bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Antitumor
Activity of Disulfiram and Cisplatin in Ovarian Cancer
Authors: Du Ruiping , Sun Feilong , Li Kai , Qi Jian , Zhong Wen , Wang Wei , Sun Qiuyan , Deng Qingmei , Wang Hongzhi , Nie Jinfu , Ding Chen , Hong Bo 
Published: May 2023

Introduction:
Among gynecological cancers, ovarian cancer has a high mortality rate. Cisplatin-based
chemotherapy is commonly used for the treatment of ovarian cancer. However, the clinical efficacy of cisplatin in
ovarian cancer is limited due to the development of chemo-resistance during treatment.

Objective:
In the study, we aimed to investigate the synergistic anti-cancer activity and targets of the FDA-approved
drug disulfiram combined with cisplatin in ovarian cancer.

Methods:
The cell viability was determined by Celltier-Glo luminescent assay. The synergistic anti-cancer activity was
assessed by combination index. Cell cycle and apoptosis were detected by flow cytometry. The in vivo anti-tumor
activity and side effects were evaluated using a xenografted mice model. The synergistic anti-cancer targets were identified
by a mass spectrometry-based proteomics analysis.

Results:
In this study, we first found that disulfiram synergistically enhanced the anti-tumor activity of cisplatin in
chemo-resistant ovarian cancer cells, which was accompanied by the enhanced induction of cellular apoptosis.
Secondly, the in vivo study demonstrated that the combination treatment of disulfiram and cisplatin dramatically
inhibited tumor growth and had no apparent side effects in ovarian cancer xenografted mice. Finally, proteomics analysis
identified SMAD3 as a potential target of disulfiram-cisplatin combined treatment, and the down-regulation of
SMAD3 could increase cisplatin-induced cell death in ovarian cancer.

Conclusion:
Combination treatment of disulfiram and cisplatin synergistically inhibited the growth of ovarian cancer
through down-regulating SMAD3. As a repurposed drug, disulfiram could be quickly transformed into a clinic to overcome
cisplatin resistance for the treatment of ovarian cancer.
KRAS Mutation Reduces Thymoquinone Anticancer Effects on Viability of Cells and
Apoptosis
Authors: Betul Yenigun Vildan , Acar Hasan , Kanimdan Ebru , Yenigun Alper , Kocyigit Abdurrahim , Cora Tulin 
Published: May 2023

Background:
Cancer is a life-threatening condition with an economic burden on societies. Phytotherapy is
rapidly taking place in cancer research to increase the success of treatment and quality of life. Thymoquinone (TQ) is
the main active phenolic compound obtained from the essential oil of the Nigella sativa (black cumin) plant seed. For a
long time, black cumin has been used traditionally for the remedy of different diseases because of its various biological
effects. It has been shown that most of these effects of black cumin seeds are due to TQ. TQ became a popular research
topic for phytotherapy studies for its potential therapeutic applications, and more research is going on to fully understand
its mechanisms of action, safety, and efficacy in humans. KRAS is a gene that regulates cell division and growth.
Monoallelic variants in KRAS result in uncontrollable cell division, leading to cancer development. Studies have shown
that cancer cells with KRAS mutations are often resistant to certain types of chemotherapy and targeted therapies.

Objective:
This study aimed to compare the effect of TQ on cancer cells with and without KRAS mutation to better
understand the reason why TQ may have different anticancer effects in the different types of cancer cells.

Methods:
TQ was investigated for its cytotoxic and apoptotic effects in laryngeal cancer cells (HEp-2) without KRAS
mutation and compared to mutant KRAS-transfected larynx cancer cells and KRAS mutation-carrying lung cancer cells
(A549).

Results:
We showed that TQ has more cytotoxic and apoptotic effects on laryngeal cancer cells without KRAS mutation
than in cells with mutation.

Conclusion::
KRAS mutations decrease the effect of TQ on cell viability and apoptosis, and further studies are needed
to fully understand the relationship between KRAS mutations and thymoquinone effectiveness in cancer treatment.
The Microneedle Drug Delivery System and some Recent Obstacles in its
Implementation
Authors: Dugad Bhagyesh , Bhattacharya Sankha 
Published: May 2023

Abstract:
Transdermal Drug Delivery (TDD) is a non-painful way of systemically delivering medications
by applying a drug formulation to intact, healthy skin. The drug particles’ limitations, including the molecular
weight and hydrophilicity, preclude TDD from being exploited extensively. Microneedle arrays
(MNA) are an efficient way for medication delivery via the skin. Microneedles enhance medication administration.
Microneedles are either long, hollow, or coated. They are designed to target the skin as
quickly and safely as possible, without the use of chemical, nanoparticle, or hypodermic injections and
without requiring micro-pen or physical strategies. Solid microneedles include micropores, whereas hollow
microneedles provide a more profound passage into the dermis. Investigations have been conducted
on the use of dissolving microneedles for the delivery of vaccines, while coated microneedles have been
utilized to efficiently deliver vaccines. This paper attempts to provide a comprehensive summary of the
current state of MNA science, with a focus on methodologies, issues, implementations, and the types of
materials lately dispersed by such devices. In addition, some information regarding the components and
manufacturing methods is provided. Metals, silicone, ceramics, synthetic materials, and biodegradable
polymers, such as carbohydrates, can be utilized to manufacture microneedles.
Microwave-assisted Synthesis of 3-amino-2-phenylquinazolin-4(3H)-one
(QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh)
Authors: Kumar Das Ranjan , Sharma Debdulal , Paul Subrata , Sengupta Devashish 
Published: May 2023

Background:
Microwave synthesis has developed as a powerful tool for the cost-effective and greener synthesis of organic molecules, including quinazolines. Irradiation with microwave leads to the excitation of molecules and equitable distribution of thermal energy in a much shorter time than conventional synthesis. This results in shorter reaction time and, more often than not, higher efficiency

Objective:
The primary objective of the work presented in this article was to prepare hydrazine hydrate or thiourea derivative of quinazolines through microwave synthesis as small-molecule scaffolds for fur-ther need-based functionalisation, isolation, and characterisation. We, herein, report the synthesis of two quinazolinone derivatives of thiourea and hydrazine, 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh), respectively.

Method:
A multi-step synthetic strategy starting from anthranilic acid was employed to synthesise the small molecule quinazolinones 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh). The compounds were synthesised by reacting hydra-zine and thiourea with 2-benzamidobenzoyl chloride in DMF under microwave irradiation (800 W at 135 °C for 4 min) in the presence of potassium carbonate. The acid chloride was prepared by chlorination of 2-benzamidobenzoic acid, which in turn was synthesised from anthranilic acid by benzoylation. This method is an efficient alternative approach to synthesising quinazolinones from benzoxazin-4-ones.

Results:
We have successfully synthesised, isolated, and characterised the quinazolinone derivative QH (yield: 81%) and QTh (yield: 85%). The structures of the compounds were established through spectro-scopic techniques. Theoretical optimisation of the structures was also achieved using DFT. The HOMO-LUMO difference for QH and QTh was calculated to be 4.60 and 4.47 eV, respectively.

Conclusion:
The reported protocol is advantageous over conventional methods of quinazoline synthesis from benzoxazin-4-ones. The time required for the reaction is much less (4 min) as compared to the usual requirements of reflux (> 4 h); the higher energy gap of QH indicates greater stability than that of QTh.
Effects of Pesticides Carried by Foods on Human Gut Microbiota
Authors: Rodríguez Lucía Varela , Lopez-Santamarina Aroa , del Carmen Mondragón Alicia , Regal Patricia , Lamas Alexandre , Rodriguez Jose Antonio , Miranda José Manuel , Franco Carlos Manuel 
Published: May 2023

Abstract:
The human gut microbiota is part of a delicate ecosystem that also involves the individual
in which it is hosted and the environment. Humans and their gut microbiota depend on each other to
maintain good health, but many external factors can contribute to the disruption of this balance and
lead to diseases. Pesticides are a good example of environmental pollutants to which humans are exposed
on a daily basis, mainly through diet. As a result, the composition and functionality of the gut
microbiota can be compromised, as the gastrointestinal tract is the first physical and biological barrier
with which they interact. Finally, through multiple and complex mechanisms, all this has repercussions
on the health status of the host, and the adverse effects of this gut microbiota–pesticide interaction
can manifest themselves in various ways, such as alteration of the diversity and abundance of the
different bacteria, both beneficial and pathogenic, that colonize the gastrointestinal tract, metabolic
and endocrine disorders, inflammation, dysregulation of the immune system and neurological disorders,
among many others. Therefore, this work aims to summarize the latest scientific evidence on the
effects of pesticides on the gut microbiota and the possible implications for human health as well as
animal models and in vitro cultures on which the different tests are carried out.
Desarrollo y evaluación de un sensor portátil para la detección de Hg2+, a través de la síntesis verde de AuNP utilizando extracto acuoso de Sargassum spp.
Authors: Molina Labastida Gustavo Andrés , López-Miranda José Luis , González-Reyna Marlen Alexis , Esparza Muñoz Rodrigo Alonso , Estevez-González Miriam Rocío 
Published: May 2023

El presente trabajo tiene la finalidad de dar a conocer el desarrollo de un prototipo de sensor para la medición de mercurio (Hg2+) en solución acuosa sobre una plataforma electroquímica basada en electrodos serigrafiados de nanotubos de carbonos (CNT-SPE) en conjunto con nanopartículas de oro (NPs-Au) realizadas a través de síntesis verde, utilizando extracto acuoso de Sargassum spp. Para esto, se realizó la caracterización de las NPs-Au por espectroscopía ultravioleta-visible (UV-Vis), infrarrojo (TF-IR), difracción de rayos X (DRX) y microscopía electrónica de barrido (SEM); obteniendo nanopartículas entre 80-100 nm las cuales poseen un recubrimiento orgánico que les confiere una sinergia al momento de ser conjugadas con CNT-SPE oxidadas/activadas. Posteriormente, las NPs-Au se utilizaron para modificar el CNT-SPE a través del método drop-casting y así ensamblar un novedoso sensor electroquímico para la medición de Hg2+, cuya validación y habilidad para medir fue demostrada utilizando voltametría diferencial de pulso (DPV). Se obtuvieron límites de detección de 2.38 uM y cuantificación de 3 uM. Los resultados demuestran que la plataforma desarrollada es una alternativa rápida, eficiente y portátil para la medición de Hg2+.
FUNDAMENTALIST DA’WAH MOVEMENT: THE STUDY OF LOCAL TABLIGHI JAMA’AH GROUP AND ITS ACCEPTANCE IN MADURA
Authors: Zamhari Arif , Ahsan Riadi  
Published: May 2023

This paper analyzes the form of religious fundamentalism displayed through Tablighi Jama'ah’s da’wah movement in Madura and uncovers the rationale for Madura’s community's acceptance of this da’wah movement group. This paper is qualitative research using a case study approach. Data collection was carried out through interviews with some main figures and followers of the group, a series of observations, and documentation of the da’wah activities undergone by the group. The result shows that the Tablighi Jama'ah’s da’wah movement in Madura can be categorized as a puritanical Islamic fundamentalist movement, particularly because it intends to purify faith, sharia, and morals. In contrast to the beliefs of other religious groups, this group prohibits an active and massive use of technology because it is perceived as a direct obstacle to da’wah and is considered full of immorality. This group emphasizes the so-called sunnah appearance, such as using robes, turbans, siwak, cingkrang trousers, and not being engaged in practical politics. Moreover, they also emphasize congregational prayers and the necessity of living a simple life. This paper also signifies that the Madura community accepts the Tablighi Jama'ah because their religious practices are congruently aligned with the teachings of Ahlus Sunnah Wal Jama'ah. In addition, the acceptance of the Madura community is due to their obedience toward the Kiai, who have previously accepted the Tablighi Jama'ah da’wah activities in Madura.
Leucine Supplementation Ameliorates Early-Life Programming of Obesity in Rats
Authors: Sun Yuchen , Sun Bo , Han Xuesong , Shan Anshan , Ma Qingquan 
Published: May 2023

The advanced cessation of lactation elevates the risk of programmed obesity and obesity-related metabolic disorders in adulthood. This study used multiomic analysis to investigate the mechanism behind this phenomenon and the effects of leucine supplementation on ameliorating programmed obesity development. Wistar/SD rat offspring were subjected to early weaning (EW) at day 17 (EWWIS and EWSD groups) or normal weaning at day 21 (CWIS and CSD groups). Half of the rats from the EWSD group were selected to create a new group with 2-month leucine supplementation at day 150. The results showed that EW impaired lipid metabolic gene expression and increased insulin, neuropeptide Y, and feed intake, inducing obesity in adulthood. Six lipid metabolism–related genes (Acot1, Acot2, Acot4, Scd, Abcg8, and Cyp8b1) were influenced by EW during the entire experimental period. Additionally, adult early-weaned rats exhibited cholesterol and fatty acid β-oxidation disorders, liver taurine reduction, cholestasis, and insulin and leptin resistance. Leucine supplementation partly alleviated these metabolic disorders and increased liver L-carnitine, retarding programmed obesity development. This study provides new insights into the mechanism of programmed obesity development and the potential benefits of leucine supplementation, which may offer suggestions for life planning and programmed obesity prevention.

Article Highlights
Early-weaned adult rats showed excess lipid accumulation and metabolic defects. Early weaning disrupts lipid metabolism and secretion of neuropeptide Y and insulin. The altered lipid metabolic gene expression in this study is vital in programming. Leucine mitigates metabolic disorders and hampers programmed obesity development.
<strong>At-home use of a pregnancy-specific Zone-MPC closed-loop system for pregnancies complicated by type 1 diabetes: a single arm, observational multicenter study</strong>
Authors: J. Levy Carol , C. Kudva Yogish , Ozaslan Basak , Castorino Kristin , O’Malley Grenye , Jeet Kaur Ravinder , M. Levister Camilla , Mei Church Mei , Desjardins Donna , McCrady-Spitzer Shelly , Ogyaadu Selassie , Charisse Trinidad Mari , Reid Corey , Rizvi Shafaq , Deshpande Sunil , Zaniletti Isabella , K. Kremers Walter , E. Pinsker Jordan , J. Doyle III Francis , Dassau Eyal , LOIS-P Diabetes and Pregnancy Consortium the 
Published: May 2023

<p> </p>
<p>OBJECTIVE: There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the United States. This study aimed to evaluate the feasibility and performance of at-home use of a zone model predictive controller based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P).</p>
<p>RESEARCH DESIGN AND Methods: Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and two days of supervised training, participants used CLC-P targeting 80-110 mg/dL during the day and 80-100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63-140 mg/dL versus run-in.</p>
<p>Results: Ten participants (HbA1c 5.8±0.6%) used the system from mean gestational age of 23.7±3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 hours per day, compared to run-in (run-in: 64.5±16.3% versus CLC-P: 78.6±9.2%, P=0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P=0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P=0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use. </p>
<p>ConclusionS: The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are indicated to further evaluate system efficacy and pregnancy outcomes.</p>
Evaluasi Program Pendidikan Jasmani Olahraga dan Kesehatan Materi Aktivitas di Air di SMP Negeri 14 Pekanbaru
Authors: Risman Iqbal , Argantos Argantos 
Published: May 2023

Penelitian ini bertujuan untuk mengetahui keterlaksananya program pembelajaran pendidikan jasmani olahraga dan kesehatan materi aktivitas dia air di SMP Negeri 14 Pekanbaru dengan mengunakan pendekatan evaluasi model Conteks, Input, Process, Product, dan Outcome (CIPPO). Subjek penelitian ini adalah kepala sekolah, dan guru PJOK, dan peserta didik. Pengumpulan data dilakukan dengan Dokumentasi, Observasi, dan Wawancara. Data analisis deskriptif dianalisis dengan teknik deskriptif kulitatif. Hasil penelitian menunjukan evaluasi Context, materi pembelajaran yang digunakan relevan dengan kurikum 2013, namun teknis pelaksanaan tidak terlaksana secara keseluruhan; Input menunjukan latar belakang pendidikan guru sesuai dengan kualifikasi guru PJOK dan latar belakang peserta didik sudah mampu melaksanakan pembelajaran, sarana prasaran PJOK yang menunjang aktivitas di air sama sekali tidak disediakan sekolah. Process meliputi pelaksanaan pembelajaran PJOK sudah berjalan cukup baik; Product hasil belajar peserta didik dan nilai rerata kelas sudah di kategori cukup Baik; Outcome yaitu dampak untuk peserta didik pentingnya pembelajaran PJOK untuk kesehatan dan kehidupan sehari-hari. Secara umum program pembelajaran telah berpedoman pada (BSNP), akan tetapi belum sepenuhnya sesuai standar nasional pendidikan, yang meliputi kesesuain pelaksanan pembelajaran dengan RPP yang disampaikan, sarana dan prasarana PJOK materi aktivitas di air masih kurang memadai, serta pelaksanaan dan cara pemberian nilai pembelajaran PJOK juga belum sesuai standar.
Atributos de la buena enseñanza universitaria
Authors: Ibarra Rosales Guadalupe 
Published: May 2023

Introducción. En este artículo se desarrollan los atributos y características de una buena enseñanza universitaria, tomando en cuenta los resultados de una encuesta sobre la buena práctica docente a nivel universitario aplicada a alumnos de la Maestría en Pedagogía de la UNAM que han egresado de este programa de posgrado.
Objetivo: Conocer los rasgos y las características de una buena enseñanza, en opinión o a juicio de los alumnos de la generación 2020-2 de la Maestría en Pedagogía de la UNAM.
Método: Una encuesta sobre la buena práctica docente a nivel universitario, cuyo instrumento fue un cuestionario con preguntas abiertas.
Referentes teóricos: Los planteamientos teóricos del modelo de competencias profesionales, así como la propuesta del nuevo paradigma educativo que tiene como eje el aprendizaje de los alumnos.
Resultados: En una buena enseñanza universitaria se estructuran dos dimensiones: la pedagógica (82%) y la ética (18%). La dimensión pedagógica está compuesta por tres tipos de competencias: a) las competencias pedagógicas y didácticas (56%), que fueron las más valoradas y se situaron en primer lugar como el atributo principal de una buena enseñanza; b) en segundo término se colocaron las competencias de enseñanza innovadoras (38%), las cuales están enfocadas al cambio y mejora de la enseñanza; c) el tercer y último lugar fue ocupado por el dominio del contenido (4%), que fue el menos valorado por los estudiantes encuestados.
Conclusiones: Los resultados obtenidos exponen los atributos que califican a una buena enseñanza universitaria y, por lo tanto, muestran aquellos elementos o aspectos que se podrían tomar en cuenta para cambiar y mejorar la enseñanza universitaria. Asimismo, estos resultados están en sintonía con el paradigma centrado en el aprendizaje, el cual constituye un modelo educativo que se está impulsando e implementando a nivel mundial.
THE EFFECT OF PROBLEM BASED LEARNING MODEL ASSISTED CONCEPT MAP TO AUTHENTIC PROBLEM SOLVING SKILLS TOPIC ON DYNAMIC ELECTRIC GRADE X SMA NEGERI 1 SIDIKALANG A.Y 2015/2016
Authors: Harahap Mara Bangun , Silalahi Novita Sari 
Published: May 2023

The purpose of this study was to determine the effect of problem based learning model to authentic problem solving skills of students topic on dynamic electric grade X SMA Negeri 1 Sidikalang . This type of research is quasi-experimental. The population of this entire class X SMA Negeri 1 Sidikalang consist of 11 classes. The sample in this study was taken by a random sampling of two classes that’s X-8 class asexperiment class with 23 students and X-7 class as control class with 26 students. The instrument used to determine student learning outcomes in the material dynamic electric in the form of essay test with numbered 10 and observation sheet. The results obtained by testing hypotheses is concluded that there is a significant relationship between use problem based learning model to authentic problem solving skills of students grde X SMA Negeri 1 Sidikalang.
PENGARUH MODEL PROBLEM BASED LEARNING TERHADAP HASIL BELAJAR SISWA KELAS X SEMESTER II PADA MATERI POKOK SUHU DAN KALOR SMA NEGERI 1 STABAT T.P. 2015/2016
Authors: Maduwu Apri Tivani , Hutahaean Juniar 
Published: May 2023

Penelitian ini bertujuan untuk mengetahui pengaruh model Problem Based Learning (PBL) terhadap hasil belajar siswa Kelas X Semester II pada materi pokok Suhu dan Kalor SMA Negeri 1 Stabat T.P. 2015/2016. Jenis penelitian ini adalah quasi eksperimen. Populasi dalam penelitian adalah seluruh siswa kelas X SMA Negeri 1 Stabat. Penarikan sampel dengan cluster random samplingyaituX MIA-3 sebagai kelas eksperimen dengan pembelajaran Model Problem Based Learning sedangkan kelas X MIA-4 sebagai kelas kontrol diajarkan dengan pembelajaran Konvensional. Instrumen yang digunakan pada penelitian adalah tes uraian berjumlah 10 soal. Data penelitian yaitu dalam bentuk hasil belajar. Untuk data hasil belajar diawali dengan uji normalitas dan homogenitas. Dengan data yang sudah telah berdistribusi normal dan homogen maka dilakukan uji statistik dengan uji t pada taraf signifikan α = 0,05. Nilai rata-rata hasil pretes kelas eksperimen adalah 28,4 dan kelas kontrol adalah 23,1. Dan nilai rata-rata postes kelas eksperimen 69,3 dan kelas kontrol 39,5. Hasil uji pretes kedua sampel antara kelas eksperimen dan kelas kontrol mempunyai kemampuan awal yang sama. Setelah diberikan perlakuan menggunakan model Problem Based Learning, kelas eksperimen lebih tinggi dari kelas kontrol sehingga terbukti ada pengaruh model Problem Based Learning terhadap hasil belajar siswa kelas X Semester II pada materi pokok Suhu dan Kalor SMA N 1 Stabat T.P 2015/2016.