bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of biosimilars as a new approach to the treatment of rheumatoid arthritis
Authors: Chichasova N. V. , Lila A. M.
Published: August 2021

The article discusses various options for the management of patients with rheumatoid arthritis (RA) in accordance with modern foreign and domestic recommendations. Data on the possibility of achieving an effect on the background of monotherapy with methotrexate (MT) are presented and options for more active therapy are discussed. The authors compare the effectiveness of sequential change of basic anti-inflammatory drugs (DMARDs), sequential addition of DMARDs to MT, treatment with a triple combination of DMARDs with an inadequate response to MT or in the debut of therapy, combination of DMARDs and biological drugs. According to the study data, in cohorts of patients with equal clinical effectiveness of the triple combination of DMARDs and the combination of DMARDs with biological drugs, however, the severity of the progression of destruction in the joints of the hands and feet is less when using biological agents. It was noted that the evaluation of the effectiveness of the double / triple combination of DMARDs was carried out in open observational studies, which has less evidence value than randomized controlled double-blind placebo-controlled trials (RCTs) for the assessment of biological drugs. Despite the importance of implementing biological drugs in clinical practice, their high cost limits their use by patients. Registration in the Russian Federation of the first biosimilar of etanercept (ETN) - the drug Erelzi is important for the treatment of patients with RA. The article describes the advantages of original ETN (tumor necrosis factor ainhibitor - iFNO a) over other iFNO a, which are monoclonal antibodies to this cytokine. The article presents data on the equivalence of the ETN biosimilar registered in the Russian Federation (Erelzi) with the original ETN in terms of clinical efficacy, safety and immunogenicity. The comparability of drugs in terms of the frequency of adverse events was demonstrated. It is shown that switching from the original ETN to its biosimilar allows you to maintain the effect, not accompanied by an increase in the frequency of intolerance or immunogenicity. It is indicated that Erelzi is registered in the Russian Federation for the treatment of RA, various variants of axial spondylitis, psoriatic arthritis, psoriasis and juvenile idiopathic arthritis.
Applications of a muscle relaxant (tolperizone) in clinical practice
Authors: Shavlovskaya O. A. , Bokova I. A. , Shavlovskiy N. I. , Yukhnovskaya Yu. D.
Published: August 2021

Tolperizone is a central type of muscle relaxant that is widely used in clinical practice for the treatment of patients with acute and chronic nonspecific lower back pain(LBP), inflammatory and degenerative-dystrophic joint diseases, and is used in the treatment of myofascial pain syndrome (MPS).The Russian market widely used drug tolperizone, which is comparable in its clinical and anti-inflammatory activity with the original tolperizone, as well as with non-steroidal anti-inflammatory drugs (NSAIDs). Tolperizone is prescribed mainly in complex therapy, as well as as monotherapy.In some studies, based on the clinical efficacy of tolperizone (200 mg 3 times a day), it is concluded that tolperizone can be considered as a promising treatment for acute muscle spasm, without causing drowsiness. In the treatment of pain syndromes and osteoarthritis (OA) of various localization, the optimal dosage regimen of tolperizone is currently recommended: oral 150-300 mg per day for a course of 14 days, or according to a 2-stage scheme of administration, first intramuscularly 1.0 ml 2 times a day for 5 injections, then switching to oral administration of 150 mg 3 times a day; with MPS, a single local intramuscular injection of tolperizone is prescribed at the trigger point. The addition of tolperizone (150 mg/s) to the scheme of complex therapy allows to achieve an earlier clinical effect in OA of the hip and ankle joints, suppressing further progression of the disease. When included in the therapy regimen of tolperizone (150 mg/s, 14 days) OA of the ankle joint, with ultrasound examination, there is a statistically significant decrease in the signs of synovitis.
Modern approaches to the diagnosis and treatment of anxiety disorders associated with a new coronavirus infection
Authors: Aronov P. V. , Belskaya G. N. , Nikiforov I. A.
Published: August 2021

The article systematizes information on the diagnosis and treatment of anxiety disorders, the frequency of which has increased significantly at the present time, in connection with the COVID-19 pandemic. The characteristic of stressful factors affecting the human psyche in the conditions of forced self-isolation and after it is given. Many people experience anxiety due to lockdown, social isolation, unemployment, and a high probability of illness and death. Uncertainty in the future, anxiety during the period of uncertainty caused by the spread of the “new coronavirus”, are a trigger for emotional exhaustion, suppress the immune system, which negatively affects the human nervous system and provokes an exacerbation of chronic ailments. The psychological consequences of a person’s stay in quarantine are considered. In the structure of mental health disorders associated with the COVID-19 epidemic, there is a large range of adaptation disorders: fear, frustration, a sense of hopelessness, expectation of threat, loneliness, social isolation and alienation. In the situation of COVID-19, there is often a depletion of mental resources and maladaptation, a disorder of adaptive reactions. Anxiety disorders occur in the form of adaptation disorders, generalized anxiety disorder, somatoform disorders, including panic attacks. Timely diagnosis of these disorders is possible not only by the psychiatric service, but also with the involvement of internists who possess screening diagnostic tools with automated conclusions (scales, mobile applications to smartphones, etc.). A brief review of domestic and foreign studies on the assessment of methods for the diagnosis and treatment of anxiety disorders is presented. Diagnostic methods and therapeutic tactics, the use of various traditional drugs in psychosomatic pathology are discussed. To correct the identified disorders, there is a choice of anti-anxiety drugs, including antidepressants (primarily selective serotonin reuptake inhibitors), tranquilizers, among which tofizopam occupies a worthy place.
Therapeutic aspects of melatonin applications
Authors: Tsenteradze S. L. , Poluektov M. G.
Published: August 2021

The results of multicenter clinical trials show the broad potential of melatonin since discovery of this adaptogen to the present day. Melatonin is a neuropeptide that is synthesized mainly in the small brain gland, the pineal gland, and has a unique effect in humans and animals. Using melatonin, the pineal gland participates in the organization of circadian periodism and regulation of cyclic processes, acting as an intermediary between the pacemaker mechanism of the suprachiasmatic nuclei (SCN) and peripheral organs. The pineal gland and the SCN of the hypothalamus form part of the system of the so-called biological clock of the body, which plays a key role in the mechanisms of regulation of the biological clock via circadian rhythms and ageing. Initially, melatonin was only considered a hormone involved in the synchronization of the mechanisms of the circadian rhythm, but later it was found that, in addition to this hormonal function, it takes part in the regulation of the seasonal cycle in animals and humans.

At present, melatonin drugs have shown high efficacy and safety in various sleep-wake disorders regardless of their genesis, disorganization of circadian rhythms, stress adjustment disorders, rapid change of time zones, shift work and in complex therapy of patients with cerebrovascular diseases.

The article considers the multimodal capabilities of melatonin, including adaptogenic, biorhythmogenic, hypnotic, immunostimu-lating, antioxidant effects. The role of melatonin in the treatment of various central nervous system disorders, including neurodegenerative diseases, has been determined.

The review emphasizes the wide-ranging effects of melatonin and offers great opportunities for measuring melatonin as a biomarker for early detection and follow-up of various diseases.
Left ventricular myocardial strain and electrocardiographic changes in children with hypertrophic cardiomyopathy
Authors: Chernykh N. Yu. , Tarasova A. A. , Groznova O. S. , Shigabeev I. M.
Published: August 2021

Abstract Introduction. Hypertrophic cardiomyopathy is one of the most common diseases of the myocardium in children. Meanwhile, the relationship between indicators of strain and electrocardiographic changes, their diagnostic significance for children with hypertrophic cardiomyopathy remains an insufficiently well-studied issue.

Purpose.Тo analyze the relationship between indicators of strain of the left ventricular and ECG in children with hypertrophic cardiomyopathy (HCM).

Materials and methods. Have been examined 61 patients with an asymmetric form of hypertrophic cardiomyopathy aged from 7 to 17 years. Of these, 45 (73.8%) children with nonobstructive form, 16 (26.2%) children with obstructive form. Electrocardiography (ECG) and 24-hour Holter monitoring ECG had performed. The parameters of global longitudinal, radial and circular of the left ventricular myocardial strain and their rates had determined by echocardiography in the 2D speckle tracking mode

Results. In children with HCM, ECG signs of hypertrophy were studied (deviation of the electrical axis to the left, the predominance of the R wave in lead I, V6 over the S wave, the predominance of the S wave in lead V1 over the R wave) and myocardial ischemia (inversion of the T wave and a decrease in the ST segment in the leads I, II, V5, V6), rhythm and conduction disorders (ventricular extrasystole, degree I atrioventricular block, expansion of the QRS complex in leads V1-V3, incomplete blockade of the anterior left branch of the His bundle, increased duration of terminal activation), which significantly prevailed in obstructive form versus non-obstructive form. A decrease in the global longitudinal, radial, circular strain of the left ventricular myocardium and their rates had found, which had significantly more pronounced in the group with obstructive HCM. Inverse correlations had found between the parameters of strain and ECG-signs of hypertrophy and myocardial ischemia, conduction disorders, more pronounced between the parameters of longitudinal strain and ECG with a significant predominance in the obstructive form of the disease.

Conclusions. In children with obstructive HCM, compared with the non-obstructive form, there have significantly more pronounced signs of myocardial hypertrophy and ischemia, rhythm and conduction disorders on the ECG and with 24-hour Holter monitoring ECG.
Interferoncontaining drugs: clinical, pharmacological, and immunological points of their use for respiratory diseases treatment
Authors: Salmasi J. M. , Kazimirskii A. N. , Kukes I. V. , Poryadin G. V. , Pozdnyakov D. I.
Published: August 2021

Nowadays pharmacological group classified by the ATX L03AX code as immunostimulants is demand among doctors of various specialties. The main area of application of such drugs is infectious respiratory viral processes, which are associated not only with the pathogenetic action of viruses, but also with a high risk of bacterial complications. Thus, the practitioner is faced with the task of preventing such complications and choosing an immunomodulatory drug with the most pronounced pharmacodynamic properties in this regard. In Russia, there are many drugs belonging to the group of immunomodulators with different mechanisms of action and end pharmacological and immunological points of application. The emphasis of the mechanisms of action of such drugs is made on the effect on the systems of both innate and adaptive immunity. At the same time, the severity of the effect on both one and the other immune system in drugs that is strong enough may differ, which requires special attention from the doctor when choosing a drug in a particular situation. A special place in the group of immunomodulatory drugs used for infectious respiratory diseases is occupied by interferoncontaining drugs that contain interferon alfa-2b (IFN-a2b). In addition, there are combination of IFN-a2b with an immunoglobulin complex, which increases the effectiveness of this drug in the treatment of various infectious and inflammatory diseases. The article describes the theoretical and practical aspects of administration this combined drug in pediatric practice and presents own experimental studies.
Interpretar o Trabalho como um Chamado Contribui para a Empregabilidade ou a Atrapalha?
Authors: Felix Bruno , Buaiz Papaleo Julia Almeida
Published: August 2021

Neste estudo, sustenta-se que chamados ocupacionais não são nem somente positivos nem somente negativos para a empregabilidade de indivíduos. Para testar esta ideia, objetivou-se analisar a existência de associações positivas e negativas indiretas entre a percepção de um chamado ocupacional e a empregabilidade, e o efeito moderador da mentalidade de paradoxo em tais relações. Para tal, foi realizado um estudo de natureza quantitativa, e os dados foram analisados por meio da Modelagem de Equações Estruturais. Os resultados mostraram um efeito direto negativo entre perceber um chamado ocupacional e a empregabilidade. Além disso, notou-se um efeito indireto positivo entre essas variáveis, via desenvolvimento profissional proativo, e um efeito indireto negativo, via inflexibilidade na carreira. Finalmente, foi identificado também um efeito moderador da mentalidade de paradoxo na relação entre perceber um chamado e empregabilidade, mediada pela inflexibilidade de carreira. Deste modo, este estudo contribui para a literatura de desenvolvimento de carreiras ao mostrar possíveis efeitos negativos da percepção de um chamado para a empregabilidade, enquanto a prática de muitos aconselhadores de carreira ignoram este efeito.
Viabilidade Estratégica e Econômica de Práticas Sustentáveis no Departamento de Compras: Estudo de Caso de uma IES Privada no Brasil
Authors: Castañeda Ayarza Juan Arturo , Ferreira Denise Helena Lombardo , Sugahara Cibele Roberta , Jacob Antonio Aparecido
Published: August 2021

O consumo consciente tornou-se imperativo em sociedades que repensam seu modelo de desenvolvimento. Por exemplo, para uma Instituição de Ensino Superior (IES), que demanda grandes quantidades de materiais, as compras sustentáveis representam uma oportunidade de múltiplos benefícios elencados nas dimensões sociais, ambientais e econômicas. As estratégias sustentáveis de compras, no entanto, podem aumentar a especulação quanto aos efeitos negativos, principalmente aqueles relacionados à parte econômica, fazendo-se necessários estudos que facilitem as tomadas de decisão. Por isso, o objetivo é avaliar a viabilidade estratégica e econômica de práticas sustentáveis no setor de compras de uma IES privada do Brasil. Os resultados mostram a importância de se considerar a sustentabilidade no planejamento estratégico, que deverá estar integrado em todas as áreas da instituição, incluindo o departamento de compras. Pretende-se mostrar, também, que, embora a viabilidade econômica das compras sustentáveis seja fundamental, necessita-se ponderar os impactos econômicos, sociais e ambientais para a instituição.
La imagen de las víctimas de los atentados de París, Niza y Cataluña en las portadas de diez periódicos españoles
Authors: Rey Muras Paula , Bellón Rodríguez Ana , Galocha López Antón
Published: August 2021

Los atentados terroristas son un claro ejemplo del conflicto ético y el derecho a la información en la publicación de la fotografía en los medios. En este contexto, se pone el foco en el tratamiento gráfico de tres atentados terroristas recientes (París, Niza y Cataluña) al acometer una investigación exploratorio-descriptiva de cómo se presentó a las víctimas de estos sucesos en la portada de diez diarios de España: El País, El Mundo, La Vanguardia, La Voz de Galicia, ABC, El Periódico, El Correo, La Nueva España, Heraldo de Aragón y La Razón. Se realiza una lectura fotográfica, técnica e interpretativa, de las imágenes y se presta atención al tipo de titular y pie de foto. En general, se otorga un tratamiento respetuoso a las víctimas, a medio camino entre el que se realizó el 11S, en el que apenas hubo imágenes, y el 11M, en el que se traspasaron fronteras éticas. Se recurre a imágenes de agencia, hay coincidencia en las fotografías seleccionadas y se apuesta por titulares breves y con pocas palabras pero llamativas y por pies de foto con diferentes modalidades. Son imágenes con valor informativo en las que, si bien se aprecia dolor, como es natural por el hecho a presentar, no se hace un uso sensacionalista.
El acto fotográfico como acto moral.
Authors: Alfaro López Héctor Guillermo
Published: August 2021

Por medio de la novela La gota de oro del escritor francés Michel Tournier, se busca ilustrar la relación entre fotografía y moral poniendo en evidencia que son relaciones ambivalentes. Para especificar el carácter de tales relaciones se estatuyeron los conceptos: acto fotográfico y acto moral. Las relaciones entre estos dos tipos de actos pueden tener un carácter negativo en el que el fotógrafo, a partir de requerimientos económicos, hace un uso no moral del acto fotográfico, por lo que, para establecer el acto fotográfico como un acto moral, se recurre a la propuesta de la filósofa Adela Cortina que fundamenta una ética mínima (filosofía práctica) la cual, apoyada en la ética kantiana, específica que, ante la destrucción de una ética general, la alternativa es una ética de mínimos, esto es, aquélla que señala una moral para situaciones concretas y fundada en el autorrespeto y en el reconocimiento humano del otro, a partir de considerarlo no como un medio sino como una finalidad en sí misma. Con lo que así queda establecido el acto fotográfico como un acto moral, es decir, como reconocimiento de lo humano y del mundo como ámbito humanizado.
Comprensión del contexto fotográfico mediante el uso del Modelo de Lectura para la indización fotográfica basada en el Método complejo y las funciones primarias de la imagen
Authors: Rodrigues da Silva Gislene , Da Consolação Dias Célia
Published: August 2021

Esta investigación tiene como objetivo discutir la importancia de comprender el contexto de la fotografía en el momento de la indización. Esta discusión se basó en la aplicación de la Matriz 1 y la Matriz 2 del Modelo de Lectura de Indización de Fotografías desarrollado en base al Método Complejo y las Funciones Primarias de la Imagen. Este modelo fue aplicado por dos grupos de estudiantes del curso de Biblioteconomía de la Universidad Federal de Minas Gerais, Brasil, utilizando Matriz 1 y Matriz 2 y también por un usuario externo a los grupos que trabajaron con Matriz 2. La investigación es de naturaleza exploratoria y aplicada. La muestra trabajada fue seleccionada convenientemente, está formada por dos fotografías que retratan temas actuales. Los participantes recibieron instrucciones de usar indización libre. Como resultado, se observó que al buscar información sobre el contexto de las fotografías, los profesionales de la información tenían más subsidios para la selección de palabras- clave al indexar usando Matriz 1. El usuario externo que usaba la Matriz 2 directamente y no buscó información sobre el contexto de las fotografías analizadas, identificó palabras clave relacionadas con el contenido que pudo ver e interpretar en la foto.
‘When They See Us’
Authors: Pineda Machuca Andros
Published: August 2021

Bajo el nombre “counter narratives” algunos textos adheridos a la llamada Critical Race Theory han impulsado el valor académico y social de las historias –personales, ajenas o recreadas– para contrarrestar narrativas hegemónicas. También son imbuidas con la capacidad de crear comunidad; proveer distintos escenarios que disipen las nociones estereotípicas más arraigadas sobre los grupos no hegemónicos. Fungen, también, como oportunidades para plantearse nuevas realidades y posibilidades distintas. En este artículo se explica, a través de conceptos de Critical Race Theory en conjunto con la Teoría de Representaciones Sociales, la importancia que tienen las historias –ficticias o basadas en hechos reales– contra hegemónicas. Se toma, en particular, el caso de la serie televisiva When They See Us, de la directora afroamericana Ava DuVernay, la cual recrea el caso real de cinco jóvenes falsamente acusados del ataque y violación a una joven blanca. En un entorno en el que las pantallas han resultado ser un importante vehículo para la lucha en contra del racismo sistémico en Estados Unidos, la serie se ha posicionado como uno de los productos más comentados en los días recientes.
Measuring the water balance in stormwater control measures
Authors: Fletcher Tim D. , Bertrand-Krajewski Jean-Luc , Bonneau Jérémie , Burns Matthew J. , Poelsma Peter J. , Thom Jasmine K.
Published: August 2021

Stormwater control measures (SCMs), also frequently referred to as sustainable urban drainage systems (SUDS), are of growing importance in cities, as part of a global move towards mitigating the impacts of stormwater on receiving environments. They need to be monitored as parts of UDSM systems but require specific and sometimes innovative methods and sensors. This is particularly the case for SCMs such as swales, rain-gardens, bioretention filters, infiltration trenches, green roofs, etc., which have complex and varied configurations and hydrologic behaviour. This chapter deals with measuring the water balance in SCMs by accounting for its various components: inflows, outflows, overflows, storage, infiltration, exfiltration, intrusion, evaporation, and evapotranspiration. It presents a range of suitable methods and tools, indicates key points to consider, and discusses possible difficulties in obtaining accurate monitoring data. Routine monitoring of decentralized and diversified SCMs is still an emerging field for both researchers and practitioners. A significant evolution is therefore expected with its generalization in the next years.
Data communication and storage
Authors: Branger Flora , Tait Simon , Chaffard Véronique , Brelot Elodie , Lecomte Vivien , Mallet Isabelle , Skipworth Peter
Published: August 2021

Monitoring programs in urban drainage systems generate, potentially, a huge amount of data from sources distributed in the urban environment, working at relatively high sampling rates for extended periods of time. Collecting data using adaptable and reliable communication systems is the first challenge. Then structuring the collected data is a first requisite for effectively managing the quality and accessibility of the data. In adjacent fields of research, the topic of managing huge collections of data has resulted in several (open) standards and protocols for database structure, transfer and storage to ensure unambiguous definitions on which parties can build their workflows/software. This chapter describes relevant approaches for urban drainage and stormwater management systems, and appropriate standards along with examples from case studies.
Data validation and data quality assessment
Authors: Clemens-Meyer Francois H. L. R. , Lepot Mathieu , Blumensaat Frank , Leutnant Dominik , Gruber Guenter
Published: August 2021

Once data have been recorded, data validation procedures have to be conducted to assess the quality of the data, i.e. give a confidence grade. Furthermore, gaps may occur in time series and, depending on the purposes, these can be given values by application of e.g. interpolation. Since both aspects are strongly correlated, this chapter gives an overview on the main data validation and data curation/imputation methods. Instead of offering exhaustive details on existing methods, this chapter aims at providing concepts for most popular techniques, a discussion of their advantages and disadvantages in the light of different cases of application, and some thoughts on potential impacts of the choices that must be made. Despite involving mathematical methods, data validation remains a largely subjective process: every data user must be aware of those subjectivities.
Data archiving and meta-data – saving the data for future use
Authors: Prodanović Dušan , Branisavljević Nemanja
Published: August 2021

This chapter covers the main aspects of data archiving, as the last phase of data handling in the process of urban drainage and stormwater management metrology. Data archiving is the process of preparing and storing the data for future use, usually not executed by the personnel who acquired the data. A data archive (also known as a data repository) can be defined as storage of a selected subset of raw, processed, validated and resampled data, with descriptions and other meta-data, linked to simulation results, if there are any. A data archive should be equipped with tools for search and data extraction along with procedures for data management, in order to maintain the database quality for an extended period of time. It is recommended, mostly for security reasons, to separate (both in a physical and in a digital sense) the archive database from the working database. This chapter provides the reader with relevant information about the most important issues related to data archive design, the archiving process and data characteristics regarding archiving. Also, the importance of good and comprehensive meta-data is underlined throughout the chapter. The management of a data archive is evaluated with a special focus on predicting future resources needed to keep the archive updated, secure, available, and in compliance with legal demands and limitations. At the end, a set of recommendations for creating and maintaining a data archive in the scope of urban drainage is given.
Fungi in dialysis water and dialysate: occurrence, susceptibility to antifungal agents and biofilm production capacity
Authors: Anversa Laís , Lara Bruna Rossini , Romani Caroline Demai , Saeki Erika Kushikawa , Nogueira Nascentes Gabriel Antonio , Bonfietti Lucas Xavier , Melhem Márcia de Souza Carvalho , da Silva Ruiz Luciana , Camargo Carlos Henrique , Pereira Virgínia Bodelão Richini
Published: August 2021

The aim of this study was to investigate the occurrence of fungi in dialysis water and dialysate, in addition to evaluating the susceptibility to antifungals and the biofilm production capacity of isolated microorganisms. The samples were collected in three hemodialysis units in Bauru (Brazil), every 15 days (July 2017–June 2018) at post-reverse osmosis, reuse, and dialysate points. The fungi were isolated by spread plate on Sabouraud dextrose agar. Filamentous fungi were phenotypically identified and yeasts were subjected to molecular evaluation of the ITS region. Susceptibility test to antifungals was carried out by the broth microdilution method and biofilm production capacity was evaluated in microtiter plates using crystal violet staining. Fungi were isolated in 52/216 (24.1%) samples, with an average count of 16.3 (10–40) CFU/mL. Overall, 61 microorganisms were identified, with 54 (88.5%) filamentous fungi and 7 (11.5%) yeasts. The main genera included were Penicillium, Cladosporium, Scedosporium, Rhinocladiella, Fusarium, and Emmonsia. Most isolates showed high values of minimum inhibitory concentration for 5-flucytosine and fluconazole and 35/45 (77.8%) isolates were classified as strong producers of biofilm. In order to increase the safety of the dialysis process, the adoption of control measures and monitoring of fungi in hemodialysis fluids is suggested.
LPS/TLR4 Pathways in Breast Cancer: Insights into Cell Signalling
Authors: Afroz Rizwana , Tanvir E.M. , Tania Mousumi , Fu Junjiang , Kamal Mohammad Amjad , Khan Md. Asaduzzaman
Published: August 2021

Background:

Cancer cells are usually recognized as foreign particles by the
immune cells. Mounting evidence suggest an important link between toll-like receptors
(TLRs) and carcinogenesis. This review article focused on the role of TLRs, especially
TLR4, in breast cancer.

Methods:

Research data on TLRs and cancer was explored in PubMed, Scopus, Google
Scholar and reviewed. Although some pioneer works are referenced, papers published in
the last ten years were mostly cited.

Results:

TLRs are widely investigated pattern recognition receptors (PRR), and TLR4 is
the most studied TLRs, implicated with the occurrence of several types of cancers, including
breast cancer. TLR4 activation occurs via the binding of its ligand lipopolysaccharide
(LPS), a component of the outer membrane of gram-negative bacteria. Upon LPS binding,
TLR4 dimerizes and recruits downstream signalling and/or adapter molecules, leading
to gene expression related to cancer cell proliferation, survival, invasion, and metastasis.
Although LPS/TLR4 signalling seems a single signal transduction pathway, the TLR4
activation results in the activation of multiple diverse intracellular networks with
huge cellular responses in both immune and cancer cells. The role of TLR4 in the
growth, invasion, and metastasis of breast cancer is attracting huge attention in oncology
research. Several clinical and preclinical studies utilize both TLR4 agonists and antagonists
as a treatment option for cancer therapy, either as monotherapy or adjuvants for
vaccine development.

Conclusion:

This review narrates the role of LPS/TLR4 signalling in breast cancer development
and future prospects for targeting LPS/TLR4 axis in the treatment of breast cancer.
Functional Group Transformation in Naphthoquinones: Strategies for the Synthesis of Mono- and Bis(Amino-1,4-Naphthoquinones)
Authors: Lima Carolina G. S. , de Souza Acácio S. , Pauli Fernanda P. , Ribeiro Ruan Carlos B. , de A. Borges Amanda , Ferreira Patricia G. , de C. da Silva Fernando , Ferreira Vitor F. , da S. M. Forezi Luana
Published: August 2021

:

1,4-Naphthoquinones are a group of natural and synthetic substances that participate
in various biochemical functions in most plants and animals, being involved in energy
production, electron transport, blood coagulation, and generation of reactive oxygen species
(ROS), among others. The performance of such biochemical functions is directly related to the
functional groups linked to the 1,4-naphthoquinone scaffold, and the introduction of nitrogencontaining
groups into this nucleus may amplify its biological activity against numerous targets.
Therefore, several methods have been developed in the last decades for preparing these
compounds, especially from 1,4-naphthoquinone derivatives. Considering these concepts, in
this review, we aim to provide insights into the chemistry, chemical synthesis, semi-synthesis,
pharmacological effects, and reactivity of low molecular weight mono- and bis(aminonaphthoquinones);
we start by discussing the use of some of the most important 1,4-naphthoquinones as starting materials
for the synthesis of amino-1,4-naphthoquinones (ANQs), examine the modification of ANQ derivatives, and conclude
by providing an outlook on this field.
Recent Developments in the Synthesis of Five- and Six-membered N-heterocycles from Dicarbonyl Compounds
Authors: Kaur Navjeet , Bhardwaj Pranshu , Gupta Mansi
Published: August 2021

Various diketones such as 1,2-diketones, 1,3-diketones, 1,4-diketones, β -
diketones and dicarbonyl compounds are used in the synthesis of core heterocyclic compounds
such as pyrazoles, isoxazoles, triazoles and quinolones. They play an important role
in synthetic organic chemistry. The diketones and dicarbonyl compounds also act as chelating
ligands for the lanthanides and a large number of transition metals in material chemistry.
50% of drugs contain nitrogen heterocyclic compounds, so organic chemists have made efforts
for the synthesis of nitrogen-containing heterocyclic compounds. This review article
has compiled different methodologies for the synthesis of five- and six-membered nitrogencontaining
heterocyclic compounds.
Numerical Characterization of DNA Sequences for Alignment-free
Sequence Comparison – A Review
Authors: Ramanathan Natarajan , Ramamurthy Jayalakshmi , Natarajan Ganapathy
Published: August 2021

Background:

Biological macromolecules, namely, DNA, RNA, and protein, have their
building blocks organized in a particular sequence and the sequential arrangement encodes the
evolutionary history of the organism (species). Hence, biological sequences have been used for
studying evolutionary relationships among the species. This is usually carried out by Multiple
Sequence Algorithms (MSA). Due to certain limitations of MSA, alignment-free sequence
comparison methods were developed. The present review is on alignment-free sequence
comparison methods carried out using the numerical characterization of DNA sequences.

Discussion:

The graphical representation of DNA sequences by chaos game representation and
other 2-dimensional and 3-dimensional methods are discussed. The evolution of numerical
characterization from the various graphical representations and the application of the DNA
invariants thus computed in phylogenetic analysis are presented. The extension of computing
molecular descriptors in chemometrics to the calculation of a new set of DNA invariants and their
use in alignment-free sequence comparison in an N-dimensional space and construction of
phylogenetic trees are also reviewed.

Conclusion:

The phylogenetic tress constructed by the alignment-free sequence comparison methods
using DNA invariants were found to be better than those constructed using alignment-based tools
such as PHLYIP and ClustalW. One of the graphical representation methods is now extended to study
viral sequences of infectious diseases for the identification of conserved regions to design peptidebased
vaccines by combining numerical characterization and graphical representation.
Taxonomy Classification using Genomic Footprint of Mitochondrial
Sequences
Authors: Mahapatra Aritra , Mukherjee Jayanta
Published: August 2021

Background:

Advancement in sequencing technology yields a huge number of genomes
from a multitude of organisms on our planet. One of the fundamental tasks for processing and
analyzing these sequences is to organize them in the existing taxonomic orders.

Method:

Recently, we proposed a novel approach, GenFooT, for taxonomy classification using
the concept of genomic footprint (GFP). The technique is further refined and enhanced in this work
leading to improved accuracies in the task of taxonomic classification based on various benchmark
datasets. GenFooT maps a genome sequence in a 2D coordinate space and extracts features from
that representation. It uses two hyper-parameters, namely block size and number of fragments of
genomic sequence while computing the feature. In this work, we propose an analysis of choosing
values of those parameters adaptively from the sequences. The enhanced version of GenFooT is
named GenFooT2.

Results and Conclusion:

We have tested GenFooT2 on ten different biological datasets of
genomic sequences of various organisms belonging to different taxonomy ranks. Our experimental
results indicate a 3% improved classification performance of the proposed GenFooT2 featured with
a Logistic regression classifier as compared to GenFooT. We also performed the statistical test to
compare the performance of GenFooT2 to the state-of-the-art methods including our previous
method, GenFooT. The experimental results as well as the statistical test exhibit that the
performance of the proposed GenFooT2 is significantly better.
A Bird's-Eye View of Proteomics
Authors: Uversky Vladimir N. , Alghamdi Mohammed F. , Redwan Elrashdy M.
Published: August 2021

:

Modern protein science is broadening horizons by moving toward the systemic description
of proteins in their natural habitats. This implies a transition from a classical reductionist approach
associated with consideration of the unique structure and specific biological activity of an
individual protein in a purified form to studying entire proteomes and their functions. This minireview
provides a brief description of structural, functional, and expression proteomics, the dark
proteome (or unfoldome), and some of the tools utilized in the analyses of proteomes.
Signal Peptides - Promising Ingredients in Cosmetics
Authors: Skibska Agnieszka , Perlikowska Renata
Published: August 2021

:

Naturally occurring peptides found in the human skin can serve particular biological activities
and play roles as signaling molecules of various physiological processes such as homeostasis,
growth, defense or immunity. Their great biological activity resulted in a growing interest in the
pharmaceutical industry. Researchers consider peptides either promising compounds with potential
application for human diagnosis, therapy or cosmetics. Peptides are becoming interesting cosmetic
ingredients with the functions to reduce premature skin aging, improve the barrier function of skin,
moisturize the skin, protect it from UV damage, and anti-inflammatory properties that alleviate acne
and irritation. Till now, peptides of different origins were investigated in formulation developed to
enhance collagen or elastin production, increase fibroblast proliferation, improve wound healing or
skin condition. Most of them are obtained by chemical synthesis or by partial digestion of animal
proteins. Short and easily synthesized peptides with alternative amino acid sequence, and combinations
have created a new field of molecules inspired by nature and implemented in the cosmetic
industry. Nowadays, peptides are cheaper and easier to produce in large quantities. The efficient
process development methods allow obtaining nearly unlimited sequences, which makes them functionally
preferred. Generally, cosmetic peptides are categorized as carrier peptides, neurotransmitter-
affecting peptides, enzyme inhibitor peptides and signal peptides. The use of signal peptides in
cosmetics increased over a few years. These molecules trigger a signaling cascade and stimulate
fibroblast collagen production, the proliferation of elastin, fibronectin, laminin, etc. Thus, a literature
search on a topical application of the most common signal peptides; and their current status in
the cosmetic industry was carried out.
Targeting the HIF-1α/Cav-1 Pathway with a Chicory Extract/Daidzein Combination Plays a Potential Role in Retarding Hepatocellular Carcinoma
Authors: Zakaria Sherin , Nawaya Reem , Abdel-Hamid Nabil M. , Eldomany Ramadan A. , El-Shishtawy Mamdouh M.
Published: August 2021

Background:

Hepatocellular carcinoma (HCC) is one of the most rapidly growing solid cancers, that is characterized by hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates tumor proliferation and metastasis. It induces caveolin-1 (Cav-1) expression, a glycoprotein found on the membrane surface, then Cav-1 triggers angiogenesis and metastasis in HCC.

Objectives:

We hypothesize that targeting HIF-1α and consequently, Cav-1 using the antioxidant natural compound such as chicoric acid and a Cav-1 inhibitor daidzein (DAZ) could be a useful approach in the management of HCC. This study was conducted to investigate the possible therapeutic efficacy of standardized chicory leaf extract (SCLE) and DAZ via modulation of HIF-1α and Cav-1 in HCC rats.

Methods:

Diethyl nitrosamine (DENA) was used for HCC induction. After the induction period, four groups (10 rats for each) were treated with SCLE, DAZ, a combination of both, as well as sorafenib, all compared to the non-treated control. We assessed hepatic HIF-1α protein expression, Cav-1 gene expression, serum level of AFP, hepatic tissue content of VEGF, MMP-9, oxidative stress markers MDA and SOD.

Results:

DAZ, SCLE, and their combination, significantly down-regulated the expression of HIF-1α, Cav-1, and consequently dampened MMP-9, VEGF, hepatic content. It has been observed that the combination treatment showed a synergistic effect compared to either treatment alone. Importantly, the combination treatment exhibited a significantly more potent effect than sorafenib.

Conclusion:

This study showed the potential role of the HIF-1α/Cav-1 pathway in HCC progression, moreover, SCLE and DAZ showed a potent efficacy in retarding HCC via modulation of this pathway.
Effectiveness of Relationship Enrichment Program (REP) on Sexual Dysfunction
and Satisfaction of Females with Multiple Sclerosis-An Educational
Study
Authors: Vakilian Katayon , Sayari Negin , Khalajinia Zohre , Hejazi Seyyed Amir , Vahedian Mostafa
Published: August 2021

Aims:

Improving sexual function in women with disability such as multiple sclerosis
was aimed.

Background:

Sexual dysfunction and the consequent low satisfaction is very common in females
with Multiple Sclerosis (MS).

Objectives:

This study aimed to investigate the effectiveness of Relationship Enhancement Therapy
(REP) on sexual function and satisfaction of females with MS.

Methods:

The present study was an educational design with two groups, in which 44 females with
MS participated and their spouses (N= 88) participated and randomly divided in two groups of intervention
(N= 22 couples) and control (N= 22 couples). They signed written consent forms and
were included in the project. The intervention group received the REP in six 90-minute sessions.
The groups completed standard questionnaires of sexual dysfunction and sexual satisfaction in
three stages of pretest-posttest and 3 months later. The Descriptive and inferential statistics (Twoway
repeated measures ANOVA, chi-square, t-test and Mann-Whitney U test) were used to analyze
data.

Results:

The results of analysis showed that there was a clinically significant difference between
the scores of sexual dysfunction in different phases of the assessment between two groups (p
<0.05). Also sexual satisfaction was higher in the intervention group vs. in the control (p <0.05).

Conclusion:

According to the findings, marital enrichment program was effective in improvement
of sexual function and sexual satisfaction of females with multiple sclerosis. It is recommended to
healthcare providers to use enrichment alongside medical services to improve patients' sexual life.
Possible Role of PTEN Expression in Discriminating Benign Endometrial
Hyperplasia from Atypical Hyperplasia/Endometrial Intraepithelial Neoplasia
in a Series of Egyptian Patients
Authors: Khalifa Sara E. , Ramzy Nevine I. , Ibrahiam Wael S. , Ali Hanan H.M. , Akle Mona M.A.
Published: August 2021

Background:

Endometrial hyperplasia represents a heterogeneous group of lesions in response to the unopposed growth-promoting action of estrogen. WHO classified endometrial hyperplastic lesions into Benign Hyperplasia (BH) and atypical hyperplasia/ endometrial intraepithelial neoplasia AH/EIN. Phosphatase and tensin homolog (PTEN) is one of the earliest and most common genetic abnormalities detected in endometrioid adenocarcinoma (type I) and even in its precursors. This study aimed at histological evaluation of hyperplastic endometrial lesions according to WHO 2014 and investigating the role of PTEN expression in highlighting the precancerous group (AH/EIN).

Patient and Method:

This study included a series of 70 Egyptian patients suffered from hyperplastic endometrial lesions. They were previously diagnosed according to WHO1994 schema simple endometrial hyperplasia without atypia (n=18), simple endometrial hyperplasia with atypia (n=2), complex hyperplasia without atypia (n=25), complex hyperplasia with atypia (n=5) and hyperplastic endometrial polyps (n=20).

Results:

Cases were histologically re-evaluated according to WHO 2014 classification; BH (62 cases) and eight cases of AH/EIN. A significant difference in PTEN expression (regarding percentage and intensity of staining) in relation to histopathological diagnosis was detected (P-value 0.02 and <0.05, respectively). The sensitivity and specificity of the absence of diffuse PTEN protein expression (>50%) to detect AH/EIN were 100% and 77.4%, respectively. Conclusion: Diffuse, dim or loss of immunohistochemical expression of PTEN protein is significantly correlated with the new WHO classification segregation of AH/EIN as precancerous lesions. However, further studies are recommended to confirm this association.
Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer
Cells
Authors: Fagundes Tatiane Renata , Bortoleti Bruna , Camargo Priscila , Concato Vírgínia , Tomiotto-Pellissier Fernanda , Carloto Amanda , Panis Carolina , Bispo Marcelle , Junior Fernando Macedo , Conchon-Costa Ivete , Pavanelli Wander Rogério
Published: August 2021

Background:

Conventional therapies for breast cancer are still a challenge due to cytotoxic drugs not being
highly effective with significant adverse effects. Thiohydantoins are biologically active heterocyclic compounds reported
for several biological activities, including anticarcinogenic properties, etc. This work aims to assess the use of
thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells.

Methods:

MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7
cells. Cell volume measurement and analysis were performed by flow cytometry. Fluorescence analysis was carried out
to determine patterns of cell death induced by thiohydantoins.

Results:

The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast
tumor cells. An increase in the ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial
depolarization, and increased fluorescence for annexin-V and caspase-3 were also observed. These findings
indicate cell death by apoptosis and increased autophagic vacuoles, stopping the cell cycle in the G1/ G0 phase.

Conclusions:

Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the
increase in ROS production. This phenomenon changes tumorigenic pathways, which halt the cell cycle in G1/G0. This
is an essential checkpoint for DNA errors, which may have altered how cells produce energy, causing a decrease in
mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy,
a vital process linked to a decrease in lysosomal viability and thus considered a cell death and tumor suppression
mechanism.
Alkylating Agents, the Road Less Traversed, Changing Anticancer Therapy
Authors: Kumar Dileep , Karati Dipanjan , Mahadik Kakasaheb Ramoo , Trivedi Piyush
Published: August 2021

:

Cancer is considered one of the gruelling challenges and poses a grave health hazard across the globe. According to the International Agency for Research on Cancer (IARC), new cancer cases increased to 18.1 million in 2018, with 9.6 million deaths, bringing the global cancer rate to 23.6 million by 2030. In 1942, the discovery of nitrogen mustard as an alkylating agent was a tremendous breakthrough in cancer chemotherapy. It acts by binding to the DNA, and creating cross linkages between the two strands, leading to halt of DNA replication and eventual cell death. Nitrogen lone pairs of ‘nitrogen mustard’ produce an intermediate 'aziridinium ion' at the molecular level, which is very reactive towards DNA of tumour cells, resulting in multiple side effects with therapeutic consequences. Owing to its high reactivity and peripheral cytotoxicity, several improvements have been made with structural modifications for the past 75 years to enhance its efficacy and improve the direct transport of drugs to the tumour cells. Alkylating agents were among the first non-hormonal substances proven to be active against malignant cells and also the most valuable cytotoxic therapies available for the treatment of leukaemia and lymphoma patients. This review focus on the versatile use of alkylating agents and the Structure Activity Relationship (SAR) of each class of these compounds. This could provide an understanding for design and synthesis of new alkylating agents having enhanced target specificity and adequate bioavailability.