bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of hub genes affecting triple-negative breast cancer using bioinformatics analysis strategies
Authors: Liu can , Kan Hongxing , Wang Yongkang , Gao Yong , Nie Yiqi , Zhang Yuxuan , Hu Jili
Published: June 2022

BackgroundBreast cancer is one of the most serious malignancies in women throughout the world, with an increasing number of people being diagnosed and dying from it. Triple-negative breast cancer (TNBC), which has a dismal prognosis, the estrogen receptor (ER), progesterone receptor (PR), and human growth factor receptor type 2 (Her2) immunohistochemistry test results are all negative. MethodsTo find differentially expressed genes (DEGs), two datasets from the Gene Expression Omnibus (GEO) were used to search for TNBC and not triple-negative breast cancer (not-TNBC) differentially expressed genes. Using weighted gene co-expression network analysis (WGCNA), the breast cancer data from the Cancer Genome Atlas (TCGA) was utilized to study the relationship between genes and TNBC features and to identify the hub genes in the most important linked modules. The Gene Ontology (GO) and Kyoto Encyclopedia of the Genes and Genomes (KEGG) enrichment analyses were performed on the differential genes in the GEO dataset and the hub genes in the TCGA dataset to study the nature of genes and to find gene enrichment pathways. A protein-protein interaction network (PPI) was created for each of the genes considered. To discover the most important genes in PPI networks, utilize the cytoHubba plugin in Cytoscape. Following that, the gene expression profiling interaction analysis (GEPIA) was used to confirm the hub gene's expression. Finally, data sets from the cBioPortal database were utilized for survival analysis. ResultsWe detected 7 genes that were up-regulated and 2 genes that were down-regulated by combining the GEO and TCGA databases.PGR, ELF5, AGR2, and GATA3 prolong life expectancy, while ESR1, TFF1, FOXA1, and AR shorten life expectancy.ConclusionOur study confirmed that PGR, ELF5, AGR2, GATA3, ESR1, TFF1, FOXA1, and AR may be potential therapeutic targets and biomarkers for TNBC.
Infection by the parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) suppresses the immune system of hybrid tilapia
Authors: Maor-Landaw Keren , Smirnov Margarita , Brekhman Vera , Ofek-Lalzar Maya , Yahav Tal , Lotan Tamar
Published: June 2022

Background: Tilapia is the second most cultured fish worldwide and in Israel, it constitutes 60% of total production. Recently, the myxozoan parasite Myxobolus bejeranoi was found to infect the gills of hybrid tilapia (Nile tilapia (Oreochromis niloticus) X Jordan/Blue tilapia (O. aureus)), causing high morbidity and mortality. Myxozoa (Cnidaria) is a large group of microscopic obligate endoparasites that can cause emerging diseases, affecting wild fish populations and fisheries. Here, we aimed to elucidate the cellular processes occurring in the fish host following infection by M. bejeranoi. Methods: Comparative transcriptomics was performed on fish that had been exposed to infectious fish pond water containing M. bejeranoi actinospores for 24 hours. We compared the effects of minor, intermediate, and severe infection levels on the sporulation site, namely the gills, as well as on the hematopoietic organs head kidney and spleen. Enrichment analyses for Gene Ontology and KEGG pathways were performed and gene network was generated based on Jaccard distance matrix and visualized with Cytoscape. Results: Enrichment analysis indicated immune system activation in the gills at severe infection stage. However, in the head kidney a broad immune suppression was observed, including deactivation of secreted cytokines that play important roles in immune response of fish and of a transcription factor responsible for T helper cell differentiation. Moreover, the cytotoxic effector proteins perforin and granzyme B were down-regulated in the spleen. Finally, significant up-regulation of insulin in the spleen may imply that it functions as an immunomodulatory hormone inducing systemic immune suppression. Conclusions: Our analysis illustrates the incapacity of the hybrid tilapia host to eliminate its pathogenic invader, the myxozoan M. bejeranoi. We hypothesize that the signal for immune suppression originates at the sporulation site and traverses to the hematopoietic organs. These findings suggest that M. bejeranoi is a highly efficient parasite that disables the defense mechanisms of its fish host.
Bi-Metallic films of Gold, MXene, and Graphene nano film-based Surface Plasmon Resonance Sensor for Malaria Detection: A Numerical Analysis
Authors: Uniyal Arun , Chauhan Brajlata , Pal Amrindra
Published: June 2022

In this proposed work, an SPR-based biosensor with dual nanofilms of a gold metal, 2-Dimensional MXene, and graphene has been proposed to detect different malaria stages. The principal obeyed by the sensor design is attenuated total reflection (ATR) with a modified Kretschmann-based configuration. Numerical computational results give the higher sensitivity for our proposed design as 227.9 degree/RIU (for single MXene and dual graphene layers at RI variation of 1.33 to 1.38 with a change of 0.01) and 258.28 degree/RIU(for trophozoite stage of malaria disease), with other performance parameters like DA computed as equal to 0.14 degree-1 , QF as 31 RIU-1 and 35.5 RIU-1, FWHM as 7.35 degree and 7.27 degree for single MXene, dual graphene nanofilms and trophozoite stage respectively. The suggested biosensor can diagnose the various stages of severe malaria disease by measuring the refractive index alteration in red blood cells (RBCs).
Inhibitory of active dual cancer targeting 5-Fluorouracil nanoparticles on liver cancer in vitro and in vivo
Authors: Cheng Mingrong , Dejian Dai
Published: June 2022

In the previous experiments, biotin (Bio) was grafted onto CS to synthesize biotin-modified chitosan (Bio-CS) with liver cancer targeting efficacy, but there is still room for improvement in the targeting of Bio-CS to liver cancer. Based on the high expression of folate (FA) receptors on the surface of liver cancers, FA was grafted onto Bio-CS by chemical synthesis to optimize the synthesis of folic acid-modified biotinylated chitosan (FA-CS-Bio), verified by infrared spectroscopy and 1H-NMR. FA-CS-Bio/Fluorouracil (5-FU) nanoparticles had an obvious sustained release effect. Compared with Bio-CS, FA-CS-Bio could promote the inhibition of the proliferation and migration of liver cancer by 5-FU, and the concentration of 5-FU in hepatoma cells was significantly increased. Laser confocal experiments confirmed that FA-CS-Bio caused a significant increase in the fluorescence intensity in liver cancer cells. In terms of animal experiments, FA-CS-Bio increased the concentration of 5-FU in liver cancer tissue by 1.6 times on the basis of Bio-CS and the number of monophotons in liver cancer tissue by in vivo dynamic imaging experiments was significantly stronger than that of Bio-CS, indicating that the targeting ability of FA-CS-Bio was further improved. Compared with Bio-CS, FA-CS-Bio can significantly prolong the survival time of an orthotopic liver cancer transplantation model in mice and has a relieving effect on liver function damage and bone marrow suppression caused by 5-FU. In conclusion, FA-CS-Bio has significantly improved liver cancer targeting ability, prolonged the survival period of tumor-bearing mice, and alleviated the toxic and side effects caused by 5-FU.
Engine Oil Quality Deterioration Estimation Using Integrated Sensory System
Authors: Shinde Harish M. , Bewoor Anand K. , Kumar Ravinder , Elsheikh Ammar H. , Singh Dheerendra vikram , Sengottain S. , Panchal Hitesh
Published: June 2022

Engine oil deterioration level affects working and performance of internal combustion engine. Hence, it is necessary to compare the deterioration level of engine oils, with focus on kinematic viscosity, oxidation, nitration etc. which are important oil testing parameters. If without quantifying the remaining useful life of the engine oil, it is changed too early, results in insufficient use of already depleting resources and also unwanted impact on environment while disposing. Changing the engine oil too late with deteriorated quality, will hamper the performance of engine. To determine optimum point for changing engine oil, in present study oil testing is carried out for vehicle which is due for servicing. The oil samples collected randomly from vehicles which came to an authorized service station for servicing covering a large range from the first servicing to the fifth servicing were tested. Oil samples were first tested by a viscometer and FTIR spectroscopy in a laboratory as per standard. The samples were then tested on a setup of sensors designed and developed by the authors. The results provided a fairly strong positive relationship between important engine oil deterioration parameters such as kinematic viscosity, oxidation and nitration with the determination coefficient R2 = 0.97.Out of total collected samples about 8% samples were within usable limit. The study uncovers different oil deterioration sensor methods which provide low cost, on-site handy solutions for oil condition monitoring and the forecasting of the remaining useful life of the engine oil.
RNA-seq analysis, targeted long-read sequencing, and in silico prediction to unravel pathogenic intronic events and predict the regulatory mechanisms underlying complex splicing abnormalities in patients with dystrophinopathy
Authors: Okubo Mariko , Noguchi Satoru , Awaya Tomonari , Hosokawa Motoyasu , Tsukui Nobue , Ogawa Megumu , Hayashi Shinichiro , Komaki Hirofumi , Mori-Yoshimura Madoka , Oya Yasushi , Takahashi Yuji , Fukuyama Tetsuhiro , Funato Michinori , Hosokawa Yousuke , Kinoshita Satoru , Matsumura Tsuyoshi , Nakamura Sadao , Oshiro Azusa , Terashima Hiroshi , Nagasawa Tetsuro , Sato Tatsuharu , Shimada Yumi , Tokita Yasuko , Hagiwara Masatoshi , Ogata Katsuhisa , Nishino Ichizo
Published: June 2022

Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation. DMD transcripts from 20 genetically undiagnosed dystrophinopathy patients in whom no exon variants were identified, despite dystrophin deficiency on muscle biopsy, were analyzed by transcriptome sequencing. Genome sequencing captured intronic variants and their effects were interpreted using in silico tools. Targeted long-read sequencing was applied in cases with suspected structural genomic abnormalities. Abnormal DMD transcripts were detected in all cases analyzed. Exonization of intronic sequences was observed in 15 cases and exon skipping in one case; 13 single nucleotide variants and three structural rearrangements were identified as causal genomic variations. DMD transcripts were aberrantly spliced and polyadenylated in two cases in which chromosome rearrangements were detected. In one case, DMD transcripts were terminated due to nucleotide repeat expansion. Our combined analysis approach successfully identified pathogenic events. Detection of diseasing-causing mechanisms in DMD transcripts could inform the therapeutic options for patients with dystrophinopathy.
Effects of Riceberry rice bran oil supplementation on oxidative stress, cardiovascular risk biomarkers, and cardiac autonomic nervous system activity in older adults with prehypertension
Authors: Prasertsri Piyapong , Boonla Orachorn , Vierra Jaruwan , Yisarakun Waranurin , Koowattanatianchai Sukrisd , Phoemsapthawee Jatuporn
Published: June 2022

Background
In this study, we aimed to measure the changes in the biomarkers of oxidative stress, cardiovascular disease risk, and the activity of the cardiac autonomic nervous system in older adults with prehypertension after supplementation with Riceberry rice bran oil.
Methods
In total, 35 women aged 60–76 years with prehypertension were randomly allocated to two groups, one of which was supplemented with rice bran oil (n = 18) and the other with Riceberry rice bran oil (n = 17) at 1,000 mg (500 mg × 2 capsules) daily for 8 weeks. The primary outcomes, including oxidative stress and cardiovascular risk biomarkers, and secondary outcomes, including heart rate variability and blood pressure, were determined before and after the 8-week supplementation.
Results
The levels of plasma malondialdehyde, blood glutathione disulfide, and tumor necrosis factor-alpha were significantly decreased, and the ratio of reduced glutathione to glutathione disulfide significantly increased in both groups after supplementation (all p < 0.05). No significant differences were noted between groups. Heart rate variability and blood pressure were not statistically significantly different after supplementation in both groups.
Conclusions
Supplementation with Riceberry rice bran oil for 8 weeks may attenuate oxidative stress and inflammation in older adults with prehypertension. The effects of a longer supplementation period or use in hypertensive persons should be further investigated, especially with regard to blood pressure and cardiac autonomic nervous system activity.
Trial registration:
This trial was registered March 22, 2019 at https://www.thaiclinicaltrials.org as TCTR20190322002.
‹Also, das wäre sehr hilfreich, wenn es dazu einfach auch einmal ein Konzept gäbe, was man Schulen an die Hand gibt. Dass nicht da jede Schule ewig ihr eigenes Süppchen kocht›
Authors: Herfurth Esther , Fereidooni Karim
Published: June 2022

Mit der These, die moderne Gesellschaft sei seit je her digital, bezeichnet Nassehi (2019) die Digitalisierung als ein alle gesellschaftlichen Teilsysteme durchdringendes Phänomen. In der Folge ist auch die Schule zur eigenen Stabilisierung angehalten, neue Strukturen auszubilden, um den Anforderungen der modernen, digitalen Arbeits- und Wissensgesellschaft und damit ihrem Erziehungsauftrag gerecht zu werden. Anhand von Interviews mit Medienberatenden konnte gezeigt werden, dass Deutschland hinsichtlich dieser Thematik noch vor grossen Herausforderungen steht, die sich insbesondere auf eine nicht angemessene IT-Infrastruktur an Schulen sowie unzureichende Thematisierungen in der Aus- und Fortbildung von Lehrpersonen beziehen, was zwingend die Zusammenarbeit aller Beteiligten erfordert. Schulen sehen sich mit neuen Lernzielen und Unterrichtsformaten konfrontiert. Die KMK-Strategie stellt darauf bezogen ein Orientierung stiftendes Hilfsmittel dar, um Digitales mit Analogem in Einklang zu bringen. Insgesamt 14 Gelingensbedingungen sind in dieser Studie unter der Forschungsfrage identifiziert worden: Welche Bedingungen sind nach subjektiver Einschätzung von Medienberatenden in NRW für einen gelingenden Digitalisierungsprozess an der Institution Schule notwendig?
Preschool teachers’ perspective on factors of intergenerational learning important for professional development
Authors: Šindić Aleksandra , Partalo Dragan , Ličen Nives
Published: June 2022

The theoretical framework of the study is represented by two concepts: intergenerational learning and professional development. Quantitative research conducted in 2021 on a sample of 108 preschool teachers of preschool institutions in the Banja Luka region (Bosnia and Herzegovina, Republic of Srpska) aimed to examine the perspective of preschool taechers on the factors of intergenerational learning important for their own professional development. Using factor analysis (Principal component analysis, PCA), three factors of intergenerational learning were singled out from the perspective of preschool teachers, and they are: professional cooperation and personal growth; inclusion of the elderly in educational work and humanities education; prejudices and stereotypes. The findings indicate that preschool teachers strongly recognize intergenerational learning in the context of personal growth, work and career, but also notice the humane and inclusive nature of intergenerational cooperation, while not prone to intergenerational stereotypes and prejudices against colleagues from other generations, and that encouraging professional cooperation, and the promotion and support of the inclusion of the elderly can contribute to the reduction of intergenerational conflicts and prejudices.
A constructive theory of the numerically accessible many-body localized to thermal crossover
Authors: Crowley Philip , Chandran Anushya
Published: June 2022

The many-body localised (MBL) to thermal crossover observed in exact
diagonalisation studies remains poorly understood as the accessible
system sizes are too small to be in an asymptotic scaling regime.
We develop a model of the crossover in short 1D chains in which the
MBL phase is destabilised by the formation of many-body resonances.
The model reproduces several properties of the numerically observed
crossover, including an apparent correlation length exponent
\nu=1ν=1,
exponential growth of the Thouless time with disorder strength, linear
drift of the critical disorder strength with system size, scale-free
resonances, apparent 1/\omega1/ω
dependence of disorder-averaged spectral functions, and sub-thermal
entanglement entropy of small subsystems.
In the crossover, resonances induced by a local perturbation are rare
at numerically accessible system sizes LL
which are smaller than a \lambdaλ.
For L \gg \sqrt{\lambda}L≫λ
(in lattice units), resonances typically overlap, and this model does
not describe the asymptotic transition.
The model further reproduces controversial numerical observations
which Refs. claimed to be inconsistent with MBL. We thus argue that the
numerics to date is consistent with a MBL phase in the thermodynamic
limit.
Особенности гемоглобинизации у пациентов периода новорожденности
Authors:   ФГБОУ ВО «Приволжский исследовательский медицинский университет», Гераськин Владимир , Гераськина Наталья ,   ГБУЗ НО «Нижегородская областная детская клиническая больница», Фёдоров Михаил ,   ФГБОУ ВО «Приволжский исследовательский медицинский университет», Гераськин Иван ,   ФГБОУ ВО «Приволжский исследовательский медицинский университет»
Published: June 2022

Определение динамики изменений фракций гемоглобинов крови при патологии в периоде новорожденности и первые месяцы жизни.
Опыт использования гибридной формы обучения на кафедре гистологии, эмбриологии и цитологии ФГБОУ ВО «Ижевская государственная медицинская академия»
Authors:   Кафедра гистологии, эмбриологии и цитологии, Ижевская государственная медицинская академия, Глушкова Татьяна , Титова Ирина ,   Кафедра гистологии, эмбриологии и цитологии, Ижевская государственная медицинская академия, Шумихина Галина , Корепанова Юлия , Осетрова Анастасия ,   Кафедра гистологии, эмбриологии и цитологии, Ижевская государственная медицинская академия
Published: June 2022

Растущий объем информации и требования современной жизни диктуют необходимость использования новых методов и подходов в обучении. В последнее время неизбежно увеличилась роль дистанционного обучения с применением электронных технологий. В практикоориентированных дисциплинах возможно использование только гибридного варианта обучения.
Система комплимента крови у пациентов с синдромом падений и постуральными нарушениями
Authors:   Тамбовский филиал ФГАУ «НМИЦ «МНТК «Микрохирургия глаза» им. акад. С. Н. Фёдорова», Гурко Татьяна
Published: June 2022

Синдром падений часто встречается у пациентов, имеющих постуральные нарушения статического и динамического характера. Однако при оценке постуральных нарушений у пациентов с синдромом падений рассматривается, как правило состояние мышечного аппарата, но неизученными остаются нарушения в системе комплимента крови.
Значение деловых игр в формировании психологического благополучия при изучении морфологических дисциплин.
Authors:   Кафедра гистологии, эмбриологии и цитологии «ФБГОУ ВО Кировского ГМУ Минздрава России, Жданова Ольга , Часовских Ольга ,   Кафедра гистологии, эмбриологии и цитологии «ФБГОУ ВО Кировского ГМУ Минздрава России, Окулова Ираида ,   Кафедра гистологии, эмбриологии и цитологии «ФБГОУ ВО Кировского ГМУ Минздрава России, Макарова Надежда ,   Кафедра гистологии, эмбриологии и цитологии «ФБГОУ ВО Кировского ГМУ Минздрава России, Мутошвили Лиа ,   Кафедра гистологии, эмбриологии и цитологии «ФБГОУ ВО Кировского ГМУ Минздрава России, Сухих Олеся ,   Кафедра физиологии «Вятского государственного агротехнологического университета»
Published: June 2022

Внедрение современных информационных, в т.ч. дистанционных, технологий в изучение морфологических дисциплин требует от студентов постоянной готовности к изменению учебных целей, смыслов, перестройке способов взаимодействия с преподавателями и однокурсниками. В связи с этим возникает вопрос об адекватных методах диагностики психологического благополучия студентов как состояния. Цель статьи- провести анализ психологического благополучия студентов при проведении деловой игры "Брейн-Ринг"
Возрастные изменения длины тела у школьниц 7-16 лет
Authors:   Кафедра физиологии человека и животных, факультет биологии и экологии, Ярославский государственный университет им. П.Г.Демидова, Митягова Анастасия , Тятенкова Наталия ,   Кафедра физиологии человека и животных, факультет биологии и экологии, Ярославский государственный университет им. П.Г.Демидова
Published: June 2022

Цель исследования - изучить возрастные особенности показателей длины тела у девочек школьного возраста г. Ярославля.
Деятельность В.Ф. Войно-Ясенецкого (Святого Луки) как земского врача, хирурга и морфолога в Курской губернии
Authors:   кафедра анатомии человека , Уральский государственный медицинский университет , г. Екатеринбург, Михалкина Марина
Published: June 2022

27 апреля 2022 года исполнилось 145 лет со дня рождения, а 11 июня 2021 года минуло 60 лет со дня смерти знаменитого хирурга и деятеля Русской Православной Церкви (РПЦ) Валентина Феликсовича Войно-Ясенецкого (Святого Луки). Достаточно короткий, но очень насыщенный период его жизни (ноябрь 1905 г. – начало 1908 г.) связан с Курской губернией (нынешней Курской областью), древнейшим историко-культурным центром русской земли.
Иммуногистохимическое исследование периневрия
Authors:   Лаборатория функциональной морфологии центральной и периферической нервной системы Отдела общей и частной морфологии Федерального государственного бюджетного научного учреждения «Институт экспериментальной медицины», Петрова Елена , Колос Елена ,   Лаборатория функциональной морфологии центральной и периферической нервной системы Отдела общей и частной морфологии Федерального государственного бюджетного научного учреждения «Институт экспериментальной медицины»
Published: June 2022

Актуальность исследования периневральной оболочки периферических нервных проводников связана с недостатком знаний о механизмах регуляции гемато-неврального барьера, который обеспечивает нормальное функционирование нерва, а клетки, его формирующие, принимают участие в регенерации нерва. Целью настоящего исследования явилось изучение распределения белка плотных клеточных контактов клаудина-1 в седалищном нерве крысы в норме и после травмы.
Морфофункциональные особенности тучных клеток при инфицировании Helicobacter pylori
Authors:   Воронежский государственный медицинский университет имени Н.Н. Бурденко., Шишкина Виктория , Клочкова Светлана ,   Российский университет дружбы народов, Алексеева Наталия ,   Воронежский государственный медицинский университет имени Н.Н. Бурденко., Самодурова Наталья ,   Воронежский государственный медицинский университет имени Н.Н. Бурденко., Герасимова Ольга ,   Воронежский государственный медицинский университет имени Н.Н. Бурденко., Самойленко Татьяна ,   Воронежский государственный медицинский университет имени Н.Н. Бурденко., Антакова Любовь ,   Воронежский государственный медицинский университет имени Н.Н. Бурденко.
Published: June 2022

Одними из ключевых промоторов в регуляции каскада воспалительных медиаторов являются тучные клетки, обладающие широким арсеналом биологически активных веществ. В патогенезе гастрита, ассоциированного с H. pylori принимают активное участие различные виды иммунокомпетентных клеток - макрофаги, нейтрофилы, эозинофилы, дендритные клетки, Т- и В-лимфоциты, а также тучные клетки. Антигенпредставляющие свойства тучных клеток представляют интерес в аспекте взаимодействия с Helicobacter pylori (H. Pylori)
Numerical methods and algorithms for reconstruction of holographic images with an flexibility choice of physical size of the object and observation area
Authors:   St. Petersburg State University, Fedorov Arthur G. ,   M. K. Ammosov North-Eastern Federal University, Trofimov Vasiliy V. ,   St. Petersburg State University, Karpov Andrey G. ,   St. Petersburg State University
Published: June 2022

Within the framework of this work, the numerical results of simulation and reconstruction of holographic images with different physical sizes of the object and observation areas are presented. Simple and practical approaches to relatively flexibility choice of physical areas (e. g., units of m2) in both planes are proposed. Algorithms are presented in the case when the dimensions of the plane of the object and observation coincide. Two-step scattering algorithms are presented for the simulation and reconstruction of holographic images with a relatively flexibility choice of the physical areas of the object plane and observation.
What Rare Disease Patient Advocacy Groups Are Doing to Mitigate the Effects of Disparities
Authors: Drell Debbie , De Silva Ashanthi , Lee Cornelia
Published: June 2022

Compared with chronic diseases affecting larger populations, rare disease (RD) patients experience great inequities in diagnosis, care, and research. Within RDs, health disparities compound these inequities, as marginalized communities experience additional barriers in accessing clinical care and are often underrepresented from participation in research and clinical trials. For almost 40 years, the National Organization for Rare Disorders (NORD), a RD umbrella organization with over 300 nonprofit organizational members, has led efforts to understand and address inequities for the RD community through innovative research, programming, and collaboration with patients, caregivers, practitioners, and external stakeholders.

The beginning of the COVID-19 pandemic in 2020 brought to light longstanding disparities and discrimination for marginalized communities as well as pivotal racial justice movements. These events spurred many RD nonprofit organizations’ interest in increasing outreach and engagement with minoritized communities within RDs and diversifying their organization internally. Building on the increased interest in diversity, equity, and inclusion (DEI), NORD has focused on collecting case studies from within NORD and its member organizations to capture current efforts to improve DEI within the RD ecosystem. One way clinicians can work to mitigate the effects of disparities is to collaborate with RD patient organizations; this article provides a means by which clinicians and researchers can understand some of the challenges RD nonprofit organizations face in bridging disparities and learn about solutions to supporting marginalized patients within their communities. Clinicians are encouraged to join NORD in our policy efforts advocating to ensure patient access to health care providers practicing in a different state vis-à-vis telehealth.
Atypical Antipsychotic Drugs in Dual Disorders: Current Evidence for Clinical
Practice
Authors: Martinotti Giovanni , Chiappini Stefania , Mosca Alessio , Miuli Andrea , Santovito Maria Chiara , Pettorruso Mauro , Skryabin Valentin , Sensi Stefano L. , Giannantonio Massimo Di
Published: June 2022

Background:

Concurrent disorder or dual diagnosis refers to a combination of substance use disorders and mental disorders that occur in the same patient simultaneously. These conditions pose significant clinical and healthcare impacts and are often underdiagnosed, undertreated, and complex to manage.

Objective:

We assessed the quality of current pharmacological recommendations for the management of dual diagnosis, particularly by evaluating the use of second-generation antipsychotics (SGA).

Method:

A literature search was performed using the PubMed and Scopus databases for publications up to September 21, 2021, without any time restrictions. The following search strings were used: (aripiprazole OR brexpiprazole OR cariprazine OR paliperidone OR risperidone OR quetiapine OR clozapine OR olanzapine) AND (psychosis OR schizophrenia OR schizoaffective) AND (“substance use disorder” OR cocaine OR alcohol OR cannabis OR heroin OR “double diagnosis” OR “dual diagnosis”)) NOT (animal OR rat OR mouse) NOT (review or meta-analysis).

Results:

The search produced a final set of 41 articles. Most patients were males and were affected by schizophrenia, with cannabis the most abused substance, followed by alcohol. Aripiprazole was the most used drug, either orally or by long-acting formulations, followed by risperidone with oral and long-acting formulations, clozapine, olanzapine, and quetiapine.

Conclusion:

The findings highlight the use of SGA for the treatment of psychotic symptoms in comorbidity with substance use. Future studies on people with dual diagnosis and focused on long-term evaluations are warranted and need to investigate the efficacy of newly introduced molecules, such as partial D2 agonists and long-acting injectable antipsychotics.
Effect of C. cyminum and L. sativum on Pharmacokinetics and Pharmacodynamics of
Antidiabetic Drug Gliclazide
Authors: I. Al-Suwaydani Abdulelah , Alam Mohd A. , Raish Mohammed , A. Bin Jardan Yousef , Ahad Abdul , I. Al-Jenoobi Fahad
Published: June 2022

Background:

Numerous herbs are reported to have anti-hyperglycemic activity and are frequently used in
combination with prescription drugs to lower the blood glucose levels in diabetic patients, without proper knowledge
about the possibility of herb-drug interaction.

Objectives:

To investigate the effect of cumin and garden cress on pharmacokinetics (PK) and pharmacodynamics
(PD) of gliclazide (GLZ) in nicotinamide-streptozotocin diabetic model.

Methods:

Diabetic animals of groups II-IV were treated with GLZ, cumin, ‘cumin + GLZ’, garden cress and ‘garden
cress + GLZ’. Herb’s treatments were given for two weeks, and GLZ was administered in a single dose. Blood glucose
levels (BGLs) were measured at pre-determined time points. Plasma samples of pharmacokinetic study were
analyzed using UPLC-MS/MS. GLZ fragment at m/z 324.1>127 was monitored.

Results:

Cumin and garden cress have shown 15.3% and 15.9% reduction in mean BGL (1-24h) (p-value < 0.001),
respectively. GLZ reduced mean BGL by 30.0%, which was significantly better than cumin and garden cress (pvalue
<0.05). Concurrently administered “garden cress + GLZ” demonstrated the highest reduction in mean BGL
(by 40.46%) and showed a prolonged effect. There was no significant advantage of simultaneously administered
‘cumin + GLZ’. Cumin did not affect PK of GLZ. Garden cress has significantly enhanced AUC0-t (by 69.8%, pvalue
0.0013), but other PK parameters Cmax, Tmax, and Kel were close to the control group.

Conclusion:

PK/PD-based herb-drug interaction was observed. Concurrently administered garden cress + GLZ
showed improved antidiabetic effect and has enhanced GLZ bioavailability.
Recent Insights of Metformin on Hepatocellular Carcinoma (HCC)
Authors: Wang Kaizhen , Zhang Kuojun , Zhang Xiangyu , Chen Dong , Jiang Sheng
Published: June 2022

Metformin is an oral hypoglycemic drug, the first option used to treat type 2 diabetes
mellitus due to its high efficacy and low cost. Recently, it has drawn attention among researchers
due to its new-found antitumor effect. Growing evidence showed that metformin could inhibit
cancer progression, especially in hepatocellular carcinoma, and several clinical trials are underway.
However, the underlying mechanisms of the inhibition of hepatocellular carcinoma remain
to be further explored and clarified. Herein, we reviewed the latest findings of how metformin
acts against hepatocellular carcinoma and the proposed mechanisms. In addition, we included related
preclinical trials, along with the limitations and perspectives of its treatment in hepatocellular
carcinoma, providing novel ideas for research to conquer hepatocellular carcinoma.
Targeting the Transforming Growth Factor-beta Signaling Pathway in the
Treatment of Gynecologic Cancer
Authors: Avan Amir , Ghanaatgar-Kasbi Sadaf , Pouya Farzaneh , Khoshghamat Negar , Ghorbannezhad Ghazaleh , Khazaei Majid , Hasanzadeh Malihe , Ferns Gordon A.
Published: June 2022

The transforming growth factor-beta (TGF-β) signaling pathway has been reported to be
dysregulated in the pathogenesis of several malignancies, including gynecologic cancers. This provides
proof of concept of its potential value as a therapeutic target and prognostic biomarker in cervical cancer.
Here we provide an overview of the biological role and clinical impact of TGF-β inhibitors either
as a single agent or as a combinatorial therapy in gynecological cancers, concentrating on phase I to
phase II/III clinical trials. Aberrant TGF-β signaling may lead to carcinogenesis. Inhibition of TGF-β
represents an interesting area of focus for the treatment of gynecological cancer. Several TGF-β inhibitors
are potential anticancer agents and are undergoing clinical trials in cancer, including galunisertib,
dalantercept, and vigil. There is a growing body of data showing the potential therapeutic impact of
targeting the TGF-β pathway in different cancer types, although further studies are still warranted to
explore the value of this strategy and finding the most appropriate patients who could most benefit from
therapy.
Cucurbitacin D Inhibits the Proliferation of HepG2 Cells and Induces
Apoptosis by Modulating JAK/STAT3, PI3K/Akt/mTOR and MAPK Signaling
Pathways
Authors: Türköz Yusuf , Mehdi Üremiş Muhammed , Üremiş Nuray , Tosun Emir , Durhan Merve , Çiğremiş Yılmaz , Baysar Ahmet
Published: June 2022

Background:

Cucurbitacin D (CuD) is a natural compound that can be isolated in various
plant families, mainly from Ecballium elaterium (L.) A. Rich. (E. Elaterium). It is a triterpenoid with
a broad spectrum of biological activity, including anti-cancer properties. Hepatocellular carcinoma,
the aggressive type of liver cancer, is an important public health problem worldwide.

Objective:

In the present study, we investigated the anticancer effect of CuD treated at different doses
on the HepG2 cell line and the underlying mechanism in vitro.

Method:

CuD was isolated from the fruit juice of E. Elaterium plant, and quantitative analysis was
performed using high-performance liquid chromatography. The cell viability effect of purified CuD
was determined by the MTT test, and also cell apoptosis and cell cycle arrest effects were determined
by flow cytometry. DNA damage was evaluated with the comet test. Proteins and genes involved in
PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 signaling pathways were evaluated by western blot
and qRT-PCR.

Result:

CuD showed both antiproliferative and cytotoxic effects against the HepG2 cell line in a dose
and time-dependent manner. It was observed that CuD induced apoptosis and blocked the cell cycle in
HepG2 cells. It was observed that the expressions of genes and some proteins that play a key role in
PI3K/AKT/mTOR, MAPK, and JAK2/STAT3 cascades were dose-dependently down-regulated and
led to activatation of the apoptotic pathway.

Conclusion:

All these results show promise that CuD may have a therapeutic effect in hepatocellular
carcinoma.
Phenolic Acids - Versatile Natural Moiety with Numerous Biological
Applications
Authors: Sehrawat Renu , Rathee Priyanka , Akkol Esra Küpelli , Khatkar Sarita , Lather Amit , Redhu Neelam , Khatkar Anurag
Published: June 2022

Background:

Medicinal uses of natural phenolic acids and its synthetic derivatives have been augmented in recent years. Phenolic acids are chemically defined secondary plant metabolitesand being moieties or leads are much versatile in nature with a widescope of biological activities which seek the attention of researchers across the worldto synthesize different derivatives of phenolic acids and screen them for their various biological properties.These compounds are of meticulous interest due to the properties they possess and their occurrence.Based on the convincing evidences reported in the literature, it is suggested that phenolic acids andtheir derivatives are promising molecules as a drug.

Objective:

The present review article aims to bring together the information on the biosynthesis, metabolism, and sources of phenolic acids and emphasize on the therapeutic potential of phenolic acid and its synthetic derivatives to comprehensively portray the current scenery for researchers interested in designing drugs for furthering this study.

Conclusion:

Phenolic acids being moieties or lead are much versatile in nature as they possess a wide range of biological activities like antimicrobial, antioxidant, antiviral, antiulcer, anti-inflammatory, antidiabetic, anticancer and many more which offers researchers to explore more about these or many untapped benefits in medicinal field. The information mentioned in this article will be helpful to the forthcoming researchers working in this area. Phenolic acids have massive potential to be investigated for novel medicinal possibilities and for the development of new chemical moieties to treat different diseases of clinical importance.
SARS-CoV-2/COVID-19: Clinical Course Among Subjects HIV-1-Infected
in Sao Paulo
Authors: Monteiro Mariana A. , Prates Gabriela S. , de Lima Nascimento Najara A. , Veiga Ana Paula R. , Magri Marcello M.C. , Polis Thales J.B. , Gascon Maria R.P. , Ferreira Mauricio D. , Tiberto Larissa , Pereira Luisa O. , Alves Wagner , Fonseca Luiz A.M. , Duarte Alberto J.S. , Casseb Jorge
Published: June 2022

Introduction:

People living with Human Immunodeficiency Virus (HIV) are under risk
for co-infection with SARS-CoV-2. This population may be more prone to complications from
COVID-19 due to persistent inflammation caused by HIV and higher incidence of metabolic syndromes,
cardiovascular diseases, and malignancies, as well as being considered elderly at 50 years
of age. The objective of this study was to report SARS-CoV-2 infection frequency, clinical evolution,
and mortality in HIV-positive patients on antiretroviral therapy.

Methods:

The period of inquiry ranged from January to September 2020. Due to the social distance
and the suspension of in-person medical care during the time of the investigation, we sent electronic
questions about demographic, epidemiological, and clinical data to 403 HIV-infected patients.

Results:

Among 260 patients who answered the questionnaire, thirty-nine patients (15%) had suggestive
symptoms and were tested for SARS-CoV-2 infection. Of this, 11 had positive results
(32.4%) and no patient died of COVID-19 complications. Nine were male (3.4%), and the mean age
of the patients with positive results was 43.2 years (± 9.6). 107 patients (41.1%) were over 50 years
of age and their mean T-CD4+ cell count was 768. Eleven patients (4.2%) had a detectable HIV
RNA viral load and 127 (48.8%) had comorbidities. These variables were not associated with an increased
risk for infection.

Conclusion:

The frequency of Sars-Cov2 infection among HIV-infected is similar to the general
population, and the clinical course is associated with the presence of comorbidities and not due to
the HIV infection. However, new studies should be done to assess if this vulnerable population
could answer the vaccine anti-SARS-Cov2.
An Active Group with Potential Anti-seizure Activity: A Review on 1,2,4-
Triazoles
Authors: Wang Ying , Quan Zheshan , Liu Dachuan
Published: June 2022

Background:

Epilepsy is one of the most common neurological disorders. Many individuals
continue to have seizures despite medical and surgical treatments, suggesting that the discovery of novel
anti-seizure drugs is vital. Triazole compounds are widely used as pharmaceuticals and have gained significant interest in medicinal chemistry. In this article, the development of triazoles, especially 1,2,4-
triazole, in the field of anti-seizure therapeutics is reviewed.

Methods:

The relevant literature was investigated, classified, and analysed. This article attempts to systematically review the research of triazole derivatives in the design and development of anti-seizure
agents during the past two decades through extensive literature research, which was based on the information accessible in PubMed, Science Direct, Google Scholar and other databases.

Results:

Research results demonstrate that triazoles occupy a distinct niche in heterocyclic chemistry and
represent a key motif in medicinal chemistry because of their ability to exhibit an array of properties and
bioactivities. Therefore, 1,2,4-triazole appears to be an important pharmacophore, especially in the field
of anti-seizure therapeutics, where its promising potential value has been explored.

Conclusion:

This review presents a summary of the research related to 1,2,4-triazole, which acts as a
potential anti-seizure pharmacophore that could be further developed. Compounds with 1,2,4-triazole or
related structures had previously shown reasonable anti-seizure activity and safety. After thorough research of this structure, it is believed that 1,2,4-triazole-containing compounds will be further developed
as anti-seizure drugs for clinical use.
Development and Validation of a Hypoxia-related Prognostic Model for Ovarian Cancer
Authors: Xie Linling , Pan Meijun , Zhang Zhaoping , Jiang Xiaotao , Chen Yi , Liu Guantong , Chen Yanfen , Zeng Yuhua , Guan Jieshan , Lu Ruling , Zeng Lei
Published: June 2022

Background:

The high heterogeneity of ovarian cancer (OC) brings great difficulties to its early diagnosis and prognostic forecast. It is an urgent need to establish a prognostic model of OC based on clinicopathological features and genomics.

Methods:

We identified hypoxia-related differentially expressed genes (DEGs) between OC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression (GTEx). LASSO Cox regression analysis was applied for building a prognostic model in the TCGA-GTEx cohorts, and its predictive value was validated in the GEO-OC cohort. Functional enrichment analysis was performed to investigate the underlying mechanisms. By constructing a hypoxia model of SKOV3 cell line and applying qRT-PCR, we investigated the relationship between hypoxia with two novel genes in the prognostic model (ISG20 and ANGPTL4).

Results:

Twelve prognostic hypoxia-related DEGs were identified and nine of them were selected to establish a prognostic model. OC patients were stratified into two risk groups, and the high-risk group showed reduced survival time compared to the low-risk group upon survival analysis. Univariate and multivariate Cox regression analysis demonstrated that the risk score acted as an independent risk factor for overall survival. The biological function of the identified prognostic hypoxia-related gene signature was involved in immune cells infiltration. Low expression of ISG20 was observed in the CoCl2-mimicked hypoxic SKOV3 cell line and negatively correlated with HIF-1α.

Conclusion:

Our findings showed that this hypoxia-related gene signature can serve as a satisfactory prognostic classifier for OC and will be beneficial to the research and development of targeted therapeutic strategies.
Formulation, Development, and in-vitro Evaluation of Escitalopram Fast Dissolving Tablets
Authors: Dhingra Ashwani K. , Bhatia Vishal , Dass Rameshwar , Chopra Bhawna , Guarve Kumar
Published: June 2022

Background:

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), acts by increasing the serotonin level in the brain and is used widely for the management of depression and anxiety disorders. However, the poor dissolution rate of escitalopram due to less water solubility is a consequential problem confronting the pharmaceutical industry in developing pharmaceutical dosage forms for oral delivery systems.

Objective:

The present work aims to deliver a novel formulation for improving the dissolution profile and, thus, the bioavailability of escitalopram.

Methods:

Fast Dissolving Tablets (FDT) are expected to enable quick drug release, which will improve the drug's dissolving profile, allowing for the initial increase in plasma concentration mandatory in an acute depression attack. The use of co-processed excipients in tablets has been shown to increase the compressibility and disintegration properties of the tablets, resulting in improved in-vitro drug release and bioavailability. As co-processed excipients, a mixture of banana powder (a natural super disintegrant with nutritional value) and microcrystalline cellulose (a highly compressible substance with good wicking and absorption capacity) was used.

Results:

The tablets were made using a response surface, randomised central composite design and a direct compression technique. The manufactured tablets were found to be released more than 95% of the drug within 10 minutes and showed an improved drug release profile than the available marketed formulation.

Conclusion:

As a result, after confirming in-vivo potential, the created fast release formulation exhibited impressive in-vitro findings and may prove to be a boon in treating acute depression attacks.
Antioxidant and Hepatoprotective Activities of Acacia jacquemontii Stem
Extract against High-fat and CCl4-induced Liver Injury in Rat’s Model
Authors: Majeed Wafa , Daud Maria , Awan Ambreen Mehmood , Aslam Bilal , Abdullah Muhammad , Syed Mahnoor , Iqbal Hafsa , Roobi Alishbah , Kanwal Hafiza Arooj , Aslam Noreen
Published: June 2022

Background:

Chronic liver injury leads to liver inflammation and fibrosis, activating
myofibroblasts in the liver and secreting extracellular matrix proteins that make the fibrous scar.

Objectives:

The purpose of our study was to characterize the polyphenolic content present in Acacia
jacquemontii stem and evaluate its antioxidant and hepatoprotective activity.

Methods:

The phenolic contents in Acacia jacquemontii polyphenolic extract (AJPPE) were
characterized using high-performance liquid chromatography (HPLC). The hepatoprotective and
antioxidant activity of AJPPE were determined through biochemical parameters (ALT, AST, and
ALP), lipid profile (TC, TG, HDL, and LDL), antioxidant biomarkers (SOD, LPO, GSH, and CAT),
anti-fibrotic activity (collagen deposition), and histopathological analysis.

Results:

HPLC analysis of AJPPE showed the presence of polyphenols, including chlorogenic acid,
P-coumaric acid, caffeic acid, and kaempferol, in a remarkable therapeutic range. Results of the in
vivo analysis showed a significant decrease in the level of lipid profile, including LDL (low-density
lipoprotein), TC (total cholesterol), triglycerides, liver function markers (AST, ALT, and ALP),
collagen deposition and significantly increased the level of anti-oxidative biomarkers (CAT, SOD,
LPO, and GSH) by using AJPPE.

Conclusion:

The above-mentioned results have shown that AJPPE possesses significant antioxidative
and hepatoprotective effects. Furthermore, histopathological results also supported the
antioxidant and hepatoprotective potential of AJPPE.