bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual Screening and Biological Evaluation of T22306 as a Potent Third-generation EGFR Inhibitor for NSCLC Treatment
Authors: Wang Ran , Ruan Wei , Fan Dang , Long Li , Zhang Han , Li Min , Xu Shan , Wang Linxiao 
Published: February 2025

Objectives:
According to the data, mutations in EGFR-related genes are the main cause of Non-Small
Cell Lung Cancer (NSCLC), necessitating the development of new drug constructs for EGFR-TKIs particularly
important. This study aimed to screen potential third-generation EGFR-TKIs to address the emerging drug resistance
challenges in NSCLC.

Methods:
In this study, virtual screening, molecular dynamics modeling, and bioactivity evaluation were carried
out to find a potential EGFR inhibitor that could overcome the L858R/T790M mutation. At first, 12 potential
compounds were screened step by step from about 250,000 structures by virtual screening. These 12 compounds
were subjected to MTT antitumor activity evaluation and kinase inhibition assay to select compounds with strong
antiproliferative effects on cancer cells. Then, the preferred compounds were subjected to time-dependent assay,
scratch assay, AO staining assay, and hemolysis assay. Finally, the preferred compound was subjected to molecular
docking and molecular dynamics simulation with 5HG7 protein.

Result:
The IC50 of T22306 on H1975 cells was 9.17 μM. In further kinase evaluation, the kinase inhibition of
EGFRL858R/T790M was 69.17%. In addition, time-dependent experiments and scratch and AO staining assays
confirmed the potential of T22306 as an EGFR-TKI inhibitor, while hemolysis assays demonstrated no significant
toxicity. Finally, molecular docking revealed the formation of critical hydrogen bonds between T22306 and
LEU-718. Furthermore, molecular dynamics simulations showed that the T22306-5HG7 complex has a low binding
energy (-117.73 ± 18.69 kJ/mol), thus suggesting that T22306 binds tightly to the target protein 5HG7.

Conclusion:
In this study, we rapidly screened potential compounds against NSCLC with the help of virtual
screening technology. Further in vitro experiments demonstrated that T22306 successfully overcame the
L858R/T790M mutation and could be a potential epidermal growth factor receptor inhibitor.

result:
The IC50 of T22306 on H1975 cells was 9.17 μM. In further kinase evaluation, the kinase inhibition of EGFRL858R/T790M was 69.17%. In addition, Time-dependent, Scratch and AO staining assays confirmed the potential of compound T22306 as an EGFR-TKI inhibitor, while Hemolysis assays showed no significant toxicity. Finally, molecular docking revealed the formation of a critical hydrogen bond between compound T22306 and the 5HG7 protein, while the T22306-5HG7 complex was shown in molecular dynamics simulations to have a low binding energy (-117.728 ± 18.688 kJ/mol), thus suggesting that T22306 binds tightly to the target protein 5HG7.
Barbigerone against Lipopolysaccharide-Induced Memory Deficit in Rodents via Alteration of Inflammatory and Oxidative Stress Pathway: In vivo and Molecular Dynamics Simulations Study
Authors: Nadeem Muhammad Shahid , Khan Jalaluddin Azam , Al-Abbasi Fahad A. , Alqurashi May M. , Bawadood Azizah Salim , Alzarea Sami I. , Sayyed Nadeem , Gupta Gaurav , Kazmi Imran 
Published: February 2025

Background:
Memory loss and cognitive decline are prominent symptoms of various
neurodegenerative diseases, impacting daily activities and posing a significant burden on healthcare
systems. The study aimed to explore the effect of barbigerone against LPS-induced memory impairment
in rats and may offer novel therapeutics for neurodegenerative diseases.

Methods:
A total of 30 male Wistar rats were utilized and subsequently divided into five distinct
experimental groups: group I received saline water as a control, group II- received LPS, group III -
received LPS, and barbigerone (10 mg/kg/p.o.), group IV- received LPS and a higher dose of
barbigerone (20 mg/kg/p.o.), and group V -barbigerone alone (20 mg/kg/p.o.). Behavioural test was
performed through the Morris water maze and Y-maze test. Biochemical markers such as oxidative,
proinflammatory, apoptotic, and further molecular docking and simulations elucidate the mechanisms
of barbigerone effects.

Results:
Barbigerone significantly improved the learning capacity of rats in both the MWM and Ymaze
tests, indicating enhanced memory and reduced latency times. Furthermore, barbigerone exhibited
beneficial effects on oxidative stress and inflammation markers, suggesting its potential to
protect against neuronal damage and promote cognitive function. Based on molecular docking,
barbigerone showed a greater binding affinity with different intermolecular interactions; among
them, NF-KB (ISVC) had the most potent interaction. Molecular dynamics simulations were performed
to assess the stability and convergence of complexes formed by Barbigerone with 1NME_
Barbigerone, 1SVC_Barbigerone, and 4AQ3 4AQ3_Barbigerone.

Conclusion:
These findings demonstrate that barbigerone possesses neuronal protective effects against
LPS-induced memory deficits in rats by restoring endogenous antioxidant and pro-inflammatory cytokines.

result:
The outcomes of this investigation revealed that the treatment of barbigerone significantly improved the learning capacity of rats in both the MWM and Y-maze tests, indicating enhanced memory and reduced latency times. Furthermore, barbigerone exhibited beneficial effects on oxidative stress and inflammation markers, suggesting its potential to protect against neuronal damage and promote cognitive function.
Computational Design of Multitargeted Ligands to Counter Drug Resistance of Mycobacterium Tuberculosis
Authors: Vummidi Varalakshmi , Talluri Sekhar 
Published: February 2025

Background
Tuberculosis (TB) is a significant global health challenge due to drug resistance. Furthermore, tuberculous meningitis (TBM), which affects the central nervous system, has a particularly high mortality rate. TBM drugs have low efficacy because of their low blood-brain barrier (BBB) permeability. Many institutions that treat tuberculosis lack the infrastructure to identify specific drug-resistance mutations. The development of drugs with the capability of treating multiple strains would contribute considerably to the advancement of TB control in countries with limited resources. Therefore, there is an urgent requirement for novel therapeutics that can target native and drug-resistant strains.

Objective
This study aimed to design a novel drug to target native as well as drug-resistant Mycobacterium tuberculosis (MTB) strains associated with pulmonary TB and TBM.

Methods
RNA Polymerase beta-subunit (rpoB) was chosen because it is a validated target for MTB. Pharmacophore features, core moiety analysis, and docking scores were used for ligand screening. Deep neural networks (DeepFrag) were used for structural optimization, and binding affinity was evaluated using AutoDock Vina. Custom scoring schemes, STWMM for TB and STWMMM for TBM, met the requirements of high binding affinity for multiple targets, optimal pharmacokinetic profiles, and chemical synthesizability.

Results
M1, M2, and M3 were the molecules with the highest STWMM and STWMMM scores, indicating their potential for TB and TBM therapy. The average binding energy of M1 was -8.83 kcal/mol for native and mutant rpoB. The average binding energy for M2 and M3 was -9.63 and -9.83 kcal/mol, respectively).

Conclusion
In this study, novel ligands for native and drug-resistant TB and TBM therapy were obtained by multi-target drug design. A major challenge for current therapeutic regimens for TB and TBM is the rise of drug-resistant strains of Mycobacterium tuberculosis and the necessity of distinguishing them from the native strains. The multi-targeted ligands developed have the potential to overcome these limitations.
Changes in Internet Activities and Influencing Factors for Problematic Internet Use During the COVID-19 Pandemic in Korean Adolescents: Repeated Cross-Sectional Study
Authors: Kim Sol I , Jin Jae-Chan , Yoo Seo-Koo , Han Doug Hyun 
Published: February 2025

Background
As adolescents increasingly engage with digital experiences, the internet serves as a platform for social interaction, entertainment, and learning. The COVID-19 pandemic accelerated this trend, with remote learning and restricted physical interactions driving changes in internet behavior. Adolescents spent more time on gaming and social media, reflecting a notable shift in use patterns.

Objective
We hypothesized that the COVID-19 pandemic changed internet use patterns among Korean adolescents, including content types, time spent on web-based activities, and pathological use prevalence. Additionally, we anticipated that these changes would correlate with shifts in adolescents’ psychological status during the pandemic.

Methods
Data from 827 adolescents aged 12 to 15 years (n=144 in 2018, n=142 in 2019, n=126 in 2020, n=130 in 2021, n=143 in 2022, and n=142 in 2023) were gathered over 6 years from 43 middle schools across 16 regions and 1 hospital in South Korea. The demographic data collected included age, sex, and school year. Participants also provided information on their internet use patterns and levels of internet addiction. Additionally, psychological status, including mood, anxiety, attention, and self-esteem, was assessed.

Results
There were significant differences in the depression scale (Patient Health Questionnaire 9). The Patient Health Questionnaire 9 scores for 2018, 2019, and 2023 decreased compared to those in 2020, 2021, and 2022 (F5=3.07; P=.007). Regarding changes in internet use behavior, game playing among adolescents decreased after the pandemic compared to before, while watching videos increased. Additionally, the rate of problematic internet use was highest for games before COVID-19, but after COVID-19, it was highest for videos, and this trend continued until 2023 (χ23=8.16, P=.04). Furthermore, this study showed that the Young’s Internet Addiction Scale (YIAS) score was highest in the game group in 2018 compared to other groups before COVID-19 (F5=14.63; P<.001). In 2019, both the game and video groups had higher YIAS scores than other groups (F5=9.37; P<.001), and by 2022, the YIAS scores among the game, video, and Social Network Service groups did not differ significantly. The degree of influence on the severity of internet addiction was also greatest for games before COVID-19, but after COVID-19, the effect was greater for videos than for games.

Conclusions
During the COVID-19 pandemic, internet use for academic and commercial purposes, including remote classes and videoconferences, increased rapidly worldwide, leading to a significant rise in overall internet use time. The demand for and dependence on digital platforms is expected to grow even further in the coming era. Until now, concerns have primarily focused on the use of games, but it is now necessary to consider what types of internet behaviors cause problems and how to address them.
Pendekatan Spiritualitas Untuk Kebermaknaan Hidup Penderita Hipertensi
Authors: Pambuka Fian Rizkyan Surya , Rahmadi Sidiq , Hidayat Wahyu , Saputra Tri Danang Nugroho Ikhwan , Alamsyah Muawwalul Bahafi 
Published: February 2025

Hipertensi merupakan penyakit kronis yang menjadi penyebab primer penyakit kronis yang lain. Penyakit hipertensi termasuk penyakit yang hanya dapat ditangani dengan obat-obatan dan modifikasi perilaku. Akantetapi, individu dengan penyakit kronis juga sering mengalami pandangan hidup yang pesimis hingga muncul kecemasan, dan kekhawatiran. Memberi makna dalam hidup dapat mendukung spiritualitas inividu. Maka tujuan dari penelitian ini adalah menjelaskan pentingnya spiritualitas untuk kebermaknaan hidup. Metode yang digunakan adalah literatir riview, peneliti melakukan pencarian artikel terkait menggunakan. Melalui penelitian ini dijelaskan bahwa spiritualitas menjadi aspek pendukung dan pelengkap pengobatan maupun terapi sbelumnya.
Gen Z's View on Islam and People's Welfare
Authors: Hanifah Khansa , Sobri Muhammad 
Published: February 2025

This research aims to provide comprehensive insights to policymakers, educators, and religious communities. This research uses a qualitative approach method with a literature review. The results of this research show that Generation Z's views on Islam in the 13-26 year age range are influenced by various factors, including the environment, media, and personal experience. It is essential to acknowledge this diversity of views and encourage open dialogue and mutual understanding among members of Generation Z to understand and respect differences. Through a literature review, I analyze Generation Z's religious perceptions, knowledge, and practices and their impact on individual and societal well-being. My results reveal the complexity of the interactions between religious values, social values, and personal aspirations in shaping Gen Z's perspective on Islam and the well-being of the Ummah, providing important insights for further understanding religious dynamics in the digital and globalization era.
The Impact of Advances in Science and Technology on The Moral and Spiritual Intelligence of Student in The Era of Globalization
Authors: Yunita Norma 
Published: February 2025

This article aims to raise awareness about science and technology and its implications for students' moral and spiritual well-being in the era of globalization. It will review the role of science and technology in assisting humans in the process of development and exploration in dealing with complex moral and spiritual issues that are common in the current era of globalization. The rapid development of information and communication makes it easy for individuals to access various facts and perspectives from various sources, which will affect their understanding of morals and spirituality. The data collection technique is observation, namely observing and recording every student's behavior related to the morals and spirituality of Jambi University students in the English Language Education study program. The sample for this study was the R-002 class of 2023, which amounted to 7 people. This research analyzes the various impacts of advances in science and technology on moral and spiritual intelligence in English Language Education students with descriptive methods using a qualitative approach.

Keywords: Science and Technology, Moral, Spiritual.
PENINGKATAN KEPUASAN PESERTA TERHADAP LAYANAN INFORMASI BPJS KESEHATAN MELALUI MEDIA: APAKAH EFEKTIF?
Authors: Nahdiana Nahdiana , Unde Alimuddin , Nasir Sudirman , Amar Yunus 
Published: February 2025

Abstract
Public Understanding of the National Health Insurance Program (JKN) is still lacking due to the limitations of health information services from the government. This study aims to find out whether the use of media in disseminating JKN Program information effectively provides information service satisfaction to BPJS Kesehatan participants. The study used a quantitative design with survey explanation methods. The population in this study was a non-PBI Health BPJS participant (not a Contribution Assistance Recipient) with a PPU category (Wage Earner Worker) of 405 people. Data retrieval techniques through questionnaires given to respondents through a google form. The data is processed using smart PLS and analyzed with the SEM (Structural Equation Model) approach. The results showed that the media had a positive and significant effect on participants' satisfaction which can be seen from the value of t-statistical media to satisfaction of 3.13 > 1.96 or p-value value of 0.00 < 0.05 and track coefficient value of 0.148 which indicates that the media aspect affects the media satisfaction of participants. Based on the results of the study, it can be concluded that the use of effective media provides satisfaction to BPJS Kesehatan participants. The results of this study are expected to be used as a consideration for BPJS Kesehatan to use more fragmented media to disseminate information taking into account the condition/ability of the community.

Keywords: BPJS Health, information services, JKN Program, media, participant satisfaction
ОСОБЕННОСТИ РЫНКА МЕДИЦИНСКИХ УСЛУГ: ТЕОРЕТИКО-ЭКОНОМИЧЕСКИЙ АНАЛИЗ
Authors: Манукянц С.В. 
Published: February 2025

Выделены основные понятия, применяемые экономистами при описании и исследовании сферы здравоохранения. Показано соответствие выявленных понятий с ключевыми категориями современной экономической науки. Описаны экономические взаимосвязи между рассмотренными понятиями.
The increased interest in health capital as part of human capital, along with the transformation of the healthcare sector, requires clarification of the key concepts in this area with regard to the contemporary methodology of economic theory. The researchobjective is to identify and systematize the theoretical approaches that are currently used in economic theory to describe the market of medical services. The research methods utilized in the study include the analysis of relevant domestic and foreign scientific publications, analysis of the Russian legislative framework, synthesis, as well as analytical and graphical modeling. Results. In modern economic research, the healthcare sector is a provider of a complex good aimed at maintaining and improving the health of the population. Health itself is perceived as a capital good, and, in contrast to investments in education, which serve to increase income due to an increase in knowledge and skills, investments in health capital help to avoid income losses by reducing the duration of periods of disability and decreased productivity caused by health problems of individuals themselves or their close relatives. The main component of the complex good produced by the healthcare sector and considered by health care economics is a medical service (or medical care as a set of services). This service may have the following characteristics: uncertainty of demand, information asymmetry, duality of the role of the service provider, lack of a price mechanism as a regulator of demand, local monopoly of producers, limited access to the market for new producers, limited interest in maximizing profits, the presence of externalities. The degree of manifestation of these characteristics is heterogeneous within the totality of medical goods. Conclusion. The variety of medical services requires a differentiated approach to modeling the economic processes associated with them. At the same time, the classification of a certain service into one category or another depends both on the characteristics of the service itself and the characteristics of the institutional environment in which its production and consumption occurs.
GRUPOS SOCIAIS MARGINALIZADOS NA CIDADE DE MANAUS - AM
Authors: Castro Brenda Sarah Cardoso de , Castro de Jesus Ana Beatriz 
Published: February 2025

O presente trabalho aborda as interpretações de grupos sociais marginalizados da cidade de Manaus a partir de análises conceituais de segregação socioespacial, sob a ótica de autores como Roberto Lobato Corrêa, que discorre sobre a realidade de áreas urbanas brasileiras. Nesse sentido, busca-se discutir o avanço de segmentos marginalizados na cidade de Manaus, além de apresentar os diferentes topônimos referindo-se aos assentamentos irregulares existentes no Brasil, enfatizando as toponímias locais. No âmbito metodológico, realizou-se um levantamento bibliográfico pautado nos principais conceitos, assim como a produção cartográfica para identificação dos aglomerados subnormais e, por fim, uma atividade de campo para fins de observar as dinâmicas de um assentamento localizado na Zona Norte da cidade de Manaus. A partir disso, foi possível identificar características sociais locais, evidenciando uma tendência de crescimento intensivo na porção Norte da cidade.
Endoscopic stent placement in the management of esophagojejunal anastomosis leakage
Authors: Dobrzhanskyi O. , Kondratskyi Y. , Kozak E. , Kolesnyk A. , Pepenin M. , Shudrak Y. , Horodetskyi A. , Turchak V. , Omelchak A. , Koval N. , Svichkar Y. , Ukrainets I. 
Published: February 2025

Objective — to evaluate the effectiveness of endoscopic stent placement compared to surgical methods for the management of esophagojejunal anastomosis leakage (AL) after gastrectomy at the National Cancer Institute (NCI) from November 2017 to November 2019.
Materials and methods. The study included patients receiving treatment at the Upper Gastrointestinal Oncology Department of the National Cancer Institute between November 2017 and November 2019. Throughout this period, 186 total gastrectomies were performed. 13 (6.9%) patients developed an anastomotic leak in the postoperative period. All patients had Roux‑en‑Y esophagojejunostomy. 6 patients (46.1%) underwent endoscopic stent placement in the AL area, along with perianastomotic drainage positioning and enteral feeding via a naso‑intestinal tube. Of the remaining patients, 7 (53.9%) underwent surgical treatment, including esophagostomy or esophageal stump formation with a nutritional jejunostomy. This manuscript employed methods of descriptive statistics.
Results. Endoscopic stent placement was successful for 5 patients. Complete defect closure following stent placement was confirmed in 5 patients (83.3%) using endoscopic and radiological methods. The mean hospital stay in the stent group was 15.4 days (range: 9—22 days). The mean time for endoscopic stent removal during rehospitalization was 49.5 (33—62 days) days after initial placement. Complications associated with AL, specifically sepsis resulting from infection in the AL area, led to the death of 1 (16.7%) patient in the stent group. Surgical treatment was successful in 5 patients (71.4%). 2 patients (28.6%) died due to infectious complications and multiple organ failure syndrome. The average hospital stay for surgical patients was 32.8 (19—40) days. Mortality rates were 16.7% and 28.6% for the stent placement and surgical groups, respectively.
Conclusions. Endoscopic endoluminal stent placement in the area of AL using self‑expandable metallic stents combined with local drainage and enteral nutrition is a promising method for treating esophagojejunal anastomotic leakage after total gastrectomy. This study demonstrates that endoscopic stent placement reduces hospital stay and mortality rates compared to surgical methods. Endoscopic stent placement provides effective defect closure with fewer complications. However, surgical treatment remains indispensable in cases of severe sepsis or failure of conservative methods, despite the high mortality risk. Further studies are needed to develop standardized approaches for selecting treatment methods based on leak size and the patient’s overall condition.