and 2k have potential anticancer activity against A549 and C6
cell lines
Ternary Copper (II) Complex Induced Apoptosis and Cell Cycle Arrest in Colorectal
Cancer Cells
Authors: Arikrishnan Sathiavani , Loh Jian Sheng , Tor Yin Sim , Teo Xian Wei , bin Norizan Faris , Low May Lee , Lee Sau Har , Foo Jhi Biau 
Published: July 2021

Background:
The lack of specificity, severe side effects, and development of drug resistance have largely
limited the use of platinum-based compounds in cancer treatment. Therefore, copper complexes have emerged as potential
alternatives to platinum-based compounds.

Objective:
Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its
anti-cancer effects in HT-29 colorectal cancer cells.

Methods:
Cytotoxic effects of ternary copper (II) complex in HT-29 cells was evaluated using MTT assay, Real-Time
Cell Analysis (RTCA) and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry.
Apoptosis induction was studied by Annexin V-FITC/Propidium Iodide (PI) staining and mitochondrial membrane
potential analysis (JC-10 staining) using flow cytometry. Intracellular Reactive Oxygen Species (ROS) were detected
by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and
PARP-1) was evaluated by western blot analysis.

Results:
Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner,
with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 μM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of
S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction
of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP-
1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential
disruption, and ROS production were observed.

Conclusion:
Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment.
Synergistic Cytotoxicity Effect of 5-Fluorouracil and SHP2 Inhibitor Demethylincisterol A3 on Cervical Cancer Cell
Authors: Liu Yang , Fu Hua , Zuo Li 
Published: July 2021

Background:
Demethylincisterol A3 (DTA3) has been identified as an SHP2 inhibitor and suppresses the
growth of many cancer cells. 5-Fluorouracil (5-FU) is widely used for the clinical treatment of various cancers. However,
the combination effects of 5-FU and DTA3 on cervical cancer cells remain unknown.

Objective:
This study evaluates the mechanism of the combination effects of 5-FU and DTA3 in cervical cancer cells.

Methods:
The synergistic cytotoxic effects of 5-FU and DTA3 in cervical cancer cells were calculated. Apoptosis was
analysed by flow cytometry. Western blot analyses were used to examine the related signalling pathways.

Results:
DTA3 and 5-FU synergized to induce apoptosis and repress proliferation of cervical cancer cells by downregulating
the activation of PI3K/AKT and NF-κB signalling pathways. We provided evidence that the upregulation of
SHP2 expression by transfection significantly inhibited the cytotoxicity of 5-FU and DTA3. SHP2 knockdown enhanced
the anti-proliferation activity of 5-FU, indicating targeting SHP2 sensitized cervical cancer cells to 5-FU.

Conclusion:
Our study demonstrates that SHP2 inhibitor DTA3 and 5-FU have a synergistic cytotoxic effect on cervical
cancer cells. The synergistic combination of SHP2 inhibitor and 5-FU may present a promising strategy for the
treatment of cervical cancer.
Implicit Surface Reconstruction via RBF Interpolation: A Review
Authors: Shou Huahao , Mo Jiahui , Chen Wei 
Published: July 2021

Background:
Implicit surface is a kind of surface modeling tool, which is widely used
in point cloud reconstruction, deformation and fusion due to its advantages of good smoothness
and Boolean operation. The most typical method is the surface reconstruction with Radial Basis
Functions (RBF) under normal constraints. RBF has become one of the main methods of point
cloud fitting because it has a strong mathematical foundation, an advantage of computation simplicity,
and the ability of processing nonuniform points.

Objective:
Techniques and patents of implicit surface reconstruction interpolation with RBF are
surveyed. Theory, algorithm, and application are discussed to provide a comprehensive summary
for implicit surface reconstruction in RBF and Hermite Radial Basis Functions (HRBF) interpolation.

Methods:
RBF implicit surface reconstruction interpolation can be divided into RBF interpolation
under the constraints of points and HRBF interpolation under the constraints of points and corresponding
normals.

Results:
A total of 125 articles were reviewed, in which more than 30% were related to RBF in
the last decade. The continuity properties and application fields of the popular global supported
radial basis functions and compactly supported radial basis functions are analyzed. Different
methods of RBF and HRBF implicit surface reconstruction are evaluated, and the challenges of
these methods are discussed.

Conclusion:
In future work, implicit surface reconstruction via RBF and HRBF should be further
studied in fitting accuracy, computation speed, and other fundamental problems. In addition, it is a
more challenging but valuable research direction to construct a new RBF with both compact support
and improved fitting accuracy.
Concentration of Droplets from Patients during Normal Breathing and Speech and Their Importance in Protection from Coronavirus SARS-CoV-2 (COVID-19) Infection
Authors: Mimura Tatsuya , Noma Hidetaka , Matsumoto Koichi , Kawashima Makoto , Kitsu Kazuma , Itoh Erina , Horikawa Hiroaki , Mizuno Yoshinobu , Watanabe Emiko , Mizota Atsushi 
Published: July 2021

Purpose:Coronavirus disease (COVID-19) has been declared a pandemic and the number of infected individuals and deaths continue to increase globally. COVID-19 is transmitted through airborne droplets formed during coughing and sneezing and from the saliva of infected patients. Medical healthcare workers are often at risk of infection. This study measured the aerosol derived from the droplets of patients during the conversation.Methods:Overall, 25 patients aged 21 to 87 years were enrolled. The amount of droplets from the patient was measured under the following four conditions: 1) no conversation with the mask on; 2) conversation with the mask on; 3) conversation without the mask; and 4) no conversation without the mask. Particulate matter (PM) with an aerodynamic diameter of 2.5 μm or less (PM2.5) and PM with a diameter of 10 μm or less (PM10) were measured as representative aerosols at a position of 1 meter from the patients.Results:The concentrations of PM2.5 (µg/m3) were as follows: 22.7 ± 10.2 before the conversation with the mask, 24.2 ± 10.2 during the conversation with the mask, 32.3 ± 14.7 during the conversation without the mask, and 23.1 ± 9.9 after the conversation without the mask. The concentrations of PM10 (µg/m3) were as follows: 39.8 ± 18.2 before conversation with the mask, 41.9 ± 18.5 during conversation with the mask, 55.5 ± 27.2 during conversation without the mask, and 40.4 ± 17.8 after conversation without the mask. The variations in the PM2.5 and PM10 correlated negatively with the age of patients (PM2.5: r = -0.51, p = 0.0009 and PM10: r = -0.53, p = 0.0063).Conclusion:Wearing a mask can prevent airborne droplet formation and reduce transmission of infection.
Prognostic Implications of microRNA-155, -133a, -21 and -205 in Breast
Cancer Patients’ Plasma
Authors: Raghu Aarthy , Magendhra Rao Arunagiri Kuha Deva , Rajkumar Thangarajan , Mani Samson 
Published: July 2021

Background:
Breast cancer, being a heterogenous disease at the intra-tumoral and intertumoral
levels, presents challenges in following the progress of the disease. Tumour-secreted aberrantly
expressed miRNAs obtained from peripheral blood represent a non-invasive alternative resource
for detecting and monitoring the development of the disease. This study evaluates the expression
of miR-155, miR-133a, miR-21 and miR-205 as non-invasive, prognostic and follow-up
markers for breast cancer.

Methods:
Plasma expression levels of miR-155, miR-133a, miR-21 and miR-205 were measured
using real-time PCR in breast cancer patients (n=63) at presentation, healthy controls (n=25), and
in post-treatment samples of 31 patients. A meta-analysis was performed using 43 studies identified
from PubMed, Google Scholar and Scopus databases. Hedge’s g values were used to calculate
the overall effect size.

Results:
Plasma miR-21 levels were higher in breast cancer patients at presentation compared to
controls, while no difference was observed for miR-155, miR-133a and miR-205. These results
were further supported by the meta-analysis. The altered levels of miR-155 during tamoxifen treatment
indicated a potential role for miR-155 in monitoring treatment response. Further, high expressions
of at least three miRNAs correlated with poor overall survival in the breast cancer patients.

Conclusion:
Plasma levels of miR-155, miR-133a, miR-21 and miR-205 may be useful as prognostic
and follow-up markers for breast cancer with further validation in a large cohort of patients.
Optimized Rod Size Design of Denim Fabric Grinding Robot Based on
Improved Cuckoo Search Algorithm
Authors: Wang Wenjie , Chen Congcong , Cao Yuting , Xu Jian , Wang Xiaohua 
Published: July 2021

Background:
Dexterity is an important index for evaluating the motion performance of a
robot. The size of the robot connecting rods directly affects the performance of flexibility.

Objective:
The purpose of this study is to provide an overview of optimal design methods from
many pieces of literature and patents, and propose a new optimal design method for ensuring the robot
completes its tasks flexibly and efficiently under workspace constraints.

Methods:
The kinematics and working space of the robot are analyzed to determine the range of
motion of each joint. Then, a dexterity index is established based on the mean value of the global
spatial condition number. Finally, an improved cuckoo algorithm is proposed, which changes the
step size control factor with the number of iterations. Taking the dexterity index as the objective optimization
function and the working radius as the constraint condition, the improved cuckoo search
algorithm is used to optimize the size of the robot rod.

Results:
The improved cuckoo algorithm and proposed rod size optimized method are fully evaluated
by experiments and comparative studies. The optimization design process shows that the proposed
method has better solution accuracy and faster convergence speed. The optimized design results
show that the robot's dexterity index has increased by 26.1%.

Conclusion:
The proposed method has better solution accuracy and faster convergence speed. The
method was suitable for optimizing the rod parameters of the robot, and it was very meaningful to
improve the motion performance of the robot.
Широкополосная ЭПР-спектроскопия ионов Tb-=SUP=-3+-=/SUP=- и Fe-=SUP=-2+-=/SUP=- в монокристаллах YAlO-=SUB=-3-=/SUB=-
Authors: Асатрян Г.Р. , Шакуров Г.С. , Ильин И.В. , Петросян А.Г. , Ованесян К.Л. , Дердзян М.В. 
Published: July 2021

Методом широкополосной ЭПР-спектроскопии изучен кристалл YAlO3 с примесью железа. Обнаружено два типа парамагнитных центров. Энергетическая схема уровней одного из них представляет собой синглет и дублет с расщеплением между ними 215.2 GHz. Этот центр предположительно связан с ионом Fe2+. Второй центр идентифицирован как ион Tb3+, вошедший в кристалл как неконтролируемая примесь. Для каждого случая определена локализация примесного иона в кристаллической решетке YAlO3. В рамках существующей теории сделаны расчеты и определены спектральные параметры. Ключевые слова: широкополосный электронный парамагнитный резонанс, ортоалюминат иттрия, примесные центры, некрамерсовые ионы.
The VICTORY (Investigation of Inflammacheck to Measure Exhaled Breath Condensate Hydrogen Peroxide in Respiratory Conditions) Study: Protocol for a Cross-sectional Observational Study
Authors: Fox Lauren , Gates Jessica , De Vos Ruth , Wiffen Laura , Hicks Alexander , Rupani Hitasha , Williams Jane , Brown Thomas , Chauhan Anoop J 
Published: July 2021

Background
More than 7% of the world’s population is living with a chronic respiratory condition. In the United Kingdom, lung disease affects approximately 1 in 5 people, resulting in over 700,000 hospital admissions each year. People with respiratory conditions have several symptoms and can require multiple health care visits and investigations before a diagnosis is made. The tests available can be difficult to perform, especially if a person is symptomatic, leading to poor quality results. A new, easy-to-perform, point-of-care test that can be performed in any health care setting and that can differentiate between various respiratory conditions would have a significant, beneficial impact on the ability to diagnose respiratory diseases.

Objective
The objective of this study is to use a new handheld device (Inflammacheck) in different respiratory conditions to measure the exhaled breath condensate hydrogen peroxide (EBC H2O2) and compare these results with those of healthy controls and with each other. This study also aims to determine whether the device can measure other parameters, including breath humidity, breath temperature, breath flow dynamics, and end tidal carbon dioxide.

Methods
We will perform a single-visit, cross-sectional observational study of EBC H2O2 levels, as measured by Inflammacheck, in people with respiratory disease and volunteers with no known lung disease. Participants with a confirmed diagnosis of asthma, chronic obstructive pulmonary disease, lung cancer, bronchiectasis, pneumonia, breathing pattern disorder, and interstitial lung disease as well as volunteers with no history of lung disease will be asked to breathe into the Inflammacheck device to record their breath sample.

Results
The results from this study will be available in 2022, in anticipation of COVID-19–related delays.

Conclusions
This study will investigate the EBC H2O2, as well as other exhaled breath parameters, for use as a future diagnostic tool.
SIMVASTATIN-LOADED NANOCAPSULES REDUCE TNF-Α EXPRESSION IN RAT PERITONEUM AFTER INFUSION OF PERITONEAL DIALYSIS SOLUTION
Authors: BARONI GILBERTO , FERRONATTO MYLENA FERNANDA , CAMARGO GUILHERME DOS ANJOS , LYRA AMANDA MARTINEZ , RECHE PÉRICLES MARTIM , NADAL JESSICA MENDES , NOVATSKI ANDRESSA , LIPINSKI LEANDRO CAVALCANTE , VITOR FARAGO PAULO 
Published: July 2021

Objective: Obteinment and characterizing polymeric nanocapsules of simvastatin (SV), and investigating their action in an experimental model of peritoneal fibrosis induced in a rat by the infusion of peritoneal dialysis (PD) solution.
Methods: Poly (ε-caprolactone) nanocapsules containing SV (NC-SV) were prepared by interfacial deposition of a preformed polymer. A suspension of nanoparticles with no drug was prepared as negative control. The average particle size and polydispersity index were measured by photon correlation spectroscopy. The morphological and surface evaluation of prepared nanocapsules was performed using field emission scanning electron microscopy. The ultra-high performance liquid chromatography with photodiode array detection method was used to evaluate the drug encapsulation efficiency. The release profiles of SV from polymeric nanocapsules were obtained by dialysis diffusion technique. The Animal Study was performed in a total of 48 male Wistar rats (Rattus norvegicus) divided in four groups: Sham, PD group, SV group, and Simvastatin-loaded nanocapsules group (NC-SV). After 28 days, tissue samples were surgically removed from the abdominal to perform histological and immunohistochemistry analysis. The statistical analysis was performed by one-way ANOVA followed by Bonferroni test, or by Kruskal–Wallis.
Results: NC-SV presented suitable particle parameters with a mean particle size of 332 nm, and an encapsulation efficiency of 99.87±0.46%. The expression of tumor necrosis factor-alpha (TNF-α) was significantly different in NC-SV group.
Conclusion: SV-loaded nanocapsules for controlled drug delivery were suitably prepared. This nanoformulation remarkable decreased the TNF-α tissue expression even at low SV dose in a chronic PD model.
COMPARISON OF PREGABALIN AND NORTRIPTYLINE ON EFFICACY AND SAFETY IN POSTHERPETIC NEURALGIA
Authors: KHAJURIA KANIKA , GUPTA SEEMA , DOGRA DEV RAJ , KUMAR DINESH , KHAJURIA VIJAY 
Published: July 2021

Objectives: Antidepressants and anticonvulsants are most commonly prescribed in postherpetic neuralgia (PHN). The aim of the present study was to compare the efficacy and safety of pregabalin and nortriptyline in patients of PHN.
Methods: The present study was conducted in 48 patients of PHN attending outpatient department of Dermatology, GMC Jammu. After obtaining written consent, the enrolled patients were randomized into two groups, one group was given pregabalin 150 mg orally per day, and other group was treated with nortriptyline 25 mg orally per day and were followed up to 8 weeks. Patients were assessed on numerical rating scale (NRS), Leeds assessment of neuropathic symptoms and signs (LANSS). Safety of the drugs was monitored by adverse drug reactions (ADRs).
Results: All patients were over 57 years and thoracic dermatome was most affected. Both drugs significantly reduced NRS and LANSS (p<0.0001). However, on comparison pregabalin was found to be better than nortriptyline at 8 weeks on mean NRS (p= 0.0073), LANSS (p=0.0032). Total of six mild ADRs occurred, two in group pregabalin and four in nortriptyline treated group.
Conclusion: Both pregabalin and nortriptyline were effective in patients of PHN, but pregabalin was found to be better than nortriptyline at 8 weeks. Both drugs were well tolerated, though pregabalin had lesser number of ADRs.
The Effect of CEO Tenure, Capital Intensity, and Firm Size On Tax Avoidance
Authors: Evi Khusnita Ulfa  , Suprapti Eny , Latifah Sri Wahjuni 
Published: July 2021

The aim of this study is to examine the effect of CEO tenure, capital intensity, and firm size on tax avoidance. The sample of this study is 88 companies listed in Indonesia Stock Exchange (IDX) in 2019 were selected through purpose sampling. The data analysis technique used in this study is multiple linear regression analysis. The results of the analysis show that CEO tenure has a positive effect on tax avoidance. This means that the longer the CEO tenure will lead to an increase in tax avoidance. Capital intensity and firm size have no effect on tax avoidance. This research has a novelty in the form impact of CEO tenure, capital intensity, and firm size on tax avoidance. Furthermore, the practical contribution to the government, especially the Directorate General of Taxes, is that long tenure of CEO can lead to tax avoidance. The limitation in this study is the number of samples is less representative in representing the population. This is because there are still companies listed on the IDX that not provide information according to the sample criteria.