bluuebunny/crossref_metadata_2025 huggingface dataset:
Ukrainian and Russian organizations in Sweden and the conflict “back home”
Authors: Voytiv Sofiya
Published: January 2020

This paper investigates whether the Maidan Revolution in Kyiv (late 2013–early 2014) and the ongoing armed conflict in Eastern Ukraine (early 2014) have been reflected in the collaboration networks of Ukrainian and Russian organizations in Sweden between 2013 and 2016.

I use ERG models to account for the probabilities of ties between the organizations, depending on the network structure and individual attributes such as ethnic identification and the choice of a side to support in the conflict.

Results suggest that it is support for a certain side in the conflict, and not ethnic self-identification, which drives the clustering of the networks during the most violent period.
The Implications of Good Governance of Village Government Office in Sidoarjo
Authors: Ambarwati Rita , Mudjib Affandy Winarko , Lestariana Fita Fitria , Handiwibowo Gogor Arif
Published: January 2020

This research examined determinant factors of good governance of a village government office in Sidoarjo. This research used a survey and a cross-section through a questionnaire as the data collection. The unit of analysis was the citizen who worked as a state civil apparatus and had used public services in a village government office. To determine the sample, the researchers used a simple random sampling. The data were analyzed using Structural Equation Modeling (SEM). The results show that the rule of law and responsiveness are dominant indicators to form good governance. However, transparency and good commitment are less dominant indicators in forming good governance. The practical implications of this research are useful for the local government as they need to increase the role of good governance in improving public service performance, especially for village service.
Employee Engagement Factors in A Higher Education Institution
Authors: Azmy Ahmad
Published: January 2020

This reseach analyzed factors that correlated with employee engagement in a higher education institution. The object of this research was the lecturers and employees with the total of 100 people. There were measured on how to produce academic quality accompanied by excellent service to students. Dimensions used were compensation, leadership and organizational planning, culture and corporate communication, job environment, supervisory relationships, employee satisfaction and training, development, and resources. The process of collecting data was through the questionnaires. The research method used Confirmatory Factor Analysis (CFA). In the results, all dimensions used have a significant influence on employee engagement because of p-values <0,05 and t-tables > t-statistics. The supervisor relationship dimension has the highest correlation of 66,5%, and employee satisfaction has the lowest correlation of 13,8%. Higher education institutions must increase employee engagement to maintain productivity and performance. Employee engagement is one of the keys to the success of educational institutions to produce exceptional academic quality and services for the entire academic community.
Halal Slaughterhouse Certification: The Comparison between Two Halal Certification Bodies
Authors: Artadita Sherly , Lestari Yuliani Dwi
Published: January 2020

This research aimed to provide information regarding the process and requirement of halal slaughterhouse certification implemented in halal certification bodies archival comparison research strategy by using the secondary data. It usedt he comparison of halal slaughterhouse certification process and requirement were conducted between two halal certification bodies, those were Lembaga Pengkajian Pangan, Obat-obatan, dan Kosmetika Majelis Ulama Indonesia (LPPOM MUI - The Assessment Institute for Foods, Drugs and Cosmetics Majelis Ulama Indonesia) and Jabatan Kemajuan Islam Malaysia (JAKIM - Department of Islamic Development Malaysia). From the comparative analysis, the result shows that certification processes of LPPOM MUI and JAKIM are similar with slight differences. There are four main activities during the certification process in both halal certification bodies, namely application process, payment process, audit process, and certificate issuance/decision process. The criteria set by both halal certification bodies, in general, are similar. Those are classified into eight categories, although there are slight differences. The eight categories are halal control/assurance system, human resource, permitted animal, production facilities, storage and transportation, packaging and labeling, slaughtering process, and stunning.
Parenting Styles Effect on Career Exploration Behavior in Adolescence: Considering Parents and Adolescent Gender
Authors: Salim Rose Mini Agoes , Preston Melly
Published: January 2020

In facing the industrial 4.0 era, adolescents, especially high school students, need to complement their knowledge and skills learnt from school with behaviors that can help their career journey, namely the career exploration behavior (CEB). Referring to the triadic reciprocal determinism theory and gender role in Indonesian culture, this study aimed to examine the effect of parenting styles and gender on CEB. Specifically, this study examined the effect of paternal and maternal parenting styles on CEB in adolescent and compared its effect on boys and girls. Participants in this study were 427 boys and 397 girls with an average age of 17 from nine high schools. Career Exploration Survey and Parental Authority Questionnaire were used to assess participants’ CEB, and paternal and maternal parenting styles. Regression analysis showed different patterns effect of paternal and maternal parenting styles on CEB between boys and girls. For boys, parenting that was found to improve CEB were paternal authoritative parenting and maternal authoritarian parenting, while for girls, parenting that was found to improve CEB were paternal authoritarian parenting and maternal authoritative parenting. These results indicated that boys and girls need different parenting factors from father and mother. Limitation and suggestion are discussed.
Modern tactics of treatment of constipation
Authors: Skvortsov V. V. , Skvortsova E. M. , Baimankulov S. S.
Published: January 2020

Constipation (constipation, obstipation) is a symptom in which the frequency of the act of defecation is less than 3 times a week and is accompanied by the release of solid, scanty feces with a feeling of incomplete emptying of the rectum and often requiring additional effort. World health organization in the « International statistical classification of diseases and health-related problems. ICD-10 « refers to constipation diseases (code K59. 0). At the same time, gastroenterological organizations such as the world organization of gastroenterologists and the American gastroenterological Association take a different position, emphasizing that constipation is not a disease, but a symptom. Most often constipation affects young children and the elderly (over 60 years). The feeling of difficulty in emptying the bowel, the impossibility of relief, despite persistent straining, the need to apply additional, stimulating the release of the rectum from the feces, actions (pressure on the perineum, the side walls of the anus, the vagina). The constant state of insufficient emptying of the rectal ampoule often leads to the development of perineal prolapse syndrome. Chronic constipation is diagnosed in cases where the frequency of stool becomes less than 3 times a week, defecation is significantly difficult and requires pronounced efforts, the consistency of the stool is dense, tubercular, there is a feeling of incomplete liberation of the rectum from feces. Constipation is a very common digestive disorder among the population, the tendency to constipation can lead to the development of serious proctological diseases, so this problem has a high degree of social significance. Due to its prevalence and pronounced deterioration in the quality of life of patients, chronic constipation is isolated in an independent syndrome, and currently the problem of constipation is actively studied by proctologists, gastroenterologists and other specialists. This article is devoted to the main issues of modern therapy of constipation.
Experience of using ursodeoxycholic acid to dissolve gallstones
Authors: Tsukanov V. V. , Onuchina E. V. , Vasyutin A. V. , Tonkikh Yu. L.
Published: January 2020

Objective of the study. A 5-year prospective study was aimed to evaluate the efficacy of Ursosan treatment for dissolving gallstones.

Material and methods. Patients who had single gallbladder stones were randomized to group A, in which 47 people completed the study (16 men and 31 women, median age is 67.6 years), and group B – 41 people 14 men and 27 women, median age is 68, 1 years). All patients of group A continuously received continuous treatment with ursodeoxycholic acid drug Ursosan at a dose of 10 mg /kg per day for 5 years. The patients of group D did not receive Ursosan; these individuals received periodic courses of spasmodic drugs. The patients passed clinical examination, laboratory tests, transabdominal ultrasound of the liver and biliary tract before the study, 2 times a year for 5 years and after the study.

Results. After 5 years of treatment, stones were detected in 10.6% of patients in group A. In group B, the incidence of gallstones did not change after 5 years of treatment, that is, calculi were detected in all patients (p <0.001). At the end of the study, no muldoi tiple stones were observed in any of the patients of group A, while multiple stones were detected in 2/3 of group B patients after 5 years of treatment. A distinct decrease in pain syndrome frequency and improvement in contractile function of the gallbladder were recorded in patients of group A as compared to the patients of group B by the end of the observation period. The side effect profile did not differ in groups A and B. The study showed good tolerance of Ursosan for 5 years of continuous administration of the drug.

Findings. The 5-year prospective study showed that Ursosan’s efficacy in dissolving gallstones accounted for 90%. Ursosan also prevented the formation of new calculi and reduced the frequency of pain, improved the gall-bladder contractile function and reduced the need for cholecystectomy by the end of the observation period.
Organoprotective effects of glucagon-like peptide-1 receptor agonists with regard to findings of evidencebased cardiovascular safety studies
Authors: Khalimov Yu. Sh. , Kuzmich V. G.
Published: January 2020

The article discusses the potential opportunities for impact of antidiabetic drugs from the group of glucagon-like peptide-1 (GLP- 1) receptor agonists on the risks of development and progression of cardiovascular complications in patients with type 2 diabetes mellitus (T2DM) and their possible role in increasing the patients’ expectancy and quality of life. The existing differences between the drugs of this class should be taken into account in using personalized approach to therapy, developing and introducing new guidelines for specialized medical care for patients with type 2 diabetes into clinical practice. The article presented data on the efficacy and safety of the use of GLP-1 receptor agonists and discusses data on the possible mechanisms of non-glycemic effects underlying their cardio and nephroprotection. The features of pharmacological characteristics affecting the clinical efficacy and development of side effects are considered. The article also provides data from randomized clinical trials of various GLP-1 receptor agonists that demonstrate the positive effect of drugs of this class on cardiovascular and nephrological outcomes in patients with type 2 diabetes.
New approaches to the impact on the pathogenetic links of sepsis
Authors: Nikitin E. A. , Kleymenov K. V. , Batienco D. D. , Akulenko D. A. , Seliverstov P. V. , Dobritsa V. P. , Radchenko V. G.
Published: January 2020

Sepsis is a systemic pathological reaction that arise because of a severe infection. Now, sepsis is considered as one of the most serious diseases and materially expensive nosology’s. For instance, out of 100% of cases of sepsis, only 40% survive. Thus, there is a high mortality rate and a wide prevalence (up to 300 thousand patients with sepsis are registered in Europe), which makes it possible to identify serious problems and the need to improve the clinical approach to the management strategy and tactics of such patients. The number of cases of detection and registration of sepsis has been expanding expansively since the thirties of the last century, and continues to grow dynamically, which obviously requires an improvement in the pathognomonic approach to therapy. The main reasons for the growth of septic conditions are the increasing use of invasive methods in medical practice, the pandemic of diabetes mellitus, the use of cytostatic and immunosuppressants, as well as the increasing number of antibiotic-resistant strains of pathogenic and conditionally pathogenic bacteria, total disruption of mucosal microbiocenoses, unreasonable use of probiotics with production strains containing foci of pathogenicity in patients with primary or secondary immunodeficiencies. Now, the main etiopathogenetic therapy of sepsis remains drugs aimed at the destruction of pathogenic microorganisms. However, based on the pathogenesis of the septic state, it seems effective to search for drugs with new points of application to individual pathogenesis links of the systemic inflammatory response. Today, studies aimed at establishing the effectiveness of influence on any individual links in the pathogenesis of sepsis - inflammatory mediators, have not yet yielded clear results.
Laboratory bleeding predictors in elderly patients with atrial fibrillation taking direct oral anticoagulants
Authors: Gabitova M. A. , Krupenin P. M. , Sokolova A. A. , Napalkov D. A. , Fomin V. V.
Published: January 2020

Atrial fibrillation (AF) is one of the most common arrhythmias in patients ≥75 years of age. The increased risk of thrombosis due to age and the large number of concomitant diseases makes it evident that anticoagulant therapy is necessary. However, the same factors increase the risk of hemorrhagic complications, which are among the most dangerous side effects of anticoagulant therapy. That is why it is very important to identify patients with the highest probability of bleeding, whether large or small clinically significant and minor. The purpose of our study was to study the prognostic value of laboratory methods of examination with regard to the development of hemorrhagic events in elderly patients with AF taking direct oral anticoagulants (DOAC). The study enrolled 102 patients ≥75 years of age with AF of non-valve etiology taking dabigatran, apixaban, rivaroxaban at full or reduced doses. Anticoagulants were administered by outpatient and inpatient physicians. Both previous experience with DOAC prior to inclusion in the trial (if DOAC was previously prescribed) and prospective patient monitoring after inclusion in the trial were analyzed. The minimum analyzed period of DOAC intake was 18 months. Patients who underwent (n = 19) and did not undergo (n = 83) hemorrhagic events (all events were considered small by ISTH criteria) did not differ in any of the laboratory indicators potentially considered as predictors of hemorrhagic events.
Efficacy of a fixed-dose combination (amlodipine/losartan) in the treatment of a patient with arterial hypertension, dyslipidemia and obesity
Authors: Mikhin V. P.
Published: January 2020

The article substantiates the feasibility of combination antihypertensive therapy in patients with arterial hypertension without target organ damage and high cardiovascular risk. The authors consider a clinical case of the use of amlodipine and losartan in a fixed-dose combination (Lozap AM) as part of complex therapy in a patient with arterial hypertension, dyslipidemia and obesity. The clinical case showed the ability of the drug to both achieve a steady level of target blood pressure and improve its daily profile by transferring the Night-peaker type to the Non-dipper type.
Prescription of chondroitin sulfate in back pains
Authors: Shavlovskaya O. A. , Romanov I. D.
Published: January 2020

One of the promising areas of pharmacotherapy in degenerative-dystrophic lesions of the joints, such as osteoarthritis (OA), is the use of chondroprotectors (CP). CPs belong to the group of Symptomatic Slow Acting Drugs for OsteoArthritis (SYSADOA). Among CPs, chondroitin sulfate (CS) is considered to be the most acceptable means capable of influencing metabolic processes in cartilage, synovial and bone tissue, suppressing the synthesis of proinflammatory mediators. CS improves phosphorus-calcium metabolism in cartilage tissue, inhibits enzymes that violate the structure and function of articular cartilage, inhibits the degeneration of cartilage tissue; stimulates the synthesis of glycosaminoglycans (GAG), normalizes the metabolism of hyaline tissue, promotes regeneration of cartilage surfaces and articular bags.The main effects that show CS on the joint in OA: anti-inflammatory, analgesic, protective. Slowing bone resorption, reduces the loss of Ca2+ and accelerates the processes of bone repair, inhibits the progression of OA. It has analgesic effect, reduces joint pain, pain at rest and when walking, the severity of inflammation, reduces the need for non-steroidal anti-inflammatory drugs (NSAIDs). The appointment of correctors of bone and cartilage metabolism is indicated at any stage of the degenerative process in the joints. One of the medicinal product (MP) based on CS is Chondroitin-ACOS (capsules, 25mg), whose effectiveness in the treatment of patients with OA has been demonstrated in a number of studies. Dosage Chondroitin-ACOS: 0,75 g 3 times a day for 3 weeks, then 0,5 g 2 times a day for 9 weeks. The therapeutic effect develops after 8-12 weeks of taking the drug. Within one month after discontinuation of Chondroitin-ACOS, its aftereffect persisted. Chondroitin-ACOS can be recommended for patients with severe pain syndrome, radiologically confirmed OA I-III stages of different localization.
TRAFİK DENEYİMLERİ VE DÜZEN SÖYLEMİ İÇİNDEN İSTANBUL’U ÜRETMEK
Authors: NUHRAT Yağmur
Published: January 2020

İstanbul’un gündelik hayatını biçimlendiren önemli
etkenlerden biri trafik. Trafikte geçirilen zamandan çoğu zaman “boş” ya da
“kayıp” olarak söz ediliyor. Oysa hareketlilik çalışmaları, kültürel coğrafya
ve kent antropolojisinin de bize anlattığı gibi zaman/mekânlar aslında boş
değil. İçlerindeki deneyimler sayesinde sürekli yeniden üretiliyorlar, yani,
boş olmaktan uzak üretken mevhumlar. Bu yazıda, bir yıl devam eden etnografik
çalışmama dayanarak, İstanbul trafiği zaman/mekânının ve buradan hareketle de
İstanbul kentinin düzen söylemi ve özellikle de idealize edilen Avrupai bir
düzen ekseninde, üretilme süreçlerini ve dinamiklerini anlatıyorum. Gündelik
hayatın sıradanlığı ve olağanlığı içinden kent ve kentlilik tahayyülünün nasıl
biçimlendiğini ve bu biçimlenmeyi anlamlandıran tarihselliği inceliyorum.
Ozonation of natural organic matter and aquatic humic substances: the effects of ozone on the structural characteristics and subsequent trihalomethane formation potential
Authors: Sadrnourmohammadi Mehrnaz , Brezinski Kenneth , Gorczyca Beata
Published: January 2020

The effect of ozonation on the structural and chemical characteristics of natural organic matter (NOM) and its isolated humic fractions, humic acid (HA) and fulvic acid, were studied using Fourier transform infrared coupled to attenuated total reflectance (FTIR-ATR), ultraviolet/visible (UV/Vis) spectroscopy, and synchronous scanning fluorescence (SSF) spectroscopy. The results were linked to the effect of ozonation on trihalomethane formation potential (THMfp) reduction for water standards with high THM precursors. Results showed that ozonation at a dose of 1 mg ozone/mg dissolved organic carbon (DOC) was capable of reducing DOC, UV absorbance at 254 nm (UV254), and THMfp by up to 42%, 95%, and 89% for the HA water standard, respectively. The study of UV/Vis, FTIR-ATR, and SSF revealed trends showing that ozone can alter the composition of DOC in the water standards, causing a significant reduction in aromaticity. The reduction of UV254 for each ozonated sample also affirms that ozone mainly targets aromatic moieties contained in NOM. FTIR-ATR results showed that the reduction of unsaturated functional groups, including aromatic rings and C = C bonds in the water standards tested, were the main components impacted by ozone application. SSF results also revealed that ozonation decreases the fluorescence intensity of the maximum peak – as well as the whole spectra.
The Roles of Programmed Cell Death Ligand-1/ Programmed Cell Death-1 (PD-L1/PD-1) in HPV-induced Cervical Cancer and Potential for their Use in Blockade Therapy
Authors: Zhang Lifang , Zhao Yu , Tu Quanmei , Xue Xiangyang , Zhu Xueqiong , Zhao Kong-Nan
Published: January 2020

Background:

Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading
cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity
and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but
the outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months.

Methods:

We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of
programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream
regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis
induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical
cancer therapies.

Results:

One hundred and twenty-six published papers were included in the review, demonstrating that expression
of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately
70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signalling pathways including
PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and microRNA, which regulate PD-L1/PD-1
axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in the immune
escape of cervical cancer through inhibition of host immune response. Creating an "immune-privileged" site for
initial viral infection and subsequent adaptive immune resistance, which provides a rationale for the therapeutic
blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PDL1/
PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the
application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment.

Conclusion:

Recent research developments have led to an entirely new class of drugs using antibodies against the
PD-L1/PD-1 thus promoting the body’s immune system to fight cancer. The expression and roles of the PD-L1/
PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted
cancer therapy.
Radiolabeled Peptides for SPECT and PET Imaging in the Detection of Breast Cancer: Preclinical and Clinical Perspectives
Authors: Fu Hao , Du Bulin , Chen Zijun , Li Yesen
Published: January 2020

Breast cancer is the most common cancer in women worldwide. Due to the heterogeneous
nature of breast cancer, the optimal treatment and expected response for each patient may not necessarily
be universal. Molecular imaging techniques could play an important role in the early detection and
targeted therapy evaluation of breast cancer. This review focuses on the development of peptides labeled
with SPECT and PET radionuclides for breast cancer imaging. We summarized the current status
of radiolabeled peptides for different receptors in breast cancer. The characteristics of radionuclides and
major techniques for peptide labeling are also briefly discussed.
Adrenergic and Cholinergic Uterine Innervation and the Impact on Reproduction in Aged Women
Authors: Kosmas Ioannis P. , Malvasi Antonio , Vergara Daniele , Mynbaev Ospan A. , Sparic Radmila , Tinelli Andrea
Published: January 2020

In recent years, the development of Assisted Reproductive Technique, the egg and embryo donation
changed substantially the role of the uterus in recent years. It provided a higher chance for a pregnancy even in
women over 45 years or post-menopause. In fact, the number of aged patients and in peri/post-menopause in
pregnancy is nowadays increasing, but it increases obstetrical and neonatal related problems. The human uterus is
richly innervated and modified especially during pregnancy and labor, and it is endowed with different sensory,
parasympathetic, sympathetic and peptidergic neurofibers. They are differently distributed in uterine fundus, body
and cervix, and they are mainly observed in the stroma and around arterial vessel walls in the myometrial and
endometrial layers. Many neurotransmitters playing important roles in reproductive physiology are released after
stimulation by adrenergic or cholinergic nerve fibers (the so called sympathetic/parasympathetic co-transmission).
Immunohistochemical study demonstrated the localization and quantitative distribution of neurofibers in the
fundus, the body and cervix of young women of childbearing age.

Adrenergic and cholinergic effects of the autonomous nervous system are the most implicated in the uterine functionality.
In such aged women, the Adrenergic and AChE neurofibers distribution in the fundus, body and cervix
is progressively reduced by increasing age. Adrenergic and AChE neurotransmitters were closely associated with
the uterine arteries and myometrial smooth muscles, and they reduced markedly by ageing. The Adrenergic and
AChE neurofibers decreasing has a dramatical and negative impact on uterine physiology, as the reduction of
pregnancy chance and uterine growth, and the increase of abortion risk and prematurity.
Green Chemistry Approaches to the Synthesis of Coumarin Derivatives
Authors: Molnar Maja , Lončarić Melita , Kovač Marija
Published: January 2020

This review is a compilation of the green synthetic methods used in the synthesis
of coumarin derivatives. Coumarins are a class of compounds with a pronounced wide
range of biological activities, which have found their application in medicine, pharmacology,
cosmetics and food industry. Their biological activity and potential application are
highly dependent on their structure. Therefore, many researchers have been performing
the synthesis of coumarin derivatives on a daily basis. High demands for their synthesis
often result in an increased generation of different waste chemicals. In order to minimize
the utilization and generation of toxic organic substances, green synthetic methods are applied
in this manner. These methods are getting more attention in the last few decades.
Green chemistry methods cover a wide range of methods, including the application of ultrasound
and microwaves, ionic liquids and deep eutectic solvents, solvent-free synthesis, mechanosynthesis
and multicomponent reactions. All typical condensation reactions for coumarin synthesis like Knoevenagel,
Perkin, Kostanecki-Robinson, Pechmann and Reformansky reactions, have been successfully performed using
these green synthetic methods. According to the authors mentioned in this review, not only these methods reduce
the utilization and generation of toxic chemicals, but they can also enhance the reaction performance in
terms of product yields, purity, energy consumption and post-synthetic procedures when compared to the conventional
methods. Due to the significance of coumarins as biologically active systems and the recent demands
of reducing toxic solvents, catalysts and energy consumption, this review provides a first full literature overview
on the application of green synthetic methods in the coumarin synthesis. It covers a literature search over
the period from 1995-2019. The importance of this work is its comprehensive literature survey on a specific
class of heterocyclic compounds, and those researchers working on the coumarin synthesis can find very useful
information on the green synthetic approaches to their synthesis. There are some reviews on the coumarin synthesis,
but most of them cover only specific reactions on coumarin synthesis and none of them the whole range
of green chemistry methods.
Does Pharmacodynamics of Drugs Change After Presenting them as Nanoparticles Like their Pharmacokinetics?
Authors: Mohammad Jafari Razieh , Ala Moein , Goodarzi Navid , Dehpour Ahmad Reza
Published: January 2020

:

Nowadays, the breakthrough in different medical branches makes it feasible to designate
new methods of drug delivery to achieve the most cost-effective and the least unpleasant consequenceimposing
solutions to overcome a wide range of diseases.

:

Nanoparticle (NP) drugs entered the therapeutic system, especially in cancer chemotherapy. These
drugs are quite well-known for two traits of being long-acting and less toxic. For a long time, it has
been investigated how NPs will change the kinetics of drugs. However, there are a few studies that inclined
their attention to how NPs affect the dynamics of drugs. In this review, the latter point will
mainly be discussed in an example-based manner. Besides, other particular features of NPs will be
briefly noted.

:

NPs are capable of affecting the biologic system as much as a drug. Moreover, NPs could arise a wide
variety of effects by triggering their own receptors. NPs are able to change a receptor function and
manipulate its downstream signaling cascade.
Trabectedin (Yondelis®) as a Therapeutic Option in Gynecological Cancers: A Focus on its Mechanisms of Action, Clinical Activity and Genomic Predictors of Drug Response
Authors: Souid Soumaya , Aissaoui Dorra , Srairi-Abid Najet , Essafi-Benkhadir Khadija
Published: January 2020

The use of predictive biomarkers provides potential individualized cancer therapeutic options to prevent therapy failure as well as serious toxicities. Several recent studies showed that predictive and prognostic biomarkers are a notable personalized strategy to improve patients’ care in several cancers. Trabectedin (Yondelis®) is a cytotoxic agent, derived from a marine organism, harbouring a significant antitumor activity against several cancers such as soft tissue sarcoma, ovarian, and breast cancers. Recently and with the advent of molecular genetic testing, BRCA mutational status was found as an important predictor of response to this anticancer drug, especially in gynecological cancers. The aim of this updated review is to discuss the mechanisms of action of trabectedin against the wellknown cancer hallmarks described until today. The current advances were also examined related to genomic biomarkers that can be used in the future to predict the efficacy of this potent anticancer natural molecule in various gynecological cancers.
MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease
Authors: Wang Dan , Fei Zhifu , Luo Song , Wang Hai
Published: January 2020

Objectives:

Alzheimer's disease (AD), also known as senile dementia, is a common
neurodegenerative disease characterized by progressive cognitive impairment and personality
changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the
pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression
of AD is still not clearly clarified.

Methods:

The protein and mRNA levels were measured by western blot and RNA extraction and
quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and
c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells
were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry
and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were
used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR-
335-5p on the cognitive deficits in APP/PS1 transgenic mice.

Results:

The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly
up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain
tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly
inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335-
5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3
and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p
obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved
the cognitive abilities of APP/PS1 mice.

Conclusion:

The results revealed that the increased JNK3 expression, negatively regulated by
miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression,
indicating a novel approach for AD treatment.
Construction of a Neuro-Immune-Cognitive Pathway-Phenotype Underpinning the Phenome of Deficit Schizophrenia
Authors: Al-Hakeim Hussein K. , Almulla Abbas F. , Al-Dujaili Arafat H. , Maes Michael
Published: January 2020

Background:

In schizophrenia, pathway-genotypes may be constructed by combining interrelated
immune biomarkers with changes in specific neurocognitive functions that represent aberrations
in brain neuronal circuits. These constructs provide an insight on the phenome of schizophrenia and
show how pathway-phenotypes mediate the effects of genome X environmentome interactions on the
symptomatology/phenomenology of schizophrenia. Nevertheless, there is a lack of knowledge how to
construct pathway-phenotypes using Partial Least Squares (PLS) path modeling and Soft Independent
Modeling of Class Analogy (SIMCA).

Aims:

This paper aims to provide a step-by-step utilization guide for the construction of pathwayphenotypes
that reflect aberrations in the neuroimmune - brain circuit axis (NIBCA) in deficit schizophrenia.

Methods and Results:

This NIBCA index is constructed using immune biomarkers (CCL-2, CCL-11,
IL-1β, sIL-1RA, TNF-α, sTNFR1, sTNFR2) and neurocognitive tests (Brief Assessment of Cognition in
Schizophrenia) predicting overall severity of schizophrenia (OSOS) in 120 deficit SCZ and 54 healthy
participants. Using SmartPLS path analysis, a latent vector is extracted from those biomarkers and cognitive
tests, which shows good construct reliability (Cronbach alpha and composite reliability) and replicability
and which is reflectively measured through its NIBCA manifestations. This NIBCA pathwayphenotype
explains 75.0% of the variance in PHEMN (psychotic, hostility, excitation, mannerism and
negative) symptoms. Using SIMCA, we constructed a NIBCA pathway-class that defines deficit schizophrenia
as a qualitatively distinct nosological entity, which allows patients with deficit schizophrenia to
be authenticated as belonging to the deficit schizophrenia class.

Conclusion:

In conclusion, our nomothetic approach to develop a nomological network combining
neuro-immune and neurocognitive phenome markers to predict OSOS and cross-validate a diagnostic
class generated replicable models reflecting the key phenome of the illness, which may mediate the effects
of genome X environmentome interactions on the final outcome phenome features, namely symptomatology
and phenomenology.
OMEGA-3 Interventions in Alcohol Dependence and Related Outcomes: A Systematic Review and Propositions
Authors: Galduróz José Carlos F. , Bezerra Andréia Gomes , Pires Gabriel Natan , Pauluci Renata , Noto Ana Regina
Published: January 2020

Background:

Pharmacological treatment for alcohol dependence has only three approved
drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited,
presenting several side effects and a modestly higher efficacy compared to placebo. The administration
of omega-3 might bring new perspectives to relapse prevention.

Methods:

This systematic review aimed to analyze the available literature, compiling the studies
that used omega-3 to prevent relapse in alcohol dependents.

Results:

The databases used were PubMed and Web of Science. We identified 2,231 studies and
only five articles addressed the administration of omega-3 and alcoholism. Preclinical studies
evaluating the effects of PUFAs related to chronic alcohol administration showed improvements in
behavioral, cellular and molecular levels. The clinical trial yielded inconclusive results.

Conclusion:

Despite the reduced number of studies, omega-3 interventions seem to be promising
for controlling issues related to alcohol dependence.
Recent Trends in the Management of Alzheimer’s Disease: Current Therapeutic Options and Drug Repurposing Approaches
Authors: Singh Rakesh K.
Published: January 2020

:

Alzheimer’s disease is one of the most progressive forms of dementia, ultimately leading
to death in aged populations. The major hallmarks of Alzheimer’s disease include deposition of
extracellular amyloid senile plaques and intracellular neurofibrillary tangles in brain neuronal cells.
Although there are classical therapeutic options available for the treatment of the diseases, however,
they provide only a symptomatic relief and do not modify the molecular pathophysiological course
of the disease. Recent research advances in Alzheimer’s disease have highlighted the potential role
of anti-amyloid, anti-tau, and anti-inflammatory therapies. However, these therapies are still in different
phases of pre-clinical/clinical development. In addition, drug repositioning/repurposing is
another interesting and promising approach to explore rationalized options for the treatment of Alzheimer’s
disease.

:

This review discusses the different aspects of the pathophysiological mechanism involved in the
progression of Alzheimer’s disease along with the limitations of current therapies. Furthermore, this
review also highlights emerging investigational drugs along with recent drug repurposing approaches
for Alzheimer’s disease.
How to Find Candidate Drug-targets for Antiepileptogenic Therapy?
Authors: Yu Nian , Lin Xing-jian , Di Qing
Published: January 2020

Although over 25 antiepileptic drugs (AEDs) have become currently available for clinical use, the incidence of epilepsy worldwide and the proportions of drug-resistant epilepsy among them are not significantly reduced during the past decades. Traditional screens for AEDs have been mainly focused on their anti-ictogenic roles, and their efficacies primarily depend on suppressing neuronal excitability or enhancing inhibitory neuronal activity, almost without the influence on the epileptogenesis or with inconsistent results from different studies. Epileptogenesis refers to the pathological process of a brain from its normal status to the alterations with the continuous prone of unprovoked spontaneous seizures after brain insults, such as stroke, traumatic brain injury, CNS infectious, and autoimmune disorders, and even some specific inherited conditions. Recently growing experimental and clinical studies have discovered the underlying mechanisms for epileptogenesis, which are multi-aspect and multistep. These findings provide us a number of interesting sites for antiepileptogenic drugs (AEGDs). AEGDs have been evidenced as significantly roles of postponing or completely blocking the development of epilepsy in experimental models. The present review will introduce potential novel candidate drug-targets for AEGDs based on the published studies.
Isolation of Morganella Morganii and Providencia Species from Clinical Samples in a Tertiary Care Hospital in North India
Authors: Sharma Shiwani , Bora Prapti , Singla Nidhi , Gupta Varsha , Chander Jagdish
Published: January 2020

Introduction:

The members of the tribe Proteeae, Morganella and Providencia are being
increasingly recognized as important pathogens. The spectrum of disease caused by them is wide
and in reported cases, the mortality is high. Previously both of these pathogens were considered to
be rare pathogens as the potential to cause nosocomial transmission and infection was not much
studied. But their phenomenal evolution and increase in multidrug-resistance (MDR) strains of
these pathogens are posing a major threat toward public health throughout the world.

Methods:

This present study was carried out from July 2018 to December 2018 on all the pus and
body fluid samples that were received in the Department of Microbiology. Samples were processed
as per the standard Microbiological guidelines and also were analyzed for their antimicrobial susceptibility
profile as per Clinical Laboratory Standards Institute.

Results:

Out of 8425 samples received, 2140 were culture positive, amongst which 19 samples
(0.89%) were positive for Providencia species (9) and Morganella morganii(10). The male : female
ratio of these 19 patients was 2.8 : 1 and maximum patients (13) belonged to 20-60 years. As far as
risk factors are concerned, maximum patients were diabetics (7) followed by abnormal liver function
tests (6), concomitant UTI (6), history of invasive procedure (5), prior exposure to antibiotics
(5) and urinary catheterization (4). About 6 were polymicrobial infections. Antibiotic susceptibility
patterns revealed that Providencia strains were sensitive to ampicillin- sulbactum (77.7%) and amikacin
(77.7%), while all Morganella strains were 100% sensitive to tobramycin and piperacillintazobactam.

Conclusion:

This study heralds in need for more research in this area as infections caused by these
two pathogens are on the rise. Moreover, resistance to antimicrobials is also an increasingly common
problem thus delaying the treatment and prognosis of the disease.
Mysterious World of Lichens: Highlights on Their History, Applications, and Pharmaceutical Potentials
Authors: Elkhateeb Waill A. , Daba Ghoson M. , Sheir Donia , Nguyen The-Duy , Hapuarachchi Kalani K. , Thomas Paul W.
Published: January 2020

Background:

Lichens play an important role in many ecosystems and exist as a symbiotic
association between fungi and algae or cyanobacteria. This symbiosis results in the production of
unique secondary metabolites known as lichen substances, which arise within the thalli and are typically
in crystal form on the surface of the fungal hyphae. Recently, lichens and their secondary metabolites
have been receiving increased attention due to their nutritional value and pharmaceutical
potential.

Objectives:

This review aims to cast a light on the importance and variety of common lichen substances (secondary metabolites), which are investigated along with their historical and contemporary applications, use in environmental research and discussion of the commercialisation of lichens-based products.

Methods:

The literature, including research and reviews articles, was analysed and the information was compiled to provide a complete review of Lichens. A desk-based study to elucidate the role of lichens in commercial products was also undertaken.

Results:

The analysis of metabolites, mostly secondary metabolites, has yielded a wide range of interesting
compounds with biological activities from antimicrobial to anticancer. 31 of these compounds
are discussed in detail. Further, the nutritional value of lichens is identified alongside a role
in environmental monitoring and a number of commercialised lichen-based products are located.

Conclusions:

Lichens are found on every continent and have a history of use as food, medicine, dyes and livestock feed. The pharmaceutical potential of lichens is high and several companies are now attempting to commercialise these unique attributes.
Research Progress and Prospect of Orthodontic Accelerating Device
Authors: Jiang Jingang , Qian Wei , Huang Zhiyuan , Zhang Yongde , Chen Houjun
Published: January 2020

Background:

Malocclusion is a disease with a high incidence rate that is harmful to humans’
health. Fixed orthodontics is an effective method for the treatment of malocclusion. However, the orthodontic
process takes a long time, requires frequent visits, causes pain, and increases the risk of complications.
Since orthodontic treatment is lengthy, painful and unbearable, and even leads patients to
abandon orthodontic treatment, therefore, how to shorten orthodontic treatment duration, and reduce
pain is a research hotspot in the orthodontic field.

Objective:

The study aimed to provide an overview of the existing orthodontic accelerating device and
introduce their classification, characteristics and development.

Methods:

This paper reviewed various productions and patents related to the orthodontic accelerating
device. The structural characteristics, differentiations, and applications of the existing orthodontic accelerating
device are also introduced.

Results:

The existing orthodontic accelerating devices were analyzed and compared, and the typical
characteristics were concluded. The main problems in its development were analyzed, the development
trend was foreseen, and the current and future research on the productions and patents related to the
orthodontic accelerating device is discussed.

Conclusion:

The orthodontic accelerating device is composed of a vibration device having electrical
stimulation, magnetic field, a low-level laser, and an ultrasonic device according to the application of
different physical loads. Orthodontic accelerating device can effectively reduce orthodontic treatment
time by 30%-50%, and can reduce the risk of complications and pain. The dose of the physical load
determines the effect of the device. So, an optimal loading dose should be selected . Compared with
vibrating devices, other types of devices are less used in clinical practice, therefore, such products and
patents should be invented in the future.