bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: A Perspective on the Role of PPT1 Enzyme
Authors: Duarte Diana , Vale Nuno 
Published: November 2021

:
Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer
cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important
role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its
derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon,
etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and
chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here,
we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial
agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin
(mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes
in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases
the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of
antimalarial and antineoplastic agents in cancer cells.
Insulin Resistance is Associated with Clinical Manifestations of Diabetic
Kidney Disease (Glomerular Hyperfiltration, Albuminuria, and Kidney
Function Decline)
Authors: Adeva-Andany María M. , Fernández-Fernández Carlos , Funcasta-Calderón Raquel , Ameneiros-Rodríguez Eva , Adeva-Contreras Lucía , Castro-Quintela Elvira 
Published: November 2021

:
Clinical features of diabetic kidney disease include glomerular hyperfiltration, albuminuria,
and kidney function decline towards End-Stage Kidney Disease (ESKD). There are presently
neither specific markers of kidney involvement in patients with diabetes nor strong predictors of
rapid progression to ESKD. Serum-creatinine-based equations used to estimate glomerular filtration
rate are notoriously unreliable in patients with diabetes. Early kidney function decline, reduced
glomerular filtration rate, and proteinuria contribute to identifying diabetic patients at higher risk
for rapid kidney function decline. Unlike proteinuria, the elevation of urinary albumin excretion in
the range of microalbuminuria is frequently transient in patients with diabetes and does not always
predict progression towards ESKD. Although the rate of progression of kidney function decline is
usually accelerated in the presence of proteinuria, histological lesions of diabetes and ESKD may
occur with normal urinary albumin excretion. No substantial reduction in the rate of ESKD associated
with diabetes has been observed during the last decades despite intensified glycemic control
and reno-protective strategies, indicating that existing therapies do not target underlying pathogenic
mechanisms of kidney function decline. Very long-term effects of sodium-glucose transporters-
2 inhibitors and glucagon-like peptide-1 analogs remain to be defined. In patients with diabetes,
glucagon secretion is typically elevated and induces insulin resistance. Insulin resistance is
consistently and strongly associated with clinical manifestations of diabetic kidney disease, suggesting
that reduced insulin sensitivity participates in the pathogenesis of the disease and may represent
a therapeutic objective. Amelioration of insulin sensitivity in patients with diabetes is associated
with cardioprotective and kidney-protective effects.
Female Sexual Dysfunction in Diabetes: Mechanisms, Diagnosis and Treatment
Authors: Di Stasi Vincenza , Maseroli Elisa , Vignozzi Linda 
Published: November 2021

:Female sexual dysfunction (FSD) is an underinvestigated comorbidity of diabetes mellitus, often not evaluated in diabetes clinics. Diabetic women should be encouraged to talk about this topic by their diabetologist, because these problems could be comorbid to cardio-metabolic alterations, as it happens in the male counterpart. This review summarizes evidence on sexual dysfunction characteristics in diabetic women, exploring possible underlying pathogenic mechanisms. The role of hypoglycemic drugs in this context was also evaluated. To date, no specific questionnaire has been designed for the assessment of sexual dysfunctions in diabetic female patients but the use of colour-doppler ultrasound of clitoral arteries has been highlighted as a useful tool for the assessment of cardiovascular risk in these women. Similarly, no specific guidelines are available for the treatment of FSD in the diabetic population but patients should be supported to have a healthy lifestyle and, in the absence of contraindications, can benefit from already approved treatments for FSD.
Impact of Several Factors on the Diagnostic Interpretability of Coronary Computed Tomographic Angiography Using a 256-Detector Row CT Scanner
Authors: Xu Lixue , Luo Nan , He Yi , Yang Zhenghan 
Published: November 2021

Objective:
This study aimed at exploring the impact of patient-related, vessel-related, image
quality-related and cardiovascular risk factors on coronary computed tomographic angiography
(CCTA) interpretability using 256-detector row computed tomography (CT).

Methods:
One hundred ten patients who underwent CCTA and Invasive Coronary Angiography (ICA)
were consecutively, retrospectively enrolled from January 2018 to October 2018. Using ICA
as the reference standard, ≥50% diameter stenosis was defined as the cut-off criterion to detect the
diagnostic performance of CCTA. Diagnostic reproducibility was investigated by calculating the interrater
reproducibility of CCTA. Multiple logistic regression models were performed to evaluate
the impact of 14 objective factors.

Results:
A total of 1019 segments were evaluated. The per-segment sensitivity, specificity, accuracy,
positive predictive value, and negative predictive value of CCTA were 76.8%, 93.7%, 91.2%,
67.8%, and 95.9%, respectively. The per-segment diagnostic reproducibility was 0.44 for CCTA.
Regarding accuracy, a negative association was found for stenosis severity, calcium load, and hyperlipidaemia.
Regarding sensitivity, calcium load and diabetes mellitus (DM) were positively related.
Regarding specificity, a negative correlation was observed between stenosis severity and calcium
load. Regarding interrater reproducibility, stenosis severity and calcium load were negatively
associated, whereas male sex and the signal-to-noise ratio (SNR) were positively related (all
p<0.05).

Conclusion:
Per-segment 256-detector row CCTA performance was optimal in stenosis-free or occluded
segments. Heavier calcium load was associated with poorer CCTA interpretability. On the
one hand, our findings confirmed the rule-out value of CCTA; on the other hand, improvements in
calcium subtractions and deep learning-based tools are suggested to improve CCTA diagnostic interpretability.
Breast MRI for Evaluating Residual Tumor Size Following Neoadjuvant
Chemotherapy: Clinicopathologic Factors and MRI Imaging Features Affecting
its Accuracy
Authors: Park Jin Young , Kim Young Seon , Lee Seung Eun 
Published: November 2021

Objectives:
The aim of the study was to investigate the accuracy of breast magnetic resonance
imaging (MRI) for evaluating residual tumor size following neoadjuvant chemotherapy
(NAC) and to identify clinicopathologic and MRI features affecting its accuracy.

Materials and Methods:
We retrospectively assessed 109 women who underwent preoperative dynamic
contrast-enhanced (DCE) MRI following NAC and subsequent surgery between April 2016
and August 2020. Preoperative MRI features, including Breast Imaging Reporting and Data System
lexicon characteristics, size of residual enhancing lesion, tumor shrinkage pattern, and clinicopathologic
features, were investigated, and MRI and pathology findings were compared.

Results:
Residual tumor size on MRI showed high agreement with residual invasive tumor size on
pathologic examination (ICC, 0.808, p<0.001). The residual tumor size measured by MRI and final
pathologic size were concordant in 63/109 cases (57.8%), while MRI overestimated the size in
35/109 cases (32.1%). For estrogen receptor (ER)-positive/human epidermal growth factor receptor
2 (HER2)-negative tumors, MRI tended to underestimate the residual tumor size compared with
HER2-positive cancers (p=0.002) and triple-negative cancers (p=0.12). On MRI, tumors with concentric
shrinkage patterns after NAC showed less size discrepancy with final pathologic tumor size
than those with non-concentric patterns (p=0.026).

Conclusion:
In ER-positive/HER2-negative cancers, MRI tends to underestimate the residual tumor
size, compared to in other subtypes. Tumors with concentric shrinkage patterns after NAC
showed less MRI/pathology size discrepancy.
Viral Encephalitis in Adults: A Narrative Review
Authors: Siciliano Valentina , Rosà Tommaso , Del Vecchio Pierluigi , D'Angelillo Anna , Brigida Mattia , Longhitano Yaroslava , Zanza Christian , Santoro Michele Cosimo , Candelli Marcello , Franceschi Francesco , Piccioni Andrea 
Published: November 2021

:
Viral infections of the central nervous system cause frequent hospitalization. The pathogenesis
of viral encephalitis involves both the direct action of invading pathogens and the damage
generated by the inflammatory reaction they trigger. The type of signs and symptoms presented by
the patient depends on the severity and location of the ongoing inflammatory process. Most of the
viral encephalitides are characterized by an acute development, fever, variable alterations in consciousness
(confusion, lethargy, even coma), seizures (focal and generalized) and focal neurologic
signs. The specific diagnosis of encephalitis is usually based on lumbar puncture. Cerebrospinal
fluid examination should be performed in all patients unless absolutely contraindicated. Also, electroencephalogram
and neuroimaging play a prominent role in diagnosis. Airway protection, ventilatory
support, the management of raised intracranial pressure and correction of electrolyte disorders
must be immediately considered in a patient with altered mental status. The only therapy strictly recommended
is acyclovir in HSV encephalitis. The use of adjunctive glucocorticoids has poor-quality
evidence in HSV, EBV, or VZV encephalitis. The role of antiviral therapy in other types of viral
encephalitis is not well defined.
Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole
linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors
Authors: Bawa Sandhya , Shalmali Nishtha , Ali Md Rahmat , Kalra Sourav , Kumar Raj , Zeya Bushra , Rizvi Moshahid Alam , Partap Sangh , Husain Asif 
Published: November 2021

Background:
Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing
biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity
of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of
isatin nucleus against various cancer cell lines.

Aims and Objectives:
A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized
as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib,
sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate
and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity.

Methods:
The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles
using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a
panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed
to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a,
5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme-
Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell
line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using
annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified.

Results:
Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines
with MID GI50 values of 1.69 and 1.54 μM, respectively. Also, both the lead compounds 5a and 5g demonstrated
promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 μM, respectively. The aforesaid
potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 μM
and 106.91 μM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic
cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed
promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores -
9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five.

Conclusion:
Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for
developing promising kinase inhibitors as cancer therapeutics.
Beneficial Effect of Saharan Propolis on Glucose Metabolism in Streptozotocin-
induced Diabetic Rats
Authors: Akdad Mourad , Azzaoui Bouchra , Eddouks Mohamed 
Published: November 2021

Aims:
The aim of the study was to evaluate the antihyperglycemic activity of propolis
from Saharan region of Morocco.

Background:
Propolis is known from ancient times for its beneficial action on health.

Objective:
The study aimed to evaluate the effect of Moroccan propolis aqueous extract from the
desert region on glycemia and lipid metabolism.

Methods:
The antihyperglycemic and antidyslipidemic activities of Moroccan propolis aqueous extract
were evaluated in streptozotocin-induced diabetic rats. Glycemia was monitored during acute
(6h) and subchronic treatments. Histopathological analysis of the liver and the serum lipid profile
was also evaluated in addition to the glucose tolerance.

Results:
This work demonstrated that the aqueous extract of Moroccan propolis exhibited a significant
antihyperglycemic effect in diabetic rats. Histopathological data demonstrated that propolis
acts positively on the liver of diabetic rats. In addition, the preliminary phytochemical screening revealed
that Moroccan propolis contains several phytochemicals. Finally, Moroccan propolis had a
potent antioxidant activity which may be due to the richness in polyphenols content (90.91 mg
EAG/1 g of extract).

Conclusion:
The present study shows that Moroccan propolis from the hot desert region possesses
a potent antihyperglycemic effect.
Workload as the most Important Influencing Factor of Medication Errors by Nurses
Authors: Ratanto  , Hariyati Rr. Tutik Sri , Mediawati Ati Surya , Eryando Tris 
Published: November 2021

Background:
This research is motivated by the fact that medication errors are serious threats to the safety of patients in hospitals. Nurses are one of the health workers who play a significant role in preventing these errors.

Objective:
The aim of this quantitative research is to determine the factors that influence the incidence of medication errors by nurses.

Methods:
The adopted method had a correlative descriptive design and used samples obtained from 164 nurses through a purposive sampling technique. The sample inclusion criteria were the nurses who worked in patient’s rooms, those who were healthy and not sick, not currently in school, and were willing to be respondents. Furthermore, the research instruments were questionnaires, which were developed through the Cronbach's alpha validity and reliability test results of 0.681 and 0.873, respectively. Analysis was conducted using the independent t test, X2 (chi-square) and multiple logistic regressions.

Results:
The results showed that the factors which influenced the incidence of medication errors were work experience, motivation, workload, managerial and environmental elements. Moreover, the variable which contributed the most, with a p-value of 0.004 and OR of 5.387 was workload.

Conclusion:
Finally, the following factors, including nurse's workload, motivation, work experience, good managerial management and environmental elements, should be considered when preventing medication errors.
Reductive Dehalogenation – Challenges of Perfluorinated Organics
Authors: Kisała Joanna , Goclon Jakub , Pogocki Dariusz 
Published: November 2021

:
In this mini-review, the problem of effective elimination of perfluorinated organic micropollutants
from aquatic environment has been touched. The extraordinary chemical stability of common
perfluorinated organic surfactants results in unsatisfactory efficiency of conventional treatment
processes, which opens perspectives for photocatalytic methods - especially for reductivedehalogenation.
To tackle this challenge by photocatalysis one have to be aware of objective, physical
limits set by very nature of the reduction process, electronic structure chemical stability, and formulation
of the catalyst as well as emission characteristic of the light source. The paper provides some
clues for rational design of reductive-dehalogenation oriented photolytic systems, which are derived
on the basis of physical principles, and, rather sparse, experimental examples.
Analytical Methods for the Quantification of Selenium Species in Biological
Matrix: Where are We?
Authors: Gaucher Caroline , Alhasan Rama , Perrin-Sarrado Caroline , Jacob Claus 
Published: November 2021

Objective:
Over the years, scientific investigations have proven the importance of selenium
as an essential element for mammals, emphasizing its activity against many diseases and even
its prophylactic effects. It is also established now that a malconsumption of selenium can be harmful.
Therefore, the nature and the concentration of selenium and its derivatives found in the diet,
the body, and even in the environment, for example, in the soil, should be determined carefully.

Methods:
In this review, analytical methods for speciation and determination of selenium concentrations
in biological samples are summarized.

Results:
Methods ranging from routine to cutting-edge are explored, focusing on their analytical
characteristics, such as specificity for discrete selenium species, sensitivity, accuracy, reproducibility,
and skills required.

Conclusion:
There are already numerous studies regarding the analysis of selenium species. Beyond
the method employed for actual measurements, we propose to review the preanalytic steps
for sample handling in biological matrices, which directly affect results that will be more accurate
with careful pretreatment. Furthermore, to reach better outcomes in terms of the identification of selenium
species, different combinations of techniques might be the answer. We highlight here the
last and the cutting-edge methods to identify and quantify selenium such as, high-performance
liquid chromatography combined to inductively coupled plasma mass spectrometry (HPLC-ICP-MS),
hydride generation atomic absorption spectrometry (HG-AAS), hydride-generation combined
to atomic fluorescence spectrometry (HG-AFS), or to inductively coupled plasma optical emission
spectrometry (HG-ICP-OES). This review emphasizes the importance of such investigations and
the need to achieve reliable, safe, and effective quantification and methods of determination.
The russification legacy of historical monuments of Uzbekistan
Authors: Yusupov Otabek Yakubovich 
Published: November 2021

This article illustrates the naming convention of historical monuments by the Russian Empire and the Soviet Union in Uzbekistan. The Russification is a form of cultural assimilation during which the non-Russian communities whether voluntary or involuntary gave up their culture or statehood or language in favor of the Russian culture. Undeniably, the Russification in the naming convention of Uzbekistan’s historical monuments still bears its legacy. For instance, the names of archaeological finding on the territories of Selengur—Kulbulak and Teshiktash—pronounced in the Russian phonetics rather than Uzbek. Rather, Kulbulak is ought to be spelled Qulbuloq; and, Teshiktash—Teshiktosh.
Aprendizagem escolar e ação pedagógica diante das dificuldades na escolarização de crianças de anos iniciais
Authors: Baum Virginia Dornelles , Rozek Marlene 
Published: November 2021

O presente artigo versa sobre uma pesquisa realizada em uma escola pública da rede federal brasileira, que se detinha a investigar de que forma ocorre a aprendizagem das crianças dos anos iniciais do ensino fundamental, as quais enfrentavam dificuldades escolares, mediante uma ação pedagógica específica. Foi utilizado como método a pesquisa qualitativa sob forma de pesquisa-ação e, como metodologia de análise, a análise textual discursiva. Para discussão dos dados, foram adotadas as principais referências da Psicopedagogia, e da ludicidade. Salienta-se que o achado de maior destaque na pesquisa refere-se à percepção de que a superação das dificuldades escolares das crianças participantes ocorreu à medida que iam modificando o lugar simbólico que ocupavam perante si, a tarefa e seus pares: do lugar da impossibilidade ou da não possibilidade, para o reconhecimento de sua capacidade. Nesse processo, fatores como as características de organização da ação, pautada pela perspectiva lúdica, e a sustentação emocional dada aos participantes foram fundamentais para a conclusão da tarefa, revelando grandes desafios que estão implicados na docência.
External Factors and the Pricing of Audit Services: A Systematic Review of the Archival Literature Using a PESTLE Analysis
Authors: Eierle Brigitte , Hartlieb Sven , Hay David C. , Niemi Lasse , Ojala Hannu 
Published: November 2021

SUMMARY
Client- and auditor-related attributes are well-documented determinants of audit pricing, but the number of empirical archival studies investigating the effects of external factors on audit pricing has grown rapidly in recent years. We extend the traditional framework used to classify audit fee research by adding a novel structure that focuses on political, economic, social, technological, legal, and environmental/ecological factors (a PESTLE analysis). We provide a systematic review of the literature on external factors and audit pricing, and we suggest opportunities for future research. Our review reveals that audit researchers focus on legal factors in terms of regulatory changes, and we find increased attention to political, economic, and social factors. However, despite increased public scrutiny, technological and environmental/ecological factors remain under-researched. Overall, our review demonstrates the importance of considering external factors to gain a more complete understanding of the audit pricing framework, especially in terms of global and regional variations.
JEL Classifications: M40; M42.