bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumhuriyet’e Giden Yol: Saltanatın Kaldırılması Sürecinde Yaşanan Siyasal Sistem Tartışmaları
Authors: ÖZKAN Asaf
Published: October 2023

Mudanya Mütarekesi gereğince Yunanistan’ın boşaltacağı Trakya’yı Türkiye Büyük Millet Meclisi Hükümeti adına teslim almakla görevlendirilen Refet Paşa, 19 Ekim 1922’de İstanbul’a geldi. Yaklaşık dört yıldır fiili işgal altında bulunan İstanbul ahalisi, Refet Paşa’yı büyük bir sevinç ve coşku ile karşıladı. Refet Paşa, kendisini karşılayan Padişah ve hükümetin temsilcilerine, TBMM Hükümeti’nin İstanbul’da bir padişah ve hükümet tanımadığını açıkladı. Yaptığı konuşmalarda, verdiği röportajlarda Anadolu’da kurulan Yeni Türk devletinin yönetim biçimine yönelik önemli açıklamalar yaptı. Bu açıklamalarda Anadolu’da kurulan sistemi saltanat-ı milliye olarak tanımlıyordu ve kurulan sistemin kuvvetler birliğine dayalı meclis hükümeti sistemi olduğunu cumhuriyet veya meşrutiyet gibi sistemlere benzemediğini, Anadolu’nun kendi ihtiyaçlarından doğduğunu savunuyordu. Refet Paşa’nın bu konuşmalarına karşı İstanbul Baro Başkanı Lütfi Fikri Bey bir risale yazarak onun görüşlerini eleştirdi. Lütfi Fikri’ye göre Türkiye’ye en uygun sistem meşrutiyet sistemiydi. Lütfi Fikri Bey’in risalesinin yayımlanmasından sonra Türkiye’deki rejimin ne olacağına dair tartışmalar hız kazandı. Bu arada 1 Kasım 1922’de TBMM kararıyla saltanat ve hilafet birbirinden ayrıldı ve saltanat kaldırıldı. Saltanatın kaldırılmasından sonra Anadolu’da uygulanan meclis hükümeti sistemi ile alakalı tartışmalar devam etti. Bu bağlamda Lütfi Fikri Bey’in risalesine karşı çeşitli risaleler yayımlandı. Aynı zamanda konu dönemin basınına da yansıdı. Tartışmalar genellikle meşrutiyet, cumhuriyet, kuvvetler ayrılığı, kuvvetler birliği, hâkimiyet-i milliye, meclis hükümeti sistemi konuları üzerinden yürütüldü.
Şark/Garp, Alaturka/Alafranga Tartışmaları Çerçevesinde Hâkimiyeti Milliye Sütunlarından Siyasal Yaşamdaki Kadın Hakları İnkılabı (1930-1934)
Authors: ÖZKAYA Olcay
Published: October 2023

Cumhuriyet dönemi, temellerini Osmanlı’nın özellikle son dönemlerinden alan ilksel girişimlerin geliştirilmesi ve somut olduğu kadar aynı zamanda köktenci bir formda yaşam bulmasını amaç edinen inkılapları içermektedir. Esasında bu bağlam belirgin bir biçimde Meşrutiyet yıllarında adımları atılmış birçok girişime dair ayak izlerini bünyesinde barındırmaktadır. Bununla beraber etkin olduğu gibi direngen bir talep ve çabanın izleri ancak Cumhuriyet döneminde ortaya çıkmaktadır. Bu mücadelede uygarlaşma, modernleşme, ilerleme, batılılaşma, gelişme mottoları ile başlamış ancak tam olarak genel çerçevede bunların hiç birinde uzlaşılamamış ve açıkça hiç birinin tam olarak anlaşılamamış olduğu görülmüştür. Nihayetinde bu durumun yarattığı karmaşa, sürecin ikircikli yaklaşımlarla yürütülecek reform ya da ıslahatlarına ortam hazırlamıştır. Burada doğu ya da batı, alaturka ya da alafranga başta olmak üzere kimi yönelimler çerçevesinde tarafların oluştuğu ya da yaklaşımların geliştiği anlaşılmaktadır. Söz konusu çerçevede birçok konuda olduğu gibi kadın hakları konusunda da geleneksel ile modern söylem, taraflar arasında bir kutup yaratmıştır. Yukarıda bahsi geçen kavramlara göre esasında tarihsel ortamın oluşturduğu çeşitli talepleri karşılamak üzere geliştirilen inkılaplara karşı belli ölçülerde bunları destekler ya da eleştiren eğilimler, görüşler olagelmiştir. Çalışma dönemin siyasal, sosyal ve entelektüel atmosferini anlamamıza olanak sağlayacak bu tartışmaları kadın hakları kapsamında ele almaya odaklanmıştır. Yanı sıra konu literatüre ve arşiv belgelerine dayalı bir yöntemden çok dönemin toplum hafızasını ve siyasal konjonktürünü ortaya koyabilecek, söz konusu sürecin tanığı Hâkimiyeti Milliye gazetesinin sütunlarından irdelenecektir.
Türkiye’de Popülizm Ve Seçimsel Demokrasiye Prelüd: İngiliz Elçilik Raporlarında 1954 Seçimleri Üzerine Bazı Düşünceler
Authors: BABAOĞLU Resul
Published: October 2023

Demokrat Parti’nin ilk iktidar döneminde girişilen icraatların ve iktidar pratiklerinin seçmen onayına sunulması açısından 1954 seçimleri yabancı temsilciliklerin de dikkatle takip ettikleri bir yarış olmuştur. Bu seçimler öncesinde Türkiye’de yaşanan ve siyasi tansiyonu yükselten birtakım gelişmelerin seçmen nezdinde nasıl karşılanacağı merakla beklenmekteydi. Cumhuriyet Halk Partisi’nin mallarına el konulması, Halkevlerinin ve Millet Partisi’nin kapatılması gibi gelişmeler 1954 seçimlerine gidilen süreçte iktidar ve muhalefet arasındaki ilişkiyi gerginleştirmiştir. Türkiye’deki siyasal gelişmeleri dikkatle takip eden İngiltere’nin Ankara Büyükelçiliği’nin dışişleri bakanlığına iletilmek üzere hazırlamış olduğu raporlar, 1954 seçimleri öncesinde vatandaşların oy tercihlerine etki edecek birtakım hususları içermesi bakımından anılan dönemi farklı bir pencereden okumaya imkân sağlamaktadır. Bu süreçte partilerin seçmen tercihlerine etki etmek için kullandığı stratejiler, dış politikanın iç politikaya ne şekilde etki ettiği ve bu bağlamda iktidar ve muhalefetin Batı ittifakı konusunda sağladığı oydaşmanın 1954 yılında çıkarılan Petrol Kanunu üzerinden belki de ilk kez sorgulanmaya başlaması gibi gelişmelerin tartışıldığı elçilik raporları, zamanın ekonomi politiğini ortaya koyması açısından dikkate alınmayı hak etmektedir.
Ege Denizi’nde Hâkimiyet Mücadelesi: Kurfürst Friedrich Wilhelm ve Weissenburg Zırhlıları Alımı Süreci (1910)
Authors: KIŞ Salih
Published: October 2023

Osmanlı Devleti’nde II. Meşrutiyet’in ilanından sonra yeni kurulan hükümetin hedefleri arasında, bahriyenin büyütülüp ıslah edilmesi öncelikli meselelerden biri idi. Özellikle isyanlar ve komitacılık faaliyetlerinin merkezinde bulunan Rumeli vilayetlerinin elde tutulması ve yeni kurulan Balkan Devletlerinin yayılmacı politikalarının engellenmesi güçlü bir donanmanın oluşturulması ile mümkündü. Bölgeye asker ve mühimmat sevkiyatı için İstanbul-Rumeli demiryolu hattının kullanılması, saldırıya son derece açık olması nedeniyle deniz yolunu tek ve güvenilir bir seçenek olarak ortaya çıkarıyordu. Denizden nakliye işlemini gerçekleştirmek ise Ege Denizi’nde Yunanistan’a karşı bir üstünlük kurmaktan geçiyordu. Fakat Yunanistan’ın İtalya/Livorno’daki Orlando Tersanesi’nde inşaatı tamamlanan ve Mart 1910 yılında denize indirilen Georgios Averof zırhlısını satın alması, Osmanlı amiralleri ve idarecilerinde büyük bir panik yarattı. Bu zırhlı ile Ege Denizi’nde güç dengeleri Yunanistan lehine değişmişti. Osmanlı idarecileri, yeni zırhlılar satın alarak dengeleri kendi lehlerine değiştirmek amacıyla, Türk donanmasının başında bulunan İngiliz Islah Heyeti Başkanı Amiral Hugh Williams aracılığıyla Kraliyet Donanması ve İngiliz tersaneleri nezdinde bir dizi girişimlerde bulunmuşlardı. Kızakta veya yeni denize indirilmiş modern iki zırhlının satış görüşmeleri gerçekleştirilmişti. İngilizler, Osmanlı yetkililerine yeni gemilerden ziyade bir alt sınıfa mensup ve 1891 yılında denize indirilmiş iki zırhlının satılabileceğini bildirmişlerdi. Modern zırhlılar talebinden geri adım atmayan Osmanlılar, yapılan bu teklifi kabul etmeyerek farklı arayışlara yönelmişlerdi. Bu süreçte Alman Hükümeti, Osmanlı Devleti’ne bir teklifte bulunmuş, birkaç yıl önce tadil ve tamir edilen ve 1890 yılında kızağa konulan Kurfürst Friedrich Wilhelm ve Weissenburg zırhlılarını satmayı teklif etmişlerdi. Toplam maliyeti 17 milyon Mark olan bu iki zırhlı ücretinin bir kısmı, ödeme planında aracı kurum olan Deutsche Bank’ın teklifi ile tahttan indirilen Sultan II. Abdülhamit’in dondurulmuş mal varlıklarından ve diğer bir kısmı ise Donanma Cemiyeti’nin bağışlarından karşılanmıştı. Bu çalışmada, Ege Denizi’nde hâkimiyet mücadelesi çerçevesinde söz konusu zırhlılarının satın alınma süreci Osmanlı arşiv vesikaları ışığında değerlendirilmiştir.
An Investigation of In-service Teachers’ Perceptions and Development of Computational Thinking Skills in a Graduate Emerging Technologies Course
Authors: Jin Yi , Harron Jason
Published: October 2023

This study investigated in-service teachers’ perceptions and development of computational thinking (CT) skills in an online graduate emerging technologies course. Participants perceived that they increased their CT problem-solving and creativity skills and decreased their collaborative learning and critical thinking skills. Additionally, teachers increased their CT test scores after taking the course. Most teachers used CT terminology correctly (i.e., algorithms and decomposition). However, only 59% correctly described abstraction and pattern recognition, while most teachers did not mention debugging. The authors call on teacher educators to address in-service teachers’ knowledge gaps in their CT skills and select appropriate strategies for CT preparation.
What Emotions do Pre-university Students Feel when Engaged in Computational Thinking Activities?
Authors: Herrero-Álvarez Rafael , León Coromoto , Miranda Gara , Segredo Eduardo , Socas Óscar , Cuellar-Moreno María , Caballero-Juliá Daniel
Published: October 2023

Emotions affect how we acquire knowledge, being one of the causes of the demotivation generated at the time of studying a new field. Computer Science does not always pique the interest of young people, so we carry out an analysis of emotions that are present in primary and secondary school students, around 8-9 years old and 12-13 years old, who engage in Computational Thinking activities, considering the educational level, gender, and type of intervention, to understand why this lack of interest. The sessions were based on 1 hour of face-to-face class in which activities related to Computational Thinking were carried out. The instrument used to measure emotions was the Developmental Channels Questionnaire which includes 13 different emotions that students must answer using the Likert scale from 0 to 10. The emotions felt have been mostly positive and ambiguous, while negative emotions have a low intensity, particularly in primary education. Regarding the educational level, there are differences between girls and boys only in the secondary education, while in the primary they are no significant. Also, girls show an evolution when carrying out this type of activity, while boys do not change.
Using selectivity to evaluate aqueous- and resin-phase denitrification during biological ion exchange
Authors: Edgar Michael , Rangan Srivatsan Mohana , Delgado Anga G. , Boyer Treavor H.
Published: October 2023

An increased fertilizer application for agricultural purposes has resulted in increased nitrate (NO3−) levels in surface water and groundwater around the globe, highlighting demand for a low-maintenance NO3− treatment technology that can be applied to nonpoint sources. Ion exchange (IEX) is an effective NO3− treatment technology and research has shown that bioregeneration of NO3− laden resins has the potential to minimize operational requirements and brine waste production that often prevents IEX application for decentralized treatment. In this work, batch denitrification experiments were conducted using solutions with low IEX selectivity capable of supporting the growth of denitrifying bacteria, while minimizing NO3− desorption from resins, encouraging resin-phase denitrification. Although only 15% of NO3− was desorbed by the low selectivity solution, this initial desorption started a cycle in which desorbed NO3− was biologically transformed to NO2−, which further desorbed NO3− that could be biotransformed. Denitrification experiments resulted in a 43% conversion rate of initially adsorbed NO3−, but biotransformations stopped at NO2− due to pH limitations. The balance between adsorption equilibria and biotransformation observed in this work was used to propose a continuous-flow reactor configuration where gradual NO3− desorption might allow for complete denitrification in the short retention times used for IEX systems.
Automação industrial: uma viagem por TCCs do curso Tecnólogo em Automação Industrial - UERGS
Authors: Alvarez Peixoto João
Published: October 2023

Um trabalho de conclusão de curso vai além de utilizar os conhecimentos, competências e habilidades desenvolvidas em aulas e disciplinas. É a mobilização deste conhecimento agregado para dar um propósito, resolvendo um problema da vida real. E tudo isto utilizando o método científico. E vai mais além! São horas e horas de dedicação, de pesquisa, de aprendizado, que só a carga horária de um semestre letivo não é suficiente. É necessário ir além! Madrugadas estudando, fim-de-semanas dedicados à pesquisa, momentos em que a família fica sem suas presenças, momentos que o mundo passa significar uma única sigla: TCC. Ao orientador, cabe a função de indicar o caminho. Mas não tem como ser só isto. Somos seres humanos também e acaba por haver um envolvimento, passando a fazer parte do trabalho do orientando, vivendo junto suas histórias. E por isso resolvi contar estas histórias, na forma de um livro, que congrega um resumo expandido de cada um dos 20 TCCs que orientei, durante a existência do curso Tecnólogo em Automação Industrial, na Universidade Estadual do Rio Grande do Sul – UERGS, em Porto Alegre, no período de 2017 a 2023.
Os povos tradicionais de terreiros e as políticas públicas governamentais face à ascensão dos neopentecostais aos cargos eletivos no Brasil
Authors: Farias Lucy Patrícia da Silva
Published: October 2023

O presente trabalho tem o objetivo de analisar alguns os avanços e retrocessos no tocante às políticas públicas voltadas para os povos tradicionais de terreiro, tendo como parâmetro os Planos Plurianuais de (2016- 2019) e (2020- 2023), as leis promulgadas nesse período que efetivaram direitos e garantias. Salientamos que em 2016 ocorreu uma maior representatividade da bancada evangélica nos cargos eletivos, o que repercutiu diretamente na forma de direcionamento das ações governamentais. Ademais, mostraremos as narrativas dos povos de terreiros diante dessa conjuntura política no país e como isso impactou a liberdade religiosa e a luta diária para que seus direitos sejam respeitados. Por conseguinte, faz-se necessária tanto uma abordagem quantitativa, quanto qualitativa, para maior elucidação da temática, tendo em vista que tais métodos não são excludentes, mas sim complementares. Minayo (2001), afirma que a pesquisa qualitativa consegue responder a certas questões particulares que não podem ser quantificadas, trabalhando com o universo de significados, motivos, aspirações e crenças, valores e atitudes, adentrando num processo mais profundo e fenômenos que não podem ser reduzidos à operacionalização de variáveis. Nesse sentido, tanto a análise documental quanto as narrativas são importantes para  demonstrar que nem sempre as ações governamentais procuram diminuir as desigualdades sociais, e reconhecer a importância dos povos tradicional na construção do país.
Metformin Preserves Insulin Secretion in Pancreatic β-cells through FGF21/Akt Pathway In vitro and In vivo
Authors: Li Jianting , Jiang Qiang , Wang Xin , Hou Lulu , Wang Lulu , Lou Kai , Pang Shuguang
Published: October 2023

Background:

In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity
in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet β-cells is still unknown. Therefore, this study focuses on the effect of metformin on
insulin secretion in pancreatic β-cells.

Aims:

Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic βcell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention.

Methods:

The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) that were subjected to damage
caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose,
and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression
were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried
out in metformin-stimulated INS-1 cells.

Results:

High-glucose could significantly stimulate insulin secretion while metformin preserved
insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets.

Conclusion:

Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.
Network Pharmacology and Molecular Docking Analysis on Mechanisms of Scutellariae Radix in the Treatment of Cerebral Ischemia-reperfusion Injury
Authors: Yang Yang , Xu Mengrong , Yuan Wenting , Feng Yue , Hou Yongqiang , Fang Fei , Duan Shiwan , Bai Lu
Published: October 2023

Background:

Multiple brain disorders are treated by Scutellaria Radix (SR), including cerebral ischemia-reperfusion (CI/R). However, more studies are needed to clarify the molecular mechanism of SR for CI/R.

Methods:

The active substances and potential targets of SR and CI/R-related genes were obtained through public databases. Overlapping targets of SR and CI/R were analyzed using proteinprotein interaction (PPI) networks. GO and KEGG enrichment analyses were performed to predict the pathways of SR against CI/R, and the key components and targets were screened for
molecular docking. The results of network pharmacology analysis were verified using in vitro
experiments.

Results:

15 components and 64 overlapping targets related to SR and CI/R were obtained. The
top targets were AKT1, IL-6, CAS3, TNF, and TP53. These targets have been studied by GO
and KEGG to be connected to a number of signaling pathways, including MAPK, PI3K-Akt
pathway, and apoptosis. Molecular docking and cell experiments helped to further substantiate
the network pharmacology results.

Conclusion:

The active compound of SR was able to significantly decrease the apoptosis of HT22 cells induced by OGD/R. This finding suggests that SR is a potentially effective treatment for
CI/R by modulating the MAPK and PI3K-Akt pathways.
Review on Natural Agents as Aromatase Inhibitors: Management of Breast Cancer
Authors: Singh Sonia
Published: October 2023

:

Breast cancer is a prevalent type of cancer that is typically hormone-dependent,
caused by estrogen. Aromatase inhibitors are frequently utilised in the treatment of hormonereceptor-
positive breast cancer because they prevent the enzyme aromatase from converting androgens
to estrogens. Natural medicines with aromatase inhibitory characteristics have attracted
interest as potential alternatives or complementary therapy to manufactured medications. This
review discusses the function of natural agents as aromatase inhibitors in treating breast cancer.
A variety of natural compounds have been investigated for their capacity to inhibit aromatase
activity and lower estrogen levels. These agents include resveratrol from red wine and grapes,
curcumin from turmeric extract and green teahigh in catechins, and other flavonoids such as
genistein, luteolin and quercetin. It has been demonstrated that by decreasing estrogen synthesis,
they can slow the growth of breast cancer cells that are dependent on estrogen. However, the
clinical evidence supporting their efficacy and safety in breast cancer treatment is inadequate.
More research is required to investigate the therapeutic potential of natural medicines, such as
aromatase inhibitors, in treating breast cancer. The clinical trials are required to assess their efficacy,
appropriate doses, and potential interactions with other therapies. In conclusion, natural
aromatase inhibitory drugs are promising adjuncts in the treatment of hormone receptor-positive
breast cancer. Their clinical value and safety profile, however, require additional investigation.
Prevalence of Toxoplasma gondii in HIV-Infected Individuals in Iran: A Systematic Review and Meta-Analysis
Authors: Shakib Pegah , Behzadifar Masoud , Mahmoudvand Hossein , Larki Sara , Kalani Hamed , Zivdari Masoomeh , Mardanshah Omid , Cheraghipour Kourosh
Published: October 2023

Introduction::

Toxoplasma gondii is an obligate intracellular protozoan that can infect
almost all warm-blooded animals, including humans. Patients with co-infection with toxoplasmosis
and HIV have a 30-40% risk of developing toxoplasmosis encephalitis. This study aimed to describe
the epidemiology and burden of Toxoplasma gondii in HIV-infected individuals in Iran.

Methods::

We searched the five English databases (Science Direct, PubMed, Scopus, Ovid, Embase,
and Cochrane) and four Persian databases (Scientific Information Database (SID), Iran
Medex, Iran Doc, and Magiran) with the terms of (Toxoplasma gondii OR “toxoplasmosis”) AND
(HIV OR “AIDS” OR immunodeficiency OR acquired immune deficiency syndrome) AND (Seroprevalence)
AND (Seroepidemiologic Studies) AND (Elisa OR IgG) AND (PCR) AND (Iran) by
two authors up to Feb 2021. Studies were included if they investigated people with HIV infection
and presented data that allowed us to establish the prevalence of Toxoplasma gondii infection in
Iran.

Results::

According to the inclusion/exclusion criteria, 15 studies were selected. A total number of
2275 HIV-infected individuals were tested and evaluated for toxoplasmosis from 2005 up to 2018
in different regions of Iran. The weighted overall prevalence of toxoplasmosis in HIV-infected individuals
with Elisa was obtained using a random-effects model, which was estimated at 47%
(95% CI = 31% – 62%). Also, the Weighted overall prevalence of toxoplasmosis in HIV-infected
individuals with PCR was obtained using a random-effects model, which was estimated at 7%
(95% CI = 3% – 12%).

Conclusion::

According to the results of this study, it can be clearly understood that a large population
of HIV patients living in Iran have toxoplasmosis. Therefore, due to the high susceptibility of
these groups to toxoplasmosis, healthcare professionals must consider measures such as training
in the ways of transmission and prevention of the infection to this high-risk group in order to reduce
the risk of infection.
Drug Repositioning: A Monetary Stratagem to Discover a New Application
of Drugs
Authors: Rohilla Ankur , Rohilla Seema
Published: October 2023

Drug repurposing, also referred to as drug repositioning or drug reprofiling, is a scientific
approach to the detection of any new application for an already approved or investigational drug. It
is a useful policy for the invention and development of new pharmacological or therapeutic applications
of different drugs. The strategy has been known to offer numerous advantages over developing
a completely novel drug for certain problems. Drug repurposing has numerous methodologies
that can be categorized as target-oriented, drug-oriented, and problem-oriented. The choice of the
methodology of drug repurposing relies on the accessible information about the drug molecule and
like pharmacokinetic, pharmacological, physicochemical, and toxicological profile of the drug. In
addition, molecular docking studies and other computer-aided methods have been known to show
application in drug repurposing. The variation in dosage for original target diseases and novel diseases
presents a challenge for researchers of drug repurposing in present times. The present review
critically discusses the drugs repurposed for cancer, covid-19, Alzheimer’s, and other diseases,
strategies, and challenges of drug repurposing. Moreover, regulatory perspectives related to different
countries like the United States (US), Europe, and India have been delineated in the present review.
Virtual Screening, Docking, and Designing of New VEGF Inhibitors as
Anti-cancer Agents
Authors: Patel Shivkant , Singh Vinay Ranjan , Suman Ashok Kumar , Jain Surabhi , Sen Ashim Kumar
Published: October 2023

Background:

VEGFR-2 tyrosine kinase inhibitors are receiving a lot of attention as
prospective anticancer medications in the current drug discovery process.

Objective:

This work aims to explore the PubChem library for novel VEGFR-2 kinase inhibitors.
1H-Indazole-containing drug AXITINIB, or AG-013736 (FDA approved), is chosen as a rational
molecule for drug design. This scaffold proved its efficiency in treating cancer and other diseases as
well.

Methods:

The present study used the virtual screening of the database, protein preparation, grid
creation, and molecular docking analyses.

Results:

The protein was validated on different parameters like the Ramachandran plot, the ERRAT
score, and the ProSA score. The Ramachandran plot revealed that 92.1% of the amino acid residues
were located in the most favorable region; this was complemented by an ERRAT score (overall
quality factor) of 96.24 percent and a ProSA (Z score) of -9.24 percent. The Lipinski rule of five
was used as an additional filter for screening molecules. The docking results showed values of
binding affinity between -14.08 and -12.34 kcal/mol. The molecule C1 showed the highest docking
value of -14.08 Kcal/mol with the maximum number of strong H-bonds by -NH of pyridine to
amino acid Cys104 (4.22Å), -NH of indazole to Glu108 (4.72), and Glu70 to bridge H of -NH.
These interactions are similar to Axitinib docking interactions like Glu70, Cys104, and Glu102. The
docking studies revealed that pi-alkyl bonds are formed with unsubstituted pyridine, whereas
important H-bonds are observed with different substitutions around -NH. Based on potential
findings, we designed new molecules, and molecular docking studies were performed on the same
protein along with ADMET studies. The designed molecules (M1–M4) also showed comparable
docking results similar to Axitinib, along with a synthetic accessibility score of less than 4.5.

Conclusion:

The docking method employed in this work opens up new possibilities for the design
and synthesis of novel compounds that can act as VEGFR-2 tyrosine kinase inhibitors and treat
cancer.
The Role of Neuronal Pathways in Gastrointestinal Cancers: Targets for Prevention and Treatment
Authors: Poudineh Mohadeseh , Mollazadeh Samaneh , Mehrabadi Shima , Khazaei Majid , Hassanian Seyed Mahdi , Avan Amir
Published: October 2023

:

In recent decades, the mortality and morbidity of Gastrointestinal (GI) cancer have remarkably increased, especially in younger individuals. Recent studies revealed that neuronal connections play an active part in GI tumor initiation and progression. Also, studies showed neurotransmitters and neuropeptides drive the activation of various oncogenic pathways downstream of neural
receptors within cancer cells, underscoring the importance of neural signaling pathways in GI tumor
malignancy. These studies show that the humoral and nervous pathways can transfer signals of tumors to the brain. But, the exact mechanism of this regulation from the brain to the gut is still unknown. In this review, we summarized the mechanism of the neuronal pathway in the regulation of
promotion or suppression of GI cancer and oncogene activation, and we summarize recent findings
linking the nervous system to GI tumor progression and highlight the importance of targeting neural
mechanisms in GI tumor therapy
In silico Investigation of Identified Major Metabolites from Coffea Arabica Leaves against Parkinson’s Disease Target Proteins for Neuroprotective Drug Development
Authors: Rejano Christine Joyce , Tayo Lemmuel , Chen Bor-Yann , Tsai Po-Wei
Published: October 2023

Introduction:

Parkinson’s disease (PD) is a prevalent neurological disease characterized
by the gradual degeneration of dopaminergic neurons leading to a dysfunctional central nervous system.
Recently, major metabolites of Coffea arabica leaves were revealed to exhibit good electronshuttling
potential in Microbial Fuel Cells (MFCs), similar to neurotransmitters dopamine and epinephrine.

Objective:

This In silico study aimed to identify the neuroprotective potentials of plant metabolites
from coffee leaves and to determine their physicochemical and pharmacokinetic properties for developing
viable anti-parkinsonian drug design.

Methods:

Molecular docking was performed to evaluate the affinity of identified major compounds
in C. arabica against PD-target proteins and compare the results with the binding activity of
existing drugs and natural ligands of the identified protein targets via LibDock scores. The druglikeness
and ADMET profiles of each ligand were also evaluated using bioinformatics tools.

Results:

C. arabica metabolites exhibited various degrees of binding activity against PD targets.
LibDock scores of test compounds showed that catechin, mangiferin, and chlorogenic acid exhibited
higher docking scores than dopamine and levodopa. Physicochemical and pharmacokinetics analysis
of the selected molecules revealed caffeine, catechin, and chlorogenic acid as promising candidates
for drug development with a low risk of drug toxicity.

Conclusion:

The present study indicates that Coffea arabica leaves contain promising neuroprotective
active compounds against Parkinson’s disease.
In silico Evaluation of the Feasibility of Magnolia officinalis Electron-shuttling Compounds as Parkinson’s Disease Remedy
Authors: Rivera Zaina Allyson , Tayo Lemmuel , Chen Bor-Yann , Tsai Po-Wei
Published: October 2023

Background:

Parkinson’s Disease is one of the leading neurodegenerative disorders in the
world. Currently, there is still no treatment that could completely cure the disease. Traditional Chinese
Medicine has been a source for drug candidates, and many studies have elucidated its pharmacokinetic
capabilities. Previous studies showed that Magnolia officinalis has anti-inflammatory, antioxidant, and
bioenergy generation activities. Furthermore, the electron-shuttling and bioenergy-stimulating capabilities of herbal and brain disorder medicines have been linked to their effectiveness as a remedy.

Objective:

This preliminary study aims to evaluate the electron-shuttling compounds of Magnolia
officinalis (i.e., acteoside, isoquercitrin, magnatriol B, obovatol, quercitrin, randaiol, and rutin) as
potential drug candidates for Parkinson’s Disease.

Methods:

The seven electron-shuttling compounds were individually docked to the five Parkinson’s
Disease-related proteins, namely aromatic L-amino acid decarboxylase, α-synuclein, monoamine
oxidase B, catechol-o-methyltransferase, and A2A adenosine receptor, using LibDock. ADMET predictions were also made to screen the compounds further.

Results:

Molecular docking results showed that all compounds have relatively high LibDock scores
against the proteins, with acteoside, isoquercitrin, and rutin having the highest scores. However,
considering the ADMET results, only magnatriol B, obovatol, and randaiol had optimal properties as
candidates for neurodegenerative drugs.

Conclusion:

The electron-shuttling compounds of M. officinalis, magnatriol B, obovatol, and randaiol, have the potential to be a remedy for Parkinson’s Disease due to their high probability of binding to the proteins.
Fish Allergy and Related Conditions in Children: A Review
Authors: Giannetti Arianna , Bettini Irene , Alfieri Eleonora , De Bona Amina , Giannì Giuliana , Ricci Giampaolo , Caffarelli Carlo
Published: October 2023

Fish allergy is the important food allergies in childhood, often persisting into adulthood.
It can cause severe hypersensitivity reactions, including fatal anaphylaxis; furthermore,
avoiding-fish diet has negative nutritional and psychological effects. Recent research studies focus
on epitope structures and aim to develop sensitive and specific diagnostic tools, which have a better
correlation with clinical reactions. Protocols with hypoallergenic parvalbumin or other recombinant
antigens are also under study and will likely lead to new immunotherapy protocols.

:

IgE-mediated fish allergy differs substantially from other forms of immunological adverse reactions
to fish, such as Food Protein-Induced Enterocolitis Syndrome and eosinophilic esophagitis.
In addition, fish ingestion can cause non-immunological adverse reactions, such as in the case of
scombroid poisoning, anisakiasis and toxic poisoning.

:

This review aims to summarize the characteristics of the main immunological and non-immunological
fish reactions, analyzing the epidemiology, clinical manifestations, diagnosis and therapy,
with a particular focus on clinical management.
Acroparesthesias: An Overview
Authors: Slouma Maroua , Ben Dhia Siwar , Cheour Elhem , Gharsallah Imen
Published: October 2023

Acroparesthesia is a symptom characterized by a subjective sensation, such as numbness,
tingling, prickling, and reduced sensation, affecting the extremities (fingers and toes). Despite
its frequency, data regarding its diagnostic approach and management are scarce. The etiological
diagnosis of acroparesthesia is sometimes challenging since it can be due to abnormality anywhere
along the sensory pathway from the peripheral nervous system to the cerebral cortex.

:

Acroparesthesia can reveal several diseases. It can be associated with rheumatic complaints such
as arthritis or myalgia.

:

Further cautions are required when paresthesia is acute (within days) in onset, rapidly progressive,
severe, asymmetric, proximal, multifocal, or associated with predominant motor signs (limb weakness)
or severe dysautonomia. Acroparesthesia may reveal Guillain-Barré syndrome or vasculitis,
requiring rapid management.

:

Acroparesthesia is a predominant symptom of polyneuropathy, typically distal and symmetric, often
due to diabetes. However, it can occur in other diseases such as vitamin B12 deficiency, monoclonal
gammopathy of undetermined significance, or Fabry’s disease. Mononeuropathy, mainly
carpal tunnel syndrome, remains the most common cause of acroparesthesia.

:

Ultrasonography contributes to the diagnosis of nerve entrapment neuropathy by showing nerve
enlargement, hypoechogenic nerve, and intraneural vascularity. Besides, it can reveal its cause,
such as space-occupying lesions, anatomical nerve variations, or anomalous muscle. Ultrasonography
is also helpful for entrapment neuropathy treatment, such as ultrasound-guided steroid injection
or carpal tunnel release.

:

The management of acroparesthesia depends on its causes.

:

This article aimed to review and summarize current knowledge on acroparesthesia and its causes.

:

We also propose an algorithm for the management of acroparesthesia.
The Possible Association of IL-6R Gene Polymorphisms in the
Development of Diabetic Nephropathy
Authors: Ebrat Ebrahim , Hejazian Seyyedeh Mina , Ahmadian Elham , Vahed Sepideh Zununi , Mobasseri Majid , Ardalan Mohammadreza
Published: October 2023

Background:

Diabetic nephropathy (DN) is a common complication of type 2 diabetes (T2D). Chronic inflammation and a combination of environmental and genetic factors are involved in the pathogenesis and development of DN.

Objective:

This case-control study aimed to determine the relationship between rs7529229 and
rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients

Methods:

Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy
were included based on inclusion criteria, along with 150 healthy individuals

Results:

The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism
in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7
and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients
compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution
and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05).

Conclusion:

The results showed that the allele and genotype distribution frequencies of
rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in
healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.
High-Altitude Pulmonary Edema Combined with Spontaneous
Pneumomediastinum: A Case Report
Authors: Li Wenzhe , Wang Yajing , Xu Li , Yuan Fang
Published: October 2023

Background:

High-altitude pulmonary edema (HAPE) is a serious life-threatening disease that occurs after rapid ascent to high altitude; its main early-stage
presentations include fatigue, headache, low-grade fever, dyspnea, and cough. X-ray and computed tomography (CT) images show pulmonary
shadows and patches, which may be localized (initial right lung field predomination) or generalized to the bilateral lung base.

Case Presentation:

In this report, we present a case of a 25-year-old man diagnosed with HAPE combined with spontaneous pneumomediastinum. After a quick
descent and effective medical treatment, this patient made a full recovery. The case may provide helpful information for the prevention and
treatment of this disease since an increased number of people, especially young men, currently travel and work at high altitudes.

Conclusion:

After accurate clinical diagnosis with the help of CT or X-ray, immediate descent and appropriate oxygen supplementation are the most effective
treatments for HAPE at high altitude.
Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification
Authors: Wang Wei , Cao Xu , Cao Yi-nan , Liu Lian-lian , Zhang Shu-ling , Qi Wen-ying , Zhang Jia-xin , Yang Xian-zhao , Li Xiao-ke , Zao Xiao-bin , Ye Yong-an
Published: October 2023

Background:

In China, Niuxi-Mugua formula (NMF) has been widely used to prevent
and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for
treating COVID-19 is not yet fully understood.

Objective:

This study aimed to explore the potential mechanism of NMF for treating COVID-
19 by network pharmacology, computational biology, and surface plasmon resonance (SPR)
verification.

Materials and Methods:

The NMF-compound-target network was constructed to screen the key
compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary
key genes. The overlapped genes (OGEs) and the preliminary key genes were further
analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the
preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation
assays were applied to clarify the interactions between key compounds and key genes.
Moreover, the SPR interaction experiment was used for further affinity kinetic verification.

Results:

Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways
were the main pathways of NMF in the treatment of COVID-19. There was a positive
correlation between almost the majority of immune signatures and all preliminary key
genes. The key compounds and the key genes were screened out, and they were involved
in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of
most key compounds binding to key genes were good, and IL1B-Quercetin had the best
binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding
affinity.

Conclusion:

Our findings provided theoretical grounds for NMF in the treatment of COVID-
19.
RHBDD1 Promotes the Growth and Stemness Characteristics of Gastric
Cancer Cells by Activating Wnt/β-catenin Signaling Pathway
Authors: Yang Yingxue , Yuan Yuan , Xia Boning
Published: October 2023

Backgrounds:

Gastric cancer (GC) is threatening public health, with at least one million
new cases reported each year. Rhomboid domain-containing protein 1 (RHBDD1) has been
identified to regulate the proliferation, migration, and metastasis of cancer cells. However, the
role of RHBDD1 in GC has not been elucidated.

Objects:

This study aimed to investigate the role of RHBDD1 on the growth, metastasis, and stemness
characteristics of GC.

Methods:

RHBDD1 expression was analyzed from the TCGA databank. qRT-PCR was conducted
to evaluate the transcription level of RHBDD1. Western blots were used to evaluate the protein
expression of RHBDD1, CD133, CD44, Nanog, β-catenin and c-myc. Colony formation assay
and transwell assay were conducted to evaluate the growth and metastasis of NCI-N87 cells, respectively.
Sphere-forming assay was performed to study the stemness characteristics. The nude
mice xenotransplantation model and immunohistochemistry (IHC) were performed to evaluate the
growth of GC in vivo.

Results:

RHBDD1 expression is elevated in GC cells and clinical tissues. RHBDD1 expression is
positively associated with cell proliferation and metastasis of GC cells. RHBDD1 knockdown suppresses
the expression of CD133, CD44 and Nanog and attenuates sphere-forming ability. RHBDD1
activates the Wnt/β-catenin pathway via promoting the expression of β-catenin / c-myc and inducing
β-catenin translocation into nuclear. RHBDD1 knockdown inhibits the growth of GC in
nude mice xenotransplantation model.

Conclusion:

RHBDD1 is highly expressed in GC, and its knockdown inhibits the growth, metastasis
and stemness characteristics of GC cells through activating the Wnt/β-catenin pathway,
suggesting that RHBDD1 has the potential to be a novel therapeutic target for GC treatment.
Artificial Intelligence in The Management of Neurodegenerative
Disorders
Authors: Dhankhar Sanchit , Mujwar Somdutt , Garg Nitika , Chauhan Samrat , Saini Monika , Sharma Prerna , Kumar Suresh , Kumar Sharma Satish , Kamal Mohammad Amjad , Rani Nidhi
Published: October 2023

Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological
function. The ability to detect and treat these conditions successfully is crucial for ensuring
the best possible quality of life for people who suffer from them. The development of effective new
methods for managing and treating neurodegenerative illnesses has been made possible by recent
developments in computer technology. In this overview, we take a look at the prospects for applying
computational approaches, such as drug design, AI, ML, and DL, to the treatment of neurodegenerative
diseases. To review the current state of the field, this article discusses the potential of computational
methods for early disease detection, quantifying disease progression, and understanding the
underlying biological mechanisms of neurodegenerative diseases, as well as the challenges associated
with these approaches and potential future directions. Moreover, it delves into the creation of
computational models for the individualization of care for neurodegenerative diseases. The article
concludes with suggestions for future studies and clinical applications, highlighting the advantages
and disadvantages of using computational techniques in the treatment of neurodegenerative diseases.
Artemisinin Attenuates Isoproterenol-induced Cardiac Hypertrophy via the
ERK1/2 and p38 MAPK Signaling Pathways
Authors: Song Renxing , Xiong Chunming , Bai Juncai , Bai Zhenzhou , Liu Wei
Published: October 2023

Background:

Artemisinin (ART) is mainly derived from Artemisia annua, a traditional Chinese medicinal plant, and has been found to affect cellular
biochemical processes, such as proliferation, angiogenesis, and apoptosis, in addition to its antimalarial properties. However, its effect on cardiac
hypertrophy and the underlying mechanisms remain unclear.

Objective:

This study aimed to investigate the effect of ART on cardiac hypertrophy and explore its possible mechanisms.

Materials and Methods::

A rat model was established by intraperitoneal injection of isoproterenol (ISO) for 3 days, and the degree of myocardial hypertrophy was compared
among 5 groups: a control (CON) group, an ISO group, and groups treated with different doses of ART (7 mg/kg/d, 35 mg/kg/d, and 75 mg/kg/d).
Echocardiography was used to evaluate cardiac function and structure. The cross-sectional area of cardiomyocytes was measured by hematoxylin
and eosin (H&E) staining. The heart weight (HW), body weight (BW), and tail length were measured, and the HW/tail length ratio and the
HW/BW ratio were calculated. H9C2 rat cardiomyocytes were cultured, and different amounts of ART were added 2 hours before ISO stimulation.
Phalloidin staining was used to evaluate the degree of cell hypertrophy. The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide
(BNP) were quantified in rat plasma and cell supernatant using enzyme-linked immunosorbent assay (ELISA), while the expression levels of p-
ERK1/2, p-JNK, and p-p38 MAPK were assessed in the myocardium and H9C2 cells via western blot analysis.

Conclusion:

The mechanism of ART against cardiac hypertrophy was related to inhibition of the ERK1/2 and p38 MAPK signaling pathways.

Result:

Intragastric administration of ART at a dosage of 35 mg/kg/d or over-mitigated the early-stage cardiac hypertrophy induced by ISO in rats led to a
reduction in left ventricular posterior wall diastolic thickness, interventricular septal thickness at diastole, lowered ANP and BNP levels, as well as
a decrease in HW/tail length and HW/BW ratio. In vitro studies demonstrated that ART at a concentration of 100 μM inhibited ISO-mediated
hypertrophy of H9C2 cells. The ISO group showed a higher p-ERK/GAPDH ratio and p-p38 MAPK/GAPDH ratio than the control group both in
vivo and in vitro. Although the p-JNK/GAPDH ratio was increased in the ISO group, there was no statistical difference. The p-ERK/GAPDH and
p-p38/GAPDH ratios were significantly lower in the ART group than in the ISO group.
Antipyretic and Anti-inflammatory Effects of Sanchen Pediatric Antipyretic
Paste
Authors: Su Li De , Hurilebater  , Chao Lu Men , Sanchula  , Yu Dong , Amguleng  , Hao Jian Hui , Li Xin
Published: October 2023

Objective::

This study aimed to investigate the antipyretic and anti-inflammatory effects
and mechanisms of Sanchen Pediatric antipyretic Paste (SPAP).

Methods::

Rats were randomly divided into 7 groups: negative control group, positive control group,
positive treatment group, SPAP high-dose, medium-dose and low-dose groups, and blank substrate
group. Except normal control group, rats in other groups were subcutaneously injected with 10% dry
yeast suspension (10mL/kg) on the back to establish a fever model, and the normal group was given
the same volume of saline. At the 4 h and 7 h after modeling, each treatment group was subjected to
corresponding SPAP intervention. Anal temperature was measured every one hour after modeling for
10 consecutive times. The average temperature-rise curve, maximum temperature and body temperature
response index (TRI) were calculated to evaluate the efficacy of SPAP. After the last temperature
measurement, abdominal aortic blood was collected, and serum was separated from blood. The
levels of IL-6, TNF-α and CRP in serum were determined by enzyme-linked immunosorbent assay.

Results::

The body temperature of the positive control group was significantly increased (p < 0.01) 4
hours after model establishment, and that of the SPAP groups significantly decreased (p < 0.01) after
5 hours of the model establishment. The levels of Serum IL-6, TNF-α and CRP were significantly
decreased (p < 0.01) in a dose-dependent manner.

Conclusion::

SPAP has an obvious antipyretic effect on fever caused by dry yeast in rats. One of its
antipyretic mechanisms may be associated with inhibiting inflammatory reactions by reducing the
production or accelerating the degradation of endogenous thermogenic cytokines, such as IL-6, TNF-
α, and CRP.