bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a phenotypic screening assay to measure activation of cancer-associated fibroblasts
Authors: Ilg Marcus M. , Lapthorn Alice R. , Harding Sophie L. , Minhas Tariq , Koduri Gouri , Bustin Stephen A. , Cellek Selim 
Published: February 2025

BackgroundIn cancer metastasis, tumor cells condition distant tissues to create a supportive environment, or metastatic niche, by driving the activation of cancer-associated fibroblasts (CAFs). These CAFs remodel the extracellular matrix, creating a microenvironment that supports tumor growth and compromises immune cell function, enabling cancer cells to evade immune detection. Consequently, targeting the activation of CAFs has been proposed as a therapeutic strategy to hinder metastatic spread. Our objective was to develop the first in vitro phenotypic screening assay capable of assessing this activation process.MethodsHuman primary lung fibroblasts were co-cultured with highly invasive breast cancer cells (MDA-MB-231) to identify changes in the expression of selected genes using RT-qPCR. An In-Cell ELISA (ICE)-based assay using human lung fibroblasts, MDA-MB-231 cells and human monocytes (THP-1 cells) was developed to measure the activation of CAFs. Another ELISA assay was used to measure released osteopontin.ResultsWhen lung fibroblast were co-cultured with MDA-MB-231 cells, among the 10 selected genes, the genes for osteopontin (SPP1), insulin like growth factor 1 (IGF1), periostin (POSTN) and α-smooth muscle actin (α-SMA, ACTA2) elicited the greatest fold change (55-, 37-, 8- and 5-fold respectively). Since osteopontin, IGF-1 and periostin are secreted proteins and α-SMA is an intracellular cytoskeleton protein, α-SMA was chosen to be the readout biomarker for the ICE assay. When fibroblasts were co-cultured with MDA-MB-231 cells and monocytes in the 96 well ICE assay, α-SMA expression was increased 2.3-fold yielding a robust Z′ of 0.56. A secondary, low throughput assay was developed by measuring the release of osteopontin which showed a 6-fold increase when fibroblasts were co-cultured with MDA-MB-231 cells and monocytes.DiscussionThis phenotypic assay is the first to measure the activation of CAFs in a 96-well format, making it suitable for medium-to high-throughput screening of potential therapeutic compounds. By focusing on observable cellular phenotypic changes rather than targeting specific molecular pathways, this assay allows for a broader and unbiased identification of compounds capable of modulating CAF activation.
Time in the therapeutic range, bleeding event, and their determinants in older patients with atrial fibrillation on warfarin in Ethiopia: multicenter cross-sectional study
Authors: Addisu Zenaw Debasu , Demsie Desalegn Getnet , Tafere Chernet , Yazie Taklo Simeneh , Endeshaw Destaw , Tefera Bereket Bahiru , Berihun Malede , Beyene Dessale Abate 
Published: February 2025

BackgroundAtrial fibrillation (AF) poses significant thromboembolism and bleeding risks, especially in older adults. Warfarin continues to be a primary treatment option, and maintaining the Time in Therapeutic Range (TTR) is critical for ensuring its effectiveness. However, suboptimal TTR is associated with increased risks of stroke, bleeding, and mortality. Despite its importance, there is limited data on warfarin management in Ethiopian older adults with AF. Therefore, this study aimed to determine the TTR, bleeding events, and their determinants, in older patients with AF in Ethiopia receiving warfarin therapy.MethodIn this study, older patients with AF who were treated with warfarin and had follow-up visits between May 2021 and May 2024, and met the inclusion criteria, were included. Patients were categorized based on TTR into two groups: poor anticoagulation (TTR &lt; 65%) and good anticoagulation quality (TTR ≥ 65%). Bivariate and Multivariate Logistic regression was performed to predict determinants of a TTR &lt; 65% and bleeding events. Odds ratios with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P &lt; 0.05.ResultsIn this study, 384 patients with AF were included. Of this 53.4% were female. Of these 71% of patients had a TTR below 65%, 29% achieved ≥65%, with a median TTR of 45%. Bleeding events were reported by 13.5% of patients. Poor TTR was significantly associated with age (AOR = 1.199, 95% CI: 1.109–1.297), chronic kidney disease (AOR = 27.809, 95% CI: 7.57–101.76), and infrequent INR monitoring at 31–90-day intervals (AOR = 0.15, 95% CI: 0.004–0.051). Regarding determinants of bleeding events, Patients with diabetes mellitus had a 2.6-fold higher bleeding risk (AOR = 2.585, 95% CI: 1.069–6.250), and a CHA2DS2-VASc score ≥3 significantly increased bleeding risk compared to scores ≤2 (AOR = 7.562, 95% CI: 2.770–20.640).ConclusionThis study highlights suboptimal warfarin therapy among older Ethiopian patients with AF. Poor anticoagulation was associated with advanced age, chronic kidney disease, and infrequent INR monitoring, while diabetes mellitus and high CHA₂DS₂-VASc scores increased bleeding risks. Close monitoring and frequent INR checks are essential to improving outcomes.
Study of Microzoobenthos diversity in the Barambang River, Siantar Marihat District, Pematangsiantar City, Noth Sumatera Utara
Authors: Pakpahan Dany Alberto , Barat Welmar Olfan Basten , Saragih Ewin Handoco 
Published: February 2025

This study aims to; identify the diversity, uniformity, and dominance of Macrozoobenthos in the Bah Biak River area, Pematangsiantar City, North Sumatra Province. This study used a combination of two transect methods, namely line transects and quadrat transects. Determination of the research location using Purposive sampling techniques. Data analysis using qualitative and quantitative analysis. The results of the study showed that there were 3 species of Macrozoobenthos consisting of 2 classes with a total of 67,35% individuals. The diversity of Macrozoobenthos in the Bah Barambang River, Pematangsiantar City, North Sumatra Province is classified as moderate with a diversity index of H' = 0,71 – 0,73, the evenness index is classified as low ranging from 0,51 – 0,53 and the dominance index is classified as low.
Keywords: Macrozoobenthos, River, Diversity
Abstrak
Penelitian ini bertujuan untuk; Untuk mengidentifikasi keanekaragaman, keseragaman dan dominansi Makrozoobenthos pada kawasan Sungai Barambang Kota Pematangsiantar Provinsi Sumatera Utara. Penelitian ini menggunakan kombinasi dua metode transek yaitu transek garis dan transek kuadrat. Penentuan lokasi penelitian menggunakan teknik purposive sampling. Analisis data menggunakan analisis kualitatif dan kuantitatif. Hasil penelitian diketahui bahwa terdapat 3 spesies Makrozoobenthos yang terdiri dari 2 kelas dengan jumlah keseluruhan 67,35% individu. Keanekaragaman Makrozoobenthos di Sungai Bah Barambang Kota Pematangsiantar Provinsi Sumatera Utara tergolong sedang dengan indeks keanekaragaman H' = 0,71 – 0,73, indeks keseragaman rendah berkisar antara 0,51 – 0,53 dan indeks dominansi rendah.
Kata Kunci: Makrozoobentos, Sungai, Keanekaragaman.
Acoustic characteristic analysis of a Langevin transducer attached with a circular plate supported on a concentric circle
Authors: Kim Jungsoon , Kim Moojoon 
Published: February 2025

Abstract
A theoretical forced vibration model for a Langevin transducer with a circular plate supported by concentric circles was proposed, and an analytical solution was derived. The vibration displacement of the plate, excited by the transducer, was found to vary with different plate sizes. Results from the proposed analytical method were compared with those obtained using a commercial finite element method, confirming the model’s validity. This study provides a practical approach to predict and analyze the acoustic behavior of Langevin transducers for effective energy transfer to the surrounding medium.
IL-22/IL-22R1 pathway enhances cholangiocarcinoma progression via ERK1/2 activation
Authors: Zhou Jin , Chen Jing-Rui , Li Jin-Ming , Han Shuang-Qing , Deng Xi-Yue , Li Zhong-Min , Tong Wen , Wang Chao , Bai Yi , Zhang Ya-Min 
Published: February 2025

BACKGROUND
IL-22 plays a pivotal role in the processes of inflammation and tissue healing., but its role in cholangiocarcinoma (CCA) remains unclear. our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.
AIM
To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.
METHODS
IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques, Western blot analysis, and quantitative reverse transcription PCR. The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation, migration, invasion, and apoptosis assays. The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects. ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.
RESULTS
IL-22R1 was overexpressed in CCA cell lines and tissues. IL-22 treatment increased the phosphorylation of ERK1/2 , promoting tumor cell proliferation, migration, invasion, and resistance to apoptosis. ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo .
CONCLUSION
The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling. Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.
Metastasizing to the colon from triple-negative breast cancer: A case report and review of literature
Authors: Wang Ben-Quan , Fang Xing-Gui , Xiang Ben-Hong , Wang Xiao-Jiao , Cao Ming , Zhuang Cheng-Le , Liu Zhong-Chen , Wang Zheng 
Published: February 2025

BACKGROUND
Breast cancer (BC) metastasis to the gastrointestinal tract is uncommon, colonic metastasis from BC (CMBC) is even rarer.
CASE SUMMARY
This report describes a 44-year-old female patient with metastatic triple-negative BC in the ascending colon who underwent laparoscopic radical right hemicolectomy. The patient had undergone left modified radical mastectomy only 15 months ago and stopped chemotherapy just 3 months ago. The diagnosis of CMBC was made based on the previous history of BC and positive results of several specific immunohistochemical markers (gross cystic disease fluid protein 15, mammaglobin, GATA-binding protein 3, and cytokeratin 7) for breast carcinoma.
CONCLUSION
CMBC should be highly cautious in patients with a previous history of BC, especially triple-negative BC, and further examination to aid in diagnosis.
Gastric gastrointestinal stromal tumor in a patient with neurofibromatosis type I presenting with anemia: A case report
Authors: Bai Guang-Yang , Shan Ke-Shu , Li Chen-Sheng , Wang Xiang-Hua , Feng Ming-Yang , Gao Yan 
Published: February 2025

BACKGROUND
Gastrointestinal stromal tumors (GISTs) are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90% of cases. A minority of wild-type GISTs are associated with neurofibromatosis type 1 (NF1), an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene, which encodes the neurofibromin protein. NF1 patients often exhibit multi-system involvement, with café-au-lait macules and neurofibromas being characteristic symptoms. GISTs are a rare complication of NF1, with the tumors most frequently occurring in the small intestine (90% of cases), while occurrences in the stomach are rare.
CASE SUMMARY
A 51-year-old woman presented to the emergency department with complaints of dizziness, fatigue, chest tightness, and dark stools. Initial examination revealed a red blood cell count of 1.99 × 1012/L and a hemoglobin level of 43 g/L. She underwent blood transfusions and fluid replacement to stabilize her condition. Further investigations identified typical café-au-lait macules on her trunk, limbs, and face, along with neurofibromas. Endoscopy showed coffee-colored fluid in the gastric cavity, a large submucosal elevation with an exudative covering, and ulcer formation on the gastric fundus. Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus, and resection of the giant GIST was performed. Pathological analysis revealed a necrotic GIST measuring 18 cm × 14 cm, classified as high-risk, with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins. Immunohistochemistry results were CD117 (+), delay of germination 1 (+), CD34 (+), and succinate dehydrogenase complex iron sulfur subunit B intact expression. Genetic testing using next-generation sequencing confirmed an NF1 gene mutation. The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy. A follow-up at one year showed no recurrence.
CONCLUSION
Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs, surgical resection with complete tumor removal remains the preferred treatment option. However, the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.
Numerical study of laminar mixed convection under steady and unsteady flow conditions
Authors: Hamadi Billel , Cherrad Mohamed Lotfi , Boucherma Djamel , Chorfi Sofiane , Boulkroune Sofiane , Achour Toufik , Chaour Mohamed 
Published: February 2025

The present work consists of a numerical study of laminar mixed convection in a square cavity, a cavity has been chosen whose left vertical wall is mobile and subjected to a cold temperature, while the right wall is considered fixed and hot. The horizontal walls are adiabatic. where configuration of the lid-driven enclosure is encountered in many realistic engineering and industrial applications, such as, contains cooling of electronic devices, materials processing, flow and heat transfer in solar ponds, thermal-hydraulics of nuclear reactors and metal coating. The governing equations are the continuity equation, the Navier-Stocks equations, and the energy equation. These equations are discretized by the finite volume method. The objective of this work is to study the effect of the Reynolds and Grashof numbers on the structure of the flow. We were able to determine the correlation between the number Gr and Re to determine the transition boundaries from one convection regime to another regime (laminar, then transient).
MERGERS IN HIGHER EDUCATION FOR SUSTAINABLE DEVELOPMENT: A SYSTEMATIC LITERATUR REVIEW
Authors: Ardie Putra Alfian Prayana , Khairusy Mirza Abdi , Prameswari Yuda Nabella , Atmaja Sukarta 
Published: February 2025

This paper discusses sustainable development issues in the higher education sector from the higher education perspective. Higher Education Institutions (HEIs) are important actors in achieving the Sustainable Development Goals (SDGs) and the 2030 Agenda set by the United Nations General Assembly in 2015. This paper aims to conceptualize impacts of higher education institutions (HEIs) on sustainable development (SD), This review aims to provide the available constructive literature on merger higher education with a theoretical and empirical background published during the past 5 years, from January 2019- November 2024, to identify impack merger higher education to sustnaible development and factors marger higher education. The author searched for articles in two databases(Scopus and Proquest). The contribution of this research becomes a reference in understanding impack merger higher education to sustnaible development and determining the factors of merger in higher education.
Penggunaan Mindfulness-Based Cognitive Therapy (MBCT) untuk Menurunkan Gejala Depresi Wanita dengan (Major Depressive Disorder (MDD)
Authors: Mailana Hasrat Listaria , Cahyanti Ika Yuniar 
Published: February 2025

Gangguan Depresi Mayor (Major Depressive Disorder/MDD) secara klinis ditandai dengan kehilangan minat dan kesulitan untuk merasa kepuasan dan kebahagiaan dalam kesehariannya. Kondisi ini harus berlangsung setidaknya 2 minggu atau lebih dan memengaruhi keberfungsian individu dalam keseharian. Individu yang mengalami gangguan ini biasanya terjebak dalam pemikiran yang negatif dan melakukan ruminasi sehingga terjebak dan kewalahan. Oleh karena itu, digunakan intervensi MBCT untuk menurunkan keparahan gejala depresi dengan praktik teknik mindfulness dan perubahan perilaku. Penelitian ini menggunakan metode eksperimen subjek tunggal (Single Case Experiment) untuk mengevaluasi efektivitas MBCT pada wanita berusa 22 tahun yang memenuhi kriteria depresi. Data-data yang berkaitan dikumpulkan dengan wawancara klinis, observasi, dan tes psikologis (DASS-42, SPM, Tes Grafis, dan SSCT). Hasil intervensi menunjukkan adanya penurunan gejala depresi pada partisipan dalam 3 minggu penanganan karena melakukan praktik mindfulness secara rutin dalam kegiatan sehari-hari dan pengaktifan kembali perilaku serta kegiatan positif yang memberikan positive reinforcement pada partisipan. Partisipan kembali berfungsi dalam kehidupannya dan keberhasilan terapi ini juga dipengaruhi oleh motivasi partisipan untuk berubah serta dukungan sosial yang adekuat dari lingkungan di sekitar partisipan.
Rechtsverwerking en klachtplichten in het verbintenissenrecht
Authors: Valk J.J. 
Published: February 2025

Rechtsverwerking en klachtplichten in het verbintenissenrecht. Bespreking van het proefschrift van mr. H. Boom
Bespreking van het proefschrift van Boom aan de hand van drie onderwerpen: Obliegenheiten als grondslag voor rechtsverwerking, het toepassingsbereik van de klachtplicht en de toepassing (vereisten en rechtsgevolgen) van rechtsverwerking en klachtplichten.
Pelayanan Jasmani Dan Rohani Yang Alkitabiah Kepada Masyarakat Kelurahan Barong Tongko
Authors: Doni A  
Published: February 2025

Kelurahan Barong Tongko merupakan salah satu tempat yang berada di Kabupaten Kutai Barat, Kalimantan Timur. Kelurahan ini walaupun dikatakan sudah maju, namun masih banyak masyarakat yang tidak mau datang beribadah di gereja dan tidak mau ikut kegiatan-kegiatan rohani lainnya. Oleh sebab itu penulis bersyukur dengan adanya pelayanan pengabdian kepada masyarakat, penulis bisa melayani mereka secara jasmani dan rohani, yang bedasarkan kasih Kristus. Penulis bersyukur juga karena masyarakat di kelurahan Barong Tongko mau dibimbing dan mau dilayani untuk mendekatkan diri mereka kepada Tuhan Yesus Kristus. Memang segala sesuatu maslah tidak ada yang tidak bisa diselesaikan bersama Tuhan Yesus, asalkan kita mau melakukan, berusaha dan berdoa.
Uso das ferramentas de geoprocessamento na caracterização morfométrica do município de Riachão do Poço - PB
Authors: Santana José Vinícius Tavares de , Silvino Guttemberg da Silva , Diniz Felipe dos Santos Silva , Silva Bruno Santana da , Arruda Filho Nivaldo Timóteo de 
Published: February 2025

Uma das grandes problemáticas quando o tema e o monitoramento de recursos naturais é o tamanho dos territórios a ser analisado. Nesse contexto, a utilização de geotecnologias mostra ser uma boa alternativa para a obtenção desses dados, auxiliando no processo e desenvolvimento de estratégias que melhore a forma de gerir os recursos hídricos. O referido trabalho teve como objetivo usar modelos digitais de elevação e as técnicas de geoprocessamento para delimitação das microbacias hidrográficas, características morfométricas e da rede de drenagem para realizar análise comparativa com a base de dados oficial já existente, disponível pela AESA – Agência Executiva de Gestão das Águas do Estado da Paraíba. A obtenção dos resultados foi realizada a partir de um modelo digital de elevação para o município de Riachão do Poço – PB, a saber, imagem SRTM que apresentam respectivamente 30 m de resolução espacial, por meio da utilização de um Sistema de Informação Geográfica de uso livre, QGIS versão 3.34. Foram delimitadas 9 microbacias para a área de estudo, onde os resultados mostraram uma média tendencia a enchentes, possuindo uma boa densidade de drenagem e hidrográfica. O relevo em sua maioria, apresentou suave ondulado, com uma altitude variando de 40 a 100 metros. A rede de drenagem obtida com o uso dos MDE’s, apresentou diferença significativa em relação a rede de drenagem existente disponível pela AESA, comprovando que as ferramentas disponibilizadas atualmente pelas geotecnologias se mostram excelentes alternativas para auxiliar na geração destes resultados
What is the Study Policy in Banyumas? Implementation of Active Learning Strategies in Junior High School
Authors: Albar Mawi Khusni 
Published: February 2025

Objective: This study aims to determine the application of active learning strategies in Islamic religious education (P.A.I) subjects in class VII MTs Ma'arif NU 1 Kemranjen Banyumas Regency. The importance of implementing active learning strategies in the learning process, especially in Islamic Religious Education subjects, is expected to reduce boredom or boredom in students.

Method: This type of research is field research. This study describes a process that occurs in the field in descriptive form, while the approach used in this research is to use qualitative research. Data collection techniques used three triangulation techniques: observation, interviews, and documentation.

Result: The results showed that the application of active learning strategies in P.A.I subjects carried out by MTs Ma'arif NU 1 Kemranjen Banyumas Regency was adjusting to the subject matter, situations, and conditions in learning. P.A.I teachers apply several active learning strategies, namely, everyone is a teacher here (everyone can become a teacher), card sorting (sorting and selecting cards), and team quiz (group quiz).

Conclusion: This strategy is carried out as an effort by Islamic Religious Education teachers to provide convenience for students in understanding P.A.I lessons.
القَلْقَلةُ والنَّبْرُ الصَّوتيُّ في القرآن عِندَ القُدَماءِ واللِّسانيّين المُحدثينَ: دراسةٌ وَصفيّةٌ دَلاليّةٌ (نماذج مُختارة)
Authors: ربايعة مروان 
Published: February 2025

تَهْدُفُ هذه الدِّراسةُ إلى الحديثِ عن قَضايا صوتيّةٍ لها حضورٌ لافتٌ في الدِّراساتِ الصّوتيّةِ، وفي العلومِ القرآنِيّةِ، وهما قَضايا القلقلةِ والنَّبرِ، وهما قَضيّتانِ شَغَلَتا بالَ الدارسينَ والباحثينَ، قديمًا وحديثًا، وكانتْ مَحَلَّ خِلافٍ في وظيفَتِهما الدَّلاليّة، فَثَمَّ مَنْ أنْكَرَها، وهناكَ مَنْ اسْتَقْرَأَ لهما معنًى ودَلَالةً يُؤَدِّيانِهما، وَلِذا تَنْبُعُ أهمّيّةُ الدِّراسةِ في كَشْفِها عن وجودِ ظاهِرَتَيِ القلقلةِ والنَّبرِ على المَقاطعِ الصَّوتيّة، في اللغةِ والقرآنِ الكريمِ، ومَدى إسهاماتِها في إبرازِ الدَّلالةِ والمعنى للآية الشَّريفة، وجاءتِ الدّراسةُ لِتُجيبَ عن أسْئلةٍ مُفْترَضِةٍ، مُؤَدّاها: هلِ تُؤَدّي القلقلةُ دَوْرًا وظيفيًّا في اللُّغةِ والقرآنِ الكريمِ؟ وهل اللغةُ العربيّةُ لغةٌ نبريّةٌ؟ وهل بمقدورِنا دراسةُ النَّبْرِ في القرآنِ الكريمِ، دراسةً صوتيّة فنولوجيّة وظيفيّة؟ ما موقِفُ علماءُ العربيّة القُدماء واللِّسانيّينِ المُحدثينَ منهما، مِنْ حيثُ الدَّلالةُ؟
وكَشفتِ الدِّراسةُ عن أنَّ القُدماءَ كانوا على علمٍ تامٍّ بالنَّبرِ والقلقلةِ، وأنَّ عدمَ تفصيلِهم للظاهرتَيْنِ الصوتيَّتَيْنِ لا ينفي وجودَهما، وتَلَمُّسَ وظيفتِهما المعنويّةِ. وأنَّ الدّراساتِ الحديثةَ قد أوْلَتْه البحثَ والتَّمحيصِ، ولا بُدَّ من أنْ تأتيَ القلقلةُ والنبرُ عندهم لدلالاتٍ يكشفها السّياقُ القرآنيّ، وأنَّ دَرْسَهما لم يَحْظَ بالبحثِ الجادِّ والحقيقيِّ.