bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosine Kinase Inhibitor Lenvatinib Causes Cardiotoxicity by Inducing Endoplasmic Reticulum Stress and Apoptosis through Activating ATF6, IRE1α and PERK Signaling Pathways
Authors: Wang Siqi , Ji Fang , Gao Xiaoli , Li Zhiyi , Lv Si , Zhang Juan , Luo Jiarui , Li Dan , Yan Jie , Zhang Huayang , Fang Kaicheng , Wu Lin , Li Miaoling 
Published: July 2024

Background:
Lenvatinib is a tyrosine kinase inhibitor that can improve
progression-free survival in patients with thyroid cancer and hepatocellular carcinoma.
However, it is limited by adverse cardiovascular events, including hypertension and
cardiac dysfunction. Activation of endoplasmic reticulum stress is involved in cardiomyocyte
apoptosis.

Objective:
This study aimed to confirm whether the cardiotoxicity of lenvatinib is associated
with endoplasmic reticulum stress by targeting the activating transcription factor 6 (ATF6), inositol-
requiring enzyme 1α (IRE1α) and protein kinase RNA-like ER kinase (PERK) signaling
pathways.

Methods:
Male C57/BL6 mice were intragastric administration with 30 mg/kg/day lenvatinib.
Electrocardiography (ECG) and echocardiography were used to detect arrhythmias and cardiac
function. Neonatal rat cardiomyocytes were treated with lenvatinib for 48h. Cell counting kit
(CCK8), 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFHDA), Hoechst 33258 and dihydrorhodamine
123 were respectively used for evaluating cell viability, the level of reactive oxygen
species (ROS), nuclear morphological changes and mitochondrial membrane potential
(MMP) level.

Results:
Lenvatinib remarkably decreased the posterior wall thickness of left ventricle
during diastole and systole but caused little decrease to the left ventricular ejection fraction
(LVEF, %). Furthermore, lenvatinib greatly prolonged the corrected QT interval (QTc) and
altered the morphology of cardiomyocytes. No significant difference in fibrosis was found
in mouse cardiac slices. Lenvatinib upregulates apoptosis-related protein expression. In
addition, lenvatinib increased ERS-related proteins expression (GRP78, CHOP, and ATF6) and
enhanced PERK phosphorylation. In neonatal rat cardiac myocytes, lenvatinib markedly
decreased the viability of cardiomyocytes and induced apoptosis. Furthermore, ROS production
increased and MMP decreased. Similar to the mice experiment, lenvatinib caused upregulation
of apoptosis-related and ERS-related proteins and increased the phosphorylation levels of PERK
and IRE1α.

Conclusion:
Lenvatinib-induced cardiotoxicity is associated with ERS-induced apoptosis by
targeting the ATF6, IRE1α, and PERK signaling pathways.
Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST
Axis to Inhibit EMT
Authors: Huang Chuan , Wang Si-Hong , Liu Tao-Tao , Wu Mei-Yi , Cai Kai-Ning , Xie Zhan-Hong , Zhao Rui-Qiang , Wen Yan 
Published: July 2024

Background:
The emergence of drug resistance to oxaliplatin (OXA) is one of the critical
obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative
of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was
found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate
the effect of Y6 on oxaliplatin resistance in HCC.

Methods:
MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore
the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant
cells and observed the morphological changes of the cells. At the same time, transwell assay
was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and
Western blot analysis were performed to determine the expression levels of the miR-338-3p gene,
HIF-1α/Twist proteins, and EMT-related proteins.

Results:
We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the
drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and
the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the
control group and OXA group showed typical mesenchymal-like cell morphology, while most of
the cells in co-administration groups showed typical epithelioid cell morphology, and the ability
of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At
the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate
the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression
of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated.

Conclusion:
Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the
process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT.
Therefore, Y6 could be considered an effective medication resistance reversal agent, which could
improve the therapeutic effect for hepatocellular cancer patients.
Unmasking Stigma: A Qualitative Exploration of Nurses in Urban and Rural Indonesia during the COVID-19 Pandemic
Authors: Marpaung Yosi Marin , Ernawati Ernawati , Fushen   
Published: July 2024

Background
Studies investigating the manifestations of stigma on nurses during COVID-19 pandemic in Indonesia are still limited. Moreover, previous studies have primarily focused on nurses directly involved in COVID-19 care.

Objective
This study aims to thoroughly explore the sources of stigma and the spectrum of stigma manifestations—enacted, anticipated, and internalized—experienced by Indonesian nurses working across different levels of healthcare in the urban and rural settings of Indonesia during COVID-19 pandemic.

Methods
A qualitative descriptive study using semistructured interviews was conducted. Thirty-three nurses who worked in the urban area of Jakarta and in rural areas of West Kalimantan participated. Data analysis was carried out using the framework method.

Results
The findings showed that Indonesian nurses, regardless of their context (i.e., place of stay, COVID-19 status, level of health service, or area of service), encountered stigma during the pandemic. Sources of stigma varied widely and included self-stigma, stigma from family members, friends, health care recipients whether in hospital or out of hospital, colleagues, and other staff in the workplace, workplace policy and practices, the community surrounding their homes, markets, transport drivers, room rental owners, religious community, and online communities (netizens). Nine forms of enacted stigma, two forms of anticipated stigma, and four manifestations of internalized stigma were identified.

Conclusion
Not only do nurses bear the stigma related to the COVID-19 threat, but nurses also endured and felt stigma related to their nursing profession and the stigma associated with mental health issues. Indonesian nurses faced a triple burden of stigma during a pandemic, such as COVID-19, as stigma perpetuated from multiple levels of sources and intersected with other issues beyond the threat of the virus itself. To enhance nurses' resilience in future health crises, greater efforts are required to mitigate stigmatization against them.
Preventive Interventions for Internet Addiction in Young Children: Systematic Review
Authors: Theopilus Yansen , Al Mahmud Abdullah , Davis Hilary , Octavia Johanna Renny 
Published: July 2024

Background
In this digital age, children typically start using the internet in early childhood. Studies highlighted that young children are vulnerable to internet addiction due to personal limitations and social influence (eg, family and school). Internet addiction can have long-term harmful effects on children’s health and well-being. The high risk of internet addiction for vulnerable populations like young children has raised questions about how best to prevent the problem.

Objective
This review study aimed to investigate the existing interventions and explore future directions to prevent or reduce internet addiction risks in children younger than 12 years.

Methods
The systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched for relevant literature from 4 research databases (Scopus, Web of Science, PubMed, and PsycINFO). We included 14 primary studies discussing the interventions to prevent or reduce internet addiction risks in young children and their efficacy outcomes.

Results
The preventive interventions identified were categorized into four approaches as follows: (1) children’s education, (2) parenting strategy, (3) strategic physical activity, and (4) counseling. Ten interventions showed promising efficacy in preventing or reducing internet addiction risks with small-to-medium effect sizes. Interventions that enhance children’s competencies in having appropriate online behaviors and literacy were more likely to show better efficacy than interventions that force children to reduce screen time. Interventions that shift children’s focus from online activities to real-world activities also showed promising efficacy in reducing engagement with the internet, thereby preventing addictive behaviors. We also identified the limitations of each approach (eg, temporariness, accessibility, and implementation) as valuable considerations in developing future interventions.

Conclusions
The findings suggest the need to develop more sustainable and accessible interventions to encourage healthy online behaviors through education, appropriate parenting strategies, and substitutive activities to prevent children’s overdependence on the internet. Developing digital tools and social support systems can be beneficial to improve the capability, efficiency, and accessibility of the interventions. Future interventions also need to consider their appropriateness within familial context or culture and provide adequate implementation training. Last, policy makers and experts can also contribute by making design guidelines to prevent digital product developers from making products that can encourage overuse in children.
REVERSE-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD DEVELOPMENT AND VALIDATION FOR THE QUANTIFICATION OF SUGAMMADEX IN BULK AND PHARMACEUTICAL DOSAGE FORM
Authors: BHAVYA SRI K  , SRIJA G  
Published: July 2024

Objective:A reproducible, precise, accurate method was developed for the analysis of Sugammadex in pharmaceutical dosage form and bulk, using RP-HPLC. This method is established in compliance with ICH guidelines Q2R1.
Method:The method development and method validation of Sugammadex was performed usingthe instrument, SHIMADZULC- 20 AD pumps with SPD- 20A UV detector. A Phenomenex C18 250mm × 4.6mm × 5µm column was employed with detection wavelength of 210 nm.
Results: The method validation was performed in accordance with ICH Q2 R(1) guidelines where the calibration curve was found to be linearwith r2as 0.9993. The LOD and LOQ were found to be 0.03784µg/ml and 0.114667µg/ml respectively.The %RSD of theprecision wasobserved to be in limits (≤2%).
Conclusion:All validation parameters, including linearity, range, detection limit, quantification limit, precision, and accuracy, were examined and found to be within the specified limits in accordance with ICH recommendations Q2 (R1). In view of this, adopting this approach for routine quality control tests of both pure and pharmaceutical formulation can be done with ease.
Las políticas de reinserción social de los sujetos privados de la libertad en la provincia de Santa Cruz, en el marco de la pandemia generada por el COVID 19. El rol de la educación superior
Authors: Navas Pablo , Alonso Alejandra , Hernández Silvia , Rotman Silvio , Scott Melisa , Frias Patricia 
Published: July 2024

El presente artículo propone un análisis sobre las condiciones actuales de acceso a la educación universitaria, por parte de la población carcelaria de los establecimientos penitenciarios de la localidad de Río Gallegos, provincia de Santa Cruz. Para el análisis propuesto tomaremos como institución de referencia la Universidad Nacional de la Patagonia Austral. El estudio que compartimos recupera un núcleo de experiencias y análisis que apuntan a dar cuenta del devenir de la educación en contextos de encierro, partiendo del reconocimiento de que el acceso al derecho a la educación universitaria por los privados/as de la libertad, identifica dificultades evidentes en su implementación concreta. En virtud de esta caracterización, nos proponemos como objetivo contribuir, partir del análisis, a trazar un esquema que oriente la implementación de políticas públicas situadas que tiendan a garantizar el acceso a la educación superior universitaria a los/as privados/as de la libertad.
Para dar cuenta de esta trayectoria sinuosa del desarrollo de la modalidad de contextos de encierro en la universidad, recuperamos las experiencias de vinculación entre la universidad y el sistema penitenciario provincial, los marcos normativos de referencia en el ámbito provincial y universitario y las voces y experiencias de actores institucionales claves: responsables provinciales de la modalidad educativa, de los programas de reinserción, docentes de la universidad y autoridades universitarias.
O rio como espaço de disputa: a política de ocupação portuguesa no Guaporé (1740-1770)
Authors: Siqueira de Melo Vanice 
Published: July 2024

A área limítrofe entre a capitania do Mato Grosso e as missões de Mojos e Chiquitos, organizadas pelos jesuítas castelhanos, foi caracterizada por uma série de episódios litigiosos envolvendo os vassalos das Coroas ibéricas, sobretudo a partir de 1750. Trata-se de um contexto no qual Portugal e Espanha assinaram o Tratado de Madri, acordo diplomático que definia seus territórios nas conquistas americanas. Por meio desse tratado, foi stabelecido que os cursos dos rios deveriam ser usados como limites territoriais entre os domínios ibéricos, a exemplo do Guaporé e do Madeira. Os rios, por sua vez, não eram apenas demarcadores de limites. Este artigo analisa de que maneira a Coroa portuguesa procurava se apropriar do Guaporé e quais mecanismos empregou com essa finalidade.
PENGAWASAN DAN PEMANTAUAN PERTUMBUHAN JAMUR TIRAM DENGAN MEMANFAATKAN TEKNOLOGI INTERNET of THINGS (IoT)
Authors: Nasution Rizka Alivia , Masthura Masthura , Nasution Nazaruddin 
Published: July 2024

Penelitian ini bertujuan untuk merancang alat pengawasan dan pemantauan pertumbuhan jamur tiram dengan memanfaatkan teknologi internet of things (IoT). Proses pembuatan alat dimulai dari perancangan hardware dengan menghubungkan semua komponen, meliputi ESP32 dan sensor DHT22 untuk mengukur suhu dan kelembaban di kumbung, sensor pH Media Tanam untuk mengukur pH di media tanam, sensor kelembaban tanah untuk mengukur kelembaban di media tanam jamur tiram, BH1750 untuk penerangan otomatis di malam hari, RTC DS3231 untuk mengatur jadwal otomatis pada pompa air, dan LCD 20 x 4 untuk menampilkan informasi suhu, kelembaban, pH, dan cahaya (lux) di media tanam jamur yang dilanjutkan dengan perancangan software pada arduino dan aplikasi blynk untuk memantau dan mengawasi pertumbuhan jamur tiram melalui alat. Suhu yang optimal untuk budidaya jamur adalah 30,20°C dengan deviasi sebesar 0,7%, sedangkan kelembaban optimal di kumbung jamur tiram adalah 72,70% dengan deviasi sebesar 3,7%. Kadar pH optimal di media tanam untuk budidaya jamur tiram adalah 6,52 dengan deviasi sebesar 0,3%.
OPTICAL PROPERTIES of the TlSbP2Se6 SINGLE CRYSTALL
Authors: Sabov V.I. , Barchii I.E. , Piasecki M. , Filep M.J. , Pogodin A.I. , Studenyak Y.I. , Sabov M.Yu. 
Published: July 2024

The scientific interest in TlSbP2Se6 compound is due to a number of factors. Firstly, this compound is characterized by congruent melting behavior, which allows obtaining high-quality bulk single crystals by the method of directional crystallization using the Bridgman technique. Secondly, it is characterized by an acentric 2 D layered structure. Previous studies of TlSbP2Se6 single crystals were limited to optimizing the conditions for growing single crystals, refinig its crystal structure, determining its qualitative and quantitative composition, determining the optical transparency region, and evaluating its physical characteristics using quantum chemical calculations. The purpose of this study was to compare the calculated values of the band gap of TlSbP2Se6 with those experimentally determined by the results of the optical absorption edge study. We prepared plane-parallel samples of single-crystal TlSbP2Se6 along the cleavage plane. The width of the band gap was determined from the transmission spectra using the Tauc method. It was established that the compound TlSbP2Se6 belongs to direct-band semiconductors with a band gap of 1.81 eV. The values calculated by the Becke-Johnson method using the modified functional with the Hubbard parameter and spin-orbit interaction (TB-mBJ+U+SO) and without (mBJ) were the closest to the experimental band gap.
Paradigma Bimbingan Konseling dalam Kurikulum Merdeka
Authors: Huda Miftahul 
Published: July 2024

Facing changes in technology and Merdeka Belajar curriculum policies, counselors need to be innovative in counseling services. The challenges of the guidance and counseling profession in the era of industrial revolution 4.0 require adaptation and innovation. This research uses qualitative methods with literature studies, utilizing various sources such as books, journals and institutional reports. The role of guidance and counseling teachers is important to align learning with the Merdeka Belajar program, encouraging the development of High Order Thinking Skills (HOTS). The implementation of the Guidance and Counseling service policy in the Minimum Competency Assessment allows for a holistic assessment and develops programs and provides appropriate intervention services. The main goal of Guidance and Counseling teachers is to help students recognize themselves, function as service providers so that each individual can develop optimally, achieve personal needs, and become a complete and independent individual. Menghadapi perubahan teknologi dan kebijakan kurikulum Merdeka Belajar, konselor perlu inovatif dalam layanan konseling. Tantangan profesi bimbingan dan konseling pada era revolusi industri 4.0 membutuhkan adaptasi dan inovasi. Penelitian ini menggunakan metode kualitatif dengan studi pustaka, memanfaatkan berbagai sumber seperti buku, jurnal, dan laporan lembaga. Peran guru bimbingan dan konseling penting untuk menyelaraskan pembelajaran dengan program Merdeka Belajar, mendorong pengembangan High Order Thinking Skills (HOTS). Penerapan kebijakan layanan Bimbingan dan Konseling dalam Asesmen Kompetensi Minimum memungkinkan penilaian holistik dan menyusun program serta memberikan layanan intervensi yang sesuai. Tujuan utama guru Bimbingan dan Konseling adalah membantu peserta didik mengenali diri mereka, berfungsi sebagai penyedia layanan agar setiap individu dapat berkembang optimal, mencapai kebutuhan pribadi, dan menjadi individu utuh serta mandiri.
Comparison of polyclonal and monoclonal antibody assays for serum amyloid A in cats: a study based on an automated turbidimetric immunoassay in a primary care veterinary hospital
Authors: Yuki Masashi , Inden Takanori , Hirano Takashi , Naito Eiji , Taira Hiroto , Yokota Shunya , Narita Momoko 
Published: July 2024

Abstract

OBJECTIVE
Comparing the utility of the anti-human serum amyloid A (SAA)-specific monoclonal and polyclonal antibodies assays (LZ-SAA) with the pure monoclonal anti-human antibody assays (VET-SAA) during clinical practice in primary care hospital populations by measuring SAA measurement in healthy and diseased domestic cats.

ANIMALS
52 healthy and 185 diseased client-owned cats.

METHODS
SAA concentration was measured using different LZ-SAA and VET-SAA measurements for healthy and various diseased cats. Sensitivity, specificity, and accuracy were calculated for each disease.

RESULTS
VET-SAA has higher sensitivity than LZ-SAA for the most common diseases presenting to primary care veterinary hospitals, including chronic kidney disease, tumors, and gingivostomatitis. Our results reveal the capability of detecting low SAA concentrations in healthy and diseased cats using VET-SAA in contrast to LZ-SAA, which found elevations of SAA concentrations only in diseased cats.

CLINICAL RELEVANCE
Our findings indicate that switching to the new VET-SAA instead of the conventional LZ-SAA will likely enhance the diagnostic performance in primary care veterinary hospitals.
A veterinary-calibrated point-of-care glucometer accurately measures blood glucose concentration in dogs and cats
Authors: Cammarano Kellie , Carney Patrick C. , Rose Hailey E. , Merkhassine Michael , Ippolito Elizabeth , Arsenault Anne , Plotsker Noah M. , Loftus John P. , Kowalczyk Marcin , Prieto Jennifer M.B. 
Published: July 2024

Abstract

OBJECTIVE
To determine the clinical and analytical accuracy of a new veterinary-calibrated portable blood glucose monitor (PBGM) compared to a reference laboratory analyzer.

ANIMALS
Client-owned dogs (n = 77) and cats (n = 64).

METHODS
Peripheral and paired capillary whole-blood glucose concentrations measured via PBGM were compared to plasma glucose concentrations measured via a Cobas c501 reference analyzer (Roche). Analytical accuracy was evaluated with the Spearman rank correlation coefficient, Bland-Altman difference plot analysis, and Deming regression. Clinical accuracy was evaluated with Parkes error grid analysis. Paired peripheral and capillary blood samples were compared with the Wilcoxon matched-pairs signed-rank test.

RESULTS
There was a high correlation between PBGM and reference analyzer readings in dogs and cats. Human quality assurance standards (International Organization for Standardization 15197:2013 guidelines) for analytical accuracy were met for 95% of feline peripheral blood samples and 89% of canine samples. Similar veterinary standards (American Society of Veterinary Clinical Pathology guidelines) were met for 89% of canine and 92% of feline peripheral blood glucose measurements. Error grid analysis showed that all peripheral canine and 97% of feline measurements were clinically accurate (zone A). Any altered clinical decision for the remaining feline measurements was expected to minimally impact outcome (zone B). No significant difference was found between peripheral and capillary blood glucose measurements in either species.

CLINICAL RELEVANCE
The PBGM produced clinically accurate results and is suitable for use in veterinary and home settings to measure blood glucose.
Treatment of subcutaneous lipomas in the horse
Authors: Kearney Molly T. , Kamm J. Lacy 
Published: July 2024

Abstract

OBJECTIVE
To describe the treatment of subcutaneous lipomas in the horse.

ANIMALS
3 horses.

CLINICAL PRESENTATION
The horses were aged 1 to 2 years old, with lipoma of the abdomen, prepuce, and tarsus.

RESULTS
All cases had surgical removal of the masses under general anesthesia. Recurrence of an invasive abdominal lipoma occurred in case 1 at the exit site of a passive drain. The recurrence was treated unsuccessfully with injectable cisplatin, and a second revision surgery with the use of an active drain resulted in resolution. In case 2, complete resection of an encapsulated lipoma of the lateral prepuce was successful with no recurrence. In case 3, incomplete resection of a tarsal lipoma resulted in a sound horse, with no further growth. Histopathologic analysis revealed that all masses were composed of well-differentiated adipocytes with no evidence of malignancy.

CLINICAL RELEVANCE
Subcutaneous lipomas are relatively rare and affect horses primarily ≤ 2 years of age. They are benign, although their presence can be deleterious due to invasion of local structures or the impact on normal locomotion. The margins of invasive tumors are difficult to identify due to their integration with normal tissue. Incomplete removal may allow for mass recurrence. Active suctions drains are beneficial if dead space is a concern.