bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanotherapeutics and Nanotheragnostics for Cancers: Properties, Pharmacokinetics, Biopharmaceutics, and Biosafety
Authors: Morsink Margreet , Parente Lucia , Silva Fernanda , Abrantes Alexandra , Ramos Ana , Primo Inês , Willemen Niels , Sanchez-Lopez Elena , Severino Patricia , Souto Eliana B. 
Published: August 2021

:With the increasing worldwide rate of chronic diseases, such as cancer, the development of novel techniques to improve the efficacy of therapeutic agents is highly demanded. Nanoparticles are especially well suited to encapsulate drugs and other therapeutic agents, bringing additional advantages, such as less frequent dosage requirements, reduced side effects due to specific targeting, and therefore increased patient compliance. However, with the increasing use of nanoparticles and their recent launch on the pharmaceutical market, it is important to achieve high-quality control of these advanced systems. In this review, we discuss the properties of different nanoparticles, the pharmacokinetics, the biosafety issues of concern, and conclude with novel nanotherapeutics and nanotheragnostics for cancer drug delivery.
A Systematic Review of Functionalized Polymeric Nanoparticles to Improve Intestinal
Permeability of Drugs and Biological Products
Authors: de Souza Myla Lôbo , de Albuquerque Wanderley Sales Victor , Alves Larissa Pereira , dos Santos Widson Michael , de Moura Ferraz Leslie Raphael , de Andrade Lima Gustavo Siqueira , dos Santos Mendes Larissa Morgana , Rolim Larissa Araújo , Neto Pedro José Rolim 
Published: August 2021

Background:
The oral route is the most frequently used and the most convenient route of drug administration
since it has several advantages, such as ease of use, patient compliance, and better costeffectiveness.
However, physicochemical and biopharmaceutical limitations of various active pharmaceutical
ingredients (API) hinder suitability for this route, including degradation in the gastrointestinal tract, low intestinal
permeability, and low bioavailability. To overcome these problems, while maintaining therapeutic efficacy,
polymeric nanoparticles have attracted considerable attention for their ability to increase drug solubility, promote
the controlled release, and improve stability. In addition, the functionalization of nanocarriers can increase
uptake and accumulation at the target site of action, and intestinal absorption, making it possible to obtain more
viable, safe and efficient treatments for oral administration.

Objective:
This systematic review aimed to seek recent advances in the literature on the use of polymeric nanoparticles
functionalization to increase intestinal permeability of APIs that are intended for oral administration.

Method:
Two bibliographic databases were consulted (PubMed and ScienceDirect). The selected publications
and the writing of this systematic review were based on the guidelines mentioned in the PRISMA statement.

Results:
Out of a total of 3036 studies, 22 studies were included in this article based on our eligibility criteria. The
results were consistent for the application of nanoparticle functionalization to increase intestinal permeability.

Conclusion:
The functionalized polymeric nanoparticles can be considered as carrier systems that improve the
intestinal permeability and bioavailability of APIs, with the potential to result, in the future, in the development
of oral medicines.
Metabolomic Connections between Schizophrenia, Antipsychotic Drugs and Metabolic Syndrome: A Variety of Players
Authors: Molina Juan D. , Avila Sonia , Rubio Gabriel , López-Muñoz Francisco 
Published: August 2021

Background:
Diagnosis of schizophrenia lacks reliable medical diagnostic tests and robust biomarkers
applied to clinical practice. Schizophrenic patients undergoing treatment with antipsychotics suffer
reduced life expectancy due to metabolic disarrangements that co-exist with their mental illness and predispose
them to develop metabolic syndrome, which is also exacerbated by medication. Metabolomics is an emerging
and potent technology able to accelerate this biomedical research.

Aim:
This review focus on a detailed vision of the molecular mechanisms involved both in schizophrenia and
antipsychotic-induced metabolic syndrome, based on innovative metabolites that consistently change in nascent
metabolic syndrome, drug-naïve, first episode psychosis and/or schizophrenic patients compared to healthy subjects.

Main Lines:
Supported by metabolomic approaches, although not exclusively, noteworthy variations are reported
mainly through serum samples of patients and controls in several scenes: 1) alterations in fatty acids, inflammatory
response indicators, amino acids and biogenic amines, biometals, and gut microbiota metabolites
(schizophrenia); 2) alterations in metabolites involved in carbohydrate and gut microbiota metabolism, inflammation
and oxidative stress (metabolic syndrome), some of them shared with schizophrenia; 3) alterations of
cytokines secreted by adipose tissue, phosphatidylcholines, acylcarnitines, Sirtuin 1, orexin-A, and changes in
microbiota composition (antipsychotic-induced metabolic syndrome).

Conclusion:
Novel insights into the pathogenesis of schizophrenia and metabolic side-effects associated with
its antipsychotic treatment represent an urgent request for scientists and clinicians. Leptin, carnitines, adiponectin,
insulin, or interleukin-6 represent some examples of candidate biomarkers. Cutting-edge technologies like
metabolomics have the power to strengthen research for achieving preventive, diagnostic, and therapeutical solutions
for schizophrenia.
DHODH Hot Spots: An Underexplored Source to Guide Drug Development Efforts
Authors: Froes Thamires Quadros , Zapata Luana Carlos Campisano , Akamine Juliana Sayuri , Castilho Marcelo Santos , Nonato Maria Cristina 
Published: August 2021

Background:
Dihydroorotate dehydrogenase (DHODH) has long been recognized as an
important drug target for proliferative and parasitic diseases, including compounds that exhibit trypanocidal
action and broad-spectrum antiviral activity. Despite numerous and successful efforts in
structural and functional characterization of DHODHs, as well as in the development of inhibitors,
DHODH hot spots remain largely unmapped and underexplored.

Objective:
This review describes the tools that are currently available for the identification and
characterization of hot spots in protein structures and how freely available webservers can be exploited
to predict DHODH hot spots. Moreover, it provides for the first time a review of the antiviral
properties of DHODH inhibitors.

Method:
X-ray structures from human (HsDHODH) and Trypanosoma cruzi DHODH
(TcDHODH) had their hot spots predicted by both FTMap and Fragment Hotspot Maps web
servers.

Result:
FTMap showed that hot spot occupancy in HsDHODH is correlated with the ligand efficiency
(LE) of its known inhibitors, and Fragment Hotspot Maps pointed out the contribution of selected
moieties to the overall LE. The conformational flexibility of the active site loop in
TcDHODH was found to have a major impact on the druggability of the orotate binding site. In addition,
both FTMap and Fragment Hotspot Maps servers predict a novel pocket in TcDHODH
dimer interface (S6 site).

Conclusion:
This review reports how hot spots can be exploited during hit-to-lead steps, docking
studies or even to improve inhibitor binding profile and by doing so using DHODH as a model,
points to new drug development opportunities.
Topomer CoMFA and HQSAR Study on Benzimidazole Derivative as
NS5B Polymerase Inhibitor
Authors: Jian-Bo Tong , Xing Zhang , Shuai Bian , Ding Luo , Tian-Hao Wang 
Published: August 2021

Background:
In recent years, the number of people infected with the hepatitis C virus
(HCV) is increasing rapidly. This has become a major threat to global health, therefore, new anti-
HCV drugs are urgently needed. HCV NS5B polymerase is an RNA-dependent RNA polymerase
(RdRp), which plays an important role in virus replication, and can effectively prevent the replication
of HCV sub-genomic RNA in daughter cells. It is considered a very promising HCV therapeutic
target for the design of anti-HCV drugs.

Methods:
In order to explore the relationship between the structure of benzimidazole derivative and
its inhibitory activity on NS5B polymerase, holographic quantitative structure-activity relationship
(HQSAR) and Topomer comparative molecular field analysis (CoMFA) were used to establish benzimidazole
QSAR model of derivative inhibitors.

Results:
The results show that for the Topomer CoMFA model, the cross-validation coefficient q2
value is 0.883, and the non-cross-validation coefficient r2 value is 0.975. The model is reasonable,
reliable, and has a good predictive ability. For the HQSAR model, the cross-validated q2 value is
0.922, and the uncross-validated r2 value is 0.971, indicating that the model data fit well and has a
high predictive ability. Through the analysis of the contour map and color code diagram, 40 new
benzimidazole inhibitor molecules were designed, and all of them have higher activity than template
molecules, and the new molecules have significant interaction sites with protein 3SKE.

Conclusion:
The 3D-QSAR model established by Topomer CoMFA and HQSAR has good prediction
results and the statistical verification is valid. The newly designed molecules and docking results
provide theoretical guidance for the synthesis of new NS5B polymerase inhibitors and for the identification
of key residues that the inhibitors bind to NS5B, which helps to better understand their inhibitory
mechanism. These findings are helpful for the development of new anti-HCV drugs.
Anti-evolution Drugs: A New Paradigm to Combat Drug Resistance
Authors: Peraman Ramalingam , Chinni Santhivardhan , Sure Sathish Kumar , Kutagulla Vinay Kumar , Peraman Muthukumaran , V.N. Azger , Y. Padmanabha Reddy 
Published: August 2021

:
Drug resistance confronts chemotherapy of neoplasm and microbial infections. A vast
array of molecular mechanisms was implicated in drug resistance, including generation of drug efflux
transporters, mutation of drug targets, and alteration of drug metabolism. With the alarming rate
of increase in drug resistance, pathogens are bolstering in such a way that many new drugs face efficacy
problems within a short span of entry into the market. Evolution is the driving force towards the
development of drug resistance. By adopting the modern genomic and functionomic analytical techniques,
scientists have now identified novel genes and signalling proteins involved in the evolution
of drug resistance in microorganisms. Given the current knowledge of bacterial evolution, antibiotic
drug discovery is ready for a paradigm shift to explore the newer ways to tackle drug resistance. The
article discusses such recent developments and reviews their merits and demerits in an attempt to
envisage the findings in this new domain of medicine.
Beyond Ejection Fraction: Novel Clinical Approaches Towards Sudden
Cardiac Death Risk Stratification in Patients with Dilated Cardiomyopathy
Authors: Pour-Ghaz Issa , Heckle Mark , Ifedili Ikechukwu , Kayali Sharif , Nance Christopher , Kabra Rajesh , Jha Sunil K. , Jefferies John L. , Levine Yehoshua C. 
Published: August 2021

:
Implantable Cardioverter-Defibrillator (ICD) therapy is indicated for patients at risk for
sudden cardiac death due to ventricular tachyarrhythmia. The most commonly used risk stratification
algorithms use Left Ventricular Ejection Fraction (LVEF) to determine which patients qualify
for ICD therapy, even though LVEF is a better marker of total mortality than ventricular tachyarrhythmias
mortality. This review evaluates imaging tools and novel biomarkers proposed for better
risk stratifying arrhythmic substrate, thereby identifying optimal ICD therapy candidates.
Robust Engineering-based Unified Biomedical Imaging Framework for
Liver Tumor Segmentation
Authors: Nguyen Hien , Pham Vuong , Nguyen Hai , Pham Bao , Nguyen Thien 
Published: August 2021

Background:
Computer vision in general and semantic segmentation has experienced
many achievements in recent years. Consequently, the emergence of medical imaging has provided
new opportunities for conducting artificial intelligence research. Since cancer is the second-leading
cause of death in the world, early-stage diagnosis is an essential process that directly slows down
the development speed of cancer.

Methods:
Deep neural network-based methods are anticipated to reduce diagnosis time for pathologists.

Results:
In this research paper, an approach to liver tumor identification based on two types of medical
images has been presented: computed tomography scans and whole-slide. It is constructed
based on the improvement of U-Net and GLNet architectures. It also includes sub-modules that are
combined with segmentation models to boost up the overall performance during inference phases.

Conclusion:
Based on the experimental results, the proposed unified framework has been emerging
to be used in the production environment.
Stem Cells in Mammary Health and Milk Production
Authors: Choudhary Ratan K . , Zhao Feng-Qi 
Published: August 2021

:
Adult stem cells like mammary and mesenchymal stem cells have received significant attention
because these stem cells possess therapeutic potential in treating many animal diseases. These
cells can be administered in an autologous or allogenic fashion, either freshly isolated from the
donor tissue or previously cultured and expanded in vitro. The expansion of adult stem cells is a prerequisite
before therapeutic application because sufficient numbers are required in dosage calculation.
Stem cells directly and indirectly (by secreting various growth factors and angiogenic factors
called secretome) act to repair and regenerate injured tissues. Recent studies on mammary stem
cells showed in vivo and in vitro expansion ability by removing the blockage of asymmetrical cell
division. Compounds like purine analogs (xanthosine, xanthine, and inosine) or hormones (progesterone
and bST) help increase stem cell population by promoting cell division. Such methodology
of enhancing stem cell number, either in vivo or in vitro, may help in preclinical studies for translational
research like treating diseases such as mastitis. The application of mesenchymal stem cells
has also been shown to benefit mammary gland health due to the ‘homing’ property of stem cells.
In addition to that, the multiple positive effects of stem cell secretome are on mammary tissue; healing
and killing bacteria is novel in the production of quality milk. This systematic review discusses
some of the studies on stem cells that have been useful in increasing the stem cell population and
increasing mammary stem/progenitor cells. Finally, we provide insights into how enhancing mammary
stem cell population could potentially increase terminally differentiated cells, ultimately leading
to more milk production.
Pharmacological Basis of Breast Cancer Resistance to Therapies - An Overview
Authors: Crucitta Stefania , Cucchiara Federico , Sciandra Francesca , Cerbioni Annalisa , Diodati Lucrezia , Rafaniello Concetta , Capuano Annalisa , Fontana Andrea , Fogli Stefano , Danesi Romano , Re Marzia Del 
Published: August 2021

Abstract:Breast Cancer (BC) is a molecular heterogeneous disease and patients with similar clinico-pathological characteristics often display different response to treatment. Cellular processes, including uncontrolled cell-cycle, constitutive activation of signalling pathways and alterations in DNA-repair mechanisms are the main altered features in breast cancer. These cellular processes play significant roles in the emergence of resistance to therapies. The introduction of target therapies and immunotherapy significantly improved the survival of breast cancer patients. The incorporation of novel biomarkers together with the introduction of new therapeutic options may help to overcome treatment resistance. Molecular profiling promises to help in refine personalized treatment decisions and catalyse the development of further strategies when resistances inevitably occurs. This review provides a summary of genetic and molecular aspects of resistance mechanisms to available treatments for BC patients, and its clinical implications.
Pathological and Biochemical Index Changes in Different Tissues of Cyprinus carpio Exposed to Cadmium
Authors: Di Guilan , Li Yanfei , Li Hui , Chen Xinhua 
Published: August 2021

Background:
Cadmium (Cd) is among the most toxic metals and is widely distributed in
aquatic environments.

Objective:
Histopathological lesions and biochemical indices can be used to reflect the toxic effects
of cadmium in fish target organs.

Methods:
In the present study, the common carp Cyprinus carpio was exposed to 0.5 mg/L of CdCl2
for 21 days. Histopathological analyses were performed in the spleen, liver, kidney, gills and head
kidney tissues of C. carpio, and tissue sections were stained with hematoxylin-eosin (HE) and observed
under an optical microscope. The acid phosphatase, alkaline phosphatase, and lysozyme activities
were determined.

Results:
The results showed that there were various pathological changes in five major tissues of C.
carpio. The kidney, gills, and liver were the most affected organs during cadmium exposure, and
deformation and disorganization of epithelial cells, vacuolization formation, serious hemorrhages
and necrosis were also observed. In addition, 0.5 mg/L cadmium exposure significantly increased
serum lysozyme and acid phosphatase activities and inhibited alkaline phosphatase activity. The
present study showed that cadmium stress causes significant pathological tissue changes and influences
lysozyme, acid phosphatase and alkaline phosphatase activities in C. carpio. Acid phosphatase
and lysozyme activities are sensitive to cadmium.

Conclusion:
In conclusion, the toxicity of cadmium caused varying degrees of pathological and biochemical
changes in fish tissues in C. carpio.
PEGylated DPPC/Anti-SNAP25 Antibody Targeted Liposomes from Langmuir Monolayer Study to Formulations
Authors: Gew Lai Ti , Misran Misni 
Published: August 2021

Background:
Molecule compatibility is an important factor to be considered before preparing
antibody-targeted liposomes, stealth-liposomes, and stealth antibody-targeted liposomes.

Objective:
To determine the intermolecular interaction of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamide-
N-[methoxy(polyethyleneglycol)-2000] (ammonium salt), DOPE PEG2000 and Anti-SNAP25
(AS25) in 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) monolayer, and their liposomes.

Methods:
In this study, DPPC was used to create a monolayer mimicking the half membrane of liposomes
to investigate its interactions with a polyclonal antibody, AS25, and DOPE PEG2000,
which are based on Langmuir-Blodgett (LB) techniques. The surface morphology of DPPC-AS25
and DPPC-DOPE PEG2000-AS25 bilayers were also imaged and analyzed by using atomic force
microscopy (AFM) to support the LB findings. The LB findings were then utilized as a reference
to prepare DPPC liposomes in this work.

Results:
The best mole ratio of DPPC-DOPE PEG2000, determined to be 50 to 1, was used to
study the interaction with the polyclonal antibody AS25. The free energy of mixing (ΔGmix) of DPPC-
DOPE PEG2000-AS25 was more negative than DPPC-AS25 in the entire investigated ranges,
indicating that the ternary mixture of DPPC-DOPE PEG2000-AS25 was more compatible than the
binary mixture of DPPC-AS25. The presence of DOPE PEG2000 in DPPC-AS25 increased the
fluidity of the membrane, which resulted in a greater interaction of AS25 with DPPC.

Conclusion:
The constant values of particle size and zeta potential measurements of DPPC-DOPE
PEG2000-AS25 liposomes showed agreement with the LB findings, indicating that LB is a good
technique to predict precise liposomal formulations.
Una aproximación al senado colombiano desde la Biopolítica
Authors: García Gamboa Daniela Fernanda , Patiño Marin Luisa Fernanda 
Published: August 2021

Regarding biopolitics, it has adopted two contrasting meanings, one based on the philosopher Michael Foucault, which associated this concept with control, that is, how from political power human life can be structured and controlled. On the other hand, biopolitics have also been defined as a subdiscipline that has the basis of incorporating life sciences with political science, comparing the different phenomena and political behaviors based on biology, genetics, evolutionary theories, neurosciences, among others, aiming at a better understanding OF the various political phenomena. From the previous clarification the following article points out analyzing the Colombian Senate (2014 -2018) taking into account the biopolitical approach, examining the behavior of the political parties that have been taken part in, comparing it with different animal behaviors, with the aim of using a novel and poorly implemented perspective in the field of Political Science
A Semiautomated Chart Review for Assessing the Development of Radiation Pneumonitis Using Natural Language Processing: Diagnostic Accuracy and Feasibility Study
Authors: McKenzie Jordan , Rajapakshe Rasika , Shen Hua , Rajapakshe Shan , Lin Angela 
Published: August 2021

Background
Health research frequently requires manual chart reviews to identify patients in a study-specific cohort and examine their clinical outcomes. Manual chart review is a labor-intensive process that requires significant time investment for clinical researchers.

Objective
This study aims to evaluate the feasibility and accuracy of an assisted chart review program, using an in-house rule-based text-extraction program written in Python, to identify patients who developed radiation pneumonitis (RP) after receiving curative radiotherapy.

Methods
A retrospective manual chart review was completed for patients who received curative radiotherapy for stage 2-3 lung cancer from January 1, 2013 to December 31, 2015, at British Columbia Cancer, Kelowna Centre. In the manual chart review, RP diagnosis and grading were recorded using the Common Terminology Criteria for Adverse Events version 5.0. From the charts of 50 sample patients, a total of 1413 clinical documents were obtained for review from the electronic medical record system. The text-extraction program was built using the Natural Language Toolkit Python platform (and regular expressions, also known as RegEx). Python version 3.7.2 was used to run the text-extraction program. The output of the text-extraction program was a list of the full sentences containing the key terms, document IDs, and dates from which these sentences were extracted. The results from the manual review were used as the gold standard in this study, with which the results of the text-extraction program were compared.

Results
Fifty percent (25/50) of the sample patients developed grade ≥1 RP; the natural language processing program was able to ascertain 92% (23/25) of these patients (sensitivity 0.92, 95% CI 0.74-0.99; specificity 0.36, 95% CI 0.18-0.57). Furthermore, the text-extraction program was able to correctly identify all 9 patients with grade ≥2 RP, which are patients with clinically significant symptoms (sensitivity 1.0, 95% CI 0.66-1.0; specificity 0.27, 95% CI 0.14-0.43). The program was useful for distinguishing patients with RP from those without RP. The text-extraction program in this study avoided unnecessary manual review of 22% (11/50) of the sample patients, as these patients were identified as grade 0 RP and would not require further manual review in subsequent studies.

Conclusions
This feasibility study showed that the text-extraction program was able to assist with the identification of patients who developed RP after curative radiotherapy. The program streamlines the manual chart review further by identifying the key sentences of interest. This work has the potential to improve future clinical research, as the text-extraction program shows promise in performing chart review in a more time-efficient manner, compared with the traditional labor-intensive manual chart review.